Combined Obstetrics pdf notes for midwifery

01.OB Hx and PE (2) Dr sami.pdf
02.Fertilization, Implantation.pdf
03.Dxs of Pregnancy.pdf
04.physiologic changes in preg.pdf
05.ANC.pdf
06.Normal Labor lect I.pdf
07.Abnormal Lbor.pdf
08.Perinatal DX.pdf
09.OPERATIVE DELIVERIES Induction(2).pdf
10.Multiple Gestation.pdf
11.ABORTION.pdf
12.ECTOPIC PREGNANCY (2).pdf
13.GTD (NOVAC).pdf
14. Preterm Labor and Delivery.pdf
15.FETAL SURVEILLANCE.pdf
16.PROM.pdf
17.IUGR.pdf
18.OH.pdf
19.Red Cell alloimmunization.pdf

20.HTN DPx..pdf
21.Diabetes Mellitus in Pregnancy.pdf
22.cervix (2).pdf
23.ENDOMETRIAL Ca.pdf
24.Endometriosis.pdf
25.Ovarian Ca.pdf
26.PCOS.pdf
27.Amenorrhoea.pdf
28.Infertility.pdf
29.STI.pdf
30. AUB.pdf
31.Meconium-stained_amniotic_fluid__MSAF_.pdf
33.POP (2).pdf
34 PELVIC ORGAN PROLAPSE.pdf
35.VIP.pdf

History Taking and Physical
Examination in OBGY

I. IDENTIFICATION
 Name (use initials when reporting for wider audience)
 Age *
 Occupation, Marital Status**
 Religion
 Address
* adolescents (< 18 ) and the elderly gravida (>35) are at
particular risk for adverse pregnancy outcome
**Information on marital status and occupation help assess the
socioeconomic status of the pregnant woman.
 Low socioeconomic status is associated with several poor
pregnanacy outcomes Eg preterm labor, PROM, low birth
weight, anemia, Pre-eclampasia, Eclampsia 2

II. chief complaints
 Most pregnant women come for routine ANC
 May have minor routine complaints
–eg abdominal discomfort, morning sickness,
back pain, leg pain, urinary frequency and
urgency,
 Some complaints may mark a serious problem
/danger signs/ and warrant
–Eg- vaginal bleeding, ↓fetal movement,
headache, visual disturbance, leakage of liquor,
persistent vomiting ,sever abd’l/epigastric pain
3

c/c………
Ex. Of Obst.C/C are:-
 Vaginal bleeding
 Leakage of liquor
 Pushing down pain
 Decreased/ absent FHB ?????
 Absent fetal movement
 Body swelling
 headache, blurring of vision, etc.
• There may be more than one chief complaint.
• If more than one chief complaints are present,
they should be arranged in a chronological
order 4

III. History of Present Pregnancy (HPP)
 HPP is the most important part of obstetric
history and is composed of
1.Summary of reproductive performance
Gravidity
refers to all previous pregnancies i.e. term,
preterm, live birth, stillbirth, abortion, ectopic
pregnancy, molar pregnancy
Primigravidity (1st pregnancy) is associated with
increased risk of PIH, labor abnormalities, CPD and
obstructed labor
5

• Ex. G 3 means she had previous 2
pregnancies, now she is pregnant
for the 3rd time
6

HPP
Parity
–all previous pregnancies that have reached
fetal viablity and delivered dead or alive
( i.e. >28 weeks of gestational age for
Ethiopia and UK , 28 weeks according to
other western countries)
–Primipara- 01 previous delivery
–Multipara- > 02 previous deliveries
–Grand multipara - > 5 previous deliveries
7

Parity…..
 Number of births delivered after age of viability
(i.e. 28wks)
 It could be live birth or still birth (born not alive)
 Twin/triplet/ quadriplet etc
deliveries considered as one
parity.
Abortion-
 Number of pregnancies terminated below the
age of viability, i.e <28 weeks
 it could be induced or spontaneous.
Ectopic pregnancies:
– number of past extra uterine pregnancies, if there
was any. 8

Examples
 Ex. This is a 38 years old G 5, P 2, Ab1, Ectop 1
mother…… means,
 she had 4 past pregnancies
o2 delivered
o1 aborted
o1 was ectopic pregnancy and
oshe is currently pregnant for the 5th time
9

HPP……
2.Last normal menstrual Period (LNMP), EDD & GA
A.LNMP- 1st day of last menses
 For LNMP to be reliable:-
1. It should be regular ( cycle length vary among
individuals ranging b/n 21 to 35 days)
2. It Should be similar to previous cycles in volume
and duration of flow
3. If the woman was on OCPs it should be
discontinued for at least 03 months ahead of
LMP
4. Lactating women should have 03 regular cycles
before LMP
10

HPP……
B.EDD:-- 280 days after LMP= 40 weeks
 EDD calculation;
1. Naegel’s Rule
– Subtract 03 months from LNMP and add 07days
– Eg If LNMP is February 12 then EDD will be on
November 19
2. Calculation according to the Ethiopian calendar
( 12 months of 30 days and pagume 5days/6
days with each leap year)
– LMP+ 9mths + 10days- if EDD doesn’t cross a year
– LMP+ 9mths + 5 days- if EDD crosses a year and
pagume is 05 days
– LMP + 09 mths + 04 days- if EDD crosses a year and
pagume is 6 days
11

EXAMPLES
 LNMP 10/1/07 if EDD not cross the yr of NLMP
EDD will be on 20/10/07
LNMP 24/3/07 then EDD will be on 4/13/07
 LNMP 30/3/01 if EDD cross the yr of NLMP;
EDD will be on 5/1/02
LNMP 6/6/01 then EDD will be on 11/3/02
12

HPP…..
C. Gestational Age
• GA is calculated in completed weeks
– Preterm pregnancy:- GA < 37completed wks
– Early Term pregnancy:- 37 – 38 6/7 Week
– Full Term Pregnancy:- 39- 41 6/7
– Post-term pregnancy:- > 42 weeks
• GA calculation is based on the assumption a
28 day regular cycle length- ovulation on the
14th day
13

HPP……
 In addition to LMP other methods are used to estimate
GA
A. Early US  before 20 weeks
– Ultrasonography may be considered to confirm menstrual
dates if there is a GA agreement
– within 1 week by CRL(crown ramp length) obtained in the
1stTM or
– within 10 days by an average of multiple fetal biometric
measurements (eg, CRL, BPD, HC, AC,FL) obtained in the
2nd (up to 20 weeks GA) . ACOG-2008
B. Quakening date
– around the 17th week for multipara ( experience from
previous pregnancies)
– Around the 19th week for primipara
C. Fundal height at umbilicus~20 weeks, 12 wks at
symphysis pubis and 38 wks at xiphysternem. 14

HPP…..
3.ANC hx
• If no ANC or delayed state – reason
• Details of ANC
– when, where started?
– what was done during each visits?
• What type counseling, examination
• investigation, medications given?
– Pre-pregnancy weight /BMI and weight at booking and on subsequent
visits
– BP recordings
– Lab investigation results
• Blood group, Rh, hemoglobin level
• UA for bacteruria, infection and hCG
• RVI,
• RPR/ VDRL test
• HBsAg 15

HPP/ANC……
• Health education about nutrition, sanitation,
labor, breast feeding and contraception
• Iron supplementation, malaria prophylaxis, TT
immunization,
• Any drug use- prescription, over-the-counter
or herbal medications
• Significant symptoms of illness early in
pregnancy like excessive nausea and vomiting,
Vaginal bleeding
16

HPP…..
4. Detailed discussion of the presenting
complaint (C/C) /xziation of symptom/
5. Always ask about the common danger signs
of pregnancy
– Headache (severe, persistent, not responsive for
analgesia)
– Visual disturbance
– Epigastric/ RUQ pain
– Vaginal bleeding
– Leakage of liquor per vagina
– Fetal movement status 17

HPP
6. Positive and negative statements directed at
possible DDx to the presenting complaint
7. Relevant informations should be switched
from other sections ( past ob Hx, Medical and
surgical hx , family hx etc. ) to the HPP.
8. Pregnancy;
– unplanned , unwanted and unsupported
18

IV. Nutritional Hx
• Detailed enquiry whether the woman takes
adequate amount of carbohydrates, fat,
proteins , minerals and vitamins
• Look for any food restrictions for cultural
reasons or taboos
19

V. Past Obstetric History
• Detailed chronological documentation of all
previous pregnancies i.e.
– Date , month and year of gestation ,
– gestation length (weather abortion , PT, term,post
term)
• Any antepartum, intrapartum or postpartum
complications
– Eg APH, PPH, IUGR, PROM, Malpresentation,
macrosomia, congenital anomalies, molar pregnancy,
GDM, Hypertensive disorder
NB- most of these complications have a significant
recurrence risk
20

• Onset of labor (spontaneous or induced
• Fetal presentation
• Duration of labor
• Mode of delivery (SVD , instrumental, C/S,
destructive delivery
• Fetal outcome (alive or dead, sex of the
newborn, weight of the newborn
malformations, current condition)
21

VI. Gynecologic History
• Menstrual history
– Age at menarchae
– Regular/ irregular, intervals (21-35 days ),intermenstrual
bleeding/ spotting
– Amount and duration of flow
– Discomfort during menses (Dysmenorrhoea)
– Premenstrual symptoms (cyclic affective and somatic
symptoms in the luteal phase)
• Contraception use history
– use , type , duration and side effects
22

• Sexual history
–assess risk of sexually transmitted
infections and HIV/AIDS
• Gynecology operations
–Female genital mutilation
–laparatomy,
–dilatation and curettage ,
–Evacuation and curettage,
–manual vacuum aspiration
23

VII. Past medical and surgical History
• Episodes of acute/ chronic illnesses, duration,
treatment outcome , follow up , current status
• Such chronic illnesses as DM, HTN, Thyroid
disease ( thyrotoxicosis and hypothyroidism),
cardiac and renal disease that affect pregnancy
outcome need to be integrated with the HPP
• Hx of blood transfusion-
– possibility of minor blood group incompatibility and Rh
isoimmunization
• STI Hx and treatment
• Hx of pelvic surgery
– Eg –myomectomy, hysterectomy, metroplasty- cause uterine
scarring and may dehisce during pregnancy and labor
• Hx of surgery involving other organ systems
24

VIII.Personal and Family History
• Place of birth and bringing up
• Education, occupation, income
• Habit of smoking, alcohol , caffein or illicit drug use
• siblings-
– Number of sisters and brothers
– Alive
– Dead – cause of death
• Parents
– Age
– Health status
– If deceased- age when dying and cause of death
• Family history of chronic illnesses ( eg DM,
Hypertension Epilepsy etc.) or any hereditary disease
• Family history of twining
25

IX. Review of System (Functional enquiry)
• Detailed orderly search for any symptoms
pertaining to each organ system LIKE medical
history
• Gus Hx & danger signs like headache and
blurring of vision are put in the HPP.
26

Physical Examination
1. General Appearance
– Comfortable, in CRD, acutely/ chronically sick
looking,
– body habitus ( obese, malnourished), stature
(extremely short?), skeletal deformities
– Facial features- chloasma of pregnancy, puffy
face
NB. some of the above descriptions can be
placed at the respective systemic examinations
27

2. Vital Signs
 BP
– Measured in the left lateral ( usually for
inpatients) or sitting positions
– The right arm should be used consistently, in a
roughly horizontal position at heart level.
– For DBP, both phases ( IV-muffling and V-
disappearance of sound) should be recorded.
 PR, RR, T0
– are taken the same way as in any medical patient
physiologic changes caused by pregnancy should be taken
into account while interpreting results 28

3. HEENT
– look for chloasma, Conjunctival pallor /PINK, icteric /jaundiced
sclera
– Hair distribution
– Buccal mucosa- wet or dry ?
– Gingival hypertrophy, gingivitis?
– Oral thrush?
4. LGS-
– Breast (engorgement, areolar pigmentation ,montgomery tubercles….),
thyroid and all accessible LN areas are examined
5. Chest
– Inspection, palpation, percussion and auscultation of RS.
6. CVS
– PMI displacement lateral to the MCL, S3 and systolic murmurs <
Grade III are usual non pathologic findings
– Look for varicose veins in the lower extremities and vulva -(DVT)
29

7. Abdomen
• Exposure
– The patient should be supine with a comfortable
pillow, the arms lie by her sides
– The abdomen should be exposed from just below
breasts to the symphysis pubis just below the pubic
hairline ( not to miss pfannenstel scar)
NB- the woman is often asked to expose the
abdomen by herself
30

Inspection
• Grossly distended abdomen?
• Protuberance- central or localized tone area
• Movement of abdomen with respiration
• Flank fullness
• Uterine dextrorotation ( abdomen tilted more to the right normally in px
women bcz of sigmoid on the left side)
• Black line (linea nigra) more prominent in the midline b/n umbilicus and and
symphysis pubis.
• Striae gravidarum- stretch marks due to disruption of collagen fibers of
dermis ( breasts and thighs can also be involved)
– NEW- purplish, few
– Old (straie albicantes)- whitish, multiple
• Umbilicus-flat, inverted, everted?
• Scar- location, size and thickness
• Distended veins and ascites portal hypertension
• Abdominal wall edema with peau-d-orange appearance  part of ana sarca
31

Superficial palpation
• In each quadrant
– areas of rigidity, tenderness, abd wall masses
– Location of appendix base in advanced
pregnancies at higher level than McBurneys point
( pushed up by the gravid uterus)
– Diffuse tenderness and rigidity /generalized
peritonitis:--
»chorioamnionitis
»abruptio placentae,
»ruptured appendicitis,
»perforated PUD
32

Deep Palpation
• Detection of;
–hepatomegally and
–splenomegally
33

Obstetric Palpations (Leopold’s maneuvers)
• Four sequential maneuvers Performed on the
gravid uterus i.e. the fundal, lateral, pelvic
palpations and the Pawlik’s grip.
NB:-
• Before 28 weeks of gestation fundal height
determination is the only palpation possible
as the fetus is too small to determine lie or
presentation
• Fetal heart beat can be auscultated from 20th
week of gestation
34

1- Fundal Palpation
Objectives:-
• Determination of Height of fundus-GA and what
occupies the fundus
• Abdominal asymmetry need to be corrected first
( if dextro or levorotation is there) and the
bladder should be empty before starting
examination
A. Fundal Height determination; two methods i.e;
– Tape measurement of symphysis fundal hgt (SFH) in
cms or
– Finger method
35

1. SFH Tape Measurement (Tape Measurement)
–In the midline along the linea nigra traversing
the umbilicus
–The fundal height in cm accurately matches
to the gestational age b/n 18- 34 weeks
–More reliable method than the finger method
36

2. Finger method
–Fundus just palpable at S.pubis  12 weeks
–Midway b/n S.pubis and umbilicus 16 wks
–At Umbilicus 20 weeks
–Generally 1 finger above umbilicus
represents 2 weeks
–At Xiphysternem 38 weeks/term
–36 week by finger is comparable to 40
weeks of GA due to decrease in fundal
height after engagement
37

NB:--
 A fundal height to GA discrepancy of up to 02
weeks is acceptable.
 A positive or negative discrepancy of more than 02
week mandates further investigation to identify the
possible underlying cause.
 The commonest cause of both +ve and –ve
discrepancies (large for date and small for date
respectively) is wrong dating.
 Other possible causes
 +ve Discrepancy multiple gestation, polyhydramnios,
macrosomia, GTD, leiomyoma, ovarian tumor,
 -ve discripancy IUGR, oligohydramnios, PROM,
transverse lie, IUFD, missed abortion
40

B. Determining What Occupies The Fundus
• Palpate and ballot the fundal area with
both hands
–Head hard, round, ballotable structure
–Breech soft, bulky, irregular, non
ballotable
41

2- Lateral Palpation
Objective:-
 Determination of fetal lie and identification of the
side of the back
1. Fetal lie
– Orientation of the fetal longitudinal axis with respect
to that of the mother i.E longitudinal, transverse or
oblique
– Lateral palpation is performed alternatively on both
sides using one hand to stabilize the uterus.
2. The back feels like hard, straight/ flat structure
while the extremities on the opposite side feel
like multiple nodular parts
– Fetal heart beat can be easily auscultated on the side
of the back
42

3.pelvic palpation
Objectives
• identification of fetal presentation and attitude ( if
cephalic)  Cephalic prominence
• The examiner faces the patient's feet and places a hand
on either side of the uterus, just above the pelvic inlet.
• When pressure is exerted in the direction of the inlet,
one hand can descend farther than the other.
• The part of the fetus that prevents the deep descent of
one hand is called the cephalic prominence.
• Presentation can be Cephalic , breech or shoulder
43

 Attitude
– Flexed; the cephalic prominence is on the same
side as the small parts.
– Extended; the cephalic prominence is on the same
side as the back.
– military
 Descent=from 5/5 ( floating) to 0/5
 Engagement=minimum of 2/5 descent
44

Descent=b/n 5/5 ( floating) and 0/5
Engagement=minimum of 2/5 descent
45

4.Pawlik’s Grip
Objective-
 Identification what fetal part lies in the lower segment
( presentation) and its mobility
 A single examining hand is placed just above the
symphysis.
 The fetal part that overrides the symphysis is grasped
between the thumb and third finger.
 If the head is unengaged, it is readily recognized as a
round, hard object that frequently can be displaced
upward.
 After engagement, the back of the head or a shoulder
is felt as a relatively fixed, knoblike part.
 In breech presentations, the irregular, nodular breech
is felt in direct continuity with the fetal back
46

 Abdominal Findings In Multiple Gestation
–multiple fetal poles
–2 FHRs at 2 sites , a difference of > 10 bpm,
FHR auscultated simultaneously by two
examiners i.e for twin pregnancy
47

PE- GUS
Inspection
• Look for Normal development of the external genitals
(The Vulva)
– Mons pubis (Veneris), Labia majora and minora, urethra, Skene
(paraurethral) Glands,Vestibule, Bartholins (Great vestibular)
glands, The Hymen, Fossa Navicularis
• Hair distribution-
– Normal findings
• Inverted triangle pattern with a base over the Mons Pubis.
• The labia majora are also covered
– Extension of hair to the abdomen is abnormal for females
( Hirsutism)
• Look for skin lesions ( warts), discharge (vaginal or
urethral),Scars, Swelling and Prolapse ( descent with or
without exertion)
48

Speculum Examination
• Speculum Types
–Bivalved ( Pederson’s, Cusco’s, Grave’s)
–Univalved (Sims ,Auvard)
49

Grave’s Speculum
Sims Speculum
Cusco’s Speculum 50

 Speculum Examination
• Position; dorso lithotomy
• Warm and lubricate the speculum (clean
speculum for most gynecologic examinations)
• Insert the speculum with the transverse
diameter of the blades anteroposteriorly and
guide the blades through the introitus in a
downward motion with the tips pointing toward
the rectum
• Then turn the blades so that their transverse axis
is along with the transverse axis of the vagina
• Open the blades after full length insertion of the
speculum the cervix should be visible b/n the
blades
51

Speculum Examination
 Inspect the vagina and Cervix
• Vagina
– Discharge , inflammation (erythema), Mass (e.g
Gartner's cyst)
• Cervix
– External OS ( shape, discharge from), SCJ, Nabothian
cysts, Lesions (polyp, ulceration, nodularity,
inflammation), bleeding
– Cervical Ca screening ( Cytology via Pap smear or visual
methods via VIA / VILA) can be performed if indicated
and possible.
– Discharge specimen is taken for wet mount and KOH test
52

Pelvic Examination
Bimanual Examination
• Palpation of the uterus and the adnexa.
• Gloved and lubricated index and middle fingers of the
dominant hand are inserted deeply into the vagina so
that they rest beneath the cervix in the posterior
fornix.
• The opposite hand is placed on the patient's abdomen
above the pubic symphysis.
• The flat of the fingers are used for palpation.
• The vaginal hand then elevates the uterus by
pressing up on the cervix and delivering the uterus to
the abdominal hand so that the uterus may be placed
between the two hands,
53

• Both adnexa are also examined in the same
way through the lateral fornices
• Bimanual Examination helps identify
– Position ( often anteverted and anteflexed) , size,
shape, consistency, and mobility of the uterus
– Whether the adnexa are papable or not
– The presence or absence of uterine or adnexal
masses
54

Bimanual examination of the Uterus
Bimanual examination of the
Adnexa
55

Notice the following while performing Bimanual
Exam
ሀ .Cervix
• Excitation / motion tenderness
– Move the cervix gently to each side with one finger.
– Pain points at a tuboovarian mass (ectopic, abscess)
or inflammation.
• Consistency
– A normal cervix is firm (tip of nose) but not hard,
– In pregnancy it is softer with a firmer core.
– In cervical cancer the cervix can be hard, broad, with
an irregular surface.
56

ለ.Uterus
• Axis/ position
– Anteverted--anteflexed (most common), retroverted or
straight
• Size
– Enlarged size pregnancy, leiomyoma, sarcoma etc
– A large tubo-ovarian mass can be mistaken for an
enlarged uterus.
– Uterine mass moves with the cervix but not adnexal
masses
• Consistency
– Normally firm , A gravid uterus is soft, uterine fibroids are
hard or at least firm; advanced uterine or cervical
malignancy is often hard but endometrium carcinoma
can present as a soft enlarged uterus as well.
57

ሐ.Adnexa
• Mass
– Ovaries normally impalpable unless the woman is too slim
– Normal tubes are impalpable too even in slim women
– Adnexal masses can arise from ovarian cysts, solid benign
tumors, ovarian malignancy, hydrosalpinx, ectopic
pregnancy, tubo-ovarian abscess or rarely tubal
malignancy.
• Tenderness
– pain in the adnexa can point to adnexitis or PID (most
often bilateral), ectopic pregnancy (unilateral) or ovarian
cysts or hydrosalpinx (uni- or bilateral).
• Mobility
– benign ovarian tumors such as a dermoid or ovarian cysts
can be freely moved
– TOA in frozen pelvis, advanced malignant ovarian tumors
immobile
59

Rectovaginal examination
• The rectovaginal palpation is not necessary in
every patient
• Often done in cases when there is suspicion of
malignancy, endometriosis or any process located
in the pouch of Douglas.
• It helps to assess the structures between the
vagina and rectum.
– Eg Rectovaginal septum, Uterosacral ligaments
• Mass, thickening, tenderness of these structures
may be caused by malignancy, inflammation or
endometriosis
• Retroverted uterus can also be examined ( size,
shape, consistency) through the RV route
60

Rectal Examination
• In virgins, a vaginal examination is avoided.
• Instead a well-lubricated finger inserted into the
rectum can be used for a bimanual assessment of the
pelvic structures.
• Today, practically all gynecologists prefer ultrasonic
scanning to rectal examination, which, apart from
being unpleasant, is not that accurate.
• A rectal examination is a very useful additional
examination whenever there is any palpable pathology
in the pouch of Douglas.
• It often allows the ovaries to be more easily identified.
• In parametritis and endometriosis, the uterosacral
ligaments are often thickened, nodular and tender.
62

• It confirms the swelling to be anterior to the rectum,
and if the rectum is adherent to that swelling.
• This is important in case of carcinoma of the cervix to
determine the extent of its posterior spread.
• A rectal examination is mandatory in women having
rectal symptoms.
• This should begin by inspecting the anus in a good
light, when lesions like fissures, fistula-in-ano, polyps
and piles may come to light.
• Introduction of a well-lubricated proctoscope to
inspect the rectum and anal canal helps to complete
the examination.
• Ultrasound today has reduced the importance of rectal
examination except in cancer cervix and pelvic
endometriosis.
63

Fertilization,Implantation
and
Placental Development

Outline
• Follicular Development
• Menstrual Cycle
• Ovulation and fertilization

Follicular Development
• Follicular development begins with primordial follicles
that were generated during fetal life
• Primordial germ cells can be identified in the yolk sac
as early as the third week of gestation
• These cells begin their migration into the gonadal ridge
during the sixth week of gestation
• In the gonadal ridge the primordial cells undergo
successive mitotic divisions and produce the OOggonia
• Starting at 12 weeks’ gestation, a subset of oogonia will
enter meiosis –which is arrested at prophase I –and
become primary oocytes .
• primordial follicles are formed by surrounding Primary
oocytes are surrounded by a single layer of flattened
granulosa cells

Primordial Follicles
– 20th wk of GA- 6-7 million
– Birth- 1-2 million Primordial Follicles (additional
oocytes cannot be generated postnatally)
– Puberty ~ 400,000 (< 500 are ovulated)
– < 1,000 follicles at the onset of menopause
• Only 400 follicles are normally released during
female reproductive life.
 > 99.9 % of follicles undergo atresia through
apoptosis
• Rate of follicular atresia
– 1000Fs/month (until age 35)
– Faster rate at > 35yrs

• Primordial Follicle
 10 oocyte ( arrested at Prophase I)
surrounded by single layer of flat Granulosa
cells

Primary Follicle
 Change in G cells ( become
cuboidal, Increase in
number (pseudo stratified)
 Develop gap junction)
 oocyte secrets zona
pellucida ( acellular,
Glycoprotein)
 ZP1, ZP2,ZP3
 ZP3- recognized by receptors on
acrosome during fertilization
 ZP2- hardens the coat after
fertilization and prevent more
fertilization

Follicular dev’t
 20 Follicle
• final growth of 10
oocyte a further
increase in granulosa
cell number.
• The stroma
differentiates into the
theca interna and theca
externa, which abuts
the surrounding stroma

Follicular Dv’t-
Tertiary/Antral/ Giraffian follicles
• 1st meiosis is completed and 20 oocyte
arrested at Metaphase II
• Follcular Fluid collection b/n granulosa cells
(antral fluid)
– Coomulus oophurus- GC around the oocyte
– Mural GC- GC surrounding the antrum
• Meiosis II is completed during fertilization
after ovulation

• Stages From Recruitment of Primordian
follicle (from the resting pool) to preantral
stage are Gtropin Independent stages, but
beyond this stage FSH is required and the follicles
undergo atresia if no FSH
• Follicular atresia since the fetal age
• Late Luteal Phase- Small rise in FSH
semisynchronous growth of Cohort of Antral
follicles
• Dominant Follicle
– the one most responsive for FSH increased E
and InhibinB decline in FSH failure of other
follicles to reach the preovulatory stage

Spermatogenesis
• Takes place in the seminiferous tubules of
testes
• The germinal epithelium cells undergo
continuous mitosis and enter meiosis
• Maturation period of spermatozoa~ 70 days

Menstrual Cycle
Ovarian and Endometrial components
1. Ovarian Cycle- two phases
– Follicular phase (Preovulatory)
• From onset of menses to just before ovulation
• Time for recruitment of cohort follicles and growth
and maturation of the dominant follicle among the
cohort
– Luteal phase (Postovulatory)
• From ovulation till the next menses
• Corpus luteum formation, both granulosa and
luteal cells produce progesterone.
• Relatively constant duration (lasts app for 13- 14
days)

2. Endometrial cycle
• Proliferative Phase
– Corresponds to the follicular ovarian phase ( usually from 6th
to 14th day)
– Endometrial glandular cells proliferate, mainly under
estrogenic influence
– Tubular Glands and straight arterioles, edematous stroma
• Secretory Phase
– Correspond with luteal phase
– Glands become tortous and with subnuclear vacuoles that
secret glycogen rich material into the lumen
– Vessels become coiled
– Mainly due to influence of progestrone

Menstrual Cycle Characteristics
Menstrual Phases
Cycle Day 1–5 6–14 15–28
Ovarian phase Early follicular Follicular Luteal
Endometrial phase Menstrual Proliferative Secretory
Estrogen/Progeste
rone
Low levels Estrogen Progesterone

Ovulation and Fertilization
• Ovulation the process by which the oocyte
cumulus is released from the follicle
• The oocyte-cumulus complex is then picked/
engulfed immediately by infindibulum of the
oviduct and infundibulum.
• Further transport through the tube is
accomplished by directional movement of
cilia and Tubal Peristalsis.
• Ovulation is preceded by LH surge 18-36 hrs
ahead

Combined Obstetrics pdf notes for midwifery

• Union of sperm and egg takes place in the
fallopian tube( site of fertilization)
• Life span of egg ~ 24hrs and that of Sperm ~ 5
days
• Window of fertilization 3days per cycle
– i.e the day of ovulation and the 2 preceding days

• Spermatozoa matures in 72 days since onset of
spermatogenesis reaches caudal epididymis
and is ready for ejaculation
• During coitus sperm cells enter cervical mucus
and swim upwards to the uterine cavity and then
to Fallopian Tubes
• The cx mucus forms linear alignment parallel
strands that guide the sperms upward
• Sperm movement is also assisted by uterine
contraction

• The cervical mucus also serves as sperm
reservoir for ~ 72hrs and medium of
capacitation of the sperm.
• Capacitation- the process which makes the
sperm capable of penetrating the ova
– Occurs in the female genital tract ( Cx and FTs)
• Capacitation of the sperm results in;
1. The ability to undergo the acrosome reaction.
2. The ability to bind to the zona pellucida.
3. The acquisition of hypermotility.

• Fertlization involves highly complex steps of
molecular activities so that the spermatozoa
can
– Pass the cumulus cells and zona pelucida (thick
glycoprotein overlying the Oocyte cell membrane)
– Penetrate and end enter into the oocyte
cytoplasm and effect Fusion of the two nuclei.
• intermingling of maternal and paternal
chromosomes creates the zygote.

Steps in Fertilization
• Sperm passes through the cumulus ,binds to zona ligands
and Penetrates ZP
• Binding of sperm head receptors and zona ligands induces
Acrosome Reaction, releasing enzymes essential for the
fusion of the sperm and oocyte membranes.
• Following sperm and oocyte fusion the cortical reaction
leading To Zona Reaction hardens the ZP and prevent more
sperm penetration.
• The cortical reaction leads to the enzyme-induced:-
– zona reaction, the hardening of the zona and
– the inactivation of ligands for sperm receptors, producing an obstacle
to polyspermy.
• Cell division begins promptly after fertilization; human gene
expression begins between the 4- and 8-cell stages.

The Zygote
• The zygote—a diploid cell with 46 chromosomes
which results from fertilization
• The zygote undergoes slow cleavage for 3 days in the
Fallopian Tubes
• The cells produced by this division are called
Blastomeres.
• As the blastomeres continue to divide, a solid
mulberry-like ball of cells— the Morula —is produced.
• The morula enters the uterine cavity about 3 days after
fertilization
• Gradual accumulation of fluid between the morula
cells leads to formation of the early blastocyst.
Zygote blastomers morula blastocyst

The Blastocyst
• Around 4 to 5 days after fertilization, the
blastocyst has 58-cells , of which ;
– 5 cells form the inner cell mass i.e, differentiate
Embryo-producing Cells.
– 53 cells comprise the outer cells called
trophectoderm destined to form Trophoblast.
• The blastocyst is released (Hatched) from the
surrounding ZP at around the 6th day after
fertilization
• Hatching is important step for the occurrence
of implantation

Blastocyst Implantation
• 6 or 7 days after fertilization, the embryo implants
in the uterine wall.
• uterine receptivity is limited to days 20 to 24 of
the cycle window of implantation
The Implantation process has 3 phases:
1. Apposition— initial contact of the blastocyst to
the uterine wall;
2. Adhesion— increased physical contact between
the blastocyst and uterine epithelium; and
3. Invasion— penetration and invasion of
syncytiotrophoblast and cytotrophoblasts into
the endometrium, inner third of the
myometrium, and uterine vasculature.

Implantation
• After gentle erosion between epithelial cells of
the surface endometrium, invading trophoblasts
burrow deeper.
• By the 10th day, the blastocyst becomes totally
encased within the endometrium.
• The mechanisms leading to Trophoblast invasion
are similar to those of metastasizing malignant
cells

Implantation
• Embryonic mesenchyme first appears as isolated
cells within the blastocyst cavity.
• When the cavity is completely lined with this
mesoderm, it is termed the chorionic vesicle, and
its membrane, now called the chorion, is
composed of trophoblasts and mesenchyme.
• Some mesenchymal cells eventually will
condense to form the body stalk.
• This stalk joins the embryo to the nutrient
chorion and later develops into the umbilical
cord.
• The body stalk can be recognized at an early stage
at the caudal end of the embryonic disc

Implantation
The Decidua;
• specialized endometrium of pregnancy
• Decidua Basalis:-directly beneath the
implanting blastocyst- 3 layers Compact,
spongy and basal
• Decidua Capsularis covers the upper
portion of the blastocyst.
• Decidua Parietalis the rest
• With obliteration of uterine cavity D. Capsularies and
D. Parietalis merge and form D. Vera

Trophoblasts
• Human placental formation begins with the
trophectoderm, which appears at the morula and
blastula stage.
• It gives rise to a Trophoblast cell layer encircling the
blastocyst.
• From then until term, the Trophoblast plays a critical
part at the fetal-maternal interface.
• Trophoblast exhibits the most variable structure,
function, and developmental pattern of all placental
components.
• Its invasiveness promotes implantation, its nutritional
role for the conceptus is reflected in its name, and
• its endocrine organ function is essential to maternal
physiological adaptations and to pregnancy
maintenance.

Trophoblasts
• By the 8th day post-fertilization, after initial
implantation, the Trophoblast has differentiated
into;
1. Syncytiotrophoblast - an outer multinucleated
primitive syncytium;
– has an amorphous cytoplasm without cell borders,
multiple nuclei that are diverse in size and shape,
and a continuous syncytial lining.
– This configuration aids transport.
2. Cytotrophoblast- an inner layer of primitive
mononuclear cells— are germinal cells for the
syncytium.
– Contrary to syncytiotrophoblast ,each cytotrophoblast
has a well-demarcated cell border, a single nucleus,
and ability to undergo DNA synthesis and mitosis

Trophoblasts
• Trophoblasts further differentiate into Villous
and extravillous
A. Villous Trophoblasts– gives rise to the
chorionic villi, feto-maternal exchange of
gases, nutrients, and other compounds
B. Extravillous trophoblasts – two types
I. Interstitial trophoblasts invade the decidua and
eventually penetrate the myometrium to form
placental bed giant cells and also surround spiral
arteries.
II. Endovascular trophoblasts- penetrate the spiral
artery lumens

Spiral Artery Invasion by Trophoblasts
• Invasion and extensive modification of spiral arteries is
carried out by extra vilous trophoblasts in the first
half of pregnancy
• It is an important action to facilitate UxP blood flow
• Interstitial trophoblasts prepare spiral arteries for
Endovascular trophoblast invasion
• Endovascular trophoblasts first enter the spiral-artery
lumens and initially form cellular plugs.
• They then destroy vascular endothelium via an
apoptosis mechanism and invade and modify the
vascular media.
• Thus, fibrinoid material replaces smooth muscle
• Invading endovascular trophoblasts can extend several
centimeters along the vessel lumen, and they must
migrate against arterial flow

Spiral Artery Invasion by Trophoblasts
• uteroplacental vessel development as Proceeds in two
waves or stages.
• The first wave occurs before 12 weeks’ postfertilization
and consists of invasion and modification of spiral
arteries up to the border between the decidua and
myometrium.
• The second wave is between 12 and 16 weeks and
involves some invasion of the intramyometrial
segments of spiral arteries.
• Remodeling converts narrow-lumen, muscular spiral
arteries into dilated, low-resistance uteroplacental
vessels.
• Failure of / defective vascular remodelling is implicated
with the pathogenesis of preeclampsia and fetal-
growth restriction

Lacunae Formation within the synctiotrophoblasts
• As the embryo enlarges, more maternal decidua
basalis is invaded by syncytiotrophoblast.
• Beginning approximately 12 days after conception,
the syncytiotrophoblast is permeated by a system of
intercommunicating channels called trophoblastic
lacunae.
• After invasion of superficial decidual capillary walls,
lacunae become filled with maternal blood
• At the same time, the decidual reaction intensifies
in the surrounding stroma.
• This is characterized by decidual stromal cell
enlargement and glycogen storage

Placental Organization- Chorionic Villi
Primary Villi
– Solid structures composed of a cytotrophoblast core
covered by syncytiotrophoblast
– Arise from Buds of cytotrophoblast protrude into
primitive sincytium Before 12 wks post fertilization
– The solid cytotrophoblastic columns partition the
complicated lbyrynth formed by fusion of lacunae
– The trophoblast-lined labyrinthine channels form the
intervillous space, and the solid cellular columns form
the primary villous stalks.
– The villi initially are located over the entire blastocyst
surface.
– They later disappear except over the most deeply
implanted portion, which is destined to form the
placenta.

Chorionic Villi
Secondary Villi
– Beginning at app 12th post fertilization day
– Formed by invasion of the solid trophoblast columns
with mesenchymal cords from the extraembryonic
mesoderm
Tertiary villi –
– formed Once angiogenesis begins in the
mesenchymal cores of the 20 villi
– By approximately the 17th day, fetal blood vessels are
functional, and a placental circulation is established.
• The fetal–placental microcirculation is completed
when the blood vessels of the embryo are
connected with chorionic vessels

Chorionic Villi
• Approximately 1 month after conception,
maternal blood enters the intervillous space in
fountain-like bursts from the spiral arteries.
• Blood is propelled outside of the maternal
vessels and sweeps over and directly bathes
the syncytiotrophoblast.
• The apical surface of the syncytiotrophoblast
consists of a complex microvillous structure
that undergoes continual shedding and
reformation during pregnancy

Chorionic Villi
• Anchoring villi- trophoblastic cell columns
formed by Cytotrophoblast proliferation at the
villous tips and they are anchored to the
decidua at the basal plate.
• Thus, the base of the intervillous space faces
the maternal side and consists of
cytotrophoblasts from cell columns, the
covering shell of syncytiotrophoblast, and
maternal decidua of the basal plate.
• The base of the chorionic plate forms the roof
of the intervillous space.

Chorionic Villi
• It consists of two layers of trophoblasts
externally and fibrous mesoderm internally.
• The “definitive” chorionic plate is formed
• The “definitive” chorionic plate is formed by 8
to 10 weeks as the amnionic and primary
chorionic plate mesenchyme fuse together.
• This formation is accomplished by expansion
of the amnionic sac, which also surrounds the
connective stalk and the allantois and joins
these structures to form the umbilical cord

Chorionic Villi
• Most villi arborize and end freely within the
intervillous space.
• As gestation proceeds, the short, thick, early
stem villi branch to form progressively finer
subdivisions and greater numbers of
increasingly smaller villi.
• Each of the truncal or main stem villi and their
ramifications (rami) constitutes a placental
lobule, or cotyledon.
• Lobules are functional units of placental
architecture

Placental Growth
• In the first trimester, placental growth is more
rapid than that of the fetus.
• By approximately 17 postmenstrual weeks,
placental and fetal weights are approximately
equal.
• By term, placental weight is approximately one
sixth of fetal weight.
• At term, the “typical” placenta weighs 470 g, is
round to oval with a 22-cm diameter, and has a
central thickness of 2.5 cm
• It is composed of a placental disc, extraplacental
membranes, and three-vessel umbilical cord.

Placental growth
Placental Lobes
• slightly elevated convex areas, from the maternal
surface,
• They are incompletely separated by grooves of
variable depth that overlie placental septa, which
arise from folding of the basal plate.
• Their number varies from 10 to 38.
• The total number of placental lobes remains the
same throughout gestation, and individual lobes
continue to grow— although less actively in the
final weeks
• Lobes are not cotyledons (cotyledons lobules)

Placental Maturation
• As villi continue to branch and the terminal
ramifications become more numerous and
smaller, the volume and prominence of
cytotrophoblasts decrease.
• As the syncytium thins, the fetal vessels become
more prominent and lie closer to the surface.
• The villous stroma also exhibits changes as
gestation progresses.
• In early pregnancy, the branching connective-
tissue cells are separated by an abundant loose
intercellular matrix.
• Later, the villous stroma becomes denser, and the
cells more spindly and more closely packed..

Placental Maturation
• Another change in the stroma involves the
infiltration of fetal macrophages called
Hofbauer cells
• Increase in number and maturational state
throughout pregnancy and appear to be
important mediators of protection at the
maternal-fetal interface.

Dx of pregnancy
 Sign and Symptom of pregnancy may
appear as early as 6 weeks
 Manifestations of pregnancy may be:-
–PRESUMPTIVE,
–PROBABLE
–POSITIVE

Dx of pregnancy
1. Presumptive symptoms
– Amenorrhea,
– Nausea and vomiting
– Breast changes
• tenderness ,enlargement, colostrum
• Montgomery Tubercles
• 2⁰ breasts prominence
– Quickening(18 -20 wks primis, 16- 18wk multis)
– Frequency+ nocturia ( bladder irritation)
– UTI ( bacteruria in preg. woman ~7% vs 3% in non-
preg)*
*Bacteruria may be asymptomatic but leads to serious complications
(pyelonephritis, which is associated with miscarriage, preterm birth,
and intrauterine fetal demise) if left untreated

Dx of pregnancy
Presumptive Signs
Skin changes
• Chloasma ( mask of pregnancy),
– is darkening of the skin over the forehead, bridge of the
nose, or cheekbones .
– It usually occurs after 16 weeks' gestation and is
intensified by exposure to sunlight.
• Linea Nigra
– is darkening of the nipples and lower midline of the
abdomen from the umbilicus to the pubis (darkening of
the linea alba)
– due to stimulation of the melanophores by an
increase in melanocyte SH.

Presumptive signs- contd.
• Stretch Marks
– striae of the breast and abdomen are caused by
separation of the underlying collagen tissue and
appear as irregular scars.
– This is probably an adrenocorticosteroid response.
– These marks generally appear later in pregnancy
when the skin is under greater tension.
• Spider Telangiectases
– are common skin lesions that result from high levels
of circulating estrogen.
– These vascular stellate marks blanch when
compressed.
– Palmar erythema is often an associated sign.
– Both of these signs are also seen in patients with
liver failure.

2.Probable Manifestations
Probable Symptoms are the same as the Presumptive
ones, above.
Probable Signs (Pelvic organ changes)
 Chadwick’s sign:-
Congestion of the pelvic vasculature causes bluish or
purplish discoloration of the vagina and cervix.
 Leukorrhea
 Hegar’s sign
this is widening of the softened area of the isthmus,
resulting in compressibility of the isthmus on
bimanual examination. This occurs by 6–8 weeks.
 Relaxation of pelvic joints(pronounced on SP)

2.Probable Manifestations…..
Abdominal Enlargement
 There is progressive abdominal enlargement
from 7–28 weeks.
 At 16–22 weeks, growth may appear more rapid
as the uterus rises out of the pelvis and into the
abdomen
Painless uterine contractions (Braxton Hicks
contractions)
 are felt as tightening or pressure usually
disappear with walking or exercise.
 They usually begin at about 28 weeks' gestation
and increase in regularity.

3.Pregnancy – Positive manifestations
 The various signs and symptoms of pregnancy are
often reliable, but none is diagnostic.
 A positive diagnosis must be made on objective
findings, many of which are not produced until after
the first trimester.
 However, more methods are becoming available to
diagnose pregnancy at an early stage. These are:-
• Fetal Heart Tones (FHTs); detected by:-
– hand held Doppler as early as 10 weeks' and
– fetoscope at 18–20 weeks'.
– The normal fetal heart rate is 120–160 bpm.
• Palpation of Fetus:
– Fetal outline after 22 wks
– Fetal movement after 18 wks

Positive manifestations-US
• A Gestational Sac—the first sonographic
evidence of pregnancy;
– a small anechoic fluid collection within the
endometrial cavity – seen by TVUS at 4 to 5 Wks GA.
• A normal GS implants eccentrically in the
endometrium, whereas a pseudosac is seen in
the midline of the endometrial cavity.
• Other potential indicators of early intrauterine
pregnancy are:-
• The Intradecidual Sign;
– an anechoic center surrounded by a single echogenic
rim or of GA within 4 days.

Others +ve US findings of px dx……
• Double Decidual Sign
– two concentric echogenic rings surrounding the
gestational sac ( D. parietalis and D .Capsularies)
• yolk sac
– a brightly echogenic ring with an anechoic center and
can normally be seen by the middle of the 5th week.
– confirms with certainty an Iux pregnancy.
• Embryo
– is seen after 6 weeks, an as a linear structure
immediately adjacent to the yolk sac, and cardiac
motion is typically noted at this point.
• Up to 12 weeks’ gestation, the CRL is predictive

• Ultrasound Examination of Fetus
– Cardiac activity- -----------------5-6 wks
– limb buds- ------------------------7-8wks
– Fingers & limbs mov’t----- ----9-10 wk
– Human appearance after--- -10 wk

• pregnancy of unknown location
–equivocal Sonography finding
–With PUL -serial serum hCG levels can help
differentiate a normal intrauterine
pregnancy from an extrauterine pregnancy
or an early miscarriage

Pregnancy-positive manifestations……..
Urine Pregnancy Test (the level of hCG detection ranging
between 5 and 50 mIU/mL, depending on the kit used.)
 Home Pregnancy tests first voided morning urine (low
sensitivity)
Serum Pregnancy test: hCG can be detected in the serum as
early as a week after conception.
 The serum pregnancy test can be quantitative or
qualitative with a threshold as low as 2–4 mIU/mL,
depending on the technique used.
 The serum pregnancy test is a reliable method to
diagnose an early pregnancy; it is widely used in the
evaluation of threatened abortion, ectopic pregnancy,
and other conditions

Positive manifestations-contd.
Pregnancy Tests
• Sensitive, early pregnancy tests measure changes in
levels of B hCG.
• hCG is produced by the Syncytiotrophoblast 8 days
after fertilization and may be detected in the maternal
serum after implantation occurs, 10–11 days after
conception.
• hCG levels peak at approximately 10–12 weeks of
gestation.
• Levels gradually decrease in the second and third
trimesters and increase slightly after 34 weeks.
• The doubling time of hCG is 1.5 days.
• Normally, serum and urine hCG levels return to
nonpregnant values (<5mIU/mL) 21–24 days after
delivery.

hCG Tests
 Several Immunoassays
 Sandwitch Immunoassay’ – Immunometric assay- all comm assays
– Monoclonal Ab against B subunit
– 2 antibodies
– capture (1st)—bound and immobilize hCG
– tracer (2nd) – -lable the immobilized hCG by radioactive or Enzyme label
– hCG is sandwithced b/n Abs ( 1st on solid phase support, second added
subsequently)
 Amount of immobilized label measured proportional to the amount of
hCG in the sandwitch
 Enzyme linked
• 2nd Ab is E linked (e.g, ALPase)
• After 2nd Ab, E substrate is added, bind to E and color change is produced
– Intense color high E conc High amount of bound 2nd Ab High hCG
conc
– Can detect as low as 1miu/ml hCG

hCG tests-Home Pregnancy tests
• HPTs are Less accurate than advertisement
–Only 1 brand detected 95% of hCG +ves at
12mu/ml
–44% of brands +VE at 100Miu/ml
only 15% are dxed at time of missed
menses
Cole and ASS 2011

hCG Test….
• Although all assays detect regular hCG, they do
not necessarily detect all hCG variants .
• For example, many over-the-counter pregnancy
tests do not measure hyperglycosylated hCG,
which accounts for most of the total hCG at the
time of missed menses when these tests are
typically performed.
• At a minimum, testing for total hCG should detect
both regular and hyperglycosylated hCG.
• The hCG variants detected depends upon the
only commercial assay used;

HCG test……………
• the only commercial assay that detects all hCG
variants is the Siemen's Immulite Series.
• It is also important to know the sensitivity of the
test.
• Clinical tests for pregnancy may only detect total
hCG levels ≥20 mIU/mL.
• Therefore, when following hCG levels to negative
(<1 mIU/mL) in women with GTD, it is important
to use a sensitive hCG test that detects both
regular and hCG-H.
• Testing for pregnancy
– The clinical use of this test for diagnosis of pregnancy
(intrauterine or ectopic) is reviewed separately

False negative test - hook effect
• At levels of hCG > 500,000 mIU/mL, a "hook effect" can
occur resulting in an artifactually low value for hCG (ie,
1 to 100 mIU/mL)
• This is because the sensitivity of most hCG tests is set
to the pregnancy hCG range (ie, 27,300 to 233,000
mIU/mL at 8 to 11 weeks of gestation);
• therefore, when an extremely high hCG concentration
is present, both the capture and tracer antibodies used
in immunoradiometric assays become saturated,
• preventing the binding of the two to create a sandwich
• Since the nonsandwiched tracer antibodies are washed
away with the excess material, the test result will be
negative.
• For this reason, a suspected diagnosis of GTD must be
communicated to the laboratory so that the hCG assay
will also be performed at 1:1000 dilution.

False-positive hCG values
 “phantom hCG,” a false +ve serum hCG result due to nonspecific
heterophilic antibodies in the serum and this often results in
inappropriate intervention (chemorx, Hysterectomy).
– Seen in people who are close to animals
– Abs against Ags of animal origin bind to the animal derived
test abs
• These false-positive levels are usually low (10 mIU/mL) but have
been reported at levels > 300 mIU/mL.
• This situation should be suspected when hCG levels plateau at a low
concentration and do not respond to further therapeutic attempts,
such as methotrexate for a persistent EP or molar gest.
• Since the H Abs are not secreted in the urine, one should measure a
urinary hCG level if suspicious.
• Also, a serial dilution of the patient’s serum can be performed, as
the false-positive test is not affected by the dilution

How to exclude Phantom hCG?
• Urinary test –VE
– Hetrophilic Abs are not excreted by the kidney
• Serial dilution of serum sample
– True hCG conc. decreases with dilution while that
of the phantom is not affected
• Alternate assay which blocks hetrophilic Abs

False hCG +VES
• Exogenous hCG-Injection for wt loss
• Tumors like;
– GI, Ovary, Bladder, Lung
– hCG may hve angiogenic role for the tumors
• Renal Failure;impaired clearance
• Physiologic Pituitary hCG
– One possible explanation is that a small amount of hCG
is produced along LH because the single LH beta-subunit
gene is buried among the seven back-to-back hCG beta-
subunit gene
– Usually 1-32mu/ml
– Pituitary production of hCG is most notable around the
time of menopause (natural or surgical) and prior to
ovulation, which are times when LH levels peak

Reproductive Tract
Uterus
• Nonpregnant uterine weight ~ 70 gm, and is
almost solid, except for a cavity of 10 mL or less.
• At term ~1110gm and total volume of ~5L ( can
be > 20Lt)
• During pregnancy, the uterus is transformed into
a relatively thin-walled muscular organ of
sufficient capacity to accommodate the fetus,
placenta, and amnionic fluid.
• By the end of pregnancy, the uterus has achieved
a capacity that is 500 to 1000 times greater than
in the nonpregnant state.

Reproductive Tract
Cervix
• As early as 1 month after conception, the cervix
begins to undergo pronounced softening and
cyanosis.
• These changes result from increased vascularity
and edema of the entire cervix, together with
hypertrophy and hyperplasia of the cervical
glands
• Proliferation of the cervical glands results in
Eversion extension onto the ectocervix
• The endocervical mucosal cells produce copious
tenacious mucus that obstruct the cervical canal
soon after conception Mucus Plug of the cervix

Reproductive Tract
Vagina
• Increased vascularity prominently affects the
vagina and results in the violet color
characteristic of Chadwick sign.
• The vaginal walls undergo striking changes in
preparation for the distention that
accompanies labor and delivery.
• These changes include a considerable increase
in mucosal thickness, loosening of the
connective tissue, and smooth muscle cell
hypertrophy.

Breast
• Tenderness and paresthesia in early weeks of
pregnancy.
• After the second month,
– the breasts increase in size, and delicate veins
become visible just beneath the skin.
– The nipples become considerably larger, more
deeply pigmented, and more erectile,
– a thick, yellowish fluid—colostrum—can often be
expressed from the nipples by gentle massage.
– the areolae become broader and more deeply
pigmented and glands of Montgomery
(hypertrophic sebaceous glands) are seen
scattered

Cardiovascular System
Anatomic Changes
• With uterine enlargement and diaphragmatic
elevation, the heart rotates on its long axis in a
left-upward displacement.
• the apical beat (point of maximum intensity)
shifts upwards and laterally.
• Overall, the heart size increases by about 12%,
which results from both an increase in myocardial
mass and intracardiac volume (approximately 80
mL).
• Vascular changes include hypertrophy of smooth
muscle and a reduction in collagen content.

 Plasma Volume
• 50% elevation in volume 20
to increased water and
Na+ retention
• ↑ Estrogen stimulates the
renin-Angiotensin syste
• This hypervolemia of
pregnancy compensates
for maternal blood loss at
delivery
 RBC Mass
• a 30% increase in red cell
mass

 Stroke volume
• increases 25–30% during
pregnancy, reaching peak
values at 12–24 weeks'
gestation
 Heart Rate
• ↑es progressively and at term
it is ~ 10-15bpm above the
non pregnant value
 Cardiac output
increases approximately 40%
during pregnancy, with
maximum values achieved at 20–
24 weeks GA.

Supine Hypotension
CO in pregnant woman
• highest in Lateral recumbent and Knee-
chest positions
• Lowest in in standing (↓by ~20%) and
supine (↓by 10-30%) positions
decreased blood return to heart--↓CO
• The finding of a decreased CO in the
standing position may give a physiologic
basis for the observation of decreased
birth weight and placental infarctions in
working women who stand for prolonged
periods.

Supine Hypotension
• Compression of IVC by gravid UX (Not seen
before 24 wks)  blood return from lower
body part only through paravertebral
collateral circulation
• Not manifest in most women b/se of
compensatory↑ SVR
• ~ 5-10% gravid women develop SH and
become symptomatic with
– increased HR and
– Decreased Bp
– dizziness,
– lightheadedness,
– nausea, and even syncope.

Peripheral Vascular Resistance (PVR)
 PVR decreases in the first trimester, reaching a
nadir of about 34% below nonpregnancy levels by
14 to 20 weeks of gestation with a slight increase
toward term.
• Likely triggered by hormonal changes of
pregnancy that enhance local vasodilators, such
as nitric oxide, prostacyclin, and possibly
adenosine.

Pregnancy BP Changes
• Despite the large increase in CO, the
maternal BP is decreased until later in
pregnancy as a result of a decrease in SVR
that nadirs midpregnancy and is followed by
a gradual rise until term.

Pregnancy BP Changes
• ↓ from 8wk onfollowng the SVR declining pattern
– May drop immediately after conception mirroring the low
BP value of women at luteal phase
• Nadir at mid pregnancy and gradually rise to Prepreg
levels at term
• DBP and MAP ( 2DBp + SBP)/3 are affected 5-10%
all over decrease.
• SBP alter little
• BP measurement
– lowest in lateral recumbent position
– Superior arm recording is 10-12mmHg lower than that of
the inferior arm
– In clinic – sitting position,
• Kortkoff 5 ( when the sound disappears) used for the
DBP instead of K4( muffling- less noticable) which may
be used only when K5 is at 0.

Blood Flow Distribution
• Blood flow increases to UX, Kidney, Breast , skin and other organs
• THE UTERUS
– GA dependent and can be as high as 800ml/min4 times the
nonpregnant value.
– This results from the relatively low resistance in the
Uteroplacental circulation
• KIDNEYS
– RBF  approximately 400 mL/min above nonpregnant levels,
• BREASTS
– blood flow to the breasts increases app 200 mL/min
• BF to the skin also increases, particularly in the hands and feet.
• The increased skin blood flow helps dissipate heat produced by
metabolism in the mother and fetus.

Normal Changes that mimic Heart Disease
 Systolic ejection murmurs
– which result from increased CO and decreased blood viscosity, can be
detected in 90% or more gravidas.
– Thus, caution should be exercised in interpreting systolic murmurs in
pregnant women.
• The first heart sound may be split
– with increased loudness of both portions, and the third heart sound
may also be louder.
• Continuous murmurs or bruits
– may be heard at the left sternal edge, which arise from the internal
thoracic (mammary) artery
• ECG changes
– can include a 15- to 20-degree shift to the left in the electrical axis.
• Changes in ventricular repolarization can result in ST Segment depression
OR T-Wave flattening.
• However, pregnancy does not alter the amplitude and duration of the P
wave, QRS complex, or T wave.

Central Hemodynamic Changes in 10 Normal
Nulliparous Women Near-term and Postpartum
a Measured in lateral recumbent position.
b Changes significant unless NSC = no significant change.
COP = colloid osmotic pressure; PCWP = pulmonary capillary wedge pressure.

The Hematologic System
RBC mass and Fe Requirement
• The red cell mass expands by about 30%, or by
approximately 450 mL of erythrocytes for the average
pregnant woman.
• The enhanced erythropoiesis of pregnancy increases
utilization of iron, which can reach 6 to 7 mg per day in the
latter half of pregnancy.
WBC count
• The total blood leukocyte count increases during normal
pregnancy from a prepregnancy level of 4,300–4,500/L to
5000–12,000/L in the last trimester, although counts as high
as 16,000/L have been observed in the last trimester.
• Counts in the 20,000–25,000/L range can occur during labor.
• Cause-unknown

Platelete count
• Studies show slightly decreased average
platelet count during pregnancy to 213,000/μL
compared with 250,000/μL in nonpregnant
control women
• Causes of Thrombocytopenia
– partially hemodilutional effects.
– There likely also is increased platelet
consumption, leading to a greater proportion of
younger and therefore larger platelets

Cogulation Factors
• Circulating levels of several coagulation factors increase in
pregnancy.
• Fibrinogen (factor I) and factor VIII levels increase
markedly, whereas factors VII, IX, X, and XII increase to a
lesser extent.
• Plasma fibrinogen concentrations begin to increase from
nonpregnant levels (1.5–4.5 g/L) during the third month of
pregnancy and progressively rise by nearly 2-fold by late
pregnancy (4–6.5 g/L).
• The high estrogen levels of pregnancy may be involved in
the increased fibrinogen synthesis by the liver
• Fibrinolytic activity is depressed during pregnancy through
a poorly understood mechanism. Plasminogen
concentrations increase concomitantly with fibrinogen,
but there is still a net procoagulant effect of pregnancy

Pregnancy Resp. Changes
• Hyperemic mucosa prone to congestion
and bleeding + polyposis (Estrogen effect)
• Costocondral relaxation
• Subcoastal angle increase from 68 to 1030
• Transverse D ↑ by 2cm
• Chest circumference ↑ by 5-7cm
• Diaphragm level raises by 4cm
• D excursion increase by 1-2cm

Resp Changes
• RR- no change
• Tidal volume (TV)
– Increased 30% to 40%
– Amount of air inspired and expired with normal breath
• Total lung capacity (TLC)
– ↓ by ~ 5% ( bse of D elevation)
– Total amount of air in lungs at maximal inspiration
(VC + RV)
• Expiratory reserve volume (ERV)
– ↓ 15% to 20%
– Maximum amount of air that can be expired from resting
expiratory level
• Residual volume (RV)
– ↓ 20% to 25%
– Amount of air in lungs after maximum expiration

Resp Changes
• FRC
– ↓ by 20% ( ERV + RV); bcz. of D elevation
– V of air in lungs at the end of quite exhalation
• Inspiratory capacity
– ↑ by 5-10% ( bse of low FRC)
– the maximum V of air that can be inhaled
• Vital capacity
– Nochange
– Maximum amount of air that can be forcibly expired after
maximum inspiration (IC + ERV)
• Inspiratory reserve volume (IRV)
– Unchanged
– Maximum amount of air that can be inspired at end of
normal Inspiration

Resp Changes
INCREASE DECREASE UNCHANGED
TV TLC RR
IC ERV VC
RV IRV
FRC

GI system
Anatomic Changes
• As the uterus grows, the stomach is pushed
upward and the large and small bowels extend
into more rostrolateral regions.
• The appendix is displaced superiorly in the
right flank area (clinical importance in the dx.
of appendicitis)
• These organs return to their normal positions
in the early puerperium.

GI system
Oral Cavity
• Salivation appears to increase although this
may be caused in part by swallowing difficulty
associated with nausea.

GI system
• Pregnancy gingivitis :
– the gums may become hyperemic and softened
and may bleed when mildly traumatized, as with a
toothbrush  typically subsides postpartum.
• Epulis gravidarum
– a focal, highly vascular swelling of the gums
– a pyogenic granuloma that occasionally develops
but typically regresses spontaneously after
delivery.
• Most evidence indicates that pregnancy does
not incite tooth decay

GI system
• Pyrosis (heartburn)
• is common during pregnancy and is most likely
caused by reflux of acidic secretions into the
lower esophagus 20 to:
– decreased lower esophagus sphincter tone and
possibly the altered stomach position.
– In addition, intraesophageal pressures are lower
and intragastric pressures higher in pregnant
women.

GI system
Gastric emptying time
• appears to be unchanged during each trimester
and compared with nonpregnant women
• During labor, however, and especially after
administration of analgesic agents, gastric
emptying time may be appreciably prolonged.
As a result, one danger of general anesthesia for
delivery is regurgitation and aspiration of either food-
laden or highly acidic gastric contents
Hemorrhoids
• are common during pregnancy
• They are caused in large measure by constipation
and elevated pressure in veins below the level of
the enlarged uterus.

GI system….
Gall Bladder
• During normal pregnancy, gallbladder contractility
is reduced (impaired by progesterone) and leads
to increased residual volume
• cholesterol gallstones in multiparas bse of;
– Impaired emptying & subsequent stasis, and
– an increased bile cholesterol saturation of
pregnancy.
• Pregnancy has the potential to cause intrahepatic
cholestasis and pruritus gravidarum from retained
bile salts.
• Intrahepatic cholestasis bcse of;
– high circulating levels of estrogen , which inhibit
intraductal bile acid transport

GI system…..
Liver
• there is no increase in liver size nor distinct morphological/
histological changes in normal pregnancy
• Hepatic arterial and portal venous blood flow, however,
increase substantively
• Lab test changes
– ALP level almost doubles ( much of the this increase is
attributed to the heat stable placental ALP isozymes)
– Serum AST,ALT, GGT, and bilirubin levels are slightly lower
compared with nonpregnant values
– The serum albumin concentration decreases during Px.
– By late pregnancy, albumin concentrations may be near
3.0 g/dL compared with approximately 4.3 g/dL in
nonpregnant women

Urinary System
• Kidney size increases approximately 1.5 cm
• The renal calyces and pelves are dilated
• The ureters are dilated above the brim of the bony
pelvis, with more prominent effects on the right (Ux
dextro rotation effect)– RF for urinary stasis and UTI.
• Both GFR and renal plasma flow (RPF) increase early in
pregnancy.
• The GFR increases as much as 25% by the 2nd wk after
conception and 50% by the beginning of the 2nd TMx.
• RPF increases by approximately 80 % before the end of
the 1st trimester
• Progesterone and relaxin may be involved in lowering
renal vascular resistance

Urinary Tract
Renal Function Tests
• Serum creatinine levels decrease during
normal pregnancy from a mean of 0.7 to 0.5
mg/dL.
• Values of > 0.9 mg/dL or greater suggest
underlying renal disease and should prompt
further evaluation.
• Creatinine clearance in pregnancy averages
30 % higher than the 100 to 115 mL/min in
nonpregnant women
– This is a useful test to estimate renal function

Urinary System
Urinalysis
• Glucosuria
– during pregnancy may not be abnormal.
– The appreciable increase in GFR, together with
impaired tubular reabsorptive capacity for filtered
glucose, accounts for most cases of Glucosuria
• For these reasons alone, about a sixth of
pregnant women should spill glucose in the urine.
• However, when Glucosuria is identified, the
possibility of diabetes mellitus should not be
ignored.

Urinary System
• Hematuria
– is often the result of contamination during collection.
– If not, it most often suggests urinary tract disease.
– is common after difficult labor and delivery because of
trauma to the bladder and urethra
• Proteinuria
– significant proteinuria during pregnancy is usually defined
as a protein excretion rate of at least 300 mg/day
• The three most commonly employed approaches for assessing
proteinuria are
– the qualitative classic dipstick,
– the quantitative 24-hour collection, and
– the albumin/creatinine or protein/creatinine ratio of a
single voided urine specimen

ANTENATAL CARE (ANC)
• ANC is the care given to a pregnant women
with the aim of improving the maternal and
perinatal outcome.
• Ultimate goal of ANC is the delivery of a
healthy baby without impairing the health of
the mother
• ANC is provided by organized health care
services

ANC – The traditional Approach
• Began in the early 1900’s
• Care is given based on risk assessment and
frequent visits.
• Based on initial Risk Assessment women are
labeled as either Low Risk ( at no risk ) or High Risk
• However this approach was shown to be ineffective in
predicting and preventing pregnancy complications
– E.g APH, Hypertensive disorders , obstructed labor,
infections can develop later in pregnancy or during
labor and delivery in both high and low risk women.

ANC-The traditional Approach
• women required to have several visits
• First visit preferably following the first missed
period followed by:
– every four-week until the 28 WKs of GA ( 6 visits)
– every fortnight from the 28 - 36 weeks of GA
– weekly, or more frequently if indicated, 36
weeks onwards

Focused ANC
• A new approach Recommended by WHO
(2002)
• Being implemented in Ethiopia
• Emphasizes the quality of care rather
than the quantity.

ANC-NUMBER AND FREQUENCY OF VISITS
• Women who came late in pregnancy ( at any
GA after the 16th week)for the first time will
get all the services required for first visit as
well as services appropriate for her gestational
age.
• Women are also advised for visiting the health
institution anytime if they have complaints or
problems.

Focused ANC
• Women are put on either the basic (routine)
or specialized care programs on the first visit
• A classifying check list is used for this purpose
• A woman with any of the conditions (risks) in
the list deserve specialized care while those
with none of these conditions are eligible for
the basic/ routine follow up.
• Pregnant women with identified risks will be
enrolled in specialized care , number and
frequency of visits depend on their specific
problem.

SAMUEL BEZABIH (MD) MEGABIT 2005
GUH

THE CLASSIFYING CHECK LIST
Obstetric History
• Previous stillbirth or neonatal loss?
• History of 3 or more consecutive spontaneous
abortions?
• Birth weight of last baby < 2500g or >400gm.
• Last pregnancy: hospital admission for PE/ HTN
/eclampsia?
• RT surgery?(Myomectomy, fistula repair, cone
biopsy, CS, repaired rapture, CX. Circlage, septum
removal..)

CURRENT PREGNANCY
• Multiple pregnancy
• Age less than 16 years? or more than 40
years?
• Isoimmunization Rh (-) in current or in
previous pregnancy
• Vaginal bleeding
• Pelvic mass
• Diastolic BP 90mm Hg or more at booking

GENERAL MEDICAL CONDITION
• Diabetes mellitus
• Renal disease
• Cardiac disease
• Chronic Hypertension
• Known 'substance' abuse (including heavy
alcohol drinking, Smoking)
• Any other severe medical disease or condition
TB, HIV, Ca, DVT..

Focused ANC-
• For normal pregnancies WHO
recommends only four antenatal visits
(Routine ANC).
–1st visit – before 16 weeks
–2nd visit- 24- 28 wks of gestation
–3rd visit- 30-32
–4th visit – 36-38

Objectives of Focused ANC
The major goal of focused antenatal care
is to help women maintain normal
pregnancies through:
1. Health promotion and disease prevention*
2. Early detection and treatment of
complications and existing diseases**
3. Birth preparedness and complication
readiness planning.

1. Health Promotion and Disease Prevention
 Counseling is offered on such issues as :
– Recognition of danger signs, what to do, and
where to get help
– Voluntary counseling and testing for HIV
– The benefit of skilled attendance at birth
– Breastfeeding
– Good nutrition and the importance of rest
– Risks of using tobacco, alcohol, local stimulants,
and traditional remedies
– Hygiene and infection prevention
– Birth spacing

Cont…
Interventions (care provision)
–Immunization against tetanus
–Iron and folate supplementation.
–Malaria protection- insecticide-treated bed
net
–PMTCT of HIV
–Protection against iodine deficiency
–Prevention of intestinal parasites.
–Establishing access to family planning

2.Early Detection And Treatment Of Complications
And Existing Diseases*
• The woman is examined and evaluated for
pre-existing or new health conditions that:
– May affect the outcome of pregnancy,
– Require immediate treatment
– Or require a more intensive level of monitoring
and follow-up care over the course of pregnancy.
*Eg. Anemia, STI,UTI, intestinal parasites,
cardiac disease, malnutrition, TB v. Etc

3.Birth Preparedness and Complication
Readiness
• Approximately 15% of women will develop a life-
threatening complication.(E.g, Vaginal bleeding)
• So, every woman and her family should have a
plan for the following:
– A skilled attendant at birth
– The place of birth and how to get there including how
to access emergency transportation if needed.
– Items needed for the birth
– Money saved to pay for transportation, the skilled
provider and for any needed medications and supplies
that may not been provided for free
– Support during and after the birth (e.G., Family,
friends)
– Potential blood donors in case of emergency

1. ANC 1st visit
• Should be before the end of the 4th month (16 week)
• To establish diagnosis of pregnancy, estimation of GA.
• To ascertain risk factors, and asses medical status of
the mother.
• To determine eligibility for routine / basic component
or the need for specialized care and referral
• To provide health promotional services (such as
education on nutrition supplements, danger signs of
pregnancy, labor, STI &, breast feeding)
• To initiates preventive measures (such as
immunizations, iron supplementation, malaria
prophylaxis and control of mother to child transmission
of HIV)
• Develop individualized birth plan.

ANC-The first visit
History
1. History of Present Pregnancy
• Name, age, address, religion, education, gravidity,
parity, abortion.
• Current pregnancy: planned/unplanned,
wanted/unwanted, supported/unsupported.
• Assessment of gestational age
– Last Normal Menstrual Period (LNMP), regularity of
menses, and use of contraception , EDD (LMP + 280 days).
– Quickening
– Symptoms & signs of pregnancy (if early gestation)
• vaginal discharge / bleeding
• Any complaints / concerns

ANC 1st ,HX…….
2.Past Ob. history
• Multiple gestation, Preterm / Post term birth,
Congenital anomalies
• Still birth/Early neonatal death (ENND) ,Abortions
and ectopic pregnancy
• Med. and surgical problems
• APH / PPH
• Hypertension / Eclampsia, SGA/LGA, IUGR,
operative deliveries
• History of female genital cutting
• Sepsis, STDs, other infections
GUH

ANC 1st ,HX…….
3.Social, Family History
• Family history of DM, HPN, multiple gestation,
Congenital abnormality
• Personal and family history
• Social status & support
• Habits of smoking, alcohol abuse or drug use
GUH

ANC -First Visit
4.Medical history
• Specific diseases and conditions: DM, renal
disease, cardiac disease, chronic hypertension, TB
, past history of HIV – related illnesses and
HAART, varicose veins, DVT, allergies other
specific conditions depending on prevalence in
service area (for example, hepatitis, malaria)
• Operations other than caesarean section
• Blood transfusions. Rhesus (D) antibodies
• Current use of medicines – specify, any
medications

ANC First visit
General Physical Examination
• General appearance,
• vital signs
• Height and weight
• Clinical signs of anemia, icterus and edema
• Systemic examination
• Signs of physical abuse

ANC First visit
Obstetric Examination
 Inspection:
– Abdominal distention & Symmetry,
– Streia, Dilated veins,
– Fetal movement, any old scars
 Palpation (Leopold’s maneuver)
– Uterine size:-Symphysis Fundal Height (SFH) with tape measure
or finger approximation.
– Fetal lie, presentation, attitude and engagement
 Auscultation: Fetal heart rate
 Pelvic assessment
– speculum examination as indicated look for:-
• vulvar ulcer, vaginal discharge, scratch marks, pelvic
mass, cervical lesion and estimate uterine size in first
trimester,
• genital malformation, severe FGM.

ANC first visit
Laboratory Tests
– Urinalysis ( dipstick for proteinuria, bacteruria)
– Blood group + Rh
– Hemoglobin/Hematocrit
– Syphilis test ( RPR, VDRL)
– HIV test ( if the woman doesn’t say 'NO’)
– The following are also done if available/affordable
• HBSAg, urine culture-sensitivity , U/S ,pap
smear

ANC -First Visit:interventions
• Iron and folate supplements to all women:
– One tablet of 60mg elemental iron and 400 micgm
folate/day.
– To enhance the absorption of iron, instruct mothers to
take iron when eating meat or vitamin-rich foods (fruits
and vegetables).
– Avoid tea, coffee, and milk at the same time when
taking iron;
• it interferes with the body’s absorption of iron.
– Iron can also be taken between meals. .
• Give first injection of Tetanus toxoid:.
• Provide ITN In Malaria Endemic Areas.

ANC -First Visit: interventions-contd.
• If rapid test for syphilis is positive:
– Treatment of the couple and counseling on safer
sex,
• Treat other STIs
• Treat UTI or asymptomatic bacteruria
• For HIV positive pregnant women Perform
additional laboratory investigations and
provide care and treatment according to the
Guideline for PMTCT of HIV in Ethiopia.
• Refer clients that need specialized care,
according to diagnosis

ANC -First Visit
Issues to be discussed
• Danger signs of pregnancy
– recognition, where to get help
• Advice on birth plan including transport facilities
to health care institutes.
• Advice to avoid alcohol, tobacco and illicit drugs
• Benefit of HIV testing, PMTCT and safe sex
– HIV testing is routine test in ANC unless the woman
says’ no’ ( opt out approach)
• Advice on exclusive breast-feeding and
postpartum contraceptive use.

ANC-2nd Visit(24-28 Weeks)
HISTORY
Revising the history:
• Identifying risk factors
• Complaints & concerns
– Vaginal bleeding and vaginal discharge
– Dysuria, frequency, urgency during micturition
– Severe/persistent headache or blurred vision
– Severe abdominal pain
– symptoms of severe anemia,.
– Opportunistic infections in HIV positive women
• Fetal movement ( Quickening)
• Social support/physical abuse

ANC- second Visit
Medical history
• Review relevant issues of medical history as
recorded at first visit.
• Note inter current diseases, injuries, or other
conditions and additional histories for HIV
positive women since first visit.
• check compliance Iron intake
• Note other medical consultations,
hospitalization or sick-leave in present
pregnancy.

ANC- second Visit
PHYSICAL EXAMINATION
–General appearance
–Vital signs
–Body weight gain
–Systemic examination
–Uterine height in centimeters
– Fetal lie & presentation
– Auscultate for fetal heart beat
– Vaginal examination if it was not done at
first visit.

ANC- second Visit
• Interventions ,Advice, questions and
answers
–The same as in the first visit

ANC 3rd Visit (30-32 wk)
• To screen for hypertension, multiple
gestation, anemia, preterm labor, DM,
Rh sensitization.
• To ascertain fetal growth & well being
• To further develop individualized birth plan.
• To further continue provision of medical care
and health promotional services

ANC 3rd Visit (30-32 wk)
• History, Physical examination, advices and
discussions similar to the previous visits
• Investigations:-
– Hgb/Hct, Urinalysis , OGTT, indirect coombs test
for Rh negative women
• Ultrasound and fetal well being surveillance if
indicated

ANC 4th Visit (36-38week)
• To screen for pregnancy related disorders like
hypertension, APH, multiple gestation
• To ascertain fetal growth, well being, fetal lie,
presentation
– If breech, ECV may be considered
• To strengthen health promotional service &
discuss client concern
• Finalize the individualized birth plan.

ANC 4th Visit (36-38wks)
• The same activities as the previous visit are
performed
• Individualized birth plan is revised,
– prepare women and their families for childbirth such
as selecting a birth location, identifying a skilled
attendant, identifying social, support, planning for
costs, planning for transportation and preparing
supplies her care and the care of her newborn.
• Danger signs are discussed ,the mother and her
family are educated on signs of labor
• Benefits of breast feeding and avalablity of
contraceptives for postpartum use are
reemphasized
• Appointment is Scheduled for postpartum visit.

ANC-4th visit
• All the usual physical examinations are
performed

Danger Signs During Pregnancy
1. Vaginal bleeding
2. Sudden gush of fluid or leaking of fluid from
vagina
3. Severe headache not relieved by simple
analgesics
4. Dizziness and blurring of vision
5. Sustained vomiting
6. Swelling (hands, face etc)
7. Loss of fetal movements
8. Convulsions
9. Premature onset of contractions (before 37
weeks)
10.Severe or unusual abdominal pain
11.Chills or fever
GUH

Tetanus Toxoid(TT) Immunization
Schedule.
• TT1 At first contact, or as early as possible
during pregnancy and do not protective
• TT2 Four weeks after TT1 ---protective For 3yrs
• TT3 Six months after TT2,--protective for 5yrs.
• TT4 One year after TT3,---protective for 10 yrs
• TT5 One years after TT4,---life long protection.

Definition of Labor
• Broadly defined as:
– A coordinated effective sequence of involuntary
uterine contractions that result in effacement and
dilatation of the cervix; and
– voluntary bearing down efforts leading to the
expulsion per vagina of products of conception.
• A physiologic process and is clinical diagnosis
• Parturient: patient in labor
• Parturition: process of giving birth

Physiologic preparations of labor
• Lightening - the settling of the fetal head into
the brim of the pelvis.
• Braxton Hicks contractions
– irregular, generally painless uterine contractions
during the last 4–8 weeks of pregnancy occur with
slowly increasing frequency.
– may occur with greater intensity during the last
weeks of pregnancy
• Bloody show - passage of a small amount of
blood-tinged mucus from vagina, as the cervix
begins to soften, efface, and dilate.

Dx of labor
• At least 2 Painful contractions in 10minute
with one of the following:
- Show
- Rupture of the membranes or
- Cervical change (Effacement and dilatation)
NB
– Rapture of membranes in the absence of painful contractions
is PROM
– Cervical change in the absence of painful contraction is either
cervical incometence or normal finding in most multipara
women.

Factors for Successful Labor
• The passage
– maternal bony pelvis & soft tissues (uterus,
cervix, pelvic floor, perineum)
• The Passenger
– The Fetus
• The Powers
– uterine contraction, maternal bearing effort,
NB. Needs the complex interaction among these three factors!

The Passage
• The passage includes the bony pelvis and the
resistance provided by the soft tissues
• The bony pelvis is comprised of;
– The two hip bones/inominate bones
• ie ilium, ischium, and pubis, which fuse at the acetabulum,
– the sacrum; and
– the coccyx .
• Fused by four joints:
- Two sacroiliac joints:
- Symphysis pubis
- Sacrococcygeal joint
SAMUEL BEZABIH HAMLE 2005EC

Female pelvis – Superior/Anterior view

False & True pelvis
• Pelvis is anatomically divided in to two:
- False pelvis and true pelvis
• Demarcation between the two is by:
– the sacral promontory,
– anterior ala of sacrum,
– arcuate line of ilium,
– the pectineal line of pubis &
– the pubic crest culminating in Symphysis
– pubis from posterior to anterior on both sides.

The False pelvis
• Formed by the iliac portions of the innominate
bone and limited by the iliac crests
• Little obstetric significance
• Only supports the uterus during pregnancy

The True Pelvis
• Forms the canal through which the fetus has
to pass
• Shallow in front (4cm), and deep posteriorly
(11.5 cm) formed by the sacrum and coccyx
• For descriptive purposes, it is divided into 3
planes
I. Inlet,
II. Mid cavity and
III. Outlet.

Pelvic Inlet
• Also called the superior strait,
• The pelvic inlet is also the superior plane of
the true pelvis.
• Boundaries:-
– Posteriorly; the promontory and alae of the
sacrum,
– Laterally ;the linea terminalis, and
– Anteriorly; the horizontal pubic rami and the
symphysis pubis.

Pelvic Inlet …….
• During labor, fetal head engagement is defined by the
fetal head’s biparietal diameter passing through this plane.
• To aid this passage, compared with the male pelvis the
inlet of the female pelvis is more nearly round than
ovoid.
• In erect position, pelvis is tilted forward making an angle
of 60° from horizontal.

The Pelvic Inlet
• Four diameters of the pelvic inlet are usually
described:
Anteroposterior (AP), transverse, and two oblique
diameters.
– Measurements are;
• clinical, x-ray or CT and MRI
1.Anteroposterior Diameters
– There are 3 distinct AP diameters (conjugates)
–True,
–Obstetric and
–Diagonal conjugates

Anteroposterior Diameters
I.The true conjugate (11-11.5 cm )
– Most cephaled, extends from the uppermost
margin of the symphysis pubis to the sacral
promontory.
– Measured indirectly
II. Obstetrical conjugate (10-10.5cm)
– clinically important and the shortest distance between
the sacral promontory and the Symphysis Pubis
– estimated indirectly by subtracting 1.5 to 2 cm
from the DC
Diagonal Conjugate – 1cm
Diagonal conjugate—1.5 cm

III. Diagonal Conjugate
• the distance from the lowest margin of the
symphysis to the sacral promontory (~12cm)
• Determined clinically (PV)

PELVIC INLET……
2.The Transverse Diameter(`13cm)
– the greatest distance between the linea
terminalis on either side
– constructed at right angles to the O/C. Diameter.
– It usually intersects the obstetrical conjugate at a
point approximately 5 cm in front of the
promontory
3.Oblique Diameters (~12 Cm)
– Each of the two ODs extends from one sacroiliac
synchondrosis to the contralateral iliopubic
eminence.

The Midpelvis
• Also called the midplane or plane of least pelvic
dimensions
• The midpelvis is measured at the level of the
ischial spines,
• During labor the midpelvis and ischial spines
serve to mark zero station.
• The Transverse (inter-spinous) diameter ~10cm;
– is the smallest pelvic diameter and, in cases of
obstructed labor, is particularly important.
• The AP diameter through the level of the ischial
spines normally measures at least 11.5 cm.

• the interspinous diameter of the midpelvis.
• The anteroposterior and transverse diameters of the pelvic inlet

Pelvic Outlet
• The pelvic outlet consists of two approximately
triangular areas whose boundaries mirror those
of the perineal triangle
• They have a common base, which is a line
drawn between the two ischial tuberosities.
• The apex of the posterior triangle is the tip of
the sacrum, and the lateral boundaries are the
sacrotuberous ligaments and the ischial
tuberosities.

Pelvic Outlet …
• The anterior triangle is formed by the
descending inferior rami of the pubic bones.
• These rami unite at an angle of 90 to 100 to
form a rounded arch under which the fetal
head must pass.
• Clinically, three diameters of the pelvic outlet
usually are described
– the anteroposterior, transverse, and posterior
sagittal.

The out let …
• Anteroposterior diameter:
- 9.5-11.5 cm and extends from the lower margin of the
symphysis pubis to the coccyx.
• Transverse diameter:
- 11 cm and is the distance between the inner edges of
the ischial tuberosities.
• Posterior sagittal diameter:
- 8 cm and extends from the tip of the sacrum to a
right-angle intersection with the line between the
ischial tuberosities.
NB :-Unless there is significant pelvic bony disease, the
pelvic outlet seldom obstructs vaginal delivery.

The Pelvic Axis (Birth axis)
• Anatomical( curve of carus):
– formed by joining the axis of inlet, cavity & outlet.
- Uniformly curved with convexity fitting the
concavity of sacrum
- Fetus doesn’t traverse the uniform curve.
• Obstetrical:
– Fetus negotiates the pelvis, not uniformly curved
- 1st downwards & backwards to the level of ischial
spines and then abruptly forwards

• 04 types of pelvis based on shape , anterior and
posterior sagital diameters of the pelvic inlet
– i.e, Gynecoid, anthropoid, android and platypelloid
• Many pelves are not pure but are mixed types.
– For example, a gynecoid pelvis with an android
tendency means that the posterior pelvis is gynecoid
and the anterior pelvis is android shaped.

Pelvic types-4
1.Gynecoid:
• The Posteriorsagital diameter of the inlet is only
slightly shorter than the Anteriorsagital diameter +
• Transverse diameter slightly greater than APD
– most common type (50%);
– overall shape is round
– straight sidewalls and ischial spines are not prominent
– a wide pubic arch
– Straight side walls
– Concave sacrum

Pelvis types-4
2.Anthropoid: Ape Type
• The AP diameter is greater than the transverse
• Seen in about 33% of women;
– Overall shape is long and oval;
– Long and narrow sacrum
– Divergent side walls
– Prominent ischial spines;
– Wide sacro-sciatic notch
– Narrow pubic arch,
most often associated with persistent OP position.

Pelvis types-4
3. Android(male type)
the posterior sagittal diameter of the inlet is much shorter
than anterior sagittal
In ~20% of women
– overall shape is heart-like;
• limiting the posterior space for the fetal head;
– S. Promontory and Ischial spines are prominent;
– Shallow sacrum
– Convergent side walls
– Narrow sacro-sciatic notch
– A narrow pubic arch
associated with persistent occiput posterior position and
deep transverse arrest.

Pelvis Types-4
4.Platypelloid:
– least frequent, seen in less than 3% of women;
– flattened shape with short anteroposterior diameter
and wide transverse diameter
– Wide sub-pubic angle
Deep transverse arrest patterns of labor are commonly
associated with this pelvic type occipito frontal
diametere accommodates it self to the long transverse axis
with no room for rotation anteriorly or posteriorly

Physiological changes during pregnancy &
labor in the passage
• Increase in width & mobility of symphysis
• Relaxation & mobility of sacro-iliac joint
• Increase in antero-posterior diameter of inlet
during labor- rotatory movement of sacroiliac
joint
• In dorsolithotomy position, the antero-
posterior diameter of outlet by 1.5-2 cm

The Passenger (the fetus)
Several fetal variables influence the course of labor and
delivery including
1. Fetal size: Estimated clinically, by ultrasound or the
mother
- Fetal macrosomia: 4500 gm (ACOG)
2. Fetal lie: relation of longitudinal axis of the fetus
with the mother and It could be
– longitudinal – > 99% of cases at labor
– transverse
– oblique- 450 with maternal axes, unstable ( change to
longtudinal or transverse lie)
NB: In a singleton pregnancy, only fetuses in a longitudinal lie
can be safely delivered vaginally 36

The Passenger
3-Presentation
• Refers to that portion of the fetal body that is either foremost within
the birth canal or in closest proximity to it.
• can be felt through the cervix on vaginal examination.
– cephalic (Head) or Breech presentations in longitudinal lies
– Shoulder presentation in transverse lie
– Compound presentation
– Funic (cord) presentation

The passenger
Cephalic presentations
• Classified according to the relation b/n the head and body ( degree
of flexion)
• Vertex/ Occiput presentation
– Well flexed head chin in contact with the chest
– Occiputal fontanel is the presenting part
• Face presentation
– the fetal neck is sharply extended so that the occiput and back come
in contact, and the face is foremost in the birth canal
– Chin/ Mentum is the denominator
• The fetal head may assume a position between these extremes,Ie
partially flexed in some cases, with the anterior (large) fontanel, or
bregma, presenting—sinciput presentation —or partially extended
in other cases, to have a Brow presentation
• Sinciput and Brow presentations are usually transient. As labor
progresses they almost always convert into vertex or face
presentations by neck flexion or extension respectively

Longitudinal lie. Cephalic presentation. Differences in attitude of the fetal body
in (A) vertex, (B) sinciput, (C) brow, and (D) face presentations.

The Passenger
Breech Presentation
• The incidence of breech presentation decreases
with gestational age. It approximates
– 25% at 28 weeks,
– 17 % at 30 weeks,
– 11 % at 32 weeks, and then decreases to
approximately 3 % at term.
• Breech presentation has three general
configurations ie frank, complete, and footling
breech presentations

Fetus- cont’d
4. Attitude/ Posture : position of head
with regard to fetal spine ie flexed,
extended or military attitude
5. Position refers to the relationship
of an arbitrarily chosen portion of
the fetal presenting part to the
right or left side of the birth canal.
• The fetal occiput, chin (mentum),
sacrum and acromion are the
determining points in vertex, face,
breech and shoulder
presentations, respectively
Posssible positions in Vertex
presentation

Longitudinal lie. Vertex presentation. A. Left occiput anterior (LOA). B. Left occiput
posterior (LOP).

Longtudinal Lie , Vertex presentation A. Right occiput posterior
(ROP). B. Right occiput transverse (ROT).

Positions of Face Presentation

Landmarks of fetal skull for determination of fetal
position-GABEE

Landmarks of fetal skull for determination of fetal
position-GABEE
• Submentobregmatic (face)-----9.5 cm
• Verticomental (brow)…13.5cm
• Occipito frontal (vertex, military)----11cm
• Suboccipitobregmatic (vetex,flexed)---9.5

The Passenger
6. Station:
– Measure of descent of bony presenting parts of fetus
through the birth canal
7. Number of fetuses
8. Congenital malformations of fetus
– Abnormalities of the above variables may affect
both the course and likelihood of vaginal delivery.
50

The Power (Uterine activity)
• Is characterized by the frequency, amplitude
(intensity) & duration of contractions.
• Assessment:
- Simple observation
- Manual palpation
- indentablity of uterine fundus during contraction
- Duration of contraction
- External objective assessment-
- Tocodynamometer
- Direct measurement by intrauterine pressure catheter (IUPC)
51

Power-cont’d
• Most precise method is the intrauterine pressure catheter.
• Adequate uterine contraction remains unclear, but classically 3-5
contraction in 10 minutes.
• Various units have been used, most common is the “Montevideo
Unit”,
- Adequate uterine contraction if 200-250 MV
• Hyper stimulation, tachysystole(Ux contraction > 5/10 minute),
hypertonus. 52

Physiology of labor
• The physiology of labor initiation has not been completely elucidated.
• Labor is species specific, mechanism in humans is unique.
• Different theories have been postulated:
1. HORMONAL FACTORS:
a. Estrogen theory:
– During pregnancy, most estrogens are in binding state.
– more free estrogen appears increasing the excitability
of the myometrium and prostaglandins synthesis.
53

Physiology- cont’d
b. Progesterone withdrawal theory
c. Prostaglandins theory:
– PGF2a was found to be increased in maternal and
fetal blood as well as the amniotic fluid late in
pregnancy and during labor w/c increase
contraction.
d. Oxytocin theory:
– The secretion of oxytocinase enzyme from the
placenta is decreased near term due to placental
ischemia leading to predominance of oxytocin’s
action
e. Fetal cortisol theory:
– Increased cortisol production by adrenal increases
estrogen production. 54

Physiology- cont’d
2. MECHANICAL FACTORS:
a. Uterine distension theory:
– explains the preterm labor in case of multiple
pregnancy and polyhydramnios.
b. Stretch of the lower uterine segment by the
presenting part at term
55

Parturition: Process of Birth
• Phase 0 (Phase of quiescence):
- Refers the time in utero before onset of labor.
- Uterine activity is suppressed by progesterone,
prostacyclin, relaxin, nitric oxide, parathyroid-
related peptide, HPL, etc.
• Phase 1 (Activation phase):
- Estrogen facilitates expression of myometrial
receptors for PGs and oxytocin- Gap junctions
- Prepares the uterus for subsequent stimulation
phase
56

Phases-cont’d
• Phase 2 (Stimulation phase):
- Uterotonics, particularly PGs and oxytocin stimulate
regular uterine contractions
• Phase 3 (Uterine involution):
- After delivery, mainly mediated by oxytocin.
The quiescence, activation and
stimualtion phases require
endocrine, paracrine and
autocrine interaction between
the fetus, membranes, placenta 57

Mechanisms of labor
• The mechanisms of labor, also known as the cardinal
movements, are described in relation to a vertex
presentation, as is the case in 95% of all pregnancies.
• Refers to the changes in
position of fetal head during its
passage through the birth canal.
• Although labor and delivery occurs in a continuous
fashion, the cardinal movements are described as 7
discrete sequences Engagement, Descent ,Flexion,
Internal Rotation, Extension, External Rotation
(Restitution), Expulsion
58

Cardinal Movements of Labor
1. Engagement
• The mechanism by which the biparietal diameter /the
greatest transverse diameter/ in an
occiput presentation, passes through the pelvic inlet is
designated engagement.
• Engaged head is at least at station ‘0 ‘ ( level of ischial spines)
• Engagement usually takes place with the the sagittal suture
directed transversely or obliquely
• The fetal head may engage during the last few weeks of
pregnancy in most nulliparous women.
• In most multiparous women the head does not engage until
after labor commencement.
 i.e. the fetal head is freely movable above the pelvic inlet
at labor onset i.e. Floating

Cardinal movements - cont’d
2.Descent:
• downward passage of presenting part through
the birth canal
• This occurs intermittently with contractions.
• Greatest descent occurs in deceleration
phase (late active stage) & second stage
60

Cont’d
3. Flexion: Occurs passively
• Helps to present the smallest presenting
diameter (i.e. from occipitofrontal (11.0 cm)
to suboccipitobregmatic (9.5 cm) for optimal
passage through the pelvis.).
4. Internal rotation:
• Passive movement due to shape of pelvis and
pelvic musculature.
• Rotation of the presenting part from its
original position to AP position & in line with
the AP diameter of the pelvic outlet.
61

Cont’d
5.Extension:
• Occurs once fetus descended to a level of interoitus
• Is because of force of uterine contraction versus
muscles of the pelvic floor.
• the result is delivery of the head
6.External rotation: also called as restitution
• Return of fetal head to the correct position in
relation to fetal torso.
• Passive movement
• Results from maternal bony pelvis & its musculature
and basal tone of fetal musculature
7. Expulsion: Delivery of rest of fetus.
62

Diagnosis of labor
• Made on the presence of :
–At least two contraction per 20 minutes
lasting 20 seconds, and
–Cervical dilatation of 3-4 cm or more
–Cervical effacement of 80% or more
–Show
–Rupture of membranes
• At least two criterias needed to make
the diagnosis /contraction is must/.
67

True labor vs. False labor
True labor pain False labor pain
Regular Irregular
Increase progressively not
Lower abdomen & back Lower abdomen
Dilatation & effacement of
cervix
No effect on cervix
Not relieved by sedatives
& antispasmodics
Relieved
68

Stages of Labor
Four arbitrary stages of labor:
 First stage of labor:
- onset of labor till full(10cm) cervical dilatation
 Second stage of labor:
- full cervical dilatation of cervix to delivery of
fetus
 Third stage of labor:
- from delivery of fetus till delivery of placenta
 Fourth stage of labor:
- one to two hours after delivery of placenta. 69

First stage of labor
• Two phases: latent and active
1. Latent phase: onset of labor to 3 cm cervical dilatation
2. Active phase: 4 cm – 10 cm cervical dilatation.
• Rate of cervical dilatation is 1.2cm/hr in primi & 1.5
cm/hr for multi.
• Active phase of first stage of labor has three phases:
acceleration, phase of maximal slope, and
deceleration phases for primigravidas.
• Average duration of first stage is 12 hrs in primi and
6 hrs in multi.
70

Stages- cont’d
 SECOND STAGE OF LABOR
• Two phases:
1. Propulsive/anatomical/ passive phase &
2. Expulsive/ Physiological phase
Second stage lasts an hour in primi and
20 minutes in multi.
Rate of descent is 1cm/ hr in primi &
2cm/hr for multi.
71

Stages- Cont’d
• THIRD STAGE OF LABOR: Average duration is
15 minutes for both.
• FOURTH STAGE: first one to two hours where
PPH is high.
– This stage is a critical time for monitoring of vital
signs and observe for blood loss & uterine
contractility.
72

Graphic illustration of the composite dilatation time and descent time
functions in normal labor.

Composite of the average dilatation curve for nulliparous labor.

Normal labor- cont’d
Uterine contractions: pace makers of uterus are at
tubal Ostia on both sides.
• Basic elements in contractile system are:
actin, myosin, ATP, calcium & myosin light chain
kinase.
• Contraction and retraction of uterine muscle.
• Effect of retraction :------------------
Effacement:
- Taking up the length of cervix expressed in
percentage OR remaining cx length in cm.
- Effacement in primi occur before cervical dilatation
75

Events in first stage of labor
• Main events are:
- Dilatation and effacement of cervix
- Full formation of lower uterine segment
 Factors responsible for dilatation:
Uterine contraction & retraction
Bag of waters
Fetal axis pressure in the proper direction
Pressure by the presenting part.
76

Events in second stage
• Descent and delivery of fetus
• Delivery effected by two factors:
- Downward thrust by uterine contraction
- Voluntary contraction of abdominal muscles
(maternal pushing)
77

Events in third stage of labor
 Phase of placental separation and expulsion
Mechanism of separation:
 Because of retraction there would be marked
decrement in surface area.
 Two types of placental separation
1. Central separation (Schultze):
–Retroplacental clot
2. Marginal separation (Mathews-Duncan):
– separation starts at the margin
– most frequent. 78

Management Of Labor
A. Initial Evaluation
• Maternal BP, PR,RR and Temp.are recorded.
• Review of ANC record
• Most often, unless there has been bleeding in
excess of bloody show, a vaginal examination is
performed.
• The gloved index and second fingers are then
introduced into the vagina while avoiding the
anal region
• The number of vaginal examinations correlates
with infection-related morbidity, especially in
cases of early membrane rupture.

Initial Evaluation- contd.
B.Pelvic Examination
– Cervical assessment
• Dilatation
• Effacement
• Position of cervix ( in relation to the fetal head)
– station of the presenting part
• Pelvis divided into 5th s above and below ischial spines
( -5-4-3-2-1 0 +1+2+3+4+5 cms)
– Position of the presenting part
– Pelvic adequacy assessment
– Status of the membranes- raptured or intact

Cont’d
C. Investigations:
– urine analysis, Hgb, rapid HIV testing if not tested.
D. preparation:
– No routine enema & perineal shaving
– No routine catheterization
– Position: can assume any position except supine.
– Diet: fluid diet, intravenous hydration when
indicated.
82

Contd.
Oral Intake
• Food should be withdrawn during active labor
and delivery.
• Gastric emptying time is remarkably
prolonged once labor is established and
analgesics are administered.
– Risk of vomiting and aspiration,
• Only sips of clear liquids, occasional ice chips,
and lip moisturizers are permitted.

Contd.
IV Fluids
• Seldom required for normal laboring women.
• An IV infusion system is advantageous during
the immediate puerperium to administer
oxytocin (both prophylactically and
therapeutically).
• Moreover, with longer labors, the administration
of glucose, sodium, and water to the otherwise
fasting woman at the rate of 60 to 120 mL/hr
prevents dehydration and acidosis.

Cont’d
• Pain Control:
- Pain is felt in 1st stage T10-L1; 2nd stage S2-S4
- psycho-prophylaxis, IV analgesics, epidural
analgesia, spinal; etc
 Amniotomy: Not performed routinely
- Indications are: - for Augmentation/induction
- Fetal distress
• Antibiotic prophylaxis: when indicated
85

MONITORING OF LABOR
First stage:
FHB
– Every 30 minutes in low risk & every 15 minutes in
high risk women
– FHB has to be counted for a full minute just after
contraction.
Uterine contraction
– every 30 minutes, monitor for 10 minutes
Pelvic evaluation every 4 hrs unless indicated.
Maternal vital signs: BP & Temp. Q 2 Hrly 86

Cont’d
Second stage:
FHB every 15 minutes & 5 minutes in low risk
& high risk mothers respectively
Monitor descent hourly.
DELIVERY
–Reduce risk of maternal perineal injury
–Prevent fetal injury
–Provide initial support to newborn
87

Management- cont’d
Delivery: Essential aseptic techniques
• No routine perineal massage , individualize
episiotomy
- Optimal position for pushing is not clear.
- Avoid closed glottis
Delivery of the head: modified Ritgen’s maneuver
Delivery of shoulders
Delivery of the rest of body. 88

 Clear oro-pharynx immediately after delivery
of head /suctioning/.
 Nuchal cord has to be slipped over head if
loose or doubly clamped & cut.
 Cord clamping:
– immediate with in one minute
89

LABOR Management- cont’d
Third stage management: Two types
1. Physiological/ expectant:
– waiting for signs and symptoms of separation and
with little assistance.
2.Active:includes
– Cord clamping & cutting,
– Uterotonic administration,
– Controlled cord traction and uterine
massage.
90

• Care of Newborn:
–APGAR score at the 1st , 5th, 10th minutes, etc.
–Drying
–Avoid heat loss & covering with cotton
clothes
–Label, anthropometric measurements
–Initiate breast feeding or other options
–TTC eye ointment & Vit. K administration
–If needed, neonatal resuscitation 91

• Examination of genitalia
• Examination of placenta, membranes & cord
• Transfer of the parturient
• Discarding and disinfecting the equipments.
92

Partograph
INTRODUCTION
• Early detection of abnormal labor and
prevention of prolonged labour
►↓ maternal - perinatal morbidity & mortality
• The Partograph was developed to this endeavor
93

Introduction
• The Partograph is the graphic recording of
1. the progress of labour and
2. the salient condition of the mother & fetus .
• It serves as an “early warning system” and
assists in:
a. early decision to transfer,
b. augmentation and
c. termination of labor.
94

Normogram for cervical dilation

The WHO Partograph
Principles:
• The active phase commences at 3 cm cervical dilation
• The latent phase should not last longer than 8
hrs
• During active phase, the rate of cervical dilation
should not be slower than 1cm/hr
• Vaginal examination;
– infrequently as compatible with safe practice (Q 4 hrs is
recommended)
• Midwives and other personnel managing labor may
have difficulty in constructing alert and action line
►pre-drawn lines 96

Modified WHO Partograph
• The WHO Partograph has been modified to
make it simpler and easier to use(2001)
• The latent phase has been removed and
plotting begins in the active phase when the
cervix is 4 cm dilated. (it was 3 cm)
97

The WHO partograph-cont’d
Components: 4
- Patient information
- Fetal condition
- Progress of labor
- Maternal condition
100

Sample
Partogr
aph
for
Normal
Labor
101

• For whom to use it?
- Make sure that there are no complications of
pregnancy that require immediate action
- Make sure that the women is in labor
- In the peripheral health units
104

• Who should use it?
Health workers who are able to:
- Observe and conduct normal labour and delivery
- Perform vaginal examination in labor and assess
cervical dilatation accurately
- Plot cervical dilation accurately on graph against time
• Where to use it?
- No place for home delivery
105

Advantages of partograph
• Prevention of prolonged labor
• Avoids unnecessary use of augmentation
• Hand over of patients
- More precise and fluent
- At a glance appreciation of preceding
hours of labor
106

Advantages of Partograph (Ctd.)
• Pictorial (graphic or clear) display of events of labor:
- Clarifies recordings
- Avoids lengthy written notes
- Facilitates recognition of any omissions
- Saves time → Companionship
• Considerable educational value:
- All interrelated variables of labor can be
seen on a single paper
• Low cost, feasible
• Improved out come of labor →↑Credibility
(trustworthiness) of formal health sector.
107

Dystocia
 Definition:
 difficult labor i.e. abnormally slow labor progress
 Underlying Causes:
 Abnormalities in P , P and P ( alone or in combination)
 POWER (expulsive powers)
 PASSENGER- (fetus) fetal presentation, position,
development
 PASSAGE
• birth canal
• Bony pelvis( pelvic contraction)
• Soft tissue abnormalities(tumors,congenital

The Power (Expulsive Forces)
• The Power in labor
–Uterine contraction and
–2nd stage Voluntary pushing

The Power-Uterine contraction
• Stimulus originate from each cornu with a time
interval of several miliseconds unite and swip over
the fundus and down to the cervix
• The force of contraction exhibits gradient of
myometrial activity
 with fundal dominance diminishing down to LS and CX
• There is also a time differential in the onset of the
contractions in the fundus, midzone, and lower
uterine segments.
• Normal spontaneous contractions often exert
pressures approximating 60 mm Hg (Hendricks, 1959).
• lower limit of contraction pressure required to dilate
the cervix is 15 mm Hg.

The Power- Uterine Contarction measurement
• The external tocodynamometer is a pressure
sensor placed over the fundal prominence of
the uterus that gives an accurate
determination of the frequency and duration
of uterine contractions
• Not adequate for assessment of the resting
tone of the uterus or the intensity of
contractions;
=> Intrauterine Pressure catheter (IUPC) is required

The Power- Uterine Contarction measurement
 Intrauterine pressure catheter (IUPC)
 measurement shows
– baseline uterine resting pressure
– contraction intensity and duration, and
– frequency of uterine activity.
• It is the most accurate method for diagnosing
uterine dysfunction and evaluating treatment.

The Power- Uterine Contraction measurement
• Normal spontaneous contractions often exert pressures
approximating 60 mm Hg (Hendricks, 1959).
lower limit of contraction pressure required to dilate the cervix is 15 mm Hg.
• Montovideounit is the widely used unit of uterine activity
MVU= (# contraction/10 min )x( average intensity of contraction)
OR sum of the range of pressures ( peak- Baseline) in 10 min
• Adequate labor uterine activity >200MVU

Calculate the average uterine contraction pressure in
MVunits

Power Abnormalities
• Power abnormalities resulting in dystocia
constitute
1. Uterine Dysfunction; uterine activity that is
ineffective in eliciting the normal progress of labor
• Hypertonic-
• Hypotonic
2. Poor Maternal Effort (inadequate Pushing) in the
2nd stage of labor

Power Abnormalities; 1.Uterine Dysfunction
A .Hypotonic Uterine Dysfunction
• No basal hypertonous, low pressure
• Normal gradient pattern (synchronous),
• But Pressure during a contraction is insufficient to dilate the
cervix. (common in primis at Active phase of labor( AFSOL)
• may be caused by
– excessive sedation,
– early administration of conduction anesthesia, or
– overdistension of the uterus (eg, twins, hydramnios)
– chorioamnionitis
Oxytocin augmentation is usually applied in
this clinical situation if active labor has already
begun.

Power Abnormalities- Uterine Dysfunction
B. Hypertonic/incoordinate uterine dysfunction
Disco-ordinated pattern high pressure contractions
• Either basal tone is elevated appreciably or
the pressure gradient is distorted.
• Gradient distortion may result from
– contraction of the uterine midsegment with more
force than the fundus or
– Complete asynchronism of the impulses
originating in each cornu or
– a combination of these two.

 Hypertonic uterine dysfunction is generally associated with :
– placental abruption
– overzealous use of oxytocin
– CPD
– fetal malpresentation and
– the latent phase of labor.
 Treatment may require
– tocolysis
– decrease in oxytocin infusion, or
– cesarean section as indicated for concomitant
malpresentation, CPD, or FHR abnormalities.

Power abnormalities; 2.inadequate Pushing
 Inadequate pushing in the second stage of
labor is common and may be caused by;*
–conduction anesthesia,
–over sedation
–exhaustion,
–underlying neurologic dysfunction
(e.g., paraplegia or hemiplegia) or
–psychiatric disorders.

Inadequate pushing……..
 RX;
 Mild sedation or a waiting period to permit
analgesic or anesthetic agents to wear off may
improve expulsive efforts, and outlet forceps or
 vacuum delivery may be effected in selected
cases.
*Heavy sedation or regional analgesia may reduce the
reflex urge to push and may impair the ability to
contract abdominal muscles sufficiently.
 In other instances, the inherent urge to push is
overridden by the intense pain created by bearing
down.

The Passage
Abnormalities of the birth canal
1. Bony Pelvis
–Contracted pelvis
–Abnormal bony pelvis ( non--gynecoid)
2. Soft Tissues of the reproductive tract

Inlet* :
– Anterio-Posterior Diameter( obst. Conj.)~10.5cm ,
– Transverse Diameter~13.5cm
*Determined clinically and/ or using X-ray pelvimetery
Mid pelvis:
– TD(Transverse Diameter)(ISD)~10.5cm
– APD(Anterio-Posterior Diameter) ~11.5cm-B/n SP lower
border& S4-S5 junction
• posterior sagittal-5cm (from the midpoint of the
interspinous line to the same point on the sacrum,).
Outlet:
– APD~9.5-11.5
– TD~11cm

The Passage- Bony Pelvis - Pelvic Contraction
• Any contraction of the pelvic diameters that
diminishes its capacity can create dystocia
during labor.
• There may be contractions of the pelvic inlet,
the midpelvis, or the pelvic outlet, or
• a generally contracted pelvis may be caused
by combinations of these

The passage-Bony pelvis contraction
 Contracted Pelvic inlet
– The shortest *APD (OC) <10cm (D.Conjugate<11.5),
– The greatest TD<12cm
*occasionally the shortest APD lie b/n anteriorly displaced body of S1 vertebra
(abnormal promontory)
 Mid pelvis ; clinical (prominent spines, converging side walls, narrow
sacrosciatic notch)
- ISD < 10Cm
- PSD + ISD < 13.5cm**
 pelvic outlet***
-ITD < 8cm,
-narrow sub-pubic arch
***Outlet contraction without concomitant midplane contraction is rare
**the midpelvis is likely contracted when the sum of the interspinous and
posterior sagittal diameters of the midpelvis falls to < 13.5 cm.
Normal- 15.5 cm (10.5 plus 5 cm).

The Passage- Bony Pelvis Types
• Refer to your note on Normal Labor

The Passage-Soft Tissues of the
Reproductive Tract
• Uterine abnormalities ( congenital , fibroids..)
• Ovarian tumors
• Cervical stenosis
• Vaginal abnormalities
– scarring due to FGM
– congenital malformations( transverse/longtuidinal
septa)
• Tight perineum

The Passenger/The Fetus
Fetal causes of Dystocia
• Macrosomia , Shoulder Dystocia
• Malpresentation
– any presentation other than Vertex Breech, Face,
Shoulder, Compound
• Abnormal lie
 Transverse, Oblique
• Malposition
– any position in labor that is not ROA, OA, or LOA
• Asynclitism
• Congenital anomalies-
– Hydrocephalus Abdominal tumours (e.g. Wilms tumor)
,Cystic hygroma ,Conjoined twins
• Conjoined Twins

Cephalopelvic Disproportion (CPD)-MOH
Definition
• CPD is failure of the fetus to pass safely
through the birth canal because the fetal
head being relatively larger than the maternal
pelvic size.
• The relative size of the maternal pelvis and fetal
head vary from one labor to another in their
dimensional sizes, shape and mouldability of the
fetal head .
• If timely intervention (CS) is not undertaken, CPD
leads to obstructed labor and its complications.

Cephalopelvic Disproportion (CPD)-MOH
The causes of CPD are:
• Contracted pelvis
– due to genetic, nutritional deficiencies or trauma.
– The commonest cause of contracted pelvis in
developing countries is poor nutrition during
childhood.
• Large fetus
– as in diabetes, post term pregnancy or hydrocephalus.
– Usually disproportion is relative rather than an absolute
fetal head or pelvic size abnormality.
• OP position may lead to a relative CPD.

CPD-Diagnostic approach and risk assessment
Suspect CPD If;
– Previous prolonged labor with bad obstetric
history or operative delivery
– Primigravida especially if age is less than 16 years
– True obstetric conjugate of 8 –10 cm (borderline
CPD)
– Prominent ischial spines, flat sacrum, converging
pelvic side walls etc
– The cervicogram crossing the alert line without
signs of CPD

MOH
Gross CPD
– EFW of > 4 kg (in an average sized Ethiopian)
– Hydrocephalus
– Gross traumatic or congenital pelvic abnormality
– True (obstetric) conjugate and/ or bituberous
diameter of < 8 cm

MOH
Diagnosis of CPD in the absence of gross CPD is
confirmed after trial of labor:
– Severe moulding at a higher station ( >3/5 above the
pelvic brim)
– Increasing moulding with no progress in descent
– 2⁰ arrest of cervical dilation and descent with good
contraction;
– In the primigravida, failure of progress of labor after
augmentation

CPD
• fetal descent largely follows complete dilatation.
• Moreover, the second stage incorporates many of
the cardinal movements necessary for the fetus
to negotiate the birth canal.
• Accordingly, disproportion of the fetus and pelvis
frequently becomes apparent during second stage
labor.

MOH
• When CPD is neglected, it will progress to
Obstructed labor (OL) with the following features
– Large caput
– Severe moulding (3+) at higher station
– Cervix poorly applied to head
– 3 tumor abdomen
Thick Upper segment, Edematous bladder, Ballooned
(thinned out ) lower segment separated from the upper
segment with pathologic retraction band (Bandls Ring)of
the lower segment
– Maternal dehydration, infection
– fetal distress / death

Complications of obstructed labor
• Perinatal + maternal M&M
• Hemorrhage (APH, PPH)
• Sepsis
• Obstetric Fistulae
– Vesico-vaginal, Urethro- vaginal, Uretero-cervical,
Recto vaginal fistulae
– 20 to necrosis from prolonged compression of bladder
against bony pelvis by the fetal head
• Uterine rupture
• Infertility- Hysterectomy, Uterine infection
• Operative complications
• Psychological trauma

Abnormal Patterns of Labor
 The progress of labor is evaluated primarily
through:
• estimates of cervical dilatation and
• descent of the fetal presenting part
• Labor abnormalities can be categorized as
–Progress slower than normal
• (Protraction Disorders)
–Complete cessation of labor progress
• (Arrest Disorders)

Abnormal Patterns of Labor
Prolonged Latent Phase
• >20 hrs for nullipara, >14 hrs for multipara
(Friedman)
– 95th percetiles
• 3- 4 % incidence regardless of parity -Sokol and
as(1977)
Causes of prolonged latent phase
1. Sedation/ anesthesia(GA or conduction) in LFSOL
2. Uterine dysfunction
3. Unfavorable Cx at labor onset
4. FPD, malpresentation, malposition
5. False labor

Prolonged latent phase
M’gt Options:
1.Therapeutic rest (Analgesia and bed rest) and 6-12
hrs later
– 85% enter labor spontaneously,
– 10% no more contraction(false labor)
• Rx. send home,
– 5% persisting ineffective ux contractions
• RX. oxytocin infusion
2.Immediate delivery (AROM and oxytocin/ CS as
necessary) for clinical indications e.g.
chorioamnionitis, severe PE
Friedman (1972) reported that latent phase prolongation did
not adversely influence fetal or maternal morbidity or
mortality rates.

Active phase Disorders
• Mean Duration (95percentile) of active phase
(according to Friedman)
– Primis 4.9hrs (max 11.7hrs) ,
– Multis -2.4 hrs (max 5.2hrs)
• Cx D rate 1.2- 6.8/hr
– multis progress faster than primis in the active phase,
minimum rate being 1.5cm/hr
– Nullipara- minimum of 1.2cm/hr
• Descent
– begins in the later stage of active dilatation,
commencing at 7 to 8 cm in nulliparous
– Descent disorders in the active phase occur in
• 25% of nulliparous and
• 15 % of multiparous labors (Sokol, 1977).

Active Phase-Contemporary data-
• Zhang (2010)- from review of 62415 SVDs
– Labor progress (Cx D) is very slow (<1cm/hr) until
cervix dilates ~ 5cm
– progress from 4cm to 5cm takes ~ 6hrs, and from
5cm to 6 cm takes ~3hrs, faster in multis after
then
– median (95th percentile) time for the cervix to
dilate from 4 to 10 cm in nulliparas and
multiparas was 5.3 hours (16.4) and 3.8 hours
(15.7), respectively
– No deceleration phase ( non sigmoid curve)

Active phase Disorders; Protraction disorders(PD)
PD  abnormally slow dilatation/ & descent
a. Protracted active phase dilatation
– <1.2cm/hr for Nullipara women
– < 1.5cm/hr for Multi Para women
b. Protracted descent
– <1cm/hr Nullipara
– <2cm/hr Multipara
• NB-much of the fetal descent takes place in the2nd stage
c. protracted 2nd stage labor (in time)
– >2hr NP(>3hr if on conduction Analgesia>)
– >1hrMP( 2>hr if on conduction analgesia)

 Causes of PD:
– Fetopelvic Disproportion ( 1/3rd of all)
– minor malposition( eg OP)
– excessive sedation
– pelvic tumors
• The most common cause of PD is inadequate
uterine activity.
• Rates of cervical change may be protracted by the
use of epidural anesthesia

 Mgt of PD
• R/o FPD –(CS if FPD is confirmed)
 reevaluate clinical pelvimetery,
 fetal presentation, position, station and EFW
• Assess uterine activity (IUPC) and fetal status
– ARM + oxytocin for inadequate uterine activity
– Conservative (Expectant) mgmt.;
• if no FPD + fetus is stable
• close observation & support
• augmentation

Active phase Disorders; Arrest Disorders(AD)
i. 2⁰ Dilatational arrest
o No Descent for 2hrs in AFSOL
5% of term nulliparous
80% 20 to inadequate ux contraction (< 180MVU)
ii. Arrest of descent
o no descent for 1hr
Friedman found 30% CPD in PDs and 45% CPD in ADs
Causes of AD
– UX dysfunction
– FPD
– Malpositions ( OP, OT, Face, Brow)
– Excessive sedation

Active phase Disorders -Arrest Disorders(AD)
Arrest of dilation, in which the cervix achieves 6 cm of
dilation but then does not change for 2 hours

Arrest of descent. The fetal head moves from a 2 station to a
0 to 1 station but then makes no further progress

 ACOG (2013) has suggested that before the
diagnosis of arrest during 1st-stage labor is made,
both of these criteria should be met: (i.e. before CS
decision for dystocia)
– The latent phase has been completed, and the
cervix is dilated 4 cm or more.
• A Ux. contraction pattern of >=200 MVU/10
minute period has been present for 2 hrs. without
cervical change
– Rouse and associates (1999) have challenged the “2-hr
rule” on the grounds that a longer time, that is, at least 4
hours, is necessary before concluding that the active
phase of labor has failed. We agree. Will 24th

New Definitions by NICHD and ACOG
Evidence for Adequate and Arrested Labor
• Arrest of labor: “. . . the diagnosis of arrest of labor
should not be made until adequate time has elapsed.”
• Adequate labor: “. . . Includes
– greater than 6 cm dilation
– with membrane rupture and 4 or more hours of adequate
contractions (e.g., greater than 200 Montevideo units) or
6 hours or more if contractions inadequate with no cervical
change. . . .”
• Second-stage labor: “. . . no progress for more than 4
hours in nulliparous women with an epidural, more
than 3 hours in nulliparous women without an
epidural. . . .”
• “No cesarean before these time limits . . . in the
presence of reassuring maternal and fetal status. Will
24th

Management of AD
– R/o FPD ; CS if present
– Treat ux dysfunction by oxytocin
NB. arrest in the face of adequate uterine contraction
has poor prognosis for vaginal delivery i.e. high
perinatal mortality if allowed to continue

Abnormal Labor Patterns, Diagnostic Criteria, and Treatment Modified from Cohen, 1983.(Will 24th

Precipitate Labor
Precipitate labor is defined as
i. delivery within< 3hrs after onset of contraction
ii. Cervical dilatation rate of > 5cm/hr for the
Nullipara and, > 10cm/hr for the multipara
Causes -little known
– Extremely strong ux contractions
– Low birth canal resistance
– Oxytocin

Precipitate Labor
Complications
Maternal
– Ux rapture( strong contractions + rigid cervix and
birth canal)
– birth canal laceration
– PPH
– AF embolism
Fetal-Increased PNM due to
– decreased UX placental perfusion,
– intracranial hemorrhage ,
– unattended delivery

Precipitate Labor
• Stop oxytocin
• Beta mimetic( terbutaline, retodrine)
NB
– Unusually forceful spontaneous uterine contractions
are not likely to be modified to a significant degree by
analgesia.
– The use of tocolytic agents such as magnesium sulfate
is unproven in these circumstances.
– Use of GA agents that impair uterine contractibility,
such as isoflurane, is often excessively heroic.
– Certainly, any oxytocin agents being administered
should be stopped immediately

Prolonged 2nd Stage of Labor
• The median duration of the second stage is highly
but estimated to be
– 50 to 60 minutes for nulliparas and
– 20 to 30 minutes for multiparas,
• 2nd stage of labor is considered prolonged if it
lasts
– In the Nullipara
• > 2hr with out regional analgesia and
• > 3hr with RA
– In the multipara
• > 1hr without regional analgesia and
• > 2hr with RA

Prolonged 2nd Stage of labor
• Factors influencing the length of the 2nd stage
include parity, maternal pushing effort, maternal
size, birth weight, OP position, fetal station at
complete dilation, and, potentially, conduction
anesthesia.
• Several studies found no increase in infant
morbidity or mortality
• However maternal morbidities including perineal
trauma, chorioamnionitis, instrumental delivery,
and postpartum hemorrhage increase with
prolonged second stages lasting greater than 2
hours.

Prolonged 2nd Stage of labor
Management Individualized
• CS if
– evidence of CPD is apparent or
– non reassuring fetal status in high station
• Instrumental delivery if;
– fetal condition is not reassuring and the station and
positions of the presenting part are appropriate.
• Expectant management if:
– No CPD and there is some degree of labor progress
– Reassuring fetal and maternal status

Introduction
• Prenatal diagnosis
– is the science of identifying Malformations,
Disruptions, Chromosomal Abnormalities, and
other genetic syndromes in the fetus.
– Its goal is to provide accurate information
regarding short- and long-term prognosis,
recurrence risk, and potential therapy and to
thereby improve counseling and optimize
outcomes
– It encompasses routine screening tests for
• aneuploidy and neural-tube defects,
• invasive diagnostic tests such as chorionic villus
sampling and amniocentesis,

Prenatal Dx-ANEUPLOIDY
-
There are three main approaches:
(1) first-trimester screening, and
(2) second-trimester screening,
(3) sequential screening in both the first and second
trimester
Screening for Down syndrome and other
aneuploidies is more complex than screening for
NTDs in that it involves more than one analyte,
and because the risk of Down syndrome is age
specific.
Sensitivity for noninvasive detection of Down
syndrome is age dependent

Screening for Downs Syndrome (Trisomy 21) - 1st
Trimester
1st Trimester screening - b/n 10 and 13 weeks
1. Nuchal translucency (NT) measurement –
• the width of the translucent space at the back of the
fetal neck determined by ultrasound.
2. Combined test- NT and maternal serum
measurements:
NT
↑β-HCGh (β-hCG: free or total), and
↓ pregnancy-associated plasma protein-A (PAPP-A),
together with maternal age.

The nuchal translucency (NT) measurement is the maximum thickness of the subcutaneous
translucent area between the skin and soft tissue overlying the fetal spine at the back of the
neck. Calipers are placed on the inner borders of the nuchal space, at its widest portion,
perpendicular to the long axis of the fetus. In this normal fetus at 12 weeks' gestation, the
measurement is 2.0 mm.

NT
-NT measured between 10 and 13weeks is a useful marker for
increased risk of chromosome abnormalities(Down syndrome-
trisomy 18 -Turner syndrome in descending order)
-Other Abnormalities are associated with large NT, even in fetuses
with normal karyotype
Eg. -Cardiac abnormalities
-Skeletal
-CNS malformations
-Diaphramatic Hernia
-Fetal demise
NT> 3.5mm-- increased risk of structural anomalies even in the
absence of aneuploidy. Such pts require targeted Us and Fetal
Echo)
2nd T NTD screening (MSAFP, US) should be offered to those who had
only 1st T aneuploidy screening who had need (ACOG, AAP-2012)

Dx of Aneuploidy- 1st Trimester
Chorionic Villous Sampling (CVS)
Invasive diagnostic test for abnormal serum marker results
Biopsy of chorionic villi is generally performed between 10 and
13 weeks’ gestation.
Purpose- Fetal karyotype , specialized genetic tests
• The primary advantage of villus biopsy is that results are
available earlier in pregnancy, allowing safer pregnancy
termination, if desired.
• A full karyotype is available in 7 to 10 days, and some
laboratories provide preliminary results within 48 hours.
• Transcervical or transabdominal approaches are
consideredequally safe and effective (ACOG, 2012a; Jackson, 1992)

CVS- Complications
• The procedure-related fetal loss rate is
comparable to that with amniocentesis ACOG, 2012a).
• overall loss rate following CVS is approximately 2
% compared with <1% following amniocentesis
• CVS has association with limb reduction defects
and oromandibular limb hypogenesis (Burton, 1992; Firth,
1991, 1994; Hsieh, 1995).
– These were commonly seen with procedures
performed at 7 weeks’ gestation (Holmes, 1993)
– . When performed at ≥ 10 weeks’ gestation, as is
commonly done today, the incidence of limb defects
does not exceed the background rate of 1 per 1000
(Evans, 2005; Kuliev, 1996).

1st T. screening Vs. multiple gestation
• For MG, NT measurements alone may be the only
screening option for fetal aneuploidy.
• Maternal serum marker screening is not as
accurate for twins and is unavailable for triplets.
• The distribution of each individual NT
measurement in multiple gestations is similar to
that in a singleton pregnancy.
• Thus, in dichorionic or trichorionic pregnancies, it
is possible to obtain an independent risk for each
fetus.
• This makes NT the marker of choice for screening
in multiple pregnancies.

2nd Trimester screening for T21
Offered b/n 15-20 weeks
• Triple test- based on measurement of
maternal serum level of
• ↓MSAFP,
• ↓unconjugated estriol (uE3), and
• ↑β-hCG (free or total), together with maternal age.
• Quadruple test (Quad test)
– Triple Test +↑ inhibin-A, together with maternal
age.

Downs Syndrome screening Tests and detection
rates- (ACOG, AAP perinatal Guidelines, 2012)
1. 1st Trimester
• NT----64-70%
• NT, βhCG, PAPP- A- 82-87%
2. 2nd Trimester
• Triple Test-
– βhCG, MSAFP, Estriol---69%
• Quad Test-
– Triple + Inhibin—81%
3. 1st and 2nd T
• Integrated
– NT, PAPP A, Quad test-94-96
• Serum integrated
– PAPP A+ Quad--- 85-88%
• Stepwise sequential---95%
– 1st T +VE dxtic test offered
(CVS????)
– 1st T –ve 2nd T test offered-
– Final Risk assessment
incorporating 1st and 2nd T
results
• Contingent sequential 88- 94
– 1st T +ve offer Dxtic test
– 1st T –veno further test
– 1st T intermidate offer 2nd T
test
– Final- Risk Assessment
incorporates 1st and 2nd
results

2nd Trimester Screening for Trisomy 18
• Trisomy 18 can be readily detected by maternal
serum analyte screening.
• Decreased levels occur for AFP, uE3 and hCG.
NB This pattern differs from trisomy 21,in which
hCG↑
• offer invasive prenatal diagnosis
(amniocentesis)whenever serum screening for
each of these three markers falls below certain
thresholds (MSAFP 0.6 MoM; hCG 0.55 MoM; uE3
0.5 MoM).
• This detects 60 to 80 percent of trisomy 18
fetuses, with a 0.4 percent amniocentesis rate

Confounding Factors in 2nd T Screening
• CF influence serum screening, and adjustments may be
necessary.
• Adjustments for maternal weight and ethnic group are
routinely employed.
• With increased maternal weight, decreased levels of
AFP, uE3, and hCG levels all occur.
• Type 1DM is associated with decreased uE3 and hCG.
• Maternal smoking increases MSAFP by 3 percent and
decreases maternal serum uE3, and hCG levels by 3
percent and 23 percent, respectively.
• Maternal serum hCG is higher and MSAFP lower in
pregnancies conceived in vitro, compared with
pregnancies conceived spontaneously

MG Vs Aneuploidy
• Since DZ twins carry independent risks of aneuploidy, the
chance of having at least one affected live-born twin at
term is twice the maternal age associated risk.
• At a maternal age of 32, the age-associated risk of
aneuploidy is
– 1 in 481 singleton births.
– 1 in 240 DZ twins , which is equivalent to a 35-year-old
woman carrying a singleton.
• For a woman carrying MZ twins, her risk of having at least
one affected live-born twin at term is the same as her age-
associated risk (i.e., 1 in 240 at 35 years of age).
Unfortunately, since her twins are MZ, this risk actually is
the risk of both fetuses being affected

Neural tube defects (NTD)
• NTDs include anencephaly, spina bifida,
cephalocele, and other rare spinal fusion (schisis)
abnormalities.
• Are the 2nd most common class of birth defect
after cardiac anomalies
• Reported frequency of NTDs is app 0.9/1000
births (Cragan, 2009; Dolk, 2010).
• NTDs are classic examples of multifactorial
inheritance.
• Their development may be influenced by
hyperthermia, hyperglycemia, teratogen
exposure, ethnicity, family history, fetal gender,
and various genes.

NTDs
• Selected risk factors are more strongly
associated with specific NTD location.
– Hyperthermia has been associated with
anencephaly risk;
– pregestational diabetes with cranial and cervical-
thoracic defects; and
– valproic acid exposure with lumbosacral defects
(Becerra, 1990; Hunter, 1984; Lindhout, 1992).

Screening for NTDs
Neural Tube Defect screening can include
– Second-trimester MSAFP and/or
– Ultrasound.
• Both have sensitivity (detection rate) of 80% to 90% for
open NTDs (However PPV of AFP 2-6%)
• MSAFP can be performed from 15 to 22 weeks‘ GA
• AFP value (MoM) adjusted for maternal age, weight,
ethnicity, gestational age, and insulin-dependent diabetes
– An elevated MSAFP is indicative of an increased risk for a
NTD and other disorders .
– A low MSAFP is indicative of an increased risk for Down
syndrome.
(MSAFP is on average 27% lower in women carrying fetuses
with Down syndrome-)
Risk of NTD in elevated MSFP ~ 1 in 50

Conditions Associated with AbnormalMSAFP Concentrations

Screening for NTDs
• US~100% sensitivity in detecting NTD
• Abnormalities of intra cranial anatomy in open
NTDs:
– Ventriculomegally
– “The Lemon Sign”  Scalloped frontal bones
– “Banana Sign”
•  Cisterna Magna Obliteration/effacement in the
anterior curvature of/with herniation of cerebral
Hemisphere

NTD Dxtic Algorithm
↑MSAFP →Amniocentesis* ( to determine AF
AFP level)-↑AF AFP →Acetylcholinestrase
assay- if this is positive→ NTD(98% sensitivity)
*Usually after US to confirm GA & fetal viablity, No of
fetuses + anatomic defects
although amniocentesis was once considered the "gold
standard" for diagnosis of open NTDs, in many centers it
has been replaced by, or used in conjunction with,
specialized sonography

contd.
• Other fetal abnormalities may be associated
with ↑ AF AFP and + ve Achsterase assay Eg.-
– ventral wall defects,
– esophageal atresia,
– fetal teratoma,
– cloacal exstrophy,
– skin abnormalities such as epidermolysis bullosa.

Amniocentesis
• Transabdominal withdrawal of AF
• the most common procedure for Dx of fetal aneuploidy
and other genetic conditions.
• generally performed between 15 -20 weeks’ gestation
but may be performed later as well.
– anterior placenta (half of all placenta locations)-60% of the
time traversed by the needle-not associated with preg loss
• The indication is usually to assess fetal karyotype
• use of FISH and array-based comparative genomic
hybridization studies have increased considerably
• Because the amniocytes must be cultured ,the time
needed for karyotyping is 7 to 10 days

Amniocentesis- Complications
• The procedure-related loss rate following midtrimester
amniocentesis is considered to be 1 per 300 to 500 (ACOG, 2012a).
• The loss rate may be doubled in women with class 3 obesity–BMI ≥
40 kg/m2(Harper, 2012).
• In twin pregnancies, Cahill and coworkers (2009) reported an
increased loss rate attributable to amniocentesis of 1.8 %.
• Some losses are unrelated to the procedure and instead are due to
abnormal placental implantation or abruption, uterine
abnormalities,
• fetal anomalies, or infection. Wenstrom and colleagues (1990)
analyzed 66 fetal deaths following nearly 12,000 2nd trimester
amniocenteses and found that 12 percent were caused by
preexisting intrauterine infection.
• Other complications of amniocentesis include amnionic fluid
leakage in 1 to 2% and chorioamnionitis in < 0.1 % (ACOG, 2012a)
• Fetal survival folloing leakage in 48 hrs > 90%(Borgida, 2000).

Selected Tests Performed on Amnionic
Fluid and Typical Volume of Fluid Required
aThe volume of fluid needed for each test may vary according to individual laboratory
specifications.
bFISH: Fluorescence in situ hybridization is typically performed
for chromosomes 21, 18, 13, X, and Y, or in the
case of a fetal conotruncal cardiac abnormality, for the
22q.1.1 microdeletion.
PCR = polymerase chain reaction.

Early Amniocentesis
• Amniocentesis performed between 11 -14 weeks,
• The technique is the same as for traditional amniocentesis,
• Sac puncture may be more challenging due to lack of membrane
fusion to the uterine wall.
• Also, less fluid is typically withdrawn—approximately 1 mL for
each gestational week (Shulman, 1994; Sundberg, 1997)
• significantly higher rates of procedure-related complications than
other fetal procedures.
• significantly Higher rates of amnionic fluid leakage, fetal loss, and
talipes equinovarus (clubfoot) than with traditional amniocentesis.
• Compared with CVS Fourfold increased rate of talipes equinovarus
(Philip, 2004).
• Anotherproblem of EA is that the higher cell culture failure rate
necessitating a second procedure.
• Forall these reasons, ACOG (2012a) recommends against the use
of early amniocentesis.

MSAFP MoM adjusted for Age, Wt, Ethnicity, GA, Type I DM
MSAFP < 2.0MoM
Normal screening result
MSAFP >2.0MoM
If not already done, standard sonographic
evaluation is performed to verify GA and
to exclude twinsb or fetal demise, with
recalculation of AFP MoM as neededb
AFP value < 2.50 MoM AFP value ≥ 2.50 MoMb
Normal screening
result
Abnormal result.
Patient counseled,
offered specialized
US ,consideration for
amniocentesis
MSAFP determined as part of multiple marker
screening at 15–20 weeksa

Second-Trimester Screening in Multiple Gestations
• Down syndrome occurs 20 % more often in twin
pregnancies than in singletons, given the known
+ve correlation between twinning and maternal
age
• Down syndrome screening using multiple serum
markers is less sensitive in twin pregnancies than
in singleton
• Using singleton cutoffs, 73 % of MZ twin
pregnancies but only 43% of DZ twin pregnancies
with Down syndrome are detected, given a 5%
false-positive rate→blunting effect of one normal
and one aneuploid fetuses in DZ twin It may be
preferable to perform invasive procedures on
both fetuses/NT in 1st T

Effect of vanishing Twin
NB A vanishing twin may cause:
• An elevated AFP level (MSAFP and amniotic fluid )
• a positive AF acetylcholinesterase assay result .
• A discrepancy between the karyotype established by
CVS and the karyotype of a surviving twin when tissue
from a vanished twin is inadvertently sampled
• Therefore, the diagnosis of vanishing twin should be
excluded to avoid confusion during maternal serum
screening for Down syndrome or neural-tube defects .
• For these reasons, amniocentesis for karyotype may
be preferable if a vanishing twin is suspected .

Components of Standard Ultrasound Examination (WILLIAMS
First Trimester
• Gestational sac location=> intrauterine vs Ectopic
• Embryo and/or yolk sac identification
• CRL
• Cardiac activity
• Fetal number, including amnionicity and
chorionicity of multiples when possible
• Assessment of embryonic/fetal anatomy
appropriate for the first trimester
• Evaluation of the uterus, adnexa, and cul-de-sac
• Assessment of the fetal nuchal region if possible

Components of Standard Ultrasound Examination by (WILLIAMS)
Second and Third Trimester
• Fetal number; multifetal gestations: amnionicity,
chorionicity, fetal sizes, amnionic fluid volume, and fetal
genitalia, if visualized
• Presentation
• Fetal cardiac activity
• Placental location and its relationship to the internal
cervical os
• Amnionic fluid volume
• Gestational age
• Fetal weight
• Evaluation of the uterus, adnexa, and cervix
• Fetal anatomical survey, including documentation of
technical limitations

Prenatal Dx of CAH- for those with risk
• Amniotic fluid anlysis for elevated level of
– 17alpha hydroxyprogesterone or
– 11 B deoxycortisol in amniotic fluid.
• Genetic diagnosis using specific probes and
cells obtained by CVS or amniocentesis also is
possible

Fetal lung maturity tests by amniocentecis
• Lecithin/sphyngomyelin ratio > 2
• Phosphotidylglycerol presence
• Florescence polarization(S:A)
Surfactant: albumin> 55( 55mg S to 1mg A)
• Optical Density(OD) 0.15
• Lamellar body count 30-40,000

Fetal lung maturity
NB:
• a mature FLM test result before 39 weeks of
gestation, in the absence of appropriate
clinical circumstances, is not an indication for
delivery.
• RDS , IVH, NEC and other complications have
been reported in premature newborns
delivered with mature lecithin
(phosphatidylcholine)/sphingomyelin ratios or
the presence ofphosphatidylglycerol
(ACOG_2008)

Operative delivery
• Abdominal
–Ceaserian Section
• Vaginal
–Instrumental Delivery
–Destructive Delivery
–Episiotomy
7/10/2016 SAMUEL BEZABIH (MD)

Cesarean section (Cesarean Delivery)
• CS is the delivery of the fetus(es), placenta and membranes
through abdominal and uterine incisions after GA of weeks
• Origin of the term Cesarean- 3 explanations
1. Julius Cesar
2. Roman Law - lex regia—king's rule or law—later became
the lex caesarea under the emperors
3. From the Latin verb caedere which means to cut
• The most logical explanation
• The term Section is derived from Latin -seco (meaning
also to cut) CS –repetitive  Cesarean Delivery (CD)
is preferable to CS
• CD is Done either on emergency or elective basis depending
on the indication

CD--Common Indications
1.Maternal-Fetal
– Cephalopelvic disproportion
– Placental abruption, Placenta previa
– Repeat cesarean delivery
– Cesarean delivery on maternal request
2.Maternal
– Specific cardiac / respiratory disease s(e.g., Marfan syndrome, unstable
coronary artery disease)
– Conditions associated with increased intracranial pressure
– Mechanical obstruction of the lower uterine segment (tumors, fibroids)
– Mechanical vulvar obstruction (e.g. extensive condylomata)
3.Fetal
– Non-reassuring fetal status
– Malpresentation, Malposition ( Breech , Brow, Face-MP, transverse lie---
– Cord prolapse
– Maternal herpes
– Congenital anomalies

CD- infection Prevention
• Prophylactic antibiotics about 30 minutes before
skin incision
– Ampicillin/cephazolin are Commonly used
agents
• Surgical site preparation
– No hair shaving ( skin break bacterial entry
site.
– If necessary the hair can be clipped before
surgery
– Skin preparation ;Chlorhexidine, alcohol,
povidone-iodine

CD - Types of Abdominal Incision
 Type of abdominal incision to be made depends
on the urgency of the delivery, prior incision
type, the potential need to explore the upper
abdomen for nonobstetrical pathology etc
• Transverse incisions
• Pfannenstiel incision
– ~3 cm cephalad to symphysis pubis, ~12cm long
ending with slight upward curving
– The most commonly employed incision , best
cosmetic results and less postop pain
• Joel- Cohen incision
• Vertical Mid line incision (often Sub umbilical)

CD-Types of Uterine incision
• Lower uterine segment transverse incision /LUSTI/
• Lower vertical (De Lee) incision
• Classical ( upper segment vertical) incision
–Has high risk uterine rupture on subsequent
pregnancies and labor
• Inverted T incision
• ‘J’ shaped

CD
 Indications For Classical Incision
Underdeveloped lower uterine segment
Breech or transverse lie with undeveloped lower
uterine segment
Inability to develop bladder flap with repeat
cesarean delivery
Lower segment anterior myoma
Anterior placenta previa

Complications of CS
• Increased Maternal mortality (2-4x that of SVD)
• Operative injuries (bladder, bowel)
• Hemorrhage
• Endomyometritis
• UTI
• Wound infection
• Thrombo-embolic disorders
• Caesarean hysterectomy
• Uterine rupture/ dehiscence in future
pregnancies
• Placenta previa /accreta

Trial of labor (TOLAC) and Vaginal Delivery After
Previous Cesarean Section (VBAC)
• Appropriately selected candidates for TOLAC
have a 60- 80% success rate of VBAC
• Risks of uterine rapture after 01 previous CD
in TOLAC
– LSTCS ~0.5-0.9%
– Classical incision-

TOLAC and VBAC
Selection criteria useful in identifying candidates
for VBAC:
One previous low-transverse cesarean delivery
Clinically adequate pelvis
No other uterine scars or previous rupture
Physician immediately available throughout active
labor who is capable of performing an emergency
cesarean delivery
Availability of anesthesia, facility, and personnel
for emergency cesarean delivery

TOLAC and VBAC
TOLAC is contraindicated in:
–Two prior uterine scars and no vaginal
deliveries
–Previous classical or T-shaped incision or
–extensive transfundal uterine surgery
–Previous uterine rupture
–Medical or obstetric complication that
precludes vaginal delivery
–Lack of anesthesia, facility, or personnel for
an emergency cesarean delivery

Operative Vaginal Deliveries
• Instrumental Deliveries; There are two forms
of
1. Forceps
2. Vacuum( Ventose)

1.Forceps Delivery

Forceps Delivery
Indications
• Prolonged second stage
• To shorten the second stage in cases with
– Maternal distress /poor voluntary pushing effort
– Preeclampsia
– eclampsia
– Cardiac or pulmonary diseases
– Glaucoma
– Cerebrovascular diseases:
– aneurysm
• Fetal distress and cord prolapse
• After-coming head in breech presentation

Prerequisites for Forceps Delivery
• Ruptured membranes
• Fully dilated cervix
• precisely known Presentation & position
– Vertex presentation with OA or Op Position
– Face presentation with mentoanterior position
– After-coming head in breech (Piper’s forceps)
• Engaged Head ( station at least 0)
• Clinically adequate pelvis (No CPD)
• Adequate maternal analgesia is available
• Bladder drained
• Knowledgeable operator
• Willingness to abandon the procedure, if necessary
• Informed consent has been obtained
• Necessary support personnel and equipment are present

Forceps Delivery
Contraindications( CI)
– Any CI for vaginal delivery
– Unengaged head
– Fetal bleeding disorder, bone dimineralization
– Maternal HIV infections (i.e.,)

Forceps Delivery
Application Types
• Outlet Forceps-
– head on pelvic floor, seen at the interoitus without
turning the labia
– sagital suture at AP diametere, Left or Right OA/OP
– rotation not greater than 45⁰
• Low Forceps-
– head below +2cm but not on pelvic floor.
– Rotation can be greater or less than 45⁰
• Mid Forceps ( station 0 - 2+cm) and
• High Forceps (above 0)are not practiced currently

Forceps Application Types (1988 classification)
• Outlet
– Scalp visible at introitus without separating labia
– Fetal skull has reached the pelvic floor
– Sagittal suture is in the AP Diameter ( OA/ OP ) ,or
ROA/LOA/ROP/LOP position
– Fetal head is at or on the perineum
– Rotation does not exceed 45°
• Low Forceps
– Leading point of fetal skull is at ≥+2 cm and not on the pelvic
floor
– Rotation ≤45° (to LOA /ROA to OA, or LOP/ROP to OP), or
– Rotation ≥45°
• Midforceps
– Station above +2 cm, but head engaged
• High
– Not included in classification

Forceps Types
• Classic (Simpson's, Elliot)
– used primarily for traction when there is to be
little or no rotation
• Specialized
– these forceps are designed for rotation or special
indications
– Kielland (for rotation)
– Barton (for rotation)
– Piper (for the aftercoming head in breech
deliveries)

Classic forceps:
A. Simpson.
B. Elliot.
C. Tucker-McLean

Specialized forceps:
A. Kielland (for rotation).
B. Barton (for rotation).
C. Piper (for the aftercoming head in breech deliveries).

Forceps Application in OA position
• First apply the left blade:
– Lubricate the blade.
– Hold the handle of the left blade with your left hand freely and
apply it to the left side of the mother guided by the two fingers
of the right hand.
• Apply the right blade:
– Hold the handle by your right hand and place it to the right side
of the mother guided by the two fingers of the left hand.
– The right is always below the left when locked.
• Locking is easy when applied correctly.
– If it is difficult, disarticulate and apply again after re-ascertaining
the position and station.
– Never apply undue force to lock.
• Check application is correct and no maternal tissue is
entrapped.

Forceps Application in OA position
In Correct Application:
• Locking is easy;
• The application is biparietal -
bimalar.
• The posterior fontanels
should be about one finger’s
breadth in front of the plane
of the shanks and equidistant
from the blades
• the sagittal suture should be
perpendicular to the middle
of the plane of the shank.

Forceps Application
Delivery of the head
• Traction is synchronized with uterine contractions .
• With each pull, the head should descend.
• Two or three pulls are usually needed to effect delivery
of the head
• In-between tractions, check FHB and application is
correct
• Perform an episiotomy with crowning of the head
• Once the head reaches the pelvic outlet, lift it out using
the forceps
• Remove the right first followed by the left forceps

Forceps Application
Further care After delivery
• Inspect the vagina and cervix; and repair if
there is any tear
• Examine the newborn for any injury

Failed Forceps
• A failed forceps is diagnosed if:
1. Fetal head does not descend with each pull,
2. Fetus is undelivered after three pulls with no
descent or after 30 minutes
• The possible causes are:
– Undiagnosed CPD
– Incomplete cervical dilatation
– Wrong diagnosis of position
– Incorrect application ,
*After a failed forceps, Cesarean delivery is
undertaken if the fetus is alive.

Complications of Froceps Delivery
1. Fetal complications:
– Facial nerve injury ( usually self-limiting )
– Facial or scalp laceration;
– cephalohematoma
– Fracture of the face or skull: Usually heal by
themselves- often only observation
2. Maternal complications:
– Genital tear/ laceration( cervix, vagina, or vulva)
– Rupture of the uterus
– Postpartum hemorrhage (traumatic PPH)

2.Vacuum/Ventose Delivery
• Vacuum delivery is effected using the ventose
(vacuum extractor).
• The main action of the ventouse is traction with
an additional effect of rotation.
• Its main components are the ;
– suction cup,
– vacuum pump and
– traction devices
• Cups could be Soft ( Plastic, silicone) or Rigid
(Metallic)

Kiwi Vacuum Device

Vacuum Delivery
• Indications and contra indications:
– the same as that of forceps
• Prerequisites and classification (outlet, low and
Mid) : the same as forceps
NB.
• In emergency conditions vacuum can be applied
with CX dilatation of > 8cm.
• Applied only on vertex presentation
• The fetus must be alive and term (not to be
applied before 34wks of GA)

vacuum –Advantages over forceps
• Easier to apply,
• Less force is placed on the fetal head,
• Require less maternal anesthesia,
• Results in less maternal soft tissue trauma,
• do not affect the diameter of the fetal head
compared to forceps
In general, vacuum delivery is probably safer than
forceps for the mother, while forceps are probably safer than
vacuum for the fetus.

Vacuum Delivery
Application:
• The ideal application of  the cup is superimposed
on the flexion point.
– The flexion point is 2--3 cm in front of the posterior
fontanels at the sagittal suture.
• A wrong application of the cup center
– anterior to the flexion point- leads to defluxion attitude
while by
– >1 cm lateral of the sagittal suture exacerbates Asynclitism
• Check for correct application and entrapment of maternal tissue.
• If there is maternal tissue entrapment, release it
before creating vacuum

Vacuum Delivery
Vacuum creation
• Create a vacuum of 0.2 kg/cm2 negative
pressure and check that maternal tissue(cervix
or vagina) is not entrapped
• Gradually increase the vacuum to 0.8 kg/cm2
in 10-12 minutes and recheck the application
and maternal tissue is not entrapped.

Vacuum Delivery-traction
• Start traction with contraction with a finger on the
scalp next to the cup to assess potential slippage and
descent of the vertex;
• Pull in line with the pelvic axis and perpendicular to the
cup; do not rotate/rock the cup to effect rotation;
traction alone is expected to bring rotation;
• Between contractions,check for fetal heart and cup
application;
• With progress and absence of fetal distress, continue traction
with contraction for 30 minutes or till three successive pulls
fail to advance the head;
• As soon as the head is delivered, release the vacuum
and proceed with the delivery of the fetus;

Vacuum- Further Care
• After delivery inspect the vagina and cervix;
and repair if there is any tear
• Immediate neonatal examination and care
– Provide vitamin k for the infant within one hour of
delivery.
– Check for scalp abrasions and lacerations;
– Measure the head circumference, and watch the
chignon (localized scalp edema after the vacuum
cup). The chignon gradually disappears in few
hours.
– Cephalhematoma may develop gradually

Failed Vacuum
Diagnosis is based on any one of the following
conditions
− The head does not advance with each pull
− The fetus is not delivered with 3 pulls
− The fetus is not delivered within 30 minutes
− The cup that is applied appropriately and pulled in the
proper direction with maximum negative pressures
slips off the head twice.
• After failed vacuum, the fetus is delivered by C/S.
• Every vacuum application should be considered
as a trial of vacuum delivery.

A
Ask for help; address the patient (inform her about what you
are going to do and get informed consent); Assess Anesthesia
needs.
B Bladder empty
C Cervix fully dilated
D Determine fetal position and think shoulder dystocia
E Extractor and resuscitation equipment ready
F Apply cup on the flexion point
G Gentle traction in the proper axis
H
Halt traction when the contraction is over; halt the procedure
if it is not progressing normally.
Mnemonic for vacuum extraction

Vacuum Delivery-Complications
Fetal
• scalp lacerations and bruising,
• subgaleal hematomas,
• cephalohematomas,
• Intracranial hemorrhage,
• neonatal jaundice,
• subconjunctival hemorrhage,
• clavicular fracture,
• shoulder dystocia,
• injury of sixth and seventh cranial nerves,
• Erb palsy,
• retinal hemorrhage, and fetal death

Complications of Vacuum
Maternal Complications
• Vaginal or cervical laceration/tear

Destructive Delivery (DD)
• Destructive vaginal operations (deliveries) are
procedures undertaken to reduce the bulk of
a dead fetus in obstructed labor to facilitate
delivery .
• The main advantages of these operations are
prevention of
– cesarean delivery
– dissemination of infection .
– maternal trauma .

Types of DD
–Craniotomy
–Craniocentesis
– Decapitation
–Evisceration
–Cleidotomy

DD---A. Craniotomy
• In craniotomy, the head of the dead fetus is
perforated to evacuate the brain tissue; and
• decrease its size to effect extraction of the
fetus.

DD-Craniotomy….
Indication
• Obstructed labor with a dead fetus due to CPD
in brow, face and vertex presentations
• Entrapped an after-coming head

DD-Craniotomy….
Prerequisites
–Dead fetus
–Fully dilated cervix
–Descent of 2/5 or less in cephalic
presentation
–entrapped after coming of head
–Ruptured membranes
–Intact uterus

DD-Craniotomy….
Contraindication
• Severely contracted pelvis with true
conjugate less than 7.5 cm won’t allow the
delivery of he uncompressible bimastoid
which has 7.5 cm diameter.
• Ruptured uterus
• Dead fetus without obstruction
• Doubtful fetal demise

Preparations for Craniotomy
• Put up an IV drip; hydrate and resuscitate the
woman as required
• Determine hemoglobin, blood group, cross
match and others based on complications
• Give broad spectrum antibiotics
• Avail consent of the patient/parent
• Use aseptic & antiseptic care

Preparation for Craniotomy
• Analgesics : pethidine (with or without
diazepam)
• local, spinal or general anesthesia as required
( It is preferred to perform the procedure in
the OR).
• Put patient in lithotomy position
• Clean and drape the vulva and perineum
• Catheterize the bladder

Craniotomy-Procedure
 Site of entry of the cranium:
• Vertex presentation:
– Make a cross-shaped incision through the skin of
the head right down to the bone.
– Push a perforator or scissors through a fontanell
or a suture and enter into the cranium
• Face presentation:
– through the orbit/ or hard palate
• Brow presentation:
– through the frontal bones

Craniotomy-Procedure…
• After coming head
–Make an incision at the base of the neck;
–inter the cranium by inserting the perforator
or
–scissors through the incision and tunneling
subcutaneously to reach the occiput.
–Perforate the occiput to drain the brain
tissue as above

Craniotomy; Procedure……
• Introduce the perforator, with closed blade,
under palmer aspect of fingers protecting
anterior vaginal wall and bladder .
• Avoid sudden sliding of your instrument over
the skull and getting into maternal tissue.
• Open the perforator or the scissors and
rotate it to disrupt the brain tissue; the brain
should now be coming out from the hole.

Craniotomy;Procedure….
• Put 3-4 strong volsellum forceps, kochers or
heavy-toothed forceps on the skin and the
bones and pull on the forceps to achieve
vaginal delivery.
• In case of breech, pull on the delivered part of
the fetus.
• Protect the vagina by avoiding sharp scalp
bone edges tearing the vaginal wall by your
finger or by removing the offending bones.

Cephalocentesis
• Puncture of the Skull in case of hydrocephalus
to drain the CSF fluid to achieve vaginal
delivery
• Can be done vaginally or trans abdomen

B.Decapitation:
• Decapitation is severing the fetal head in
Obstructed labor with a dead fetus and
neglected shoulder presentation
• The decapitate head and the trunk are
delivered separately through the birth canal.

C. Evisceration
• Evisceration is removal of thoracic and or
abdominal contents through an opening at
most accessible site on the abdomen or
thorax.
• Indications
– Neglected shoulder presentation with dead fetus
& neck not accessible for decapitation
– Fetal malformation (fetal ascitis, monsters,
distended bladder & hydronephrosis)

D. Cliedotomy
• Cliedotomy is used to reduce the bulk of the
shoulder girdle of the dead fetus by cutting
one or both clavicle(s).
• It is indicated in shoulder dystocia.
• The preparations are as in craniotomy.

Post-destructive Operation Care
• Explore the uterus, cervix and vagina and treat
accordingly.
• Keep catheter for 7-14 days if there is prolonged
pressure of the presenting part on the bladder
(obstructed labor) or trauma to the wall of the
vagina;
• Manage the third stage actively and start 1000
ml D/S, Ringer’s or saline fluid with oxytocin
• Treat infection: Broad spectrum antibiotics.
• Continue with IV fluid and record vital signs and
input/ output.
• Correct anemia and shock as indicated

Complications of destructive operations
• Trauma to the birth canal including vaginal
fistula Recto-vaginal fistula
• Post partum hemorrhage /PPH/due to atonic
uterus or genital trauma
• Shock due to hemorrhage or sepsis

II. Episiotomy
• An episiotomy is an incision of the perineum
made to enlarge the vaginal outlet to
facilitate delivery.
• It is made at the end of the second stage of
labor just before delivery, when indicated.
• It increases the area of the outlet for the fetal head
during delivery, particularly in assisted deliveries with
forceps or the vacuum extractor.
• An episiotomy is used to prevent major
perineal lacerations.

Episiotomy Types
1. Median or medial episiotomy:
– Vertical incision from the posterior forchette to
the rectum in the midline of the perineal body.
– Advantages:
• less blood loss,
• easier to repair,
• more comfortable during healing
– Disadvantage:
• possible extension into the anal sphincter
and rectum.

Episiotomy Types…….
2. Mediolateral episiotomy:
– incision at a 45 degree to the posterior forchette
on either side .
– Advantage:
• more room with less risk of injury to the rectum
and sphincter
– Disadvantages:
• more difficult to repair,
• more blood loss,
• more discomfort during healing

I
INDUCTION OF LABOR
• Induction of labor is the artificial stimulation of uterine
contractions before the spontaneous onset of true labor at GA
of 28 or more weeks
• Induction methods
– Membrane Stripping,
– Amniotomy (ARM)
– Nipple stimulation
– Pharmacologic methods:
• Oxytocin,
• prostaglandin analogs

Common Indications of Induction
1. Preeclampsia/eclampsia,
2. chronic hypertension , Gestational HTN
3. Diabetes mellitus
4. PROM
5. Chorioamnionitis
6. Abruptio placentae
7. Post term pregnancy
8. IUFD
9. Rh iso-immunization
10. IUGR

Contraindications To Labor Induction
CI. for labor or vaginal delivery such as;
– Placenta Previa, Vasa Previa
– Transverse and Oblique Lie ,
– Breech With Contraindication For Vaginal Deliver
(E.G., Footling, Extended Neck).
– CPD, Brow Presentation, Face With Mento
Posterior,
– Cord Presentation
– Twin Pregnancy,
– Extensive Genital Wart, Active Genital Herpes
– Cervical Cancer

Contraindication of induction…..
• Contraindications to oxytocin use such as
–uterine scar after:-
• Caesarean section,
• myomectomy,
• perforation,
• ruptured uterus etc
–meconium stained amniotic fluid,
–NRFHRP

Induction- CIs
Relative Contra Indications
• Relative CIs to oxytocin use such as
– breech presentation (e.g., frank, complete),
– bad obstetric history,
– grand multi parity
• presenting part above the pelvic inlet (relative)

Induction-Confirmation of Term Gestation
• US at < 20 weeks supports >39 wks of GA
• Fetal Heart Tones documented by Doppler
before 30 weeks
• 36 weeks have passed since hCG test +ve

Induction- Cervical assessment
• Before induction the cervx should be
assessed by bishops score to ensure that
it is favourable for vaginal delivery

Bishop Score
Score Dilatation
(cm)
Effacem
ent (%)
station consistency Position
0 closed 0—30 -3 Firm Posterior
1 1—2 40—50 -2 Medium Mid
2 2—3 60—70 -1,0 soft anterior
3 >=5 >=80 +1,+2
7/10/2016 *Station is graded from -3 to +3

Induction- Bishop Score
Interpretation of the Bishop’s score:
1. Score<4: Unfavorable cervix
– is unlikely to yield for induction.
– Cervical ripening is needed for success with induction.
– Postpone induction for next week if possible or
– use cervical ripening and plan induction for next day.
2. Score 5-8: Intermediate
3. Score ≥ 9: Favorable cervical condition and
– induction is likely to succeed.
– No need for cervical ripening.
– Induction using Oxytocin can be planned for next day.

Cervical Ripening
• Cervical Ripening:
– to facilitate the process of cervical softening, thinning,
and dilating with resultant reduction in the rate of
failed induction and induction to delivery time.
• Cervical Ripening Methods
– Mechanical cervical dilators-
• Osmotic dilators (eg Laminaria japonicum), Foley
catheter, extra-amniotic saline infusion
– Prostaglandin analogues (also stimulate contraction)
• PGE1 analogue- misoprostol
• PGE2 analogue- dinoprostone

Induction Procedure
• Artificial rupture of membrane( ARM) is
usually performed.
• Oxytocin infusion
– 0.2IU oxytocin/1000ml NS
– Start with 20 drops/min Increase drop by 20 every
30 min till a maximum of 80drops/min
– If no adequate contraction at 80drops/min add a
2nd 2IU of oxytocin.(50, 60, 80 drops/min
increasing the drop every 30 min)
– If still no adequate contraction add a 3rd dose of
2IU oxytocin (50,60, 80 drops )

Failed induction
Definition:
• Failed induction is failure to initiate good
uterine contraction.
• It is diagnosed if;
–adequate uterine contractions are not
achieved after 6 to 8 hours of oxytocin
administration and
–use of the maximum dose for at least one
hour.

Complications
• Failed induction (increased risk of CS )
• Atonic PPH
• Iatrogenic prematurity
• Tachysystole (< 5 contractions/10min)*
• Fetal heart rate abnormalities
• Uterine rupture
*-Stop oxytocin infusion
- Use tocolytics if available

Complications-cont’d
• Chorioamnionitis (prolonged ROM ,repeated PV)
• Fetal sepsis and MTCT of HIV (ARM)
• Cord prolapse (ARM)
• Placental abruption (ARM)

Augmentation of Labor
• Augmentation of labor is stimulation of the
uterus to increase the frequency, duration
and/ or strength of spontaneously initiated
labor.
• The main indication of augmentation is:-
– weak and ineffective uterine contractions leading
to abnormal progress of labor.
• Methods and procedure are generally similar
to induction (ARM + Oxytocin)

Thank you !!!!!

Multifetal Gestation (MFG)
• Multifetal pregnancies may result from
– two or more fertilization events,
– a single fertilization followed by an “erroneous”
splitting of the zygote, or
– a combination of both.
NB. Either or both processes may be involved in the
formation of higher numbers.
• Quadruplets, for example, may arise from as few as
one to as many as four ova

Types OF MFG
• Monozygotic or Identical twins
• Dizygotic or Fraternal twins-
• Higher Order MG

MFG-Incidence
• Dramatic increase in the past 30 years
– ART
– Old maternal age at birth
• b/n 1980 and 2009
– Twinning rate rose from 18.9 to 32.1 per 1000 live
births in i.e. 76 % rise (Martin, 2012). During the same
time,
• The number higher-order multifetal births
increased more than 400% to a peak in 1998 and
decreased since then and it is 138 per 100,000
births in 2010.

Superfetation Vs Superfecundation
• In superfetation, an interval as long as or longer
than a menstrual cycle intervenes between
fertilizations
– Common in mares, as yet unproven in humans
• Superfecundation refers to fertilization of two
ova within the same menstrual cycle but not at
the same coitus, nor necessarily by sperm from
the same male.

Monozygotic (Identical) Twining
• MZ twins Arise from a single fertilized ovum
that divides
• Relatively constant incidence world wide
(~ 1set in 250 births)
• No identifiable Risk Factor  independent of
race, heredity, age, and parity
– However incidence of MZ T ↑es in ART– may be
due to minor trauma to the blastocyst during
manipulation
• Among natural conceptions, MZ twins;
– Consist of 30% of all twin pregnancies
– Occur in 1 in 250 pregnancies

MZ Twinning
• Despite virtually the same genetic heritage,
MZ twins Usually are not identical bs/e of
– Unequal sharing of protoplasm
– Discordant mutations
• Postzygotic mutation
• Inherited mutations with varying expression
Eg. differential expression of sex linked traits and
diseases in female fetuses due to skewed lyonization
(Glinianaia, 2008).
• Post zygotic loss of Y chrs – X0 (Turners) with female phenotype
and Normal 46XY male sibling
– Teratogenic effect of MZ twining process
discordant malformation
• Eg one with congenital heart disease the other Normar.

MZ Twining
• MZT may vary by amniocity and chorionicity
depending on division time after fertilization.
1. Dichorionic, Diamniotic
– cleavage at 0-4days (at morula stage)
– single fused or two separate placenta
– The lowest risk among monozygotic
2. Monochorionic+diamniotic
– cleavage at 4-8days( Blastula)
– I.e.one placenta two AF.
– Risk of TTT
3. Monochorionic+monoamniotic
– 8-12 days( embryonic disc cleavage)
– The highest risk ( mainly cord entanglement)
4. Conjoined( MC+MA) >13days

Dizygotic(Fraternal) Twining- DZT
• DZTs result from fertilization of two separate ova
• More common than MZ
• Have identifiable risk factors ;affected by
– race, age, parity,heredity,fertility rx
• Among natural conceptions DZ twins
– Consist 70% of all Twin pregnancies
– Occur in ~ 1% to1.5% of pregnancies

Dizygotic(Fraternal) Twining- DZ
Risk factors
• Race ( Yorube tribe of Nigeria ,1/ 20 birth ,
– high level of FSH- High rate of DZ twins, the reverse is true
for Japanese women) (Knox and Morley (1960)
• Age
– peak at the age of 37:,
– Maximal FSH stimulation - multiple follicles (Beemsterboer, 2006)
– Increased ART use- more likely older women Ananth 2012 )
– DZT frequency 4x increase b/n 15 and 37 (painter 2010)
• Heredity
– the family history of the mother is more important than
that of the father

Risk factors---DZT
• Parity
– Increasing parity has been shown to
independently increase the incidence of twinning
in all populations studied.
• Infertility Treatment
– Ovulation induction (FSH +CGTH /Ccitrate) and ART
(IVF-Transfer of multiple embryos- ↑ lkelihood of MG)
• Maternal Nutritional status/ size
– increased twining with good Nutritional status
– Taller and heavier mom  well nourished 25-30%
greater twining than smaller/ malnourished mom.
WWII- malnutrition- marked fall in DZT rate.

Dizygotic (Fraternal) Twining- DZ
Pituitary FSH secretion
• The common factor linking race, age, weight,
and fertility to Multifetal gestation may be FSH
levels (Benirschke, 1973).
• This theory is supported by the fact that
increased fecundity and a higher rate of
dizygotic twinning have been reported in
women who conceive within 1 month after
stopping oral contraceptives, but not during
subsequent months (Rothman, 1977).

DZT….RFs
• This may be due to the sudden release of
pituitary gonadotropin in amounts greater
than usual during the 1st spontaneous cycle
after stopping hormonal contraception.
• Indeed, the paradox of declining fertility but
increasing twinning with advancing maternal
age can be explained by an exaggerated
pituitary release of FSH in response to
decreased negative feedback from impending
ovarian failure (Beemsterboer, 2006).

Sex Vs Zygosity
• Twins of opposite sex are almost always dizygotic.
• Rarely , the karyotype or phenotype of a MZ twins can be
different.
– This can be due to somatic mutations or chromosome
aberrations.
• Most reported cases are related to postzygotic loss of the Y
chromosome in one 46,XY twin.
• This results in a phenotypically female twin due to Turner
syndrome (45,X).
• Zech and colleagues (2008) reported a rare case of a 47,XXY
zygote that underwent postzygotic loss of the X
chromosome in some cells and loss of the Y chromosome in
other cells.
• The phenotype of the resultant twins was one male and
one female.
– Karyotype analyses revealed both to be 46,XX/46,XY genetic
mosaics.

Chorionicity Vs Zigosity
• Monochorionic twins are always MZ,
• Approximately 70% of MZ twins are
monochorionic and 30% will have a
dichorionic placentation
– Rarely, however, MC twins may in fact be dizygotic
(Hack, 2009).
– Mechanisms for this are not yet clear but all
reported cases were concieved by ART
procedures. Ekelund and coworkers (2008)
• All DZ twins will be dichorionic

Diagnosis Of MFG
• Clinical
• Ultrasound is used to determine Fetal number,
Chorionicity and Amniocity
– Chorionicity
• DC-lambda/ Twin Peak sign
• MC- inverted T sign

Maternal Physiology in MFG
• In general, the degree of maternal physiological
change is greater with multiple fetuses than with a
single fetus.
– Higher serum β-hCG level early in 1st trim
– Excessive N & V
– Blood volume expansion- 50-60%  in excess of
~500ml compared with singleton (40-50% increase)
– RBC mass expansion---proportionately less than that
of singleton P
• Both the remarkable increase in maternal BV and the increased iron and folate
requirements predispose to a greater prevalence of maternal anemia.
– average blood loss at delivery- 2x that of singleton ~
1000ml

Maternal Physiology in MFG
• Typical BP pattern in twin pregnancies
– Lower DBP than in singletones as early as 8wk, but
generally higher at term
• Vascular resistance- significantly lower than in
singletons through out pregnancy
• CO – 20% more than singleton P
– Mainly due to greater SV and to a lesser degree to increased
heart rate
• Pulmonary functions same as that of singleton preg.
• If hydramnios develops, maternal renal function can
become seriously impaired, most likely as the
consequence of obstructive uropathy (Quigley, 1977).
– Therapeutic Amniocentesis for symptomatic relief and avoidance
of preterm labor

Vanishing Twin
• Loss /death of one fetus before 2nd trimester
The other develop to term and delivered as
singleton
• The incidence of twins in the first trimester is
much greater than the incidence of twins at
birth.
• one twin is lost or “vanishes” before the
second trimester in up to 10 to 40 percent of
all twin pregnancies (Brady, 2013).
• The incidence is higher in the setting of ART.

Pregnancy Complication in MG
Fetal and infant complications
– Abortions/Miscarriages
– Preterm delivery
– Low birthweight
– FGR
– Cerebral Palsy
– PNM
– Fetus acardiacus
– Fetus papyraceous
– Congenital anomalies

• The incidence of congenital malformations is appreciably increased
in multifetal gestations compared with singletons.
• Glinianaia and associates (2008) reported that the rate of
congenital malformations was 406 per 10,000 twins versus 238
per10,000 singletons.
• MC 2X more risk than DC
• ↑ incidence in MG than singletons manly due to
structural defects in MZ twins- 03 categories
I. 20 to Teratogenic event in twining- Conjoined Twins, cardiac
anomallies, NTD , Sirenomelia
II. 20 to vacsular anastomosis- TRAP, DIC and embolization from
dead fetus, BP fluctuations resulting in microcephally
hydranencephaly intestinal atresia aplasia cutis, or limb
amputation.
III. 20 to fetal crowding EG. talipes equinovarus (clubfoot)
congenital hip dislocation. ( DZ Ts are also affected)

• Proportion of DZ Twins with congenital
malformation has been increasing in the past
30 yrs ( by 30%) while that of MZ remained
stable Possible consequence of ART

• PTB complicate up to 50 percent of twin, 75 percent of
triplet, and 90 percent of quadruplet pregnancies
(Elliott, 2007).
Preterm Birth
• The duration of gestation decreases with increasing
fetal number .
• According to Martin and colleagues (2012), more than
five of every 10 twins and nine of 10 triplets born in
the US in 2010 were delivered preterm.
• Prematurity is increased six-fold and tenfold in twins
and triplets, respectively (Giuffre, 2012)
• Preterm Birth – GA?
– 60 percent of twins,
– 90 percent of triplets, and
– virtually all of quadruplets

Pregnancy Complications
Low Birth Weight
– LBW more in MG than singletones due to FGR and
PT birth
– Weight parallels that of singleton till 28 -30wk, then
lags with clear divergence beginning 35-36 weeks
– Incidence of overt FGR at 38 wk- 4x & half of twins
are affected
Based on growth curve of singletons
• MZ more likely to have FGR than DZ bcse of
– Unequal allocation of blastomeres,
– vascular anastomosis  unequal O2 and nutrient
ditribution, the twining event MZT eg in quintiplets of
3 DZ (all >1400gm) and 2 MZ twins (860and 990 gm )

Maternal Complications
• Increased medical complications than in
singleton pregnancies
– HEG, GDM, HTN, Anemia
• Hemorrhage
• Polyhydramnios + 20 obstructive uropathy
• Cesarean Delivery
• Post partum Depression(BLUE)

Cumulative percent of singleton, twin, and triplet or higher-order multifetal
births according to gestational age at delivery in the US during 1990. (From Luke,
1994, withpermission.)

Pregnancy Complications
Prolonged Pregnancy
• Bennett and Dunn (1969) suggested that a twin
pregnancy of > 40 weeks should be considered
postterm.
– Twin stillborn neonates delivered at > 40 weeks
commonly had features similar to those of
postmature singletons
• From an analysis of almost 300,000 twin births,
Kahn and coworkers (2003) calculated that > 39 weeks, the
risk of subsequent stillbirth was greater than the
risk of neonatal mortality.
• Parkland- emprical 40weeks or more- Postterm

Incidence of Twin Pregnancy Zygosity and Corresponding Twin-
Specific Complications Will 24th

Monoamniotic Twins
• 1% of MZ / 1 in 20 MC twins
• High fetal death rate -10% resulting from
– Cord entanglement (>50%),
– Cong anomally,
– preterm birth,
– TTT
• No M'gt to ascertain good outcome
• unpredictability of cord entanglement and lack of
effective method to monitor it
• Morbid cord entanglement appears to occur
early, and MA pregnancies that have successfully
reached 30- 32 weeks are at reduced risk.
• Rupture of separating membrane in DA Ts
convert to MA with the same risk of MM

MA Twins
• Color flow Doppler Sonography can be used to
diagnose entanglement
• women with Monoamniotic twins are
recommended to undergo 1 hour of daily fetal
heart rate monitoring, beginning at 26- 28 weeks.
• With initial testing, a course of betamethasone is
given to promote pulmonary maturation.
• If fetal testing remains reassuring, cesarean
delivery is performed at 34 weeks and after a
second course of betamethasone.

MC Twins- Vascular Anastomosis
• Placental vascular anastomosis is unique to
MC twins.
– Superficial AA (commonest), VV, AV,
– Deep AV at the capillary bed of a villus
• Deep AV anastomosis
Common villous compartment/3rd circulation
Shunt depending on pressure and gradient
Consequences-
Twin Twin Transfusion syndrome (TTTS) ,
TRAP Sequence, Acardiac Twinning

TTTS
• The prevalence TTTS is app 1- 3 /10,000 births (Simpson, 2013).
• Unidirectional Blood flow through AV anastomosis
(Donor Recipient)an imbalance in blood volumes
• Deoxygenated O blood in the Donors (D) Umbilical Artery is pumped
into shared Cotyledon  Oxygenation in the chorionic villus  Blood
leaves Villus through the Recipient’s (R) placental Vein
Donor
• anemic, growth restricted, oligohydramnios- Stuck, Pale
• contractures, and pulmonary hypoplasia
Recipient
• polycythemic, Plethoric appearance
• Circulatory overload/ Hypervolemia-Heart Failure-Hydrops,
Hydramnios
• Hyperviscosity~~ Occlusive thrombosis,
Hyperbilirubinemiakernicterus

TTTS
• Clinically important TTTS chronic with significant
vascular volume difference
• Typical presentation ( mid pregnancy )
• Hypovolemic Donor- reduced RBF Oliguria,
Oligohydramnios stuck (No AF, No motion)
• Recipient- too much urine- Severe Hydramnios
 polyhydramnios-oligohydramnios–syndrome—“poly-oli.”

TTTS- Brain Damage
• Cerebral abnormalities in ~8% of affected live births.
• Common in TTTS are;
– Cerebral Palsy,
– Microcephaly,
– Proencephaly, Multisystem encephalomalecia
• Mechanism - not well understood
• Ischemic necrosis  Cavitary brain lesions
– D- Hypotension, Anemia
– R- Hypotension sec to BP unstablity
• Death of one Twin
– Acute Hypotension in the living twin:-
– Embolization of thromboplastic matter from dead
(less likely)

TTTS- Dx and Staging
Diagnosis
• Previously- Wt Discordance and HGB
differences in MC twins late onset findings
• Society of Feto-maternal Medicine criteria
(2013)
– Mc, DA twins
– Hydramnios (SDP > 8cm) in one sac and
Oligohydramnios (SDP < 2cm) in the other
Staging
• Quintero staging system(1999)

TTTS-Dx and staging
 Harkness and Crombleholme (2005) propose the following sonographic
findings as being suggestive of this diagnosis:
1. monochorionicity,
2. same-sex gender,
3. Hydramniosis defined if the largest vertical pocket is >
8 cm in one twin and oligohydramnios defined if the
largest vertical pocket is < 2 cm in the other twin,
4. umbilical cord size discrepancy,
5. cardiac dysfunction in the recipient twin with
Hydramniosis,
6. abnormal umbilical vessel or ductus venosus Doppler
velocimetry, and
7. significant growth discordance

TTTS- Staging
• Once identified, TTTS is typically staged by the Quintero staging
system (Quintero and colleagues, 1999). These are defined as follows:
• Stage I
– MC- DA Gestation with discordant amnionic fluid volumes
(R SDP>8cm, Donor SDP<2cm), but urine still visible
sonographically within the donor twin's bladder.
• Stage II
– criteria of stage I, but urine is not visible within the donor's
bladder.
• Stage III
– criteria of stage II and abnormal Doppler studies of the umbilical
artery, ductus venosus, or umbilical vein
– Umbilical Artery- Abscent/Reverse EDF,
– Ductus Venosus- abscent/ REDF,
– Umbilical Vein-Pulsatile flow
• Stage IV
– ascites or frank hydrops in either twin; and
• Stage V
– demise of either fetus.

TTTS- Prognosis and Management
• Prognosis depends on stage and GA
– Stage I- >3/4th remain stable/ regress without
intervention
– Stage III or more- worse prognosis, 70-100%
perinatal loss if no intervention
• Treatment Options
– Serial amnioreduction
– Laser ablation of anastomosis
– Septostomy
– Selective feticide

TTTS-Selective Fetal Reduction
• Selective reduction has generally been considered if
severe AF and growth disturbances develop before 20
weeks
• In such cases, both fetuses typically will die without
intervention
• Which Twin to be selected for reduction?-
– depending on evidecce of damage and comparison of
prognosis
Methods
• UV/Umbilcal cord occlusion of the selected T using;
– radiofrequency ablation,
– fetoscopic ligation, or
– coagulation with laser, monopolar, or bipolar cauterization
(Challis, 1999; Chang, 2009; Donner, 1997)
• Injection of lethal substances is inappropriate;both can
be affected through the shared circulation

Growth Discordance
• Affects ~15% of Twin pregnancies
• More common in MC than DC (b/se of
unequal sharing of the common placenta,
aside from TTTS)
• Typically occurs late 2nd or 3rd T
• Poor prognosis if seen before 20week
• Diagnosis
– AC difference of > 20mm
– Wt difference of > 20% ( >25-30%- most accurately
predict adverse perinatal outcome)

Growth Discordance Causes
MZ
• Vascular anastomosis
• Unequal sharing of
placenta (probably the
most important
determinant)
• Discordance for
structural anomalies
DZ
• Difference in genetic
growth potential Esp.
in opposite sexes
• Placental implantation
site difference- sub optimal
implantation site- GR
• Placental pathology
• Iux crowding

Growth Discordance-Management
• Growth assessment and calculation of wt
discordance- mainstay
– MC more frequent assessment than DC- b/se of
increased risk of death and neurologic damage
– Eg Q2wk for MC and Q 4week for DC
• Fetal surveillance if GR in one or both fetuses
– NST, BPP, Umb A Doppler recommended, but no
prospective trial evaluation
• Delivery
– no sufficient data about optimal time
– Size discordance alone doesn’t prompt delivery,
except occasionally at advanced GA
– RCOG (2008)- 37wk for MC and 38wk for DC

Delivery Timing in MFG
• Risk of PNM start to increase after 38
wks of GA
• > 40wk- post-term for twins
• Delivery recommendations for
uncomplicated twin pregnancies are
–DC- DA- 38 weeks
–MC-DA- b/n 34 and 37 weeks
–MC-MA- 32-34 week
( ACOG 2014)

Delivery Route in MFG
• The optimal Route of delivery depends on
type of twins, presntation and GA.
– MA twins
• C/D, to avoid cord complications
– DA Twins
• Twin-A Vertex, GA> 32wk- Vaginal delivery
• Twin A Breech- Most prefer CD b/se of fear of Chin-
Chin locking in vaginal delivery
• Optimal delivery route for high order MFGs is
unknown

ABORTION
• Termination/end of pregnancy before the
age of viability.
• WHO, CDC, NCHIS Def.-
– pregnancy termination before 20 wks OR
–With a fetus weighing 500gm
( however 500gm is a mean wt at 22-23 wks,
Wt at 20 wk~320gm)

Abortion Types
• Spontaneous
– Clinical stages:-threatened, inevitable, incomplete,
complete, missed
– Recurrent
• Induced
– medical vs surgical
– safe vs unsafe (illegal)
• Early (<12wk), Late (> 12wk)
• Septic
– any form of abortion complicated by infection

Epidemiology
• approximately 15% of all clinically recognized
pregnancies end in spontaneous abortion
• About 80% of spontaneous pregnancy losses
occur in the first trimester;
• the incidence decreases with each gestational
week

Spontaneous Abortion (SAB)
• Expulsion of POCM with out any intervention
80 % of SAs are in < 12 weeks
 at least half of these caused by
chromosomal anomalies.
 Male: Female Ratio in early abortuses
~ 1.5 (Benirschke and Kaufmann, 2000).
After 1st trimester, both the abortion rate
and the incidence of chromosomal
anomalies ↓es.

SAB -Pathogenesis:
• 1st Trimester losses, nearly always , are
preceded by embryonal/fetal death
– in most later pregnancies losses no fetal death
before expulsion
• Death of the fetus is usually accompanied by
Hemorrhage into the decidua basalis followed
by adjacent tissue necrosis  stimulation of
uterine contractions that result in expulsion.
• The expelled gestational sac
• may contain small macerated fetus or
• may be a Blighted Ovum ( without fetus).

Clinical Classification of SAB
• The clinical aspects of spontaneous
abortion can be classified a number of
ways.
• Commonly used subgroups Include
–Threatened,
– Inevitable,
–Incomplete, and
–Missed Abortion.

I. Threatened Spontaneous Abortion
• DIAGNOSIS:-
– bleeding/ bloody discharge through closed Cx os.
– The bleeding may be followed by cramping
abdominal pain a few hours to several days later.
• Incidence; in 20-25% of early pregnancies ~1/2
of which will abort
• +ve Cardiac activity  good prognostic sign
(better chance of pregnancy continuation)
• Surviving fetuses are at increased risk for preterm
delivery, low birth weight, and perinatal death
(Johns, 2006; Weiss, 2002).
• Maternal risks;antepartum hemorrhage, manual
removal of the placenta, and cesarean delivery
(Wijesiriwardana, 2006).

Risks in Pregnancies that survived TA

Threatened Spontaneous Abortion (STAB)
DDX:-
• Physiologic/Implantation bleeding
(at time of expected menses),
• Cervical lesion (Polyp, Cx, Decidual rxn),
• Epx. (should always be considered)

How to RO EP
• TVUS:-to determine pregnancy location
– Gestational Sac(GS);may be seen by 4.5 weeks
– an anechoic fluid collection that represents the
exocoelomic cavity
– Pseudo GS may have similar appearance Dx of Iux
pregnancy should be made cautiously if the yolk sac is
not yet seen
• yolk sac is visible by 5.5 wks, and MGSD(mean
gestation sac diameter) of 10 mm.
• At 5 to 6 weeks, a 1-2mm embryo adjacent to the
Yolk Sac can be seen
– If no embryo in a Gestational Sac with MSD of 16 to 20
mm  a dead fetus

How to RO EP ???
– detection at 6 to 6.5 wks with 1 to 5 mm embryonic
length and MSD of 13 to 18 mm.
– A 5-mm embryo without cardiac activity is likely dead
• Pregnancy of unknown location (POUL)
• serial quantitative serum β-hCG and
progesterone levels
– β-hCG increase 53 to 66 percent every 48hrs-alive
Inra-uterial pregnancy
– Serum P > 20ng/ml- alive, < 5ng/ml- dying

Mgt
• Ascertain viability and location of pregnancy
Serum beta hCG, TVUS, serum progesterone,
• Hct ( if heavy bleeding)
RX- no effective therapy
• Bed rest (doesn’t change the coarse),
• Analgesic (acetaminophen) for discomfort.
• Evacuation for heavy bleeding causing
hypovolemia and significant anemia (some prefer
transfusion if Fetal is alive)
• No evidence based support for antiD administration
( some administer 50micg Anti D for all 1st T bleedings)

II. Inevitable Abortion
• Findings in inevitable abortion
– Gross rupture of membranes/Gush of fluid
– Vaginal bleeding
– Open cervical OS on pelvic exam
– No tissue expulsion
• Commonly, either uterine contractions begin
promptly,
– resulting in miscarriage, or infection develops
• Management
– Uterine evacuation

III. Incomplete Abortion
• Bleeding that follows partial or complete placental
separation and dilation of the cervical os.
• The fetus and the placenta partially extrude
through the dilated os or may remain entirely
within the uterus
• Management options of IA include completion via:
– curettage (MVA, Sharp curettage)
– medical abortion (Misoprostol) or
– expectant management in clinically stable women.
• In others, retained placental tissue simply lies
loosely within the cervical canal and can be easily
extracted with ring forceps

IV. Complete Abortion
 Expulsion of the entire pregnancy(may be completed
before a woman presents to the hospital)
 History
• heavy bleeding, cramping, and
• passage of tissue or a fetus is common.
– Can be complete gestation, blood clots, or a
decidual cast
 Physical Examinationa
closed Cx Os , often no uterine contraction

Complete Abortion………..
Diagnosis
1. Examination of passed tissue (Patients are
encouraged to bring it )
2. US: Empty Utires with minimal endometrial
thickening + previously documented intrauterine
pregnancy
 If neither of the above two is possible, EP should be
ruled out
 Serial B-hCG levels drop quickly With complete
abortion

V. Missed Abortion
• A missed abortion is the retention of a failed
intrauterine pregnancy for an extended
period, usually defined as more than two
menstrual cycles.
• These patients have an absence of uterine
growth and may have lost some of the early
symptoms of pregnancy.
• Management
– Expectant or evacuation

VI. Septic Abortion
• Commonly results from unsafe/ illegal abortions
• 1 to 2 % of women with threatened or incomplete
miscarriage develop a pelvic infection and sepsis syndrome
• Elective abortion, either surgical or medical, is also
occasionally complicated by severe and even fatal
infections (Barrett, 2002; Ho, 2009)
• Bacteria gain uterine entry and colonize dead POC ,may
invade myometrial tissues and extend to cause
– parametritis,
– peritonitis,
– septicemia, and,
– rarely, endocarditis (Vartian, 1991).
• Particularly worrisome are severe necrotizing infections
and toxic shock syndrome caused by group A
streptococcus—S pyogenes (Daif, 2009).

Septic Abortion Management
Management of clinical infection includes
– prompt administration of broad-spectrum antibiotics
– Suction curettage If there are retained products or fragments.
• Most respond to this Rx within 1 to 2 days,
• Discharge-when afebrile.
• Follow-up with oral antibiotic Rx is likely unnecessary (Savaris, 2011).
• Intensive Supportive Care
– for those very few women who develop ARDS, AKI, or DIC 20 to Severe
Sepsis Syndrome .
• Prevention of postabortal sepsis:-- prophylactic antibiotics
• For induced or Spontaneous Abortion that require medical or
surgical intervention ACOG (2011b) recommends:-
– Doxycycline, 100 mg PO 1 hr before and then 200 mg po after a
surgical evacuation.
• For MAs, Doxycycline 100 mg po bidx7days beginning with
abortifacient administration (Fjerstad, 2009b

SAB-Etiology A. Fetal Factors
• Chromosomal abnormality (Aneuploidy)
– 50 % of 1st trim (75% <8wks),
– 20-30% in 2nd T,
– 5-10% of 3rd trim. losses
Aneuploidy:
• An abnormality involving a
chromosome number that
is not an exact multiple of
the haploid number
• (one chromosome set is
incomplete)

SAB-Etiology Fetal Factors
Causes of chromosomal abnormalities
– ~95%-maternal gametogenesis errors,
– ~5% -due to paternal errors
1. Monosomy x/45x (Turner syndrome)
– the only monosomy compatible with life
– single most common cause of abortion ~ 20%
– Autosomal monosomy:-rare and incompatible with life
2. Trisomies (autosomal):
– the most common cause as a group( > 50% of aneuploidies)
– Results of isolated non dysjunction
– Autosomal trisomies for all except chromosome number 1
have been identified in abortuses, and those with autosomes
13, 16, 18, 21, and 22 are most common
– Trisomy 16 is the most common among trisomies + always
lethal

SAB Etiology-Fetal Factors, Aneuploidy
Polyploidy( usually Triploidy)
• 20% of miscarriages, Usually cause blighted ovum
or partial mole .
– Triploidy often associated with hydropic placental
(molar) degeneration - Incomplete (partial) HFM.
• Trisomy16 can also result in PHFM.
– Although these fetuses frequently abort early, the few
carried longer are all grossly malformed
– Tetraploid abortuses ;rarely live born , most often
aborted in early gest .
• Chromosomal structural abnormalities
– infrequently cause abortion.
– Some infants who are live born with a balanced
translocation may appear normal

Chromosomal Findings in First-Trimester Abortuses
• CHROMOSOMAL STUDIES . INCIDENCE RANGE(%)
1. Anembryonic (blighted ovum) ∼50%
2. Embryonic ∼50%
• Euploid 46,XY and 46,XX 45 to 55
• Aneuploid
– Autosomal trisomy 22 to 32
– Monosomy X (45,X) 5 to 20
– Triploidy 6 to 8
– Tetraploidy 2 to 4
– Structural anomaly 2

SAB Etiology-Maternal Factors
Age — advancing maternal age is the most
important risk factor for spontaneous miscarriage
in healthy women.
• The overall rate of SAB was 11% and the
approximate frequencies of clinically recognized
miscarriage according to maternal age were:
– 20 to 30 years -----9 to 17%,
– 35yeras -------------20 %
– 40 years ------------40 % and
– 45 years-------------80 %

Etiology; B.Maternal Factors
1. Infections -Uncommon causes of abortion
• L.monocytogenes, parvovirus, CMV, or HSV appear
to have no abortifacient effects
• Brucella abortus, Campylobacter fetus, and T. gondii
infections (abortificents in livestock)- unclear role
• Mycoplasma hominis and U. urealyticum, syphillis,
HIV infections-Conflicting data
• C. trachomatis was found to be present in 4% of
abortuses compared with < 1% of controls ↑ed risk
• polymicrobial infection from periodontal disease has
been linked with a two- to fourfold increased risk
• BV-increased 2nd T loss risk-Oakeshott and
associates (2002)

Etiology-Maternal Factors
2. Medical disorders
• Endocrine( hyper/hypothyroidism, DM)
• Celiac disease -RPL
• Cyanotic heart disease,
• Renal diseases,
• CT (SLE)
• IBD
• Chronic HTN- no significant risk

Maternal Fs…..
3. Immunologic Factors-- RPL
– autoimmune Fs (APA commonly seen in SLE
pts., ),
– Alloimune Fs(Parental HLA similarity failure to
produce blocking Abs,altered NK cells activity,
↑ed lymhocytotoxic Abs---)
4. Inherited Trombophilias-RPL
– mutations of the gene for factor V Leiden,
prothrombin, antithrombin, proteins C and S, and
methylene tetrahydrofolate reductase
(hyperhomocysteinemia)

Etiology-Maternal Factors……
5. Malnutrition
– increased risk observed with morbid obesity and
severe dietary Deficiency.
6. Drugs and Environmental factors
– Alcohol
• Increased risk with frequent alcohol use in the 1st 8wks
• Insignificant risk with low level alcohol consumption
– Coffee-
• slightly ↑ed risk with >5cups/day (~500mg caffeine)
– Tobacco
• ↑ed risk , proportional to number of cigarettes smoked/day
– Radiation

Maternal factors- Anatomic
7. Uterine Factors
– Congenitally ↓ed uterine cavity( unicornuate,
Bicornuate, septate ux)
– DES associated malformations (T- shaped/hypo-
plastic ux)
– Myomas ( esp.submucosal,intramural)
– Scarred uterus( D&C, Myomectomy…
– Incompetent cervix

Estimated Prevalence of Some Congenital Uterine
Malformations and Their Associated Pregnancy Loss Rate-
will Gyn 2nd ED

Cervical Incompetence
• Recurrent sequential events in CI.
– 2nd Trimester Painless Cx Dilatation-- Membrane
prolapse and ballooning into vagina-- Expulsion of
immature fetus
– Prediction via midpregnancy TVUS cx length < 25
mm and funneling—ballooning of the membranes
into a dilated internal os, but with a closed external os
to guide circleage– no proven benefit

C.Paternal Factors---Will 24thED
• These factors in the genesis of miscarriage are
not well studied.
• Chromosomal abnormalities in sperm reportedly
had an increased abortion risk (Carrell, 2003)
• Increasing paternal age was significantly
associated with increased risk for abortion in the
Jerusalem Perinatal Study (Kleinhaus, 2006).
• This risk was lowest before age 25 years, after
which it progressively increased at 5-year
intervals.

Recurrence
• In women who have had one prior SAB , the
rate of spontaneous abortion in a subsequent
pregnancy is about 20%;
• in women who have had three consecutive
losses, the rate is 50%.
• The causes of this condition are varied and
most often unknown .
• Patients should be reassured that, in most
cases, spontaneous abortion does not recur.

Complications of abortion
1. Coagulopathy
• Serious disruption of the coagulation
mechanism as the consequence of abortion
may develop in the following circumstances:
– Prolonged retention of a dead fetus
– Sepsis syndrome—a notorious cause
– Labor induction with a prostaglandin
– Instrumented termination of the pregnancy
– Intrauterine instillation of hypertonic saline or
urea solutions

Complications of abortion
2. Resumption(restarted) of Ovulation Following
Miscarriage
• Ovulation may resume as early as 2 weeks after an early
pregnancy is terminated, whether spontaneously or
induced.
• Lahteenmaki and Luukkainen (1978) detected surges of
LH at 16 to 22 days after abortion in 15 of 18 women
studied.
• Plasma progesterone levels, which had plummeted after
the abortion, increased soon after LH surges.
• These hormonal events agree with histologic changes
observed in endometrial biopsies (Boyd, 1972).
• Therefore, if pregnancy is to be prevented, effective
contraception should be initiated soon after abortion.

Recurrent Pregnancy Loss(RPL)
• Dx.as > 3 consecutive pregnancy losses at < 20
wks of GA or fetus weighing < 500gm ( most
occur before 14 wks)
• Affects 5% of couples
• Incidence increases with increasing maternal age
• The 3 widely accepted causes of RPL are:
1. Parental chromosomal abnormalities
2. Antiphospholipid antibody syndrome
3. Uterine abnormalities
• Other causes (suspected but not proven) are
– alloimmunity,
– endocrinopathies,
– various infections, and environmental toxins

Induced Abortion
1. Therapeutic – indicated
– surgical or medical indications E.g.
• Persistent Cardiac Decompensation,
• Advanced Hypertensive Vascular Disease, And
• Invasive Carcinoma Of The Cervix.
– Other indications- rape, inscest, significant fetal
deformity
2. Elective/Voluntary- no indication
– Performed on request of the woman
– Surgical and medical methods

Abortion Techniques
1. Surgical
D and C
• MVA <12wk
• Menstrual aspiration (1-3 wks after
missed period)
• Sharp curettage < 15wks
D and E (> 16 wks)
– Destruction and evacuation of fetal
parts
D and X (> 16 wks)
– Partial Birth Abortion- politicians
term
– Brain matter aspirated after
delivery of body
• Laparotomy-
– Hysterotomy,
– Hysterectomy
2. Medical
• IV oxytocin
• PG ( E1, E2, F2ἀ)
• Intraamnotic
hyperosmolar solution
– 20% saline
– 30% urea
• Antiprogesterones—RU 486
(mifepristone) and epostane
• Methotrexate— IM and PO
• Various combinations of
the above

Surgical Vs Medical Techniques
Factor Medical Surgical
• Invasiveness Usually no Yes
• Pain More Less
• Vaginal bleeding Prolonged unpredictable Light,
predictable
• Incomplete abortion More common Uncommon
• Failure rate 2–5% 1%
• Severe bleeding 0.1% 0.1%
• Infection rate Low Low
• Anesthesia Usually none Yes
• Time involved Multiple visits, follow-up exam Usually 1 visit no
follow-up, exam

Post Abortion Care
• A global initiative in response to the problem of
maternal mortality resulting from unsafe abortion
• Elements Of PAC:
1. Treatment of incomplete, unsafe abortion and
life threatening conditions;
i.e. resuscitation, antibiotics ,uterine evacuation etc.
2. Counselling to respond to women`s need +
Emotional support
3. Contraceptive service
4. Provide other reproductive and other health
services or link/ refer to appropriate facilities
(units within the same facility)
5. Community & provider partnership

Dr.SAMUEL BEZABIH
yekatit 2008
SAMUEL BEZABIH (MD)

ECTOPIC PREGNANCY
• An ectopic or extrauterine pregnancy is one
in which the blastocyst implants anywhere
other than the endometrial lining of the
uterine cavity
SAMUEL BEZABIH (MD)

Epx………
• Tubal EP >95% EP
Ampullary-Isthmic-Fimbrial-Interstitial ( in descending order of freq.)
• Ovarian- 3%
• cervical <1%
• CS scar <1%
• Abdominal -1%
• Hetrotopic
• Bilateral ectopic
SAMUEL BEZABIH (MD)

Incidence
• The prevalence of EP among women
presenting to an emergency department with
– 1st trimester vaginal bleeding,
– abdominal pain, or
– both reported to be as high as 18% .
• It is the leading cause of maternal death in the
first trimester (4 to 10 percent of all pregnancy related deaths-UPTO date)
=>6% of all pregnancy-related deaths;
SAMUEL BEZABIH (MD)

Risk Factors
• Previous EP ( 15-20% recurrence in either the same or other
tube)
• Salpingitis- (50% risk)
• Peritubal adhesions 2⁰ to:
– infections (postabortal, peurperial)
– appendicitis,
– endometriosis
• Tubal surgery-(ligation, reanastomosis, TS for EP/
infertility
• IUDs: lower incidence of ectopic pregnancy than non-contracepting
women because IUDs prevent pregnancy but if pregnancy Occurs
it has high likelihood of being ectopic
– Risk:-1.02/10,000 WY,( less than half of the risk posed on
women who use no contraceptive)
SAMUEL BEZABIH (MD)

Risk factors….
• Progestin only contraception( POPs , injectables) =>4-6% of
pregnancy in users are EP
• History of infertility
• ART
• Developmental abnormalities of the tube
– (e.g. diverticula, hypoplasia…)
– mainly associated With intrauterine DES exposure. * DES=diethylstilbestrol
• Increased maternal age
• Multiple sexual partners (Due toincreased risk of PID)
SAMUEL BEZABIH (MD)

Contraceptives Vs EP
• The incidence or absolute risk of EP is reduced with all
methods of contraception.
• For any method, the EP rate (pregnancy rate X the
proportion of pregnancies with ectopic implantation) is
lower than for women using no contraception (2.6
EP/1,000 woman-years).
• Vasectomy and OCPs
– the lowest EP absolute incidence (0.0005/ 1000WY)
• IUDs and BTL:-relatively higher incidence
– IUD risk:- 1.02/10,000WY, less than half of the risk posed
on women who use no contraceptive
– BTL:- a 10 year risk of 7.2/ 1000 procedures ( ~1/3rd of the
sterilization failures (18.5 pregnancies/1000procedures)
SAMUEL BEZABIH (MD)

Natural history of EP
Because of unfavorable environment, early
interruption is inevitable.
• Possibilities include:
1. Tubal abortion:
• complete or incomplete.
• Common way in Ampullary & infundibular
• May be resorbed or implant on peritoneum / viscera
and develop as 20 abdominal pregnancy
2. Tubal rupture:
• common in interstitial & isthmic pregnancies
3. Tubal perforation
4. Continuation of pregnancy- rarest

Rupture of EP
• Mostly spontaneous, but can also be caused by trauma as
in bimanual pelvic examination or coitus.
• Timing of tubal rupture is partially dependent on pregnancy
location
– Isthmic (narrow space=>the earliest rupture, in 6- 8wks)
– Ampullary (in ~8-12 wks)
– Interstitial * (in 12-16 wks))
• After rupture embryo may;
- be resorbed
- remain as a mass in abdominal Cavity or culde sac
- implant in abdominal cavity.
* may cause fatal bleeding from uterine and ovarian
arteries
SAMUEL BEZABIH (MD)

Acute VS Chronic EPs
• Acute Eps.
– Healthy, rapidly growing trophoblastic tissue
– High level of serum hcG.
– No early bleeding late Dx.
– carry the highest risk of tubal rupture compared
with chronic
• Chronic Eps.
– Abnormal trophoblastic cells that die early
– Early bleedingearly Dx
– Low /static serum hCG
SAMUEL BEZABIH (MD)

DDx of EP
– Normal pregnancy
– Abortion ( incomplete, threatened..)
– Ovarian cyst rupture
– ovarian torsion
– AGE
– Appendicitis
– Salpingitis
– Molar pregnancy
SAMUEL BEZABIH (MD)

Dx-Signs and symptoms
• Clinical symptoms of an EP usually appear 6
to 10 weeks after the LNMP
– Abdominal Pain
– Vaginal Bleeding
– Amenorrhea
– Uterine changes of pregnancy
– Adnexal mass
– Abdominal Tenderness
– Hemodynamic instability
– Syncope
SAMUEL BEZABIH (MD)
TRIAD OF
EP

EP Dx- Ruptured vs unruptured
Unruptured EP
• Symptoms of early
pregnancy
irregular spotting or
bleeding,
– N,V ,swelling of breasts,
– bluish discoloration of
vagina and cervix,
– softening of cervix, slight
uterine enlargement,
– increased urinary
frequency)
• Abdominal & pelvic pain
Ruptured EP
– Collapse, weakness, syncope
– Fast, weak pulse (>110/min)
– Hypotension
– Hypovolaemia
– Acute abdominal pain and
– Abdominal distension(SD)
– Rebound tenderness
– Anemia
SAMUEL BEZABIH (MD)

DX- TVUS
• TV US should be considered for all women with
suspected early gestational pathology.
• An initial transvaginal ultrasonography (TVUS) is
used to visualize:
– An intrauterine pregnancy or
– a definite extra-uterine gestation
– or it can be nondiagnostic/NDUS (nothing seen to
confirm a gestation inside or outside the uterus)
*TVUS is the most useful test for determining the location of a
pregnancy.
*combination of TVUS and hCG will permit a definitive
diagnosis in almost all cases at a very early stage of pregnancy.
SAMUEL BEZABIH (MD)

EP-DX
EP is likely with TVUS findings of:
– Empty ux** ( EP or dead Intrauterine fetus/complete
abortion) plus
• Adnexal mass separate from ovary and uterus (may be
corpus luteum cyst)
• Tubal ring/gestational sac with yolk sac/embryo (Definitive)
• Dilated tube with cul-de-sac fluid (rapture)
**Intra uterine gestational sac rules out EP (Neverthless,
there is Increased chance of hetrotropic pregnancy in ART
cases)
*hetrotropic pregnancy : the combination of an intrauterine
pregnancy and a concurrent pregnancy at an ectopic location.
SAMUEL BEZABIH (MD)

EP-DX
• The woman with a NDUS examination result
requires further evaluation, including
measurement of serum hCG and progesterone
levels
• The "Discriminatory Zone" of hCG is that level of
hCG which when reached is associated with the
appearance, on TVUS, of a normal singleton
intrauterine gestation
– generalized 1,500-2,000 mIU/mL (International Reference
Preparation.
SAMUEL BEZABIH (MD)

DX-Serum progesterone
• Serum progesterone level (SPL) determination may
help confirm DX of EP.
• Serum progesterone values are independent of hcG
levels, and an abnormal progesterone level is
consistent with an abnormal, failing pregnancy but
does not identify the site of the pregnancy (failed
intrauterine or ectopic pregnancy).
– <5 ng/mL an abnormal pregnancy (100% specific ).
– >20 ng/mL=> usually normal intrauterine pregnancies,
– 5-20 ng/mL are considered equivocal.
• Most ectopic pregnancies are associated with a serum
progesterone level between 10--20 ng/mL, limiting the
clinical utility of this assessment.
SAMUEL BEZABIH (MD)

Dx-NDUS
What to do with NDUS finding?
1. If HCG > discriminatory level
– Do D&C to detect presence of villi
• villi found*  Iux pregnancy
• No villi (arias stella Rxn)  EP pregnancy
2. If HCG < discriminatory level
– Follow HCG titer( doubling time)**
• Normal increase Do US when hCG reaches DZ
• Sub-normal doubling  EP/ abnormal iux preg
*villi can be identified by floating the uterine contents in saline
and searching for characteristic bubble like structures joined by
strands of tissue
**hCG ↑ rate <53% in 48 hrs => abnormal pregnancy (99% sensitivity in early pregnancy)
***mean doubling time for the HCG ranges from 1.4 to 2.1 days in early pregnancy (UPTO date)

DX
• In NDUS or SPL consistent with failed pregnancy
serial hCG levels must be used to evaluate an
ongoing pregnancy.
• hCG ↑ rate <53% in 48 hrs => abnormal pregnancy
(99% sensitivity in early pregnancy)
• Therefore, a NDUS examination result with a serum
progesterone level < 5 ng/mL and an inappropriate
increase in hCG are each associated with an
abnormal pregnancy.
• If necessary, endometrial sampling can be used to
differentiate between a failed intrauterine
pregnancy and ectopic pregnancy by confirming the
presence or absence of intrauterine chorionic villi.
SAMUEL BEZABIH (MD)

Dx- NDUS
 Repeat TVUS examination when the hCG
reaches the discriminatory zone if :
– an initial US examination has non diagnostic
result,
– SPL is equivocal or normal, and
– hCG level increases appropriately, and
– the patient is clinically stable,
 The same diagnostic possibilities then should
be considered.
SAMUEL BEZABIH (MD)

Endometrial Sampling
There are a number of endometrial changes
associated with EP that include:-
– decidual reactions found in 42 % of samples,
– secretory endometrium in 22 %, and
– proliferative endometrium in 12 % (Lopez, 1994).
– Trophoblasts are not seen.
• Barnhart and associates (2002) recommend that
absence of trophoblastic tissue be confirmed
by curettage before methotrexate treatment
is given.
SAMUEL BEZABIH (MD)

Arias – Stella reaction
ASR; Nuclear enlargement, irregularity and
hyperchromesia and cytoplasmic vacuolation
of endometrial cells.
– Described by Arias-stella (1954)
• May also be seen in normal pregnancy or
spontaneous abortion
• Cause – poorly understood, two hypothesis
– Exaggerated proliferative and secretory response
to elevated hormones of pregnancy???
– Involutional/ regressive endometrial changes in
response to declining hormonal levels???
SAMUEL BEZABIH (MD)

The Arias-Stella reaction of the endometrium. The glands are closely packed and
hypersecretory with large, hyperchromatic nuclei suggesting malignancy.
SAMUEL BEZABIH (MD)

EP- Dxtic Procedures
• TV Color Doppler sonography:-“Ring of Fire” of an ectopic
pregnancy placental blood flow around the periphery of
the pregnancy. This finding, however, may also be seen with
corpus luteum cysts.
• Laparoscopy:- ahead of D&C for desired pregnancy
• Laparotomy:-for unstable pt with presumed DX of EP
• Culdocentesis- (largely replaced by TV US)
– positive(along with symptoms)- aspiration of non clotting blood(5cc)
– negative-serous fluid
– non-diagnostic- little clotting blood
 Nonclotting blood indicates active intraperitoneal bleeding.
 Determine the hematocrit:
 A Hct>15% is most consistent with hemorrhage from a ruptured EP or
actively bleeding ruptured corpus luteum
 while a hematocrit less than 8 %t is more consistent with blood tinged
fluid from a ruptured ovarian cyst or pelvic inflammation. UPTODATE
SAMUEL BEZABIH (MD)

Rx of EP
I.Expectant Mgt (EM)
Waiting for possible Tubal abortion,
separation and resolution
 candidates -asymptomatic, compliant pt.
– with low HCG(<200mu/ml) and
– low chance of rupture
SAMUEL BEZABIH (MD)

Medical Mg’t
• Early detection of EP can lead to successful
management without surgery.
• Methotrexate, a folic acid antagonist, can be
used successfully to treat early, non ruptured EP.
• The overall success of treatment of EP in
observational studies ranges from 71.2% to
94.2%
• Success of medical rx of EP depends on the:
– treatment regimen used,
– gestational age, and
– hCG level (If hCG levels are higher than 5,000 mIU/mL, multiple
doses may be appropriate*)
SAMUEL BEZABIH (MD)

Medical Mg’t-ACOG 2008
*Several observational studies reported a
failure rate of >14.3% with single-dose
methotrexate when pretreatment hCG levels
are > 5,000 mIU/mL, compared with a 3.7%
failure rate for hCG levels <5,000 mIU/mL
SAMUEL BEZABIH (MD)

Medical Mg’t
Methotrexate rx can be considered for those
women with;
– confirmed, or high clinical suspicion of, ectopic
pregnancy
– hemodynamic stability
– un ruptured mass.
– compliance for follow-up surveillance.
• Methotrexate affects all rapidly dividing tissues
within the body, including bone marrow, the GI
mucosa, and the respiratory epithelium.
• Hepatotoxic , cleared by renal system
SAMUEL BEZABIH (MD)

Methotrexate for EP
• Before administering methotrexate, a woman
should have;
– a confirmed normal serum creatinine level,
– normal liver transaminases, and
– no bone marrow dysfunction indicated by significant
anemia, leucopenia, or thrombocytopenia
• Typically, these laboratory tests are repeated 1
week after administering methotrexate to
evaluate any possible impact on renal, hepatic,
and hematologic function. (pre and post
treatment LFT, RFT, CBC )
• Rx response- elimination of trophoblastic activity
(revealed by serum HCG level)
SAMUEL BEZABIH (MD)

Medical Mgt of EP
Absolute contraindications of methotrexate:
– breast feeding,
– Immunodeficiency,
– Alcoholism ,alcoholic liver disease ,any CLD,
– previous blood dyscrasias( BM hypoplasia,
thrombocytopenia, leukopenia, significant
anemia)
– methotrexate hypersensitivity,
– pulmonary disease,
– PUD,
– renal, hepatic, hematologic dysfunction.
SAMUEL BEZABIH (MD)

Medical mg’t
Relative CI:
– adnexal mass >3.5cm,
– fetal heart motion ( high failure rate)
SAMUEL BEZABIH (MD)

Medical mg’t- systemic methotrexate
Regimen
Three protocols are published for
methotrexate treatment of EP.
1. Single Dose,
2. Two Dose, And
3. Fixed Multidose
SAMUEL BEZABIH (MD)

Medical mg’t- systemic methotrexate
1. Single dose=> 50mg/m2 IM stat
Follow up
– Check HCG on days 4&7
• ( 15% ↓se is expected b/n days 4&7)
– Then check weekly until comes to non pregnant
level
– If HCG decreases by < 15%, repeat 2nd dose of
50mg/m2 and check HCG on days 4&7.
– This can be repeated as necessary
– If HCG level increases/plateaus on follow up
consider repeating MTX
SAMUEL BEZABIH (MD)

Medical Rx of E
1. Two dose*50mg/m2 IM on day 0 and 4
Follow up
– Measure HCG on days 4 & 7
– If HCG decrease by > 15%- weekly measurement till
non-pregnant levels reach
– If HCG level decreases by< 15% - repeat the same
dose on days 7 &11 measuring HCG concomitantly
– if HCG decreases by>15% b/n days 7 and 11, continue
weekly follow-up, if not opt for surgical management)
* A recent prospective study evaluating a two-dose regimen
found high patient satisfaction, few side effects, and 87%
treatment success
SAMUEL BEZABIH (MD)

Medical Rx of EP
3. Fixed multi dose*=>
 1mg/kg IM on days 1,3,5,7 + folinic acid 0.1mg/kg IM on days 2,4 6, 8
Follow-up :
– Measure HCG on MTX days until its level is 15%
below the previous value,
– then weekly until reaching non prepregnant level
*a recent meta-analysis has shown the fixed multidose
regimen to be more effective, especially in treating
women with more advanced gestations and those with
embryonic cardiac activity
SAMUEL BEZABIH (MD)

Medical Treatment Protocols for EP.ACOG 2012
SAMUEL BEZABIH (MD)
The single-dose and multidose methotrexate protocols are associated with
overall resolution rates for ectopic pregnancy that approximate 90 %

Medical Rx of EP
• Methotrexate also can be used after surgical
management of an ectopic pregnancy.
• Treatment failure (persistent EP.) ranges:-
– 2% to 11% after laparotomy and salpingostomy,
– 5% to 20% after laparoscopic salpingostomy .
• A non-ruptured, persistent EP after
salpingostomy diagnosed by monitoring
serial hCG levels almost uniformly resolves
with a single dose of methotrexate.
SAMUEL BEZABIH (MD)

Methotrexate-Direct Injection into EP
• In efforts to minimize systemic side effects of
methotrexate, local injection into the
gestational sac under sonographic or
laparoscopic guidance has been evaluated.
• Pharmacokinetic studies with 1 mg/kg of
methotrexate injected either into the sac
under sonographic guidance or by traditional
IM injection showed similar success rates.
• However, fewer drug-related side effects were
seen with local injection (Fernandez, 1995).
SAMUEL BEZABIH (MD)

Other Regimens for Med Rx
1.Mifeprostone + Meth
• It seems logical that the addition of 600 mg of
mifepristone orally to single-dose methotrexate
might improve efficacy and speed resolution of
unruptured EPs.
• In a randomized trial of 212 cases, however,
Rozenberg and coworkers (2003) documented no
differences in success rates.
SAMUEL BEZABIH (MD)

Other Regimens for Med Rx…..
2.Hyperosmolar Glucose.
• In a small prospective trial, Yeko and colleagues
(1995) reported that direct injection of 50-%
glucose into the ectopic mass using laparoscopic
guidance was 94% successful in women with an
unruptured ectopic whose serum β-hCG level was
<2500 IU/L.
• Gjelland and coworkers (1995) reported that
treatment success was significantly better in a
similar population in which sonographic-rather
than laparoscopic-guided injection was used.
SAMUEL BEZABIH (MD)

Med mg’t….
• Available studies comparing MTX to traditional surgical
management report similar subsequent tubal patency
and tubal preservation ,fertility rates ,repeat ectopic p,
• Arguments against its use include its toxicity,
=> marrow suppression, dermatitis, and stomatitis, as
well as potential for treatment failure and tubal
rupture.
• Chronic ectopic, with decreasing but persistent -hCG
titers, pose a management dilemma.
– Some will resolve on their own, whereas others will
require surgery.
• Unfortunately, at present it is impossible to predict
which patients will fail expectant management.
SAMUEL BEZABIH (MD)

Surgical m’gt
Surgical mgt.
– Salpingostomy
– salpingotomy
– Salpingectomy
– Segmental resection and anastomosis
– Oophorectomy ( for ovarian EP)
– Hysterectomy for interstitial & cervical EP with
excessive bleeding
– Abdominal pregnancy- deliver and leave placenta
to avoid hemorrhage
SAMUEL BEZABIH (MD)

Surgical management
• Milking to effect tubal abortion
– Milking the tube to effect a tubal abortion has
been advocated; if the pregnancy is fimbrial,
• this technique may be effective. However,
when milking was compared with linear
salpingostomy
• for Ampullary ectopic pregnancies, milking
was associated with a twofold increase in the
recurrent ectopic pregnancy rate (NOVAC)
SAMUEL BEZABIH (MD)

Medical Vs Surgical Mgt
 Several studies compared medical and laparascopic rx of EP
 Overall
• women who are:-
– hemodynamically stable and
– in whom there is a small tubal diameter,
– no fetal cardiac activity, and
– serum β-hCG concentrations <5000 IU/L
• have similar outcomes with medical or surgical management.
• Despite lower success rates with medical therapy for;
– women with larger tubal size,
– higher serum β-hCG levels, and
– fetal cardiac activity,
• medical mgt. can be offered to the motivated woman who
understands the risks of emergency surgery in the event of rx.failure.
SAMUEL BEZABIH (MD)

Studdiford ‘s Dxtic Criteria for 1o abdominal
ectopic pregnancy1942:
– Both tubes and ovaries must be in normal
condition with no evidence of recent or remote
injury.
– No evidence of uteroperitoneal fistula should be
found.
– The pregnancy must be related exclusively to the
peritoneal surface and be early enough to
eliminate the possibility that it is a secondary
implantation following a primary implantation in
the tube.
Primary ABDOMINAL ECTOPIC PREGNANCY
SAMUEL BEZABIH (MD)

Ovarian Ectopic Pregnancy -
 Spiegelberg’s Dxtic criteria for an
intrafollicular pregnancy;
1. the tube, including the fimbria ovarica, is intact
and is clearly separate from the ovary;
2. the gestational sac definitely occupies the
normal position of the ovary;
3. the sac is connected to the Ux by the
uteroovarian ligament; and
4. ovarian tissue is unquestionably demonstrated in
the wall of the sac.
SAMUEL BEZABIH (MD)

CERVICAL ECTOPIC PREGNANCY DX
Rubin’s criteria 1911:
– Cervical glands must be opposite the placental
attachment.
– Placental attachment to the cervix must be
situated below the entrance of the uterine vessels
or below the peritoneal reflection of the anterior
and posterior surfaces of the uterus.
– Fetal elements must be absent from the corpus
uteri.
SAMUEL BEZABIH (MD)

Non-tubal EP mg’t
Abdominal (1⁰ or 2⁰ )
– ~0.003% of all pregnancies
– remove the fetus by tying the cord close to the
placenta and leave the placenta in place to avoid
bleeding
Cervical
– suction , hysterectomy for severe bleeding
Ovarian
– cystectomy/opheroctomy+ some times
salpingectomy on the affected side
SAMUEL BEZABIH (MD)

The
10Qs
End
SAMUEL BEZABIH (MD)

Gestational Trophoblastic
Disease (GTD)
By Dr. SAMUEL/2008 E.C.

GTD
• Spectrum of tumors of placental origin
• Modified WHO Classification of GTD
1.Molar pregnancies ( have villi )
• Hydatidiform Mole (10 non metastatic disease)
– Complete HF mole
– Partial HF mole
• Invasive Mole
2. Trophoblastic Tumors( no Villi)
• Choriocarcinoma
• Placental site Trophoblastic Tumor (PSTT)
• Epitheloid Trophoblastic Tumor

GTD-Epidemiology
• The incidence of GTD
–~ 1 to 2 per 1000 deliveries-North America
and Europe (Drake, 2006; Loukovaara, 2005;
Savage, 2010; Smith, 2003)
–Hispanics and Native Americans have higher
incidence

GTD-Risk Factors
• Maternal age extremes (> 35yrs,< 20yrs)-↑ed risk of CHFM, no
signifcant difference in PHFM
– Upper age extreme has more risk than lower age extreme
~Ova of older women higher rate of abnormal fertilization
• At age of 45yrs ~1%, 50yrs ~17% risk
• Personal history of GTD ( not familial)
– ~1% chance of recurrence after one GTD hx (10X
increased risk)
– ~23% after two episodes of GTD
– Recurrent GTD usually mirrors histology of the preceding
• Old paternal age
• Infertility ,
• Abortion Hx

GTD-Risk Factors
• Smoking (>15 cigarettes per day)
• OCPs
– prolonged use, use during the cycle of conception,
previous use- appear to increase risk of GTD (2X)-
– Many of these associations, however, are weak
and could be explained by confounding factors
other than causality (Parazzini, 2002).
• vitamin A deficiency and low dietary intake of
carotene are associated with an increased risk
of only complete moles (Berkowitz, 1985, 1995; Parazzini,
1988).

• Partial moles have been linked to :
– higher educational levels,
– smoking,
– irregular menstrual cycles, and
– obstetric histories in which only male infants are
among the prior live births
• (Berkowitz, 1995; Parazzini,1986)

Hydatidiform Mole (HFM)/Molar Pregnancy
• Aberrant histologic changes within the Placenta;
classically Chorionic villi show
– Varying degrees of trophoblastic proliferation
– Villous stromal edema
• HFM has 2 forms
– complete hydatidiform moles (CHFM)or
– partial hydatidiform moles (PHFM)
• CHFM and PHFM differ in Karyotype, Histology and
clinical presentation.
• Cytogenetic studies have shown that chromosomal
abnormalities play an integral role in the
development of hydatidiform moles (Lage, 1992).

Complete vs partial Mole
69XXX/69XXY

Molar Pregnancy
A.CHFM
 Diploid, paternal chromosomes (46XX in 85-90%)
 Pathogenesis
• Inactivated Ova chrs. Fertilization by haploid
sperm  Androgenesis(Chr. duplication) 46xx
Or
• Dispermic Fertilization may produce 46XY or 46XX

Molar Pregnancy
B.PHFM-
• Triploid- maternal (one set) and paternal (2sets)
chromosomes (69,XXX, 69,XXY, or less commonly 69,XYY)
• Pathogenesis
• Dispermic fertilization of Haploid Ova with active gens-
Or
• Fetilization with diploid sperm (46xy)

Complete Hydatidiform Mole
• Enlarged, edematous villi resulting from
diffuse, abnormal trophoblastic proliferation
• Macroscopically, these changes transform the
chorionic villi into clusters of Grape Like
Vesicles
– the name hydatidiform mole stems from this
“bunch of grapes” appearance.
• this mass of placental tissue completely fills
the endometrial cavity.
• No fetal tissue or amnion is produced.

Complete HFM- clinical presentations
• Painless 2nd T Vaginal bleeding
– molar tissue separation from the decidua,
– passage of vesicles in 90% molar pregnancies in 1st TM.
• Excessive ux size~50%
– chorionic tissue + retained blood
– associated With markedly elevated HCG level.
• No fetal parts and fetal heart tone
• Early Preeclampsia (27%) * usually in the 1st or early 2nd trimester
• Hyperemesis G.* ( nausea and vomiting)
• Hyperthyroidism-7%*
• Trophoblast embolization 2%- RD *
• Prominent Theca lutein cysts*(> 6cm diameter)
• *mostly associated With marked HCG elevation and excessive ux
size( Signs of marked trophoblastic proliferation)

Complete HFM- clinical presentations
• In any woman who presents with findings
suggestive of severe hypertension prior to 20
weeks in pregnancy, a molar pregnancy
should be immediately suspected.

CHFM- DX
• US imaging –
– snow storm appearance , with no fetal parts
• Quantitative B hCG level elevates excessively
• Histopathology-Definitive Dx

Sonographic ‘snow storm’ appearance Of CHFM

PHFM- Clinical presentation
Uterine growth is less than expected for the gestational age
Less trophoblastic proliferation and villous edema compared
with CHFM
• Patients with partial moles typically present with signs and
symptoms of an incomplete or missed abortion.
• vaginal bleeding
• Dramatic clinical features are rare (i.e. PE , theca-lutein
cysts, hyperthyroidism, etc)
• β-hCG levels much lower than those for CHFM (often <
100,000 mIU /ml)
• For this reason, partial moles are often not identified until
after a histologic review of a curettage specimen.
• Ultrasound reveals molar degeneration of the placenta and
a grossly abnormal fetus or embryo

Ectopic Molar Pregnancy
• The true incidence ~1.5 per 1 million births
(Gillespie, 2004).
• > 90 % of cases are in the fallopian tube
– suspected cases will reflect an over diagnosis of
florid extra villous trophoblastic proliferation
(Burton, 2001; Sebire, 2005b).
• Other sites of ectopic implantation are even
less common (Bailey, 2003).
• As with any ectopic pregnancy, initial
management usually involves surgical removal
of the conceptus and histopathologic
evaluation.

Molar pregnancy with Cotwin
• Twin pregnancies with a normal fetus coexisting
with a complete or partial mole are exceedingly
rare.
• Women with these pregnancies should be treated
in a tertiary hospital center with specialized care.
• Medical complications in molar twin gestations
rarely allow these pregnancies to reach term.
• These pregnancies also have a higher risk of
persistent metastatic or nonmetastatic
gestational trophoblastic disease (GTD)

Treatment Of HFM
• Uterine Evacuation
• Hysterectomy-
– If no fertility wish (family completed), approaching
menopause
– Ovaries are preserved ( Theca lutein cysts regress
in few months)

Preoperative Evaluation of Molar Pregnancy
1. Baseline quantitative hCG level
2. Baseline chest x-ray to check for metastatic Disease.
3. Complete blood count
4. Blood type with RH and screen
5. Clotting function studies
6. Other appropriate tests if clinical evidence of
hyperthyroidism and/or gestational hypertension

Molar Pregnancy Rx
Uterine Evacuation
– Dilatation of the cx and Suction curettage followed by
gentle sharp curettage
– Concomitant Oxytocin infusion
– No prostaglandin use for Cx ripening/induction 
contraction with the risk of trophoblastic embolization
+ profuse bleeding
– Subject specimen for histopathologic study
– Administer anti D for Rh –ves (50micgm)

Molar Pregnancy Rx
Complications of curettage in molar
pregnancy
– Trophoblastic embolization,
• A patient can present with dyspnea and cyanosis within
4–6 hours after evacuation
– Perforation
– Hemorrhage

Prophylactic Chemo
• In settings where BhCG follow up is not
possible and for ‘ High Risk complete moles’
• High Risk- no standard classification
– Mostly Age > 40, previous GTD, BhCG > 100,000
before evacuation
– In a prospective Double Blind clinical trial-A single
dose D actinomycin has reduced Post molar GTN
from 50% to 14 % , but toxicity was significant
• prophylactic chemotherapy is generally only
used in those countries with limited resources
to reliably monitor patients after evacuation

Molar Pregnancy-Postevacuation Prognosis
• Post evacuation (Persistent) GTN develops in
– 15% of CHFM (3/4th locally invasive, 1/4th metastatic)
– 4-6% of PHFM (0.1% metastatic)
• No pathologic or clinical features at presentation
accurately predict which patients will ultimately
develop GTN.
• The risk of recurrence with subsequent pregnancies
is 1% to 2%.

Molar Pregnancy-postevacuation Surveillence
• Close follow up for 6-12 months after
evacuation
– periodic physical examination to check for vaginal metastasis
and appropriate involution of pelvic structures.
– Quantitative hCG levels should be checked
• within 48 hours following evacuation,
• every 1 to 2 weeks until it becomes undetectable
• and at 1 to 2 months thereafter.
• Effective contraception should be used until
completion of follow up  to avoid βhCG
interpretation difficulties
– OCPs are the preferred methods

Molar Pregnancy-Postevacuation surveillence
• β-hCG usually becomes normal within 9weeks after
evacuation
• Post molar GTN/ Persistent GTD is diagnosed
– β-hCG plateau of 4 measurements over 3weeks or more
(days 1, 7, 14 and 21)
– β-hCG rise in 3 consecutive measurements over 2 weeks
( days 1, 7 and14)
– β-hCG persistence for 6 months or more
– Histologic Dx
FIGO oncology committee-2002

Gestational Trophoblastic Neoplasia (GTN)
• GTN- malignant varieties of GTD (also named Persistent /
Malignant GTD)
– Invasive Mole
– Choriocarcinoma
– placental site trophoblastic tumor/PSTT
– Epitheloid Trophoblastic Tumor/ETT
• GTN develops wks to yrs after any form of gestation
– 50% after molar pregnancy (post molar GTN)
– 50% after term pregnancy, abortion or Ectopic Pregnancy
• GTN Dx usually relies on β-hCG levels rather than
histopathology (lack of tissue)
– i.e. unless PSTT or non-gestational Choriocarcinoma is
considered
• GTN can be either metastatic or Non-metastatic

Clinical Classification of Malignant Gestational
Trophoblastic Disease

GTN- non-metastatic Vs metastatic
Non Metastatic GTN:
 locally invasive
– May perforate Myometreum and cause Intra Peritoneal bleeding
– Erosion into uterine vessels- Vaginal bleeding
– Excellent prognosis
 Invasive moles
• comprise Most of the Non metastatic GTN
• 12% of CHFM after evacuation, `
• 4-6% of PHFM
 PSTT and ETT are other rarer causes of Non metastatic GTN
Metastatic GTN-
– commonly Choriocarcinoma
– Metastasis to- lungs (80%), vagina (30 %), pelvis (20 %), liver (10 %)
and brain (10 %)

GTN-Invasive Mole
• Invasive moles originate almost exclusively
from complete or partial molar gestations
• Are locally invasive, lack widespread
metastases
• penetrate deep into the myometrium,
sometimes to involve the peritoneum,
adjacent parametrium, or vaginal vault.
• Characterized by whole chorionic villi that
accompany excessive trophoblastic
overgrowth and invasion.

GTN- Gestational Choriocarcinoma
• Extremely malignant-
• Invades Endometriumm, Myometrium
• Early hematogenous Metastasis to-
– lungs (80%), vagina (30 %), pelvis (20 %), liver (10 %) and
brain (10 %)
• Most follow molar pregnancy
– Follows 3-4% of CHFM evacuation,
• Rarely arise from other gestations
– 1 in 30,000 non- molar pregnancies (2/3rd after term preg,
1/3rd after miscarriage or termination)
• Choriocarcinoma after term pregnancy:-
– poor prognosis b/se of delayed Dx.
– higher Mortality rate (14%)
– >50% of those with brain metastasis

GTN- Gestational Choriocarcinoma
– Bleeding for >6weeks after any form of pregnancy
requires β-hCG evaluation
• Patients with pulmonary metstasis
infrequently present with cough, dyspnea,
hemoptysis, pleuritic chest pain, or signs of
pulmonary hypertension

GTN-Placental Site Trophoblastic Tumor (PSTT)
• Rare, follow any pregnancy but mostly after term pregnancy
• Consist of intermediate Trophoblasts at the placental site
• Local infiltration of Ux.
• Rarely metastatic (liver, lung, vagina)
• Less hCG production, better followed by Human Placental Lactogen (HPL )
level
Clinical Manifestation- irregular Vaginal bleeding months to yrs after
antecedent pregnancy
DX- Endometrial sampling, analysis of β-hCG proportion may also help
distinguish from other GTNs
RX
• Non-Metastatic-
– Hysterectomy ( b/se of relative chemo insensitivity)
• Metastic:-poorer Poor than choriocarcinoma
– combination Chemorx(EMA/EP)
– Radio therapy may also have a role
10 yr survival~70%,(however poor in metastatic and > 4yr antecedent
pregnancy)

GTN- Epitheloid TT
• Rare, develops from chorionic type
intermediate trophoblasts
• Microscopically resemble PSTT
– Difference- small cells, less nuclear pleomorphism
• Growth- nodular ( unlike infiltration of PSTT)
• Dx:-Endomerial biopsy
• Rx-
– Hysterectomy (presumed chemo-resistance)
– 1/3rd present with metastasis-
– Too few reports to evaluate Chemorx efficacy

FIGO Staging of Gestational Trophoblastic
Neoplasia

Sores 0 1 2 4
Age < 40 > 40
Antecedent
Preg
Mole Abortion Term
Interval from
index preg
<4mths 4-6 7-12 >12
Pretreatment
BhCG
< 103 103 -<104 104 -<105 > 105
Largest
Tumor size
<3 cm 3-4 > 5
Met Sites Spleen,
Kidney
GI Liver, Brain
No of Mets 1-4 5-8 >8
Failed
Chemorx
drugs
1 > 2
Modified WHO Prognostic Scoring System as Adapted by FIGO Low Risk 0 - 6, High
Risk > 7
GTN-Prognostic Scoring System

GTN- Rx
Surgery
– 20 evacuation
– Hysterectomy
– Thoracotomy ( for chemo resistant lung metastasis)
Chemotherapy
– Single agent ( low risk)
– combination

GTN Treatment-Repeat D and C for post molar
• Most patients diagnosed with post molar GTN
have persistent tumor confined to the
endometrial cavity.
• Repeat Ux curettage has been shown to
significantly reduce both the number of patients
needing any further treatment and the number of
courses in those who do require chemotherapy
(Pezeshki, 2004; van Trommel, 2005
• However it has associated increased morbidity and
mortality from perforation, Hemorrhage, Infections, Ux
Adhesions, ansthetic comps

GTN Treatment- Hysterectomy
• For PSTT , ETT and other chemo resistant Tumors
• Emergency mg’t of severe vaginal or intra
abdominal bleeding
• Adjuvant Rx for low risk GTN-
– reduce total dose of chemorx needed for clinical
remission
• For Patients with disease apparently confined to
the uterus who do not desire future fertility
should be counseled about this option
• However, the risk of GTN persistence after
hysterectomy remains approximately 3 to 5
percent, and these patients should be monitored
postoperatively (Soper, 2004).

GTN Treatment- Thoracotomy
• Residual lung metastases may persist in 10 to 20 %
of patients achieving clinical remission of GTN after
completion of chemotherapy.
• These patients do not appear to have an increased
risk of relapse compared with those having normal
CXRS or CT scans.
• Thus, thoracotomy is not usually necessary unless
remission cannot otherwise be achieved (Powles, 2006)
• In general, the optimal patient to be counseled for
thoracotomy will have
– Stage III GTN,
– a preop β-hCG < 1500 mIU/mL, and a
– solitary lung nodule resistant to chemotherapy.

GTN Treatment- Single agent Chemotherapy
• Single agent chemotherapy for Low risk GTN Rx- (score
0- 6) or Non-metastatic  Methotrexate or Actinomyycin D
1. Methotrexate
– IM Two regimens
– Complete Response 67-81%, resistance 19-33%
I. 50mg/m2 ( maximum dose with escalation)weekly till BhCG
is undetectable, then 2 more doses (GOG)
II. 1mg/kg on D 1357 alternating with Lucoverin 7.5mg po on
D 2468 Q 2week
– IV:---
• 100mg/m2 bolus then 200mg/m2 in 12 hrs
• Folinic acid not required non toxic levels reached in 24 hrs
• 65% complete response ( less effective than IM regimens)
• Usually successful with single dose appropriate for non-
compliant pts

IM Methotrexate Regimens for Treatment of
Low-Risk GTN

Methotrexate Rx Toxicities
• Methotrexate is a folic acid antagonist that
inhibits DNA synthesis
– Mild Stomatitis the most common and
– pleurisy in 3rd of pts treated with low dose Meth
– infrequently peritonitis, pericarditis or
pneumonitis

‘Lucoverin Rescue’
• Administration of Lucoverin (folinic acid) along
with MTX to overcome toxicity
• MTX- prevents Nucleic Acid synthesis by
inhibiting Dihydrofolate Reductase 
Blockage of Purine synthesis
– DHFR converts dihydrofolate to Tetrahydrofolate
(active form of folic acid)
• Lucoverin readily converts to THF with out the
need for the enzyme DHFR

Low Risk GTN Rx- Single Agent Chemotherapy
2.D-actinomycin
–Less commonly used b/se of fear of toxicity
–May have higher toxicity (2x alopecia risk)
and superior efficacy than methotrexate

Low risk GTN- Treatment Failure
Failure to have persistent BhCG drop
• Recalculate the risk score and if still low risk switch to
2nd line single agents.
• Methotrexate-resistant GTN
– often responds to D-actinomycin(Chen, 2004).
– The GOG phase II trial (protocol #176)- 74% success rate in
pulse D-act salvage rx of 38 MTX-R GTN pts(Covens, 2006)
– Etoposide is less commonly used in this setting, but is also
effective (Mangili, 1996).
• D-act resistant GTN
– Patients initially treated with pulse d actinomycin who
develop resistant GTN may still be successfully treated
with the 5-day course of d actinomycin (Kohorn, 2002).
– Alternatively, single-agent methotrexate or etoposide is
effective (Matsui, 2005).

High Risk GTN (score >7) Chemotherapy
Multi agent/combination Chemotherapy
EMA/CO:-
– well-tolerated and highly effective regimen
– 78% complete remission rate in 272 consecutive
women (Bower and associates (1997) at Charing Cross Hospital
reported .
– other investigators have observed a 71-78%
complete response rate with the EMA/CO regimen
(Escobar, 2003; Lu, 2008).
– Overall survival-86-92%
– Quarter of pts- relapse or become refractory

20 Rx for resistant cases
–Platinum based chemo rx + possible
surgical excision of resistant tumor site
• Chemorx
–EMA/ EP
–TP/TE
–BEP

Secondary treatment usually involves platinum-based
chemotherapy combined with possible surgical
excision of resistant disease.
EMA/EP
– Newlands and colleagues (2000) at Charing Cross Hospital
reported an 88-percent survival rate among 34 patients by
replacing the CO component with etoposide and cisplatin
TP/TE
– comparable efficacy to EMA/ EP and appears less toxic
EP(Kim, 2007; Mao, 2007; Osborne, 2004; Patel, 2010; Wang, 2008).
BEP
– Bleomycin, etoposide, and cisplatin (BEP) is another
potentially effective regimen (Lurain, 2005; Patel, 2010).

Current Treatment Regimens for High-Risk Gestational Trophoblastic Disease.

Chemotherapeutic Agents
• A- D actinomycin
• B-Bleomycin
• C-cyclophoshomide
• E-Ethoposide
• M-methotexate
• O-vicristine
• P-cisplatin
• T- Paclitaxale

Post treatment Surveillance.
• Monitoring of patients with low-risk GTN
consists of weekly β-hCG measurements until
the level is undetectable for 3 consecutive
weeks.
• This is followed by monthly titers until the
level is undetectable for 12 months.
• Patients with high-risk disease are followed for
24 months due to the greater risk of late
relapse.
• Patients are encouraged to use effective
contraception

Post treatment Pregnancy
• Chemorx may cause menopause by 3 years
earlier, no significant effect on fertility(Bower, 1998).
• High probablity of successful Pregnancy
outcomes after EMA/CO completion(Lok, 2003)
• Pregnancy within 6 months of completion may
have more frequent maternal adverse
outcomes and spontaneous abortion(Braga, 2009).
• 1% recurrence for histologically confirmed
HFM (complete and partial)

Preterm Labor and Delivery
Dr.Samuel Bezabih
Nehassie 2006 EC
Gondar

Preterm Birth
• Preterm birth (PTB) is delivery prior to the
completion of 37 weeks (259 days) of
gestation.
• it is the most common cause of perinatal
morbidity and mortality the United States,
• Incidence-11% to 12% of babies born
prematurely
• Account for 75% of all perinatal mortality and
50% of long-term neurologic impairment in
children

Perinatal mortality rate (PMR)
• The NCHS uses two different definitions of perinatal mortality rate.
• first PMR definition is the sum of fetal deaths (≥20 weeks gestation) plus neonatal
deaths (ie, deaths within the first 28 days of birth) during a year divided by the sum
of live births plus late fetal deaths during the same year, expressed per 1000 live
births plus late fetal deaths.
• 2nd definition is the sum of fetal deaths (≥20 weeks gestation) plus early neonatal
deaths (ie, deaths within the first seven days of birth) during a year divided by the
sum of live births plus late fetal deaths during the same year, expressed per 1000
live births plus late fetal deaths.

Preterm Birth
• Preterm births may be spontaneous or
indicated.
• Approximately 40% to 50% of PTBs result from
spontaneous preterm labor with intact
membranes;
• 25% to 40% result from preterm premature
rupture of membranes (PROM)
• The remaining 20% to 30% occur following
deliberate intervention for a variety of
maternal or obstetric complications (e.g.Pre
eclampsia, eclampsia, IUGR, APH----).

Complications of preterm delivery
• Common neonatal complications in
premature infants include:-
– respiratory distress syndrome (RDS),
– intraventricular hemorrhage (IVH),
– bronchopulmonary dysplasia (BPD),
– patent ductus arteriosus (PDA),
– Necrotizing enterocolitis (NEC),
– Sepsis,
– Apnea, and retinopathy of prematurity.

Complications of preterm delivery
Long-Term Outcomes
• Follow up studies of infants born preterm and
LBW infants reveal increased rates of
– chronic lung disease,
– cerebral palsy,
– neurosensory impairment-vision and hearing
impairment
– reduced cognition and motor performance
– academic difficulties, and attention deficit disorders
• The incidence of long-term morbidity in survivors is
especially increased for those born before 26 weeks

Preterm Labor (PTL)
• Preterm labor (PTL) is defined as
– the presence of regular uterine contractions
associated with cervical changes before 37
weeks of gestation
• PTL may represent a final common pathway for a
number of pathogenic processes.
• The four main processes include:-
1. Activation of the maternal or fetal hypothalamic
pituitary- adrenal axis due to maternal or fetal
stress,
2. Decidual-chorioamniotic or systemic inflammation
caused by infection,
3. Decidual hemorrhage, or
4. Pathologic uterine distention

PRETERM LABOR-Dx
• Labor at GA>20wks & < 37wks
– Frequent + Regular ux contractions
• may manifest as abdominal pain /tightening, back pain
or pelvic pressure
– Cervical change (E&D) along with the
contractions
• NB. At least 4cont/hr is required to cause cx
change
– Late Preterm --------34-36 wks
– Moderately PT-------32-34
– Very PT---------------28 - 32
– Extremely PT---------<28

PTL Risk Factors
1.Obstetric complications (in previous or current PX.)
• Previous premature or low-birth-weight infant
(2x increase in subsequent pregnancy)
• Severe hypertensive state of pregnancy
• Anatomic disorders of the placenta
– eg, abruptio placentae, placenta previa, circumvallate
placenta
• Placental insufficiency
• PROM
• AFV disorders-Poly/oligo
• Low socioeconomic status
• Maternal age < 18 years or > 40 years
• Low pre-pregnancy weight

PTL Risk Factors
2. Medical complications
– Pulmonary or systemic hypertension
– Renal disease
– Heart disease
3. Infection systemic or FGT:(mainly at
earlier GA, <32wk)
– acute systemic infection, (eg, pneumonia, influenza,
malaria, periodontal infection ),
– UTI,Pyelonephritis,
– GT infection( gonorrhea, H. simplex, mycoplasmosis--)
– Bacterial Vaginosis
– fetotoxic infection (CMV, toxoplasmosis, listeriosis-
– maternal intra-abdominal sepsis (eg, appendicitis,
cholecystitis, diverticulitis)

PTL Risk Factors
4.Surgical complications
–Any intra-abdominal procedure
–Conization of cervix
–Previous incision in uterus or cervix (eg,
cesarean delivery)

PTL- Prediction
• A number of factors are used to predict the
potential to develop preterm labor.
1. Fetal fibronectin ( f FN) in cervicovaginal
secretions
– A preterm rise in the concentration of fFN may be
associated with an increased likelihood of birth
between 22 and 34 weeks of gestation and birth
within 7–14 days of the test.
– However, data combined from several studies reveal
that the positive predictive value for delivery within a
week is only 18%.
2. Cervical length
– Shortened cervical length < 2.5cm in midpregnancy is
associated with the risk of preterm labor and delivery.

PTL- Management
• The purpose in treating preterm labor is to
delay delivery, if possible, until fetal maturity
is attained
• more than 50% of patients with preterm
contractions have spontaneous resolution of
abnormal uterine activity

PTL Management-Interventions
• Non-pharmacologic methods of
Uncertain efficacy include:-
–Bed rest
–Abstinence from intercourse and orgasm
–Hydration ( oral/parentral)

Rx of PTL…….
• Pharmacological methods :-
–Tocolytics agents
–Administer Steroids
–Adjuvant antibiotics

PTL Mgt-Interventions
ሀ: TOCOLYSIS
• pharmacologic inhibition of ux activity to suppress labor
– at least for 48 hrs. after administration Of corticosteroids or
– if possible to take pregnancy to >34wks
• In those with high risk of preterm birth, i.e.
– Hx of PT birth,
– contraction sustained,
– short cx
– fibronectin positive
– cervical dilatation change
*tocoytics may prolong gestation for 2-7 days ( time for steroid
adminstration & transportation to facility having NICU, no other clear
benefits)

PTL- Management
Tocolytics Agents:-
–Magnesium sulfate
–Prostaglandin synthetase inhibitors
(indomethacin)
–Calcium-channel blockers (nifedipine)
–β-adrenergic agents (ritodrine, terbutaline)

Some Cases in Which Preterm Labor Should Not
Be Suppressed.
Maternal Factors
Severe HTN disease (eg,
acute exacerbation of chronic
HTN , eclampsia, severe PE)
Pulmonary or cardiac
disease (eg, pulmonary
edema, adult respiratory
distress syndrome, valvular
disease, tachyarrhythmias)
 Advanced cervical dilatation
(> 4 cm)
 Maternal hemorrhage (e.g,
abruptio placentae, placenta
previa, DIC)
Fetal Factors
• Fetal death or lethal anomaly
• Fetal distress
• Intrauterine infection
(chorioamnionitis)
• Therapy adversely affecting the
fetus (eg, fetal distress due to
attempted suppression of labor)
• EFW OF 2500 g
• Erythroblastosis fetalis
• Severe IUGR

Potential Complications of Tocolytics Agents
 BETA-ADRENERGICS
 Hyperglycemia
 Hypokalemia
 Hypotension
 Pulmonary edema
 Cardiac insufficiency
 Arrhythmias
 Myocardial ischemia
 Maternal death
 INDOMETHACIN
– Hepatitisb
– Renal failureb
– GI bleedingb
 NIFEDIPINE
– Transient hypotension
 Magnesium Sulfate
– Pulmonary edema
– Respiratory depression
– Cardiac arresta
– Maternal tetanya
– Profound muscular
paralysisa
– Profound hypotensiona
• aEffect is rare; seen with
toxic levels.
bEffect is rare; associated
with chronic use

PTL Mgt-intervention cont’d.
ለ፡Steroid administration
• for GA 24-34 weeks & for PPROM,
• efficacy b/n 33-34 not clear, my be given esp if pulmonary immaturity is
documented ACOG 2013)
• the most beneficial intervention for pts with true PTL
• to facilitate lung maturity and reduce incidence and severity of Neonatal
RDS and
• Reduce incidence of IVH and NEC
 Indication- Risk of PTB (24-34wk GA) in one week
 Regimen
 Betamethasone 12mg Im/24hrx2 or
 Dexamethasone 6mg IM BIDx4
• No multiple regular doses
• Rescue dose- 01 repeat course may be given if
– 2 weeks passed after the first dose
– GA < 32 weeks
– Delivery is anticipated within 01 week (ACOG 2013)

PTL Mgt-intervention cont’d.
ሐ፡Adjuvant antibiotcs
–No evidence that Antibiotic administration
prolongs gestation or reduces neonatal
complications
–May be used for GBS prophylaxis in those
delivery is imminent

FETAL SURVEILLENCE
Samuel Bezabih
(MD)
GUH- OB-GY R2
Miazia 2005

A.ANTEPARTEM
FETAL
SURVILLANCE
B.ANTEPARTUM
FETAL
SURVEILLANCE
SAMUEL BEZABIH (MD)- MIAZIA 2005

ANTEPARTUM FETAL ASS/SURVEILLANCE
• Tests carried out on fetuses that are thought
to be at risk of intrauterine jeopardy
(hypoxia, acidosis, neurologic injury).
• Goals
1. Prevention of fetal death
2. Avoiding unnecessary intervention
(safe prolongation of intrauterine life )
[ACOG and Academy of pediatrics (2007)]

Significance of Antenatal Testing
• Decreased perinatal mortality and morbidity
• No definitive randomized clinical trials on
APFS techniques regarding
– Optimal use (timing, frequency, choice of test…..)
– Effectiveness in improving perinatal outcomes
(e.g.early detection of asphyxia (lack of oxygen)
to prevent neurologic injury )

Significance of Antenatal Testing
• Negative predictive Value of
Normal(Negative) tests > 99.8%
 Highly reassuring  Very low fetal death rate
within one week after negative test
• Positive predictive value of Abnormal
(positive) tests~ 10- 40%.
• Nb.“more likely to the assessment of fetal
wellness than fetal illness”

Indications…APFS
 Pregnancies with ↑risk of perinatal MM.
– Post term pregnancy
– DM
– Hypertensive disorders
– IUGR
– ↓Fetal movement
– Rh sensitization
– Hx of unexplained perinatal loss
– PROM
– Maternal medical Disorders(cardiac ,renal
,pulmonary illnesses, CLD…….)

Indications for antepartum fetal surveillance
I.Maternal
• Antiphospholipid syndrome
• Poorly controlled
hyperthyroidism
• Hemoglobinopathies
• Cyanotic heart disease
• SLE
• Chronic renal disease
• diabetes mellitus
• Hypertensive disorders
II.Pregnancy complications
• Preeclampsia
• Decreased fetal movement
• Oligohydramnios
• Polyhydramnios
• IUGR
• Post-term pregnancy
• Isoimmunization
• Previous unexplained fetal demise
• Multiple gestation

Timing
• The optimal GA for initiation of fetal testing is
not established.
• For most high risk pregnancies APFS started at
32 to 34 WKs of GA
• As early as 26 to 28 weeks in Pregnancies
with severe complications.
• The frequency of tests; arbitrarily set at 7
days, but more frequent testing is often done

Timing….
• Too late ( > 41wk):- ↑ perinatal morbidity and
mortality
• Early testing:-↑ iatrogenic prematurity
– The authors of one study estimate that antenatal
testing before 37 weeks of GA results in a 1.5%
rate of iatrogenic prematurity for intervention
based on false- positive test results ( ACOG 2009)

Types of Antenatal Testing
1. Fetal movement counting-----Cardiff count
2. Contraction stress test
3. Non-stress test
4. Amniotic fluid volume assessment
5. Biophysical profile (FT,FGBM,FBM,AFV,NST)
6. Doppler velocimetry

Types of Antenatal Testing
• There is no "best test" to evaluate fetal
well-being
• Parallel vs branched testing schemes

Fetal Activity Evaluation
• The presence of fetal movements is a
reassuring sign of fetal health.
• Natale etal. Using a sheep model
demonstrated that;
– A small fall in fetal Po2 was associated with a
cessation of limb movements in the fetal lamb
fetal activity is extremely sensitive to a decrease
in fetal oxygenation.

Maternal Assessment of Fetal Activity
• The mother is able to appreciate about 70 to
80 % of GBMs
• Maternal evaluation of fetal activity may
reduce fetal deaths caused by asphyxia.
• No universally agreed counting protocol

1. Movement alarm signal /MAS/
• Sadovsky et al. recommended that mothers
count fetal activity for 30 to 60 minutes each
day, two or three times daily.
• “the movement alarm signal”=> further
evaluation of fetal condition needed
– If the mother has fewer than 3 movts. in 1 hour,
OR
– if she appreciates no movements for 12 hours

2. Cardiff Count To Ten /CCT-10/
• A minimum of 10 movements should be
perceived in a 12-hour period.
• The patient is asked to start counting the
movements in the morning and to record the
time of day at which the 10th movement has
been perceived.
• Further evaluation if
– No 10 movements during 12 hours, or
– It takes longer each day to reach 10 movements.

Causes Of Decreased Fetal Movement
• Fetal sleep state
• Obesity
• Anomaly
• Drugs
• Anterior placenta
• Chronic smoking
• Hydramniosis
• Hypoxia

1. Contraction Stress Test (CST)
• Assessment of placental sufficiency during
uterine contraction
• Placental pathology  low fetal O2 reserve
Fetal Hypoxia during contraction  FHR
pattern change
Procedure:
• Uterine contraction stimulation ( 3/10’/ 40-60”)
– IV oxytocin
– Nipple stimulation
• FHR and uterine contraction tracing by external
monitor
• May take as long as 90 min. to complete

Contraction Stress Test (CST)
CONTRAINDICATIONS
• High risk of premature labor, such as
– PROM,
– multiple gestation, and
– cervical incompetence,
• conditions in which uterine contractions
may be dangerous, such as
– placenta praevia
– previous classic cesarean section or
– Extensive uterine surgery.

Criteria for Interpretation of the CST
• Negative:
– no late or significant variable decelerations
• Positive:
– late decelerations following > 50% of contractions
• Equivocal suspicious:
– intermittent /inconsistent LDs or significant VDs
• Equivocal- hyper-stimulatory:
– FHR decelerations that occur in the presence of >
5 contractions/10min or lasting longer than 90
seconds
• Unsatisfactory:
– fewer than three contractions in 10 minutes or an
un interpretable tracing

Negative Contraction Stress Test (CST)
• consistently associated with good fetal
outcome.
• permits safe prolongation of a high-risk
pregnancy
– perinatal death within 1 week < 1 / 1,000.
(~0.04%)
– Mostly 20 to acute fetal compromise (e.g. Cord
accident, placental abruption, acute glycemic
control deterioration
• a repeated study is usually scheduled in 1
week after negative CST

Contraction Stress Test (CST)…..
• False positive CST results ~30%
Overall, the likelihood of perinatal death after a
positive CST has ranged from 7 to 15 %
Positive CST + Short lag time (<45sec) &no base line
acceleration  omnious
further evaluation of +ve cases by BPP is needed
• Equivocal/unsatisfactory results
 repeat tests in 24 hrs

2. NON-STRESS TEST (NST)
• The most widely employed 1⁰ Method
currently
– Easy, fast, in outpatient setting
• Employs Doppler + maternal perception of
movement
• Premise of the test
– FHR accelaration accompanies fetal movement if
no neurologic injury/depression
Rules out fetal acidosis 20 to hypoxemia

NON-STRESS TEST (NST)
• GA dependent;-
– premature (<32wk) otherwise healthy fetuses may
show abnormal test
• Most predictive when normal (reactive) .
• Overall, a reactive NST has been associated
with a perinatal mortality ~3 per 1,000 in 1
week

NST INTERPRETATION
• Reactive test: Reassuring  fetus is not acidotic/hypoxemic
nor neurologically depressed
• > 2 accelerations occurring in 20 minutes
– GA > 32 WK: FHR increase from base line by> 15
beats /min lasting for> 15 seconds -02minutes
– GA< 32 wk: FHR increase from base line by> 10 beats
/min lasting for> 10seconds -02minutes
• Non-Reactive test : 0-1 acceleration in 40 min of
the NST
NB
• A NST should last for > 40 min (accounting for the 40min sleep cycle)
before concluding it is NR
• Accelerations with/without fetal movement are accepted as reactive
• In one review 01 acceleration was as reliable as 02 acceleratins in
predicting fetal healthy status (Miller etal 1996b)

Normal NST- Will 24th
 Many different definitions exist with variations about
the number, amplitude and duration of acceleration as
well as test duration
Definition currently recommended by ACOG(2012)
> 2 accelerations that peak at 15 bpm or more above
baseline, each lasting 15 seconds or more, and all
occurring within 20 minutes of beginning the test
It was also recommended that
– accelerations with or without fetal movements be
accepted, and
– Tracing should be performed for > 40-minute before
concluding that there was insufficient fetal reactivity
to account for fetal sleep cycles

NST

Acoustic Stimulation
• Startling the fetus with external sound to
provoke acceleration
• Commercial ac stimulator positioned on
maternal abdomen and stimulus for 1-2 secs
(can be repeated 3x for upto 3sec)
• Shorten the test duration
• Laventhal and colleagues(2003) reported that fetal
tachyarrhythmia was provoked with
vibroacoustic stimulation.

False Normal NST
• Smith etal (1987) analyse fetal deaths;Fetal death in 7
days of R NST
– Mean test- death interval 4 days
– Most common indication for NST was post term preg
– Single most common autopsy finding was Meconium asp.
Acute asphyxia insult caused gasping
NST is inadequate to preclude such acute asphyxia
event other BP characters may be beneficial esp AFV.
• Other ascribed frequent causes of fetal death included;
– intrauterine infection,
– abnormal cord position,
– malformations, and
– placental abruption.

NST
• Although a normal number and amplitude of
accelerations seems to reflect fetal well-being, their
absence ( Non reactive test)does not invariably
predict fetal compromise (hypoxemia,acidosis).
• Some investigators have reported > 90% false +ve
rates (Devoe, 1986).
• healthy fetuses may not move for up to 75
minutes
 longer duration of test suggested to increase PPV of
NR NST ( for 80- 120 min) (Brown, 1981)
– May become reactive in 80 min or
– If the test remained NR for 120 min very ill fetus

NR NST
NR tests where fetal compromise is likely:-
• ‘Silent Oscillatory Pattern ‘ FHR baseline
that oscillated less than 5 bpm.
– Presumably indicates no acceleration and beat-
to-beat variability [Hammacher and co-workers (1968) ]
• ‘Terminal Cardiotocogram’ which included:
(1) baseline oscillation of less than 5 bpm
(2) absent accelerations, and
(3) late decelerations with spontaneous uterine
contractions [Visser and associates (1980) ]

NR NST
• Non- reactivity ,not due to maternal sedation, is
an ominous finding
• A longer duration of NST testing might increase
the PPV of nonreactive test
• If the NST is extended and non- reactivity
persists , the fetus is likely to be severely
compromised
• Devoe and co-workers (1985) concluded that NST that were
nonreactive for 90 minutes were almost
invariably;
– 93 % associated with significant perinatal pathology

Benign Causes of abscent
acceleration
• Quiet fetal sleep state (most often )
• fetal immaturity
• CNS depressants such as narcotics and
phenobarbital
• Beta-blocker ( propranolol ).
• Chronic smoking
is known to decrease fetal oxygenation through an
increase in fetal carboxyhemoglobin and a decrease in
uterine blood flow.
– FHR accelerations are also decreased in smokers.

NR NST Management
• Management options of NR NST
– Delivery if term
• Preterm
– a BPP or CST should be performed.
• Of those fetuses that exhibit a NR NST, ~25% will
have a +VE CST on further evaluation.
• When a NR NST is followed by a positive CST, the
incidence of PNM has been ~10 %
– Vibroacaustic stimulation (to elicit reactivity
and to shorten the duration)
– Modifying underlying causes e.g, DKA
– Extending the test

Decelerations during NST
• Fetal movement produces decelerations
• Non-repititive and brief (<30sec) variable Ds
during NST benign, no intervention needed
• If repetitive (at least 3x/20min)- even mild VDs
are ass with an increased risk of cesarean
delivery for fetal distress. ACOG (2012a)
• Decelerations lasting 1 minute or longer have
been reported to have an even worse
prognosis (Bourgeois, 1984; Druzin, 1981; Pazos, 1982).

NST-Testing Interval
• Weekly- arbitrary
• More frequent testing is advocated by some
investigators for women with
– Post-term Pregnancy,
– Multifetal Gestation,
– Type I DM
– Fetal-growth Restriction, Or
– Gestational Hypertension (Devoe, 2008; Freeman, 2008;
Graves, 2007; Kennelly and Sturgiss, 2007).
2x weekly, daily……..

BIOPHYSICAL PROFILE
• Manning and colleagues (1980) proposed the
combined use of 5 fetal BP variables as a more
accurate means of assessing fetal health than a
single element
1. FHR acceleration ( NST)- can be omitted if the rest 4 are normal
2. Fetal breathing /FB/
3. Fetal movements/FBM/,
4. Fetal tone/FT/, and
5. Amnionic fluid volume/AFV/.

BPP…..
• Normal variables were assigned a score of 2
each, and abnormal variables were given a
score of 0.
– the highest score possible for a normal fetus is 10.
• Performed at least for 30 minutes (takes 30-60
min)
• Maternal medications such as morphine can
significantly decrease the score (Kopecky, 2000).
• Ozkaya and associates (2012) BPP test scores are
higher in the late evening (8 to 10 pm)
compared with 8 to 10 am.

BPP
• Manning and colleagues (1987) False normal test 
~ 1/1000
– Antepartum Death of structurally normal fetus (??after
Normal BPP with in 01 week??)
– Causes-include fetomaternal hemorrhage, umbilical cord
accidents, and placental abruption (Dayal, 1999).
• Extensive experience with BPP testing in high-risk
populations indicates a PNM rate of 0.73 per
1,000/week of normal test results with normal AFV .
• observational studies showed BPP is accurate for
predicting the absence of significant fetal acidemia
• Significant decrease seen in umbilical vein PH of
fetuses with abnormal BPP score

BIOPHYSICAL PROFILE
Variables And Normal Results
• NST – Reactive
• Fetal breathing movement >1FBM/30’’/ 30’’
• Fetal Body movement > 3/30min
• Fetal Tone >1extension - flexion of
extremities
• AFV minimum of 2cmX2cm pocket

BPP Interpretation

BPP scores and interpretations & mgmt.
1. Normal AFV- normal 10, 8/8
(no NST) 8/10
– No need for intervention repeat BPP
weekly
– 2x weekly for GDM and post term
2. 8/10 +↓AFV
• Suspect chronic hypoxia
• MGT- deliver
3. 6 score
• Possible chronic hypoxia
(equivocal)
• Mgmt.
– Deliver if > 36 wks. + favorable cx/
if AFV is abnormal
– Repeat test and deliver if < 6,
– Observe + repeat per protocol if>6
4. 4 score
• Probable asphyxia
• Mgmt.
– Repeat BPP same
day and if < 6 deliver
5. 0-2 score-
• Nearly certain
asphyxia.
• Mgmt.- deliver

BPP-Studies
• Manning and collegues (1997)-BPP + Cordocentesis (Umb
vein) on 493 fetuses,( 20% IUGR, 80% allo-
immunized)
– BPP scores correlate well with fetal PH and outcome.
(Except score 6-equivocal-poor predictor of outcome)
• Salvesen and associates (1993)-41 diabetic pregnancies
– BPP had poor association with fetal PH- 9 acidemic
fetuses had NBPP
• Weiner and coworkers (1996) assessed 135 overtly GR
fetuses and came to a similar conclusion.
– Morbidity and mortality in these latter fetuses were
linked primarily to GA and birthweight and not to
abnormal fetal test results.

BPP- studies
• Lalor and associates (Cochrane review 2008) -concluded that
there is insufficient evidence to support the use
of BPP as a fetal well-being test in high-risk
pregnancies.
• Kaur and colleagues (2008) performed daily BPP to
ascertain the optimal delivery time in 48 growth-
restricted preterm fetuses who weighed < 1000 g.
– Despite scores of 8 in 27 fetuses and 6 in 13, there
were six deaths and 21 acidemic fetuses.
• These investigators concluded that a high
incidence of false-positive and -negative results is
seen in very preterm fetuses

Modified BPP
• NST + AFI ( normal AFI> 5cm)
• Short time (10min)
• No need for experienced sonographer
• Comparable prediction with BPP
– 0.8/ 1000 death (False negative rate) in a week after
normal test
– 1.5% false +ve rate
• ACOG and AAP (2012) have concluded that the
modified BPP test is as predictive of fetal well-
being as other approaches to biophysical fetal
surveillance.

MBPP….
Normal M BPP
 Reactive NST and AFI > 5 cm.
Abnormal M BPP.
 Non-reactive NST and/or AFI< 5cm.
 Note: Abnormal M BPP should be supported by standard
BPP and CST
 Initiation Of Ante partum Fetal Well Being Evaluation
 Gestational age 32- 34 wks, for most high-risk mother
 Pregnancy with multiple risk factors, evaluation can be
started at any gestation
 Inform all mothers to follow fetal movement and report of
abnormalities.

DOPPLER VELOCIMETERY
• Assessment of blood flow impedance by Doppler
US to evaluate wellbeing of the fetus
• Reduces interventions and improves out comes of
IUGR pregnancies
• Decision of delivery time of growth restricted
fetuses
• Hemodynamic changes due to placental vascular
insufficiency are reflected on Doppler study of;
– Umbilical artery
– Middle cerebral artery
– Ductus venosus
– Uterine artery ( for utero-placental insufficiency)

• Umbilical artery is the most widely studied
test by controlled randomized trials
• No benefit other than in suspected IUGR
(ACOG 2013)-
– No benefits have been demonstrated for other
conditions such as postterm pregnancy, diabetes,
SLE, or APSsyndrome.
– Not of proved value as a screening test for
detecting fetal compromise in the general
obstetrical population

• Obliteration of placental vessels ↑afterload
(↑ Umbilical A resistance) Fetal hypoxia
↓ impedance and ↑ blood flow to MCA (
brain sparing)
• ↑ Right heart pressure  ↑ pressure in
ductus venesus

UMBILICAL ARTERY
• UA Doppler abnormality obliteration of 60- 70% of
placental vascular tree
Abnormal UA Doppler studies;
• S/D ratio > 95 percentile for gestational age
• Absent /Reverse end diastolic flow
– perinatal mortalty
• 10% and 33% in absent and RED flow respectively (Zelop and
colleagues (1996))
– cerebral palsy prevalence at the age of 2 (IUGR
deliverd at 24-35 GA ) [(Spinillo and assoiates (2005) ]
• Absent or RED flow -8%
• Normal Dopppler- 1%

• Randomized trial ( doppler Umbilical Artery vs
NST) higher incidence of CS delivery in the
NST group
• Obido et al. compared BPP scoring and
Doppler assessment in monitoring fetus with
IUGR.
– They concluded that a model using BPP only
would be best to minimize neonatal death or
disability

MIDDLE CEREBRAL ARTERY
• Increased MCA blood flow and velocity/
decreased impedance
– Fetal hypoxia
– Fetal anemia ( eg erythroblastosis fetalis)
• no significant difference in outcome b/n modified
BPP alone and mod.BPP+ MCA doppler followed
pregnanacies (Ott and co-workers (1998)
• MCA Peak systolic velocity measurement Can
safely replace serial amniocentesis in the mg’t of
RH isoimmunized pregnancies[Oepkes and colleagues
(2006)]

DUCTUS VENOSUS
• Absent/ reversed diastolic flow
– better prediction of perinatal outcome than
umbilical artery studies
• Of limited use
late manifestation after severe hypoxemia
caused irreversible mulltiorgan damage

UTERINE ARTERY
• Most helpful in assessing pregnancies at high risk of
complications related to Uteroplacental insufficiency
• High resistance in the uterine artery  Uteroplacental
insufficiency pregnancy complications
– EG. early fetal death from placental abruption, preeclampsia,
growth restriction
• This has led to suggestions for continued research of UxA
DV as a screening tool to detect pregnancies at SB risk
(Reddy, 2008).
• Sciscione and Hayes (2009) reviewed the use of UXADV
studies in obstetrical practice.
• Because standards for the study technique and criteria for
an abnormal test are lacking, they noted that uterine artery
Doppler studies should not be considered standard practice
in either low- or high-risk populations.

Intrapartum Fetal
Surveillance

Surveillance Low-Risk
Pregnancies
High-Risk
Pregnancies
Acceptablemethods
Intermittent auscultation Yes Yes
Continuous electronic monitoring
(internal or external)
Yes Yes
Evaluation intervals
First-stage labor (active) 30 min 15 min
Second-stage labor 15 min 5 min
Guidelines for Methods of Intrapartum FHR Monitoring

EFM
Fetal Heart Rate Tracing
– Baseline HR
– Beat to beat variablity
– Acceleration
– Decelerations
Baseline Fetal Heart Activity
– refers to the modal characteristics that prevail apart
from periodic accelerations or decelerations
associated with uterine contractions.
– Descriptive characteristics of baseline fetal heart
activity include rate, beat-to-beat variability, fetal
arrhythmia, and distinct patterns such as sinusoidal or
saltatory fetal heart rates.

EFM- Baseline
• The mean FHR rounded to the increament
of 5bpm in 10 minutes segment tracing
excludindg
– Periodic or episodic changes
– Periods of marked variablity
– Baseline segments that differ >25bpm
NB. The baseline must be for a minimum of 2 min in any 10-min
segment or the baseline for that time period is indeterminate.
• In this case, one may refer to the prior 10-min window for
determination of baseline.

Baseline FHR
At term;
–Normal FHR baseline: 110-160 bpm
–Tachycardia: FHR baseline >160bpm
–Bradycardia: FHR baseline < 110bpm
Baseline change is an increase or
decrease in FHR that lasts longer than 10
minutes

Causes of Abnormal Baseline
• Bradycardia
– Post-term fetus
– OP, OT fetal position
– Fetal heart block
– Congenital heart
disease
– Fetal Hypoxia
– Abruption
– Maternal SLE
– Maternal
Hypothermia (under
GA)
• Tachycardia
– Preterm fetus
– Fetal movement
– Fetal arrhythmia (usually
>200bpm)
– Congenital defect
– Maternal fever
dehydration, or anxiety
– Maternal Ketosis
– Maternal Thyrotoxicosis
– Maternal Anemia
– Medications ( atropine,
terbutaline)
– Chorioamnionitis – even
before maternal fever

Baseline Variablity
• Fluctuations in the baseline FHR that are
irregular in amplitude and frequency
• Variability is visually quantitated as the
amplitude of peak-to-trough in bpm .
– Absent—amplitude range undetectable
– Minimal—amplitude range detectable but < 5
bpm
– Moderate(normal) —amplitude range 6–25 bpm
– Marked—amplitude range > 25 bpm
• Decreased baseline BBV is the single
most reliable sign of fetal compromise (

Causes of decreased Variability
• Normal causes
– Fetal sleep cycle
(usually lasts 20-40
minutes)
– Extreme prematurity
– Medications
• Narcotics
• Sedative-Hypnotic
medications
• Barbiturates
• Phenothiazines
• Magnesium sulfate
• General anesthesia
• Abnormal causes
– Fetal hypoxia *
– Fetal metabolic acidosis
– Fetal neurologic anomalies
(Anencephaly)
– Chorioamnionitis
– Fetal Heart Block
– Fetal Tachycardia
*mild degrees of
hypoxemia often
increase BBV ( at least
at the outset);
• loss of BBV likely results
from metabolic acidemia
which depresses fetal
brain stem and the Heart
( will 23rd)

BBV …….Will 23rd
• Several physiological and pathological processes can affect
or interfere with beat-to-beat variability.
• Dawes and co-workers (1981) described increased
variability during fetal breathing.
• In healthy infants, short-term variability is attributable to
respiratory sinus arrhythmia (Divon and associates, 1986).
• Fetal body movements also affect variability (Van Geijn and
colleagues, 1980).
• Pillai and James (1990) reported increased baseline
variability with advancing gestation.
– Up to 30 weeks, baseline characteristics were similar during
both fetal rest and activity.
– After 30 weeks, fetal inactivity was associated with diminished
baseline variability and conversely, variability was increased
during fetal activity.
– Fetal gender does not affect heart rate variability (Ogueh and
Steer, 1998).

Periodic FHR changes
Deviations from baseline along with uterine
contraction
• Accelerations
• Decelerations
– Early ( head compression)
– Late (Uteroplacental insufficiency)
– Variable ( cord compression pattern)
• Decelerations that occur with 50 % or more of
contractions in any 20-minute period are
referred to as recurrent decelerations (NICHD
Research Planning Workshop, 1997).
• Prolonged Ds- last >2- 10 min
• If Ds last for > 10 min Baseline change

Acceleration
• A visually apparent abrupt increase in the FHR
• onset to peak in less than 30 seconds=> ABRUPT
• Accelerations vary with GA in peak↑ and
duration
– Beyond 32wk - 15bpm or more above baseline,
with a duration of > 15 sec but <2min from
onset to return.
– Before 32 wk GA - >10 bpm above baseline, with
a duration of 10 sec to 2min from onset to return.
• Prolonged acceleration- duration of 2 – 10min.
• Baseline change- an acceleration lasts for > 10
min.

Accelerations

Accelerations
• Accelerations seem to have the same
physiological explanations as beat-to-beat
variability in that they represent intact
neurohormonal cardiovascular control
mechanisms linked to fetal behavioral states
• are common in labor and are nearly always
associated with fetal movement.
• acceleration can occur during labor without
any apparent stimulus.

Accelerations
• Proposed mechanisms for intrapartum
accelerations include;
– Fetal Movement,
– Stimulation By Uterine Contractions,
– Umbilical Cord Occlusion, And
– Fetal Stimulation During Pelvic Examination.
– Fetal Scalp Blood Sampling And Acoustic
Stimulation Also Incite Fetal Heart Rate
Acceleration (Clark And Associates, 1982).

Accelerations
• Accelerations are virtually always reassuring
and almost always confirm that the fetus is
not acidemic at that time

Decelerations Will 23rd
• Decrease ≥15 bpm, lasting ≥ 15sec min but < 2 min in
duration- below baseline return
• If duration > 2min but < 10 min-- Prolonged D and If
> 10 min  Baseline change
• Decelerations are calculated from onset to nadir /lowest point/
– Gradual- Onset to Nadir > 30 sec, curvilinear and
symmetric/ uniform waveforms
– Abrupt- Onset to Nadir < 30sec, jagged appearance of
Waveforms
• Early, Late,Variable- depending on the timing with
respect to uterine contraction
• Early and Late Ds- Visually apparent, often symmetric
gradual and associated with uterine contraction
• Recurrent Ds- that occur with > 50% of
contractions in any 20min time

Decelerations
Early D-Head compression
• Nadir occurs at the time of peak contraction
• Often, Onset, Nadir and Recovery of ED coincide with
beginning, Peak and ending of contraction respectively
Late Ds-UP insufficiency
• Delayed timing, nadir occurs after peak of contraction
• Often, onset, Nadir and Recovery of LDs occur after
beginning, peak and ending of uterine contraction
respectively
Variable Ds-Cord compression D
• Abrupt (onset-nadir < 30sec )/ erratic
• Onset, depth and duration vary with in successive
contraction

uniform
> 100 bpm
uniform
> 100 (120) bpm
not uniform
< 100 bpm
early
late
variable
Decelerations

Early Deceleration
• A gradual (i.e,Onset-Nadir > 30s),
symmetric decrease and return to
baseline associated with a contraction
–The nadir of the deceleration occurs at the
same time as the peak of the contraction
–Mostly Onset, nadir and recovery of ED
coincide with beginning, peak and end of
Ux contraction respectively
– The decrease in FHR is calculated from the
onset to the nadir of the deceleration. (ACOG
2010) SAMUEL BEZABIH (MD)- MIAZIA 2005

Features of Early Fetal Heart Rate Deceleration

Early Decelerations

Early Deceleration
• Head compression, probably ,causes vagal
nerve activation as a result of dural
stimulation, and that mediates the heart
rate deceleration
• Common during active labor and are not associated
with tachycardia, loss of variability, or other FHR
changes nor fetal hypoxia, acidemia, or low APGAR

Early Decelerations
• Freeman and co-workers (2003) defined early
decelerations as those generally seen in active
labor between 4 and 7 cm dilatation.
• In their definition, the degree of deceleration
is generally proportional to the contraction
strength and rarely falls below
–100 to 110bpm or
–20 to 30bpm below baseline

Late Decelerations
• Visually apparent usually symmetrical gradual
decrease and return of the FHR associated with a
uterine contraction
A gradual FHR decrease is defined as from the
onset to the FHR nadir of 30 seconds or more .
• The decrease in FHR is calculated from the onset
to the nadir of the deceleration.
• The deceleration is delayed in timing, with
the nadir of the deceleration occurring after
the peak of the contraction.
• In most cases, the onset, nadir, and recovery of
the deceleration occur after the beginning, peak,
and ending of the contraction, respectively.

Late Decelerations
• Typically not more than 10-20bpm below
baseline, rarely 30-40bpm below baseline
• the initial response of hypoxia due to
compromised UP perfusion
• usually not accompanied by accelerations.

Late deceleration of FHR

Late Decelerations
• Contraction ↓UP blood flow….lag
time…fetal hypoxia/low Po2- chemoreceptor
activation Deceleration
• ‘Lag time’-
– time interval b/n onset of contraction and
deceleration
– is indicator of fetal basal oxygenation but not PH
• Low precontraction Po2 – short lag time
• LD precedes acidemia
• Variability of the baseline heart rate disappeared
as acidemia developed. (experiment on monkeys)

Late Decelerations – causes:---
• Any process that causes maternal hypotension,
excessive uterine activity, or placental
dysfunction can induce late decelerations.
• The two most common causes are:-
– hypotension from epidural analgesia and
– uterine hyperactivity caused by oxytocin stimulation.
• Maternal diseases such as hypertension,
Diabetes, and collagen-vascular disorders can
cause chronic placental dysfunction.
• Placental abruption can cause acute late
decelerations

Variable Decelerations
Visually apparent ,Abrupt decrease of FHR from base
line by >/= 15bpm lasting 15sec-2min
• The most common deceleration patterns encountered
during labor , attributed to umbilical cord occlusion
• Variable pattern of onset with respect to ux contraction
• The decrease in FHR is calculated from the onset to the
nadir of the deceleration.
• Onset-Nadir : <30secs=> abrupt
• Vagally mediated via baro and chemo receptors
• Itskovitz and co-workers (1983) observed that variable
decelerations in fetal lambs occurred only after
umbilical blood flow was reduced by at least 50%.

Features of variable fetal heart rate decelerations

• Intermittent VDs
– occur with < 50% contractions
– The most common FHR abnormality during labor ,
– most often do not require any treatment, and are
associated with normal perinatal outcomes
• Recurrent VDs
– occur with >50% of contractions
– RVDs that progress to greater depth and longer
duration are more indicative of impending fetal
acidemia .
– In FHR tracings with recurrent variable decelerations,
the presence of moderate FHR variability or a
spontaneous or induced acceleration suggests that
the fetus is not currently acidemic.

• ACOG(1995) has defined significant variable
decelerations as those decreasing to less
than 70 beats/min and lasting more than 60
seconds.

Prolonged Decelerations
• Ds that last b/n 2-10min
• Causes
–Cervical examination
–Uterine hyperactivity
–Cord entanglement
–Maternal supine hypotension
–Epidural, spinal, or paracervical analgesia
may induce prolonged deceleration

Sinusoidal Pattern
• Visually apparent, smooth, sine wave-like
undulating pattern in FHR baseline with a cycle
frequency of 3-5 per minute which persists for 20
minutes or more. ACOG 2010
• may be observed with ;
– severe fetal anemia from Rh isoimmunization, feto-
maternal hemorrhage, TTTS or vasa previa with
bleeding; with fetal intracranial hemorrhage; and
– with severe fetal asphyxia (Modanlou and Murata,
2004). Insignificant sinusoidal patterns have been
reported
• following administration of meperidine,
morphine, alphaprodine, and butorphanol

Saltatory Bseline Pattern
• Saltatory baseline heart rate was first described by Hammacher and
colleagues and linked to umbilical cord complications during labor.
• The pattern consists of rapidly recurring couplets of acceleration
and deceleration causing relatively large oscillations of the
baseline fetal heart rate.
• We also observed a relationship between cord occlusion and the
saltatory pattern (Leveno and associates, 1984).
• In the absence of other fetal heart rate findings, these do not signal
fetal compromise.
• Lambda is a pattern involving an acceleration followed by a variable
deceleration with no acceleration at the end of the deceleration.
• This pattern typically is seen in early labor and is not ominous
(Freeman and colleagues, 2003).
• This lambda pattern may result from mild cord compression or
stretch.
• Overshoot is a variable deceleration followed by acceleration.
• The clinical significance of this pattern is controversial (Westgate
and associates, 2001).

3-Tiered Fetal Heart Rate Interpretation System
(2008 NICHD Workshop on EFM)
1. Category I ( Normal)
• Category I FHR tracings include all of the
following:
– Baseline rate: 110-160bpm
– Baseline FHR variability: moderate
– Late or variable decelerations: absent
– Early decelerations: present or absent
– Accelerations: present or absent

Three-Tiered Fetal Heart Rate Interpretation System
(2008 NICHD Workshop on EFM)
2. Category II ( indeterminate)
• Includes all FHR tracings not categorized
as Category I or Category III.
• May represent an appreciable fraction
of those encountered in clinical care.

Some Features of category II FHR Tracings
• Bradycardia with baseline
variability
• Tachycardia
• Minimal baseline
variability
• Absent baseline
variability with no
recurrent decelerations
• Marked baseline
variability
• Absence of induced
accelerations
• Recurrent variable
Decelerations + minimal
or moderate baseline
variability
• Prolonged deceleration
• Recurrent late
decelerations+ moderate
baseline variability
• Variable decelerations
with other characteristics
such as slow return to
baseline, overshoots, or
shoulders

•
Three-Tiered Fetal Heart Rate
Interpretation System (2008 NICHD Workshop on EFM)
3. Category III ( abnormal)
• Category III FHR tracings include either Absent
baseline FHR variability and any of the
following:
– Recurrent late decelerations
– Recurrent variable decelerations
– Bradycardia
– Sinusoidal pattern

Intrauterine Resuscitations for Category II and/or Category III Tracings or Both-
GOAL FHR abnormality Potential intervention
Promote fetal
oxygenation and
improve
Uteroplacental
blood flow
RLD, Prolonged
decelerations or
bradycardia
Minimal or absent FHR
variability
Initiate lateral positioning (either left or
right)
maternal oxygen administration
Administer intravenous fluid bolus
Reduce uterine contraction frequency
Reduce uterine
activity
Tachysystole with
Category II or III tracing
Discontinue oxytocin or cervical ripening
agent
Administer tocolytic medication (eg,
terbutaline)
Alleviate umbilical
cord compression
Recurrent variable
decelerations
Prolonged
decelerations or
bradycardia
Initiate maternal repositioning
Initiate amnioinfusion
If prolapsed umbilical cord is noted,
elevate the presenting fetal part while
preparations are underway for operative
delivery

The Three Tier System
• Cahill and colleagues (2012) Ret study ,None of the three FHR
categories demonstrated a significant association with cord
blood acidemia(pH ≤ 7.10) in 30 mins peceding delivery
• ACOG and AAP (2014)
– concluded that a category I or II tracing with a 5-minute APGAR
score > 7 or normal arterial blood acid-base values was not
consistent with an acute hypoxic-ischemic event
• Sholapurkar (2012) challenged the validity of the three tier
system because most abnormal fetal heart rate patterns fall
into the indeterminate category II, that is, one for which no
definite management recommendations can be made.
• Parer and King (2010) comment that the NICHD three-tier
system is inadequate because category II— indeterminate
FHR—consists of a “vast heterogenous mixture of patterns”
that prevents development of a management strategy

• It is apparent that, after 50 years of
continuous electronic fetal heart rate
monitoring use, there is not a consensus on
interpretation and management
recommendations for FHR patterns (Parer, 2011).

Summary of Randomized Studies
EFM Vs Auscultation
• Thacker and associates (1995) identified 12
randomized clinical trials of electronic fetal monitoring
from 1966 to 1994.
• There were 58,624 total pregnancies included in these
studies.
• These authors concluded that the benefits once
claimed for electronic monitoring are clearly more
modest than were believed and appear to be primarily
in the prevention of neonatal seizures.
• Long-term implications of this outcome, however,
appear less serious than once believed.
• Abnormal neurological consequences were not
consistently higher among children monitored by
auscultation compared with electronic methods.

EFM……Will 24th
• Using the Cochrane Database, Alfirevic and colleagues (2013)
reviewed 13 randomized trials involving more than 37,000
women.
– They concluded that EFM increased the rate of cesarean and
operative vaginal deliveries but produced no declines in rates
of perinatal mortality, neonatal seizures, or cerebral palsy.
• Grimes and Peipert (2010) wrote a Current Commentary on
electronic fetal monitoring in Obstetrics & Gynecology.
– They summarized that such monitoring, although it has been
used in 85 percent of the almost 4 million annual births in the
United States, has failed as a public health screening
program.
– They noted that the positive predictive value of EFM for fetal
death in labor or cerebral palsy is near zero—meaning that
“almost every positive test result is wrong.”

Fetal Echo and Pusoximetry

Fetal Scalp Sampling-Will 24th
• Measurements of the pH in capillary scalp blood may help
to identify the fetus in serious distress.
• according to ACOG (2009 )neither normal nor abnormal
scalp pH results have been shown to be predictive of
infant outcome
• Decreasing rate of use recently (absent in some hospitals)
• The only benefits reported for scalp pH testing are fewer
cesarean deliveries for fetal distress (Young, 1980b)
• Zalar and Quilligan (1979) recommended the following
protocol to try to confirm fetal distress.
– pH > 7.25, labor is observed.
– pH b/n 7.20 and 7.25, repeat measurement within 30 min .
– PH < 7.20, Delivery is performed promptly if the low pH is
confirmed with immediate repeat test.
• Otherwise, labor is allowed to continue, and scalp
blood samples are repeated periodically.

Fetal Scalp Sampling- Will 24th
• Goodwin and coworkers (1994), however, in a study of 112,000
deliveries,showed a decrease in the scalp pH sampling rate.
• The rate dropped from approximately 1.8 percent in the mid-1980s to
0.03 percent by 1992 but with no increased delivery rate for fetal
distress.
– They concluded that scalp pH sampling was unnecessary.
• Kruger and colleagues (1999) have advocated the use of fetal scalp blood
lactate concentration as an adjunct to pH.
• Wiberg-Itzel and associates (2008) randomized 1496 fetuses to scalp
blood pH analysis and 1496 to scalp blood lactate analysis.
• They found either to be equivalent in predicting fetal acidemia.
• The advantage of lactate measurement was that a smaller amount of
blood was needed, which led to a lower procedural failure rate
compared with scalp sampling for pH.
• Fetal scalp stimulation amd Vivbroacaustic stimulations to elicit A are
suugestedc as non invasive replacements for FS blood sampling

References
• Williams Obstetrics- 23rd ED
• Gabbe – obstetrics normal and problem
• Uptodate
• ACOG practice bulletin no 116, 2010

Premature Rupture Of
Membranes (PROM)

PROM
Definition:
PROM is the Spontaneous rupture of membranes
after 28 weeks of gestation before the onset of labor.
Occurs in ~ 10% of pregnancies
• Term PROM:
– after 37 weeks
• Preterm PROM:
– Before 37 weeks
• Latency period:
– Time between rupture of membranes to onset of labor.
• Prolonged PROM:
– latency longer than 12 hrs.

PROM- cont’d
Incidence: average around 10%, ranges 3-19 %.
Causes: Not known in majority.
• Possible causes include:
– Increased fragility of membranes
– Decreased tensile strength of membranes
– Polyhydraminos
– Cervical incompetence
– Multiple pregnancy
– Infection: Chorioamnionitis, UTI, lower genital
tract infection
– Emergent circlage

RISK FACTORS
• The pathogenesis of PPROM is not completely
understood.
• It shows association with;
– A history of PPROM in a previous pregnancy,
– Genital tract infection,
– APH
– Cigarette smoking
– Low socioeconomic status
– Polyhydraminos
– Cervical incompetence
– Multiple pregnancy
– Emergency circlage

PROM- Dx
 Diagnosis is generally clinical
 History:
– a sudden "gush" of clear or pale yellow fluid from the vagina.
– Intermittent or constant leaking of small amounts of fluid or
– just a sensation of wetness within the vagina or on the perineum
 Physical findings:
- Negative uterine size discrepancy
- Meconium or vernix on the vulva
- Sterile speculum examination with or without valsalva
maneuver( leakage or pooling)
direct observation of amniotic fluid coming out of the cervical canal
or pooling in the vaginal fornix
NB
 Digital examination should be avoided unless induction is
planned or the woman is in labor because it may decrease the
latency period (ie, time from rupture of membranes to
delivery) and increase the risk of intrauterine infection

Diagnosis-cont’d
 Nitrazine paper test:
– testing the pH of the vaginal fluid (color change
– Amniotic Fluid- alkaline (PH~7.3)
– False positive result alkaline fluids in the vagina Eg
blood, semen, bacterial vaginosis, and trichomoniasis
 Ferning Test :arborization (ferning).
– Fluid from the posterior vaginal fornix is swabbed onto a
glass slide and allowed to dry for at least 10 minutes.
– Amniotic fluid produces a delicate ferning pattern ( High
Na+ and protein contents)
 Pad Test
– Perinea Pad wetting
 Dye test;a definitive dx in equivocal cases,
– Indigo caramine is instilled into the amnotic cavity,
– tampoon placed in the vagina inspected after 30 min for
blue staining
 Ultrasonography- decreased AF volume

PROM- Differential diagnosis
• Stress Urinary incontinence
• Vaginal discharge
–Leucorrhea gravidarum or
–pathological)
• Perspiration

PROM- investigations
• CBC
• U/A, Culture & Sensitivity
• High vaginal swab for culture
• Phosphatidylglycerol from vaginal pool
(for fetal lung maturity)
• US

Complications of PROM
• Preterm Labor
– In Preterm PROM, labor starts in 70-80% of cases
in one week time
• Ascending infection: one third
• Increased incidence of cord prolapse
• Fetal pulmonary hypoplasia
• Prematurity
• Operative delivery
• Abruption

PROM- Managemet
Management of pregnancies complicated by PROM
depends on
• Gestational age
• Availability of neonatal intensive care
• Presence or absence of maternal/fetal infection
• Presence or absence of labor
• Fetal presentation (breech and transverse lies are
unstable and may increase the risk for cord prolapse)
• Fetal heart rate (FHR) tracing pattern
• Likelihood of fetal lung maturity
• Cervical status (by visual, not digital, inspection unless
induction is planned or the woman is in labor)

Indications for pregnancy termination in
PROM
• Term PROM
• Labor
• Presence of infection (chorioamnionitis)
• IUFD
• Congenital anomalies of fetus incompatible to
life
• Abnormal fetal surveillance

Preterm PROM
 GA > 34 weeks either conservative management or
termination
 GA< 34 weeks, conservative management
 Components of conservative management:
– Avoid digital vaginal examination
– Bed rest
– Monitor maternal PR, Temp., FHR every 4 hours
– CBC, U/A, ESR/CRP twice per week
– BPP/NST twice per week
– Corticosteroids if less than 32 weeks
– Administer antibiotics: ampicillin (iv)+ erythromycin X
48hrs followed by amoxacillin(po) & erythromycin to
complete a total of seven days

Chorioamnionitis
• Clinical or subclinical
• Criteria for clinical chorioamnionitis:
- Maternal temperature > 38o C
- Uterine tenderness
- Foul smelling amniotic fluid
- High WBC count (leukocytosis)
- Maternal &/ or fetal tachycardia

Sub clinical chorioamnionitis
• Amniocentesis: intramniotic infection is
present if:
1. Culture: bacterial colony count > 102 / ml
fluid
2. Presence of bacteria on gram stain
3. Glucose level<15 mg/dl
4. WBC> 100/ml

Management of chorioamnionitis
Antibiotics:
1. Ampicillin+ Gentamycin+
clindamycin/metronidazole/chloramphenicol
2. Ceftriaxone +/- metronidazole
Terminate pregnancy: Vaginal route is
preferred

PROM
( uncomplicated)
GA< 34 weeks
Conservative management
GA 34-37 weeks
Deliver/conservative
GA> 37 weeks
Deliver

Fetal Growth Disorders
by Dr.Samuel Bezabih

Fetal Growth
Determining Factors
• Maternal provision of substrates
• Placental transfer of the substrates
• Genome controlled Growth potential (major
determinant in early fetal life)
– IGF 1- produced in all fetal organs , potent stimulators
of cell division and differentiation
– Adepokines- hormnes derived from adipose tissue
( Leptin included- protein of obesity gene), Fetal leptin
conc increase through gestation , Birth wt correlate
with conc
– EGF, platlete derived GFs,Fibroblast derived GFs,
Leptin and Adeponectin implicated in macrosomia n

Fetal Growth
Fetal cellular growth has 3 consecutive phases [Lin and
Santolaya-Forgas (1998)]
– The 1st 16 wks- Hyperplasia
– 16- 32 wks- Hyperplasia + Hypertrophy
– > 32weeks- Hypertrophy ( deposition of much of
the fetal fat and glycogen)
• The corresponding fetal-growth rates during
these three phases are
– 5 g/day at 15 weeks,
– 15 to 20 g/day at 24 weeks, and
– 30 to 35 g/day at 34 weeks (Williams and co-workers, 1982).

Non pathologic factors that affect fetal birth
weight
• Parental (maternal paternal )height/ weight
• Parity
– First-born infants tend to be smaller and more often
categorized as IUGR.
– This effect decreases with successive deliveries and is not seen
beyond the third birth
• Ethnicity and
• Fetal sex
– At term, female fetuses are an average 5% (150 g) smaller and 2% (1
cm) shorter than male fetuses

Fetal Growth Disorders
• Abnormal fetal growth now is defined
according to percentiles:
– infants <10th percentile are classified as having
intrauterine growth restriction(IUGR)
– those >90th percentile are classified as large for
gestational age (LGA).
• Standards also vary among different
populations.
• Both IUGR and LGA fetuses have increased risk
for perinatal morbidity and mortality

Intrauterine Growth Restriction (IUGR)
• IUGR is defined as EFW at or below the
10th percentile for GA.
• Incidence~10% of infants in any population
– NB- ~25-65% of infants that are < the 10th
percentile are constitutionally small
 Are appropriately grown but small due to
normal biological factors ( not pathologically
growth restricted )
• Distinguishing between normal and pathologic
growth can be difficult

IUGR Types
I. Symmetric-20% of IUGR infants
– all organs decrease in wt. proportionally
(proportionately small,)
– Small brain due to decreased neuron cells
• Decreased cellular size and number due to early
insult from nutritional deprivation/ genetic,
infectious etc factors/
– eg global insults such as from chemical exposure, viral
infection, or cellular maldevelopment with aneuploidy
– are more likely to have an endogenous defect that
results in impairment of early fetal cellular hyperplasia

IUGR Types
II. Asymmetric~80%
• brain is preferentially spared  ‘Brain Sparing’
• AC affected more than HC (disproportionately lagging
abdominal growth ) small fetal liver size
• brain has little size difference from AGAs due to
decreased neuronal size- not number
• usually due to deprivations in late pregnancy
• likely caused by IU deprivation that leads to
redistribution of flow to the brain and heart at the
expense of less important organs, such as the liver and
kidneys.
– Eg placental insufficiency due to hypertension

Asymmetrical IUGR
• Might follow a late pregnancy insult such as placental
insufficiency from hypertension.
• Resultant diminished glucose transfer and hepatic
storage would primarily affect cell size and not number,
and fetal AC—which reflects liver size—would be
reduced.
• Such somatic-growth restriction is proposed to result
from preferential shunting of oxygen and nutrients to
the brain.
• This allows normal brain and head growth, that is—
brain sparing
• the ratio of brain weight to liver weight during the last
12 weeks—usually about 3 to 1—may be increased to 5
to 1 or more in severely growthrestricted infants.

IUGR –Fetal Effects
• Compared with an appropriate-for-
gestational-age (AGA) fetus, the IUGR fetus
has altered:
– body composition
• including decreased body fat, total protein, whole
body DNA and RNA, glycogen, and free fatty acids
– distribution of weight among organs, and
– body proportions

IUGR- Fetal Effects
• Cerebral abnormalities include
• decreased myelination,
• decreased utilization of metabolic substrates
other than glucose, and
• altered protein synthesis.
• Liver
– Decreased size ( low glycogen storage-low
nutritional state)=> decreased AC
– Functional abnormalities ( abnormal LFT of the
neonate/ cord blood)

IUGR
Lung
• ↓ed blood flow
low pulmonary contribution to AFV-
olygohydramnios
 Numerous reports describe Accelerated lung
maturity I complicated pregnancies ass with FGR
(Perelman, 1985). ??? Stressadrenal Glucocorticoid secretion???
(Laatikainen, 1988). Negligible evidence
Kidneys
• ↓ed renal blood flow-
↓ed GFR- olygohydramnios

Complications
MATERNAL
• Complications due to underlying
disease, preeclampsia,
premature labor, CS delivery
FETAL
• Stillbirth, Hypoxia and Acidosis,
• Malformations
NEONATAL
• Hypoglycemia,
• Hypocalcemia,
• Hypoxia and Acidosis,
• Hypothermia,
NEONATAL—contd.
• MAS
• Polycythemia,
• Congenital Malformations,
• Sudden Infant Death
Syndrome
LONG-TERM Comps.
• Lower IQ,
• learning and behavior
problems,
• major neurologic handicaps
(seizure disorders, cerebral
palsy, mental retardation),
• hypertension

Perinatal Risks
• fetal-growth restriction is associated with
substantive perinatal morbidity and mortality
rates. Increased rates of
– stillbirth,
– birth asphyxia,
– meconium aspiration, and
– neonatal hypoglycemia and hypothermia
– Neonatal death
– the prevalence of abnormal neurological development
(Jacobsson, 2008; Paz, 1995).
• This is true for both term and preterm growth-
restricted infant

Long-term Sequel
• Numerous reports of relationship between
suboptimal fetal nutrition and an increased
risk of subsequent adult
– hypertension,
– atherosclerosis,
– type 2 diabetes, and
– metabolic derangement (Gluckman, 2008).

Long term Sequel
• There is increasing evidence FGR may affect
organ development, particularly that of the heart.
• Individuals with LBW demonstrate cardiac
structural changes and dysfunction persisting
through childhood, adolescence, and adulthood.
• Deficient fetal growth is also associated with
postnatal structural and functional renal changes.

IUGR-causes
A. Fetoplacental Causes
Genetic disorders
• Autosomal:
– trisomy 13, 18, 21; partial trisomies
– ring chromosomes;
– chromosomal deletions;
• Sex chromosomes:
– Turner's syndrome,
– multiple chromosomes (XXX, XYY)
Congenital Malformations
Neural tube defects
Skeletal dysplasias:
• achondroplasia, chondrodystrophies, osteogenesis imperfecta
Abdominal wall defects- Gastroschesis--
Other rare syndromes: Smith-Lemli-Opitzs, Meckel's ,
Robert's s, Donohue's s, and Seckel's, potters syndromes

Fetoplacental Causes of IUGR
• Infants with renal anomalies such as renal
agenesis (Potter's syndrome) or complete
urinary tract outflow obstruction often have
IUGR.
• Other congenital anomalies associated with
an increased incidence of IUGR outcome are
duodenal atresia and pancreatic agenesis

Fetoplacental Causes of IUGR-contd.
• Congenital infection
– Viral: CMV, Rubella, Herpes, Varicella-Zoster
– Protozoan: toxoplasmosis, malaria
– Bacterial: listeriosis
• Placental disorders:
– placenta previa, placental infarction, chorionic
villitis, chronic partial separation,
– placental malformations (circumvallate placenta,
battledoreplacenta, placental hemangioma, TTT)
– Placental mosaicism
• Multiple gestation

IUGR Causes
B. Maternal Factors
• Coexistent maternal disease:
– hypertension,
– anemia (hemoglobinopathy, sickle cellA,decreased normal
hemoglobin [especially < 12 g/dL]),
– renal disease(hypertension, protein loss),
– Pregestational DM Congenital anomally, substrate deprivation
from vascular disease, Nephropathy and Prolifer retinopathy
increase the risk
– Chronic Hypoxia 20 to HTN, PE Asthma, Smoking, High altitude
– malnutrition (inflammatory bowel disease [ulcerative colitis,
regional enteritis], pancreatitis, intestinal parasites),
inadequate intake Hunger winter (1944, Holland) 600kcal/day
for 6mths average Bwt decline was 250g
– cyanotic cardiopulmonary disease
– APS, Thrombophillias

IUGR Causes- Maternal Factors contd.
• Substance abuse/drugs: alcohol, cigarette
smoking, cocaine, heroin, warfarin, folic acid
antagonists (methotrexate, aminopterin),
anticonvulsants
• Small maternal stature, wt
– Women <100IB on conception- increased SGA
– Inadequate Weight gain during pregnancy

IUGR causes
NB-IUGR outcome also may develop in
pregnancies without identified risk factors.

IUGR Screening
Serial fundal height –
– routine screening for all pregnancies ( but not Dxtic
for interventional decision)
– Comparable to US
– Single record of fundal height at 32- 34 wk
• ~85% Ss, 96% SP
US-mainly reserved for those with RFs, previous Hx
lagging growth ---
– single 3rd T AC measurement ~80% Sp
– AC, serial growth --
• Doppler US- not useful for screening

IUGR- Antenatal Diagnosis- ACOG 2010
Two essential steps
I. Maternal risk factors assessment + clinical
evaluationt of uterine size in relation to GA.
II. Ultrasonographic assessment of fetal size and
growth, supplemented by invasive fetal testing
for aneuploidy or viral infection in select cases.

IUGR-Antenatal Diagnosis
• EDD should be determined initially /GA
determination
• Careful attention to fundal height – smaller than
expected for the GA / lagging fundal height??
– measurements is associated with a diagnostic sensitivity
of 46–86%.
• US Evaluation
– GA estimation
– Weight estimation- mainly using AC (liver size and SC fat
amount)
– Serial growth ( growth Velocity)
– FL/AC (> 23% in IUGR) ,
– HC/AC As high as 5:1 ,Normal ~3:1
– Genetic and congenital/ structutal anomalies
– AFV ( oligohydramnios in 77-83% of IUGR fetuses)

Antenatal Diagnosis-Gabee
AC
• is the single best measurement for the detection of
IUGR. (the highest sensitivity and NPV for the US dx
of IUGR)
• Using the 10th percentiles as cutoffs, the AC has a
higher sensitivity (98% versus 85%) but lower PPV
than the SEFW (36% VS 51%).
• Its sensitivity is further enhanced by serial
measurements at least 14 days apart.
• Because of its high sensitivity, some type of
abdominal measurement should be part of every
sonographic growth evaluation.
• But because the AC reflects fetal nutrition, it should
be excluded from the calculation of the composite
gestational age after the early second trimester.

Antenatal Diagnosis-Gabee
• Sonographically estimated fetal weight
(SEFW):the most important calculated US
variable of fetal growth
– All of the techniques incorporate an index of
abdominal size as a variable contributing to the
estimation of fetal weight.
– SEFW has a lower sensitivity but higher PPV than the
AC and does not add to the AC percentile for the
diagnosis of IUGR
• The FL/AC ratio
– is 22 at all GAs from 21 weeks to term and so can be
applied without knowledge of the GA.
– An FL/AC ratio greater than 23.5 suggests IUGR

Antenatal Diagnosis
Elevated MSAFP levels
• predict increased risk for IUGR outcome, regardless of
maternal weight.
• It also predict an increased risk for other obstetric
problems, including preeclampsia, placental abruption,
preterm labor, and stillbirth
Fetal blood sampling
• can provide useful information on fetal karyotype,
acid–base balance, fetal metabolism, and possible fetal
infection,
• associated with much increased morbidity and
mortality in the presence of IUGR.

Antenatal Diagnosis
Amniocentesis.
• If clinically indicated, studies should be performed to
exclude infection.
• Initially to determine maternal immune status (Ig M
against CMV , rubella virus, and T gondii).
• If these levels are suggestive of recent infection, direct
assessment of the amniotic fluid by PCR and culture
may be required.
• A careful targeted ultrasound examination should be
performed to determine the degree of fetal
involvement, particularly of the central nervous
system.

Management Of IUGR
• Currently no IU therapy for IUGR fetuses
• Options of management
– Delivery vs Expectant management
depending on maturity and risk of IU death
Principles of management of IUGR include
I. Further evaluation with doppler US
II. Follow up ( growth, fetal wellbeing , Doppler)
III. Delivery

Doppler Velocimetry
• To see the severity of compromise in fetuses
after dx ( suspicion ) of IUGR
• Reduces interventions and improves out
comes of IUGR pregnancies
i.e normal doppler study  no acidemia no
need of intervention + less frequent antenatal
surveillance
• Fetuses with normal flow pattern donot
benefit from early delivery

Umbilical Artery Doppler Velocimetry (UADV)
• UADV is considered standard in the evaluation
and management of the growth-restricted
fetus
• UADV has been shown to improve clinical
outcomes. It is recommended in the
management of fetal-growth restriction as an
adjunct to standard surveillance techniques
such as NST and BPP (ACOG 2013)

• Abnormal placental circulatory insufficiency
due to ↑ placental resistance is evident from
abnormal flow patterns of UADV ie
– S/D ratio > 95 percentile for gestational age
– Decreased/ Absent diastolic flow
– Reverse diastolic flow (severest injury- has long
been correlated with hypoxia, acidosis, and fetal
death)

Umbilical Artery Doppler Velocimetry (UADV)
• Abnormal flow pattern is associated with poor
perinatal outcome and high mortality
• Normal flow- excellent NPV delivery can be
delayed safely

Normal velocimetry pattern with a systolic to diastolic (S/D) ratio of < 3.
The diastolic velocity approaching zero reflects increased placentalvascular
resistance

During diastole, arterial flow is reversed (negative S/D ratio), which is
an ominous sign that may precede fetal demise.

Monitoring a pregnancy complicated with IUGR
• Term – delivery
• Remote from term- optimal method of
monitoring not established
• Acceptable methods of monitoring include -
weekly
– Doppler velocimetery
– BPP/ modified BPP
– CST
– NST
• Serial growth determination Q 2-4 wk

M’gt of GR Fetus Remote from Term
• If growth restriction is identified in an
anatomically normal fetus before 34 weeks,
and amnionic fluid volume and fetal
surveillance findings are normal, then
observation is recommended.
• Weekly assessment of UA Doppler
Velocimetery and AFV is combined with
periodic NST
• growth assessment Q 3-4wks

• Antepartum surveillence tests are performed to
determine the optimal time of delivery
– Identification of fetuses at risk of inutero demise so that
preterm delivery is preferable
• More frequent testing is indicated ( eg daily) if there is
abnormal test ( eg low BPP, AFV---)
• APFS is not necessary If lethal anomaly is identified
• administer Corticosteroid- if at risk of birth at < 34
weeks- (ACOG 2013)
• GR Fetuses may not tolerate the metabolic effects of
corticosteroids in the same way as an unstressed fetus.
 Increased surveillance during administration is
required -Vidaeff and Blackwell (2011)

• When corticosteroids are administered, it is important to
account for their effect on fetal testing parameters when
interpreting antenatal surveillance results.
• Betamethasone, for example, temporarily reduces FHR
variation on day 2 and 3 after the first injection, together
with a 50% decrease in fetal BMs and an almost cessation
of FBMs .
• Subsequently the number of fetuses with an abnormal BPP
score increases significantly by 48 hours after steroid
administration, with a return to the preadministration state
at 72 hours.
• In contrast, maternal and fetal Doppler findings are not
affected to the same degree during this period.
• A transient decrease in the MCA blood flow resistance has
been reported 48 hours after betamethasone
administration

Identification of underlying causes-adds little for management
• Maternal medical condition-
– Rx may not improve fetal condition
• US for structural anomalies
– Lethal anomalies- further surveillence may be deferred
• Karyotyping ( not routinely indicated)
– May be for early/ severe IUGR with structural anomalies ( 10%
association)
• Amniocentesis/ Crdocentesis-
– dx of inutero viral infections ( PCR or Abody) Eg rubella,
varicella, CMV
– Viral infections- no Iu Rx
– Toxo- maternal rx may prevent spread to fetus

Any Intervention to improve outcome?
• Few evidence based beneficial interventions
– cessation of smoking
– Treatment of malaria
• Interventions of unknown of efficacy ( No randomised
controlled trial -RCT- conclusive of benefit or harm)
– Bed rest
– Nutrient supplementation ( Zn, Ca,)
– Plasma volume expansion
– Maternal oxygen therapy
– Heparin, low dose aspirin
• No evidence that treating maternal medical Condition
improves fetal condition ( Eg antihypertensives )

Delivery
• Timing – when risk of fetal death exceeds that
of the neonate
• Usually based on abnormal fetal assessment
and complete cessation of growth in the 2-
4weekly serial growth evaluation
• Considerations
– Prematurity in early delivery
– Fetal death or long term neurologic ( acidotic,
hypoxic infant) sequele from delayed delivery

IUGR- Delivery
• As long as there is interval fetal growth and fetal
surveillance test results are normal, pregnancy is
allowed to continue until fetal lung maturity is
reached
Or
• Delivery of a suspected growth restricted fetus
with normal umbilical artery Doppler velocimetry,
normal AFV, and RFHR testing can likely be
deferred until 38 weeks’ GA
• Consensus statements by SMFM and ACOG
(2013) recommend delivery between 34 and 37
weeks when there are concurrent conditions such
as oligohydramnios

Labor and Delivery
• With a reassuring fetal heart rate pattern, vaginal
delivery is planned.
• However, some of these fetuses do not tolerate
labor due to
– Worsening of Placental insufficiency,
– Cord compression in oligohydramnios
• This often necessitates cesarean delivery
NB
• Labor should be followed as a ‘ High Risk’ continuous EFM/
frequent intermittent FHR auscultation
– Readiness to manage neonatal complications
• Hypothermia, Hypoglycemia ,MAS, polycythemia----

Prevention
• Ideally begins preconceptionally
– -optimization of medical conditions and
medications ,nutrition, smoking cessation
– Adressing specifc RFs antimalarial rx for those in
endemic areas, nutritional deficiencies correction
• Accurate dating
• Surveillence in those with prior hx of SGA (
associated with adverse outcomee-stillbirth
and preterm birth- in subsequent pregnancies

• LGA and Macrosomia ---- reading assignment

Blood Volume
Non pregnant BV calculation
– Non-pregnant blood volume ~ 3500 ml
– Pregnant blood vlume~5000ml

Blood Volume
Pregnant blood volume:
• Increases across GA and plateaus at app.34 weeks
• Ovaerall average increase over calculated
nonpregnant volume
– 30 - 60 % in Singleton Pregnanacy
– 40 - 80 % with MF gestation
• Average increase is less in women with hypertensive
disorder of pregnanacy ; ~9% less than in
normotensives
preeclamsia severity is inversely related with volume
• Thus, these women are very sensitive to, or even
intolerant of, what may be considered normal blood
loss

Classification of Hemorrhage
• Class I hemorrhage
– Involves a blood volume loss of up to 15 % (~1000ml)
– The heart rate is minimally elevated or normal, and
– No change in BP , pulse pressure, or RR .
• Class II hemorrhage
– Involves 15 – 30% blood volume loss (1200-1500ml)
– clinically manifests as:-
• Tachycardia (HR 100 -120’) ,tachypnea (RR :20 – 24’),
• A decreased pulse pressure, although SBP changes
minimally if at all.
• The skin may be cool and clammy, and
• Capillary refill may be delayed.

• Class III hemorrhage-
• involves a 30 to 40 % blood volume (~2000ml)
loss, results in
– a significant drop in BP
– Changes in mental status.
– Markedly elevated HR (≥ 120 and thready) and RR
– Diminished urine output.
– Delayed Capillary refill .
• Any hypotension (SBP< 90 mmHg) or drop in BP > 20 -30 % of the
measurement at presentation is cause for concern.
• While diminished anxiety or pain may contribute to such a drop, the
clinician must assume it is due to hemorrhage until proven
otherwise.

Class IV hemorrhage
• > 40 % (> 2500ml) BV loss leading to:-
– significant depression in BP and mental status.
– Most patients are hypotensive (SBP < 90 mmHg).
– Pulse pressure is narrowed (≤25 mmHg), and
– tachycardia is marked (>120).
– Urine output is minimal or absent.
– The skin is cold and pale, and
– capillary refill is delayed

Obstetrical Hemorrhage (OH)
• Obstetrics is "Bloody Business.“
• Hemorrhage is the single most important
cause of maternal death worldwide.
• Obstetrical hemorrhage (OH) accounts for
almost half of all postpartum deaths in
developing countries
• Fatal hemorrhage is most likely in
circumstances in which blood or components
are not available immediately

Obstetrical Hemorrhage
• Generally speaking,OH can be
– antepartum (28 wk to delivery of last fetus) or
– postpartum (more common)

Special Considerations
The following may be sensitive for a blood loss
considered normal;
• Small women
– proportionally small BV despite normal pregnancy
induced expansion
• Preeclamptic/Eclamptic
• Chronic renal insufficiency
– Inadequate pregnancy induced hypervolemia

Causes and Predisposing Factors of OH
1. Abnormal Placentation
– Placenta previa
– Placental abruption
– accreta/increta/percreta
– Ectopic pregnancy
– Hydatidiform mole
2. Labor and Delivery Trauma
– Episiotomy
– Complicated vaginal
delivery
– Low- or midforceps
delivery
– C/D or hysterectomy
3. Uterine rupture
• risk increased by:
– Previously scarred uterus
– High parity
– Hyperstimulation
– Obstructed labor
– Intrauterine manipulation
– Midforceps rotation

4. Small Maternal BV.
– Small women
– Pregnancy hypervolemia
not yet maximal
– Pregnancy hypervolemia
constricted
– Severe preeclampsia
– Eclampsia
– Sepsis syndrome
– Chronic renal
insufficiency
6.Other Factors
• Obesity
• Previous PPH
5.Uterine Atony
• Over-distended uterus
– Large fetus
– Multiple fetuses
– Hydramniosis
– Distension with clots
– Labor induction
• Anesthesia or analgesia
• Halogenated agents
• Conduct analgesia with
hypotension
• Exhausted myometrium
• Rapid labor
• Oxytocin or PG stimulation
• Chorioamnionitis
• Previous uterine atony

Coagulation Defects—Intensify Other Causes
– Massive transfusions
– Sepsis syndrome
– Severe preeclampsia and eclampsia
– Anticoagulant treatment
– Congenital coagulopathies
– Amniotic fluid embolism
– Prolonged retention of dead fetus
– Saline-induced abortion

Percentages are approximations because of different classification schemata
used. DIC = disseminated intravascular coagulation. (Data from Al-Zirqi,
2008;Berg, 2010; Chichakli, 1999; Zwart, 2008.) Will 24th
Contributions to maternal death from
various causes of obstetrical hemorrhage

Antepartum Hemorrhage (APH)
Causes:-
• Obstetric causes
– Bloody Show (excessive)
– Placenta Previa
– Vasa Previa
• Local causes
– Cervicitis
– Premalignant/ malignant cervical lesions
• Unexplained

Antepartum Hemorrhage
1.“Bloody Show"
–common, Slight vaginal bleeding in active
labor
–The consequence of effacement and
dilatation of the cervix, with tearing of small
vessels
–insignificant blood loss.
Uterine bleeding, however, coming from above the cervix,
is cause for concern

Unexplained APH
2.Unexplained APH
• The source of uterine bleeding is not always identified.
• In that circumstance, antepartum bleeding typically
begins with few, if any, symptoms and then stops.
• At delivery no anatomical cause is identified.
• In many of these cases, bleeding likely is the
consequence of slight marginal placental separation.
• A pregnancy with such bleeding remains at increased
risk for a poor outcome even though the bleeding soon
stops and placenta previa appears to have been
excluded by sonography
• delivery should be considered in any woman at term
with unexplained vaginal bleeding.

APH……
3.Vasaprevia
– B.Vesselss overlie the cervix extending from the
cord insertion (within the membranes)
– velamentous insertion of the umbilical cord,
rare~ 1%
– hemorrhage may follow laceration of these
vessels at the time of membrane rupture (digital
manipulation, fetal descent).
– Common in placenta previa and multiple gestation

APH…..Placenta Previa
4.Placenta Previa
• Implantation Of the placenta over or very near to the
internal cervical OS.
– Total Placenta previa:-covers the entire internal OS
– Partial Placenta Previa:-covers the internal OS partially
– Marginal Placenta Previa:-placenta reaches the edge of the
internal OS (within 2cm) but did not overlie it.
– Low-lying Placenta:-implantation in the lower uterine
segment , the placental edge does not reach the internal os
and remains outside a 2-cm wide perimeter around the os.
• Incidence-~ 1/300 deliveries (0.3%)

APH-Placenta Previa……
• Reported incidences for placenta previa
average 0.3 percent or 1 case per 300 to 400
deliveries.
• Risk Factors Incidence of PP increases with
– Advancing age
– Multiparity
– Multifetal gestation
– Prior Cesarean delivery
– Smoking
– Elevated MSAFP at early screening

APH- Placenta Previa
Clinical Manifestations
– Profuse bright red bleeding of sudden onset
– Often- painless ( no uterine contraction) and without
apparent cause
– The bleeding May be recurrent
• A few nulliparous patients even reach term without
bleeding, possibly because the placenta has been
protected by an un effaced cervix.
• The uterus usually is soft, relaxed, and nontender.
• A high presenting part that cannot be pressed into the
pelvic inlet.
• FHR abnormalities are unlikely unless there are
complications such as hypovolemic shock, placental
separation, or a cord accident

APH- Placenta Previa….
Pathogenesis Of Bleeding
• Uterine remodeling and Lower uterine segment
formation  Dilatation and effacement
separation of part of the placenta and avulsion
of vessels
• Bleeding is augmented by the inability of lower
segment fibers to contract + lacerations in the
friable cervix and lower segment.
• bleeding from the lower segment implantation
site also frequently continues after placental
delivery.

Diagnosis
Placental localization
–US
• Trans abdominal US ( average accuracy of 96%)
• Trans vaginal US (safe and more accurate)
• Trans perineal US
–MRI
–Double set-up technique- clinical dx
(i.e. Everything should be ready in OR to precede c/s.)

• Diagnosis by clinical examination Double
set-up technique
– A cervical digital examination is done with the
woman in an operating room and with all
preparations for immediate cesarean delivery
(prepped and draped).
• NB
– Never do PV exam (Contraindicated) in APH
patient with placenta previa unless in double set
up exam
– Even the gentlest examination can cause torrential
hemorrhage.

APH- Placenta Previa…….
Management of PP.
• Management of APH 20 to placenta previa Depends
on:
– Fetal age and thus maturity;
– Labor; and
– Bleeding and its severity.
1.Expectant management if:-
– Preterm fetus
– No persistent/ active bleeding
– Stable fetomaternal condition
 Close observation for recurrent bleeding,
 Tocolytics if there is labor
 Steroids (If < 34 wks)
 Fetal wellbeing surveillance.

Expectant Management principles ( inpatient or OP)
– Close observation for any vaginal bleeding
– Steroids if GA < 34 weeks
– Tocolytics to arrest labor??
– Serial US to assess placental location and fetal
growth,
– Avoidance of cervical examinations and coitus
– Activity restrictions,
– counseling regarding labor symptoms and
vaginal bleeding,
– Dietary and nutrient supplementation to avoid
maternal anemia,

Delivery
• Delivery in asymptomatic patients is typically
recommended at 37 completed weeks
• Scheduled (elective) CS for nearly all cases of
PP
• Vaginal delivery may be attempted in;
– low lying placenta & anterior PP.

APH-Placenta Previa
 Conditions associated with placenta previa
• Morbid adherence of placenta (accreta syndromes) in 5-10% of
placenta previa.
– Placenta accreta (80%):--villi are attached to the
myometrium
– Placenta increta (15%):--villi actually invade the
myometrium.
– Placenta percreta (5%):--villi that penetrate through the
myometrium and to or through the serosa
• Congenital anomalies
• Malpresentation ( transverse, oblique--)
• PROM
• IUGR
• Vasa previa and velamentous insertion of umb cord
• Amniotic fluid embolism

APH-Abruptio Placentae (Placental
Abruption)
Abruptio Placentae
 The premature separation of a normally implanted
placenta from the uterus i.e. before delivery of the
fetus
• Reported frequency averages ~1 in 200
deliveries.

Frequency of placental abruption by gestational age.

APH-Abruptio Placentae
Etiology
Inciting causes- not known in most cases,
• Defective Trophoblastic invasion with
subsequent atherosis
– proposed in some cases of PE
• Infection and inflammation; may be
contributory.
– Histologic evidence of inflammation (nutrophil
infiltration in baboon AP)

AP- pathogenesis
 Rapture of Decidual Spiral Arteriole Hemorrhage into the
decidua basalis * Decidual hematoma formation and
expansion separation of placenta, destruction of placental
tissue, and a loss of maternal-fetal surface area for nutrient and
gas exchange.
 *Thrombin, which is released in response to decidual
hemorrhage or hypoxia, appears to play an active role in
the pathogenesis of AP
• Thrombin acts as a direct uterotonic,
– enhances the action of matrix metalloproteinase,
– up regulates apoptosis genes, and
– increases the expression of inflammatory cytokines.
• These thrombin-mediated events initiate a cyclic pathway
of vascular disruption, hemorrhage, inflammation,
contractions, and rupture of membrane

• Bleeding is always maternal as separation is
from maternal decidua
• Fetal bleeding is possible on traumatic
abruption ( fructure/ tearing of placenta)

AP-CLINICAL MANIFESTATIONS
• The clinical manifestations of placental
abruption are dependent on a variety of
factors, including whether it is:
1. acute or chronic,
2. concealed or clinically evident, and
3. mild or severe

 An acute, overt and progressive abruption typically
presents with
– vaginal bleeding,
– abdominal pain,
– uterine contractions.
– uterine tenderness,
– tachysystole,
– non-reassuring fetal heart rate patterns, and fetal death
– Coagulopathy (DIC), Hemorrhage, Shock
• The amount of vaginal bleeding correlates poorly with the
extent of placental separation and its potential for fetal
compromise.
• With severe abruptions ( > 50% of the placental surface
area separates) Consumptive coagulopathy may result
from activation of coagulation cascade triggered by
hemorrhage and extensive thrombin deposition

 Bleeding from AP can be either External or
Concealed

Chronic Abruption
• Some abruptions may start early in pregnancy
• Association seen b/n Elevation of serum markers of some
aneuploidies and subsequent abruption; Dugo+ and
coworkers(2004)
• Ananth (2006) and Weiss (2004) and their associates have
also correlated 1st and 2nd T bleeding with3rd T AP.
• In some cases of a chronic abruption, subsequent
oligohydramnios develops chronic abruption
oligohydramnios sequence---CAOS (Elliott, 1998).
• Even later in pregnancy, hemorrhage with Retroplacental
hematoma formation is occasionally arrested completely
without delivery.
• These women may have abnormally elevated AFP (Ngai,
2012).

Chronic abruption
• Insidious and is often associated with ischemic
placental disease.
• Typically present with intermittent, light vaginal
bleeding and evidence of chronic placental
inflammation and dysfunction, such as
– oligohydramnios,
– fetal growth restriction,
– preterm labor,
– premature PROM , and
– preeclampsia.

APH-Abruptio Placentae, clinical
Vaginal Bleeding
1. Concealed Hemorrhage(10%-20%)
– no visible bleeding( confined to uterine Cavity)
– likely complete ( total) separation
– Extent of the hemorrhage is not readily
appreciated  Delayed DX  greater maternal and
fetal hazards
• often severe complications E.g, consumptive coagulopathy.
2. External Hemorrhage(80%- 90%)
– blood drains via cervix
– likely incomplete placental detachment(marginal/rim
involvement)
– fewer and less severe complications
(premature labor is the most important complication)

APH-Abruptio Placentae,Classification
1. Grade 1, mild (40% of abruptions):
– Vaginal bleeding is slight or absent (<100 ml).
– Uterine activity may be normal/ slightly increased
with localized pain.
– No fetal heart rate abnormalities are present.
– There is no evidence of shock or coagulopathy

2. Grade 2, moderate (45%):
– External bleeding may be absent to moderate(100-
500 ml)
– 25-50% of placental surface detached
– Uterine tone may be ↑ed with tetanic contractions
and uterine tenderness .
– Fetal heart tones may be absent / evidence of fetal
distress (tachycardia, decreased variability or mild late
decelerations).
– Maternal tachycardia, narrowed pulse pressure, and
orthostatic hypotension may be present.
– Early evidence of coagulopathy may be present
(fibrinogen 150-250 )

3. Grade 3, severe (15%):
– External bleeding may be moderate or excessive
(>500 ml) but may be concealed.
– > 50% of placental surface is detached
– The uterus is tetanic, board like and tender to
palpation (knife like pain).
– Fetal death is common/ severe late decelerations,
bradycardia or death).
– Maternal shock is usually present.
– Coagulopathy is frequently present

APH-Abruptio Placentae, Dx
Diagnosis
• Placental abruption is primarily a clinical diagnosis
• Any patient with findings of;
– Vaginal bleeding,
– Preterm labor,
– Abdominal pain, or
– Trauma
• should prompt an investigation of placental
abruption
• Radiographic, laboratory, and pathologic studies
support the clinical Dx.

APH-Abruptio Placentae,Dx
US:-----
• Sonography infrequently confirms the diagnosis of
placental abruption at least acutely, because the
placenta and fresh clot have similar sonographic
appearances.
• Acute hemorrhage may be misinterpreted as a
thickened placenta or fibroid
• Early hemorrhage is typically hyperechoic or
isoechoic, whereas Resolving hematomas are
hypoechoic within 1 week and sonolucent within 2
weeks of the abruption.
• In an early study, Sholl (1987) used sonography and
confirmed the clinical diagnosis in only 25% of women.
• Importantly, negative findings with sonographic
examination do not exclude placental abruption.

Sonography
• Ultrasound can identify three
predominant locations for placental
abruption. These are
–subchorionic (between the placenta and
the membranes)
– retroplacental (between the placenta and
the myometrium), and
– preplacental (between the placenta and
the amniotic fluid

 The classification system of placental abruption.
A. Retroplacental abruption: The bright red area represents a blood
collection behind the placenta (dark red).
B. Subchorionic abruption: The bright red area represents subchorionic
bleeding, which is observed to dissect along the chorion.
C. Preplacental abruption: The bright red area represents a blood
collection anterior to the placenta within the amnion and chorion
(subamniotic).

APH..PA
• LABORATORY FINDINGS
• Few laboratory studies assist in the diagnosis
of placental abruption.
– Hypofibrinogenemia and evidence of
consumptive coagulopathy are supportive of a
severe abruption;
– Abnormal serum markers early in pregnancy, such
as an unexplained elevated maternal serum α-
fetoprotein (MSAFP) and human chorionic
gonadotropin (hCG), have been associated with an
increased risk for subsequent placental abruption.

Other Lab Studies
• Hct/ HGb not reliable( hemoconcentration)
• Peripheral Blood Film : low platelates, shisctocytes ( suggest
IV coagulation)
• Coagulation profile( PT, PTT, Platlate count, fibrinogen, fibrin
split products) is necessary
• Bed side clot observation test Draw venous blood Q1hr, keep
it in clean test tube, if no clotting in 5-10min/ if the clot dissolute
with gentle shaking i.e fibrinogen deficiency
• Apt test may be used to determine maternal or fetal source
of bleeding.
• Mix vaginal blood with an equal part 0.25% sodium hydroxide.
• Fetal blood remains red
• maternal blood turns brown.
• Kleihauer–Betke test

 Kleihauer–Betke stain of a smear of maternal blood after fetal
death.
 The dark cells that constituted 4.5 percent of peripheral cells are
fetal in origin,
 whereas the empty cells are of maternal origin.

APH-Abruptio Placentae, RX
• Management of placental abruption depends on the
– severity,
– gestational age, and
– maternal-fetal status.
I. Emergency Management
– baseline laboratory assessment-(HGB, HCT, platelet count,
type and screen, fibrinogen, and coagulation studies),
– IV line access (large-bore catheter),
– Resuscitation with Crystalloid and blood products as
indicated ( whole blood, PRBC, FFP, cryoprecipitate,
platelet )
– continuous FHR and contraction monitoring, and
– communication with OR and neonatal personnel  for
possible emergency CD and neonatal resucitation

II. Expectant Management for;
– Small, non progressive abruption
– Preterm fetus and
– Stable maternal and fetal condition
• Monitor maternal VS, uterine activity
• Continuous electronic FHR monitoring then
fetal surveillance after stabilization
• Tocolysis
• Steroids if < 34 week

III. Delivery
• INDICATIONS if;
– Term/ near-term ,
– active brisk bleeding,
– fetus is dead,
• Routes of delivery:
– vaginal delivery is preferred
– induction if no spontaneous labor
– Amniotomy to facilitate labor and it is believed to
decrease coagulopathy by preventing entry of
thromboplastin into maternal circulation to persistent
uterine atony

APH..PA;RX…..
Indications for CD:
• Fetal compromise
• Living, Viable sized fetus and vaginal delivery
not imminent
• Uncontrollable active bleeding ( even for dead
fetus)
• Any other obstetric indication E.g. transverse
lie
• Hysterectomy:- for PPH secondary

APH-Abruptio Placentae,Complications
1.Maternal
• Hemorrhagic shock + 2⁰
– Acute kidney injury
– Sheehan’s syndrome*
– CHF
• DIC( consumptive coagulopathy)**
• Couveiler Uterus,
• Uterine atony-- PPH
*Pitutary failure resulting failure of lactation, amenorrhea, breast
atrophy, loss of pubic and axillary hair, hypothyroidism, and adrenal
cortical insufficiency
In some but not all instances of SD, there may be varying degrees of
anterior pituitary necrosis and impaired secretion of one or more
trophic hormones.
**10% of abruptions ass. With clinically significant coagulopathy (mainly
depletion of fibrinogen) due to release of tissue thromboplastin from
disrupted placenta

APH-Abruptio Placentae,Complications
Fetal
• Fetal Distress 2⁰ to, maternal hemorrhage,
fetal hemorrhage, Uterine hypertonus
• Increased PNM,
• preterm labor,
• IUGR/IUFD ( utero placental insufficiency)
• Neurological deficit( eg cerebral palsy) on
surviving infants

APH-Abruptio Placentae-prognosis
• Overall Perinatal mortality~5%
• MMR~0.5-5%

Post Partum Hemorrhage
• PPH has been variably defined in the literature.
• Definitions have included:-
– subjective assessments greater than the standard
norms
– > 500ml in SVD, >1000ml in CD
– a 10% decline in Hct, and
– the need for a blood transfusion.
• Because of these varied definitions, the exact
incidence of PPH is difficult to ascertain;
• however, estimates suggest that PPH
complicates 4 - 6% of all deliveries

PPH DEFINITION AND DIAGNOSIS
• The most common definition of PPH is EBL ≥500 mL
after vaginal birth or ≥1000 mL after cesarean delivery.
• The inadequacy of this definition was illustrated in
studies that assessed blood loss using various objective
methods:
– the mean blood loss reported after vaginal and CD was
approximately 400 to 600 mL and 1000 mL, respectively,
and clinicians were more likely to underestimate than
overestimate the volume of blood lost
• Blood loss estimation/Markers hemorrhage incidence
– Direct measurement,
– Predetermined Hct/HGB decline
– counting Number of women transfused

• PPH is best defined and diagnosed clinically as
excessive bleeding that makes the patient
symptomatic (eg, pallor, lightheadedness,
weakness, palpitations, diaphoresis, restlessness,
confusion, air hunger, syncope) and/or results in
signs of hypovolemia (eg, hypotension,
tachycardia, oliguria, low oxygen saturation
[<95%]) .
• Vaginal bleeding is usually noted, but may not be
present in cases where hemorrhage is related to
abdominal bleeding from a C/D. or a broad
ligament hematoma after a sulcus laceration.

• Another classic definition of PPH is a 10 % decline
in postpartum hemoglobin concentration from
antepartum levels.
• not useful clinically for several reasons:
rapid blood loss may trigger a medical emergency
prior to observation of a fall in hemoglobin
concentration;
laboratory changes that are not correlated with
events that endanger the patient should not be used
to define a medical emergency;
 and antepartum hemoconcentration (eg, from
preeclampsia or dehydration) may cause a large fall in
serum hemoglobin concentration following delivery in
the absence of excessive intrapartum blood loss.

PPH
1. Primary PPH
–in the 1st 24 hrs
2. secondary (late) PPH
–after 24 hrs PP
–in 1% of women

PPH
• Postpartum blood volume with serious
hemorrhage
• Assume acute return to nonpregnant total volume—
with fluid resuscitation—because pregnancy
hypervolemia will not be attained again

PPH-Etiology
• It may be helpful to think of the causes of PPH
in terms of the 4 “T”s:
– Tone: uterine atony, distended bladder.
– Trauma: uterine, cervical, or vaginal injury.
– Tissue: retained placenta or clots.
– Thrombin: pre-existing or acquired coagulopathy

Postpartum Hemorrhage
• PPH describes an event rather than a diagnosis,
and when encountered, its etiology must be
determined.
• Common causes include
–bleeding from the placental implantation
site,
–trauma to the genital tract and adjacent
structures, or both

Predisposing Factors and Causes of Immediate
PPH
1. Bleeding from Placental
Implantation Site
2. Hypotonic myometrium—
uterine atony:
– Some GAs- halogenated HCs
– Poorly perfused
myometrium—hypotension
– Hemorrhage
– Conduction analgesia
– Overdistended uterus: large
fetus, twins, hydramnios
– Prolonged labor
– Very rapid labor
– Induced or augmented labor
– High parity
– Uterine atony in previous
pregnancy
– Chorioamnionitis
– Retained placental tissue
– Avulsed lobule, succenturiate
lobe
– Abnormally adhered: accreta,
increta, percreta
3. Trauma to the Genital Tract
– Large episiotomy, including
extensions
– Lacerations of perineum, vagina,
or cervix
– Ruptured uterus
4. Coagulation Defects
– Intensify all of the above

Hemostasis at the Placental Site
• Near term, it is estimated that at least 600
mL/min of blood flows through the intervillous
space .
• This flow is carried by the spiral arteries—
which average 120 in number—and their
accompanying veins.
• With separation of the placenta, these vessels
are avulsed .

• Hemostasis at the placental implantation site
is achieved by
– contraction of the myometrium that compresses
this formidable number of relatively large vessels
– This is followed by subsequent clotting and
obliteration of their lumens
• Thus, adhered pieces of placenta or large
blood clots that prevent effective myometrial
contraction can impair hemostasis at the
implantation site

PPH-Clinical Characteristics
• PPH may begin before or after placental separation.
• Instead of sudden massive hemorrhage, there IS
usually is steady bleeding.
• At any given instant, it appears to be only moderate,
but may persist until serious hypovolemia develops.
• Especially with hemorrhage after placental delivery,
constant seepage can lead to enormous blood loss.
• The effects of hemorrhage depend to a considerable
degree on
– the nonpregnant blood volume and
– the corresponding magnitude of pregnancy-induced
hypervolemia.

• In some women after delivery, blood may not
escape vaginally
• but instead may collect within the uterine
cavity,
• which can become distended by 1000 mL or
more of blood

• Bp and PR-poor markers of magnitude of
blood loss (treacherous)
– change moderately until large volume is lost=>
hypovolemia is identified late
– Bp may initially↑ in response to hemorrhage in
the normotensive pt.
– Hypertensive pt. ,with significant bleeding, may
appear normotensive

PPH- Management
• Secure IV line resuscitate with crystalloid
and cross-matched blood as necessary
• Identify the underlying cause
• Palpate the uterus for Atony
• Inspect the genital tract for lacerations
• Draw blood for coagulation profile study
• If the uterus is atonic
– Intermittent massage
– Uterotonics

PPH Management
• If Atony persists despite the above
measures;
–Bimanual compression of the uterus
–Surgical interventions
• Uterine artery ligation
• Internal iliac / Hypogastric artery
ligation
• Hysterectomy

PPH Prevention
• Active management of 3rd stage of
labor:
–Administered Uterotonic agents
–Cutting controlled cord traction
–Intermittent uterine massaging until the
uterus remains persistently well contracted

PPH
• Uterotonics for prevention and Treatment of
PPH:-
– Oxytocin IV or IM
– Ergometrine IM ( contraindicated in hypertension
and cardiac diseases)
– Misoprostol ( PR, sublingual--)
– Carboprost promethazine— Hemabate
• is the 15-methyl derivative of prostaglandin F2ἀ

Red Cell alloimmunization
7/10/2016 By Dr Samuel --Gynecologist 1

Red Cell Alloimmunization (RCA)
• Currently- 30 different blood group systems and
328 red cell antigens are recognized
• Alloimmunization
– anti body production by an individual when
exposed for specific antigen which the individual
lacks .
• RCA may occur due to ;
– Fetomaternal hemorrhage during pregnancy
– Transfusion
• Such antibodies can be harmful;
– To the individual if transfused with incompatible
blood (i.e, a blood +ve for the antigen)
– To her fetus during pregnancy if the fetus carries the
antigens

RCA in pregnancy
• Fetus +ve and Mother –Ve for certain RBC antigen
• Trans-placental passage of fetal antigen to maternal
circulation Maternal alloimmunization (Antibody
synthesis by maternal immune system against Fetal
Ags) then;
• Trans-placental Passage of maternal IgGs to the fetal
circulation then;
• Fetal RBC hemolysis by the maternal Abs Fetal
Anemia, Erythroblastosis Fetalis, Hydrops Fetalis
• Most cases of severe fetal anemia requiring
antenatal transfusion are attributable to anti- D,
anti-Kell, or anti-c alloimmunization.

RCA
RCA in pregnancy is uncommon for the
following reasons:
1. low prevalence of incompatible red cell antigens;
2. Insufficient trans-placental passage of fetal
antigens or maternal antibodies;
3. Maternal-fetal ABO incompatibility, which leads
to rapid clearance of fetal erythrocytes before
they elicit an immune response;
4. variable antigenicity; and variable maternal
immune response to the antigen.
In population-based screening studies, the
prevalence of red cell alloimmunization in pregnancy
is approximately 1 percent (Howard, 1998; Koelewijn, 2008)

RCA
Fetal-Neonatal Complications
–Hemolytic Disease of fetus and newborn
(HDFN)
–Anemia
–Extra-medullary hematopoiesis-
• Erythroblastosis Fetalis
• Liver failure
• Hydrops fetalis
• Fetal death
–Hyperbilirubinemia, Kernicterus

Rh Alloimmunization
History
• 1609-Hemorrhagic disease of fetus & newborn (HDFN)
described by midwife
• 1932- hydrops fetalis, icterus gravis neonatrum &
erythroblastosis fetalis are different manifestations of
same disease- Diamond
• 1940/1941- discovery of rhesus factor in monkey-
Landsteiner & Weiner
• 1960-Anti-D immunoglobin extraction

Rh Alloimmunization
• The Rh ( rhesus) system includes 5 red cell
proteins or antigens: C, c, D, E, and e.
– No “d” antigenRh D-negative means the D antigen
is absent.
• The two responsible genes—RHD and RHCE—are
located on the short arm of chromosome 1
• Rh C, c, E, and e antigens have lower
immunogenicity than the Rh D antigen,
• More than 200 D antigen variants exist
(Daniels, 2013).
– a single exposure to as little as 0.1 mL of fetal
erythrocytes may be sufficient to sensitize Rh D-Ve
mother(Bowman,1988).

Rh-D Alloimmunization
• The prevalence of Rh D alloimmunization
complicating pregnancy ranges from 0.5 to 0.9 %
(Howard, 1998; Koelewijn, 2008; Martin, 2005).
• Risk of alloimmunization in Rh-ve woman with
Rh+ve fetus and with out anti-D immune globulin
prophylaxis is;
– 16%- if there is ABO-compatiblity
• 2% will become sensitized by the time of delivery,
• 7 % by 6 months postpartum, and
• 7 % will be “sensibilized”—producing detectable antibodies
only in a subsequent pregnancy (Bowman, 1985).
– 2%- If there is ABO incompatibility, without
prophylaxis (Bowman, 2006).
• With immunoprophylaxis the alloimmunization
risk is reduced to < 0.2%

Rh D Alloimmunization
• An estimated 25 to 30 % of fetuses from
Rh D-alloimmunized pregnancies will
have mild to moderate hemolytic
anemia, and without treatment, up to
25% will develop hydrops (Tannirandorn,
1990).

Rh Alloimmunization
The Grand mother Theory
• Rh-ve female fetus of Rh +ve mother can be
sensitized inutero.
• This sensitization may affect her Rh +ve fetus
when she become adult and get pregnant
 The fetus is jeopardized by antibodies provoked
by his/her grandmother erythrocytes

Minor RBC Antigens
• Some of the blood groups with Minor
RBC antigens that may cause
alloimmunization and fetal hemolysis
are;
–Kell
–Duffy
–Kidd
–Lewis

RFs for Red Cell Antigen Alloimmunization (RCA)
 RCA is the result of Fetomaternal Hemorrhage Associated with
• Pregnancy Loss
– Ectopic Pregnancy
– Spontaneous abortion
– Elective abortion
– Fetal Death (at any trimester)
• Procedures
– Chorionic Villous Sampling (CVS)
– Amniocentesis
– Fetal Blood Sampling
– CS
– Manual removal of the placenta
• Other
– Delivery
– Trauma
– Placental abrubtion
– Unexplained vaginal bleeding during pregnancy
– ECV

Dx of RCA
• Indirect Coombs Test
– detection of antibodies in the maternal serum
• With positive results,
– specific antibodies are identified,
– Their Ig subtype-IgG or IgM- is determined and the
titer is quantified.
– Only IgG antibodies are of concern because IgM
antibodies do not cross the placenta (1st pregnancy is
less affected).
• Direct Coombs Test
– detection of maternal Abs in the infant serum

Clinical management of Rh -ve mother
Evaluation:
• Rhesus blood type of mother
• Rhesus blood type of father
• History of prior blood transfusion
• Past pregnancies including abortion
• Previous administration of RhIG
• Predisposing factors like trauma
• Presence of vaginal bleeding
• Invasive obstetric procedures.

Management of Alloimmunized Pregnancy
• Fetal Risk Assessment:
– Paternal blood group & zygosity
• Rh-ve, father- no fetal risk
• Heterozygous Rh+ve father- 50% Rh+ve and 50% Rh –ve
fetuses
– Fetal blood group ( via amniocentesis for PCR)
• Determined If the father is Heterozygous Rh+ve
• Subsequent management is individualized and
may consist of
– maternal antibody titer surveillance,
– sonographic monitoring of the fetal MCA peak systolic
velocity,
– amnionic fluid bilirubin studies, or
– fetal blood sampling.

Management of Alloimmunized Pregnancy
A. For 1st affected pregnancy
• Serial maternal antibody titer follow up 4 weekly
until it reaches the critical level
– ‘Critical Titer’ is the level at which significant fetal anemia
could potentially develop.
– Different for each Ab and across laboratories.
– Generally b/n 1:8- 1:32
• Further Evaluation (MCA doppler or AF bilrubin) If
critical titer is reached.
NB
• If the woman has previous pregnancy complicated by
alloimmunization, titer follow up should be skipped
and evaluation for hemolysisi should be started.

Middle Cerebral Artery (MCA) Doppler Velocimetry
• MCA Doppler is done 1-2 weekly
• Fetal anemia causes
– Blood shunt to brain
– Increased CO
– Decreased blood viscosity
increased blood velocity in MCA
• Peak MCA velocity of ~1.5 multiple of the median
for the GA Anemia (moderate to severe)
• When peak systolic velocity of MCA is > 1.5
MOM fetal blood sampling (Hct) is necssary to
determine the need for transfusion

MCA Doppler studies

Amnionic Fluid Spectral Analysis
• Serial amniocentesis and bilirubin level
determination by spectrophotometer
change in optical density absorbance at
450 nm—∆OD450.
• AF bilirubin level;
– indirect indicator of severity of fetal Hemolysis
and anemia.
• Values are plotted on the Liley graph
(modified) that has several zones
• The original Liley graph has 3 zones and is
valid for GAS 27-42

27 wks 35wks 40wks
Zone III
Zone II
Zone I
o.o1
0.1
0.5
Modified Liley’s Curve

Zone I
– Fetus with Mild disease
Zone II
– indicates moderate fetal anemia with HGB
level of
– 11.0 to 13.9 g/dL for values in lower zone 2 and
– 8.0 to 10.9 g/dL for upper zone 2.
Zone 3
– indicates severe anemia, with hemoglobin
concentration < 8.0 g/dL.

• Lileys graph was modified by Qeenans and associates
(1993) to include GAs as early as 14 week.
• This graph contains a large indeterminate zone due to
the naturally high AF bilirubin level at midpregnancy.

Intrauterine Transfusion
• Preterm fetus with elevated MCA or hydrops is
evaluated with blood sampling.
• Transfusion is recommended if Hct <30%
• Target Hct~40-50%
• Intra venous (Umbilical Vein) or Intraperitoneal.
• Packed RBC (80% Hct ) that are;
– type O, Rh D negative,
– cytomegalovirus-negative,
– irradiated (to prevent fetal graft-versus-host reaction)
– leukocyte-poor.

Intrauterine Transfusion
Outcomes of transfusion
–Overall survival~90%
–Fetal death~3%
–Neonatal death~2%
–Emergent CD~6%

Hydrops Fetalis
• Fluid accumulation in 2 or more spaces
–Ascites
–Subcutaneous
–Pleural effusion
–Pericardial effusion

Hydrops Fetalis
Pathogenesis
• Hemolysis- anemia….....CHF
• Increased capillary permeability due to
hypoxic injury.
• Extramedullary hemopoiesis ( liver, spleen)
– Hypoprotenemia (liver failure)
– Portal hypertension

Prevention of Rh D sensitization
Anti D immunoglobulin
• Derived from human plasma donated by individuals
with high-titer anti-D antibodies.
• Half life: 16-24 days
• Standard dose 300mic gm / 1500IU IM-protect the
average-sized mother from a fetal hemorrhage of up
to 30 mL of fetal whole blood or 15 mL of fetal red cells
Timing
• At 28 weeks GA (if indirect coombs test –ve)
• Within 72 hrs postpartum (can be protective if given
until 28 days)
• Anti D Ig is also recommended when there are RFs
fetomaternal Hemorrhage ( mentioned previously)

ABO Blood Group incompatibility
• Incompatibility for the major blood group
antigens A and B is the most common cause
of hemolytic disease in newborn infants,
• but it does not cause appreciable hemolysis in
the fetus.
• ~20 % of newborns have ABO incompatibility,
• however, only 5 percent are clinically affected,
and
–the resulting anemia is usually mild.

ABO Blood Group incompatibility
• ABO incompatibility differs from Rh CDE
incompatibility in several respects;
1. First born are often affected by ABO incompatibility
is but not by Rh sensitization
• most group O women have developed anti-A and
anti-B isoagglutinins before pregnancy from
exposure to bacteria displaying similar antigens.
2. ABO alloimmunization can affect future
pregnancies, but unlike CDE disease, it rarely
becomes progressively more severe.
3. most anti-A and anti-B antibodies are IgM which
don't cross placenta.
4. Fetal red cells have fewer A and B antigenic sites
than adult cells and are thus less immunogenic.

ABO Blood Group Incompatibility
Mg’t
• There is no need to monitor for fetal hemolysis
or to deliver the fetus early.
• Careful neonatal observation is essential,
because Hyperbilirubinemia may require
treatment with phototherapy or occasionally
transfusion
ABO alloimmunization is generally a pediatric
disease rather than an obstetrical concern.

PREGNANCY HYPERTENSION
BY SAMUEL
BEZABIH
Meskerem
2004
SAMUEL BEZABIH,MD

Pregnancy Hypertension
• Hypertensive disorders (HDP) complicate 5 to 10
% of all pregnancies,
• One of the deadly triad that contribute for MMM
– ( Hemorrhage---HTN----Infection),
• WHO’s systematic review of MM worldwide and
in developed countries reported 16% of maternal
deaths are caused by Htnsive disorders. (Khan, 2006)
Greater than other leading MM
causesHmge~13%, Abortion~8%, Sepsis~2%
• Of HDPs ,preeclampsia syndrome is the most
dangerous
– i.e, either alone or superimposed on chronic
hypertension.
• PE is identified in 3.9 % of all pregnancies

HDP- Terminologies
• ACOG Task force (2013) describes four types
of hypertensive disease (retaining the basic
classification of NHBPEP-2013):
1. Gestational Hypertension
 Evidence for the PE syndrome does not develop and
hypertension resolves by 12 weeks postpartum
2. Preeclampsia and eclampsia syndrome
3. Chronic hypertension of any etiology
4. Preeclampsia superimposed on chronic
hypertension.

Dx of Pregnancy HTN
• HTN is diagnosed empirically when
appropriately taken BP exceeds 140
mmHg( S) and 90 (D)
–SBP > 140 or DBP > 90 mmHg ( kortkof V)
NB, use 2x msnt

Dx of Hypertensive Disorders Complicating Pregnancy
1.Gestational Hypertension-GH
 BP > 140/90 mmHg after 20 weeks in previously normotensive
women but proteinuria is not identified.
• Almost half of these women subsequently develop PE
syndrome, which includes signs such as proteinuria and
thrombocytopenia or symptoms such as headaches or
epigastric pain.
• 10 % of eclamptic seizures develop before overt proteinuria
can be detected.[ Chesley (1985)]
• GH is reclassified as
– Pre-eclampsia ( as the foregoing above)
– Transient hypertension; if evidence for PE does not develop, and the
BP returns to normal by 12 weeks postpartum or
– Chronic Hypertension if persisted beyond 12 weeks postpartum.

Dx. of Hypertensive Disorders Complicating Pregnancy
2. Preeclampsia
I. Hypertension + Proteinuria
 Proteinuria
I. >=300mg/24hr,
II. Urine Protein: Creatinine > 0.3 or
III. Dipstick persistent +1 (only if no other quantitative method)
II. HTN , no proteinuria but with any of the following;
• Thrombocytopenia (<100,000),
• Impaired liver function (transaminase elevation( >2xN))
• Renal Insufficiency-
– serum creatinine >1.1mg/dl / doubling of baseline serum Cr. In
the absence of known renal disease),
• cerebral / visual symptoms ;Headache, visual disturbances,
convulsions
• pulmonary edema

PE -Severe Vs Non Severe-Will 24th
Abnormality Nonsevere Severe
DBP <110 mm Hg >110 mm Hg
SBP <160 mm Hg >160 mm Hg
Proteinuria Nill to +ve Nill to +ve
Headache Absent Present
Visual disturbances Absent Present
Upper abdominal pain Absent Present
Oliguria Absent Present
Convulsion (eclampsia) Absent Present
Serum creatinine Normal Elevated
Thrombocytopenia Absent Present
S TAMinase elevation Minimal Marked
Fetal-growth restriction Absent Obvious
Pulmonary edema Absent Present

Severe Pre Eclampsia-any of the following findings
• SBP > =160 /DBP>=110;2x 4hrs apart while the patient is on
bed rest.
• Thrombocytopenia --< 100,000/microlitre
• Impaired liver function
– Elevated liver enzymes to 2x N or
– RUQ/ epigastric pain- unresponsive to rx. and no alternative dx.
• Progressive renal insufficiency
– serum creatinine > 1.1mg/dl or doubling of serum Cr. In the
absence of known renal disease,
• Pulmonary edema
• New onset cerebral/ visual disturbance
NB.
IUGR* and 24hr protein > 5g** are no more signs of severity.
*same mgt as IUGR with no PE
**based on evidence from studies indicating minimal relation b/n amount of
proteinuria and disease severity

Preeclampsia-Risk Factors
• Young and nulliparous women are particularly
vulnerable to developing PE , whereas older
women are at greater risk for CHWSIPE
• the incidence of PE is markedly influenced by
– Race and Ethnicity  genetic predisposition
– environmental, socioeconomic, and even
seasonal factors
 variable incidence among nulli and multis
• NP populations :3 to 10 %.
• Multiparas - less than that for nulliparas~1.4
to 4% (Roberts, 2011).

PE Risk Factors……
• Age > 35 mainly superimposed PE
• Obesity -risk parallels BMI
– < 4.3% in BMI <20kg/m2
– 13.3% in BMI>35
• Twin gestation (Unrelated Zygosity) Vs singleton
– PE 13% vs 5%
– GHTN 13% vs 6%
• Hyperhomocysteinemia, and
• Metabolic Syndrome
• PE in 1st pregnancy ( higher risk subsequently)

PE-Protective Factors
• Smoking has consistently been associated with a
reduced risk of hypertension during pregnancy
(Bainbridge 2005; Zhang , 1999).
– Kraus and associates (2013) posit that this is because
smoking upregulates placental adrenomedullin
expression, which regulates volume homeostasis
• Placenta previa has also been reported to reduce
the risk of hypertensive disorders in pregnancy
(Ananth and colleagues, 1997).
• If 1st pregnancy is Normotensive, PE incidence
becomes much lower than that for 1st pregnancy
PE incidence in secondigravidas (Getahun and colleagues (2007)
– 1.8 % in white women
– 3 % in African-American women.

PE- Recurrence
• Nulliparous who developed PE at < 30
week ~40% risk of PE in subsequent preg
(Sibai 1986, 1981)
• Those Delivered at 37 week for PE 23% risk
of PE in subsequent pregnancies (Bramham, 2011)
• These investigators also found an increased risk
during subsequent pregnancies for preterm delivery
and fetal-growth restriction even if these women
remained normotensive.

Maternal and Fetal Complications in Severe
Preeclampsia
Maternal
 Abruptio p. (1%-4%)
 DIC /HELLP (10%-20%)
 Pul.Ed/aspiration (2%-5%)
 ARF (1%-5%)
 Eclampsia (<1%)
 Liver failure or
hemorrhage (<1%)
 Stroke (rare)
 Death (rare)
 Long-term CV morbidity
Fetal
 PT delivery (15%-67%)
 FGR/IUGR (10%-25%)
 Hypoxia “neurologic
injury (<1%)
 Perinatal death (1%-2%)
 Long-term CV
comorbidity associated
with LBW (fetal origin of
adult disease)

Prevention Of PE
• Dietary manipulation
– low sodium diet, fish oil, Calcium
supplementation
–Antioxidants; Vit.C and Vit.E
• All the above have no evidence of effectiveness
except Ca for those with low dietary intake.
• Low dose aspirin ;
– better result ( 10% decrease in 30000 women's
trial)

Prediction of PE
Read Williams Obstetrics 24th Ed Page 746

3.Chronic Hypertension:
• BP 140/90 mm Hg
–before pregnancy or
–diagnosed before 20 weeks' gestation not
attributable to GTD or
–first diagnosed after 20 weeks' gestation
and persistent after 12 weeks postpartum

4.Superimposed Preeclampsia On Chronic HTN:
– New-onset proteinuria 300 mg/24 hours in
hypertensive women but no proteinuria before 20
weeks' gestation
– A sudden increase in proteinuria Or Sudden
exacerbation of BP or platelet count < 100,000/L in
women with hypertension and proteinuria before 20
weeks' gestation
– Same severity criteria as PE
Compared With ‘Pure PE’:
 Often Develops At Earlier GA,
More Severe And Accompanied By IUGR
• Preeclampsia often affects young and nulliparous
women, whereas older women are at greater risk for
chronic hypertension with superimposed preeclampsia.

WILL 24th
5.Eclampsia:
– Seizures that cannot be attributed to other
causes in a woman with preeclampsia.
• The seizures are generalized and may appear
before, during, or after labor.
• approximately 10 % convulsions develope
beyond 48hrs Postpartum (Sibai, 2005).
• In some reports, up to a fourth of eclamptic
seizures develop beyond 48 hours postpartum
(Chames, 2002).

Eclampsia……….
Incidence :-
• Because it is somewhat preventable by adequate
prenatal care, the incidence of eclampsia has
decreased over the years.
• In developed countries, its incidence probably
averages 1 in 2000 deliveries
• in developed countries, the maternal mortality
rate is about 1 percent in women with eclampsia.

Eclampsia------
Convulsions:-
• violent muscular C-R that may last for about 01
min
– Tongue biting, trauma…..
• Postictal; When muscular actions gradually
diminish the woman remain motionless/ at times
coma of variable duration.
• With Infrequent seizures
– inter convulsion recovery of consciousness or
– in Severe cases ; persistent coma in b/n convulsions
culminating in death ( rarely after single episode of
convulsion)
– As a rule Death occurs after several convulsions

Eclampsia------
• 5% ~altered state of consciousness ( including
persistent comma)
• after seizure ; extensive cerebral edema and
transtentorial herniation may cause death.
• There may be status epilepticus;
– require deep sedation and even GA to obviate
anoxic encephalopathy.

Eclampsia…….
Witnessed after convulsion are:
• Tachypnea ( >50’)
2 0 to hypercarbia, lactic acidemia, transient hypoxemia
• Cyanosis-in severe cases
• High grade fever ~ IC hemorrhage
• Oligo/anuria , pronounced proteinuria.
• Hemoglobinuria (hemoglobinemia-rare)
• Pronouncement of peripheral and facial edema (may
also be absent)
• substantively altered consciousness, including
persistent coma (App. in 5 % ),
– This is due to extensive cerebral edema, and transtentorial
herniation may cause death
• Death – mostly after frequent attacks , rarely comma
from single convulsion may lead to death

Eclampsia contd.
• Rare Events:-
– Status Epilepticus (requires deep sedation? GA)
– comma and death after single attack
• Occasionally, sudden death synchronously with an
Eclamptic convulsion, or shortly thereafter (usually 20 to
massive cerebral hemorrhage)
• Blindness / visual impairement (In~10%)
– Retinal detachment ( also in severe PE WO convulsion)
– Occipital lobe ischemia and edema ( almost always in E)
– Good prognosis- complete reversal with in 01-2 week post p.
• Hemiplegia may result from sub-lethal hemorrhage
• Fetal bradycardia after seizures 
– maternal hypoxemia and Lactic Acidemia
– improves in 3-5 min
– If bradycardia persists for > 10min---suspect abruption or
imminent delivery

ECLAMPSIA WILLIAMS 24th
Post Eclampsia Psychosis:-
• Rarely, eclampsia is followed by psychosis, and
the woman becomes violent.
• usually lasts for several days to 2 weeks,
• good prognosis for return to normal function , if
no preexisting mental illness.
• It is presumed to be similar to postpartum
psychosis
• Antipsychotic medications in carefully titrated
doses have proved effective in the few cases of
posteclampsia psychosis treated at Parkland
Hospital.

Eclampsia ……
• Major maternal complications of eclampsia
include:-
– Neurological deficits
– Aspiration pneumonia
– Pulmonary edema
– Cardiopulmonary arrest
– Acute renal failure
– Death

Eclampsia…..
Complications:-
• Pulmonary edema immediately/several hrs after
convulsions 20 to:-
• aspiration pneumonitis (Common)- inhalation of gastric
content
• Ventricular failure ( ↑ ed after load from severe HTN and
aggressive IV fluid therapy) – esp. in morbidly obese ,
previous chronic hypertension
• Cerebral Hemorrhage
– more likely in older women with underlying CHTN,
– Rarely, may be due to a ruptured cerebral berry aneurysm
or AV malformation.
– Massive CH may cause sudden death ( during or shortly
after seizures)
– Hemiplegia may result from sublethal hemorrhage

Eclampsia- DDx
• Epilepsy, Encephalitis, Cerebral Tumor
neurocysticercosis, AF embolism, postdural
puncture cephalgia, and ruptured cerebral
aneurysm during late pregnancy and the
puerperium may simulate eclampsia.
Until other such causes are excluded, however,
all pregnant women with convulsions should be
considered to have eclampsia.
• These alternative Dx may be more likely in
Seizures Occurring;
– after 48- 72hrs postpartum
– while on MgSO4 rx (2013 ACOG task force)

ATYPICAL ECLAMPSIA
Atypical Eclampsia ;Occurrence of
Eclampsia:-
– before 20 weeks of GA
– after 48 hours postpartum or
– in absence of typical signs of PE i.e
hypertension and/or proteinuria; Sibai (
known HTN d/o investigator)
SAMUEL BEZABIH YEKATIT 2005

HELLP Syndrome
• The HELLP syndrome is a variant of PE characterized by
hemolysis, elevated liver enzymes, and low platelets.
• It complicates
– 10% of cases of severe PE and
– up to 50% of cases of eclampsia.
• RUQ pain, nausea, vomiting, and malaise are common.
• Transaminase levels are elevated, thrombocytopenia is
present, and DIC may be evident.
• Hypertension and proteinuria are variable
– Approximately 10% of women with HELLP
syndrome are normotensive, which is classified as
atypical HELLP syndrome.

Criteria for the Diagnosis of HELLP Syndrome
• Hemolysis
– Abnormal peripheral smear (schistocytes, burr cells,
echinocytes)
/schizocytosis, spherocytosis, and reticulocytosis in
peripheral blood/ (Cunningham, 1985; Pritchard, 1954, 1976).
– LDH >600 U/L (of the 5 isoforms, only LDH1 and 2 result
from hemolysis)
– Bilirubin >1.2 mg/dL
– Decreased Hepatoglobulin (< 2.5mg/dl)
• Elevated liver enzyme
– Serum AST >70 U/L
– LDH >600 U/L
• Low platelets
– Platelet count <100,000/mm3

HELLP Classification (GABEE)
• Based on a retrospective review of 302 cases of
HELLP syndrome, Martin et al.devised the
following classification based on the nadir of the
platelet count.
– Class I:-a platelet nadir below 50,000/mm3,
– class 2:-a platelet nadir between 50,000 and
100,000/mm3,
– class 3:-a platelet nadir between 100,000 &
150,000/mm3.
• These classes have been used to predict the
rapidity of recovery postpartum, maternal-
perinatal outcome, and the need for
plasmapheresis.

HELLP classifications…
1. Complete HELLP syndrome
– those with hemolysis, elevated liver enzymes, and
low platelets
2. Partial HELLP syndrome
– either 1 or 2 but not 3 of these laboratory findings.
3. Severe PE without HELLP syndrome lab findings.
– Perinatal outcomes were similar in each group and
outcomes were not improved with
procrastination.
– Despite this, the investigators recommended
expectant management for women with partial
HELLP syndrome, as well as those with severe
preeclampsia alone.

Recurrence
• women with HELLP syndrome have a substantive
risk for recurrence in subsequent pregnancies.
• In two studies the risk ranged from 5 to 26 %,
but the true recurrence risk likely lies between
these two extremes (Habli, 2009; Sibai, 1995).
• Even if HELLP syndrome does not recur with
subsequent pregnancies, there is a high
incidence of;
– preterm delivery,
– fetal-growth restriction,
– placental abruption, and
– cesarean delivery (Habli, 2009; Hnat, 2002).

Management Of HDP
• Pregnancy complicated by gestational HTN
disorder is managed according to
– Severity,
– Gestational age, and
– Presence of preeclampsia
Goals of Management:-
1. Pregnancy termination with the least possible
trauma to mother and fetus
2. Birth of an infant who subsequently thrives
3. Complete restoration of health to the mother

CHTN Mgt
• Prenatal Visit Q2-4wk till 34-36 wk then weekly
• Detection of fetal growth ,Bp, UA, Wt. ,SS of PE
at each visit
• Ante partum fetal assmt. starting from 32-34 wks
• Rest
• salt restriction
• AntiHTN medications for Severe HTN (> 160/ 110)
to prevent end organ damage i.e. nephropathy,
retinopathy, CHF, stroke

PE Management
Termination of pregnancy is the
only cure for preeclampsia.

Mild PE/ Gestational Hypertension Management
For women with mild stable hypertension
whether or not preeclampsia has been
confirmed; continued surveillance is carried
out;
– in the HOSPITAL or
– at HOME for reliable patients

Mild PE Mg’t
• Outpatient – continued observation with
– Maternal kick count and symptoms (head ache, visual blurring,
RUQ pain) weight daily.
– BP 2x/ week
– Platelet ,liver enzymes and serum creatinine,- weekly
– Fetal surveillance
– US for evaluation of growth and AFV 3x weekly
– Reduced physical activity
• Not recommended are;
– Strict bed rest
– Sodium and fluid restriction
– antihypertensive
– MgSO4 administration
• Delivery- at 37+ 0 weeks

Severe PE Mgmt.
• Termination of pregnancy is the only cure for
preeclampsia.
• Headache, visual disturbances, or epigastric pain
is indicative that convulsions may be imminent,
• Severe preeclampsia demands anticonvulsant
and antihypertensive therapy followed by
delivery.
• The prime objectives are to:-
– forestall convulsions,
– prevent intracranial hemorrhage and serious
damage to other vital organs, and
– deliver a healthy infant.

Severe PE/E Management
Tenets of mgmt.
– Control /prevent convulsions with MgSO4
– Intermittent antihypertensive for dangerously
high BP.
– Limit fluid therapy
– Avoid diuretics unless there is obvious pulmonary
edema
– Avoid hyperosmotic agents
– Deliver the fetus to achieve ‘cure’

Severe PE Mgmt.
• Delivery if:-
 GA > 34wk
 Lung matures
 Deteriorating maternal/fetal status
• Antihypertensive to keep BP S<160 D<105**
• MgSO4 to prevent seizure
**The aim of antihypertensive therapy is to keep
– systolic pressure between 140 and 155 mm Hg
– and diastolic pressure between 90 and 105 mm
Hg. (i.e,mild range, not normotensive bse BV In PE is low.)

Severe PE Management
• GA < 34 week with stable Fetomaternal
condition, expectant management can be
considered (until 34 wk) in facilities that
have adequate maternal and neonatal
ICU.

Indications for Delivery in Women < 34 Weeks’
Gestation Managed Expectantly
a Initial dose only, do not delay delivery.
From the Society for Maternal-Fetal Medicine, 2011, and the Task Force of ACOG, 2013b.
a

Eclampsia Management
Tenets of mgt
1. Control of convulsions using an IV loading dose of
magnesium sulfate that is followed by a maintenance
dose, usually intravenous, of magnesium sulfate
2. Intermittent administration of an antihypertensive
medication to lower blood pressure whenever it is
considered dangerously high.
3. Avoidance of diuretics unless there is obvious
pulmonary edema, limitation of IV fluids
administration unless fluid loss is excessive, and
avoidance of hyperosmotic agents
4. Delivery of the fetus to achieve a remission of
preeclampsia.

Antihypertensive rx in Severe PE and Eclampsia
• The three most commonly employed
antihypertensives for acute BP control are
LABETALOL, HYDRALAZINE and NIFEDIPINE
• Methyldopa- long acting
– Diuretics – Not recommended before delivery except
in Pulmonary edema
• IV volume depletion of already contracted volume
Utero-Placental insufficiency
– Diuretics are used postpartally to augment
diuresis and hasten BP normalization
• ACEIs and ARBs- contraindicated in pregnancy

Management of ECLAMPSIA -MOH
Treatment of eclampsia is symptomatic & consists of
six aspects:
1. General measures ( ensure patency of airway, prevent injury and
aspiration of gastric contents)
2. Control of convulsions (to stop ongoing convulsion & prevent
repeated convulsion)
3. Correction of hypoxia & acidosis
– by clearing airway & giving O2 by mask at 6L/min
4. Blood pressure control & stabilization of the condition of the
mother & fetus
5. Fluid balance & diuresis
6. Delivery & intra partum/post partum care
– if vaginal birth is not possible within a reasonable period
of time, cesarean delivery is performed in most cases.

PE/E Fluid Therapy
• Severe PE Excessive EC fluid with maldistribution
 constricted IV and excessive EV fluid volume
• Aggressive IV fluid M'gt worsening of the
maldistribution risk of pulmonary edema and
Cerebral edema
• Conservative IV fluid management needed
• RL 60ml/hr to maximum of 125ml/hr unless there
is:-
–unusual fluid loss from vomiting, diarrhea, or
diaphoresis, or
–more likely, there is excessive blood loss with
delivery.

Intrapartum mgmt. of PE/E
• In the absence of CI to labor, vaginal delivery
is the preferred approach.
• Cervical ripening agents and oxytocin are
used as needed
• MgSO4 is administered for seizure prophylaxis
as loading and maintenance doses.
• To avoid pulmonary edema, total IV fluids
should not exceed 100 mL/h.
• Pain control is achieved with regional
anesthesia or with IM or IV narcotic
analgesics.

Intrapartum mgmt. of PE/E
• Invasive hemodynamic monitoring is reserved
for:-
– Refractory pulmonary edema,
– ARD syndrome
– Oliguria unresponsive to fluid challenge.
• If CS is required, platelets should be available
for possible transfusion for patients with
platelet counts < 50,000/mm.
• Use of other blood products is guided by
clinical and laboratory findings.

Postpartum management of PE/E
• Magnesium sulfate should be continued for
24 hours
• Indications for acute antihypertensive therapy
are the same as for the antepartum or
intrapartum period.
• Women who continue to have hypertension
but have a persistent diastolic blood pressure
of less than 100 mmHg may be discharged on
oral therapy.
• Pregnancy-induced hypertension usually
disappears completely by 2 weeks postpartum

Postpartum Mgt of PE/E
• High risk of Pulm. edema-IP fluid
administration ( preepidural, with Mg
and oxytocin) + mobilization of
extracellular fluid)
–Close monitoring of BP, symptoms , chest
auscultation and SO2.

Postpartum M’gt
• Hypertension may develop PP time:-
– Educate all PP women about severity symptoms
on discharge
– severe range + symptoms hospitalize, Mgso4 for
24 hrs

MgSO4 Protocols
Continuous IV infusion VS intermittent IM—
equal efficay
1. Cont. IV infusion
– Loading dose,4-6gm/100ml Fluid IV over 10-
15min
– Maintainance Dose;2g/Hr in 100ml maintainance
IV fluid may not be adequate in obese women, 40%
obese women in PK Hosp required 3g/Hr maint. for
effective plasma level.
– Followup
• Assess DTR perioducally
• Measure serum Mg if creatinine > 1
• DC 24 hrs after delivery
2. Intermittent IM (national protocol)

MgSO4 mgmt.(National protocol)
Indications
• Severe PE, Eclampsia
• Intrapartum & postpartum (irrespective of severity)
1. loading dose
– 4gm MgSO4 as 20% solution IV over 5min( 8ml 50%
MgSO4+12ml DW/NS=20% MgSO4)
– 10gm 50% MgSO4 IM ( 5gm on each buttock)
2. Maintenance dose
– 5gm 50% MgSO4 IM Q 4hr for 24 hrs from last seizure or after
delivery(which ever is later)
– ↓dose by half with signs of renal impairement- oliguria,↑
creat/BUN
3. 2gm 20% MgSO4 IV if seizure occurs: may be repeated

MgSO4 Protocol
MONITORING TOXICITY( hypermagnesiumia)
–Check resp. rate Q 1hr ( it should be >12/min)
–Check patellar DTR Q 1hr ( should be present)
–UOP Q 4hr( should be >100ml/4hr)

MgSO4
Management of toxicity
• If DTR is depressed :
– Discontinue/DC/ MgSo4 and follow pt. closely
• If RR< 12 :
– give Ca gluconate 1gm as 10% solution (10ml) IV over
2 min and monitor patient for bradycardia (HR<60)
– If severe RR depression is present transfer Pt. to ICU
for tracheal intubation and mechanical Ventilation.
• ↓dose by half with signs of renal impairment-
oliguria, ↑creatinine/BUN
– The loading dose (4g) shouldnt be reduced in derranged RFT
since after distribution it achieves the therapeutic level  only maint.
Dose needs alteration

Serum Magnesium Levels
• Therapeutic range
– 4.8 to 8.4 mg/dl, ( 4 to 7 mEq/L)
• Loss of patellar reflexes,Weakened breathing;
– at ~ > 12 mg/dL (10 mEq/L) ~curariform effect
• Respiratory paralysis may occur;
– at > 15 mg/dL/12 mEq/L
• Cardiac arrest is possible with;
– levels > 25 mg/dL**

Mg Serum Levels
• In the presence of patellar reflexes,
monitoring serum magnesium levels usually
are unnecessary
• Currently most do not recommend routine
magnesium level measurements (ACOG,
2013b; RCOG, 2006). .

MgSO4- when, How and for whom?
• Effective anticonvulsant
– (reduce convulsion risk by 50%- ie E rate from 05% to
0.25% ACOG2013),
• No maternal & fetal depression (unlike other regimens)
• Labor and delivery- high risk of convulsion
MgSO4 is administered at Late and 24 hrs PP
Needed in mild PE????
60 pts with severe PE and 100 pts with mild PE
need to be treated to prevent 1 seizure (MAGPIE
trial)
MS doesnt affect disease progression unrelated
to convulsion
~10-15% laboring women with mild PE develop SS
of severity or abruption irrespective of Mg treatment

MgSO4- Will 24th
• MgSo4 should not be given to treat
hypertension
• Based on several studies and extensive clinical
observations, magnesium most likely exerts a
specific anticonvulsant action on the cerebral
cortex.
• Typically, the mother stops convulsing after
the initial 4-g loading dose.
• By an hour or two, she regains consciousness
sufficiently to be oriented to place and time

MgSO4-Will 24th
• When magnesium sulfate is given to arrest
eclamptic seizures, 10 to 15 % of women will
have a subsequent convulsion.
• If so, an additional 2gm dose of MgSO4 in a 20%
solution IV is slowly administered.
• In a small woman, this additional 2gm dose may
be used once, but it can be given twice if needed
in a larger woman.
• Maintenance MgSO4 therapy is continued for 24
hours after delivery.
• For Eclampsia that develops postpartum, MgSO4 is
administered for 24 hours after the onset of convulsions.

Abbrevated PP Mg Regimen- Will 24th
Postpartal Maintainance dose for 12 hrs
• 200 women with Mild PE randomized for 12 and
24 hrs
• Of the 101s randomized for 12 hr treatment
– 7 had worsening PE, and treatment was extended to
24 hours.
– None ( and none of the other cohort of 95 reciving
the 24-hour magnesium infusion) developed
eclampsia Ehrenberg and Mercer (2006)
• This abbreviated regimen needs further study
before being routinely administered for severe
preeclampsia or eclampsia

Supplementary Anticonvulsants
• In only 5 of 245 women with eclampsia at
Parkland Hospital was it necessary to use
supplementary anticonvulsant medication to
control convulsions (Pritchard, 1984).
• For these, IV barbiturate is given slowly.
• Midazolam or lorazepam may be given in a small
single dose, but prolonged use is avoided because
it is associated with a higher mortality rate (Royal
College of Obstetricians and Gynaecologists, 2006).

MgSO4-Mechanism of action will 23rd
• Magnesium is anticonvulsant and
neuroprotective in a number of animal
models.
• Some proposed mechanisms of action include:
– reduced presynaptic release of the NT glutamate,
– blockade of glutamatergic N-methyl-D-aspartate
(NMDA) receptors,
– potentiation of adenosine action,
– improved mitochondrial calcium buffering, and
– blockage of calcium entry via voltage-gated
channels (Arango and Mejia-Mantilla, 2006).

Serum Magnesium Levels and Associated
Clinical Findings (Danforth 10th)
Clinical Finding Serum Level(mg/dl)
• Loss of patellar reflex 8-12
• Feeling of warmth, flushing 9-12
• Double vision â€”
• Somnolence 10-12
• Slurred speech 10-12
• Muscular paralysis 15-17
• Respiratory difficulty 15-17
• Cardiac arrest 30-35

WILL 23rd
• Parenterally administered magnesium is cleared
almost totally by renal excretion, and magnesium
intoxication is unusual when the glomerular filtration
rate is maintained or only slightly decreased.
• Adequate UOP usually correlates with preserved GFR.
• However Magnesium excretion is not urine flow
dependent, and urinary volume per unit time does not
predict renal function.
• Thus, serum creatinine levels must be measured to
detect signs of declining GFR .
• Whenever plasma creatinine levels are > 1.0 mg/mL,
serum magnesium levels are used to adjust the
infusion rate.

WILL 24th
• Because magnesium is cleared almost exclusively by
renal excretion, the dosages described will become
excessive if glomerular filtration is substantially
decreased.
• The initial 4-g loading dose of magnesium sulfate can
be safely administered regardless of renal function.
• after distribution, a loading dose achieves the desired
therapeutic level, and the infusion maintains the
steady-state level.
• Thus, only the maintenance infusion rate should be
altered with diminished glomerular filtration rate
• With severe renal dysfunction, only the loading dose of
magnesium sulfate is required to produce a steady
state therapeutic level.

MgSO4-Mechanism of action
(Uptodate
 MS mechanism of action
as an anticonvulsant in
PE/eclampsia is not
clearly understood.
• Some possibilities include:
1. vasodilatation of the
cerebral vasculature,
2. inhibition of platelet
aggregation,
3. protection of endothelial
cells from FR damage.
4. prevention of Ca ++
entry into ischemic
cells,
5. ↓ing the release of
acetylcholine at motor
end plates within the
NMJ
6. and as a competitive
antagonist to the
glutamate N-methyl-D-
aspartate receptor
(which is epileptogenic)

MgSO4-------CV Effect
• After 4g IV loading over 15min
– Slight decrease in MAP and systemic vascular
resistance
– Increased CO
– No evidence of cardiac depression
• Coincident with transient flushing and nausea
• CV effects persist Only for ~15min despite
continued Mg infusion

Uterine EFFect
• MgSO4 can depress myometrial contractility at
serum levels of at least 8 to 10 mEq/L
Higher than the therapeutic levels in E/PE
• No effect on uterine activity while used in E/PE
except transient decrease in activity during and
immediately after the initial IV loading dose.
• MgSO4- not effective tocolytic agent

Fetal and Neonatal Effects
• MgSO4- crosses placenta and reaches equilibrium in fetal serum + AF.
• Overall Maternal Mg appears safe for perinates
Eg MFMU Network study of >1500 exposed preterm neonates found no
association between the need for neonatal resuscitation and cord blood
magnesium levels (Johnson, 2012).
• Clinically insignificant effects on FHR tracings– without adverse
outcomes
– B-B variablity decrease
– Prolonged decelerations
– Lower Baseline FHR(in N range)
• Few neonatal adverse out comes E.g, use. In a Parkland Hospital study
of 6654 mostly term exposed newborns,
– Hypotonia (6%),
– low APGAR,
– higher intubation rate,
– higher special nursery unit admission
 The study also shows Neonatal depression only with severe
hypermagnesiemia at delivery.

Fetal and Neonatal Effects…..
• long-term use of magnesium, given for several
days for tocolysis, has been associated with
neonatal osteopenia (ACOG, 2013c).
• Observational studies have suggested a
protective effect of magnesium against the
development of cerebral palsy in very LBW
infants. (Nelson, 1995; Schendel, 1996).
• At least five randomized trials have also assessed
neuroprotective effects in preterm newborns

Danforth
• Patients receiving MgSO4 are at
increased risk for postpartum
hemorrhage due to uterine atony.

Persistent Severe Postpartum Hypertension Will 24th
• Persistent or refractory hypertension is likely due to
mobilization of pathological interstitial fluid and
redistribution into the intravenous compartment,
underlying chronic hypertension, or usually both
(Sibai, 2012; Tan, 2002).
• In women with CHTN and LVH, severe postpartum
hypertension can cause Pulmonary Edema
• Mgt
– Increasing/changing antihypertensive rx delivery
obviates the UP compromise.
– Frusemide- hastens mobilization of interstitial fluid to IV
compartment and diuresis ( comparing ante and post
partum weight may help estimate extent of interstitial
fluid retention)

PP-Thrombocytopenia
• After delivery, the platelet count may continue to
decline for the first day or so.
• It then usually increases progressively to reach a
normal level within 3 to 5 days.
• in some instances with HELLP syndrome, the platelet
count continues to fall after delivery.
• If these do not reach a nadir until 48 to 72 hours, then
preeclampsia syndrome may be incorrectly attributed
to one of the thrombotic microangiopathies (George, 2013).

Reversible Cerebral Vasoconstriction Syndrome
Will 24th
• This is another cause of persistent hypertension,
“thunderclap” headaches, seizures, and CNS findings.
• It is a form of postpartum angiopathy.
• characterized by diffuse segmental constriction of
cerebral arteries and may be associated with ischemic
and hemorrhagic strokes.
• several inciting causes that include pregnancy, and
particularly preeclampsia (Ducros, 2012).
• It is more common in women, and in some cases,
vasoconstriction may be so severe as to cause cerebral
ischemia and infarction.
• The appropriate management is not known at this time
(Edlow, 2013).

ETHIOPATHOGENESIS OF HDP Will 24th
• Women who are likely to develop HDP are those who:-
– Are exposed to chorionic villi for the first time
– Are exposed to a superabundance of chorionic villi,
(e.g twins, hydatidiform mole )
– Have preexisting conditions of endothelial cells activation
or inflammation such as DM, Renal or CV disease
– Are genetically predisposed to HTN developing during
pregnancy.
chorionic villi (of intra or extra uterine pregnancy )are the
essential agents for dv’t of HDP (but fetus is not a
prerequisite)
Worley and associates (2008) reported an incidence of 30% in
extrauterine pregnancies exceeding 18 weeks' gestation.

Ethiopathogenesis ……..Will 24th
• The cascade of events leading to PE
(irrespective of the etiology) is characterized
by a host of abnormalities that result in
vascular endothelial damage with
subsequent
–Vasospasm
–plasma leak (transudation) and
–ischemic and thrombotic sequelae,

PATHOGENESIS….
• The PE syndrome is widely variable in its clinical
phenotypic expression.
• At least 2 major subtypes differentiated by whether or
not EV Trophoblastic remodeling of SAs is defective.
• This concept has given rise to “two-stage disorder” theory
of PE etiopathogenesis.
• Ness and Roberts (1996) consider that the two stage disorder
includes “maternal and placental preeclampsia”
• Such compartmentalization (into S1 and S2?)is artificial, and it
seems logical to us that PE syndrome presents clinically as
a spectrum of worsening disease
• Moreover, evidence is accruing that many “isoforms”
exist.
– Examples include differences in maternal and fetal
characteristics, placental findings, and hemodynamic findings
(Phillips, 2010; Valensise, 2008; van der Merwe, 2010).

PE- ‘two stage disorder’ theory
Stage 1 (Early)
• Faulty trophoblastic endovascular remodeling of uterine
spiral arteries (poor placentation) leads to; placental
hypoxia+??ischemia
Stage 2 (late)
• Placental Oxidative Stress Resulting In:-
I. IUGR
II. Systemic release of placental factors SIRS + Endothelial
activation PE syndrome
– stage 2 is susceptible to modification by preexisting
maternal conditions that are manifest by endothelial cell
activation or inflammation.
– Eg cardiovascular or renal disease, diabetes, obesity,
immunological disorders, or hereditary influences.
Artificial compartmentalization as PE is a clinical spectrum of
worsening diseases.

Pathogenesis Contd.
• Incomplete/faulty invasion of the SAs with
extravillous trophoblasts (persistence of)
low caliber high resistance SAs  diminished
placental perfusion and upstream increased
uterine artery resistance.
– Increased uterine artery velocimetry determined
by Doppler ultrasound—in the first or middle
trimester—should provide indirect evidence of this
process and thus serve as a predictive test for
preeclampsia
• Increased flow resistance results in an
abnormal waveform represented by an
increased Diastolic Notch.

Etiology
• Instead of being simply "one disease," PE appears to be a
culmination of factors that likely involve a number of maternal,
placental, and fetal factors
• Several mechanisms are proposed to explain the cause of PE
and currently considered important include:
1. Placental implantation; with abnormal trophoblastic invasion of
uterine vessels
2. Immunological maladaptive; tolerance between maternal,
paternal (placental), and fetal tissues
3. Maternal maladaptation; to CV or inflammatory changes of
normal pregnancy
4. Genetic factors; including inherited predisposing genes as well as
epigenetic influences.

Normal Trophoblastic Invasion of Spiral Arterioles
• In their summary of uteroplacental vasculature,
Ramsey and Donner (1980) described UP vessel
development as proceeding in two waves or stages.
• The first wave
– occurs before 12 weeks’ post-fertilization
– consists of invasion and modification of SAs up to the
border between the decidua and myometrium.
• The second wave
– between 12 and 16 weeks and
– involves some invasion of the intramyometrial
segments of SAs.
• Remodeling converts narrow-lumen, muscular SAs
into dilated, low-resistance Uteroplacental vessels.

A.Abnormal Trophoblastic Invasion (Defective Implantation)
• Partial invasion of decidual spiral arterioles by extravillous
endovascular trophoblasts.
• Deeper myometrial arterioles are not invaded at all.
 intact endothelial and intimal layer  indestensible wall with
narrow lumen (half the mean D of vessels in N placenta)
resistant to blood flow impaired placental blood flow.
• In general, the magnitude of defective trophoblastic
invasion is thought to correlate with severity of the
hypertensive disorder (Madazli, 2000).
– Decreased soluble antiangiogenic GFs may be involved in
faulty endovascular remodeling. McMahon and colleagues (2014)
• Diminished perfusion and a hypoxic env’t eventually lead to
release of placental debris or microparticles that incite a
systemic inflammatory responses.

Abnormal Trophoblastic Invasion (Defective Implantation
• Defective placentation is posited to further
cause the susceptible (pregnant) woman to
develop Gestational Hypertension, the PE
syndrome, preterm delivery, a growth-
restricted fetus, and/or Placental Abruption
(Brosens, 2011; Kovo, 2010;McElrath, 2008; Nelson, 2014).

Defective Implantation…..
• Electron Microscopy of implantation site arteries:-
– SA narrowing, endothelial damage, transudation of
plasma constituents into vessel walls, proliferation of
myointimal cells, and medial necrosis.
– Lipid accumulated first in myointimal cells and then
within macrophages (Atherosis). De Wolf and
coworkers (1980)
• It is hypothesized that acute atherosis identifies a
group of women at increased risk for later
atherosclerosis and cardiovascular disease. Staff
and coworkers (2013)

B. Immunologic Factors/Immune Maladaptation
• Maternal Tolerance Dysregulation
– Impaired placental site blocking Abs formation;1st
pregnancy carries higher risk.
– ↑ risk with increased paternal antigenic load Eg.GTD 2N
Paternal Chrs( Double Dose) early PE,
– Trisomy 13 ;30-40% increased risk--↑ antiangiogenic
factors  one of the genes for these factors is on
chromosome 13 (which is in 3sets)
– Low immunosuppressive HLA from extravillous
trophoblasts high levels of placental oxidative
products  defective placental vascularization
• Immunization previous exposure for antigens of
the same partner  less risk on subsequent
pregnancies
• Multis impregnated by new partner ↑ risk

Immunologic Factors
• Loss / Dysregulation of maternal, immune
tolerance to Paternally derived fetal and
placental antigens:-
–Histology at maternal-placental interface-
suggestive of Graft Rejection
• Possible associated factors ;
–immunization from previous pregnancy,
–Inherited HLA and NKCs,
–shared susceptiblity genes with DM and
HTN (Fukui, 2012; Ward, 2014)

Immunologic Factors…..
• Immune Tolerance Dysregulation may explain the
appreciably ↑ risk of PE in:-
– Impaired placental antigenic site blocking Abs
formation (higher risk with 1st pregnancy)
– Higher paternal antigen load ( Eg 2N paternal
chrs in molar preg.
– Trisomy 13 Extra Chr 13 carrying the genes for
antiangiogenic Factors .
– Elevated serum AGF 30-40% PE incidence
– In women who would develop PE,Reduced
amounts of non classic immunosupressive HLA
G production from EV trophoblasts early in
pregnancy (Associated with high levels of
placental oxidative products)

Immunologic Factors….
• These changes may contribute to defective vasc
in Stage 1 of PE synd.
• women previously exposed to paternal antigens,
such as a prior pregnancy with the same partner, are
“immunized” against preeclampsia. (does not include
abortions)
• multiparas impregnated by a new consort have an
increased risk of preeclampsia (Mostello, 2002).

Immunologic Factors …….
• Normal pregnancy
– Th2 production and activity increase  ‘Type 2
bia’  more humeral immunity (Th2) than
cytokine inflammatory rxns (Th1)
• PE
– loss of Type2 bia Since early 2nd T ↑Th1:Th2
ratio increased inflammatory activity of Th1
stimulated by placental microparticles and
adipocytes

Endothelial Activation
• In many ways, inflammatory changes are believed
to be a continuation of the stage 1 changes
caused by defective placentation :
• Endothelial cells injury is thought to be provoked
by antiangiogenic and metabolic factors + other
inflammatory mediators
• Endothelial cell dysfunction may result from an
extreme activated state of leukocytes in the
maternal circulation (Faas, 2000; Gervasi, 2001)-Cytokines
( TNF, ILs ) contribute to Oxidative stress of PE s
Placental ischemia oxidative stress release of unknown
placental factors into maternal circulation inflammatory
reactions  wide spread endothelial cell activation and damage
via FREE RADICALS PE syndrome

• OS is characterized by formation of reactive Oxygen
species and FRs formation of self propagating
lipid peroxides generation of highly toxic radicals
that injure endothelial cells, modify their NO production,
and interfere with PG balance.
• Damaged or activated endothelial cells
– May produce less NO and
– secrete substances that promote coagulation and
increase sensitivity to vasopressors
i.e contrary to Normal Endothelial Cells of Normal
endothelium with Anticoagulant properties and NO
production ( Blunted vascular SMm cells response to
pressors )

• Consequences of inflammation due to oxidative
stress on capillaries
– Atherosis (production of lipid-laden macrophage foam
cells
– Activation of Microvascular Coagulation
(thrombocytopenia)
– Increased Capillary permeablity ( edema, proteinuria)
– Altered PG balance and NO production
– Increased sensitivity to vasopressors
• The clinical syndrome of PE is thought to result
from these widespread endothelial cell changes
NB- dietary supplementation with vitamins E (α-tocopherol)
and C (ascorbic acid) to prevent preeclampsia has thus far
proven unsuccessful (Task Force, 2013)

Endothelial activation….
• Endothelial activation causes vascular constriction
with increased resistance and subsequent
hypertension.
• At the same time, endothelial cell damage causes
interstitial leakage through which blood
constituents, including platelets and fibrinogen are
deposited subendothelially.
• Wang and associates (2002) have also demonstrated
disruption of endothelial junctional proteins.
• Suzuki and coworkers (2003) described
ultrastructural changes in the subendothelial region
of resistance arteries in preeclamptic women.

Endothelial activation………..
• The much larger venous circuit is similarly
involved, and with diminished blood flow
because of maldistribution, ischemia of the
surrounding tissues can lead to necrosis,
hemorrhage, and other end-organ
disturbances characteristic of the syndrome.
• One important clinical correlate is the
markedly attenuated blood volume seen in
women with severe preeclampsia (Zeeman,
2009

Endothelial activation……
• Further evidence of endothelial activation includes
• The characteristic changes in glomerular capillary
endothelial morphology [glomerular capillary endotheliosis
(swollen Endothelial cells partially/ totally block Cap lumen)
blocking the filtration barrier]
• Increased capillary permeability, and
• Elevated blood concentrations of substances associated
with endothelial activation
– These latter substances are transferable, and serum
from women with preeclampsia stimulates some of
these substances in greater amounts.
– It seems likely that multiple factors in plasma of preeclamptic
women combine to have these vasoactive effects

Hereditary Factors
• From a hereditary viewpoint, preeclampsia is a
multifactorial, polygenic disorder.
• In their comprehensive review, Ward and Taylor (2014)
cite an incident risk for preeclampsia of;
– 20 to 40 percent for daughters of preeclamptic mothers;
– 11 to 37 percent for sisters of preeclamptic women; and
– 22 to 47 percent for twins.
• In a study by Nilsson and colleagues (2004) that
included almost 1.2 million Swedish births, there was a
genetic component for gestational hypertension and
for preeclampsia.
• They also reported 60-percent concordance in
monozygotic female twin pairs.

Pressor Response
• In preeclamptic/ those who will develop PE or
GHTN loss of refractoriness to angiotensin II
is lost many weeks ahead of onset of the
disease --increased sensitivity to agtensin II
• Normal pregnancy blunted pressor
response/ refractoriness

Pressor Response
PROSTAGLANDINS
PE
• Decreased prostacycline ( PGI2) from endothelial
cells (mediated by phospholipase A2)
• Increased Thromboxane A2 from platelates
↓prostacycine: thromboxane A2 ratio net
result of ↑ed sensitvity to pressor (AGT II)
vasoconstriction
Chavarria and co-workers (2003) have provided
evidence that these changes are apparent as
early as 22 weeks in women who later develop
preeclampsia.

Pressor response
NITRIC OXIDE
• Potent vasodilator synthesized from L-arginine by
endothelial cells
• It also is produced by fetal endothelium and is
increased in response to PE, DM, and infection(Parra, 2001;
von Mandach, 2003).
• In humans, NO likely is the compound that maintains
the normal low-pressure vasodilated state
characteristic of fetoplacental perfusion
• Withdrawal of nitric oxide results in a clinical picture
similar to preeclampsia in a pregnant animal model
(Conrad,1989)
– Inhibition of NO synthesis increases MAP, decreases HR ,
and reverses the pregnancy induced refractoriness to
vasopressors
• The effects of NO production in PE are unclear(Taylor and
associates, 2009).

Pressor response-NO
• It appears that PE is associated with decreased
endothelial NO synthase expression, thus
increasing NO inactivation.
• Inhibition of NO synthesis
– ↑es MAP,
– ↓esHR, and
– reverses the pregnancy-induced refractoriness to
vasopressors.

Pressor Response-ENDOTHELINS (ET)
• ET-21 aa peptides, Potent vasoconstrictors
• ET-1 is the primary isoform produced by
human endothelium
• Not of placental origin-> likely arise from
systemic endothelial activation
• Plasma ET-1 levels are↑ed in normotensive
pregnant women, but more elevated in PE
• MgSO4 rx lowers ET-1 concentrations in
Preeclamptic women.

Angiogenic-Antiangiogenic Factors
• Pro and antiangiogenic (AA)substances are
involved in Placental vasculogenesis (at 21 day
post conception)
• PEplacental AA Fs over production conc of AA Fs >
PA Fs (maternal circulation) Angiogenic Imbalance
• Cause of placental overproduction of AA protein- not
clear yet, hypothesized as
– Hypoxia in the U-P interface stimulation of
excessive AA Fs
• AA substances donot enter fetal circulation or AF
and dissipate from maternal circulation after
delivery

Angiogenic-Antiangiogenic Fcators
• Two antiangiogenic peptides are known to be
produced excessively by trophoblasts and enter
maternal circulation months before PE
development
1.Soluble Fms like Tyrosine Kinase 1 (sFlt-1)
– Variant of Flt-1 receptor of VEGF and PlGF
– ↑ed sFlt-1  inactivates and ↓ses circulating free
VEGF and PlGF levels of mat circulation leading to
endothelial dysfunction (Maynard, 2003)
• High 2nd T SFlt-1 level 2x risk of PE,If the elevation occurs earlier-- high risk of early PE
2. Soluble Endoglin (sEng) / also called CD 110
• Inhibits binding of many isoforms of TGFβ to
endothelium by blocking Endoglin(surface co-receptor
of TGFβ family)  Decreased NO induced
vasodilatation

Angiogenic-Antiangiogenic Fs for PE prediction
• Clinical research is directed at use of
antiangiogenic proteins in the prediction and
diagnosis of PE.
• In a systematic review, Widmer and associates
(2007) concluded that 3rd T elevation of sFlt-1
levels and decreased PlGF concentrations
correlate with preeclampsia development after 25
weeks.
• These results require verification in prospective
studies.
• Subsequently, Haggerty and coworkers (2012)
reported that doubling of expressions of sFlt-1
and sEng increased the preeclampsia risk 39 and
74 percent, respectively.

Angiogenic-Antiangiogenic Fcators ACOG 2014 Task Force
Utilization for PE Prediction
• sFlt-1
– The higher the conc the more predicitive of early
development of PE
– However SFlT-1 elevation occurs 4-5weeks ahead of
clinical SS not useful as screening test early in
gestation
• PlGF-
– begin to decrease 9-11 weeks prior to clinical SS and
accelerate in the 5weeks preceding onset of disease
– Studies reveal modest predictive value of for use of
PlGF in the 1st T prediction of early PE
sFlt-1/ PlGF ratio > 85% indicator of maternal/ fetal
adverse outcome in HDP pts within 2 weeks of
presentation

Pathogenesis
• VASOSPASM evident from;
– Direct observation of nail bed, fundal, bulbar
conjunctivae
– Histological changes in affected organs
• Vascular constriction↑ed resistance
Hypertension
• With diminished blood flow because of
maldistribution;
– ischemia of the surrounding tissues would lead to
necrosis,
– hemorrhage, and
– other end-organ disturbances
• Are characteristic of the syndrome

Blood Volume
• Normal Pregnancy- ~1500ml extra blood volume
• PE- Hemoconcentration Reduced Blood volume
expansion
• Hemoconce. is proportional with severity
– Eclampsia- little/no volume expansion
– PE- hemoconcentration not marked
– GHTN- normal pregnancy volume
• Cause
– endothelial activation followed by generalized
vasoconstriction ,
– leakage of plasma

Kidneys
• Decreased GFR 20 to;
– Decreased RBF (decreased palsma volume)
– Renal afferent arterioles resistance (5x increased)
– Morphologic changes- Glomerular Endotheliosis
which blocks the filtration barrier
• Diminished filtration causes serum creatinine
levels to rise to values seen in nonpregnant
individuals~ > 1 mg/mL, and
(Lindheimer,2008a).
• Abnormal values usually begin to normalize 10
days or later after delivery (Spaan, 2012a).

Kidneys
• Serum U.acid elevates- exceeds GFR
reduction rate  likely due to enhanced T
Reabsorption
• In most PEtic women, urine sodium
concentration is elevated.
• Urine osmolality, urine:plasma creatinine
ratio, and fractional excretion of sodium also
indicate that a prerenal mechanism is
involved.
• Urinary Ca excretion is reduced~T
Reabsorption

Liver Pathophysiology
• Hepatic ifarction and
hemorrhage
–Histopathology periportal hemorrhage
+ infarction peripherally
–Hepatocellular necrosis ↑ Taminases
(ALT AST)
• Hemorrhage may extend and form
Hepatic Hematoma then Sub
capsular Hematoma
–May rapture,CT/ MRI Dx

Diabetes Mellitus in Pregnancy
1
By Dr Samuel,Gynecologist

DM in Pregnancy
• Diabetes mellitus is the most common
medical complication of pregnancy
2

DM in Pregnancy
• DM in pregnancy can be separated into two;
1. Pregestational or overt Diabetes
• diagnosed before pregnancy
– Type I, Type II, Other forms
2. Gestational Diabetes (GDM)
• any degree of glucose intolerance
diagnosed during pregnancy.
3

Modified Whites Classification Scheme of
Diabetes Complicating Pregnancy
Class Onset Fbs 2hrpp Rx
A1 Gestational <105 <120 Diet
A2 Gestational >105 >120 Insulin
Class Onset age Duration Vascular
disease
Rx
B >20 <10 None Insulin
C 10-19 10-19 None Insulin
D <10 >20 Benign rpthy Insulin
F Any Any Nephropathy Insulin
R Any Any Proliferative
rrtinopathy
Insulin
H Any Any Heart Insulin 5

Effects of Pregnancy On Carbohydrate
Metabolism
• Pregnancy is characterized by increased
insulin resistance and reduced sensitivity to
insulin action.
• Late in the first trimester, relatively higher
levels of estrogen enhance insulin sensitivity
and,
• when associated with nausea and vomiting,
increase the risk for maternal hypoglycemia.
7

Effects of Pregnancy On Carbohydrate
Metabolism
• The increase in insulin resistance is largely
the result of a mixture of placental
hormones, including;
–hPL, progesterone, prolactin, placental
growth hormone, and cortisol.
• More recently, TNFα and Leptin have been
implicated as contributors to the insulin
resistant state of pregnancy
• Insulin resistance is greatest in the 3rd TMx.
8

Effects of pregnancy on CH Metabolism
• In the 1st trimester, increasing maternal estrogen
and progesterone levels are associated with:-
– a decrease in fasting glucose levels, which
reach a nadir by the 12th week
• The decrease averages 15 mg/dL; thus, fasting
values of 70–80 mg/dL are common by the 10th
week of pregnancy
• Insulin sensitivity decreases as gestation
advances in all pregnant women, mainly due to
anti-insulin signals produced by the placenta.
9

• In the 2nd trimester, as the placenta increases
secretion of anti-insulin hormones,
• higher fasting and postprandial glucose levels
occur;
– that facilitate transfer of glucose from mother
to fetus.
• Glucose transfer occurs via a carrier-mediated
active transport system that becomes saturated
at 250 mg/dL.
• Fetal glucose levels are 80% of maternal levels.
10

• In contrast, maternal amino acid levels are
lowered due to active placental transfer to the
fetus.
• Lipid metabolism in the second trimester
shows continued storage until midgestation,
then enhanced mobilization (lipolysis) as fetal
fuel demands increase
11

Effects of pregnancy on CH Metabolism- Hormones
HPL
• Resembles GH
• Major culprit of insulin resistance and lipolysis
• Decreases affinity of receptors to insulin
• Diverts CHO metabolism to fat metabolism +
decreases mat. Hunger sensation
• NET Effect:-↑maternal glycemia+↓Glucose use
↑se placental transfer to fetus.
• The hPL levels rise steadily during the first and
second trimesters, with a plateau in the late third
trimester.
12

Effects of pregnancy on CH Metabolism- Hormones
• Cortisol:-
–Its levels rise during pregnancy and
–stimulate endogenous glucose production
and glycogen storage and decrease glucose
utilization.
• Prolactin
–increased 5- to 10-fold during pregnancy
and may impact CH metabolism.
–Thus, women with hyperprolactinemia also
should undergo early glucose screening. 13

I. Pregestational/ Overt DM
14

Pregestational/ Overt DM
• Observed in 1% of all pregnancies
• Type 2 PGDM is most common and is
characterized by;
–onset later in life;
–peripheral insulin resistance;
–relative insulin deficiency;
–obesity; and the development of vascular,
renal, and neuropathic complications
15

Pregestational/ Overt DM
Diagnosis:
• Random plasma glucose level > 200 mg/dL
plus polydipsia, polyuria, and unexplained
weight loss or;
• Fasting glucose level > 125 mg/dL (ADA (2012))
Incidence
• >1% of all pregnancies
16

• aApply to women without known diabetes antedating Px.
• The decision to perform blood testing for evaluation of glycemia
on all pregnant women or only on women with characteristics
indicating a high risk for diabetes is based on the background
frequency of abnormal glucose metabolism in the population
and on local circumstances----- Williams 24th
17

Pregestational DM-Impact on pregnancy
• Outcome of pregnancy depends on;
–Degree of glycemic control
• Poor control poor outcome
–the stage/ Whites Class
• Advanced stage less favorable
outcome
18

Fetal Effects
• Spontaneous abortion
• Preterm delivery
• Malformations
• Growth abnormalities
– IUGR
– Macrosomia
• Unexplained fetal
demise
• Hydramniosis
Neonatal Effects
• Respiratory distress
syndrome
• Hypoglycemia
• Hypocalcaemia
• Hyperbilirubinemia
• Polycythemia
• Hypertrophic
cardiomyopathy
19

• The frequency of major congenital malformations
in newborns of women with Pregestational
diabetes stratified by hemoglobin A1c levels at
first prenatal visit. (Data from Galindo,
2006.)
20

 Congenital Anomalies in Fetuses of 91 Women with Type 1 Diabetes between
1999 and 2004 in Norway
Cardiovascular system is the most involved organ.
21

Maternal Effects
• Vascular complications
– Retinopathy progression worsened by;
• Pregnancy – independent risk factor for Rpathy
• poor early pregnancy glycemic control
• Hypertension
• Rapid tight glycemic normalization
• long duration DM , advanced rpathy,
– Nephropathy
• Pregnancy has no effect on progression of preexisting
or dv’t of new Npathy.
22

Maternal effect……
• Preeclampsia (3-4X increased risk, ~12x risk if
there is CHTN)
• Diabetic neuropathy
– in the form of Gastropathy (N, V, malnutrition,
difficult Glucose control)
• DKA- in `~1% of pregnancies with DM
• Infections
– candidia vulvovaginitis, UTI, Respairatory Tract
Infections, puerperial sepsis
23

Pregestational DM- Management
Preconception Care
 Conception with uncontrolled glycemic level- increased risk of
early pregnancy loss and congenital malformations
 Optimal preconceptional self monitored Glucose control using
insulin (ADA- 2012)
– Pre-prandial: 70-100mg/dl
– Peak postprandial 100- 129mg/dl
– Mean daily glucose level < 110 mg/dl
– HGB A1C < 7%*
*Reflects an average of circulating glucose for the past 4 to 8 weeks, is useful to
assess early metabolic control. Substantially fourfold increased risk for
malformations at HGB A1clevels > 10 %
• If indicated, evaluation and treatment for diabetic complications
such as retinopathy or nephropathy should also be instituted
before pregnancy.
• Folate, 400 μg/day orally is given periconceptionally and during
early pregnancy to decrease the risk of neural-tube defects.
24

Pregestational DM- Management
Management during pregnancy
• Treatment with insulin
• Careful monitoring of glucose control to attain
glycemic goals
• US for fetal anatomy at 18-20wks
• Testes for anomalies- maternal serum analytes
• Fetal well being tests initiated at 32-34 weeks
of GA.
25

Antepartum care
• Maternl glycemic control evaluation by SMBG
• Eye exam( laser rx if needed)
• RFT( creat./ 24hr urine p/urine alb: creat ratio)
• Electrocardiography( if age>30 + disease >5yr)
• TFT for those with Type I preg.DM
• Urine culture & rx( 3x risk of asymp. Bacterutria)
• Early US for GA
• Fetal growth US
• US for fetal anatomy at 18-20wks
• Testes for anomalies( 1st trim NT, serum
screening, 2nd trim. Triple/ quadriple tests)
26

Pregestational DM Rx
Blood Glucose Goals in pregnancy
27

Action Profiles of Commonly Used Insulins
28

Pregestational DM-Management
Delivery
• Timing- balance of risks i.e, IUFD vs prematurity
• Early delivery may be indicated in some patients
with vasculopathy, nephropathy, poor glucose
control, or a prior stillbirth.
• patients with well-controlled diabetes and
reassuring antenatal testing may be allowed to
progress to their EDD.
• Expectant management beyond the estimated
due date generally is not recommended.
• For EFW > 4500gm cesarean delivery may be
considered to prevent traumatic birth injury
(ACOG 2014) 29

Pregestational DM-Postpartal Management
• No insulin needed for the 1st 24 hrs
• Breast feeding should be encouraged
• Calorie intake- 500kcal in excess of the
Prepregnancy requirement.
• Contraception
– Low dose OCP-if non smoker and no vasculopathy
– POPs- if there is vasculopathy
– IUCD- may have increased infection risk
– Sterilization for those with serious vasculopathy
and in those who have completed their family.
30

II.Gestational Diabetes Mellitus (GDM)
31

GDM
• Gestational diabetes is defined as
carbohydrate intolerance of variable
severity with onset or first
recognition during pregnancy (ACOG,
2013).
32

GDM-Epidemiology
• GDM complicates approximately 4% of
pregnancies.
• 90% of diabetes cases encountered during
pregnancy are GDM
• > 40% will have recurrent GDM in subsequent
pregnancy.
• more than one half of women with GDM
eventually develop type 2 PGDM later in life
(in 10-20yrs).(ACOG 2014)
33

GDM risk assessment
Risk factors
• Obesity (nonpregnant body mass index > 30),
• Prior history of GDM( > 60% recurrence)
• Heavy glycosuria (> 2+),
• Unexplained stillbirth,
• Prior infant with major malformation, and
• Family history of diabetes in a first-degree
relative
34

Screening
A.Universal or
B. selective screening
35

Selective screening
Screening Strategy Based on Risk Assessment for
Detecting GDM (Recommendation by 5th
International Workshop-Conference on GD)
A. Low risk
• Routine screening is not required
– Ethnic group with low GDM prevalence
– Age < 25,
– No diabetic 10 relative
– Normal birth weight, normal prepregnant wt.
– No hx of glucose intolerance
– No hx of poor obstetric outcome
36

Selective screening……
B. Moderate risk
– screen at 24-28 week using either the 2 step
(50gm GCt---threshold---100g- 3hr OGTT) or 1 step
test ( 75gm–OGTT)
C. High Risk
– screen as soon as possible,
– if –ve repeat at 24-28wk and whenever SS suggest
hyperglycemia
– severity sign are:-
• Severe obesity
• Strong Family Hx of type 2 DM
• Hx of GDM, IG metabolism, glucosuria 37

screening one step vs Two step tests
I. One-step procedure:
– diagnostic ,OGTT performed on all subjects
II. Two step Procedure
1. 50 gm glucose administered regardless of timing of prior
meal;
• Blood Sugar is checked after 1hr screening test
• No strict cut off is set for abnormal value (usually 130-
140 are acceptable+ the lower the cutoff the higher the
sensitivity)
2. 3hr100gm OGTT/ 75gm 2hrOGTT preceded by
obtaining the FBS  Diagnostic test
– After unrestricted diet, at least 150gm CH,for 3 days
to avoid CH depletion and subsequent spurious ↑ GTT
values 38

Screening-one step vs Two step tests
• WHO (1998) and the American Diabetes
Association (ADA ,2013) recommend the 75-g
2-hour oral glucose tolerance test (one step).
• In the US , however, the 100-g, 3-hour OGTT
test performed after an overnight fast is
recommended by ACOG (2013).
39

Screening - 0ne step procedure*
• aOne or more of these values from a 75-g OGTT must be equaled
or exceeded for the diagnosis of gestational diabetes.
• Recommended by IADPSG Consensus Panel (2010) and ADA
(2013)
• *Not accepted by ACOG and NIHIt would increase the
prevalence of GDM in US to 17.8% the No of women with
mild GDM would increase almost threefold with no evidence of
treatment benefit(Cundy, 2012). 40

5th International Workshop Conference on
GDM Diagnostic Criteria of GDM by OGTT.
• aThe test should be performed in the morning after an overnight fast of at
least 8 hr but not more than 14 hr and after at least 3 days of unrestricted
diet ( >150 g/d) and physical activity.
• The subject should remain seated and should not smoke during the test.
• bTwo or more of the venous plasma glucose concentrations listed must be
met or exceeded for a positive diagnosis.
Data from Metzger, 2007. 41

GDM- complications
• Unlike overt diabetes, rates of fetal anomalies do
not appear to be substantially increased in
GDM(Sheffield, 2002).
• Excessive fetal size (macrosomia)
– Excessive trunk and shoulder fat predisposing for
shoulder dystocia and CD
• Neonatal Hypoglycemia
• Women with a history of gestational diabetes are
also at risk for cardiovascular complications
associated with dyslipidemia, hypertension, and
abdominal obesity—the metabolic syndrome
• The women also have increased cardiovascular
morbidity risk in the long-term.
42

GDM- Management
Glycemic control can be achieved via;
1. Life style modification
• Diet modification, moderate exercise
2. Pharmacologic rx.
• if diet modification doesn’t result in the target
glucose level
• Insulin - preferred
• Oral hypoglycemic- studies show safety and
efficacy of either glyburide (Micronase) or
metformin (Glucophage)
43

GDM-Management
Target Glucose levels in GDM treatment
–Fasting plasma glucose levels < 95 mg/dL
–1hr postprandial plasma glucose< 140mg/dl
–The 2-hour postprandial plasma glucose <
120 mg/dL (ACOG, 2013).
44

GDM- Obstetric Management
• Often expectant management as long as
glycemic control is good.
• Fetal surveillance ; not routine-may be used
only when there is poor glycemic control
• Elective induction to prevent shoulder
dystocia??? Controversial.
• EFW > 4500gm elective CD to avoid
shoulder dystocia and brachial plexus injury.
45

GDM- Postpartum Evaluation
46

PREMALIGNANT AND
MALIGNANT LESIONS OF
CERVIX
By Dr Samuel -2016 G.C.

Cervix- Gross Anatomy
• Cylindrical or conical in shape,
• Measures 3-4 cm in length and 2.5-3.5 cm in
diameter
• Two portions
– Portio vaginalis; The lower half of the cervix, protrudes
into the anterior vagina
• Fornices ( lateral, anterior, post.)- Upper vaginal cavity
surrounding PV
– Supravaginalis- upper half, above vagina
• Two openings
– External OS- opening into vagina
• Wide, gaping, transverse slit in parous woman
• A small circular (pinhole) opening in nulliparous women
– Internal OS- opening b/n supra vaginal part and uterine
body

Cervical Anatomy
• Ectocervix
– exterior to external OS,
– Pale pink
– Covered with stratified squamous epithelium
 Basal-Parabasal-Intermidate- Superficial cells
• EndocerviX
– Endocervical canal b/n internal and ext OS
– Lined by a single layer of columnar epithelium
– bright red
• Squamocolumnar junction (SCJ)
– the point at which the squamous and columnar
epithelia meet

Columnar Epithelium
Stratified squamous epithelium

Cervical Anatomy
SquamocolumnarJunction (SCJ)
• The SCJ is a dynamic point that changes in
response to
– Puberty,
– Pregnancy,
– Menopause, and
– Hormonal Stimulation
The division may be at the external os or
inside the endocervical canal depending on
age and hormonal status

Cervical Anatomy-SCJ
• In high E state (neonates, adolescents ,
pregnancy, and OCP users ):
– the SCJ is located on the exocervix  the
columnar epithelium often extends well
beyond the external os (ectropion/
Eversion)
• In low Estrogen states (postmenopausal and
lactating women or prolonged use of POPs):
– the SCJ may be high in the canal where it
cannot be seen.

Cervical Anatomy-SCJ
• In ectropion, the columnar epithelium is exposed
to the acidic vaginal environment.
• This triggers Metaplasia ( columnar to
squamous) Formation of new SCJ
• Transformation Zone the metaplastic area
b/n the old and new SCJs.
• Metaplasia is most active during adolescence
and pregnancy

Premalignant lesions of the
cervix
Cervical Ca is a preventible disease
– It has a premalignant/ preclinical phase that can
be detected ,by screening methods,
– The premalignat lesions are curable
– Vaccine against major etiologic agents (HPV 16
and 18) is available

Premaliganat Lesions of the Cervix
Cervical Intraepithelial Neoplasia (CIN)
CIN  disordered growth and development of the
epithelial lining of the cervix.
• histologic findings of cervical biopsy.
significant features are
– cellular immaturity & disorganization
– nuclear abnormalities and
– increased mitotic activity.
The extent of the mitotic activity, immature
cellular proliferation, and nuclear atypicality
identify the degree of neoplasia.

Premalignant Lesions of the cervix-CIN
HISTOLOGY
CIN I(mild dysplasia) dysplasia of the lower
1/3rd of cervical epithelium
CIN II(moderate dysplasia) dysplasia of 2/3rd
of the epithelium
CIN III( severe dysplasia)  > 2/3rd of the
epithelium involved with carcinoma in situ (
full thickness dysmaturity)

CIN- Clinical Findings
Symptoms and Signs of CIN
• There are usually no symptoms or signs of CIN,
and
• the diagnosis is most often based on biopsy
findings following an abnormal routine cervical
cytology smear

CIN-epidemiology
• CIN is most commonly detected in women in
their 20s
• the peak incidence of carcinoma in situ is in
women ages 25–35 years,
• whereas the incidence of cervical cancer rises
most significantly after the age of 40 years.

CIN
• From the time that mild dysplasia is identified,
it usually takes 10 to 20 years for invasive
cancer to develop;
• this means that cervical cancer control is
possible through screening and treatment.

Risk Factors for Cervical Neoplasia
Demographic risk factors
Ethnicity (Latin American countries, U.S. minorities)
Low socioeconomic status
Age
Behavioral risk factors
Infrequent or absent cancer screening Pap tests
Early coitarche
Multiple sexual partners
Male partner who has had multiple sexual partners
Tobacco smoking
Dietary deficiencies(vitamins such as A, C, E, beta carotene, and folic acid)
Medical risk factors
Cervical high-risk human papillomavirus infection
Parity
Immunosuppression
CIN Risk Factors- similar to that of Cervical Ca

Natural History of Cervical Intraepithelial Neoplasia Lesions
CIN grade Regression (%) Persistence (%) Progression to CIS
(%)
Progression to
Invasion (%)
CIN 1 57 32 11 1
CIN 2 43 35 22 5
CIN 3 32 <56 – >12
CIN- Natural History

Human Papilloma Virus (HPV)
Nonenveloped DNA virus with a protein capsid.
Infects epithelial cells exclusively.
• more than 120 types of HPV are identified,
• 30 of these 10ly infect the squamous epithelium of the lower
anogenital tract of men and women
• HPVs are a prime etiologic factor in the development of CIN and
cervical cancer.
• HPV is detected in
– > 80% of all CIN lesions and
– 99.7% of all invasive cervical cancers
• Low risk HPV subtypes
– Ass with condyloma lata/ low grade lesions(CINI)
E.g.. Subtypes 6,11, 42,43,44
• High risk HPV subtypes
– Associated with high grade lesions & cx ca
E.g.. 16,18, 31,33, 35,39, 45, 51,52,56,58,59,68,73,82

Schematic representation of the circular HPV genome.
Transcription by the “early” (E1–7 or nonstructural) genes and the
“late” (capsid protein) genes is controlled by the upstream regulatory
region (URR).

Viral Life Cycle
The circular, double-stranded HPV genome consists of
nine identified open reading frames.
The “Early" (E) genes govern functions early in the
viral life cycle such as DNA maintenance, replication,
and transcription.
The “Late" (L) genes encode capsid proteins needed
late in the viral life cycle to complete assembly into
new, infectious viral particles.
Completion of the viral life cycle takes place only
within an intact squamous epithelium.
HPV is a nonlytic virus, and therefore infectiousness
depends upon desquamation of infected cells
Human papiloma virus

Transmission
Sexally transmitted
Vertical infection (Conjunctival, laryngeal, vulvar, or perianal
warts present at birth or develop within 1 to 3 years)
Outcome of HPV Infection
HPV infection can be
transient or persistent
latent or expressed.
Expression is either productive, with formation of new virus, or
neoplastic, causing preinvasive disease or malignancy.
HPV Contd.

Latent Infection :
Latent infection  HPV remains quiescent.
Expressed Productive Infection:
Productive infections have little or no malignant potential
because eventual host cell death is required to complete the viral
life cycle.
The intact, circular HPV genome remains unintegrated into the
infected cell's chromosomes and its oncogenes are expressed at
only very low levels .
In both the female and male genital tracts, productive HPV
infections produce
visible genital warts, called condylomata acuminata, or
subclinical infections known as low-grade squamous intraepithelial
lesions (LSILs).
HPV Contd.

Expressed Neoplastic Infection
In cancerous lesions, the circular HPV genome integrates linearly at
random locations into a host chromosome and begins transcription of
the E6 and E7. i.e E7 protein binds to the retinoblastoma (Rb) tumor
suppressor protein, whereas E6 binds to the p53 tumor suppressor
protein
Their products, the E6 and E7 oncoproteins, interfere with the
function and accelerate degradation of p53 and pRB, key host tumor
suppressor proteins.
This leaves the infected cell vulnerable to malignant transformation
by loss of cell cycle control, cellular proliferation, and accumulation
of DNA mutations .
HPV Contd.

HPV infection
• HPV infections are acquired by young women
shortly after initiation of sexual intercourse
• Usually, HPV infections do not persist
• In most cases infection is cleared in 1-2 years
• Persistent HPV infection carries increased risk
of neoplastic changes in the metaplastic sq TZ
• HPV infection
– high prevalence in teenage,
– peak in the 3rd decade of life ,
– decreases after wards

Risk factors
Strong association
- sexual risk factors
- Low socio economic status
- Multiparty
- Cigarette smoking
- Immunosuppression
- In utero DES exposure
Weak risk association/controversial
OCP, Nutrition

HPV
• HPV infection is a necessary, but not a sufficient, cause of cervical cancer;
• Host factors, as well as behavioural and environmental factors, may facilitate cancer
development
• Factors that may have a role in this progression include
– smoking,
– contraceptive use,
– infection with other STI,
– Immunosuppression (Eg HIV infection)
– malnutrition .
• Any factor that influences the integration of HPV DNA into the human
genome may cause progression to invasive disease

Prevention of HPV infection
Behavioral Interventions
Condoms use??
Prophylactic Vaccines
Recombinant quadrivalent vaccine against types 6, 11, 16, and
18 (Gardasil) or Bivalent against HPV 16 and 18 (Cervarix)
Indicated for women aged 9 to 26 years
Administered in three intramuscular doses over 6 months.
It elicits humoral antibodies that neutralize HPV before it can
infect host cells
Prevent establishment of persistent infection and therefore,
the development of cervical neoplasia.
Testing for HPV is not recommended prior to vaccination
HPV Contd.

Cervical cancer screening
Aims to detect disease before symptoms occur.
Basis for cervical cancer screening are:
long preinvasive state (10-15yrs) of the disease
Existence of effective treatment for pre cancerous lesions
Screening can be organized or opportunistic
Organized screening
Is designed to reach the highest possible number of women at
greatest risk of cervical cancer with existing resources.
Opportunistic screening
Is screening done on women who are visiting health services
for other reasons

Screening Contd.
Methods of cervical cancer screening include:
1. Cervical Cytology-the Pap smear (cytology) is the only
test that has been used in large populations and that
has been shown to reduce cervical cancer incidence
and mortality.
– Conventional PaP collection
– Liquid-based pap collection
2. HPV DNA testing
3. Combined test (cytology + HPV test for women > 30)
4. Visual method ( VIA, VILI)

Screening- Cytology
I.Conventional pap smear
Introduced in 1941 by Papanicolaou
Standard screening test for lower genital tract neoplasm
Historical success in developed countries in reduction of
cervical cancer.
The Pap test's specificity is 98 % with sensitivity of 51
In conventional pap
sample is taken, then
quickly spread as evenly as possible over one half to two
thirds of a glass slide.
fixation immediately by spray or immersion of slide with 95%
alcohol

• Sensitivity~51%
High (49%) false negative rate
• ~30% of cx ca Dx in women with –ve Pap test
• Sampling, preparation (fixation) and
interpretation errors

Screening- Cytology
II. Liquid Based Cytology
• Introduced in the mid 1990s
• Sample transferred from brush/spatula to liquid
preservative
• Smear prepared at the lab
Advantages over the conventional
– More representative
– Higher sensitivity ~80%
– Specimen can also be used for HPV DNA test
Disadvantages
– Expensive
– Specially trained lab staff needed

Timing of sample
Avoid menstruation period
Abstain for 24 to 48 hours from
– Vaginal intercourse,
– Douching, and use of
– Vaginal tampons and
– Medicinal or contraceptive cream preparations
Location of sample
Sample transformation zone
Sampling Tools
Spatula, the broom, and the endocervical brush
Cervical Cytology Contd.

Pregnancy
Cervical changes in pregnancy
• Proliferation of endocervical – columnar cells- eversion/ extension onto
the portio
• Secretion of copious mucus – mechanical obstruction and IgA and cytokine
prevention of ascending infection
• Hyperplasia and hypersecretory appearance changes of endocervical
glands (Arias Stela Reaction) difficultto differentiate from atypical
glandular cells on Pap smear
• Not the ideal time for screening
• interpretation of screening tests, such as cytological tests, is more difficult.
• Regression of CIN during pregnancy is minimal, but there is a significant rate of
spontaneous regression postpartum.
• A biopsy for diagnosis should be taken from a pregnant woman only if invasive
cancer cannot be ruled out.
• Treatment of preinvasive disease is contraindicated during pregnancy.
• AT ANC should be advised to return for screening 12 weeks after giving birth.
• However, if a cervical abnormality is noted on speculum examination, or if the

Screening- Cytology
Dysplastic cells
• Anaplasia
• Nucleus larger than CP( high N:CP ratio)
• Hyperchromatism + change in Nuclear
Chromatin with loss of polarity in the deeper
layer+ increased abnormal mitotic figures
• Multinucleation
• Abnormality of differentiation

The 2001 Bethesda System for Reporting Cervical Cytology
I. Negative for intraepithelial lesion or
malignancy (Normal)
No neoplastic cellular evidence
• Non-neoplastic findings may be noted
– Infectious organisms ( T Vag, Candida, BV,
Actinomyces, H simplex)
– Reactive cellular and reparative changes ass. with eg
inflammation, radiation, IUD
– Glandular cells status- post hysterectomy atrophy
– Other- endometrial cells in women > 40

The 2001 Bethesda System for Reporting Cervical Cytology
II.Epithelial cell abnormality
A.Squamous cells
– ASCUS (atypical squamous
cells of undetermined
significance)
– ASC- H( high grade lesion
can’t be excluded)
– LSIL (low grade squamus
intraepithelial lesion)
• encompass HPV
(koilocytosis)/ Mild
Dysplasia/ CIN1
– HSIL (High grade SIL)
• Encompass moderate
and Severe dysplasia,
CIS/CIN 2 and CIN3 ( +
suspicion for invasion)
– Squamous cell Ca
B.Glandular cells
• Atypical
– Endocx cells,
– Endometria cellsl,
– GC Not otherwise specified
(NOS)
• Atypical
– Endo cx cells favor neoplasia
• Endocx ACI
• Adenocarcinoma
– Endocx
– Endometrial
– Extrauterine
– Not otherwise specified
III. Other malignant neoplasia

ACOG 2012- Revised Screening Guidelines
• Initiation of screening-
– at the age of 21 yrs
• Subsequent Tests
– 21- 29 yrs of age-
• cytology every 3 yrs
– 30- 65 (cytology alone or Cytology- HPV cotesting)
• Every 3 yrs with cytology test alone
• Every 5 yrs with Cytology- HPV co-testing
– >65
• No need to screen if 3 consec pap tests are –ve in 10 yrs the
latest test done 5 yrs or earlier
• Women with Total Hysterectomy-
• no need for screening unless they had > CIN2 hX
• Women with Hx of CIN2, CIN3, AIS will continue screening for 20 yrs
after spontaneous regression/ treatment even if age is > 65

ACOG 2012- Revised Cx Screening Guideline (ASCCP, ASC, ASC
•Beginning of Test- at the age of 21 yrs
•Subsequent Tests
•21- 29 yrs of age- Cytology alone every 3 yrs
•30- 65 years of age- ( Cytology alone or HPV cotesting)
•Every 3 yrs with cytology test alone
•Every 5 yrs with Cytology- HPV co-testing ( preferred)
•Stop screening at > 65
• if no Hx of > CIN 2 and if 3 consecutive cytology or 2 consec -
Cotesting results are –ve in the previous 10 yrs the most recent test
done in the past 5 yrs
•Women with Total Hysterectomy-
•no need for screening unless they had > CIN2 hX
•Women with Hx of CIN2, CIN3, AIS will continue screening for 20 yrs
after spontaneous regression/ treatment even if age is > 65

Special Groups that deserve More frequent screening
•HIV +ves-
•CDC Recommendation for HIV +ves
• initiate testing at the time of Dx even for those < 21
•Twice in the year of Dx then annually
•Immunocompromise of other cause (eg Transplant)
•ACOG- annual cytology from age 21 on
•CIN 2+
•age specific routine tests for 20 years after the initial
post rx surveillence period, even if age is past 65
•Iux DES Exposed

Further evaluation of abnormal cervical cytology
• All abnormal Pap smears require further
evaluation ,to exclude the presence of invasive
carcinoma and to determine the degree and
extent of any CIN.
– colposcopy directed biopsy
– repeat cytology
– HPV testing
– endocervical curettage or
– diagnostic conization

Special Examinations
• All patients with ASC-H, LSILs, HSILs, atypical
glandular cells (AGCs), or smears suspicious for
cancer should be referred for immediate
colposcopy
• There are three acceptable initial evaluation steps
for patients with minimally abnormal cervical
cytology smears ( ASC-US):
– accelerated serial cytology smears,
– immediate referral to colposcopy
– HPV testing and triage to colposcopy based on a
positive result

Colposcopic Examination
• Colposcopy is the primary technique for the
evaluation of an abnormal cervical cytology
smear.
• The colposcope uses illuminated low-power
magnification (15x-30x) to inspect the cervix,
vagina, vulva, or anal epithelium
• Reveals abnormalities in the appearance of
cervical epithelium and its capillaries (usually
after addition of 3-5% acetc acid VIA)

Colposcopy normal findings
• The original squamous epithelium b/n vulvovaginal junction&
original SCJ
• The transformation zone
• The endocervical columnar epithelium
NB
• A colposcopically directed punch biopsy of the most
severely abnormal areas should be done
• Endocx curettage(ECC) for (ACOG 2013)
– ASCUS/LSIL
• with unsatisfactory colposcopy,
• TZ destroyed by previous abaltive or excision rx,
• no lesion identified by colposopy
– All ASCS-H, HSIL, Atyipical Gcells and AIS,
• ECC is contraindicated in pregnancy

Satisfactory colposcopy
Satisfactory colposcopy-the entire new
squamocolumnar junction is visible
(otherwise unsatisfactory)

Abnormal colposcopy indicative of dysplasia/ CIS
1. Leukoplakia or hyperkeratosis, which is an area of
white, thickened epithelium that is appreciated
prior to the application of acetic acid and may
indicate underlying neoplasia.
2. Acetowhite epithelium- epithelium that stains
white after the application of acetic acid.
3. Mosaicism or punctation reflecting abnormal
vascular patterns of the surface capillaries. As a
general rule, capillary thickness and intercapillary
distances correlate with the severity of the lesion
and thus tend to be larger and coarser in higher-
grade lesions.
4. Atypical vessels with bizarre capillaries with so-
called corkscrew, comma-shaped, or
configurations suggest early stromal invasion
HPV can produce white flat lesion seen best colposcopically 
thought to be CIN precursor (Clinical Gyn Onco)

Mg’t of CIN
• Mg’t depends on
– correlation of test results( cytology, colposcopy,
biopsy, ECC) +
– specific patients conditions(EG pregnancy, young
age, HIV status, compliance…..)
• CIN1- follow with serial cytology as much of them tend
to resolve spontaneously
• CINII in adolescents can also be followed similarly

Mg’t of CIN
RX of CIN II & III has two categories
1- ablation of abnormal tissue( cryotherapy, laser
ablation, ) if
– ECC is negative
– Colposcopy is satisfactory
– Lesion confined to ectocervix
• No specimen will be avilable for biopsy

Management of CIN
2- Excision( cold knife conization, laser cone excision, deep LEEP) If
– the lesion extends into the endocervical canal
– the endocervical curettage contains dysplastic epithelium or
– the colposcopic examination is otherwise unsatisfactory
– adenocarcinoma in situ or microinvasive carcinoma is suspected.
• allows specimen for further histologic exam

CIN Management
A conization procedure is also indicated for
diagnostic purpose in cases of
– a significant discrepancy between cervical
cytology and colposcopy/biopsy results,
– suspected microinvasive carcinoma or
adenocarcinoma in situ(AIS).

CIN Management
The role of Hysterectomy
• Used to be the Primary treatment of CIN In the past,
However:
– the maximum depth of dysplasia at the SCJ 5.2 mm;
– 99.7% of dysplasias (including ca in situ) are located within
3.8 mm of the epithelial surface .
• Therefore, more conservative treatments such as
cryotherapy, laser, or LEEP can be effective in
treating the disease, making hysterectomy
unnecessary in most women with these conditions
• For patients with recurrent high–grade dysplasia who
do not desire to preserve fertility, hysterectomy is an
appropriate treatment option.
• Even after hysterectomy, however, patients are at
increased risk for vaginal intraepithelial neoplasia

Visual Methods
1.Visual Inspection with Lugols Iodine (VILI)/ Schillers Test
• Lugol’s iodine+ Epithelial cell
– Negative Result (Normal)
• Mahogany brown stainning ie normal(glycogen containing)
cells
– positive Result (Abnormal)
• non-staining (yellow iodine non uptake) abnormal
epithelial Cells(devoid of glycogen)
• VILI has Sensitivity =87.2 Specificity =84.7%
*Positive ST result indcates
– Dysplastic cells
– scarring,
– cyst formation, or
– Immature metaplastic epithelium/TZ

Visual Methods
2.Visual Inspection Using Acetic acid (VIA)
Viewing the cervix with the naked eye to identify color changes
on the cervix.
acetic acid is a mucolytic agent.
It reversibly clumps nuclear chromatin causing lesions to assume
various shades of white depending on the resultant degree of
abnormal chromatin density.
Applying 3- to 5-percent acetic acid to mucosal epithelium results
in the acetowhite change characteristic of neoplastic lesions as
well as some non-neoplastic conditions

VIA
• Acetic acid reversibly coagulates celluar proteins in the
epithelium the epithelium becomes opaque to the
underlying vascularized stroma  White Apearance
• Acetowhite Apearance  in areas of high celluar proteins
/ high nuclear and DNA content as in CIN /invasive C)
• Other conditons that cause acetowhite
– immature squamous metaplasia,
– healing and regenerating epithelium (associated with
inflammation),
– leukoplakia (hyperkeratosis) and condyloma-intense grayish
white
• Acetowhite of Inflammation and ISM- Less pale,thin,
transluscent, patchy, illdefined margins wide distributin
(not confined to TZ), disappear qickly (in a minute)
• That of CIN dense, thick, opaque with well demarcated
margin from surrounding normal epithelium, rapid
appearance and slow reversal ( 3-5min)

VIA test performance
Sensitivity Specificity
Minimum 65% 64%
Maximum 96% 98%
Median 84% 82%
Mean 81% 83%

Strengths of Visual Method
Simple, easy-to-learn
Minimally infrastructure requirement
Low start-up and sustaining costs.
Many types of health care providers can perform the
procedure.
Test results are available immediately.
Requires only one visit.
May be possible to integrate VIA screening into
primary health care services.

Limitations of Visual method
Moderate specificity
No conclusive evidence regarding the health or cost
implications of over-treatment .
There is a need for developing standard training
methods and quality assurance measures.
Likely to be less accurate among post-menopausal
women
Rater dependent.

Management of abnormal VIA /VILI
What to do if the VIA (VILI) test is positive?
Refer for confirmatory diagnosis or adjunctive test.
Offer to treat immediately.

CIN- Post Treatment Follow up
• Pap smear Q6 months for 18-24mths (ECC too if
the endocervix is involved)or
• HPV test + cytology smear at the 6th month(if
both are negative start annual follow-up)
• Rx failure dxed within in1-2 years mainly in
those with positive margin tissue
• Recurrent dysplasia – hysterectomy if fertility
completed

Cervical cancer
Cervical cancer is the most common gynecologic cancer
in women
Worldwide, cervical cancer is common, and ranks second
among all malignancies for women
Compared with other gynecologic malignancies, cervical
cancer develops in a younger population of women
The median age at diagnosis ~ 40 to 59 years
Most early cancers are asymptomatic
Advancing cervical cancer present with bleeding, watery
discharge, and signs associated with venous, lymphatic,
neural, or ureteral compression

Risks factors
Risk factors of cervical cancer are similar with
risk factors for CIN
Tumorigenesis of cervical Ca
Squamous cell carcinoma of the cervix typically arises at
the squamocolumnar junction from a pre-existing
dysplastic lesion, which in most cases follows infection
with HPV
Following tumorigenesis, the pattern of local growth is
exophytic if a cancer arises from the ectocervix, or may
be endophytic if it arises from the endocervical canal
Cervical cancer Contd.

Cervical cancer spread
Direct Extension predominant way
– involvement of the vagina, paracervical and
parametrial tissues, and the bladder and rectum.
– Obstruction of the ureters is particularly common
because of their proximity to the cervix.
Lymphatic Metastases
– to the pelvic, inguinal, and retroperitoneal nodes are
common.
Hematogenous Metastases
– to the lung, bone, and brain occur only late in the
course of the disease.

Histologic Types
Squamous Cell Carcinoma (85 %of all cervical cancers)
Adenocarcinoma (10-15%)
Adenosquamous carcinoma
Neuroendocrine tumors of the cervix(Large cell
neuroendocrine, Small cell carcinoma
Sarcomas of the cervix
Malignant lymphomas

Cx Ca – Diagnosis
Clinical Presentation
symptoms
• Many are asymptomatic for months ( eg pts with stage III and IV
disease may have symptoms of 3mths)
• Abnormal vaginal bleeding ( metrorrhagia, postcoital bleeding,
or postmenopausal bleeding).
• Profuse often malodorous discharge, especially when the
disease is advanced.
• Pain – uncommon unless the disease is advanced
• bladder and rectal symptoms- more advanced
• Chronic Pelvic bone pain Radiating to the leg- involvement of
pelvic side walls, L sacral and sciatic nerves
• Lower extremities edema- venous and lymphatic obstruction
• Ascitis - uncommon

Cervical Ca
Physical Exam- PV and speculum reveal different growth patterns
• Exophytic –Fungating (can also be polypoid/ Paoillary)
– Fryable,rough ,granular bleeding surface with foul smelling(FS)
discharge
– May be infected
• Ulcerating
– Usually irregular crater with necrotic bleeding base and FS
dischrge
– Sometimes clean punched out ulcer
• Infiltrative
– Develops beneath sstroma of the ectocervix,Causes cx
enlargement
– Smooth surfaced cx but nodular or firm consistency
– Feature of endocervical Ca before breaking through exocervical
mucosa
– Is also charactersstic of most postmenopausal Cx Ca
• Occult
– Uncommon, Cancer high in the endocervical canal invade the

Cervical Ca
Staging
• Clinical

FIGO Staging
Clinical
• Inspection, Palpation ( examination under GA)
• Colposcopy
• Endocervical cureatage
• Conization
• Proctoscopy, sigmoidiscopy, Cystoscopy,
• Biopsy confirmation of suspected bladder and
rectal involvement
• X ray (lung, skeleton), IVP, CT, MRI-not compnents of FIGO clinical
staging
• Lab
– CBC (anemia before surgery, Chemo or radiation), LFT
( liver met.), RFT ( Hydronephrosis), Urinalysis (

Testing Used during Cervical Cancer Staging
Testing To Identify:
Laboratory
CBC Anemia prior to surgery, chemotherapy, or
radiotherapy
Urinalysis Hematuria
Liver function Liver metastasis
Creatinine and BUN levels Hydronephrosis
Chest radiograph Lung metastasis
Intravenous pyelogram (IVP) Hydronephrosis
CT scan (abdomen and pelvis) Lymph node metastasis, metastasis to other
distant organs, and hydronephrosis
MR imaging Local extracervical invasion + those for CT
scan
PET scan Lymph node metastasis
Procedural
Cystoscopy Tumor invasion into the bladder
Proctoscopy Tumor invasion into the rectum
Examination under anesthesia Extent of pelvic tumor spread

FIGO Staging of Cervical Ca
Stage 0- Carcinoma insitu
Stage Ia (Microinvasive Disease ) Cancer invasion identified only
microscopically Measured stromal invasion with
• maximum depth of 5 mm and no wider than 7 mm* stromal
invasion not more than 7mm width and 5mm depth
– Microscopic Dx of cone biopsy ( cold knife cone biopsy is
preferable to LEEP)
– Dxed only Microscopically , No grossly visible lesion. ( All gross
lesions, even with superficial invasion, are stage Ib cancers.)
– Applies for SCCa only???? , no agreed def for microinvasive
disease of cx adenocarcinoma?????
– According to FIGO the overall volume of microinvasive Cx Ca
shouldnot exceed 350mm3
– LV involvement doesn’t alter the stage
Stage1a1 Max stromal invasion depth of 3mm, width 7mm
stage Ia2 Maximum Depth 3-5mm, Width max 7mm

FIGO Staging of Cervical Ca
• Stage Ib- clinically visible lesion
– Ib1- >Ia2- < 4cm
– Ib2- > 4cm
• Stage II- tumor extends beyond Cx, no lower 3rd vagina and
PSW involvement
– IIa- upper 3rd vagina, no parametrial involvement
– IIb- obvious parametrial extension
• StageIII- lower 3rd vagina, Pelvic side wall (PSW )involvement
– IIIa- lower 3rd vagina, No PSW extension
– IIIb- PSW extension or Hydroneprosis/ Non functioning kidney
• Stage IV- clinical involvement of B / R mucosa, spread beyond
true pelvis
– IV a- extension to adjascent organs
– IV b- distant metastasis

Cervical Ca
Prognostic Factors
• FIGO clinical stage ( the most important)
• other reported prognostic factors include
– Regional (pelvic) and distant (paraaortic) lymph
node metastases,
– Tumor volume
– Histologic tumor grade
• significant prognostic role in Cx adenocarcinoma
– lymphovascular space invasion (LVSI).

Treatment
Early stage disease( stage I to IIA)
surgery + Radiotherapy
Late stage disease ( stage IIB and beyond )
Radiotherapy, Chemotherapy (often pllative purpose)

ENDOMETRIAL HYPERPLASIA
and
CARCINOMA
SAMUEL BEZABIH
GY-OB RII,GUH
MESKEREM 2005-
Gondar
SAMUEL BEZABIH(MD)- MMeskrem 2005 1

Endometrial Hyperplasia (EHP)
EHP-Endometrial thickening with a proliferation of
irregularly sized and shaped glands and an
increased gland-to-stroma ratio (Ellenson, 2011a)
↑gland:stroma ratio compared with proliferative
endometrium
• In the absence of such thickening, lesions are best
designated as Disorderly Proliferative
Endometrium or Focal Glandular Crowding
EHP is the only known direct precursor of Endometrial ca
A continuum of histopathologic findings that range from
anovulatory endometrium to monoclonal precancers.

Endometrial Hyperplasias
Types of EHP
• Simple vs complex
=> based on the presence of architectural
abnormalities ( glandular complexity or crowding)
• Atypical vs Non-atypical
=>based on cellular atypia within glands (nuclear
enlargement, nucleoli, variation in nuclear size
and shape, and atypical mitoses.)
• Only atypical EHP are clearly associated with
the subsequent development of
adenocarcinoma.

EHP- Anna

WHO Classification of Endometrial Hyperplasia
Types Progression to Cancer(%)
I. Simple hyperplasia…………………………..1
II. Complex hyperplasia………………………..3
III. Simple atypical hyperplasia ….............8
IV. Complex atypical hyperplasia …………29

Endometrial Intraepithelial Neoplasia (EIN)
• Recently, the term EIN has been introduced to
more accurately distinguish the two very different
clinical categories of hyperplasia:
I. Normal polyclonal endometria diffusely responding
to an abnormal hormonal environment, and
II. Intrinsically proliferative monoclonal lesions that arise
focally and confer an elevated risk of adenocarcinoma
(Mutter, 2000).
• This nomenclature emphasizes the malignant
potential of endometrial precancers, in keeping
with similar precedents in the cervix, vagina, and
vulva

EIN
• Using the EIN schema, EHPs and EIN are
described distinctly
– EHP;nonatypical anovulatory or prolonged estrogen
exposed endometria .
– EIN; is used to describe all endometria delineated as
premalignant by a combination of three
morphometric features.
1. glandular volume,
2. architectural complexity, and
3. cytologic abnormality
• The EIN classification system is a more accurate
and reproducible way of predicting progression to
cancer (than the WHO) but has not been
implemented universally (Baak, 2005; Hecht, 2005).

EIN Schema - ACOG 2015
Pathologic criteria were used to develop three
disease categories:
1. Benign (benign endometrial hyperplasia),
2. Premalignant (EIN), and
3. Malignant (Em Adenoca, endometrioid
type, well differentiated)

SAMUEL BEZABIH(MD)- MMeskrem 2005
Diagnostic Criteria for Endometrial Intraepithelial Neoplasia*
ACOG Committee Opinion 2015
Nomenclature Topography Functional
Category
Treatment
Benign EHP Diffuse Prolonged
Estrogen Effect
Hormonal,
Symptomatic
EIN Focal progressing
to Diffuse
Precancerous Hormonal/
Surgery
Endometrial
Adenocarcinoma-
Endometroid,Well
Differentiated
Focal progressing
to diffuse
Malignant Surgery- Stage
based
*Previously known as Atypical EHP
9

Definitions of Endometrial Intraepithelial Neoplasia* Criteria ACOG
Committee Opinion 2015
* Previously known as atypical EHP
EIN *Criteria Comments
Architecture Area of glands greater than stroma ( Volume
percentage stroma < 55%)
Cytology Cytology differs b/n architecturally crowded
focus and background
Size > 1mm Maximum linear dimension exceeds 1mm
Exclude Mimics Benign conditions with overlapping criteria (ie
basalis, secretory, polyps, repair)
Exclude Cancer Carcinoma if maize-like glands, solid areas or
appreciable cribriforming
10

ENDOMETRIAL HYPERPLASIAS
Symptoms
– Dysfunctional bleedings,
– perimenopausal menstrual bleeding disorders
(menorrhagia, metrrorhagia---)
Diagnosis
– Sonography Highly built-up endometium
– Fractional curettage of endocervix and uterine
cavity.
– Diagnosis depends exclusively on the histological pattern,
and not on the volume of tissue.
– Hysteroscopy does not allow diagnosis.

HYSTEROSCOPY
– Hysteroscopy delivers an additional information
on the uterine cavity, the endometrium and the
location of tumors (polyps, carcinoma).
– A final diagnosis however is only possible
through fractional curettage and histology.

Hysterescopy
A.Simple, glandular-cystic B. Focal hyperplasia of the
hyperplasia endometrium

Typical EHP rx
Premenopausal women
• Low dose Progestin for 3-6 mths-MPA 10-20mg/d for 10-12 days Q mth
• OCP can also be initiated if no CI
• LNG IUD also found effective in small case series
Surveillence biopsy
– after 3-6 mths of rx , 2-6 weeks after bleeding with disscontinuation of P
– Shouldn’t be done while the woman is taking Progestin- confounds pathologic
Dx by Em remodelling
– Withdrawal bleeding should be completed before EmB
– Can be performed with LNG IUD insitu
• Response ~ 90% regression,
• if no residual hyperplastic Em- continue P and observe till menopause
• If HP persists- switch to higher dose ( MPA 40-100mgpo/d , Mesogestrel acetate
160mg/d) ; If refractory- Hysterectomy
Postmenopausal
• Make sure that atypia is excluded obtaining adequate sample
• Low dose cyclic or cont (2.5mg) MPA

Atypical EHP Rx
• Hysterectomy- the best rx for any age group
• Exceptions
– Strong fertility desire
– Poor surgical candidates
• These can be rxed with high dose progestin
with serial EmB Q 3 mths until resolution is
documented
• Post resolution- long-term P and surveillance
continue b/se of the potential for eventual
progression to Ca.

ENDOMETRIAL
CANCER
16

Endometrial Ca
 Uterine corpus malignancies - 3 types
A. Carcinoma-----epithelial
B. Sarcoma--------stromal/connective tissue
C. Carcinosarcoma
• mixed tumors demonstrating both epithelial
and stromal components and are also known
as malignant mixed müllerian tumors
(MMMTs)
 The latter two categories (B and C)
– rare
– tend to behave more aggressively and contribute
to a disproportionate number of uterine cancer
deaths

 Correlation between endometrial thickness and incidence of E. cancer
% carcinomas
Endometrial thickness in mm (postmenopausal women only)

Endometrial Ca -Epidemiology
 Age distribution of endometrial cancer (n = 1,797, FIGO Annual
Report).
 Median age 66 years, highest incidence 55 - 65 years,
 20 % before menopause, 5 % < 40 years.

Endometrial Ca Epidemiology
• 75% postmenopausal
• 25% - premenopausal-
– 20% > 40 , 5%< 40
• Risk factors
– most obese
– chronically anovulatory

Endometrial Ca- Epidemiology
• During their lifetime, 1 in 38 American women
(3 %) will develop endometrial cancer.
• In the US, 46,470 new cases are estimated to
develop in 2011, but only 8120 deaths are
expected.
• Most patients are diagnosed early and are
subsequently cured.
• As a result, among women, endometrial cancer is
– the 4th leading cause of cancer,
– but only the 8th leading cause of cancer
deaths(Siegel, 2011).
• The average age at diagnosis is in the early 60s
(Creasman, 1998; Farley, 2000; Madison, 2004).

Endometrial Ca
• Fortunately, patients typically seek medical
attention early due to vaginal bleeding, and
endometrial biopsy leads quickly to diagnosis.
• The primary treatment for most women is
hysterectomy with BSO and staging
lymphadenectomy.
• ¾ of patients will have stage I disease that is
curable by surgery alone.
• Patients with more advanced disease typically
require postoperative combination
chemotherapy, radiotherapy, or both.

Risk Factors for Endometrial ca
• Conditions triggering increased estrogenic environment
– Obesity
– Unopposed E therapy
– Granulosa cell tumors ( more associated with EHP than Eca
– Menstrual factors=> Anovulatory cycles, uninterrupted menstrual
cycle
– PCOS
– Nulli/low parity
– Early menarchae; Late menopause
• Older age (peak at 70)
• Family hx (HNPCC (lynch syndrome)-
– 40-60% life time risk in mutation carriers)-mostly premenopausal
<5% of all Em Ca are 20 to HNPCC
• Tamoxifen rx of breast ca-creates modest “ unopposed” E state,
– 2-3x↑ risk ,almost exclusively in postmenopausal women
• DM, HTN, GB disease
– (frequent seqeie of obesity/ chronic excess E environment)

Em Ca- Protective factors
 OCP
– 01yr use confers 30-50% risk reduction
– Risk reduction extends to 10-20 yrs
– Chemoprevention via progestin component
 LNG IUD is protective too-longterm
 Smoking
– Smokers have reduced risk of developing Em ca
– Multifactorial biologic mechanism which in part
involves
• reduced levels of circulating E through weight reduction,
• an earlier age at menopause, and
• altered hormonal metabolism.
– Both current and past smoking has a long-lasting
influence (Viswanathan, 2005).

Risk Factors for Endometrial Cancer
 most risk factors are associated with direct or indirect creation of an
excessive estrogen environment.

Clinical Forms
TYPE I (Estrogen Dependent)
– The most common(~75%) and most indolent
– Usually in younger and perimenopausal women
– Lower grade nuclei (well differentiated, high
estrogen receptor content)
– derived from atypical endometrial hyperplasia.
– Endometroid histologic cell type
– Phosphatase and tensin homologue mutation
– Good prognosis

Clinical Forms
TYPE II
–More lethal variety, 10% of all cases
– In older post menopausal women
– Aggressive high grade nuclei (less/poorly
differentiated) or serous/papillary, clear cell
Histology
– no precursor lesion
– P53 tumor supressor mutation
– Underlying (back ground) endometrium is
Atrophic/ associated with polyps
– No clear epidimologic profile

TYPE I Vs Type II( Germ. PPT)
•
FEATURES TYPE I TYPE II
ESTROGEN DEPENDENCE E-Dependent E-independent
ASSOCIATION WITH
MENOPAUSE
Pre/Postmenopausal Post Menopausal
DIFFRENTIATION Grade I/II Grade III
MYOMETRIAL INVASION Minimal Deep
HYPERPLASIA Yes No
Sub types Endometroid
adenocarcinoma,
secretory
Adenosquamous,
clear cell, serous
prognosis good Poor

pathology
WHO Histologic Classification of Endometrial Carcinoma 29

Endometrial Ca Diagnosis
Symptoms
• Prolonged, heavy, irregular menstruation
• Postmenopausal V bleeding ( 5-10% likelihood)
• Abnormal vaginal discharge may be another
symptom in older women.
• In more advanced disease, pelvic pressure and
pain may reflect uterine enlargement or extra-
uterine tumor spread.
• Patients with serous or clear cell tumors often
present with signs and symptoms suggestive of
advanced epithelial ovarian cancer

Endometrial Biopsy
• Office pipelle biopsy,
– if inadequate D and C
• Outpatient hysteroscopy is more sensitive for
focal endometrial lesions and thus has proved
less helpful in diagnosing hyperplasia (Ben Yehuda,
1998).
• Hysteroscopy is shown to have a risk of
Intraperitoneal contamination with malignant
cells.

Pap smear
• Not sensitive, ~ 50% False Negative
• LBC- better detection of abnormal cells
• inadequate for shift of practice
.

Lab and Imaging
 Ca 125
 CXR
 CT

Histologic Grade
• Grading is determined microscopically by the
architectural growth pattern
– Arch is judged by the percentage of differentiated
(glandular) versus nondifferentiated (solid) elements
within the tumor specimen.
• If nuclear atypia is advanced (NG 3) relative to the
architectural grade, then grades 1 or 2 will be
raised by one level
this modification was shown to have prognostic value
in the GOG study(protocol #33) (Zaino, 1995).
– The nuclear grade depends on the appearance of the
nucleus, e.g., size of nucleus, chromatin pattern, and is
more subjective
• Acc. to FIGO Nuclear Grading is used for all serous
and clear cell adeno cas

Histologic Grading
• The most widely used grading system for Em
Ca is the three-tiered FIGO system.
• Grade 1:
– lesions typically are indolent with little
propensity to spread outside the uterus or
recur.
• Grade 2:
– tumors have an intermediate prognosis.
• Grade 3:
– cancers are associated with an increased potential
for myometrial invasion and nodal metastasis.

Histopathologic Criteria for Assessing Grade
GRADE DEFFINITIONS(growth pattern)
1 < 5% of a non-squamous or non-morular
solid growth pattern
2 6–50% of a non-squamous or nonmorular
solid growth pattern
3 > 50% of a non-squamous or nonmorular
solid growth
 Areas of squamous differentiation are not considered to be
solid tumor growth.
36

Patterns of Spread
• Endometrial cancers have several different potential
ways to spread beyond the uterus (Morrow, 1991).
• Type I endometrioid tumors and their variants most
commonly spread, in order of frequency, by:
1. Direct extension,
2. Lymphatic metastasis,
3. Hematogenous dissemination, and
4. Intraperitoneal exfoliation.
• Type II serous and clear cell carcinomas have a
particular propensity for extra-uterine disease, in a
pattern that closely resembles epithelial ovarian
cancer.
• In general, the various patterns of spread are
interrelated and often develop simultaneously.

Spread Pattern
• Lymphatic channel invasion and metastasis to
the pelvic and paraaortic nodal chains can
follow tumor penetration of the myometrium.
– The lymphatic network draining the uterus is
complex, and patients can have metastases to any
single nodal group as well as combinations of
groups (Burke, 1996).
– This haphazard pattern is in contrast to cervical
cancer, in which lymphatic spread usually follows
a stepwise progression from pelvic to paraaortic
to scalene nodal groups.

Spread Pattern
• Hematogenesis dissemination
– most commonly results in metastases to the
lung and less commonly, to the liver, brain,
bone, and other sites.
– Deep myometrial invasion is the strongest
predictor of this pattern of spread (Mariani,
2001a).
• Retrograde transtubal transport of exfoliated
endometrial cancer cells is one mechanism
by which malignant cells reach the peritoneal
cavity.

Spread Pattern
• Serosal perforation of the tumor is another possible
pathway.
• Most types of endometrial cancer cells found in the
peritoneal cavity disappear within a short time and
have low malignant potential (Hirai, 2001).
• Alternatively, in the presence of other high-risk
features, such as adnexal metastases or serous
histology, widespread intraabdominal disease may
result.
• Port-site metastasis is a rare but potential method of
cancer spread.
– Martínez and coworkers (2010)evaluated nearly 300
laparoscopic staging procedures for endometrial cancer.
Port-site metastases complicated 0.33 percent of cases.

Surgical Staging
• Peritoneal washing/asciteis sampling
• Pelvic and abdominal exploration and resection
of visible lesion
• TAH + BSO
• Pelvic and paraaortic lymphadenectomy
• Patients with low grade T seem at low risk for LN
met ( G1 and 2 Endometroid T, <50%MM, < 2cm T Diam-
Preop biopsy + intraop FS) may not need LN
dissection (ACOG 2015)
• UPSC (uterine papillary serous ca) histology
should have extended surgical staging with an
infracolic omentectomy and bilateral peritoneal
biopsies of the pelvis, percolic gutter, and
diaphragm and resection of any met as in Ov Ca.

I. Tumor confined to corpus uteri
Ia:-No or < ½ MM invasion
Ib:-> ½ Myometrial (MM)
II.Cx stromal invasion, but no
extension beyond UX (Ecx
glandular involvement alone- S1)
III.Local regional spread of T
IIIa.Serosa of corpus and/or
adnexa.
IIIb.Vagina and /or parametrium
IIIc. Met to pelvic or Paortic LN
IIIc1- Positive Pelvic LN
IIIc2-Paortic LN + Pelvic LN
IV.T invades bladder/bowel
mucosa (distant
metastasis)
– Iva.Bladder and /or bowel
mucosa invasion
– Ivb.Distant Metastasis
•Any stage can be Grade 1, 2 or 3
•Endocervical G involvement alone- no
more S2
•Positve cytology doesn’t change stage,
reported separately
FIGO Staging of Endometrial Ca- ACOG 2015

Poor Prognostic Variables in Endometrial Cancer
• Advanced surgical stage
• Older age
• Histologic type:
– UPSC or clear cell adenocarcinoma
• Advanced tumor grade
• Presence of myometrial invasion
• Presence of lymphovascular space invasion
• Peritoneal cytology positive for cancer cells
• Increased tumor size
• High tumor expression levels of ER and PR

Treatment
• Primary RX
– Primary Surgical rx (staging)
• Hysterectomy + Bilateral Salpingoophorectomy
– Primary radiation therapy
– Primary hormonal therapy
• Adjuvant
– Chemotherapy
– Radiation
– Hormonal

Surgical Rx
• Hysterectomy, BSO with surgical staging
• Few CIs to surgery:
• Fertility desire,
• Massive obesity,
• High operative risk,
• unresectable tumor
– Often Extrafacial (simple) Hysterectomy is
sufficient
– Class III Hysterectomy may be preferable if there
is clinically obvious extension of Em Ca to Cx.
– VH + BSO- an option for those who can’t tolerate
systematic S staging due to comorbidities

Distribution of Endometrial Cancer by FIGO Stage
(n =5281 patients)
47

Endometrial Cancer 5-Year Survival Rates for Each Surgical
Stage (n = 5562 Patients)

Post Op Surveillance
• Follow up visit Q 3-6 mths for 2yrs, then Q6mths for 01
year , annually there after.
• At each visit;
– Hx on symptoms of recurrence V bleeding, pelvic pain,
wt loss, lethargy
– Thorough speculum, pelvic and RV exam
• Not recommended are:-
– Vaginal cytology and annual CXr -recurrences are detected
by clinical exam, Cxr low utility in detecting recurrence.
– Routine radiologic exm (CT,PET) unless in suspicion of
recurrence (ACOG 2015)
• Advanced disease that requires chemo/Radiorx warrant
more aggressive monitoring.
– Ca125 for UPSC
– Intermittent CT? MRI

Adjuvant Chemorx
• For advanced or recurrent disease
• Only three cytotoxic drugs with definite
activity have been identified to date:
– doxorubicin, cisplatin, and paclitaxel (Barrena Medel, 2009).
• Other agents, 5-fluorouracil, vincristine,
ifosfamide, and ixabepilone, have possible
activity based on collected data (Miller, 2009a).
• TAP Paclitaxel (Taxol),doxorubicin
(Adriamycin), and cisplatin chemotherapy is
the adjuvant treatment of choice for
advanced endometrial cancer following
surgery. SAMUEL BEZABIH(MD)- MMeskrem 2005 50

Treatment of UPSC
• Comprehensive surgical staging
–Peritoneal washing
–TAH + BSO
–Infracolic omentectomy
–pelvic/and Para aortic LN dissection
–Peritoneal biopsy
–Aggressive debulking

Treatment of UPSC ……
Postop. Follow up
• Stage IA
– simple observation
• Stages Ib and Ic
– chemoradio ( taxol + Carboplatin 3-6 cycles and
vaginal brachytherapy)
• stageII
– benefit from chemo +/- radio
• Stage III
– prone to have recurrence ,Chemoradiatio Taxol
cisplatin+ tumor directed radio
• Stage IV
– debulking- prognostic, atleast 6cycles of Taxol and
Cplatin SAMUEL BEZABIH(MD)- MMeskrem 2005 52

Prevention of Endometrial Ca
Screening
• No role for those with average or increased
risk
• Only for high risk group>35, potential
HNPCC mutation carriers ( family Hx---)
• Genetic counselling to identify those who may
benefit from specific germ line testing
• EmCa- common ‘sentinel Ca’ for Lynch S (Em,
Colonic,Small B, ureter, Renal Pelvis, Ovarian Ca) Gynecologists
play a pivotal role in identification of those
with the syndrome

Prevention of Endometrial Ca
Prophylactic Surgery
• Since women with HNPCC have such a high
lifetime risk of developing endometrial cancer
(40 to 60 %) prophylactic hysterectomy is
another option.
• In a cohort of 315 HNPCC-mutation carriers,
Schmeler (2006) confirmed the benefit of this
approach by reporting a 100-percent risk
reduction.
• In general, BSO should also be performed due
to the 10--12% lifetime risk of ovarian cancer.

Prevention of Endometrial Cancer
Can phyto-estrogens prevent EC ?
(Xu WH et al. BMJ 328, 2004:1285-1288)
• Case control study 832 patients
• RR for EC 0.67 in group with highest soya intake
Explanation:
• Soya contains “isoflavones“ (Genistein, Daidzein)
• Isoflavones block the estrogen receptor and are
• therefore not phytoestrogens, but phyto-SERM‘s
(selective estrogen receptor blockers)
• Therefore women with high BMI profit the most in
the study!

Uterine Sarcomas
56

Uterine Sarcomas
• Arise from myometrium or CT element of
the Em
• ~8% of Ux corpus cancers
• Rapidly growing
• early lymphatic or hematogenous spread
• poor prognosis .

Pathology
WHO classification of UX mesenchymal Tumors
Pure mesenchymal Ts
• Smooth Muscle Tumors
– Leiomyoma
– Leiomyosarcoma
– Smooth M T of
uncertain malignant
potential (STUMP)
• Endometrial Stromal Ts
– Em Stromal nodules
– Em stromal sarcoma
– High grade
undifferentiated
sarcoma
Mixed epithelial and
Mesenchymal Tumors
• Malignant Mixed
Mullerian Tumors
(MMMT)/
Carcinosarcoma
• Adenosarcoma (benign
epithelial and
sarcomatous
mesenchymal elements)

Pathology – WHO classification of UX mesenchymal Tumors
• Homologus Ts Ts that differentiate into a tissue
similar with the one in which it is developing
• Hetrologus Ts differentiate to a tissue unlike that in
which it developed
• Pure sarcomas
– Almost all are homologus differentiate into
mesenchymal tissue present in the ux i.e, SmM ( LMS) and
Endometrial stroma ( EST)
– Hetrologus eg Uterine Chondrosarcoma exceedingly rare
• MMMTsThe mesenchymal component of can be
either homologous or heterologous, reflecting the
potentiality of the uterine primordium.
– heterologous elements of MMTs may include
rhabdomyosarcoma , chondrosarcoma, osteosarcoma, or
liposarcoma SAMUEL BEZABIH(MD)- MMeskrem 2005 59

Uterine Sarcomas- RFs
• Because of the small number of these tumors,
the epidemiology of uterine sarcomas has not
been studied extensively.
• As a result, relatively few risk factors have been
identified, but they include
– chronic excess estrogen exposure,
– tamoxifen use,
– African-American race,
– prior pelvic radiation.
• RFs parallel those observed in endometrial
carcinoma
• In contrast, combination OCP use and smoking
appear to lower the risk for these tumors.

USs- Dx
SS
– VB + N sized Ux commonest presentation
• Pelvic/ abdominal pain
• Rapid uterine growth
• Prolapsed sarcomatous polyp through effaced Cx
• Foul smelling discharge
• GI and GU complaints
SS may mimic degenerating myoma with necrosis

Uss- Dx
Dx of Most cases post op
(hysterectomy/myomectomy) histopathologic
study
Em Sampling ( Office biopsy/ D and C)
• Less sensitive than in Em ca
– Leiomyosarcomas~ 25- 50% correct Dx
due to Myometrial origin of the tumor
– Endometrial stromal nodules and sarcomas may
be undetectable by pipelle biopsy, especially if the
neoplasm is entirely intramural
– MMMT better dx ( usually carcinomatous
component is detected)

Dx
Histopathologic Dx of Leiomyosarcoma– controversial,
includes
• Mitotic figures frequency (10 MF per high power field) ,
• Nuclear atypia,
• Coagulative Tumor Cell necrosis presence
No universally accepted grading system
Diagnostic Criteria the following table:-
Coagulative TCN Mitotic Index Degree of Atypia
Present > 10MF/ 10HPF None
Any Diffuse Significant
Absent > 10MF/ 10HPF Diffuse Significant
63

Uss Dx
Laboratory Tests
– Ca125
• Elevated in selected pts may be used as rx markers
• Elevation may not correspond with T burden limited utility
Imaging
– CT and MRI ( unlike Em Ca only Cxr is needed) affect
management for S dxed preoperatively
– Abdominopelvic CT
• Soft tissue plane disruption tumor resectablity is determined
• Extrauterine metastasis
– MRI ( if dx is is questinable in CT)
• Differentiation b/n uterine sarcoma and benign mimic
• Eg- whether a pedunculated mass is leyiomyoma or Em ST
– PET- effective monitoring after rx completion
– US- less helpful

Treatment
• surgery
• Adjuvant chemotherapy

Endometriosis
• Presence of endometrial tissue (glands
and stroma) in extrauterine sites
• Chronic, estrogen dependent benign
disorder
• Commonly involves pelvic structures, but can
develop in any part
• Common in active rep. Age  25-35
• Rare during pre/postmenarchae,
postmenopause (if not on HRT) estrogen
dependence of growth

Endometriosis- DDx.
Gynecologic
• PID
• Tubo-ovarian abscess
• Salpingitis
• Endometritis
• Hemorrhagic ovarian cyst
• Ovarian torsion
• Primary dysmenorrhea
• Degenerating leiomyoma
Nongynecologic
• Interstitial cystitis
• Chronic UTI
• Renal calculi
• Inflammatory bowel disease
• Irritable bowel syndrome
• Diverticulitis
• Mesenteric lymphadenitis
• Musculoskeletal disorders

Endometriosis- Risk Factors
• Nulliparity
• Early menarhae/ late menopause
• Short menstrual cycles
• Prolonged menses
• Anatomic Defects
– Non-communicating uterine horn,
– imperforate hymen, and
– transverse vaginal septum
• More association with thin, tall habitus and low BMI
• Surgery (CS, Hysterectomy)- anterior abdominal wall
seeding
• Genetic Factors /Familial clustering

Endometriosis- Risk Factors
Environmental Toxins
• Numerous studies suggest the role of ET
exposure in the dv’t of endometriosis.
• Most commonly implicated toxins are 2,3,7,8-
tetrachlorodibenzo-p-dioxin (TCDD) and other
dioxin-like compounds (Rier, 2003).

Endometriosis
• Protective Fs
– Multiple birth
– Extended lactation intervals
– Late menarche

Endometriosis- Pathogenesis
Not well understood, but theories with some evidences
Theories for the Histogenesis of Endometriosis
• Transtubal regurgitation or retrograde Menstruation
• Direct implantation of endometrial cells
• Metaplasia of coelomic epithelium
• Lymphatic dissemination
• Hematogenous spread
• Activation of embryonic cell rests
• Metaplasia of urothelium
• Hereditary factor
• Immunologic factor

Endometriosis-Pathogenesis
Retrograde menstruation (RGM)
• Reflux of EM tissue through FT to peritoneal
cavity, during menstruation adherence to
peritoneal mesothelium and proliferation with
d’vt of blood supply
• Evident from ↑ed incidence of E in those with
menstrual outflow obstruction
• Uterine hyperperistalsis and dysperistalsis
have been noted in women with Ems and
resulted in subsequent ↑ed endometrial reflux

Endometriosis- Pathogenesis
RGM- evidences
RGM occurs in 70% to 90% of women, and it may be more common
in women with E than in those without the disease .
E is most often found in dependent portions of the pelvis—the
ovaries, the anterior and posterior cul–de–sac, the USLs, the
posterior uterus, and the posterior broad ligaments
E has been found in 50% of Rhesus monkeys after surgical
transposition of the CX to allow intra–abdominal menstruation.
Increased RGM by obstruction of the outflow of menstrual fluid from
the uterus is associated with a higher incidence of E in women.
Women with shorter intermenstrual intervals and longer duration
of menses are more likely to have RGM and are at higher risk for E.

Altered Immune system
• Deficient CMI to to recognize endometrial
tissue in abnormal site
• Defective NKC – less cytotoxicity against
autologous EM tissue
• Cytokines and growth factors released by
implants and inflammatory cells that favor
growth of implants on peritoneal surfaces

Lymphatic/vascular spread of EM tissue-
• few experimental studies
Evidences
• Endometrial implants in the lungs
• E in retroperitoneal space (rich L drainage)
while absent in other areas
• E in unusual locations- groin, perineum
• Lymphatic dissemination of E Ca

Coelomic Metaplasia Theory
• Peritoneal epithelium (mesothelium) are
pluripotential- capable of proliferation and
differentiation
• Ovaries and Mullerian ducts( progenitor of
endometrium) are derived from coelomic
epithelium explanation for ovarian endometriosis
via coelomic metaplasia

Most common sites nvolved with E in
decreasing order of frequency
•Ovaries-
•cul-de-sac (ant.and post)-
• posterior broad ligaments-
•US ligaments-
•Uterus
•Fallopian tubes
• Sigmoid colon and appendix and
• Round ligaments
Less common sites are
•vagina,
•cervix,
• rectovaginal septum,
•cecum, ileum
•inguinal canals,
•abdominal or perineal scars,
• urinary bladder,
• ureters, and umbilicus
Rarely, endometriosis has been reported in
•breast,
• pancreas,
• liver
• gallbladder,
• kidney,
•urethra,
•extremities,
• vertebrae,
•bone, peripheral nerves, lung, spleen,
diaphragm , and CNS
Sites Of Endometriosis
Multiple sites are involved in most patients

Common locations of endometriosis within the abdomen and pelvis.
(Redrawn after Olive, 2005.)

Endometriosis-Pathology
Gross
– Implants have variable appearance and size
On Peritoneum
• raised flame-like patches, whitish opacifications, yellow-brown
discoloration, translucent blebs, or reddish or reddish-blue
irregularly shaped islands .
• “powder burns” - blue/brown lesions “The peritoneal surface
may be scarred or puckered, or may give rise to nodules or cysts.
• Rarely, endometriosis appears as a polyploid mass, which may
mimic the appearance of malignant tumor.
• Dense fibrous adhesions may be present, and signify severe
disease
• In young women,Ems may have an atypical appearance
characterized by nonpigmented or vesicular lesions, peritoneal
windows, and puckering NOVAC

• E of the ovary may present as
– Superficial implants, or
– Endometriomas -cyst-like pelvic masses that
contain blood, fluid, and menstrual debris.
– endometriomas often have thick fibrotic walls and
surface adhesions, and are usually filled with a
thick syrup-like chocolate colored material. They
are often firmly adherent to adjacent structures.
i.e. unlike most hemorrhagic physiologic ovarian
cysts,
• Both ovaries are involved in 1/3rd of cases

• Endometriomas are cystic endometrial lesions
contained within the ovary.
• Typically, they have the appearance of smooth-
walled, brown cysts filled with thick, chocolate-
appearing liquid .
• These ovarian masses may be unilocular, but are
often multilocular when >3 cm in diameter

EndometriosisClassification
Stage I-isolated implants and no
significant adhesions
Stage II superficial implants < 5 cm in
aggregate, scattered on the peritoneum
and ovaries. No significant adhesions
Stage III multiple implants, both superficial and
invasive. Peritubal and periovarian adhesion
Stage IV multiple S and Deep implants,
including large ovarian endometriomas. Filmy
and dense adhesions are usually present.

Clinical Features
• Symptoms of E may overlap with that of other
gyn. disorders or may be seen in healthy
individuals  often results in diagnostic delay
of several years
• Women with E may be completely
asymptomatic

Symptoms Associated with Endometriosis
Pelvic
Dysmenorrhea
Dyspareunia
Chronic pelvic pain
Sciatica
Premenstrual spotting
Gastrointestinal
Constipation
Diarrhea
Dyschezia
Tenesmus
Hematochezia
Urinary
Flank pain
Back pain
Abdominal pain
Urgency
Frequency
Hematuria
Pulmonary
Hemoptysis
Catamenial chest pain
Pneumothorax
Infertility

Symptoms
PAIN
• The most common symptom  (3/4th of symptomatic
patients have pelvic pain or dysmenorrhoea)
• Cyclic/chronic
• Severity is associated with depth of infiltration rather than
disease stage (volume)
• Pain in E is may be 20 to
– Bleeding
– Inflammatory/pain mediators
– Invasion neuronal invasion of endometriotic implants that
subsequently develop a sensory and sympathetic nerve supply,
which may undergo central sensitization  cause for
hyperxciablity of the neurons and persistence of pain after
surgical excision of E implants

Symptoms-Pain
Dysmenorrhea –
• Cyclic pain with menstruation .
• Typically, endometriosis-associated dysmenorrhea
– precedes menses by 24 to 48 hours and
– is less responsive to NSAIDs and COCs.
• more severe in comparison with primary
dysmenorrhea
• Pain severity correlates with depth of
infiltration (>5mm below pritoneal surface
more severe dysmenorrhoea)

Symptoms- Pain
Dyspareunia –
• most often related to RV septum or US disease,
• less commonly associated with ovarian involvement.
• During intercourse, tension on diseased US
ligaments may trigger this pain (Fauconnier, 2002).
• Although some women with E may describe a history
of dyspareunia since coitarche, E-associated
dyspareunia is suspected if pain develops after years
of pain-free intercourse (Ferrero, 2005).
• The degree of discomfort, however, appears to be
independent of disease severity (Fedele, 1992).

Symptoms- Pain, WILL GYN.
Urinary symptoms
• Dysuria -Although less frequent symptoms of
endometriosis, bladder complaints of painful
urination as well as cyclic urinary frequency and
urgency may be noted in affected women.
• Endometriosis may be suspected if these symptoms
are concurrent with negative urine cultures.
• colicky flank pain or gross hematuria in association
with Ureteral endometriosis.
• Endometriosis-related hydroureteronephrosis may
result in loss of renal function

Symptoms-Pain,
Defecatory Pain –
• less common than the other manifestations of
pelvic pain
• typically reflects rectosigmoid involvement
with endometriotic implants (Azzena, 1998).
• Symptoms may be chronic or cyclic, and they
may be associated with constipation,
diarrhea, or cyclic hematochezia (Remorgida, 2007

Symptoms-Pain
Noncyclical Pelvic Pain/ Chronic pelvic pain
• is the most common symptom associated with E.
• Approximately 40 to 60% of women with CPP are
found to have E at the time of laparoscopy (Eskenazi,
1997).
• The focus of chronic pain may vary from woman
to woman.
• If the RV septum or USLs are involved, pain may
radiate to the rectum or lower back.
• Alternatively, pain radiating down the leg and
causing cyclic sciatica may reflect posterior
peritoneal endometriosis or direct sciatic nerve
involvement (Possover, 2007; Vercellini, 2003a; Vilos, 2002).

Symptoms
• Infertility/subfertility
• Incidence of E in subfertile women~20 -30%
• Infertile women appear to have more E than
fertile controls
 13-33% Vs 4-8% (D’Hooghe, 2003; Strathy, 1982)
Infertility – more with severe forms
• One investigation comparing mild, moderate, and severe endometriosis
revealed a monthly fecundity rate of 8.7 % in those with mild disease, 3.2%
with moderate disease, and no pregnancies with severe disease (Olive,
1985a).
association with minimal/Mild disease- evidences show lower fecundity but not
conclusive
RCT on improvement woth surgocl exicision o mnimal/Mild disease conflicting

Endometriois- Infertility
Moderate to Severe E (Stages III and IV)
• Few studies on Fucundity rate of severe E
• One investigation(Olive, 1985a) comparing mild,
moderate, and severe Es revealed a monthly
fecundity rate of
– 8.7% in those with mild disease,
– 3.2% with moderate disease, and
– no pregnancies with severe disease
• No well designed trials on effects of surgical therapy
of severe E on fucundity
– But cumulative preg rates reach 30% after surgical
excision greater than in expectant management
(Adamson, 1993; Osuga, 2002).

E-Infertility Pathogenesis(Will 2nd )
• Adhesion- distortion of ovarian and tubal archtechture (mild to
severe E)
– Mechanical impairment of ovulation, Ocyte pickup and transport
Other Suggested Mechanisms
• Impaired Folliculogenesis and embryogenesis
– During IVF , embryo of Etic women exhibits significantly fewer no of
blastomer and arrested embryo development compared with that of
women with tubal infertility  decreased developmental competence
of oocytes from ovaries of women with E
• oocyte No may be decreased in women with Es (Suzuki,2005)
• Apoptosis, altered follicular environment (steroidogenesis) may
cause the ocyte developmental competence defect
Endometrial Effect of E
• Women with E- Em development abnormalities implantation
defects a possible cause of subfertility
– EG -Gene expression abnormalities- AV B3 integrin is deficient in the
peri-implantation Em Decreased uterine receptivity(Lessey, 1994).
– Possible role of periimplantation Em Apoptosis

E-Infertility Pathogenesis
Other Possible Factors
• Abnormalities in inflammatory and cytokine
functions
• Altered sperm function (motility, acrosomal
reaction- binding to ZP)
• Increased sperm phagocytosis

Infertility-possible mechanism,
Telinde
Mechanical interference
Pelvic adhesions
Chronic salpingitis
Altered tubal motility
Distortion of tuboovarian
relations
Impaired oocyte pickup
Alterations in peritoneal fluid
Increased PG concentration
Increased number of activated
macrophages
Increased cytokines producti
Enhanced sperm phagocytosis
Abnormal systemic immune system
response
Increased cell-mediated gamete
injury
Increased prevalence of
autoantibodies
Antiendometrial antibody
production
Hormonal or ovulatory dysfunction
Defective folliculogenesis
Luteinized unruptured follicle
syndrome
Hyperprolactinemia
Luteal phase deficiency
Fertilization or implantation failure
Early spontaneous abortion

EndometriosisDx-Physical Findings
• variable and depend upon the location and size of implants
• There are often no abnormal findings on PE.
• the most common finding is tenderness when palpating
the post.fornix.
• Other frequent findings include:
– Localized tenderness in the posterior cul-de-sac ( PCS-pouch
of Douglas) orUSLs
– Palpable tender nodules in the PCSc, USLs, or RV septum
– Thickening and induration of uterosacral ligaments
– Pain with uterine movement
– Tender, enlarged adnexal masses
– Fixation of adnexa or uterus in a retroverted position.

Endometriosis Dx
Physical Findings
• Nongynecologic findings more common in
women with endometriosis than unaffected
women include:
– red hair,
– freckles,
– skin sensitivity to sun exposure, and
– dysplastic nevi

Endometriosis-Dx-
Laboratory Tests
• Ixs to exclude other causes of pelvic pain
(STI/PID, UTI) .
• Initially tests
– CBC, UA and urine cultures,
– vaginal cultures, and cervical swabs .

Laboratory Tests
Ca 125-
• Women with E often have high serum CA 125 concentrations .
• In one study, 54 % of women with stage III or IV E had a CA
125 level > 35 U/mL
• the mean serum CA 125 conc in stage I, II, III, and IV disease
were 19, 40, 77, and 182 IU/mL, respectively [93].
• Levels >100 IU/mL were primarily associated with the
presence of extensive adhesions or ruptured endometrioma.
• Serum CA 125 is not a sensitive indicator of E with the best
correlation seen in women with stage III or IV disease [94].
• However, knowledge of an elevated preoperative CA 125
concentration may be useful for selecting women who are at
high risk for bowel injury because of dense pelvic adhesions,
and thus most likely to benefit from preoperative bowel
preparation [9

Endometriosis Dx-
Diagnostic Imaging
• Trans vaginal US
• MRI
• Diagnostic Laparoscopy

Transvaginal sonogram demonstrating ovarian endometrioma. A cyst with diffuse
internal low-level echoes is seen.

• Endometriomas in TVUS often present as
cystic structures with low-level internal
echoes, and occasional thick septations,
thickened walls, and echogenic wall foci

Treatment
• Treatment for endometriosis depends on
– the woman's specific symptoms,
– severity of symptoms,
– location of endometriotic lesions,
– goals for treatment, and
– desire to conserve future fertility.
Importantly treatment varies depending on the
presenting symptom Infertility Vs Pain,
– If infertility  fertility-preserving treatment without
ovulation suppression will be required.
– In contrast, if the patient has severe, recalcitrant pain and
has completed childbearing, definitive surgery may be
warranted.

Endometriosis- Treatment
Treatment options
• Expectant management
• Medical management
– NSAIDS
– OCPS
– Progestins
– Androgen-Danazol
– GnRH agonists
– Aromatase inhibitors
• Surgical management

Adenomyosis
• Adenomyosis is defined as presence of endometrial
tissue within the myometrium, at least 1 high-power
field from the basis of the endometrium.
• Enlarged ( usually < 12wks), spongy uterus
• Diffuse or Focal
• Origin- basalis layer
–  no proliferative and secretory changes little
hemmorhage within adenomyosis
• Adenomyosis, endometriosis, and uterine
leiomyomas frequently coexist.
• the average age of symptomatic women is usually
older than 40 years.
• Increasing parity may be a risk factor according to one study

Adenomyosis
Symptoms
• often asymptomatic.
• Symptoms typically associated with adenomyosis include
– excessively heavy or prolonged menstrual bleeding,
– dyspareunia, dyschezia, and dysmenorrhea.
• Symptoms often begin up to a week before the onset of a
menstrual flow and may not resolve until after the cessation
of menses
• 10ly develops in multiparous older women (>35) contrary to
the young age devlopment of Emetriosis
Signs
• The uterus is diffusely enlarged, although usually less than 14
cm in size, and is often soft and tender, particularly at the
time of menses.
• Mobility of the uterus is not restricted, and there is no
associated adnexal pathology

Adenomyosis- DX
• Adenomyosis is a clinical diagnosis and can be
confirmed only by pathology review.
• 20dysmenorrhea + diffuse uterine enlargement + a
negative pregnancy test results ~ adenomyosis;
• Confirmation- Pathology after hysterectomy
– In one study to confirm preoperative diagnosis of
adenomyosis before hysterectomy, the clinical diagnosis of
adenomyosis was confirmed in only 48% of the cases
• Imaging studies not recommended routinely
– not definitive (negligible improvement in diagnostic
accuracy) and cost

Adenomyosis -Management
• Hysterectomy- definitive for relief of 20
dysmenorhoea
• NSAIDS, OCPS, Menstrual suppression using
progestin contraceptives
• The same rx prortocol as endometriosis

Malignant Ovarian Tumors
• Classified based on their cells of origin
– Epithelial ovarian Tumors
– Germ Cell Ovarian Tumors
– Sex cord Stromal Tumors
– Tumors metastatic to the ovary
• From GIT(krukenberg),breast, endometrium
• Approximately 90% of malignant ovarian tumors in adults are of epithelial
origin followed by sex cord -stromal tumors (6%) and germ-cell tumors

Ovarian Ca -CGO
• 6% of all cancers in women
• 5th most frequently occurring fatal ca in women in US
• At some time during their lives, 1% to 2% of all women develop
ovarian carcinoma.
• The risk increases after 40 years of age, with a peak incidence
between 55 and 60 years of age, closely paralleling the peak
incidence of menopause in Western countries
• Develop in
– 1 of every 68 women in US
– App. 14 of every 1000 women in the US older than age 40 years but
only 4 of the 14 will be cured
• 27% of gynecologic cancers but cause of more deaths than any
other female GT cancer
– 53% of all deaths from Gynecologic cancers
– 1death Q 44 min in US

Epithelial Ovarian Ca- Histology
Will Gyn 2nd

Epithelial Ovarian Ca
• Predominant histologic types of EP Ovarian
malignant Tumor:
– Serous cystadenocarcinoma 42%
– Mucinous cystadenocarcinoma 12%
– Endometrioid carcinoma 15%
– Undifferentiated carcinoma 17%
– Clear cell carcinoma
• Are either franlky invasive or border line (Low
Malignant Potential)

Risk Factors
• Nulliparity
• Family Hx
• Age
– Rare before 40
– Peak at 65- 75
• Early menarchae
• Late Menopause
• Estrogen
• Clomiphen
• Talc use
Protective Factors
• Parity
• Breast feeding
• OCP
• Late menarchae
• Early Menopause
• BTL
• Hysterectomy

Familial ovarian Ca
• ~5-10% of O Ca patients have +VE family Hx
• Life Time risk
– ~5% if One 10 first degree relative has O Ca
– ~7% if > 2 10 relatives
• autosomal Dominant iheritance of Germline
Mutations of BRCA1 and BRCA2 account for
much of the hereditary O Ca
– BRCA1 Tumor Supressor Gene mutation ( q 17)
responsible for 80- 90% of familial O Ca
– BRCA2 TSG ( q 13) ~15% of hereditary O Ca

Familial ovarian Ca -Syndromes
1.Hereditary Breast Ovaria Ca Syndrome(HBOC)
– Early age (<50) onset breast and O cancers
– ~75- 90% of familial O Cas
2. Hereditary Site Specific Ovarian Ca Syndrome (HSSOC)
– Early onset O ca
– Commonly serous histology
– ~5% of hereditary O Cas
3.Nonpolyposis Hereditary Colon Cancer (NPHCC)/ Type II Lynch
syndrome
– Early onset proximal colon Ca + Endometrial and O Ca CEO
– Mismatch repair genes mutation ( MLH1, MSH2, MSH6)
– Life time risk of O Ca in women with HNPCC~10-12%

Epithelial Ovarian Ca- Pathogenesis
Theories
I. Incessant Ovulation
• Ovulation--Epithelial surface rupture---
– Proliferation and repair +
– Invagination of SE into the stroma formation of
inclusion cysts malignant transformation of
epithelium of the cyst
• Observations in favor of this hypothesis
– Protective effect of parity, Breast Feeding, late
menarchae, early menopause and OCPs + viceversa

II. Retrograde Menstruation
Transportation of carcinogens from Ux and
LGT to ovaries through FTs with RGM
Observations in favor of this thought
protective effect of BTL and Hysterectomy
OCPs less menstrual flow less RGM less
risk of OT
HRT increased AUB  increased Retrograde
flow– increased risk

III. Exposure for high level gonadotropins
• Invitro fertilization, FSH promotes growth of
Ovarian Ep cancer cellsEp cells
• FSH Estrogen in stroma –abnormal
proliferation of adjacent epithelium
• Observations
– OCP, BF ( low FSH level + low Ovarian Ca)
– Fertility drugs Eg. Clomiphen- ( high FSH + High
Risk)

Epithelial O Ca Differentiation
• Serous adenocarcinoma- endosalpinx like differentiation
– well-differentiated -predominantly papillary and
glandular structures;
– poorly differentiated characterized by solid sheets of
cells, nuclear pleomorphism, and high mitotic activity;
– Moderately differentiated -intermediate between these
two lesions
• Mucinous Adenoca- endocervix like differentiation
– resemble endocervical, gastric pylorus or intestinal
epithelium
• Endometroid- endometrium like differentiation
– well differntiated-When there are back-to-back glands
with no intervening stroma

Epithelial Ovarian Ca Pattern Of Spread
• Transcoelomic- commonest
– Malignant cells Exfoliation- follow path of peritoneal fluid-and
implant to peritoneal surface
– The fluid move from the pelvis by resp force up PC gutters (
mainly on the right side), along the intestinal mesenteries to
the right Hemidiaphragm
– Met involves the posterior cul-de-sac, paracolic gutters, right
hemidiaphragm, liver capsule, the peritoneal surfaces of the
intestines and their mesenteries ( Lumen involvement is
unusual), and the omentum.
• Lymphatic- particularly in advanced disease
– Pelvic and paraortic LNs
– Supraclavicular LNs ( through L channels of diaphragm and
reteroperitoneal LNs)
• Hematogenous- late
– Spread to vital organ parenchyma, such as the lungs and liver,
occurs in only about 2% to 3% of patients.

Epithelial Ovarian Cancer-Dx
• Early stage SS
– Abdominal pain, bloating, indigestion, constipation,
Urinary frequency
– Non specific and usually ignored or misdxed by the
patient or primary HC providers
• Advanced O Ca
– Abdominal swelling, fatigue, weight loss
• The 4 common target symptoms before Dx are
1. Abdominal pain (frequency 30%, OR 6.0),
2. Abdominal swelling (frequency 16.5%, OR 30),
3. GI symptoms Eg Dyspepsia (frequency 8.5%, OR 2.3)
4. Pelvic pain (frequency 5.4%, OR 4.3).

EpithelialOvarian Ca-Dx
• Vaginal Bleeding-
– rare, metastasis to Ux, E from stromal T
• Pelvic mass on pelvic examination
• SOB, Chest- dullness, decreased air entry (metastatic Pl
Effusion-mainly Rt side)
– Spread to the right lung occurs through the trans diaphragmatic
lymphatics in the right hemidiaphragm, often producing a right
pleural effusion

Epithelial Ovarian Ca-Dx
Imaging
US
– Adnexal mass
– Ascites
• CT
– Ascitis
– Lymph Node involvement
– Omental cacking

Epithelial Ovarian Ca-Screening
• For screening to be effective the disease should
– Be Major Cause of mortality
– Have High prevalence
– Have Preclinical phase to be detected and the
treatment improves survival

Epithelial Ovarian Ca-Screening
• No feasible screening method to date (specific , Sensitive,
High PPV and NPV)
• Individualized approach for high risk women
• Current methods
– Pelvic Exam
– TVUS
– Serum markers ( Ca 125)
– Morphologic Index

Which ovarian T is Malignant?
High risk indicators
• Pelvic exam- fixed, bilateral, irregular
• TVUS ( morphologic indexing)- size > 10cm, volume , solid
component/ papillary projections (complex)---
• Doppler – low impedance ( low RI and PI)
Vessels of malignant tissue are tortuous + no muscular
component low impedance
• High Ca 125 (>35IU)
• Proteomic profile- spectophotpmetery to identify proteins
whose size and chrarge is indicator of malignancy

FIGO’s Surgical Staging of O Ca
Stage I-Tumor limited to ovary
– 1a- one ovary involved, cpsule
is intact, no surface tumor
– 1b- same as 1a ,both ovaries
involved
– 1c- one or two ovaries involved,
surface tumor/ ruptured capsule/
malignant ascitis/ peritoneal
washing positive for malignant
cells
Stage II- Pelvic Extension
– IIa-Extension to Tubes/ Uterus
– IIb extension to other pelvic
parts
– IIc – IIa or IIb + surface
tumor/Ruptured capsule/
Malignant ascitis
Stage III- tumor grossly limited
to pelvis but with
• extrapelvic peritoneal
implants/
• +ve Retroperitoneal LNs/
• superficial liver metastasis
IIIa-T grossly limited to true
pelvis, Microscopic implants
of abdominal peritoneum,
negative nodes
IIIb-abdominal implants < 2cm,
negative nodes
IIIc- > 2cm implants / +VE
nodes
Stage IV-Distant metastases,
including malignant pleural
effusion or parenchymal liver
metastases

Epithelial Ovarian Ca- Rx
• Surgery
– Primary cytoreductive / debulking surgery
• Adjuvant Chemotherapy-
– current standard chemorx is paclitaxale +
Platinium( Carboplatin/Cisplatin)

Prognostic Factors for Ovarian Cancer
Most important Favourable Prognostic Factors
– Younger age
– Good performance status
– Cell type other than mucinous and clear cell
– Well-differentiated tumor
– Smaller disease volume prior to any surgical
debulking
– Absence of ascites
– Smaller residual tumor following primary
cytoreductive surgery

Germ Cell Tumors
• In the first two decades of life, almost 70% of
ovarian tumors are of germ cell origin, and one
third of these are malignant.
• Germ cell tumors represent a relatively small
proportion (20%) of all ovarian tumors
• In contrast to the relatively slow-growing
epithelial ovarian tumors, germ cell
malignancies grow rapidly
• The most common types of malignant GCTs are
– Dysgerminomas,
– Immature Teratomas, and
– Endodermal Sinus tumors.

Modified WHOClassification of Ovarian GCTs

Ovarian Germ cell Tumors-Histogenesis
• Primitive germ cells migrate from the wall of the yolk sac to the
gonadal ridge
• As a result, most GCTs arise in the gonad.
• Rarely, they may develop primarily in extragonadal sites such as
the CNS , mediastinum, or retroperitoneum (Hsu, 2002).
• Ovarian GCTs have a variable pattern of differentiation
• Dysgerminomas are primitive neoplasms that do not have the
potential for further differentiation.
• Embryonal carcinomas are composed of multipotential cells that
are capable of further differentiation.
• Embryonal Ca is the precursor of several other types of
extraembryonic (yolk sac tumor, choriocarcinoma) or embryonic
(teratoma) GCTs .
• The process of differentiation is dynamic, and the resulting
neoplasms may be composed of different elements showing
various stages of development (Teilum, 1965).

Differentiation pathway of germ cell tumors.

Tumor Markers of Ovarian Germ Cell Tumors

Diagnosis-Signs and Symptoms
• SS associated with GCTs are varied, but in general, most arise
from tumor growth and the hormones they produce.
• Subacute abdominal pain is the presenting symptom in 85 % of
patients and reflects rapid growth of a large, unilateral tumor
undergoing capsular distension, hemorrhage, or necrosis.
• Less commonly, cyst rupture, torsion, or intraperitoneal
hemorrhage leads to an acute abdomen in 10 % of cases.
• In more advanced disease, ascites may develop and cause
abdominal distension.
• Because of the hormonal changes that frequently accompany
these tumors, menstrual irregularities may also develop.
• Although most individuals note one or more of these
symptoms, one quarter of individuals are asymptomatic, and a
pelvic mass is noted unexpectedly during physical or sono-
graphic examination.

• Individuals typically seek care within 1 month of
the onset of abdominal complaints, although
some note subtle waxing and waning of
symptoms for more than a year.
• Most young women with these tumors are
nulligravidas with normal periods,
• But individuals with dysgenetic gonads are at
significant risk for development of these tumors
(Curtin, 1994).
• Therefore, adolescents who present with pelvic
masses and delayed menarche should be
evaluated for gonadal dysgenesis

Initial symptoms in young patients with malignant
germ cell tumors.

Ovarian Germ Cell Tumors
• Staging-
– same as epithelial Tumors
• Treatment
– Surgery
• B/se the bulk of patients are in the reproductive age
group Preservation of fertility should be standard in
most pts
– Adjuvant chemotherapy
– The most effective chemotherapy is BEP
(bleomycin, etoposide, and cisplatin
combination)

Sex cord Stromal Tumors (SCST)
• Arise from ovarian matrix
• Most hormone secreting
 E/ Androgen excess presentation
• Excellent overall prognosis-
– early stage Dx (Confined to one ovary by time of Dx) and
curative surgery
• Rarely require chemorx
• Most-Indolent, low malignant potential
• If recurrent- poor response for treatment, however long
patient survival due to slow progression
• Scarce
– difficulty in understanding their NH, RX and prognosis

SCSTs
• < 5% OTs, the least common major sub-types
– Age adjusted incidence rate0.20 per100,000 women
• Affect women of all ages with bimodal
distribution ( Juvenile and Adult form) Egs
– juvenile granulosa cell tumors, Sertoli-Leydig cell
tumors, and sclerosing stromal tumors are found
predominantly prepubertally and in the 1st 3 decades
(Schneider, 2005).
– Adult granulosa cell tumors commonly develop in
older women, average age of app 50 years (Boyce, 2009;
Fotopoulou, 2010)

SCST
• Mostly-
– low malignant potential,
– unilateral, remain localized,
– hormone secreting function,
– rare relapse,
– bone metastasis rare,
– Reccurrences late and develop in the abdomen
and pelvis

SCSTs
• No proven RFs- Case control studies show
– association with Obesity
– Parity, smoking, OCPs- protective effect
• Etiology unknown
– FOXL2 gene mutation (402C→G) has recently been shown to be
present in virtually all adult-type granulosa cell tumors
• No known inherited predisposition, familial cases are rare
• However, ovarian SCSTs do frequently develop in
association with several defined hereditary disorders
Eg of Associated disorders include
– Ollier disease, which is characterized by multiple benign but
disfiguring cartilaginous neoplasms, and
– Peutz- Jeghers syndrome, characterized by intestinal
hamartomatous polyps (Stevens, 2005).

SCST Histology-WHO Classification

SCSTs Dx-
SS
• Isosexual precocious puberty ( 80% of prepubertal cases)
• In teenagers-
– 20 Amenorrhoea ,Abdominal pain and distension
• In adult women
– menometrorrhagia and postmenopausal bleeding – frequent
symptoms
• mild hirsutism that rapidly progresses to frank virilization
should prompt evaluation to exclude SCSTs.
• The classic presentation is a postmenopausal woman with
rapidly evolving stigmata of androgen excess and a complex
adnexal mass.
• Abdominal pain or a mass palpable by the patient herself
are other telling signs and symptoms (Chan, 2005).

SCSTs Dx-PE
SS
• most women have a palpable abdominal or
pelvic mass ,of varying size, on PE regardless of
their age.
• A fluid wave or other physical findings
suggestive of advanced disease, however, are
rare

SCSTs Dx-Lab
• Elevated circulating levels of testosterone or
androstenedione or both
– strongly suggestive of an ovarian SCST in a woman with SS of
virilization.
• Clinical hyperandrogenism is more likely to be idiopathic
or related to PCOs, but serum T levels >150 g/dL or DHEAS
>8000 g/L should strongly suggest the possibility of an
androgen-secreting tumor (Carmina, 2006).
• In most instances, tumor marker studies are not usually
obtained preoperatively, because the Dx of ovarian SCST is
often not suspected.
• When the diagnosis is confirmed, the appropriate tumor
markers may be drawn during or following surgery

Tumor Markers of SCSTs with
Malignant potential

SCST Dx-Imaging
• Radiologic findings Range from large multi
cystic to small solid Em thickening may be
seen
• No unique features on US , CT , MRI no
definitive radiologic study to dx SCSTs

SCST-Dxtic Procedures
• Laparotomy/ Laparoscopy- tumor resection-
Histopathologic study
• distinguished histologically from germ cell
tumors, epithelial ovarian cancers, or other
spindle-cell neoplasms by immunostaining for
inhibin(Cathro, 2005; Schneider, 2005).
• No role for CT guided PC biopsy nor lap visualisation
without excision

SCST-Rx
• The majority of SCSTs are benign or low
malignant potential tumors.
• As a result, surgical therapy is adequate in
most cases and remains the cornerstone of
treatment

PCOS
Williams Gyn.
August 2013
Samuel Bezabih

PCOS
• No universally accepted definition
• Many expert dxtic criteria are avilable

PCOS- Dxtic criteria
• NIH (1990) def - both of the following (+_ Polycystic
ovaries) are required
I. Hyperandrogenism/Hyperandrogenimia
II. Oligo/Anovoulation(oligomenorrhoea/ Amenorhoea
• ESHRE/ASRM Definition( Roterdam 2003) replaced the NIH
– 2 or more of the following are required
I. Oligo/Anovoulation (oligomenorrhoea/ Amenorhoea)
II. Hyperandrogenism (clinical Hirsutism , acne and/or biochemical
serum hormone level)
III. Polycystic Ovaries on US ( >12, 2-9mmD or/and increased ovarian
volume,>10ml)
• Androgen Excess society 2006
• Hyperandrogenism Plus one of the following
• Oligomenorhoea/Amenorhoea
• Polycystic Ovaries by US
NB: Other disorders should be excluded before dxing PCOS Eg Late
onset CAH, Hyperprolactinemia,Androgen secreting neoplasms)

PCOS – Incdence and P-ACOG 2009
Incidence
• ~7% of reproductive age women with
hyperandrogenic chronic anovulation (Acc to NIH
criteria)
• Prevalence of PCOS in normogonadotropic
anovulatory woman according to :
– Roterdam- 91%
– NIH- 55%
– AES in b/n the above
• Roterdam criteria- broader, criticized for ↑ing
prevalence of PCOS by including more mild
phenotypes

PCOS
• The most common endocrine disorder of
reproductive-aged women
– Incidence~ 4 to 12%
• One of the most frequent causes of infertility in
couples
• The most common cause (80-85%) of androgen
excess in women

Etiology
• the underlying cause of PCOS is unknown.
• However, a genetic basis that is both
multifactorial and polygenic is suspected, as
there is a well-documented aggregation of the
syndrome within families

Etiology of PCOS
Candidate genes in PCOS:
• Steroid biosynthesis and action
– (CYP17, CYP11A, AR-androgen receptor, SHBG,
CYP21…)
• Gonadotrophic action and regulation
– (Follistatin, LH ß-subunit, FSH ß-subunit, FSH
receptor…)
• Insulin secretion and metabolism
– (Insulin receptor, IRS1, IRS2, PPARG, IGF2…)
• Cardiovascular disease (PAI-1, IL6, Adiponectin…)

Consequences of Polycystic Ovarian Syndrome
Short-term consequences
1. Irregular menses
2. Hirsutism/acne/androgenic alopecia
3. Infertility
4. Obesity
5. Metabolic disturbances
6. Abnormal lipid levels/glucose intolerance
Long-term consequences
1. Diabetes mellitus
2. Cardiovascular disease
3. Endometrial cancer

Pathophysiology
• Altered GnRH pusatility (?Hypothalamic vs 20)
 more LH secretion than FSH
– 50% PCOS- elevated serum LH
– 60% LH:FSH > 2
• Affected ovaries secrete elevated levels of
androgens (testosterone and androstenedione).
• Specifically,
– elevated free T levels in 70 to 80% of women with
PCOS,
– elevated levels of DHEAS in 25 to 65%

Pathogenesis of PCOS (2)
2 cell theory bild?
LH
Liver
Granulosa cells
Theca
cells
Diffusion of
Testosterone
Aromatization Estradiol
Excess
Testosterone
binds to SHBG
T-SHBG
2% 20%
95%
T-SHBG
normal
80%
T-SHBG
in PCOS
free-Testost.
free-Testost.
• Functional-
hyperandro-
genemia
• Inhibition of
follicle growth
• Low estradiol
with poor -ve
feed back
• LH high
Insuline, IGF
+
+
+
Ovary
Follicle
+
SHBG

Pathophysiology
• Elevated androgen level may result from
– High LH and low FSH level (↑LH: FSH)
• stimulation of Theca Cells by LH , androgen synthesis in
the face of low granulasa cell aromatase activity 
Decreased androgen conversion to E increased
intrafollicular androgen ( and ↑serum level too)
– Hyperinsulinemia 20 to insulin resistance
suppression of liver production of SHBG by insulin
increased circulating free androgens
– Adrenal secretion

Patophysiology
Effects of ↑ed androgen level ( IF and serum)
• ↑ed intrafollicular androgen
– follicular atresia
• ↑ed circulating androgens
Dyslipidemia, Acne, Hirsuitism , Alopecia
Suppression of SHBG synthesis (↑ed free androgens )
↑ed peripheral conversion of androstenidione to
Estrone (E2)??E1??
 chronic unopposed exposure of endometrium to
Estrogen E. hyperplasia , Eca
Chronic –ve feedback on pitutary and
hypothalamusAnovulation

Pathophysiology-IR
• Positive correlation between insulin resistance (IR) and
hyperandrogenism
• Women with PCOS display greater degrees of IR and
compensatory hyperinsulinemia than non affected
women
• Icreased rate of IR in both lean and obese women with
PCOS, compared with weight matched unaffected
controls
– β-cell dysfunction that is independent of obesity reported
in PCOS
• The mechanism of this decreased insulin sensitivity
appears to be due to a post binding abnormality in
insulin receptor-mediated signal transduction

Insulin Resistance
• IR  hyperinsulinemia , Effects of insulin
– Suppression of SHBG production of liver
– Stimulation of Androgen production by theca cell
– Stimulation of LH-secretion
– Acanthosis nigricans
– Contribution to follicular atresia
• IR is associated with high risk of
– Type ll DM,
– hypertension,
– dyslipidemia and
– CV diseases

Insulin sensitivity in obese and Non-obese, normal (NL) and
affected(PCOS) women

Impaired Glucose Tolerance and Type 2 DM
• women with PCOS are at increased risk for IGT and
type 2 DM.
• Based on OGT , the prevalence of IGT and DM is
approximately 30% and 7 %, respectively .
• Similar findings were reported in a group of obese
adolescents with PCOS (Palmert, 2002).
• Over time, IGT in PCOs worsens , with a reported
conversion rate of about 2% per year to type 2 DM
• In addition, β-cell dysfunction that is independent
of obesity has been reported in patients with PCOS

Sex Hormone-Binding Globulin
• Glycoprotein, produced in the liver, binds most sex
steroids.
• Only~1% of sex steroids are unbound and thus free and
bioavailable.
• The synthesis of SHBG is suppressed by Insulin as well
as Androgens, Corticoids, Progestins, and growth
hormone (Estrogen and thyroxine stimulate SHBG
synthesis )
– Suppressed SHBG liver production ↑free androgen to
bind with end-organ receptors
• Women with PCOS display decreased levels of SHBG.
 Clinical hyperandrogenism in the face of normal total
serum T level ( because of Elevated free T levels)

Dyslipidemia
• The classic atherogenic lipoprotein profile seen in
PCOS is characterized by
– Elevated LDL& TG
– Depressed HDL levels ,
– Elevated total cholesterol:HDL ratios
• These changes may increase the risk of CV
disease in women with PCOS independent of
total cholesterol levels.
• Following criteria of the National Cholesterol
Education Program, the prevalence of
dyslipidemia in PCOS approaches 70%

Ovarian Hyperthecosis
Ovarian Hyperthecosis
• is a rare condition characterized by nests of
luteinized theca cells distributed throughout the
ovarian stroma with increased production of
testosterone
• Often Hx of gradual onset of hirsutism and frank
virilization
– Affected women exhibit severe hyperandrogenism,
and may occasionally display frank virilization signs
such as clitoromegaly, temporal balding, and
deepening of the voice
• It is still unclear if hyperthecosis is a distinct
disorder or is part of the spectrum of PCOS

HAIRAN syndrome-
Hyperanderogenic Insulin Resistant Acanthosis
Nigricans
• Uncommon and consists of
– marked Hyperandrogenism,
– severe IR and
– Acanthosis Nigricans (Barbieri, 1994).
• Etiology -unclear, and
• HAIRAN syndrome may represent either a variant
of PCOS or a distinct genetic syndrome.

Metabolic Syndrome
• MS is associated with an increased risk of CV
disease and type 2 DM
• characterized by:Insulin Resistance,Atherogenic
dyslipedimia,Obesity Hypertension
• Dxtic criteria (Adult Treatment Panel III)
– ↑BP (> 130/85)
– Waist circumference > 35 inches
– FBS > 100mg/dl
– HDL < 50mg/dl,
– TG > 150mg?dl
• Prevalence of MS ~45% in women with PCOS

Signs and Symptoms
• Various endocrine effectsVarious
complaints
• Symptoms classically become apparent within
a few years of puberty
• Symptoms may include
– menstrual irregularities,
– infertility,
– manifestations of androgen excess, or
– other endocrine dysfunction.

Menstrual Dysfunction
• Range from amenorrhoea to oligomenorhoea and
menometroragia with anemia
– Effect of unopposed estrogen  unpredictable bleeding
– Androgens counteract against E endometrial atrophy
and amenorrhoea
• women with oligo-ovulation or anovulation typically
have
– fewer than eight menses per year,
– often skip menses for several months at a time,
– or simply have amenorrhea.
– Flow may be scanty or very long and heavy, resulting in
anemia.

Menstrual Dysfunction
• Menstrual abnormality in PCOS begins at
menarchae
difficult to differentiate from anovulatory cycles
common in postmenarchal girls (50%) due to H-P-O axis
immaturity
Girls with PCOS continue to have M irregularity in the
mid teenage years while the unaffected etstablish
regular ovulatory cycles
Menses may become more regular with age( in 30s
and 40s ) as the no of antral follicle cohort
decrease ↓in androgen production

SS of Hyperandrogenism
• Androgen excess symptoms and signs vary b/n
races/ ethnicities
• SS HA Typical in PCOS are
– Hirsutism
– Acne
– Androgenic Alopecia
• Virillization is uncommon in pcos (↑ muscle mass,
cliteromegally, frontal balding, voice deepening) –
 sign of highly elevated androgen levels from androgen
secreting adrenal or ovarian tumors

SS of Hyperandrogenism
Hirsuitism
• Terminal hair (Coarse, dark pigmented) in male
like pattern i.e. On androgen sensitive regions
upper lip, chin, chest, thighs, lower abdomen
– Distinct from Hypertechosis- generalized increase
in lanugo hairs( soft, lightly pigmented) usually 20
to drugs, malignancy--
• PCOS is the commonest cause of hirsuitism (70-
80% of cases)
• Women with PCOS typically report hirsutism
beginning in late adolescence or the early 20s.

SS of Hyperandrogenism-Hirsuitism
• 5 alpha reductase converts testestorone to DHT in the
hair follicles
• Sexual Hair  androgen dependent( face, pubic,
chest,back, thigh, breast-----)
– Vellus hair (short soft,downy, unpigmented) converted to
terminal hair (coarse, pigmented ) by the action of DHT( to
some extent Testosterone) in the hair follicles
 Hirsuitism is a vellus to terminal hair transformation
Irreversible even after androgen withdrawal
• DHT has reverse effect on scalp hair ( non sexual)
 conversion of TH to VH and balding

SS of Hyperandrogenism-Hirsuitism
• IGF 1 stimulate 5 alpha Reductase activity
• Anovulatory hyperandrogenic women with IR and
Hyperinsulinemia have ↑ed IGF1 activity
Intensified Hirsuit response
• Extent of hirsuitism varies with race or ethnicity (
concentration of hair follicles)
• Asians-low HF concentration/unit area  less
likely to have overt hirsuitism

Hirsuitism
• Ferriman-Gallwey scoring system of hirsuitism

SS of Hyperandrogenism-Acne vulgaris
• Acne that is particularly persistent or of late onset
should suggest PCOS
Hyperandogenism  overstimulation of androgen receptors in the
pilosebaceous unit  increased sebum production that eventually
leads to inflammation and comedone formation
• Type 1 5-alpha-reductase in sebacious glands is
implicated ( high DHT production in the glands)
• Pathogenesis
– blockage of Hair follicle openings by hyperkeratosis
– Excessive sebum production
– Proliferation of propionibacetrium acne
– inflammation

SS of Hyperandrogenism-Alopecia
• Female androgenic alopecia is a less common finding in
women with PCOS.
• Hair loss progresses slowly and is characterized either by
diffuse thinning at the crown with preservation of the
frontal hairline or by bitemporal recession .
• Its pathogenesis involves an excess of 5-alpha-reductase
activity in the hair follicle leading to a rise in DHT levels.
• In addition, there is an increased expression of androgen
receptors in these individuals .
– Under the influence of androgens, terminal hairs that were not
previously dependent on androgens revert to a vellus form and
balding results
• Alopecia, however, may reflect other serious disease. For
this reason, affected women should also be evaluated to
exclude thyroid dysfunction, anemia, or other chronic
illness.

Acanthosis Nigricans
• Thickened, gray-brown velvety plaques seen in areas of
flexure such as the back of the neck, the axillae, the crease
beneath the breast, the waist, and the groin .
• May be found in individuals with or without PCOS
• Thought to be a cutaneous marker of insulin resistance,
• IR leads to hyperinsulinemia, which is believed to stimulate
keratinocyte and dermal fibroblast growth, producing the
characteristic skin changes .
• Among women with PCOS, AN is more common in obese
women (50 %incidence) than in those with normal weight
(5 -10 %).
• Less commonly, it is seen with genetic syndromes or
malignancy of the GI tract, such as adenocarcinoma of the
stomach or pancreas

Obesity
• Compared with age-matched controls, women
with PCOS are more likely to be obese, as reflected
by an elevated BMI and Waist:Hip ratio
• Pear shaped vs. Apple shaped .
• This ratio reflects an android or central pattern of
obesity, which itself is an independent risk factor
for cardiovascular disease
• However women with PCOS donot necessarily
present with obesity `
• ~ 20% of women with PCOS are not obese (ACOG 2009)

Anovulation
• Unknown Precise mechanism
• Indirect evidences attribute anovulation to the
Large number of antral follicle cohort and IR
resumption of fertility/regular menses after
wedge resection/ laparascopic ovarian drilling and
metformin treatment

Infertility
• Infertility or subfertility is a frequent
complaint in women with PCOS
• results from anovulatory cycles.
• PCOS is the most common cause of infertility
secondary to anovulation  80 to 90 percent
of cases

Pregnancy Complications- Will Gyn 2nd
• Several pregnancy and neonatal complications have been
associated with PCOS.
• One large metaanalysis found women with PCOS to have a 2-
3x higher risk of GDM, PIH, preterm birth, and PNM,
unrelated to multifetal gestations (Boomsma, 2006).
• Metformin has been studied as a tool to mitigate these
complications.
• However, investigators in one study found that metformin
treatment during pregnancy did not reduce rates of these
complications (Vanky, 2010).
• Many women with PCOS require the use of ovulation
induction medications or in vitro fertilization to conceive.
• These practices substantially increase the risk of multifetal
gestations, which are associated with increased rates of
maternal and neonatal complications

Diagnosis Of PCOS
• PCOS is a diagnosis of exclusion
other disorders that have clinical appearance
similar to PCOS need to be routinely ruled out
DDX

PCOS DDX ACOG 2009
• Androgen secreting tumors
• Exogenous androgens
• Cushing Syndrome
• NC CAH
• Acromegally
• Insulin action genetic defects
• 10 hypothalamic amenorrhea
• 10 ovarian failure
• Thyroid disease
• Prolactin disorders

PCOS DDx
Anovulation/Menstrual dysfunction
– Hypo/hyperthyroidism --↓ or ↑ TSH levels
– Hyperprolactinemia-- ↑Prolactin level
– Hypogonadotropic hypogonadism --↓ FSH, LH, E2
– POF--↑FSH and LH ,↓E2
– PCOS – LH:FSH> 2
LH and FSH levels have little additive value to the diagnosis
of PCOS. Although classically LH levels measure at least
twofold higher than FSH levels, this is not found in all
women with PCOS. Specifically, one third of women with
PCOS have circulating LH levels in the normal range, a
finding more common in obese patients (Arroyo, 1997; Taylor, 1997).
Moreover, serum LH levels are affected by sample timing
within a menstrual cycle, use of oral contraceptive pills,
and body mass index

PCOS DDx
Hyperandrogenism
• Late onset CAH—
– ↑17ydroxyprogesteroneP(>200ng/dl)
• Androgen secreting tumors*
– Ovarian tumor--↑ t T(>200ng/dl),
– Adrenal tumor--↑ DHEAS(>200ng/dl)
• Exogenous androgens--↑ A in toxicology screen
• Cushings Syndrome—
– ↑ cortisol level (24hr urine cortisol >300micg),DMST
• PCOS
– Testosterone- usually elevated
– DHEAS- may be mildly elevated
– LH:FSH ratio typically > 2
*women with an abrupt onset, typically within several months, or
sudden worsening of virilizing signs should prompt concern for a
hormone-producing ovarian or adrenal tumor

Clinical Evaluation ACOG 2009
Hx-
• Onset and duration of hperandrogenic SS
• Menstrual hx
• Medication hx ( exogenous androgens)
• Family Hx of DM,CV diseases
• PE- BP, BMI,
– Waist circumference (fat distribution) >35inches abnormal
– Hyperandrogenism stigmata
• Hirsuitism,Acne, Androgenic alopecia, clteromegaly
– IR signs-
• HTN, Obesity, centripetal fat distribution, Acanthosis nigricans

Workup ACOG 2009
Laboratory
Biochemical Hyperandrogenism
(HA)
• Total and Free T, SHBG
• Other HyperA causes
– TSH
– Prolactin
– 17OH progestrone (CAH)
– Cushing S screening
Metabolic abnormalities
– OGTT
– Fasting lipid and lipoprotein level
US
– Polycystic ovaries, Em
abnormalities
• Optional tests
– LH,FSH (cause of amenorrhea)
– Fasting insulin level (young with
severe stigmata of IR, HA or on
Ovuation Induction)
– 24hr urine free cortisol/ low dose
DST for late onset PCO symptoms
and stigmata suggesting Cushing
Syndrome)

Imaging for Hyperandrogenism
• Pelvic sonography is the preferred method to
exclude an ovarian neoplasm in a female with
very high androgen levels.
• Alternatively, CT or MRI may also be used in
this setting.
• Adrenal imaging with abdominal CT or MRI is
indicated for any patient with DHEAS levels
that exceed 700ng/dl

Sonography
• Sonographic criteria for polycystic ovaries from the
2003 Rotterdam conference include > 12 small cysts (2
to 9 mm in diameter) or an increased ovarian volume
(>10 mL) or both
• Only one ovary with these findings is sufficient to
define PCOS.
• However, criteria do not apply to women taking
combination oral contraceptive pills
• Sonography is particularly important for women with
PCOS seeking fertility and in women with signs of
virilization.
• TVUS is superior to TABUS
• TABUS-preferable for virgin adolescents

Sonography
• studies using sonography have shown that at
least 23% of young women have ovaries that
exhibit PCO morphology, yet many of these
women have no other symptoms of PCOS .
• In addition, a polycystic appearance of the ovaries
can often be found in other conditions of
androgen excess, such as CAH, Cushing syndrome,
and exogenous use of androgenic medications.
• For this reason, PCO morphology found during
sonographic examination is not used solely to
make the diagnosis of PCOS.

IR and Dyslipidemia
• a 2-hr GTT is frequently used to exclude
impaired glucose tolerance (IGT) and type 2
DM
• a fasting lipid profile is used to evaluate any
signs of dyslipidemia.
– Abnormal values
• Total cholestrol, HDL < 50 mg/dl
• TG > 150 mg/dl
LDL are alculated using Fridewald equation

PCOS TREATMENT
Laser drilling of ovary for surgical treatment of polycystic ovarian disease- Telinde

Treatment
• The choice of treatment for each symptom of
PCOS depends on a woman's goals and the
severity of endocrine dysfunction
Observation –
• women with PCOS who have fairly regular cycle
intervals (8 to 12 menses/ year) and mild
hyperandrogenism may choose not to be treated.
• In these women, however, periodic screening for
dyslipidemia and DM is warranted.

Treatment of PCOS-General
Weight Loss- (by obese women) – life style/diet modification
• Wt loss lowers circulating androgen levels and
improves reproductive and metabolic abnormalities
• Improved pregnancy rate, hirsutism, glucose and lipid
profile
• Even a modest amount of weight loss (5% of body
weight) can result in restoration of normal ovulatory
cycles in some women.
• This improvement results from reductions in insulin
and androgen levels, the latter mediated through
increases in SHBG levels
• Effect of wt loss in women with PCOS and normal wt is
unknown

Wt Loss
• Phamacologic wt loss agents show improved
ovarian function
– Orlistat- intestinal lipid absorption inhibitor
– Sibutramine- anorexic agent

Insulin sensitizers
• Biguanides and Thiazolidinediones
– Lower androgen level
– Improve ovulation rate
– Improve glucose tolerance
• Effects on body wt
– Biguanides (Metformin) decrease body wt
– TZ increase body wt

Insulin sensitizers:
Metformin (used ‘ off label‘ in PCOS)
– Low circulating insulin levels increased SHBG level
Decreased androgen levels
– Regular cycles
– Increased ovulation rate(Cochrane Review, Lord 2003)
– Improves hirsutism
– Improved results of CC- or FSH-stimulation
Placebo Metformin Clomiphene
citrate (CC)
Metformin +
CC
Ovulation 26% 46% (OR 3.88) 42% 76% (OR 4.41)
NNT 4.4 3
Lord 2003

Insulin sensitizers:
Metformin in pregnancy:
• reduces LH and androgen concentration
• enhances uterine vascularity (Jakubowicz et al, 2001)
• reduces PAI-I and endothelin-I (Palomba et al., 2005; Orio et al.,
2005)
• seems to be safe during pregnancy (Glueck et al. 2004)
• beneficial effect on gestational diabetes?
• decrease rate of early abortions
 miscarriage rate in 328 pregnancies with metformin
20% vs. 65% in 319 previous pregnancies without
metformin (Glueck et al., 2002)

Insulin sensitizers
Note: „off-label“ use for metformin in PCOS patients (pregnant and
non-pregnant)!!!
Thiazolidinediones: (troglitazone, rosiglitazone,
pioglitazone)
- enhances glucose uptake in adipocytes and muscle
- promissing results in patients with PCOS
- limited data for rosiglitazone, pioglitazone
- liver toxicity for troglitazone (not available)
Acarbose:
- promising results in patients with insulin resistance
- limited data

Treatment of menstrual dysfunction
COC pills ( alternatively patch or vaginal ring)
• 1st line rx for menstrual irregularities
• Lower androgen level through
– Supression of gonadotropin release
– ↑ing SHBG level due to the E component
• The P component ↓ risk of Em hyperplasia
• Withdrawal bleeding is induced by progesterone
before initiation of COC

Treatment of menstrual dysfunction
Cyclic Progestins –
• in patients who are not candidates for COCs ,
• progesterone withdrawal is recommended every
1 to 3 months.
• Examples of regimens used include:
– MPA, 5- 10 mg PO/Day for 12 days, or
– micronized progesterone, 200 mg po/evening for 12
days.
• Patients should be counseled that intermittent
progestins will not reduce symptoms of acne or
hirsutism nor provide contraception.

Amenorrhoea
Williams Gynecology

10 Vs 20 Amenorrhoea
10- No prior menses
– no menses at the age of 13 in the absence of
pubertal changes
– no menses at 15 even in the presence of pubertal
growth
20- Ceasation of menses for 3 consecutive cycles
or for 6months in previously menstruating
woman

Causes of Amenorrhoea
Broadly Anatomic and Endocrinologic Causes which
can be either Inherited or Acquired

Anatomic Causes
• Inherited
– Labial fusion
– Imperforate hymen
– Vaginal septum
– Cervical/vaginal atresia
– Mullerian defects (MMRKH syndrome)
• Acquired
– Cervical stenosis( conization, cryo, electrosurgery)
– Ashermans syndrome
– Labial adhesion/agglutination
• develops in 1 to 5 % of prepubertal girls and in
approximately 10 % of female infants within the first year of
life

Endocrinologic Causes
Hypergonadotropic Hypogonadism
• POF
• Chromosomal
– Gonadal dysgenesis/ agenesis
• Genetic
– CY17 gene mutation ( 17OHase, 1lyase def)
– ROS
– Galactosemia
• Acquired
– Infection, autoimmune, iatrogenic

Endocrinologic Causes
ሀ. HYPERGONDOTROPIC HYPOGONADISM
• Mainly due to Premature Ovarian Failure(POF) –
– loss of Primordian follicles-oocytes i.e. ovarian function
before the age of 40
DX -↑ FSH level ( > 40mu/l)

POF- inherited causes
I. Chromosomal
• GONADAL DYSGENESIS- fetal primordial follicles undergo
accelerated atresia and ovaries are replaced by
fibrous streaks
• Abnormal Karyotype
– 45X –Tuner syndrome
– 45X/46XX mosaicism 45X/46XY mosaicism (gonadal
agenesis) may exhibit some degree of pubertal dv’t
– Loss of long/short arm of X chromosome
• Normal karyotype (pure gonadal dysgenesis)46XX, 46XY
– 46XY with female phenotype( Female RT)-
SWEYRS syndrome
– due to failure of testes to secret testosterone and MIS

TS
• 60% of TS cases-total loss of one X chromosome-,
• the rest have either a structural abnormality in
one of the X chromosomes or mosaicism with an
abnormal X.
• 99% of conceptuses with only one chromosome
abort, the rest 1% account for the TS incidence of
1 in 2500- 5000 live born girls
• The most common cause- meiotic non-
disjunction, 70%- maternal chrs, the rest-
paternal

TS
• In the absence of gonadal development, these individuals are
phenotypic females.
• The well-known characteristics are short stature (142-147 cm, 56-58
inches), sexual infantilism, and streak gonads.
• The streak gonad is composed of white fibrous stromal tissue, 2- 3 cm
long and about 0.5 cm wide, containing no ova or follicular
derivatives.
• Other congenital problems in TS are a webbed neck, a high arched
palate, cubitus valgus, a broad shield-like chest with widely spaced
nipples, a low hairline on the neck, short fourth metacarpal bones,
disproportionately short legs, and renal abnormalities (horseshoe
kidney, unilateral pelvic kidney, rotational abnormalities, and partial or
complete duplication of the collecting system).
• Autoimmune disorders are common, such as Hashimoto's thyroiditis,
Addison's disease, alopecia, and vitiligo. Hypothyroidism is present in
about 10% of young patients and can reach 50% later in life. Mild
insulin resistance, progressive hearing loss, and hypertension are also
common.
• Patients with Turner syndrome are very prone to keloid formation

TS
• About 20% of patients with TS have CV
abnormalities, including bicuspid aortic valves,
coarctation of the aorta, mitral valve prolapse,
and aortic aneurysms.
• Often the Dx is not made until puberty when
amenorrhea and lack of sexual development
become apparent.
• At birth, however, lymphedema (due to
hypoplasia of superficial vessels) of the
extremities may indicate the condition.
• It is important to assess the aorta, aortic root,
and aortic valve with ultrasonography at least in
infancy and again during the teens.

TS
• Female gender identification is unambiguous with
Turner syndrome
• Spontaneous puberty has been reported in 10-20%
and spontaneous menstruation and pregnancy in 2-5%
of girls with Turner syndrome.
• The presence of menstrual function and reproduction
in a patient with Turner phenotype is probably due to
an undetected mosaic complement, such as a 46,XX
line in addition to 45,X.
• When pregnancy does occur in an X deficient subject,
the infant has a 30% chance of congenital anomalies,
including Down syndrome, spina bifida, and congenital
heart disease

Pure Gonadal Dysgenesis
• Normal stature + Gonadal abnormality of Turners
• Karyotype- XX or XY
46XY- sweyr syndrome
– No SRY/ TDF on Ychrs No AMH, Testosterone
Normal Mullerian Dv’t and EFG Normal prepubertal
Female appearance ( sexual infantlism)
– Y Chrs presence increases risk of Gonadal Tumors The
streak Gonad need removals
• Gonadal developmental defect not clarified in PGD
of 46XX

II. Specific Gene defects
A.CYP 17 gene mutation
 ↓17 ἀhydroxylase and 17 lyase acivity No
androgens, estrogen and cortisol production
Effects
– 10 amenorrhoea and sexual infantilism ( no breast,
pubic and axillary hair, small uterus)
– ↑ ACTH ↑ mineralocorticoid  hypokalemia +
Hypertension

B.Resistant Oavrian Syndrome-
LH, FSH receptors mutation ( no response for
gonadotropic stimulation)
C.Galactosemia-
GALT gene mutation(aut. Recessive) deficiency of
galactose-1-phosphate uridyl transferase  abnormal
metabolism of galactose ↑ Galactose metabolites
toxic to germ cells POF
– Suboptimal ovarian function in hetrozygous carriers
– Dxed in new borns on evaluation for associated
growth and dvtal impairments

POF-Acquired Causes
I.Infectious
– Rare and Poorly understood
– Mumps oophoritis-frequently reported
II. Auto immune
Commonly associated with other AI disorders Eg.
– As Component of Polyglandular failure with
hypothyroidism & Adrenal insufficiency
– SLE, mysthenia Gravis, ITP, R. arthritis, Vitilligo,
autoimmune Hemolytic Anemia

POF-Acquired Causes
III. Iatrogenic
– Surgical removal or significant resection of ovaries
– Pelvic Radiation ( eg for Hodgkins D)
• Prohylaxis-oophoroplexy (surgical repositioning of
ovaries from the radiation field)
– Chemotherapy (alkylating agents are particularly
damaging to ovaries)
• Prophylaxis –pretreatment with GnRH agonists
/antagonists to minimize oocyte depletion)

Prophylaxis in Chemotherapy
A number of mechanisms by which GnRH analogs exert their
protective effects have been proposed.
• decrease ovarian blood flow, and thereby, decrease exposure
of the ovaries to chemotherapeutic agents (Blumenfeld,
2003).
• Dividing cells are known to be more sensitive than cells at rest
to the cytotoxic effects of these agents. Therefore, it has been
suggested that inhibition of the pituitary-gonadal axis may
protect the germinal epithelium by inhibiting oogenesis. .
• Alternatively, as GnRH receptors have been identified in the
ovary, GnRH agonists may act directly at the ovary to
decrease granulosa cell metabolism (Peng, 1994). However,
this explanation is not totally satisfactory, as the early stages
of oogenesis occur independently of gonadotropin
stimulation

POF-Acquired Causes
IV. Environmental Toxins
– A wide variety of Ets have a clear detrimental
effect on follicular health.
– These include cigarette smoking, heavy metals,
solvents, pesticides, and industrial chemicals

ለ፡HYPOGONDOTROPIC HYPOGONADISM

HYPOGONDOTROPIC HYPOGONADISM
• Primary abnormality in the H-P axis
• Hypothalamic GnRH release or GT secretion disorder
followed by loss of ovarian function due to ↓ GT
stimulation
• Low LH and FSH levels
– maybe in the detectable range(<5miu/ml) in most
disorders
– undetectable in Kallmans syndrome and severe pitutary
damage or dvtal abnormality complete absence of
Hypothalamic stimulation
• Constitutional delay of puberty is the most
common cause of this problem (prepuberty low
FSH and LH)
• 2-3% of children have const. puperty delay

HYPOGONDOTROPIC HYPOGONADISM-NOVAK
• At least 6 gene mutations identified ( account for
< 20% of Cases)
I. KAL1,
II. FGFR1/KAL2,
III. DAX 1 (the gene for X -linked CAH),
IV. GNRHR (the gene for the GnRH receptor),
V. PC1 (the gene for prohormone convertase 1), and
VI. GPR54 (encoding a Gâ€“protein coupled receptor
• Constitutional delay of puberty is the most
common cause of this problem (prepuberty
low FSH and LH)
• 2-3% of children have const. puperty delay

HYPOGONDOTROPIC HYPOGONADISM
Inherited Hypothalamic Disorders
a.Idiopathic Hypogonadotropic Hypogonadism
b.Kallmans syndrome
– Hypogonadism with Anosmia +?? Color blindness??
• can be inherited as an X-linked, autosomal dominant or
autosomal recessive disorder
– Failure of GnRH neurons migration from olifactory placode to
the hypothalamus
– These neurons fail to migrate and remain near the nasal
epithelium (Quinton, 1997). As a result, locally secreted GnRH fails
to stimulate gonadotropin secretion by the anterior pituitary
gland.
– Marked decreases in ovarian estrogen production result in a
lack of breast development or menstrual cycles.

HYPOGONDOTROPIC HYPOGONADISM- Inherited Hypothalamic
Kallmans syndrome
– Hypogonadism with Anosmia +?? Color blindness??
• can be inherited as an X-linked, autosomal
dominant or autosomal recessive disorder
– Failure of GnRH neurons migration from olifactory
placode to the hypothalamus
– These neurons fail to migrate and remain near the
nasal epithelium (Quinton, 1997). As a result, locally
secreted GnRH fails to stimulate gonadotropin
secretion by the anterior pituitary gland.
– Marked decreases in ovarian estrogen production
result in a lack of breast development or menstrual
cycles

HYPOGONDOTROPIC HYPOGONADISMInherited Hypothalamic
GnRH neurons
• Develop in the olfactory placode
• Migrate through the forebrain to the arcuate nucleus of the
hypothalamus by 11 weeks’ gestation
• They form axons that extend to the median eminence and to
the capillary plexus of the pituitary portal system

HYPOGONDOTROPIC HYPOGONADISMInherited Hypothalamic
Kallmann Syndrome
• Associated anosmia migration failure of olifactory neurons from OP to the olifactory
cortex
• KS is also associated with midline facial anomalies such as cleft p., unilateral renal
agenesis, cerebellar ataxia, epilepsy, NS hearing loss, and synkinesis (mirror movements
of the hands) (Winters, 1992; Zenaty, 2006).
• KS can be distinguished from idiopathic hypogonadotropic hypogonadism (IHH) by
olfactory testing.
• This can be done easily in the office with strong odorants such as ground coffee or
perfume. Interestingly, many of these patients are unaware of their deficit.
• Ovulation induction is possible by Exogenous pulsatile GnRH adminstration
• For women not seeking pregnancy, therapy with exogenous estrogen and
progestin is indicated

HYPOGONDOTROPIC HYPOGONADISM-
Acquired Hypothalamic Disorders (AHD)
a.Functional Disorders/Hypothalamic amenorrhoea
GT deficiency that arises from functional disorders
of the hypothalamus or higher brain centers leading
to chronic anovulation
this Dx encompasses three main categories
1. Eating disorders ( A.Nervosa & Bulemia)
2. Extreme exercise
3. Stress
• The three May overlap
– EG. Eating disorder may be accompanied by extreme
exercise and anxiety/stress to lose weight

HYPOGONDOTROPIC HYPOGONADISM-AHD
Hypothalamic Amenorrhoea
Eating disorders Anorexia Nervosa / Bulemia
• AN -associated with severe caloric restriction, weight
loss, self-induced vomiting, excess use of laxatives, and
compulsive exercise .
• Bulimic women eat in binges then purge to maintain
weight. Weight loss is generally less severe.
• Consequences of weight loss
Insulin Glucagon,cathecolaminesaltered GnRH pusatility
decreased body fat ↓ leptin↑Neuropeptide-Y 
Hunger sensation + altered GnRH pusatility
• Hypothalamic dysfunction is severe in anorexia and
may affect other H-P axes in addition to the
reproductive axis

Exercise
• Am most commonly seen in women whose exercise
regimen is associated with significant loss of fat, such as
ballet, gymnastics, and long-distance running (De Souza, 1991;
Frisch, 1980).
• In those women who continue to menstruate, cycles are
notable for their variability in cycle interval and menses
length due to reduced hormonal function, including
shortened luteal phases (De Souza, 1998).
• Puberty may be delayed in girls who begin training before
menarche
• Exercise ↑ endogenous opioids( beta endorphins)
altered GnRH pulsatility

Stress-Induced Amenorrhea
• may be associated with clearly traumatic life
events, such as death of a family member or
divorce.
• Nevertheless, much less severe life events and
even positive events may be associated with
stress.
• For example, stress-related amenorrhea is
frequently associated with leaving for college,
taking examinations, or wedding planning
• Stress  ↑CRH  ↑cortisol
– ↑CRH &↑cortisol  Altered GnRH pulsatility

simplified model for the development of amenorrhea in women with
eating disorders, high stress levels, or rigorous exercise

Anatomic Destruction Of The Hypothalamus
impaired GnRH secretion  hypogonadotropic
hypogonadism  amenorrhea
– TUMORS
– INECTIONS (eg TB),
– INFILTRATION by sarcoidosis,
– TRAUMA,
– RADIATION

Anatomic Destruction Of The Hypothalamus
Tumors
Eg craniopharyngiomas, germinomas, endodermal sinus tumors,
eosinophilic granuloma (Hand-Schüller-Christian syndrome),
and gliomas
craniopharyngiomas,( NOVAK)
• The most common (other forms rare),
• usually suprasellar in location and may be asymptomatic well
into the second decade of life
• Frequent presentations- headaches and visual changes,
• short stature or growth failure, delayed puberty, or diabetes
insipidus
• PE may reveal Visual field defects (including bilateral temporal
hemianopsia), optic atrophy, or papilledema
• Laboratory-Hypogonadopism is evident and
hyperprolactinemia may also be there as a result of interruption
of hypothalamic dopamine inhibition of prolactin release

Anatomic Destruction Of The Hypothalamus-Tumors
NOVAK
• Langerhans cell histiocytosis,( particularly the form known
previously as Hand-Schüller-Christian syndrome)- Infiltrative
disease
• Diabetes insipidus is the most common endocrinopathy
(because of infiltration of the supraoptic nucleus in the
hypothalamus),
• Short stature (GH deficiency) and delayed puberty
(gonadotropin deficiency) are not uncommon in this disorder
• Treatment of HP tumors may involve surgical excision or
radiotherapy (with adequate pituitary hormone replacement
therapy)
• best managed by a team of physicians that includes an
endocrinologist, a neurosurgeon, and a radiotherapist.

Anatomic Destruction Of The Hypothalamus- NOVAK
• Irradiation of the CNS for treatment of any
neoplasm or leukemia may result in
hypothalamic dysfunction.
• Although GH deficiency is the most frequent
finding, partial or complete gonadotropin
deficiency may develop in some patients.

• Pseudoceiesis-
– amenorrhea + other pregnancy symptoms
demonstrated by a woman who falsely, believes that
she is pregnant
– No consistent pattern of hormonal derangements
– Amenorrhea may result from altered LH pulse
frequency in conjunction with elevated androgen
levels
– ↑serum PRL + galactorrhea were noted in a subset of
pts.
– Growth hormone secretion appears to be blunted.
– A common link in these patients is a history of severe
grief, such as recent miscarriage or infant death
– Psychiatric rx is generally required for the associated
depression, which is often exacerbated when the
patient is informed that she is not pregnant

Anterior Pitutary Defects
defects in gonadotropes or other anterior
pituitary cells
Inherited-
– Pitutary hypoplasia
– septoptic dysplasia-combined pituitary hormone
deficiency and central facial and/or neurologic
defects due to a failure of midline fusion. Many of
these patients have a mutation in the PROP1 gene
– Mutations in the genes of LH or FSH β-subunits or
the GnRH-receptor
– a no of genetic mutations under study

Acquired-
– commonly develop after menarchae mainly 20
amenorrhoea after normal pubertal growth
PITUTARY ADENOMAS-the most common cause of
acquired pituitary dysfunction
Prolactinomas-
• the most common pituitary adenomas
• Secret PRL↑serum PRL (10 hyperprolactinomia)
 reflex central DOPAMINE secretion 
DOPAMINE interaction with Rs on GnRH neurons
 alteration of GnRH pulsatile secretion
disrruption of normal cyclic gonadotrope
secretion anovulation + Amenorrhoea

• Other pitutary adenomas
– Their scretions affect GnRH secretion pattern in
different ways
– Mass effect-may compress lactotropes or
the pitutary stalk blockage of dopmine
passage to anterior pitutary↑20 PRL
elevation↑ dopamine production
NB. Hypothyroidism can also cause hyperprolactinomeia
↑TRH Rs On lactotropes stimulation of PRL secretion

• Pituitary Destruction
– Inflammation EG. peripartum lymphocytic
hypophytis (rare cause of pit. Failure)
– Infiltration E.g. sarcoidosis, hemochromatosis
– Metastatic lesions
– Sheehans syndrome
– Iatrogenic – radiation, surgical resection of pit
adenomas

Sheehan syndrome
• Refers to panhypopituitarism that develops after
massive PPH complicated by hypotension (Kelestimur,
2003).
• In its most severe form, patients develop shock and
pituitary apoplexy. Loss of gonadotrope activity results
in anovulation and subsequent amenorrhea.
• Damage to the other pituitary cell types may present
as failure to lactate, loss of sexual and axillary hair,
hypothyroidism, and adrenal insufficiency.
• The pituitary cell types are differentially sensitive to
damage. Prolactin secretion deficiency is the most
common, -->followed by loss of gonadotropin and
GH release, -->loss of ACTH, and--> least commonly, by
decreases in TSH secretion

Other Causes of Hypogonadotropic
Hypogonadism
• Hypogonadotropic amenorrhea may be
observed in a wide variety of chronic diseases
including
– end-stage kidney disease,
– liver disease,
– malignancies,
– acquired immunodeficiency syndrome, and
– malabsorption syndromes

ሐ፡EUGONADOTROPIC AMENORRHOEA (EGA)
• not associated with significantly abnormal
gonadotropin levels.
• chronic steroid secretion interferes with the
normal feedback between the ovary and the
H-P axis.
• The lack of cyclicity interferes with normal
oocyte maturation, and menstruation fails to
occur

EUGONADOTROPIC AMENORRHOEA (EGA)
• Relatively normal gonadotropin levels
Estrogen secretion chronic anovulation
with estrogen present (CAWEP).
• This is in contrast to the patients with ovarian
failure or hypothalamic-pituitary failure in
which estrogen is low.
• This distinction may be useful during
evaluation and treatment.

EGA-Polycystic Ovarian Syndrome
PCOS-by far the most common cause of CAWEP
• a wide variety of menstrual presentations
– occasional ovulatory cycles
– Menometrorrhagia (unopposed Em E stimulation)
– complete amenorrhea.
• Amenorrhea in PCOS patients may be
attributable in part to the atrophic effects of
androgens on endometrial proliferation.

EGA-Polycystic Ovarian Syndrome
• PCOS can be appropriately characterized as an
inherited form of eugonadotropic amenorrhea.
• an increased incidence of PCOS in the mothers and
sisters of affected individuals(but no identified
specific gene defect)
• in most patients-↑LH:FSH levels ratio (>2) ,
• however, the LH level remains in the normal or
high-normal range

EGA-Late/adult onset CAH
Adult-Onset / late-onset Congenital Adrenal Hyperplasia (CAH)
• Closely mimics the presentation of PCOS, 
hyperandrogenism and irregular menstrual cycles.
• Most common cause -CYP21mutation gene, which
encodes the 21-hydroxylase enzyme.
• Patients with CAH are unable to convert an adequate
percentage of progesterone to cortisol and aldosterone,
thus increasing the production of androgens
• With a mild mutation, patients are asymptomatic until
adrenarche and its associated requirement for ↑ed
adrenal steroidogenesis
• As in PCOS, elevated androgen levels blunt oocyte
maturation and thereby result in anovulation and
amenorrhea

EGA-Ovarian Tumor
• Although uncommon, CAWEP can also be
observed with ovarian tumors producing
either estrogens or androgens.
• Examples of these neoplasms include
granulosa cell tumors, and theca cell tumors

EGA-Hyperprolactinemia and Hypothyroidism
Hyperprolactinemia can be categorized as a cause
of pituitary hypogonadotropic hypogonadism.
• Of note, however, many of these patients may
have relatively normal gonadotropin levels,
although as a group their estrogen levels will be
mildly depressed.
• Thyroid disease is also a relatively common cause
of oligomenorrhea associated with
gonadotropins in the normal range.
• Classically, hypothyroidism is stated to cause
amenorrhea, where as hyperthyroidism is
implicated in menorrhagia.

Patient Evaluation-Hx
• Pubertal development achieved?
– Normal onset and progression?
• ever achieved regular menstrual cyclicity?
– cycle interval, duration, and amount of menstrual flow
– Timing of change in the cycle pattern?
– Sudden or gradual?
– Any correlation with pelvic infection, radiation,
surgery, chemotherapy or other illness?
• Surgical and medical History
– Hx of/ coincidence of amenorrhoea with pelvic
surgery (particularly intrauterine surgery, including
D&C) ,radiotherapy , pelvic nfection, other llnesses?
– Thorough medical history

Patient Evaluation-REVIEW OF SYMPTOMS
• New-onset headaches or visual changes 
likelihood of CNS or pituitary gland tumor.
• Outer visual felds loss Pit tumors impinging on
optic chiasm Bitemporal Hemanopsia
• Spontaneous bilateral breast discharge 
?HYPERPROLACTINEMIA --Galactorrhoea.
• Heat or cold intolerance, weight changes, and
sleep abnormalitiesprobable thyroid disease .
• Hot flashes and vaginal dryness 
hypergonadotropic hypogonadism or POF.
• Hirsutism and acne ? PCOS, late-onset CAH.
• Cyclic pelvic pain  ?a reproductive tract outlet
obstruction.

Patient Evaluation-FAMILY AND SOCIAL HISTORY
Important questions include:
– a history of premature cessation of menses or
autoimmune disease, including thyroid disease, which
would suggest an increased risk for POF.
– A family Hx of irregular menses, infertility, or signs of
excess androgen production may be noted in a patient
with PCOS.
– Sudden neonatal death may have occurred in family
members carrying mutations in the CYP21 gene
responsible for classic CAH.
– exposure to environmental toxins, including
cigarettes.
– Any medications, especially those that increase
prolactin levels such as antipsychotics should be noted

Patient Evaluation-PE
GENERAL APPEARANCE can be helpful in the evaluation
of amenorrhea.
– A low BMI, perhaps in conjunction with loss of tooth
enamel due to recurrent vomiting, is highly suggestive for
an eating disorder.
– Signs of Turner syndrome should be evaluated, including
the presence of short stature and other stigmata such as
webbed neck or shield-shaped chest.
– Midline facial defects, such as cleft palate, are consistent
with a developmental defect of Hypothalamus or the
anterior pituitary gland.
• VITAL SIGNS
– HYPERTENSION IN A PREPUBERTAL GIRL would be
consistent with mutation in the CYP17 gene 
steroidogenesis shunted towards Aldostrone production.

• VISUAL FIELD CHANGES, particularly bitemporal
hemianopsia, or other visual defects may be
indicative of apituitary or CNS tumor in the gland or
central nervous system.
• Thyroid
– enlargement,delayed reflexes, and bradycardia
Hypothyroidism
• SKIN
– acanthosis nigricans, hirsutism, acne 
Hyperinsulinemia/ hyperandrogenism eg. PCOS
– Supraclavicular fat, Abdominal striae, HTN cushings s
• BREAST
– bilateral galactorrhea  hyperprolactinemia

THE GENITALIA
• Hair Pattern.
– Sparse or absent female pubic hair  ? lack of adrenarche or AIS .
– a male pattern (hair extends to the umbilicus, forming a triangle, or male escutcheon) 
↑androgen levels .
• A vaginal smear to demonstrate a majority of . (SEE NEXT SLIDE)
• signs of virilization, most noticeably clitoromegaly result from
Markedly elevated levels of androgens . Voice deepening and
male pattern balding may also be noted
• Evidenceof estrogen production - pink moist vagina , cervical
mucus. Vagnal smear -Superficial epithelial cells dominate
• Determination of müllerian anomalies
• PR may help identify a uterus above an obstruction at the level
of the introitus or in the vagina.
– The presence of hematocolpos suggests normal ovarian and
endometrial function

• cytologic specimens illustrate key points of the
maturation index. This index provides insight into the
cytohormonal status of the patient and is based on a
count of parabasal, intermediate, and superficial (P:I:S)
cells. Generally, a predominance of
– superficial or superficial and intermediate cells - in
reproductive-aged women.
– intermediate cells -seen in the luteal phase, pregnancy,
with amenorrea, and in newborns, premenarchal girls, and
women in early menopausal transition.
– parabasal cells (D) - seen in menopausal patients with
atrophy

WorkUps
• Progesterone Challenge test
• Serum hormone level

Tests Commonly Used in the Evaluation of Amenorrhea
Primary laboratory tests Diagnosis
β-hCG Pregnancy
FSH Hypogonadotropic versus hypergonadotropic
hypogonadisma
Estradiol Hypogonadotropic versus hypergonadotropic hypogonadism
Prolactin Hyperprolactinemia
TSH Thyroid disease (hypothyroidism)
Secondary laboratory tests
Testosterone PCOS and exclude ovarian tumor
DHEAS Exclude adrenal tumor
17-OH-P Late-onset CAH
2-hour glucose tolerance test PCOS
Fasting lipid panel PCOS
Autoimmune testing Premature ovarian failure
Karyotype Premature ovarian failure <35 years
Radiologic evaluation
Sonography PCOS or to determine presence of uterus
HSG or saline-infusion
sonography
Müllerian anomaly or intrauterine synechiae
Magnetic resonance imaging Müllerian anomaly or hypothalamic-pituitary disease

Imaging
• N umber of modalities depending on the
suspected etiology.
• A sonographic examination is frequently
useful as a first screen in those with a grossly
normal uterus
• HSG or SIS excellent for the detection of
intrauterine synechiae or developmental
anomalies

Imaging
• MRI and CT of Sella Turcica- to RO anatomic causes of
hypogonadotropic hypogonadism
• Imaging is highly sensitive for identification of
destructive disorders such as tumors or infiltrative
diseases of the hypothalamus or pituitary.
• Patients with Kallmann syndrome frequently
demonstrate defects in the development of the
olfactory bulbs and sulci of the rhinencephalon (Klingmuller,
1987).
• Functional Hypothalamic A (stress, Eating disorder,
exercise)- Dx by exclusion

Treatment
• Depends on etiology as well as goal of
treatment

Outline
• Definition
• Causes
• Evaluation
– Hx
– PE
– Workup
• Treatment
2
ሳሙኤል በዛብህ ህዳር 2006 ጎንደር

Definitions
• Infertility
• Subfertility
• Fecundity
• Fecundablity
• Sterility
ሳሙኤል በዛብህ ህዳር 2006 ጎንደር 3

DEFINITIONS
INFERTILITY- the inability to conceive after 1 year of
unprotected intercourse of reasonable frequency .
• affects 10 to 15% of reproductive-aged couples.
– primary infertility-no prior pregnancies, and
– secondary infertility-infertility following at least one prior
conception.
– 1/3rd of time attributed to the male , another 1/3rd to the
Female, 1/3rd to both
• Most couples will ultimately conceive if given enough time.
 SUBFERTILE, rather than infertile
– This concept of subfertility can be reassuring to couples
• In those attempting conception, approximately
– 50 % of women will be pregnant at 3 months,
– 75% will be pregnant at 6 months, and
– > 85% will be pregnant by 1 year (Guttmacher, 1956; Mosher, 1991).
4

DEFINITIONS
FECUNDABILITY is the ability to conceive,
– data from large population studies have shown a
monthly probability of conceiving of 20 to 25 %.
Fecundity - the probability that a single
menstural cycle will result in a live birth
STERILITY: incapablity to become / be
induced to become pregnant or to induce
pregnancy
5

Etiology
Female infertility
Ovulatory Dysfunction
Tubal /Peritoneal Factor
Uterine Factor
Cervical Factors
Vaginal Factors
Chronic systemic
diseases
Social personal
habit(illicit drugs)
Unexplained
Male factors
Pre-testicular
Testicular
Post-testicular
Idiopathic
6

Etiology of Infertility
• Male factor-------25%
• Ovulatory----------27%
• Tubal/ uterine----22%
• Other---------------9%
• Unexplained------17%
7

• Hypothalamic Disorders
• Anterior pitutary disorders
• Ovarian Abnormalities
– Premature Ovarian Failure (POF)
– Androgen excess
• Polycystic ovarian syndrome
• Nonclassic congenital adrenal hyperplasia
• Androgen-secreting tumors NMS
– Decreased ovarian reserve ( often age related)
8

WHO clasification of anovulatory disorders
Group I-
• Hypogonadotropic Hypogonadism
/ Hypoth. amenorrhea/ H-P failure
• Low GnRH/ Unresponsive Pitutary
Low FSH & E level, normal
prolactin level
• Stress, eating disorders, kallman S.
• Excludes women with P, H masses
GROUP II- PCOS
Normogtrotpic Normoestrogenic
anovulation/ H-P Dysfunction
Normal gonadotropin ( ~low follicular
Phase FSH), E, Prolactin level
Oligo/amenorrhoea, some may
occasionally ovulate
GROUP III Hypergonadotropic-
Hypoestrogenic anovulation
• Premature OF absence of follicles
b/se of early menopause
• Ovarian Resistance ( follicular form)
• Amenorrhoea + elevated FSH level
Hyperprolactinemic Anovulation
(Distinct entity)
• Elevated PRL inhibition of G and E
secretion
• Amenorrhoeic/
Oligomenorrhoeic/regular
anovulatory cycles
• Usually normal seum Gtropin level
9

ሀ፡Hypothalamic Disorders
result in Hypogonadotropic Hypogonadism
– Acquired-
• eating disorders,
• stress or
• extreme exercise
– Inherited-
• Kallmans Syndrome/ idiopathic hypothalamic
hypogonadism
10

OVULATORY DYSFUNCTION
ለ: Anterior Pitutary Disorders
Result in Hypogonadotropic hypogonadism
– Adenomas –
• most commonly prolactinomas
• Others that may compress gonadotropes or anterior P stalk
– Destruction by infiltrating tumors, sarcoidosis, TB,
inflammation
• Hyperprolactinemia
– Medications (many medication classes, including
antipsychotics that are dopamine receptor antagonists; a
typical example is haloperidol)
– Pituitary tumors
– Hypothyroidism (Increased thyrotropin-releasing hormone
[TRH] secretion stimulates prolactin secretion.) NMS
11

ሐ: Ovarian abnormalities-
Premature Ovarian Failure (POF)- loss of ovarian
function before 40
• At 35- 1/ 250 at 40 -1/ 100 woman
POF results in Hypergonadotropic
Hypogonadism
– ↑ LH, FSH, ↓ E, P
– menst irregularity,amenorrhoea,
– Symptoms of Hypoestroginism-hot flashes,
genital atrophy
– Family history of POF, up to 10% of cases of POF
may be familial.
12

POF causes
• Chromosomal
– 45X0 (Turner’s Syndrome)
– Mosaicism ( 45X/46XX, 45X/ 46XY)
– 46XX with defective X chromosome
 long arm deletion, Partial X chr Deletion, Fragile X chromosome
syndrome, ---
– Gondal agenesis 46XX
– Gonadal dysgenesis 46XY
• Other POF causes
– Autoimmunity, Infection,
– Iatrogenic chemo/radiotherapy, surgical removal of ovaries
– Resistant ovary syndrome
– Enzyme deficiencies ( 17 alpha OH, aromatase)
– Galactosemia ( toxic to oogonia)
– Idiopathic 13

መ: Habits
– Smoking
• accelerated follicle depletion + mutation in gametes (and early
embryos)
– Alcohol
• heavy alcohol intake decreases fertility in women
• Based on a number of studies, 5 to 8 drinks per week negatively
impacts female fertility
– MALE-heavy alcohol intake has been associated with a
decrease in sperm counts and increase in sexual
dysfunction in men
– Caffein- increased dose response r/n ship b/n Caffein and
infertility and miscarriage
– illicit drugs
14

Age related Infertility (Depletion of O reserve)
• Advancing age loss of viable oocytes ( depletion of
ovarian reserve + genetic abnormality in the remaining
like mitochondrial deletions ) decreased fertility/
increased misscarriage/Infertility
– Miscarriage risk at> 40yrs ~ 50-75%
• No of follicles
– at mid gestation
– 3million at birth
– 300,000at puberty
– < 1000 at onset of menopause

Female Aging and Infertility
Female Age (years) Infertility
• 20–29 8.0%
• 30–34 14.6%
• 35–39 21.9%
• 40–44 28.7%

TUBAL + PERITONEAL FACTORS
• Pelvic adhesion and/ tubal obstruction
• Manifest with chronic pelvic pain and dysmenorrhoea
• Interfer with tubal motility, ovum pick up and
transport of fertilized ovum
• RFs
– Hx of Pelvic infections/PID
– Hx of ectopic pregnancy- tubal damage even with
medical treatment
– Hx pelvic surgery- residual adhesions are inevitable
– Emdometriosis -chronic bleeding and
inflammation tubal obstruction or pelvic adhesion
17

UTERINE FACTORS
Congenital Anomalies
• In general, developmental uterine anomalies are
not causative for infertility, but may be associated
with miscarriage or later fetal loss, creating a
management dilemma
Acquired Abnormalities
– Endometrial Polyps-3-5% of women
• Intermenstrual and postcoital bleeding
– Leiomyomas- implantation
– Ashermans Syndrome/ synechae
18

CERVICAL FACTORS
• The cervical glands secrete mucus that is normally
thick and impervious to sperm and ascending
infections.
• High estrogen levels at mid cycle change the
characteristics of this mucus, and it becomes thin,
copious, clear and stretchy (5cm)  SPINNBARKEIT.
• Estrogen-primed cervical mucus:
– filters out non sperm components of semen and
– forms channels that help direct sperm into the uterus
– also creates a reservoir for sperm, allowing ongoing
release during the next 24 to 72 hours and extending the
potential time for fertilization . 19

Cervical Factor
• Mucus inadequacy/ hostile mucus
– Chronic infection,
– cervical surgery Eg Chryotherapy, LEEP, Conization
– anti E Tx ( Chlomiphe Citrate for OI),
– Sperm antibodies
– Unexplained ( most)

EVALUATION OF PATIENT

Evaluation
• The infertility evaluation can be conceptually
simplified into confirmation of:
1. ovulation,
2. normal female reproductive tract anatomy, and
3. normal semen characteristics.
23

Evaluation
• Timing
– After an attempt to conceive for one year
– Earlier initiation ( as soon as possible) of evaluation
is recommended for
• those with Hx PID or pelvic surgery
• anovulatory woman (with irregular or absent menses)
• old age (>35-40),
• heavy smokers or in women with a history of ovarian
surgery, chemotherapy, or pelvic irradiation
• stigmata of chromosomal abnormalities(eg :turners
syndrome) or
• a significant history in the male partner
24

Female History
GYNECOLOGIC
• Duration of infertility, 10 Vs 20 infertility
• Menstrual history-
– Frequency, duration, recent changes in pattern, dysmenorrhoea, hot
flashes
• Coital HX
– Frequency , dyspareunea (? Endometriosis)
• Prior use of contraceptives
• Hx of recurrent ovarian cysts, endometriosis, leiomyoma, STI/ PID
• Prior conception ( tubal patency and ovulation HX)
• Pregnancy complications
– eg. miscarriage, EP, preterm delivery, retained placenta, postpartD & C,
chorioamnionitis or fetal anomalies should be noted
• Abnormal pap smears + cervical conization abnormal cervical
mucus + cervical incompetence
25

Female History
Gynecologic Hx.
Menstrual Pattern- ovulation is likely with
– cyclic menses Q 25-35 days, 3-7 days duration
– MITTELSCHMERZ,
• midcycle pelvic pain associated with ovulation
– MOLIMINAL SYMPTOMS
• breast tenderness, acne, food cravings, and mood changes
– DYSMENORRHEA,
• Ovulatory cycles are more likely to be associated with
dysmenorrhea, although severe dysmenorrhea may suggest
the presence of endometriosis
26

Female History
Medical
– Symptoms of hyperprolactinemia, hypothyroidism,
Kallmans s
– Symptoms of androgen excess
• Eg hirsuitism, acne PCO, CAH
– Prior chemo / and radiotherapy  ovarian failure
– Medications Eg.
• NSAIDS ( ovulation inhibition  luteinized unruptured follicle
syndrome
• antipsychotics ( phenothyazines??block dopamine Rs
↑PRL
• MAOs ↓catecholamines↑PRLannovulation +
amenorrhoea
SURGICAL
– History of pelvic and abdominal surgery pelvic
adhesion, tubal blockage, Intraux adhesion 27

Female History
SOCIAL
• Eating habits ( AN , BN) ,exercise and stress
–  hypothalamic functional amrnorrhoea + anovulation
– BMI <17 & >25 associated with GnRH and gonadotropin
secretion Abnormalities
• Smoking
– accelerated follicle depletion + mutation in gametes (and
early embryos)
– High failure rate of ART
– Increased miscarriage + trisomy 21
• Alcohol
– heavy alcohol intake decreases fertility in women
• Based on a number of studies, 5 to 8 drinks per week negatively
impacts female fertility
– heavy alcohol intake has been associated with a decrease
in sperm counts and increase in sexual dysfunction in men
28

Female History-SOCIAL CONTD
• CAFFEIN
– 1cup of coffee ~ 115 mg caffein
– Caffeine consumption has also been linked to
decreased fecundability.
– Most studies suggest that consumption of > 250 mg
caffein per day by the female partner is associated
with a modest, but statistically significant, decrease
in fertility and increase in time to conception.
– Caffeine intake greater than 500 mg per day has also
been demonstrated to increase recurrent miscarriage
rates
29

Female History-SOCIAL CONTD
Illicit drugs may also impact fecundability.
– Marijuana suppresses the H-P- gonadal axis in both men
and women, and
– cocaine can impair spermatogenesis
Env’tal Exposures
• Heavy metals and Pesticides should also be avoided,
may decrease fertility rates as well as increase the risk
of recurrent miscarriage (Orejuela, 1998).
• Although uncommon, fecundability is reduced with
occupational exposure to the dry cleaning fluid
Perchloroethylene, and to Toluene used in the printing
business.
30

Female History
FAMILY HISTORY
• of infertility, POF, recurrent miscarriage, or
fetal anomalies may point to a genetic
etiology.
• Although the inheritance pattern is complex,
data suggest that both PCOS and
endometriosis occur in familial clusters
– For example, it has been estimated that a woman
carries a sevenfold increased risk of endometriosis
over the general population if a single first-degree
family member has the disease
31

Obesity and Environmental Factors Vs Fertility

Female PE
• Vital signs, height, and weight
– BMI <17 & >25 associated with GnRH and gonadotropin
secretion Abnormalities
• Hirsutism, alopecia, or acne indicates the need to
measure androgen levels.
• Acanthosis nigricans is consistent with insulin
resistance associated PCOS or much less commonly,
Cushing syndrome.
• Galactorrhea- Hyperprolactinemia
• Skin Hyperpgmentation~~ adrenal insufficiency
• Stigmata of Turners syndrome- short sture, schield
chest
• thyroid abnormalities- Goitre~~Aimmune
Thyroiditis
33

Female PE
A PELVIC EXAM
• Inability to place a speculum through the
introitus may raise doubts about coital frequency.
• Estrogen Adequacy- moist and rugated vagina,
and a reasonable amount of cervical mucus ,
– Hypoestrogenism-atrophic vaginitis
• uterus-
– enlarged or irregularly shaped uterus ~ leiomyomas,
– fixed uterus ~ presence of pelvic scarring due to
endometriosis or prior pelvic infection.
– Uterosacral nodularity or ovarian masses may
additionally implicate endometriosis.
34

Female PE
NB
– All women should have a normal Pap smear result
within the year preceding treatment.
– cultures for Neisseria gonorrhoeae and Chlamydia
trachomatis should be Negative --> to avoid
ascending infection on cervical manipulation .
• Breast- bilateral discharge galactorrhoea
due to hyperprolactinemia
35

Laboratory
• The initial laboratory tests to consider for the
female partner include
– CBC, blood type and antibody screen,
– cervical cytology,
– TSH , serum prolactin
– routine prenatal labs including rubella
antibodies,HBSAG , HIV and rapid plasma
reagent (RPR).
36

Summary of Workup
• Ovulatory dysfunction
– Serum mid luteal progesterone
– Ovulation predictor kit
– Early follicular FSH ± estradiol level (ovarian reserve)
– + Serum AMH level
– ± Serum measurements (TSH, prolactin, androgens)
– ± Ovarian sonography
• Follicle Dvt & collapseovulation
• Early F antral follicle count- < 10 ↓ ovarian
reserve↓response for gonadotropin stimulation
• PCOS
– ± Basal body temperature chart
– ± Endometrial biopsy (luteal phase defect)???
37

contd.
Additional workups for ovulation
POF-
– ↑ serum FSH level (~>40)
• RO Polyglandular autoimmune failure look
for Endocrinopathies
– Thyroid(TSH) Parathyroid (serum Ca,
Phosphorus) FBS, Adrenal autoandibodies
• R/O other causesn of
anovulation/oligo/amenorrhea
– PRL, TSH, hCG, Androgen
• Serum Testesterone PCOS , Ovarian
Tumos
• DHEAS adrenal Tumors
• 17-hydroxyprogesterone (to rule out 38

Summary of Workups
• Tubal/pelvic disease
– HSG
– Laparoscopy with
chromotubation
• Uterine factors
– HSG
– Transvaginal sonography
– Saline-infusion sonography
– MRI
– Hysteroscopy
– Laparoscopy
• Cervical factor
– ± Postcoital test
• Male factor
– Semen analysis
39

Determination of Ovulation
Clinical features suggestive of ovulation
Eg Menstrual Pattern, MITTELSCHMERZ, MOLIMINAL
SYMPTOMS , Basal body temprature
40

BASAL BODY TEMPRATURE
• BIPHASIC TEMPERATURE pattern on graphically
charted morning oral tempratures
• Oral temp. 97.0- 98.0°F during the follicular
phase.
• Postovulation –BBT increases by ~ 0.4-0.8° F 
due to rise in progesterone levels
NB
– BBT method is insensitive in many women.
– Increase in BBT follows ovulation the window of
maximal fertility* is missed for couple wishing to
concieve
* 05 days preceding the presumed day of ovulation through the ovulation
day 41

OVULATION PREDICTOR KITS -LH surge determination
• Measure urinary LH conc by colorimetric assay
• Testing should begin 2 - 3 days prior to the
predicted LH surge, and testing should be
continued daily.
• There is no clear consensus regarding the
optimal time of day to test.
• LH surge spans only 48 to 50 hours.
• In most instances, ovulation will occur the day
following the urinary LH peak
42

MID LUTEAL SERUM PROGESTRONE (MLP)
• At day 21 ( 7days after ovulation)
• Levels > 4-6ng/ ml high correlation with
ovulation
– Hull and colleagues (1982) have reported that a MLP > 9.4
ng/mL is predictive of higher pregnancy rates than
those observed in patients with < 10 ng/mL.
• Follicular phase level < 2ng/ml
– NB. the midluteal progesterone level is best regarded
as an excellent measure for the occurrence of
ovulation, but not an absolute indicator of adequate
luteal function.
43

SONOGRAPHY
• Serial ovarian sonography
– demonstrate the development of a mature antral
follicle and its subsequent collapse during ovulation.
– time consuming and ovulation can be missed.
• Secretory endometrium  ovulation
– May be confounded with Prior hormonal rx
• Excellent approach for supporting the diagnosis
of PCOS with its associated oligo-anovulation -
44

1.ENDOMETRIAL BIOPSY
Biopsy taken late in the luteal phase
Luteal Phase Defect/ Out of Phase Biopsy histologic
appearance lagging >2 days relative to the actual day of
the cycle determined retrospectively (eg Day 22 histology
on Day 26)
Inadequate progesterone from the CL/ endometrial
response
Frequency in infertile women is agreed to be between 5
and 10 percent
NB
– High intra-observer and inter-observer variability
– Nearly comparable incidence of LPD among infertile and fertile
groups little predictive value
NO longer considered a routine part of the infertility evaluation.
45

Ovarian Reserve Assessment
• ↑ Age depletion of follicles + mutation↓
ovarian reserve ↓ fertility

Early Follicular phase FSH level (days1-3)
• Classically “Cycle Day 3” FSH level is measured,
but tests b/n days 2 to 4 are reasonable
– Declining Ovarian function↓ inhibin secretion (from
Gcells and Luteal cells)↓ luteal Inhibin↑ FSH level
– FSH >10miu/ml  significant loss of OR a need for
more rapid evaluation and more intensive treatment.
• In a large study evaluating IVF cycles, a day-3 FSH
level exceeding 15 mIU/mL was predictive of
significantly lower pregnancy rates (Muasher, 1988;
Scott, 1995; Toner, 1991).
47

Early Follicular Phase Estradiol level
• Along with FSH level measurement
• Decreases false positive results in FSH alone
• Elevated estradiol (>80pg/ml)  abnormal
Despite an overall follicular depletion, E level rises
early in the cycle of old women due to the
elevated FSH level which stimulates
steroidogenesis
48

Anti Mullerian Hormone level measurement
• AMH is expressed by Gcells of preantral follicles ,
but very limited expression from Gcells of larger
follicles
may have a role in recruitment of the dominant
follicle
• AMH Level corresponds to the number of
primordial follicle and not cycle stage dependent
• Advantageous over FSH and E , Inhibin B tests
– Drop before changes in FSH and E level are evident
– Expression of AMH is independent of cycle stage
can be tested at any stage of Menst cycle
• Elevated AMH in PCOS consistent with the
multiple early follicles seen in PCOS

Sonography
• TVUS to measure ovarian volume and obtain
an early follicular phase antral follicle count
• The number of small antral follicles reflects
the size of the resting follicular pool.
• Less than 10 antral follicles predicts poor
response to gonadotropin stimulation
50

Radiologic Evaluation
HSG
– Tubal patency
– Contour of the intrauterine cavity + shape and size
– Polyp, leiomyoma, intrauterine adhesion-
intrauterine filling defect
– Developmental uterine abnormalities
51

HSG-
• on days 5-10 b/se of less likelihood of
– clots that block tubal outflow or falsely appear pathologic
– pregnancy
• excellent predictor of tubal patency
• 65% sensitivity, 83% specificity for tubal obstruction
• less effective at identifying normal tubal function &
peritubal/pelvic adhesion
• False positive commonly due to proximal
tubal/cornual spasm
• Unilaterally patent tube is rare as tubal diseases affect
both tubes=>unilateral obstruction with Normal
contralateral tube ~ascent of dye along the low
resistance path
• pregnancy may be facilitated by the flushing of
intratubal debris with oil based dyes during HSG
52

HSG
• Powerful Ux cavity evaluating tool
• intrauterine “defect” in dye opacity –
– A polyp, leiomyoma, or adhesion within the cavity
• false positives may be obtained due to
– blood clots, mucus plugs, or shearing of the
endometrium during placement of the intrauterine
catheter
• One study- 98% sensitivity, 35%specificity,
70%PPV, 8% NPV
• Most misdiagnoses were due to an inability to
distinguish polyps from submucous leiomyomas.

Sonography
• TVUS may also be helpful in determining
uterine anatomy, particularly during the
luteal phase, when the thickened
endometrium acts as contrast to the
myometrium.
• Although not yet widely available, the
development of three-dimensional ultrasound
machines is advancing the discriminatory
abilities of sonography.
54

SIS
• SALINE ULTRASOUND, HYSTEROSONOGRAPHY,
SONOHYSTEROGRAPHY, OR SALINE-INFUSION
SONOGRAPHY (SIS) -the infusion of saline into
the endometrial cavity during follicular phase
provides another approach for achieving
contrast between the cavity and uterine walls
55

SIS
• SIS has been reported to have a sensitivity of 75%
and specificity of over 90%.
• It has an acceptable PPV of 50% and an excellent
NPV of 95%, which greatly exceeds the negative
predictive value of HSG (Soares, 2000).
• Moreover, SIS may be more sensitive than HSG in
determining whether a cavitary defect is a
pedunculated leiomyoma or a polyp .
• Perhaps more importantly, SIS can help determine
what portion of a submucous leiomyoma is within
the cavity, as only those with less than a 50%
intramural component should be approached by
hysteroscopy
56

SIS
• SIS is generally less painful than HSG and does
not require radiation exposure.
• Therefore, it is the preferred method if
information about tubal patency is not required,
such as in patients who are known to require IVF.
• The primary limitation of SIS is that it does not
provide information about the fallopian tubes,
although rapid loss of saline into the pelvis is
certainly consistent with at least unilateral
patency.
57

Laparoscopy
• The gold standard approachDirect inspection provides
the most accurate assessment of pelvic pathology . .
• Allows both diagnosis and immediate surgical treatment Eg
.Laparoscopic ablation of endometriotic lesions or adhesions
may increase subsequent pregnancy rates.
• Chromotubation may be performed for tubal patency, a
dilute dye is injected through an acorn cannula placed
against the cervix or a balloon catheter positioned within the
uterus . Tubal spill is evaluated through the laparoscope
Indigo carmine dye is preferable to methylene blue, as the
latter rarely may induce acute methemoglobinemia,
particularly in patients with G-6-PD deficiency
• As laparoscopy is an invasive procedure, it is not advocated
in place of HSG as part of the initial infertility evaluation.
58

Hysteroscopy
• Endoscopic evaluation of the intrauterine cavity is
the primary method for defining intrauterine
abnormalities.
• Hysteroscopy can be performed in an office or
operating room.
• With improved instrumentation, the ability to
concurrently treat abnormalities in the office is
increasing,
• However, substantially more extensive
hysteroscopic surgery is possible in an operating
room setting
59

Post Coital test-PCT/Sims-Huhner test
• PCT provides basic information regarding Cervical mucus
production, appropriate intercourse practices, and presence
of motile sperm
• A couple will have intercourse on the day of ovulation.
• within a few hours, a sample of the cervical mucus is
obtained from the cervical os with forceps or by aspiration
and examined
• Normal findings
– Spinnbarkeit- clear, copious, stretchable to 5cm 9 b/n slides)
– At least five motile sperm /HPF some authorities feel that a
single, forward-moving sperm is adequate.
– a minimal number of other cell types, such as inflammatory
cells.
– ferning pattern When dried, due to an increased salt conc. in
the mucus prompted by ↑ preovulatory E levels
60

2 and 3
Decreased sperm motility
in Thick Hostile Mucus
1-Columns within
adequate cervical
mucus help direct
sperm into the
uterine cavity

Evaluation of the male Partner
History
• Pubertal development
• Sexual dysfunction
– Erectile D + decreased beard low testosterone level
• Ejacualtory dysfunction , dev’tal anomalies
– Eg Hypospadia sboptimal semen diposition
• STI, GU infections ( Epidimytis, Prostatitis) VD obstruction
• Mumps abnormal sperm stem cells 20 to testicular inflammation
• Cryptorchidism, testicular torsion .Trauma abnormal
spermatogenesis
• Varicocele  increased scrotal temprature
– Effect of V on fertility- controversial
62

Evaluation of the male Partner
• Illicit drugs,
– alcohol, environmental toxins
– Anabolic steroids supress intratesticular Testosterone
productiondecreased sperm production ( may have
irreversible effect)
Medical Hx
– DM, HTN, Neurologic disorders Erectile dysfunction,
Retrograde ejaculation
– Chemo or localized radiotherapy
– Medications that worsen semen parameters
• Eg cimetidine, erythromycin, TTc, Gentamycin, spironlactone

Evaluation of the male Partner - PE
• As signs of testosterone production, normal SSCs Eg beard growth,
axillary and pubic hair, and perhaps male pattern balding should be
present.
• Gynecomastia or eunuchoid habitus may suggest Klinefelter
syndrome (47,XXY karyotype) (De Braekeleer, 1991).
• The penile urethra should be at the tip of the glans for proper
semen deposition in the vagina.
• Testicular length should be at least 4 cm with a minimal testicular
volume of 20 mL (Charny, 1960;Hadziselimovic, 2006). Small testes are unlikely to
be producing normal sperm numbers.
• A testicular mass may indicate testicular cancer, which can present
as infertility.
• The epididymis should be soft and nontender to exclude chronic
infection. Epididymal fullness may suggest vas deferens obstruction.
• pampiniform plexus of veins should be palpated for varicocele
(Jarow, 2001).
• Importantly, both vas deferens should be palpable. Congenital
bilateral absence of the VD is associated with mutation in the gene
responsible for cystic fibrosis (Anguiano, 1992).
• The prostate should be smooth, nontender, and normal size.

Male Workups
• Causes of male infertility can roughly be
categorized as
1. abnormalities of sperm production,
2. abnormalities of sperm function, and
3. obstruction of the ductal outflow tract.

Male Workup- Semen analysis
• Reflects events of the past 3months
– spermatogenesis requires an overall 90days
• Refrain from coitus for 2-3 days- masterbate/
sciilastic non lubricated condom--Sample to lab
within one hr
• Ideally the test is done 2x- at least a month apart
(once if N result)
• Doesnot provide information about sperm
function ultimate abilty to fertilize lack
absolute predictive value

Male Workup-Abnormalities In semen A
Low volume
• causes
– Short absteinence
– VD obstruction (partial/complete)- infection, tumor,
Test or inguinal surgery, trauma
– Retrograde Ejaculation(RE )- backward flow of semen
into bladder bse of failure of closure of bladder neck
during ejaculation
• RE causes- neuropathy in DM,SC injury, Prostate/ Retrop
surgery. Beta blockers contribute
• DX- Post ejaculatory UA ( Viable sperms can be retrieved frpm a
well alkalinized urine for CSI)

Male Workup-Abnormalities In semen A
• Oligospermia (low count)-concentration of fewer than 20 million sperm
/ml,(counts less than 5 m/ml are considered severe)
• Azoospermia (No sperm)
– Prevalence ~1% of all men
– Obstructive- outflow obstruction- infection, vasectomy, Congenital absence of
VD
– Non-Obst- Testicular Failure)-careful centrifugation and analysis may identify a
small number of motile sperm adequate for IVF use. Alternatively, viable sperm
may be obtained through either epididymal aspiration or testicular biopsy
• Asthenospermia- decreased total progressive movement
Progressive Movement graded in some labs
G 3 and 4- rapid, G 2- slow G 0-1- no progressive movement
Total progressive motility- %ge of sperms exhibiting forward movement ( G2-4)
• cause- prolonged absteinence , antisperm Abs , GT infections and vaicocele
• Hypo Osmotic swelling test differentiate b/n dead and alive non motile
sperms- alive sperms swell (functional membrane) and coil their tail – can
be used for ICSI
• Teratospermia- abnormal morphology

Male workup-Abnormalities In semen A
• Round cells in a sperm sample may represent either
leukocytes or immature sperm.
Lukocytospermia
• WBCs can be distinguished from immature sperm using
a variety of techniques, including a myeloperoxidase
stain for WBCs (Wolff, 1995).
• True leukocytospermia is defined as greater than 1
million WBCs per milliliter and may indicate chronic
epididymitis or prostatitis. In this scenario, many
andrologists consider empiric antibiotic treatment
prior to obtaining a repeat semen analysis.
• A common protocol would include doxycycline at a
dosage of 100 mg orally twice daily for 2 weeks.
• Alternative approaches include culture of any
expressible discharge or of the semen sample.

Male Infertility Workup
Other workups for male infertility include
• Antisperm antibodies assay
• DNA Fragmentation test
• Sperm Function assays
– Mannose fluoresence assay
– Hemizonal assay
– Sperm penetration assay
– Acrosomal reaction
• Hormonal Tests
– FSH
– Testosterone
– Prolactin
– Tyroid Function Tests
• Testicular Biopsy

Male Genetic Testing
• Genetic abnormalities- incorrectable but need
identification bse of their implication on the
health of the pt and offsprings
• Kleinfelters S (47XXY)
• Y chr microdeletion
• Cystic Fibrosis (Congenital Bilateral Absence of
Vas Deferens)

TREATMENT
74

Infertility Rx
• Treatment of infertility depends on
– cause
– Duration of problem
– Age (esp. of females)
75

Infertility Rx
Life style Therapy
– Environmental toxins
– Smoking
– Alcohol
– Caffeine
– Weight optimization
– Nutrition
– Exercise
– Stress management
Correction of identified causes
– Correction of ovarian dysfunction
76

Hyperprolactinomeia rx
• Treat/ correct underlying causes
– Treat hypothyroidism
– Avoid triggering drugs-----
• Treatment of PRL secreting Pitutary adenomas
– Medical mg’t -Dopamine agonists (bromocriptine,
cabergoline)
– Surgical mg’t – for medical rx resistant adenomas
77

Ovulation Induction
• Stimulation of ovulation for
– Ovarian dysfunction or
– Normally ovulating woman ( super ovulation, ---
• Frequent causes of OD are
– PCOS
– Diminished ovarian reserve
• Less commonly-Central ( H, P) disorders, Thyroid D,
• Rarely Ovarian tumors and adrenal abnormalities
Common ovulation inductions agents
– Clomiphene citrate
– CC + glucocorticoids
– Insulin sensitizers--Biguanides and Thiazolidinediones
– Gonadotropins
– Aromatase inhibitors 78

Correction of Anatomic Abnormalities
• Impair ova , sperm , embryo transport,
implantation of fertilized ovum
• Three primary types
– Tubal
– Peritoneal
– uterine
79

Tubal Factors
• Tubal occlusion Congenital, Infection,
Iatrogenic, idiopathic (rare)
– Proximal- ostium, isthmus ampulla
• Resection, obliteration,mucus/debris plugging
– Distal- on fimbrae-
• typically 20 to prior pelvic infection and adnexal
adhesion
Rx- IVF, Surgical
80

Tubal Factors-Treatment
• Proximal Occlusion
– Tubal Cannulation
• Selective salpingography for proximal occlusions
• Hysteroscopic cannulation
– Resection and anastomosis
• Distal occlusion
– Neosalpingostomy- new opening
• ( high risk of EP, low~50% pregnancy, reocclusion)
– Fimbrioplasty- adhesion release,
81

Treatment of Uterine Factors
• Leiomyomas
– Myomectomy appears to improve fertility
ie Both spontaneous and assisted conception
• Endometrial polyps- surgical removal
Studies show
– increased pregnancy rate and few early losses after
polypectomy
– Pregnancy rate doubled in intraux insemination( IUI )
after polypectomy than in those without
polypectomy
• IU adhesions- surgical release, Estrogen
82

Cervical abnormalities- Treatment
• Rx of infection if Mucus exam reveals cervicitis
• E estradiol supplementation, Guaifenesin rx (
mucolytic expectorant)
– Unconfirmed benefit+ EE may affect follicular dv’t
• Intra Uterine Insemination- for non infectious
cervical mucus abnormalities(preferd by most
clinicians)
83

ART
• ASRM Def of ART: procedures and treatments
that involve handling of human oocytes and
sperm or embryo with the intent of establishing
pregnancy
– Includes IVF +- ICSI but not artificial insemination and
superovulation drug therapy (ACOG, AAP Perinatal care guideline)
• ART, conventionally, involves egg retrival at one
point
• employed when direct correction of 10 cause is
not feasible
85

ART- perinatal Risks
• Perinatal risks associated with ART include
– High order MG
– Prematurity
– LBW,
– SGA
– C Delivery
– Pprevia
– Abruptio placentae
– PE
– Birth Defects
• The extent of relation, of these adverse outcomes
specifically to ART procedures Vs underlying factors in
the couple, is unclear,
(ACOG,AAP- Guidelines for perinatal care 7th Ed , 2012)

ART
Invitro Fetilization( IVF )
• Controlled Ovarian Hyperstimulation (COH)
egg retrival ( US guided vaginally) mixing with
sperm insertion of embryos/ zygote
transcervically ( US guided)
• COH with Gonadotropin ( FSH/ hMG) + ovulation
supression with GnRH analog
• Removal of hydrosalpinx/ salpinges and tubal
interruption facilitates implantation and
decreases miscarriage risk
87

ART
Intracytoplasmic Sperm Injection (ICSI)
• A variant of IVF
• Single sperm injected into ovum through ZP
and Cell memebrane after enzymatic digestion
of cumulus
• Applicable for male factor infertility ( eg by
sperm extraction from testes / epidydimis in
azospermia)
88

ART
Gestational Carrier Surrogacy
• Variant of IVF- fertilized ovum is placed in the
uterus of a surrogate mother for Women
– with incorrectable Ux factor
– Pregnancy poses life threatening hazards
– With repeatitive unexplained miscarriages
89

ART
Egg donation
– In ovarian failure/ diminished OR
– To protect the offspring from maternal genetically inheritable
diseases
• Fresh egg is preferable to croypreserved one
 need to synchronize cycle of the donor(D) with endometrial
preparation of recipient (R)
• For premenopausal R- GnRH is adminstred followed by
Estrogen to create artificial cycle
• D recieves GT and finally hCG and eggs are retrived after 36
hrs
• When D gets hCG, R starts to get progestrone
• E and P adminstration continues through 1st trimester
90

ART
Gamete Intrafallopian Transfer (GIFT)
For unexplained infertility
Largely replaced by IVF
• Egg retrival after COH
• Deposition of sperm and egg in FTs through
the fimbrae laparoscopically
91

Downregulation GnRH agonist protocol.
/long protocol. COCpill pretreatment- to
avoid cyst formation by initial GT flare
effect of GnRH rx .
GnRH agonist supress endogenous GT
secretion and premature LH surge
hCG- LH surge surrogate

GnRH agonist flare cycle protocol/ Short protocol–GnRH agonists initially bind
gonadotropes and stimulate FSH and LH release. This initial
flare of gonadotropes stimulates follicular development. Following this initial surge of
gonadotropins, the GnRH agonist causes receptor downregulation and an ultimately
hypogonadotropic state. Gonadotropin injections begin 2 days later to continue follicular
growth. As with the long protocol, continued GnRH agonist therapy prevents premature
ovulation.

GnRH antagonist protocol. As with GnRH agonists, these agents are combined with
gonadotropins to prevent premature LH surge and ovulation. This protocol attempts
tominimize risk of ovarian hyperstimulation syndrome (OHSS) and GnRH side effects,
such ashot flashes, headaches, bleeding, and mood changes.

Physiology of the vagina
• Normally vaginal PH is maintained bn3.8-4.5 by the lactic
acid from glycogen metabolism by the lactobacilli.
• Vaginal Epithelium squamous Epithelium
– Superficial cells
• main cell types in rep age
• Predominate when estrogen stimulaltion is present
– Intermidate Cells predominate in the luteal phase bse of
progesterone
– Parabasal cells predominate in the absence of either hrmone
ie menopausal state with no HRT
• Superficial cells of the vaginal wall epithelium contain
glycogen=mm effect of estrogen exposure ( reproductive
age, replacement therapy, OCPs, topical estrogen creams)

Bacterial Vaginosis*
A state of alteration of composition of vaginal flora
– H2O2 producing LB disappear ,mainly anaerobic bacteria
dominate eg G.vaginalis, mobilincus, Bacteriodes,
Mycoplasma)
• the concentration of anaerobes, as well as G. v and
Mycoplasma hominis, is 100 to 1,000 times higher
than in normal women.
• Lactobacilli are usually absent.
• It is not known what triggers the disturbance of normal vaginal
flora. It has been postulated that repeated alkalinization of the
vagina, which occurs with frequent sexual intercourse or use of
douches, plays a role
*BV is not considered as STI

BVDX
Amsel criteria
Graysh Discharge with fishy odor( tiny coat of vaginal
wall)-
Vaginal PH > 4.5
Microscopy- clue cells, no leucocytes
Whiff test positive ( with KOH)
Clue cells are superficial vaginal epithelial cells with
adherent bacteria, usually Gardnerella vaginalis, which
obliterates the crisp cell border when visualized
microscopically
In advanced BV >20% of epithelial cells are clue cells
no irritation , fever, no lymph nodes, no inflammation
NB. T.vag should be ruled out as it also causes anaerobic
overgrowth+ positive whiff test( BV accompanies~60% of
Trichomonas vaginalis infections)

Bacterial Vaginosis Risk Factors
(WILLIAMS G.)
• Oral sex
• Douching
• Black race
• Cigarette smoking
• Sex during menses
• Intrauterine device
• Early age of sexual intercourse
• New or multiple sexual partners
• Sexual activity with other women

BV
Treatment
Ideally, treatment of BV should inhibit anaerobes but not
vaginal lactobacilli
• Metronidazole (75-84% cure rate)
– Po 500mg bidx07days
– 0.75% 5gm gel PV QD/BID x5days
• Clindamycin
– 2% 5gm cream PV at bed time for 7days
– 300mg po bid for 7days
– 100mg ovules PV at bed time for 03 days
NB- treatment of partners is not necessary as it doesn’t
improve therapeutic response

BV
Complications
– Acute PID (non gonococcal/chlamydial)
– Post procedure /post abortal endometritis
– Post hysterectomy cuff cellulites
– PROM, Preterm labor/delivery,
– chorioamnionitis

Trichomonas vaginitis
Etiology –
– anaerobic flagellated, parasite
– high rate of sexual transmission-
– responsible for acute vulvo vaginitis

Trichomonas vaginitis-DX
Profuse, malodorous, purulent Vaginal discharge + vulvar
pruritis
Patchy vaginal erythema/colpitis macularis( strawberry cx) if
high amt of organisms are present
PH of vaginal discharge > 5.0
Microscopy-(wet mount)
– many wbc
– Leukocytes +++,
– no lactobacilli,
– mixed flora +++.
– Presence of motile trichomonads
Culture for resistant varieties after treatment
Clue cells+ whiff test positive may be seen on concomitant BV

Trichomonas vaginitis
• Appearance of symptoms usually 5 - 28 days
after exposure
• Infected men are usually asymptomatic but
may have nongonococcal urethritis.

Trichomonas vaginitis-Treatment
• Metronidazle (highly effective ~95% cure rate)
– 2gm po stat
– 500mg po bid x07 days
– If no response repeat the 7 day regimen
– If no response again 2gm po/dx5days or Tinidazole
2gm po/day x 05days
NB
• partner should be treated
• Metronidazole jell should not be used for
treatment of TV

Gonorrhea(NMS)
• cause - Gram-negative diplococcus Neisseria
gonorrhoeae with a predilection for columnar
and transitional epithelium
• Humans are the only natural host of this
bacterium
• In women, who often have mild or no symptoms,
gonorrhea may cause :
– cervicitis,
– urethritis,
– PID, and
– acute pharyngitis.

Gonorrhea
• Men, usually symptomatic, present with
– urethritis
– prostatitis and
– epididymitis.
• Systemic sequelae later develop in both men
and women.
• In newborns, exposure at birth may cause
blindness, infection of the joints, or even
serious sepsis

Gonorrhea(NMS)
Risk factors include:
• Young age
• Multiple sexual partners
• Failure to use barrier contraception
• Early sexual activity

Gonorrhea
– Disseminated gonococcal infection occurs in 1% to
3% of infected patients and is more common in
men than in women.
• Arthritis (both tenosynovitis and purulent, mono- or
polyarticular)
• Pustular or vesicopustular skin lesions may accompany
arthritis.
• Septicemia
• Endocarditis, meningitis and osteopyelitis (all rare)

Gonorrhea-Clinical presentation
Symptoms include:
– Mucopurulent discharge, ( in acute cervicitis in women urethritis in men)
– Lower abdominal pain, anorexia, and fever, as is characteristic of acute PID;
– perihepatitis can also occur because of peritoneal spread of infection.
– Dysuria (men and women)
– Pharyngitis (in men and women after oral contact with an infected penis)
– Proctitis in male or female recipients of anal intercourse

Gonorrhea-Other sequelae
• Women:
– increased risk of infertility,
– chronic pelvic pain,
– ectopic pregnancy
• Men:
– risk of epididymitis with subsequent infertility and
urethral scarring,
– chronic prostatitis
• Both sexes:
– 3-5X increased risk of acquisition of HIV infection with
HIV exposure

Gonorrhea-Diagnosis.
Exact diagnosis depends on identification of
N. gonorrhoeae by one of several methods:
– Thayer-Martin culture medium.
– Gram stain, looking for Gram-negative diplococci
in PMN leukocytes.
• This test is actually useful only in male intraurethral
specimens because samples from other sites may yield
results that can be confused with normal flora,
decreasing both sensitivity and specificity.
– Nucleic acid amplification test (NAAT).

Gonorrhea-Treatment
Because coinfection with Chlamydia trachomatis occurs
often in patients infected with N.gonorrhoeae,
consideration should be given to treatment plans that
cover both organisms, especially in populations at high
risk for STDs.
– For uncomplicated gonococcal infection of the urethra,
cervix, and rectum, all recommended regimens involve a
single treatment, which is important in increasing
compliance

Treatment Regimens for Gonococcal
Infections (NOVAC)
Neisseria gonorrhoeae endocervicitis
• Cefixime, 400 mg orally (single dose), or
• Ceftriaxone, 125 mg intramuscularly (single dose), or
• Ciprofloxacin, 500 mg orally (single dose) or
• Ofloxacin, 400 mg orally (single dose)a, or
• Levofloxacin 250 mg orally (single dose)

Chlamydia -(NMS)
• C trachomatis -obligate intracellular gram negative
bacterium associated with a wide range of diseases
• C. trachomatis serovars A,B, Ba and C cause trachoma,
the world’s leading cause of infectious blindness.
• Serovars D through K are most commonly associated
with
C. trachomatis serotypes B, D, E, F, G, H, I, J, and K cause
sexually transmitted chlamydial genital infection.
Diagnosis
• Culture- limited sensitivity( technical difficulty)
• Nucleic acid amplification test

Reproduction cycle of Chlamydia.

Clinical presentation
– Women are asymptomatic in 75% of the time.
– In symptomatic women, mucopurulent cervicitis
can be demonstrated.
– Symptoms of urethritis and pyuria and a negative
urine culture in sexually active women suggest a
chlamydial infection.

Clinical - Chlamydia t.
– Fever and lower abdominal pain suggest PID,
which occurs in as many as 40% of women with
untreated chlamydia .
– These infections may be more insidious and
protracted in duration than those associated with
gonococcal PID.
– Although 50% of chlamydial infections in men are
asymptomatic, urethritis may occur.
– In exposed infants, C. trachomatis may cause
conjunctivitis and pneumonia.

Rx
RX- Chlamydia trachomatis endocervicitis
• Azithromycin, 1 g orally (single dose), or
• Doxycycline, 100 mg orally twice daily for 7 days, or
• Ofloxacin, 300 mg orally twice daily for 7 days, or
• Levofloxacin, 500 mg orally for 7 day
Sequelae:Complications may include :
PID
ectopic pregnancy, and
infertility

Lymphogranuloma venereum (LGV)-(NMS)
• Etiology-
– C. trachomatis, serotypes L1 L2, and L3,
• produce a wide variety of local and regional
ulcerations and destruction of genital tissues.

LGV-Clinical presentation
• 1⁰ genital ulcers at the site of inoculation B/n 34 and 21
days after exposure,
– The lesions resolve spontaneously.
• 2 ⁰ unilateral inguinal or femoral tender, adenopathy
develops 2-6 weeks later ,
– This can develop into buboes and rupture.
• When the rectum is infected, both men and women
experience proctitis with accompanying perianal
inflammation and lymphatic involvement, which can lead
to 30 fistula formation and strictures.
• Genital elephantiasis and infertility can also occur in
tertiary disease.
• Only about 10% of patients with LGV present with a
complaint of a genital ulcer, which has usually resolved by
the time the patient seeks care.

LGV-Diagnosis
• Usually, diagnosis is made serologically or by
exclusion of other causes of inguinal LAP .
• Complement fixation is the test of choice.
• Titers > 1:64 indicate active infection
• Culture is a difficult and therefore unreliable
diagnostic tool.
• DDX- syphilis, Chancroid, granuloma
inguinale, Malignancy, HSV

LGV-Treatment
– Doxycycline 100 mg PO BID for 21 days
– Erythromycin 500 mg PO QID for 21 days
– Surgical reconstruction may be required for patients with
considerable tissue destruction in the tertiary stage.
– Buboes may need to be incised and drained
– Sexual partners of patients diagnosed with LGV should
be treated as well.
– If asymptomatic, partners can be treated with 1 mg
azithromax or doxycycline 100 mg bid for 7 days.

Chancroid (NMS)
• The Gram-negative coccobacillus Haemophilus ducreyi
causes this genital ulcerative disease
Clinical presentation.
• Lesions begin as small papules and progress to painful
genital ulcers in 2 to 3 days.
• Painful lesions that progress from smallpapules to
pustules and to ulcer with soft margins (soft chancre)
• If the lesions are left untreated, buboes and inguinal
ulcers may develop, accompanied by regional LAP.

Diagnosis
• Culture is not widely available and is only 80%
sensitive.
• PCR tests are being developed,
• Probable diagnosis is made when painful genital
ulcers are present without evidence of herpes
(culture) or syphilis (darkfield examination and
serologic testing).
• Diagnosis is supported by coexisting painful
inguinal adenopathy, which occurs in up to one-
third of cases.

RX of chancroid
Therapeutic regimens include:
– Azithromycin 1 g orally stat
– Ceftriaxone 250 mg intramuscularly stat
– Ciprofloxacin 500 mg orally twice daily for 3 days
– Erythromycin base 500 mg orally three times daily for 7 days
*Sexual partners should receive treatment as well. Ulcers should
start to improve by 3 days post treatment and resolve by 7
days; larger ulcers may take longer to heal. Lack of response to
treatment should cause reconsideration of the diagnosis

Granuloma inguinale(donovanosis)
This genital ulcerative disease is caused by
Calymmatobacterium granulomatis –current STI)a
Gram-negative intracellular bacterium.
Clinical presentation.
Chronically Progressive ulcerative disease
- a painless, beefy red, friable usually non purulent
which starts as small firm papule
- No regional LAP but with accompanying inguinal groin
swelling caused by subcutaneous spread of granuloma.
- No systemic symptoms
-This condition may lead to lymphedema and
elephantiasis of the external genitalia.

Granuloma inguinale(donovanosis)
Clinical course:
• Initial papular lesion, typically ulcerates and
develops into a soft, red, painless granuloma
that can be covered by a thin, gray membrane.
• Spread to the neighboring anus and rectum
or inguinal region occurs over the course of
many months.
• Lymph nodes are moderately enlarged,
painless, and without abscess formation.

Granuloma inguinale
Typical granulomatous ulceration of granuloma inguinale in a 32-year-old woman. A
soft, red, painless granuloma that can be covered by a thin gray membrane. The
lymph nodes are moderately enlarged and painless.

Donovanosis
DDx
– LGV, chancroid, spinalioma
– In its exuberant hypertrophic form, donovanosis can be
mistaken for carcinoma, tuberculosis, or condylomata lata.
-It is generally not painful
Diagnosis
• Culture of C. granulomatis is difficult.
• When the diagnosis is expected based on appearance
of lesions, scrapings of ulcers show Donovan bodies
,pathognomonic=> MN cells with inclusion cysts
containing Gram-negative pleomorphic rod-like
organisms

Granuloma inguinale
Leukocyte with Donovan body.

Treatment of Donovanosis
One of the following therapeutic regimens may be
used:
– Doxycycline 100 mg orally twice daily for at least 3
weeks
– Trimethoprim-sulfamethoxazole 160 mg/800 mg
orally twice daily for at least 3 weeks
– Ciprofloxacin 750 mg orally twice daily for at least 3
weeks
– Erythromycin base 500 mg orally four times daily for
at least 3 weeks
– Azithromycin 1 g orally once a week for at least 3
weeks

Complications of donovanosis
• Genital pseudo elephantiasis
• Adhesion
• Urethral, vagina, rectal stenosis

Syphilis Essentials of Diagnosis
CURRENT OBG
Primary Syphilis
• Painless genital sore (chancre) on labia, vulva,
vagina, cervix, anus, lips, or nipples.
• Painless, rubbery, regional lymphadenopathy
followed by generalized lymphadenopathy in
the third to sixth weeks.
• Dark-field microscopic findings.
• Positive serologic test in 70% of cases.

Syphilis-CURRENT OBG
Secondary Syphilis
• Bilaterally symmetric extragenital papulosquamous
eruption.
• Condyloma latum, mucous patches.
• Dark-field findings positive in moist lesions.
• Positive serologic test for syphilis.
• Lymphadenopathy.
Tertiary Syphilis
• Cardiac, neurologic, ophthalmic, and auditory lesions.
• Gummas.

Syphilis-CURRENT OBG
Congenital Syphilis
• History of maternal syphilis.
• Positive serologic test for syphilis.
• Stigmata of congenital syphilis (eg, x-ray changes of bone,
hepatosplenomegaly, jaundice, anemia).
• Normal examination or signs of intrauterine infection.
• Often stillborn or premature.
• Enlarged, waxy placenta.
Latent Syphilis
• History or serologic evidence of previous infection.
• Absence of lesions.
• Serologic test usually reactive; titer may be low.

Vulvo vaginal candidiasis
Risk factors
• Antibiotic rx
• DM
• Pregnancy

Dx of VVC
• Cheese like vaginal discharge( watery to thick)
• Vaginal soreness, dysparunia, vulvar irritation,
erythema pustulopapularvulvar/ vaginal lesions,
• external/splash dysuria
• Healthy looking cervix
• Normal vaginal PH
• Fungal elements ( budding yeast/mycellia)
• Whiff test negative

Rx of vvc
Azoles( more effective than nystatyn)
• Topial-butocnazole, terconazole, ticonazole,
miconazole,clotrimazole
• Oral-fluconazole
Nystatin topical

Genital herpes simplex (HSV)-CURRENT STI
• incurable, recurrent viral disease.
• can be caused by type 2 virus (HSV-2), or less
frequently by type 1 (HSV-1).
• HSV-2 transmission is almost always sexual,
whereas HSV-1 is usually transmitted through
nonsexual skin-to-skin contact
• Although most infections are asymptomatic,
genital HSV infection can cause vesicular and
ulcerative disease in adults and severe systemic
disease in neonates and immunocompromised
individuals.

Genital Herpes
• Genital HSV infection increases the risk of HIV
acquisition in infected persons.
• a cause of recurrent genital and oral ulcerative
disease
• Primary HSV infection may cause systemic
manifestations- fever, myalgia
• Affects the pharynx, urethra, external genitalia
and cervix

Genital Herpes
Symptoms – Clinical Course
burning sensation-clear blisters-become cloudy
(leukocytes)-red borders (!)-often confluent-
flat epidermal ulcer-healing without scar

Clinical Findings
Genital infection with HSV can be differentiated
into five categories:
i. first recognized episode,
ii. primary first episode,
iii. non primary first episode,
iv. recurrent episode, and
v. subclinical shedding.

Primary First Episode
• This refers to infection with either HSV-1 or HSV-2 in an
individual who has never had infection with a herpes
simplex virus.
• In immunocompetent hosts, this event often goes
unrecognized.
• After IP (1-14days, Av. 4days) a small papule appears
that quickly evolves into a vesicle within 24 hours.
• Vesicles can be clear or pustular, are multiple, and
rapidly evolve into shallow, nonindurated, painful
ulcers .
• Crops of lesions may occur over 1–2 weeks, and
crusting and healing of lesions requires an additional
1–2 weeks

Primary First Episode-SS
• In the typical presentation, signs or symptoms
are minimal and usually are not recognized as
primary genital herpes.
• dysuria, inguinal lymphadenitis, vaginal
discharge, and cervicitis.
• systemic symptoms including myalgias,
malaise, fever, and other "flu-like" symptoms
may be associated with the appearance of
genital lesions.

Nonprimary First Episode
• This refers to infection in individuals who have
had a previous infection with either HSV type.
• The typical scenario is an individual with prior
HSV-1 orolabial infection who subsequently
acquires new genital HSV-2 infection.
• Typically, the first genital herpes outbreak
tends to be less severe clinically than a true
primary episode due to an existing, partial
humoral and cellular immunity.

Non primary First Episode
• NPFEs are clinically similar to recurrent
disease and are often mistaken for recurrent
genital herpes, if they are recognized at all.
• Fewer lesions that resolve more rapidly than
with a primary first episode.
The first episode usually resolves within 5–7 days.
• pain and systemic symptoms are less

HSV-Recurrent Episode
• Recurrent genital herpes refers to the second or
subsequent episodes of genital herpes with the
same virus type.
• HSV-2 is much more likely to recur then HSV-1
and accounts for more than 90% of recurrent
genital herpes. The median number of
recurrences is four per year, but up to 38% of
individuals have six or more recurrences per year.
• .

• Recurrences are, in general, clinically fairly
mild and are often unrecognized. The
outbreak usually is not associated with
systemic symptoms but may be preceded by a
prodrome of local paresthesia or dysesthesia.
• Recurrent genital herpes may occur as a
cluster of localized vesiculopustular or
ulcerative lesions

• Lesions tend to lateralize to one side of the
midline. "Atypical" lesions are common and may
be mistaken for excoriation or irritation. The
predominant locations of lesions are on the glans
penis or penile shaft , the vaginal introitus or
labia , and the buttocks and anal area in both
sexes.
• A neuropathic prodrome characterized by pain or
a burning sensation may occur 6–24 hours prior
to the appearance of lesion

Subclinical Shedding
• Subclinical shedding refers to the detection of
virus in the absence of visible lesions.
• understanding of natural history of GH has
shifted from that of intermittent outbreaks to
one of low-grade frequent shedding of virus
that can be detected by viral antigen detection
methods (culture or PCR) of the genital tract
on 5–20% of days.

Subclinical Shedding
• Subclinical shedding is most common during the
first 6–12 months following acquisition of
infection, approaching 40% of days.
• Subclinical shedding of HSV-2 occurs in almost all
infected individuals, equally in both women and
men, and tends to diminish in frequency over
time.
• HSV-1 subclinical shedding is much less common
than HSV-2, occurring on 3–5% of days.

Genital Herpes-Diagnostic Tests
viral culture ("gold standard" until recently)
• allows definitive diagnosis and permits distinction of HSV-1
from HSV-2, which is important for prognosis and
counseling.
• most sensitive while lesions are in the vesicular-pustular
stage. Sensitivity rapidly declines as lesions ulcerate and
crust.
• Negative result doesnot RO genital herpes
PCR (3-5 x sensitive than culture)
is quickly replacing viral culture as the "gold standard."
Type-specific antibody testing based on HSV glycoprotein G
is the most important and reliable diagnostic tool for
chronic HSV infection

Genital herpes DDX
• Syphilis(chancre of primary syphilis is classically non tender,
indurated, and non purulent),
• primary HIV,
• chancroid,
• lymphogranuloma venereum,(LGV)and
• donovanosis

Treatment of genital herpes
Initial infection Acyclovir, 400 mg PO tid x 7–10d or
Valacyclovir, 1 g PO bid for 7–10 d or
Famciclovir, 250 mg PO tidfor 7–10 d
Recurrent infection Acyclovir, 400 mg Po tid for 5 d or
Acyclovir, 800 mg PO tid for 2 d or
Acyclovir, 800 mg PO bidfor 5 d or
Valacyclovir, 500 mg PO bidfor 3 da
Valacyclovir, 1 g PO/dfor 5 d or
Famciclovir, 125 mg PO bid for 5 d or
Famciclovir, 1000 mg PO bid for 1 d

Suppressive therapy
Acyclovir, 400 mg PO bid or
Valacyclovir, 500 mg PO daily (↑ to 1.0 g daily
in pts with >9 outbreaks/yr) or
Famciclovir 250mg po bid

Rx of HSV
• Antiviral therapy for initial genital herpes
prevents new lesion formation and rapidly
reduces viral shedding, infectivity, and the risk of
autoinfection.
• However, it has no effect on the frequency of
subsequent recurrences.
• Patients should be encouraged to inform sex
partners of their infection but may need help in
learning how to disclose their status to partners.

Oral Treatment of Herpes Genitalis.
(CURRENT OBGY)
First episode of genital herpes
Acyclovir 400 mg po tidfor 7–10 days
Famciclovir 250 mg po tid for 7–10 days
Valacyclovir 1000 mg po bidfor 10 days
Recurrent genital herpes
Acyclovir 400 mg po tiddaily for 5 days
Famciclovir 125 mg po bid for 5 days
Valacyclovir 500 mg po bid for 5 days
Genital herpes prophylaxis
Acyclovir 400 mg po bid
Famciclovir 250 mg po bid
Valacyclovir 500–1000 mg orally daily

PID
Infection of the upper genital tract ( endometritis,
salpingitis, peritonitis) by organisms ascending from
lower genital tract by colonizing the endocervix
Micro biology
• N. Gonorrhea & C. trachomatis- most common
• BV organisms( G.v, peptostreptococci, prevotela)
• Rarely respiratory bacteria that may be found in the
vagina (H.influenza, G A strep., pneumococci)
• Actinomyces israelii, which is found in 15% of IUD-
associated cases of PID, particularly in unilateral
abscesses. It is rarely found in women who do not use
an IUD.

Etiology-Telinde
• Within certain geographic areas or populations,
N. gonorrhoeae is a common cause of PID;
• however, most cases of acute PID are the result of
a polymicrobial infection caused by organisms
ascending from the vagina and cervix to infect the
lining of the endometrium and fallopian tube.
• Approximately 85% of cases are natural,
noniatrogenic occurring infections in sexually
active women of reproductive age.
• The remaining 15% of infections occur after
procedures that break the cervical mucous
barrier, such as placement of an IUD, endometrial
biopsy, or uterine curettage, which allow vaginal
flora to infect the upper genital tract.

Etiology-Telinde
• In the US PID categorized as Gnococcal and
Non-gonococcal based on endocervical
cultures
• Endocervix- polymicrobial- difficult to tell b/n
simple colonizers as normal flora and the
etiologic agents
• UGT organisms- better indicators , but difficult
to obtain without cervical contamination

Etiology-Telinde
• Bacterial organisms cultured directly from tubal fluid
may commonly include
– N. gonorrhoeae,
– Chlamydia trachomatis,
– endogenous aerobic and anaerobic bacteria,
– and genital Mycoplasma species.
• Laparoscopic studies have demonstrated a correlation
of no more than 50% between endocervical and tubal
cultures,
• but the presence of N. gonorrhoeae is usually
considered an important causative factor.
• However, endocervical gonorrhea does not necessarily
indicate its sole pathogenic nature in all cases.

Etiology-Telinde
• Direct fallopian tube cultures have demonstrated that
tubal infections are often polymicrobial.
• The type and number of species vary depending on the
stage of the disease.
• Gonorrhea, for example, is often cultured from the
cervix during the first 24 to 48 hours of the disease but
is often absent later.
• Similarly, fewer organisms are cultured late in the
disease, and anaerobic bacteria such as Prevotella,
Bacteroides, Peptococcus, and Peptostreptococcus
species tend to predominate.
• Whether these anaerobes play a causative role or
increase in number and frequency as a result of the
inflammatory response is uncertain.

Etiology-Telinde
• In addition to N. gonorrhoeae, Chlamydia, and aerobic and
anaerobic bacteria, other microorganisms have been
implicated as etiologic agents in acute salpingitis.
• Bacterial vaginosis related organisms such as Gardnerella,
Mycoplasma hominis, and Ureaplasma urealyticum have
also been suggested as causal agents in acute salpingitis by
Ness and colleagues (2005)
• However their role remains controversial, and this study contradicts a
study from the previous year by a similar group of investigators.
• Cervical cultures positive for both M. hominis and U.
urealyticum have been recovered from women with PID.
However, the rate of isolation can be as high as 75%, which
is not statistically different from that of women who are
sexually active but without PID (baseline rate of about
50%), as found by Lemeke and Lsonka.

N.g Vs C.t Telinde
• N. g- fast growth cycle  divides every 20-40 min
Acute inflammatory symptoms in short time
• C.t- obligate intracellular (lack mitochondria)- slow
growth cycle (Q 48-76 hrs)-
• Can remain in FTs for months to yrs –unlike N. g
• Clinically silent with minimum symptoms– difficult/ delayed
Dx and delayed or no treatment
 no symptoms for long period of time until no of
organisms reach to the level that incite acute
symptoms delayed treatment  serious sequale (tubal
Infertility, EP from intra and peritubal adhesion) as it
silently damages cells durig release of elementary
bodies via rupture of cells resulting in
• Epithelial damage and
• Creating favourable condion for invasion and abscess

RFs Telinde
• There is a strong correlation between exposure
to STDs and PID.
– Age at first intercourse,
– frequency of intercourse,
– number of sexual partners, and
– marital status
are all associated with the frequency of exposure to
STDs and thus are associated with PID.
• Women with multiple partners have an increased
risk (four to six times normal) for development of
acute salpingitis, compared with women who
have monogamous sexual relations

PID RFs Telinde
AGE
• Adolescent girls are at significant risk for development
of acute salpingitis
• The incidence of acute PID decreases with advancing
age.
• PID risk
– 1:8 for sexually active adolescent female patient was
– 1:80 for a sexually active woman 24 years of age or older
 Due to greater endocervical exposure in the
ectocervix of adolescents accessible for N.g & C.t (
inciting agents of PID) which have predilection for
columnar epithelium

RF- Telinde
IUD
• Multiple case-controlled studies have shown an
increased risk of acute PID in women who wear
an IUD.
• It has been estimated that IUD users have a
threefold to fivefold increased risk for
development of acute PID.
• In a report by Tatum and colleagues of animal
model investigations, it was suggested that
multifilament strings may be a major contributing
factor in the increased risk of PID.

PID RFs- Telinde
Surgical procedures of the female genital tract
• . About 15% of pelvic infections occur after procedures
that break the cervical mucous barrier, allowing for
colonization of the upper genital tract.
• Eschenbach and Holmes reported that these
procedures include endometrial biopsy, curettage, IUD
insertion, hysteroscopy, and HSG
• The incidence of UGTI associated with first-trimester
abortions is about 1 in 200 cases.
• Recent practice has emphasized the use of
prophylactic antibiotics in high-risk cases to attempt to
decrease the incidence of iatrogenic acute PID.
• Tubal ligation

RF- Telinde
• Previous acute PID is also a risk factor for future
episodes of the disease.
• Another acute tubal infection develops in about 25% of
women who have had acute PID.
• The exact mechanism for this increased susceptibility
has not been determined, but it may be loss of the
natural protective mechanisms of the fallopian tube
lining against microorganisms.
• This increased risk may be related to the sexual habits
of the woman involved, such as reinfection from an
untreated male partner or genital tract damage from
the initial infection.
• Eschenbach has documented that more than 80% of
male contacts are not treated.

PID RFs Telinde
Previous acute PID
• Another acute tubal infection develops in
about 25% of women who have had acute PID.
Probably due to:
Loss of natural protective mechanism of tubal
linining as a result of damage from previous
infection
Sexual habit of the woman eg sex with untreated
partner

PID RF (NMS)
• Frequent sexual activity,
• early onset of sexual activity,
• multiple sex partners, and a
• recent new sex partner are associated with
risk for developing PID.

PID protective factors Telinde
Contraceptives
Barrier Methods
condoms,diaphragms,and,spermicidal
preparations
OCPs
Mechanism of protection- probably due to:
– cervical mucus thickening
– short menstrual flow period
– ovulation inhibition
 no nidus for abscess formation on
ovary

PID Protective Factors-Telinde
• Barrier contraceptives ( mechanical and
chemical)- 60% decrease with consistent use
• Oral contraceptives
– Cervical mucus thickening
– Decreased menstrual flow duration shorter
interval for bacterial invasion
• OCPs are associated with a better prognosis
for future fertility in women with acute PID
 No ovulation no nidus for TOA formation

Inciting events of PID
• Menses,
• sexual intercourse,
• Iatrogenic
– Elective abortion
– Dilation and curettage or endometrial biopsy
– IUD insertion or use
– Hysterosalpingography
– Chromopertubation at laparoscopy

DX
Traditionally
Lower ab. Pain,
cx motion tenderness + Fever
adnexal tenderness
This dx is not reliable( less sensitive) due to the diversity
of manifestation of symptoms( no pathognomonic SS)
High degree of suspicion is needed for dx and rx of PID,
with any abdominal Pain, vaginal discharge, urinary
symptoms

Clinical Criteria for the Diagnosis of PID (NOVAC)
Symptoms
• None necessary
Signs
• Pelvic organ tenderness (UX
tenderness, cervical motion tenderness /
adnexal tenderness)
• Leukorrhea and/or mucopurulent
endocervicitis

Dx
Additional criteria to increase the specificity of the
diagnosis
• Endometrial biopsy showing endometritis
• Elevated C-reactive protein or ESR
• Temperature higher than 38°C
• Leukocytosis
• Positive test for gonorrhea or chlamydia
Elaborate criteria
• Ultrasound documenting tubo-ovarian abscess
• Laparoscopy visually confirming salpingitis

Telinde
• Pain in the lower abdomen and pelvis is by far the most
common symptom of acute PID.
• seen in > 90% of patients at initial presentation.
• The pain is
– usually described as constant and dull and is accentuated
by motion and sexual activity. Generally,
– of recent onset, usually less than 7 days.
• About 75% of patients with PID have an associated
endocervical infection and coexistent purulent vaginal
discharge.
• Nausea and vomiting are comparably late symptoms in
the course of the disease.
• Abnormal vaginal bleeding, especially menorrhagia, or
spotting, is noted in about 40% of patients.

CDC CLINICAL DIAGNOSIS OF PELVIC INFLAMMATORY DISEASE
(current STI)
Minimum criteriaa
Acute lower abdominal or pelvic pain, plus at least one of the
following on examination:
– Uterine tenderness
– Adnexal tenderness
– Cervical motion tenderness
Additional criteria b (enhance the specificity of the minimum
criteria)
– Oral temperature >/= 38.3C
– Abnormal cervical or vaginal mucopurulent discharge
– Vaginal fluid neutrophils on saline micscopy 1/400 x field)
– Elevated C-reactive protein,
– Elevated ESR,
– Cervical N. gonorrhoeae or C. trachomatis infection

CDC- PID DX: contd.
• The most specific criteria for diagnosing PID
include the following:
– Endometrial biopsy with histopathologic evidence of
endometritis
– Transvaginal sonography or MRI techniques showing
thickened, fluid-filled tubes with or without free pelvic
fluid or tuboovarian complex, or
– Doppler studies suggesting pelvic infection (e.g., tubal
hyperemia)
– Laparoscopic abnormalities consistent with PID
• Endometrial biopsy is warranted in women
undergoing laparoscopy who do not have visual
evidence of salpingitis, as some women with PID
have endometritis alone.

Contd.
• aEmpiric treatment should be started in women with a
mild to moderately severe clinical presentation if they
– meet the minimum criteria,
– are at risk for a sexually transmitted disease, and
– have no other cause for illness identified.
• bAdditional criteria can be used to more accurately
diagnose PID and should be reserved for women with
severe presentations to help rule out other serious
diagnoses.
• Further evaluation of women with uncertain diagnoses
can be made histologically, laparoscopically, and
sonographically

Telinde
• The majority of women with PID have either
mucopurulent cervical discharge or evidence of
WBC on a microscopic evaluation of a saline
preparation of vaginal fluid.
• If the cervical discharge appears normal and no
WBCs are observed on the wet prep of vaginal
fluid, the diagnosis of PID is unlikely, and
alternative causes of pain should be investigated.
• A wetprep of vaginal fluid offers the ability to
detect the presence of concomitant infections
(e.g., bacterial vaginosis and trichomoniasis).

Laparascopy -Telinde
• Jacobson and Westrom attempted to correlate the clinical
diagnosis of acute salpingitis with laparoscopic pelvic
findings. Of 814 women in whom laparoscopy was
performed for presumed acute PID, 512 (65%) had visual
evidence of salpingitis; 184 (23%) had normal visual
findings; and 98 (12%) had other pelvic pathology.
• Because of the positive clinical findings, many of the
patients with normal findings were suspected to have early
PID with endometritis and endosalpingitis without visual
evidence of tubal or pelvic damage.
• Thus, laparoscopy is limited as a method of diagnosing
the early stages of PID, but it is important to rule out non-
PID surgical emergencies, such as appendicitis, and
otherentities requiring different treatment modalities, such
as endometriosis.

• Although it is suggested that laparoscopy be
offered to all patients with an uncertain
diagnosis, it is strongly indicated for patients
who are not responding to therapy in an effort
to
– confirm the diagnosis,
– obtain cultures from the cul-de-sac or
– fallopian tubes, and drain pus if necessary

Laparascopy Telinde
• Despite these shortcomings of early diagnosis,
laparoscopic visualization of the pelvis is still
the most accurate method of confirming the
diagnosis of acute PID

Laparascopy Telinde
• In summary, laparoscopic studies have shown the
following:
1. The clinical diagnosis of acute PID may be inaccurate.
2. Acute PID is sometimes found in patients undergoing
laparoscopy for other causes of pelvic pain.
3. Laparoscopy is a relatively safe method for making
the visual diagnosis of the latter stages of PID,and
thus assessing future fertility prognosis and planning.
4. Laparoscopy is an excellent means of obtaining
cultures directly from the tube.

Laparoscopy Telinde
• The appearance of the pelvic organs can vary
from erythematous, indurated, edematous
oviducts, to pockets of purulent material, to a
large pyosalpinx or tuboovarian abscess.
• However, although no disease may be evident
in early stages, it is imperative to render
treatment to all stages to avoid long term
sequelae.

• Ultrasonography is of limited value for patients
with mild or moderate pelvic PID.
• Thus, the routine use of sonography in patients
with acute salpingitis does not appear to be
indicated.
• Ultrasound is helpful in distinguishing an adnexal
mass, especially in patients who demonstrate a
lack of response to antimicrobial therapy in the
initial 48 to 72 hours of therapy

Telinde
• Sonohysterography - not indicated at this time
for patients suspected of having PID because
no studies have been performed to
demonstrate its safety in the event that
pathogens are dispersed into the upper
genital tract in the process of instilling the
saline.

• Culdocentesis, with evidence of purulent
peritoneal fluid, is helpful in the diagnosis of
acute PID.
• With acute PID, the WBC count of peritoneal
fluid is greater than 30,000 cells/mL, compared
with a WBC count of 1,000 cells/mL in women
without peritoneal inflammation.
• However, other infections, such as appendicitis
and diverticulitis, among others, can also cause
purulent pelvic fluid and a false diagnosis of PID

Telinde the Fitz-Hugh-Curtis syndrome
• Perihepatic inflammation and adhesions,
• develop in 1% - 10% of patients of acute PID.
• Signs and symptoms include
– RUQ pain,
– pleuritic pain, and
– RUQ tenderness when the liver is palpated.
• Usually the symptoms and signs of this
syndrome are preceded by the clinical onset
of acute PID.
• The condition is often mistakenly diagnosed as
either acute cholecystitis or pneumonia.

Telinde
• Fitz-Hugh-Curtis syndrome is believed to
develop from vascular or transperitoneal
dissemination of either N. gonorrhoeae or C.
trachomatis to produce the perihepatic
inflammation.
• Other organisms may be involved, but limited
data exist on their causality

Grading of PID
Clinical
I- disease limited to adnexa
II- PID with inflammatory mass
III- ruptured TOA
Operative
Mild- adnexal erythema and edema
Moderate- purulent exudate of fallopian tubes
Severe- pyosalpynx , inflammatory complex,
TOA
Source???????

Differential Diagnosis of Pelvic Inflammatory
Disease (current STI).
• Ectopic pregnancy
• Septic abortion
• Rupture, torsion, hemorrhage of an ovarian cyst
• Endometriosis
• Acute appendicitis
• Inflammatory bowel disease
• Urinary tract infection
• Nephrolithiasis

Mg’t
Admission if
– Dx is uncertain
– Clinical disease is severe
– Compliance uncertainity
– Suspicion of pelvic abscess
– Pregnant/HIV positive patient
Discharge when
– Temprature lyses for 24 hrs or more
– Lucocytosis normalize
– No rebound tenderness
– Pelvic organ tenderness improved

PID Rx
• Therapy regimens for PID must provide
empirical, broad-spectrum coverage of likely
pathogens , including N. gonorrhoeae, C.
trachomatis, gramnegative facultative
bacteria, anaerobes, and streptococci.
• Sexual partners of women with PID should be
evaluated and treated for urethral infection
with chlamydia or gonorrhea

Outpatient treatment of PID
Regimen A
• Ofloxacin, 400 mgPO BID X14 days, or
• Levofloxacin, 500 mg po /D X 14 14 days
– Cover both N. g and C. t, no anaerobic coverage
With or without:
• Metronidazole, 500 mg orally 2 times daily for
14 days

Outpatient Treatmentof PID
Regimen B
• Cefoxitin, 2 g IM stat, plus probenecid, 1 g orally
concurrently, or
• Ceftriaxone, 250 mg IM stat , or
• Equivalent cephalosporin (parentral 3rd G)
Plus:
• Doxycycline, 100 mg orally 2 times daily for 14
days
• With or without Metronidazole, 500 mg orally 2
times daily for 14 days

CDC 2006 Admission criteria for patients with
acute PID Telinde
• Surgical emergencies (such as appendicitis)
cannot be excluded.
• The patient is pregnant.
• The patient does not respond clinically to oral
antimicrobial therapy.
• The patient is unable to follow or tolerate an
outpatient oral regimen.
• The patient has severe illness, nausea and
vomiting, or high fever.
• The patient has a tuboovarian abscess

Inpatient Treatment of
PID
Regimen A
• Cefoxitin, 2 g intravenously every 6 hours, or
• Cefotetan, 2 g intravenously every 12 hours,
Plus:
• Doxycycline, 100 mg PO/IV BID
• Parenteral therapy may be discontinued 24 hours after
a patient improves clinically, and oral therapy with
doxycycline (100 mg PO BID ) should continue to
complete 14 days of therapy.
• When tuboovarian abscess is present, many health
care providers use clindamycin or metronidazole with
doxycycline for continued therapy rather than
doxycycline alone, because it provides more effective
anaerobic coverage.

Inpatient Treatment of PID
Regimen B
• Clindamycin, 900 mg IV TID Plus:
• Gentamicin, loading dose IM/IV (2 mg/kg ) followed
by a Maintenance dose (1.5 mg/kg) every 8 hours
• Parenteral therapy can be discontinued 24 hours after
a patient improves clinically; continuing oral therapy
should consist of doxycycline 100 mg PO BID or
clindamycin 450 mg PO QID to complete a total of 14
days of therapy.
• When tuboovarian abscess is present, many health
care providers use clindamycin for continued therapy
rather than doxycycline alone, because clindamycin
provides more effective anaerobic coverage

PID rx – National guidelinerecommendation
Out patient*
Ciprofloxacin 500mg po stat OR spectinomycin
2gm im stat
+
Doxicycline 100mg po bid for 14 days
+
Metronidazole 500mg po bid for 14 days
*admit if no improvement in 72 hrs

PID rx – National Guideline Recommendation
Inpatiet
Ceftriaxone 250 mg iv/IM daily OR
Spectinomycin gm IM bid
+
Doxicycline 100 mg po BID for 14 days
+
Metronidazole 500mg po bid for 14 days
+
CAF 500mg IV QID

complications
• Infertility(tubal factor)~12%
• EP~7-10x increased risk
• Chronic pelvic pain~20%
– Hydrosalpinx
– Periovarian adhesions
• Mortality( neglected cases with ruptured TOA)
• adhesion and intestinal obstruction
• Peritonitis and

Tubo-ovarian Abscess
• An end-stage process of acute PID,
– tubo-ovarian complex (a mass of matted bowel, tube, and
ovary),
– tubo-ovarian abscess (a mass consisting primarily of an abscess
cavity within an anatomically defined structure such as the
ovary), pyosalpinx, or, chronically, hydrosalpinx
• TOA is diagnosed when a patient with PID has a pelvic
mass that is palpable during bimanual examination.
• The condition usually reflects an agglutination of pelvic
organs (tube, ovary, bowel) forming a palpable complex.
• TOA is treated with an antibiotic regimen administered in a
hospital .
• About 75% of women with tubo-ovarian abscess respond
to antimicrobial therapy alone
• Failure of medical therapy suggests the need for drainage
of the abscess

syndromes
• Urethral discharge/ burning sensation on
urination in men
• Vaginal discharge
• Genital ulcer
• Lower abdominal pain
• Scrotal swelling
• Inguinal bubo

SYNDROMES
Genital Ulcer
Common causes
• Syphillis ( hard chancre)
• HSV
• Chancroid (soft chancre)
• LGV
• Granuloma inguinalae ( donovanosis)

DX
Syphilis- painless, indurate, minimum
tenderness, no inguinal LAP
HSV- group of vesicles + superficial inflamed
ulcers
Chancroid- 1-3 extremely painful ulcers +
inguinal LAP( usually fluctuant)
An inguinal bubo accompanied by one or
several ulcers is most likely chancroid.
if no ulcer LGV is probable

Genital ulcer rx
Non vesicular ulcer( cover syphilis, chncroid,LPV)
• B. penicillin2.4m iu im stat/ doxycycline 100 mg po bid
for 14 days(if penicillin allergic) plus
Ciprofloxacin 500mg po bid for 3days/
erythromycin500mg po qid for 7D
Vesicular lesions( treat HSV)
Acyclovir 200mg 5x/ day for 10 days/ 400mg tidx10days
Recurrent infection
400mg po tid x5 days
Suppressive rx
400mg daily continuously

Vaginal Discharge Syndrome(National
Guideline)
Common Causes
I. N. Gonorrhoe
II. Chlamydia trachomatis
III. T. Vaginalis
IV. G. Vaginalis
V. C. albicans
I-III-sexually acquired
IV-V- endogenous
N.B.IV & V are not STI
N.g & C.t cause cervicitis, the rest cause vaginitis
G.Vaginalis (BV)is the most common cause of VD in Ethiopia
followed by candidiasis,trichomoniasis,gonococcal and chlamydial
cervicitis respectively

RF for gonococcal/ Chlamydia cervicitis
• Age <25
• Single
• Multiple sexual partners
• Recent new partner
• Sex trading

Recommended Rx for VD
1- risk assessment positive
ciprofloxacin 500mg po stat/ spectinomycine 2gm
IM stat Plus Doxicycline 100mg po bid for 7 days Plus
metronidazole 500mg po bid for 7 days
2- risk assessment negative
metronidazole 500 mg po bid for 7 days plus
Clotrimazole 200 mg PV/ night 3 doses

HIV Vs. other STI
• STI increase HIV acquisition significantly
• Both share similar risk factors
• Most STI exhibit atypical manifestations extensive
lesions in HIV coinfection
Eg- syphilis- atypical facial plaques negative serology, rapid progress to NS
-Recurrent/persistent,multiple,extensive extra genital( perianal) lesions of HSV
-Atypical H. ducrey lesions(less purulent extensive , multiple, with induration
mimicking Primary syphilis)
• HIV coinfection renders STI less sensitive for
conventional treatment

STIs in pregnancy
• STDs can cause significant maternal and fetal complications.
• Adverse pregnancy outcomes directly and indirectly
attributable to STDs include
– Ectopic pregnancy,
– Spontaneous abortion,
– Fetal demise,
– Perinatal infections,
– IUGR, congenital abnormalities,
– PROM, chorioamnionitis,preterm birth,
– puerperal infections
– Low-birth-weight infants, and neonatal infections.
• The immunologic mechanisms involved in STDs and adverse
pregnancy outcomes are not well understood.
• Inflammatory cytokines, in response to infection, may be
involved in the pathogenesis of preterm premature rupture of
membranes and preterm labor, as well as adverse fetal
conditions

• Most STDs are commonly asymptomatic or
present with nonspecific symptoms-need high
index of suspicion
• 1st ANC visit- complete STD history and
appropriate screening studies
• STDs routinely screened for in pregnancy
include syphilis,HBV, HIV, and chlamydia.

Menstrual Cycle
• Typical Cycle
– Every 28 +/_ 7days
– Flow for 4+/- 2 days
– 20- 60 ml bl00d

Menst Blood Loss Estimation
• Patients perception- doesn’t correlate with
objective measurementnot reliable
• HGB/ Hct- evaluation
– Hgb <12g/dl menorrhagia ( >80ml) likely
– Hct may be normal with heavy bleeding, at early
months until blood store depletes
• Direct measurement
– HGB extracted from sanitary pads and measured via
spectrophotometery
– Inconvenient for clinical setting
• Clots size, type and no of pads used
– Clot> 1.1inch and changing pad Q < 3hrcorrelates
with objective menorrhagia

Pictorial Bleeding Assessment Chart
• Point is assigned for Each used pad/tampoon and
clots passed
• Pads
– Lightly stained- 1pt
– Moderately saturated- 5pt
– Fully soaked- 20
• Tampoons
– 1, 5 1nd 10 pts of same order as pads
• Clots
– Small- 1pt
– Large- 5pt
>100pts/ menst cycle menorhagia ( >80ml loss)

Definitions
• AUB patterns
– Menorrhagia
– Metrorrhagia
– Breakthrough bleeding
– Menometrorrhagia
– Hypomenorrhoea
– Oligomenorrhoea
– Withdrawal bleeding

Symptoms
• Menorrhagia, Metrorrhagia, Menometrorrha
• Postcoital bleeding
– Eversion, Cervicitis( mostly Chlamydia t.),
Endocervical polyps, Endometrial polyps
– CIN, Invasive Cx Ca, Vaginal Ca, Em Ca
• Pelvic pain
– Role of PGs in menorrhagia and dysmenorrhoea +
AUB from leyomyomas, polyps, Adenomyosis,
infections, Preg comp.

AUB Incidence
• Uncommon in prepubertal and
postmenopausal
• Reproductive age- 10-30%
• Perimenopausal ~50%

DDX Of AUB
I.DUB
a.Anovulatory
• Immature H-P-O axis
( perimenarcheal)
• Insensitive Follicles
(Perimenopausal)
• Endocrinopathies
• Drugs (H depressants,Steroids)
b.Ovulatory
II.Organic lesions
a.Pregnancy associated- abortion,EP,
GTD, postabortal/Ppartal infections
b.Anatomic Uterine lesions
– Neoplasms-myoma, polyp, EH,Ca
– Endometrial atrophy
– Infections eg STI, TB
– Mechanical causes—IUD, perforation
– AV malformation
– Partial outflow obstruction—congenital
müllerian defect, Asherman syndrome
c.Anatomic nonuterine lesions
– Ovarian lesions—hormonally
functional neoplasm
– FT lesions—salpingitis, cancer
– Cervical and vaginal lesions—
cancer, polyp, infection, atrophic
vaginitis, foreign body, trauma
d.Systemic abnormalities
– Exogenous hormone
administration—sex steroids,
corticosteroids
– Coagulopathies
– Hepatic failure
– Chronic renal failure
– Endocrinopathies—
hypothyroidism, hyperthyroidism,
adrenal disorders, diabetes mellitus,
hypothalamic-pituitary disorders,
polycystic ovarian syndrome, obesity

AUB -ExternalCauses
Copper containing IUDs
• Associated with Menorrhagia and metrorrhagia
• Several explanations at various levels
At cellular level- unbalanced ratios of prostaglandins and
thromboxane  improvement with NSAID rx
At tissue level
– Increased EM vascularity congestion and degeneration interstitial
hemorrhage Metrorrhag
– poor spiral arteriolar contraction and inadequate thrombus
formation mennorhagia
• Arteriolar wall degeneration and lumen dilatation Menno
• diminished local platelet count and less fibrin thrombus
At organ level-
IUD rotation, embedding, or perforation may cause excessive bleeding
(conflicting evidences)
RX- empirically with NSAID, if no response –look for GYNecologic
pathology –EMB using small catheters is possible wile IUD is
in situ, US may be limited by IUD shadowing

AUB -ExternalCauses
Levonorgestrel-Containing Intrauterine System
• LNG-IUS (Mirena) causes AUB in some users which
• Gradually resolve with atrophy and amennorhoea
• Cause of bleeding – unclear, proposed mechanisms-
– downregulation of estrogen and progesterone receptors,
increased local leukocyte populations, and
– alterations of endometrial vascular morphology, hemostasis,
and endometrial repair
• EM effects
– Increased EM vascular fragility superficial, thin walled ,
dilated vessels + Irregular EM surface Breakthrough
bleeding RX- same as CU IUD

AUB -ExternalCauses
PO Contraceptions
• Bleeding caused by POCs is characterstically irregular and
light, but may also be frequent and prolonged.
COCs ( patch, Vaginal ring, IM EP contraception too)
• AUB in ~30-50% of first 3 mths of use ( Break through)-
incidence decrease with time  expectant mg’t
• Presumably from EM atrophy caused by the P component
• May also result from inconsistent use
• EM effect
– spiral arterioles become thinner and more sinusoidal and do
not characteristically coil
– venules become dilatated and prone to thrombosis. This often
leads to local tissue infarction and is thought to be the cause of
breakthrough bleeding
Tamoxifen
HRT

AUB causes by age
Childhood-
• bleeding may be of vaginal, rectal, urethral origin.
– Vulvovaginitis, vulvar dermatitis ( Lichen sclerosis--)/
neoplasms, Trauma ( accident, Abuse), Foreign body,
Urethral prolapse
– UX bleeding (uncomon)-Precocious puberty, accidental
ingestion of exogenous hormones, ovarian tumors
Adolescence
– Anovulation, Coagulopathy
– Pregnancy comps, STI, sexual abuse
– Neoplasms (Polyp, myoma, ovarian T)- rare

Prepubertal Vaginal Bleeding-
NOVAC
• Vulvar –
– vulvitis with excorationLichen sclerosus,
Condyloma, Molluscum contagiosum, urethral
prolapse
• Vaginal
– Vaginitis, Trauma/Abuse, Foreign body, Vaginal
tumors (RM sarcoma/ Butroyid sarcoma),
• Uterine-
– precocious pubety, Exogenous Hormones,
• Ovarian –
– Germ Cell tumors, Granulossa cell tumors

AUB cause by Age
• Reproductive Age
– Pregnancy and STI related-↓ with age
– Myoma, endometrial polyp-↑ with age
– Exogenous hormones
– Endocrine disorders
– Systemic abnormalities
• Perimenopausal
– Anovulation
– Neoplasms (benign/malignanat), Thyroid Dysfunction
– Systemic abnormalities
• Postmenopause-bleeding from the rectum, vagina, or urethra may
be confused with uterine bleeding
– Endometrial polyp, EM atrophy,
– Eca, Ovarian Tumors (E producing)
– ulcerative vulvar, vaginal, or cervical neoplasms

AUB Causes
• Systemic abnormalities
– CLD
– Chronic Renal failure
– Coagulopathies
– Endocrinopathy
• Thyroid dysfunction ( hypo/ hyper Thyroidism)
• Adrenal disorders, DM, PCO, Obesity
– Hematologic malignancies

PALM–COEIN Classification System for Abnormal Uterine
Bleeding in Reproductive-Aged Women ACOG 2014
PALM: Structural Causes
• Polyp (AUB-P)
• Adenomyosis (AUB-A)
• Leiomyoma (AUB-L)
– Submucosal myoma (AUB-LSM )
– Other myoma (AUB-LO)
• Malignancy & hyperplasia
(AUB-M)
COEIN: Nonstructural Causes
• Coagulopathy (AUB-C)
• Ovulatory dysfunction (AUB-O)
• Endometrial (AUB-E)
• Iatrogenic (AUB-I)
• Not yet classified (AUB-N)
Each postulated cause of AUB is
linked with one (or more) letter
qualifiers that indicate its
etiology or etiologies. The new
classification system
recommends that the term
dysfunctional uterine bleeding
be abandoned.

Anovulation Causes- ACOG 2014
Physiologic
• Adolescence
• Perimenopause
• Lactation
• Pregnancy
Pathologic
• Hyperandrogenic anovulation (eg, polycystic ovary syndrome,
congenital adrenal hyperplasia, or androgen-producing tumors)
• • Hypothalamic dysfunction (eg, secondary to anorexia nervosa)
• • Hyperprolactinemia • Thyroid disease • Primary pituitary disease
• Premature ovarian failure
• Iatrogenic (eg, secondary to radiation or chemotherapy)
• Medications Ovulatory

DX
• Initial approach
• Exclude pregnancy, STIs ,malignancies—
• For women of normal weight between the ages of
approximately 20 and 35 years who do not have clear
risk factors for STDs, who have no signs of androgen
excess, who are not using exogenous hormones, and
who have no other findings on examination,
management may be based on a clinical diagnosis.
Additional laboratory or imaging studies may be
indicated if the diagnosis is not apparent on the basis
of examination and history NOVAC

Dxtic Evaluation
Laboratory Studies
• In any patients with excessive bleeding, an objective measurement of
hematologic status should be performed with a complete blood count to
detect anemia or thrombocytopenia. A pregnancy test should be performed
to rule out pregnancy-related problems. In addition, because of the
possibility of a primary coagulation problem, screening coagulation studies
such as a prothrombin time and partial thromboplastin time should be
considered; an assessment of platelet function may be appropriate as a
screening test for von Willebrand's disease (85).
Women with abnormal bleeding who have a history consistent with chronic
anovulation, who are obese, or who are older than 35 to 40 years of age
require further evaluation
Imaging
• TVUS (uterine contour, endometrial thickness, and ovarian structure )
• SIS
• Hysterescopy
• Endometrial biopsy
– EmH/Ca, Polyps, GTN, Infection,atrophy,proliferative/ Secretory

Dxtic Evaluation
Endometrial Sampling
• to evaluate AUB in women who are at risk for
endometrial polyps, hyperplasia, or carcinoma.
• mandatory in the evaluation of anovulatory bleeding
in those
– older than 35 to 40 years of age,
– younger women who are obese, and with a history of
prolonged anovulation .
• The technique of D & C, has been replaced largely by
endometrial biopsy in the office using disposable
flexible plastic sheath with an internal plunger that
allows tissue aspiration (Eg Pipelle catheter)
• Hysteroscopy, either diagnostic or operative, with
endometrial sampling, can be performed either in the
office or operating room

.
Summary of Diagnostic Procedures
• There is no one clear sequence to use of endometrial
biopsy, TVS, SIS, and hysteroscopy when evaluating
abnormal uterine bleeding.
• None of these will distinguish all anatomic lesions with high
sensitivity and specificity.
• That said, TVS for several reasons is a logical first step.
– It is well-tolerated, cost-effective, and requires relatively
minimal technical skill.
– Additionally, it has the advantage of reliably determining
whether a lesion is diffuse or focal.
– Once anatomic lesions have been identified, subsequent
evaluation requires individualization.
– If endometrial hyperplasia or cancer is suspected, then
endometrial biopsy may offer advantages.
– Alternatively, possible focal lesions may be best investigated
with either hysteroscopy or SIS.
– Ultimately, the selection of appropriate tests depends on their
accuracy to characterize the most likely anatomic lesions.
25

Lab
• Beta HCG
• PT, PTT, BT, Plt count
• T. C and N. G test (in the presence of
mucopurulent cervicitis)
• Thyroid function
• Liver enzymes
• Cytologic examination
– Squqmous cell abnormality- cervicitis, CIN, Ca
– Atypical glandular,endometrial cells

DUB
• Dx after exclusion of organic causes of AUB (confusing /less
informative terminology)
• DUB ~50% of AUBs
Anovulatory DUB 
– H-P-O axis dysfunction
– 80- 90% of DUB
– irregular bleeding episodes with Menorrhagia, Metrorrhagia and
amennorrhoea
Anovulation No progesterone persisitent proliferative Em
– stromal breakage, decreased spiral arteriole density, and
increased dilated and unstable venous capillaries
– Low cellular AA impaired PG production
Bleeding in Anovulatory DUB results from:
– alterations in vascular architecture and tone, PG concentration
– and ↑ed Emetrial responsiveness to vasodilatory PGs

DUB
• Most anovulatory bleeding is a result of what has been
termed estrogen breakthrough.
• In the absence of ovulation and the production of
progesterone, the endometrium responds to estrogen
stimulation with proliferation.
• This endometrial growth without periodic shedding
results in eventual breakdown of the fragile
endometrial tissue.
• Healing within the endometrium is irregular and
dyssynchronous.
• Relatively low levels of estrogen stimulation will result
in irregular and prolonged bleeding, whereas higher
sustained levels result in episodes of amenorrhea
followed by acute, heavy bleeding.( NOVAC)

DUB
Ovulatory DUB –
• 10-20% of DUBs
• thought to stem predominantly from vascular
dilatation alone ( vascular tone)
↓ed vascular tone Vasodilatation ↑ed blood
flow ↑ed loss
• No change in the number of spiral arterioles but
at the rate of blood loss
3x faster than in women with normal menses
PGs are strongly implicated

Menorrhgia Medical Treatment
• If low risk for Em cancer-empirical Rx with
• NSAIDS
– Mefenamic acid- 550mg tid from day1
– Ibuprofein- 600mg/day through out menses
– Naproxen-550 mg on day1, then 275 mg daily
– Flurbiprofen100 mg bid for 5 days, since day1
– Meclofenamate100 mg tid for 3 days, from D1
• COC-One orally daily
• Tranexamic acid (antifibrinolytic)-1 g qid for 5 days, beginning with menses
• Norethindrone -5 mg tid D5- D26 of cycle (ovulatory DUB) ,5 mg
tid D15 - D26 (anovulatory DUB)
• Danazol-100 mg or 200 mg daily throughout cycle
• GNRHagonists- 3.75 mg IM each month (maximum 6 months)
• LNG- IUS-Intrauterine placement

DUB Medical Rx
NSAIDs
• PG synthesis inhibition through COX1 and COX2
inhibition
• Taken from day1 through the entire menstrual period
• Advantages
– Required only during menstruation
– Improve associated dysmenorrhoea
• Non specific COX inhibitors may disrupt platelet
function (COX1) ??? May not be ideal choices
• Use of COX2 selective NSAIDs- no RCT on effectiveness
+ major longterm SEs (↑ed MI, stroke, CHF risk)

DUB Medical Rx
Tranexamic Acid
• Antifybronylitic
• Inhibits activation of plasminogen to plasmin
• No effect on plt count aPTT, PT---
• Shown clinical effectiveness of reducing
bleeding in ~1/2 of women with DUB related
menorrhagia

DUB Medical Rx
Oral progestins (norethindrone, MDPA)
• For anovulatory DUB
• Acute bleeding
– 10mg po/d MDPA OR 5mg po tid NE- 10 days withdrawal
bleeding after 3-5days of cessation
• Long term control
– Cyclic adminstration -On days 16- 25 followed by withdrawal
bleeding
• Ovulatory DUB may respond for prolonged hdose P rx
– MDPA 10mg po TID/ NE 5mg po TID from D5-D26
• SE of prolonged high dose Pweight gain, bloating,
headaches, and atherogenic changes in the lipid profile

NOVAC
• The benefits of progestins to the patient with
oligomenorrhea and anovulation include a regular flow
and the prevention of long intervals of amenorrhea,
which may end in unpredictable, profuse bleeding. This
therapy reduces the risk of hyperplasia resulting from
persistent, unopposed estrogen stimulation of the
endometrium. Depot formulations of
medroxyprogesterone acetate also have been used to
establish amenorrhea in women at risk of excessive
bleeding. Oral, parenteral, or intrauterine delivery of
progestins may be used in selected women with
atypical endometrial hyperplasia who wish to maintain
their fertility

DUB Medical Rx
COCs
• Reduce 40-70% of flow on long term use
• Mechanism~ Em atrophy
• Advantages- reduced dysmenorrhoea, cotraception
Acute management
• At least 30micgEE, 4tabs Q 6hr until bleeding ceases for
24hrs 3tabs/day for 3days 2tabs/day for 3days
1tab/D for 21days withdrawal bleeding
• NB
– Antiemetics needed
– Lower dose and less frequent regimens may also be
effective

DUB Medical Rx
Estrogen
• Regrowth of denuded endometrium
• Conjugated Equine E
– 2.5mgpo Q6hr
– 25mg IV Q4hrs upto 3doses
• Once bleeding has slowed, patients can be
transitioned to an oral taper using COCs.

DUB Medical Rx
LNG- IUS
• Improves menorrhagia in some women
• ↓es menstrual blood loss by 74 to 97% after 3
months use (Singh, 2005; Stewart, 2001).
• can be used in all women as a 1st line of
menorrhagia treatment in place of oral
medications.
• It is particularly useful for reproductive-aged
women who also desire contraception.

DUB Medical Rx
Androgens
• Danazol
– 100- 200mg PO/day for heavy bleeding
– Creates hypoestrogenic- Hyperandrogenic environment
– Reduce Menstrual flow by half and May some times
induce amenorrhoea
– Reserved as 2nd line short term preop rx due to significant
Androgenic SEs- wt gain, oily skin, acne, alopecia,
irreversible voice change
• Gestrinone –
– 2.5mg po q3-4days
– Same mechanism, indication and SE as Danazol

DUB Medical Rx
GnRH Agonists
• Induce Em atrophy and amenorrhea via
profound hypoesterogenic state
• Dramatic SEs  bone loss + typical
Menopausal symptoms
 not suitable for longterm use
 can be used on short term basis
 induction of amenorrhoea and preop RBC mass
rebuilding

Surgical Management
• For failure or significant SE in conservative management
• The choice of procedure depends on the cause of the
bleeding, the patient's preferences, the physician's
experience and skills, the availability of newer
technologies, and a careful assessment of risks versus
benefits based on the patient's medical condition,
concomitant gynecologic symptoms or conditions, and
desires for future fertility..
• The surgical options range from endometrial ablation or
resection to hysterectomy to a variety of conservative
surgical techniques for management of uterine leiomyoma,
including hysteroscopy with resection of submucous
leiomyomas, laparoscopic techniques of myomectomy,
uterine artery embolization, and MRI guided focused
ultrasonography ablation

Surgical Management
Dilatation and Curettage (D&C)
• Sharp D&C, Pippelle Em sampling,
• performed to arrest severe bleeding refractory
to high-dose estrogen administration (ACOG, 2000;
Stabinsky and associates 1999).
– Temporary effects rarely used for long-term
treatment.
• Pipelle Em sampling- office procedure

Surgical Management- Sharp D&C
Indications
• persistent bleeding despite normal findings with
sonography and pipelle endometrial sampling (
may be used alone or more commonly in
combination with hysteroscopy.)
• to gain access to the uterine cavity when a
stenotic cervical os prohibits in-office
endometrial sampling,
– Although suction curettage is used more commonly
for removal of products of first-trimester pregnancy,
sharp D&C also may be an option.
• to document the absence of intrauterine
trophoblastic tissue in suspected EP

Surgical Management- Sharp D&C
• GA, RA, local block with sedation
• Preop
– No need for prophylactic antibiotic
– Pretreatment with misoprostol for stenotic Cx
• Vagina prepped, bladder drained Bimanual Exam(to
determine uterine size and inclination so that instruments are inserted along the long
axis of the uterus to avoid perforation.) Sounding (sims uterine sound-
determination of the depth to which dilators and curettes can be inserted safely ) 
Dilatation (dilators of sequentially increasing caliber – Hegar, Hank or Pratt
Dilators) Uterine Curettage Uterine exploration for
missed polyps (using Randall kidney stone forceps)
• Postop- Doxicycline 100mg po bid x 10days
• Complications-
– rare (<1%)- infection, perforation ( + associated bowel,
BV and abdominal viscera laceration)

Endometrial Destructive Procedures
• Ablation

M&M Presentation
Darinka Shaw MD
Pediatrics Resident
February 2009
Meconium-stained amniotic fluid (MSAF)
Pediatrics point of view

Objectives
 Definition
 Epidemiology
 Etiology
 Pathophysiology
 Clinical features
 Management
 Morbidity&Mortality

Definition
Meconium aspiration syndrome (MAS) is a
respiratory disorder in an infant born
through
Meconium stained amniotic fluid whose
symptoms cannot be otherwise explained.

MAS
Cleary&Wiswell proposed severity criteria to define MAS:
 Mild: requires <40%O2 for <48hrs
 Moderate: >40%O2 for >48hrs, no air leak.
 Severe: assisted ventilation for >48hrs often with PPH.

Epidemiology
 MSAF observed in 13% of all live births.
 MAS occurs in 5% of newborns delivered through MSAF.
 25,000 to 30,000 cases and 1,000 deaths related to MAS
annually in US.

Epidemiology
 More frequently in infants who are postmature and small for
gestational age.
 Decline from 5.8% to 1.5% (1990–1997), attributed to a
33% reduction in the incidence of births >41 weeks
gestation.

Physiology
 The passage of meconium from the fetus into amnion is
prevented by lack of peristalsis (low motilin level), tonic
contraction of the anal sphincter, terminal cap of viscous
meconium.
 MSAF may be a natural phenomenon that
doesn’t indicate fetal distress but mature GI
tract in post term fetus with increased motilin
level.
 Vagal stimulation by cord or head compression may
be associated with passage of meconium in the
absence of fetal distress.

Risk factors for MSAF
 Maternal HT
 Maternal DM
 Maternal heavy cigarette smoking
 Maternal chronic respiratory or CV Dx
 Post term pregnancy
 Pre-eclampsia/eclampsia
 Oligohydramnios
 IUGR
 Poor biophysical profile
 Abnormal fetal HR pattern

Pathophysiology
 The pathophysiology of MAS is complex.
 Intrauterine fetal gasping, mechanical airway
obstruction, pneumonitis, surfactant inactivation, and
damage of umbilical vessels: all play roles in the
pathophysiology of meconium aspiration.
 There is also a strong association between MAS and
persistent pulmonary hypertension of the newborn
(PPHN).

Pathophysiology
 The timing of the initial insult resulting in MAS remains
controversial.
 Chronic in-utero insult may be responsible for most cases of
severe MAS.
 In contrast to these severe cases, the vigorous infant who
aspirates meconium-stained fluid from the nasopharynx at
birth usually develops mild to moderate disease.

Pathophysiology
 The traditional belief was that meconium aspiration
occurs immediately after birth.
 Aspirated particulate or thick meconium can be carried
rapidly by the first breaths to the distal airways.
 Studies of neonatal puppies with tantalum-labeled
meconium instilled into the trachea before the first
breath have confirmed that the distal migration of
particulate matter can occur within 1 hour of birth.

Pathophysiology
 Several investigators have suggested that most cases of
meconium aspiration occur in utero when fetal gasping is
initiated before delivery.
 Meconium has been found distally as far as the alveoli in
some stillborn infants and in some infants that die within
hours of delivery.
 There is currently no way to distinguish between the infant
who has developed MAS by intrauterine respiration or
gasping and the infant who has developed MAS by inhalation
of meconium at the first breaths after delivery.

Mechanism of injury
1.Mechanical Obstruction of the Airway
 It is commonly thought that the initial and most
important problem of the infant with MAS is obstruction
caused by meconium in the airways.
 Complete obstruction of large airways by thick
meconium is an uncommon occurrence.
 The exact incidence of large-airway obstruction is
unknown, thoughThureen et al, in an autopsy study of
infants who died of MAS, found no evidence of such
obstruction.

Pathophysiology
 Usually, small amounts of meconium migrate slowly to the
peripheral airways.
 This mechanism can create a ball valve phenomenon, in
which air flows past the meconium during inspiration but is
trapped distally during expiration, leading to increases in
expiratory lung resistance, functional residual capacity, and
anterior posterior diameter of the chest.

Pathophysiology
 Regional atelectasis andV/P mismatches can be
developed from total obstruction of the small airways.
 Adjacent areas often are partially obstructed and over
expanded, leading to pneumothorax and
pneumomediastinum air leaks.
 Pulmonary air leaks are 10x more likely to develop in
infants with MAS than those without, and leaks often
develop during resuscitation.

Pathophysiology
2. Pneumonitis
 Pneumonitis is a usual feature of MAS, occurring in about ½
of the cases.
 Meconium has a direct toxic effect mediated by
inflammation.
 An intense inflammatory response in the bronchi and alveoli
can occur within hours of aspiration of meconium.

Pathophysiology
 The airways and lung parenchyma become infiltrated
with large numbers of polymorphonuclear leukocytes
and macrophages.
 Produce direct local injury by release of inflammatory
mediators-cytokines (TNF-α, IL-1β, IL-8) and reactive
oxygen species.
 Lead to vascular leakage, which may cause toxic
pneumonitis with hemorrhagic pulmonary edema.

Pathophysiology
 Meconium contains substances such as bile acids that also
can cause direct injury.
 Clinicians should maintain a high index of suspicion for
bacterial pneumonia in infants with MAS.
 Presence of fever, an abnormalWBC or a decline in
respiratory function are indications of bacterial
pneumonia and/or sepsis and should prompt the
clinician to obtain relevant cultures and initiate
antimicrobial therapy.

Pathophysiology
3.Pulmonary vasoconstriction
 The release of vasoactive mediators, such as eicosanoids,
endothelin-1 and prostaglandin E2 as a result of injury
from meconium seems to play role in the development
of persistent PH.
 The pulmonary vasoconstriction is, in part, the result of
the underlying in utero stressors.

Pathophysiology
4. Surfactant inactivation
 Recognized in the early 1990.
 Meconium displaces surfactant from the alveolar surface
and inhibits its surface tension lowering ability.
 A full term baby born with a sufficient quantity of
surfactant may develop surfactant deficiency by
inactivation that leads to atelectasis, decreased lung
compliance/volume and poor oxygenation.

CLINICAL FEATURES
History
Infants with MAS have a history of MSAF.
They often are postmature or small for
gestational age.
Many are depressed at birth.

CLINICAL FEATURES
Physical examination
 Evidence of postmaturity: peeling skin, long fingernails, and
decreased vernix.
 The vernix, umbilical cord, and nails may be meconium-
stained, depending upon how long the infant has been
exposed in utero.
 In general, nails will become stained after 6 hours and
vernix after 12 to 14 hours of exposure.

CLINICAL FEATURES
 Affected patients typically have respiratory distress with
marked tachypnea and cyanosis.
 Reduced pulmonary compliance and use of accessory
muscles of respiration are evidenced by intercostal and
subcostal retractions and abdominal (paradoxical) breathing,
often with grunting and nasal flaring.

CLINICAL FEATURES
 The chest typically appears barrel-shaped, with an
increased anterior-posterior diameter caused by
overinflation.
 Auscultation reveals rales and rhonchi -immediately after
birth.
 Some patients are asymptomatic at birth and develop
worsening signs of respiratory distress as the meconium
moves from the large airways into the lower
tracheobronchial tree.

Diagnosis
MAS must be considered in any infant born
through MSAF who develops symptoms of RD.

Diagnosis
 The diagnosis of MAS is confirmed by chest radiograph.
 The initial CXR may show streaky, linear densities
similar in appearance to transient tachypnea of the
newborn (TTN).
 As the disease progresses, the lungs typically appear
hyperinflated with flattening of the diaphragms.
 Diffuse patchy densities may alternate with areas of
expansion.

Coarse focal consolidation with emphysema.

Hyperinflation and patchy asymmetric
airspace disease that is typical of MAS.

Coarse interstitial infiltrates +L side pneumothorax

Areas of opacification due to atelectasis
bilaterally.

Close up of left lung demonstrating the streaky lucencies
of the air in the interstitium (red arrows) complicated by a
pneumothorax (yellow arrow).

Diagnosis
 In infants with severe disease who require high
concentrations of supplemental oxygen and mechanical
ventilation, the lungs may develop an appearance of
homogeneous density similar to respiratory distress
syndrome (RDS).
 Radiographic changes resolve over the course of 7 to 10
days but sometimes persist for several weeks.
 Air leak occurs in 10 to 30 percent of infants with MAS.

Homogeneous density similar to respiratory
distress syndrome (RDS).

Diagnosis
 Arterial blood gas measurements typically show hypoxemia
and hypercarbia.
 Infants with pulmonary hypertension and right-to-left
shunting may have a gradient in oxygenation between
preductal and postductal samples.
 2D Echocardiogram for evaluation of PPH.

Management
 Sept 2007 theACOG revised recommendations and
recommended that “all infants with MSAF should not longer
receive intrapartum suctioning.If meconium present and the
newborn depressed,the clinician should intubate the trachea
and suction meconium from beneath the glottis”.
 Intrapartum suctioning not effective in removing
meconium aspirated by the fetus into the lungs prior
delivery.

Management
 Skilled resuscitation team should be present at all
deliveries that involve MSAF.
 Pediatric intervention depends on whether the infant
is vigorous.
 Vigorous infant is if has:
1. Strong resp.efforts
2. Good muscle tone
3. Heart rate >100b/m
 When this is a case-no need for tracheal suctioning,
only routine management.

Management
 When the infant is not vigorous:
1. Clear airways as quickly as possible.
2. Free flow 02.
3. Radiant warmer but drying and stimulation should be delayed.
4. Direct laryngoscopy with suction of the mouth and hypopharynx under
direct visualization,followed by intubation and then suction directly to
the ET tube as it slowly withdrawn.
5. The process is repeated until either‘‘little additional meconium is
recovered,or until the baby’s heart rate indicates that resuscitation must
proceed without delay’’.

Postnatal Management
Apparently well child born through MSAF
 Most of them do not require any interventions besides close
monitoring for RD.
 Most infants who develop symptoms will do so in the first 12
hours of life.

Postnatal Management
Approach to the ill newborns:
 Transfer to NICU.
 Monitor closely.
 Full range of respiratory support should be available.
 Sepsis w/up andABx indicated.
 Transfer to ECMO center may be necessary.

Treatment in NICU
Goals:
 Increased oxygenation while minimizing the barotrauma
(may lead to air leak) by minimal MAP and as short IT as
possible.
 Prevent pulmonary hypertension.
 Successful transition from intrauterine to extrauterine
life with a drop in pulmonary arterial resistance and an
increase in pulmonary blood flow.

Treatment in NICU
 Severe MAS can spiral into vicious cycle of hypoxemia that
leads to acidosis, which together cause pulmonary vein
constriction.
 May lead to persistent pulmonary hypertension.
 The resultant right-to-left shunting at the level of the
ductus arteriosus, the atrial level, or both causes further
cyanosis and hypoxemia, which perpetuate the cycle.

Treatment in NICU
Ventilatory support depends on the amount of respiratory distress:
 O2 hood
 Mechanical ventilation (40%).
 CPAP (10%).
 Observational study showed worse outcome for infants treated with
hyperventilation.
 High-frequency ventilators should reduce air leak syndromes in MAS,
but animal and clinical models have yielded conflicting results.
 High-frequency ventilators may slow the progression of meconium
down the tracheobronchial tree and allow more time for meconium
removal.

Treatment in NICU
Surfactant
 Two randomized controlled studies have evaluated the efficacy of
exogenous surfactant administration. Results showed decreased
number of infants requiring ECMO and possible reduction of
pneumothorax, but no difference in mortality.
 A Cochrane meta-analysis of 4 randomized trials confirmed that
surfactant replacement showed no effect on mortality but reduce
the use of ECMO (RR 0.64,95% CI,0.46-0.91).
 Lavage with dilute surfactant-increases oxygenation and decrease
the need of MV (need additional trials).

Treatment in NICU
Inhaled NO
 NO causes selective pulmonary vasodilation by acting directly on the
vascular smooth muscle-activates guanylate cyclase and increases
cGMP.
 By dilating blood vessels in well ventilated areas of lung, NO decreases
theV/P mismatch and improved oxygenation in infants with PPH.
 Decreases need for ECMO (RR 0.61,95%CI 0.51,0.72)
but no difference in mortality.
 In a large randomized multicenter trial infants with MAS responded
well to the combination of inhaled nitric oxide and HFOV, likely
because of improved lung inflation and better delivery of the drug.

ECMO
 40% of infants with MAS treated with inhaled NO fail to
respond and require bypass.
 35% of ECMO patients are with MAS.
 Survival rate after ECMO 93-100%.

Morbidity & Mortality
Pulmonary morbidity
 Pulmonary outcome evaluated in 35 infants with MAS
and 70 controls.
 During the first 6mo after birth, the infants with MAS
were significantly more likely to have one or more
episodes of wheezing and/or coughing lasting ≥3 days
(49% vs.20%) and receive bronchodilator therapy (23% vs.
3%) compared to controls.

 Pulmonary function testing was performed at 8y of age
in 11 children who had MAS and 9 controls.
 The MAS group had evidence of mild airway
obstruction, hyperinflation, and increased closing
volumes compared to controls, and had more exercise-
induced bronchospasm (4 vs.0 children).
 However, during graded exercise stress tests, MAS
children had normal maximal oxygen consumption and
anaerobic threshold without significant hypoxemia or
hypercarbia.

 Respiratory symptoms, pulmonary function tests, and chest
radiographs evaluated in 18 children age 6-11y who had MAS.
 7 children had recurrent cough and wheezing consistent with
asthma, and 5 of these had exercise-induced bronchospasm that
responded to bronchodilators.
 Of the 11 asymptomatic children, 2 had mild expiratory airflow
limitation, 1-exercise-induced bronchospasm, and 8 had normal
pulmonary function. Chest radiographs were normal in all the
children.

Neurologic outcome
 Outcome is good in uncomplicated MAS with no underlying
disorder.
 Most cases of severe MAS are associated with intrauterine
asphyxia and/or infection and neurologic outcome depends
upon these conditions.

 In retrospective comparison, perinatal mortality
significantly higher in singleton pregnancies with/ than
without MSAF (1.5 vs.0.3/1000).
 The mortality rate for MAS resulting from severe
parenchymal pulmonary disease and pulmonary
hypertension is as high as 20%.
 Severe fetal acidemia-cord arterial pH<7.0 was
significantly more common with meconium-stained fluid
(7 vs.3/1000).
 Cesarean delivery was doubled in the meconium group
(14 vs.7%).

Summary
 Optimal care of an infant born through MSAF involves close
collaboration between OBs and Pediatricians.
 Effective communication and anticipation of potential
problems is a corner stone of the successful partnership.

References:
1. Meconium Stained Fluid:Approach to the Mother and the Baby Michele C.Walsh, MD, MS;
Jonathan M. Fanaroff, MD, JD Clin Perinatol 34 (2007) 653–665
2. The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and
outcome. Dargaville PA; Copnell B Pediatrics. 2006 May;117(5):1712-21.
3. Delivery room management of the apparently vigorous meconium-stained neonate: results of
the multicenter, international collaborative trial.WiswellTE; Gannon CM; Jacob J; Goldsmith
L; Szyld E;Weiss K; Schutzman D; Cleary GM; Filipov P; Kurlat I; Caballero CL;Abassi S;
Sprague D; Oltorf C; Padula M Pediatrics 2000 Jan;105(1 Pt 1):1-7.
4. Defecation in utero: a physiologic fetal function. Ramon y Cajal CL; Martinez RO Am J Obstet
Gynecol 2003 Jan;188(1):153-6.
5. Surfactant and surfactant inhibitors in meconium aspiration syndrome. Dargaville PA; South M;
McDougall PN J Pediatr 2001 Jan;138(1):113-5.

SAMUEL BEZABIH MESKEREM 2004 EC
GONDER

POP(Williams Gyn.)
• Prolapse is the downward displacement of one of the pelvic
organs from its normal location that results in vaginal wall
protrusion or bulge
• The terms traditionally used to describe
location of protrusion are cystocele,
cystourethrocele, uterine prolapse, rectocele,
and enterocele .
a vaginal bulge due to herniation of the bladder,
bladder/urethra, uterus, rectum, or small bowel,
respectively
GONDER

POP(Williams Gyn.)
• However, these terms are imprecise and
misleading, as they focus on what is presumed
to be prolapsed rather than what is actually
seen.
• More importantly, such assumptions can lead
to unforeseen problems.
– For example, a posterior vaginal prolapse that is
presumed to be a rectocele may require an
alternative reconstructive repair if an undetected
enterocele is discovered at the time of surgery.
GONDER

POP (Will Gyn)
• Although these terms are deeply entrenched in the
literature, it is more clinically useful to describe
prolapse in terms of what one actually sees:
– anterior vaginal wall prolapse,
– apical vaginal wall prolapse,
– Cervical prolapse,
– posterior vaginal wall prolapse,
– Perineal prolapse, and
– Rectal prolapse.
• These descriptors do not presuppose what is behind
the vaginal wall, but rather describe the tissues that
are objectively noted to be prolapsed.
GONDER

Involved V Compartments -Anna
• Anterior Compartment
– Midline defect-attenuation of pubocervical facsia
– Lateral/paravginal defect-detachment of PCF from
ATFP
• Cystocele, cystourethrocele
• Central/ Apical-
– uterus , vaginal fornices, upper portion of posterior vaginal
wall
– Involves USLs
• Posterior Compartment
– Lower part of posterior vaginal wall
– rectocele
GONDER

Anterior V Compartment- Telinde
• The anterior vaginal compartment extends from the
PS anteriorly to the posterior aspect of the cervix
• separates the bladder from the lumen of the vagina
• Lateral boundaries are the white lines/ ATFP .
Pubocervical septum-a trapezoid-shaped fascia that provides
support for the anterior vagina under the bladder , attached
distally to pubic ramus, Superior- Pericervical ring, Lateral – ATFP)
– EPF b/n anterior Vaginal epithelium and bladder
– Anterior vaginal epithelium firmly adhered to PCS- Rugae
– Laterally- linear attachment to the ATFP forms the
anterior lateral sulci of the vagina
– Defects in the pubocervical septum are associated with
anterior vaginal compartment failure.
GONDER

GONDER
Cystocele-
 a defect within the central pubocervical septum(PCS) that allows
the floor of the bladder to descend.
Cystoceles are normally caused by transverse apical defects in the PCS
Paravaginal defect-
 A lateral defect at or near the attachment of the PCS to the ATFP
 It create a direct connection between the vesicovaginal space and
the paravesical space on the affected side of the patient.
Anterior V Compartment Defects Telinde

SAMUEL BEZABIH MESKEREM 2004 EC GONDER
1. Laterally, where the pubocervical
fascia attaches to arcus tendineus
fascia pelvis (paravaginal defect)
2. Transversely, in front of the cervix
where the pubocervical fascia
blends into the pericervical ring of
fibromuscular tissue, or in the case
of a woman who has had a
hysterectomy, at the vaginal cuff
(transverse defect)
3.Centrally, in the area immediately anterior to the vaginal mucosa in between
the lateral margins of the pubocervical fascia (midline or central defect)
4.Distally, where the urethra perforates the urogenital diaphragm
Anterior V Compartment Defects Telinde
There are four clinically identifiable areas in which defects in this
support are likely to occur

Pathophysiology
• POP results from attenuation of the supportive
structures, whether by actual tears or “breaks”
or by neuromuscular dysfunction or both.(NOVAC)
• Neuropathy of the pudendal nerve and
myopathy of the levator muscles are believed to
be significant contributing factors in the
development of pelvic organ prolapse (Telinde)
GONDER

GONDER
Will Gyn 2nd

Etiology/RFs
• Vaginal delivery-
– trauma(streching and laceration of DECT, LA, perineal
muscles)
– pudendal Nerve neuropathy LA weakness (Myopathy)
• Age-
– hypoestrogenism,
– kyphosis due to osteoporesis pelvic inlet become more
horizontal weight of pelvic content act more directly over
the UGH and pelvic floor
• Life style-
– heavy lifting, straining at stool/urine, obesity, smoking
• Connective tissue disease, DM ,chronic cough, Ascitis,
Constipation
• Corticosterod therapy
GONDER

RFs-Vaginal Delivery-Childbirth trauma
• Vaginal Delivery-the most likely major contributing factor
– Necessary but not sufficient cause
• In the vast majority of women , the process of POP
development begins with their first vaginal delivery.
• Each subsequent vaginal delivery contributes to the likelihood
that a clinically symptomatic prolapse will occur
• The pelvis is contoured so that even in a normal labor and
delivery, substantial forces are applied to the endopelvic fascia,
muscular floor of the pelvis, and pudendal nerve.
• The greatest forces generated are at
the level of the interspinous diameter.
• This plane is the location of the singularly important
pericervical ring and its junction with every other septa
and ligament associated with normal vaginal support
and suspension
GONDER

Vaginal Birth
GONDER

Vaginal Birth Vs POP
• No recommendation regarding optimum
length of 2nd stage of labor, vaginal operative
deliveries, Management of macrosomia etc in
the context of preventing POP risk
GONDER

Risk Factors Associated with POP Will Gyn
• Pregnancy
• Vaginal childbirth
• Menopause
• Aging
• Hypoestrogenism
• Chronically increased
intra-abdominal
pressure
• COPD
• Constipation
• Obesity
• Pelvic floor trauma
• Genetic factors
• Race
• Connective tissue
disorders
• Hysterectomy
• Spina bifida
GONDER

POP- Protective Factors
• Inflammatory reactions on the paracervical
and parametrial tissues with 20 fibrosis and
adhesion reduces the risk of POP
– Eg PID, Puerperial/posstabortal metritis,
Endometriosis, Pelvic radiation
• Cesarean Delivery ?????
GONDER

Clinical Evaluation-History
Clinical Presentations
• Usually asymptomatic
• Vaginal fullness/ pressure sensation
• Back/sacral pain on standing
• Spotting from ulceration
• Lower abdominal discomfort
• Urinary/coital/ defecatory difficulties
GONDER

Clinical Evaluation-History
• Complaint and perception of the problem
– Eg may consider it as life threatening that may rapture or malignant
• A careful micturition, defecation, and sexual history
– Stress, urge, and neurogenic urinary incontinence
– number of trips to the toilet and the compensatory measures/
splinting necessary to complete evacuation,
– continent or incontinent of gas, liquid, or solids.
• The past surgical history helps the surgeon assess the status of
the patient in general and of the pelvis in particular. Specific
interest should be placed on previous attempts to correct pelvic
organ prolapse.
MED Hx
• cardiac function, thromboembolic risks, entrenched tobacco
addiction, or limited mobility are not ideal candidates for this
type of surgery. A complete list of current medications, including
herbals and over-the-counter preparations, and treating
physicians is also helpful.
GONDER

Clinical Evaluation-Pelvic Examination
• Patient in lithotomy position
• Separate labia, inspect interoitus
– Prolapse could be internal ( prox to hymen) or
external
• Inspect under straining/ valsalva
– Straining causes pronounced difference in
prolapse in pts with healthy Pfloor muscles and
undecended levator plate
• If no prolapse is apparent on exam
– Switch to Standing position and valsalva man
GONDER

• Identify and Reduce dominant prolapse
– The first hernia to descend / the most dependent part of a
descended prolapse
– Anterior prolapse.( Eg Lateral paravaginal/apical transverse
defect) - easily replaced by placing a tongue blade or Ayre
spatula in each anterior lateral sulcus. If replacement is not
possible by this maneouver likely a central anterior
defect
– A dominant posterior segment prolapse may be replaced
with the posterior blade of a disjoined Sims' speculum.
– A dominant superior segment prolapse may be replaced
with a large cotton swab, a sponge stick, or, in advanced
cases, by attaching a tenaculum to the cervix.
• Look for 20 prolapses after replacement of the
dominant prolapse
GONDER

Paravaginal Defect Dx-Telinde
• Baden and Walker have recommended the use of a
curved ring forceps to elevate the lateral aspects of the
anterior vagina to their normal points of attachment
along the pelvic sidewall. The curved arms of the ring
forceps are directed laterally and posteriorly toward the
ischial spines as the patient bears down. When this
lateral elevation corrects the support defect, the
diagnosis of a paravaginal defect can be
• If the patient continues to have a bulge of tissue
through the open arms of the forceps, she either has a
midline loss of support or a combined midline and
lateral loss of support.
• Imaging studies such as magnetic resonance imaging
and ultrasound provide details not only about
connective tissue support in the pelvis but also about
muscle integrity. SAMUEL BEZABIH MESKEREM 2004 EC
GONDER

• Inspect rugae presence or absence of underlying EPF,
Vaginal epithelium- atrophy??
• Rcto-vaginal examination- posterior and superior segment
evaluation US ligaments – medial to I spines
Enterocele Vs Rectocele
• Push finger anteriorly towards posteror vaginal wall, patient
strains
– Enterocele- bulging down the vaginal wall proximal to the rectal
finger
– Rectocele- palpation of transverse detachment of the proximal RV
septum
• Integrity of S3 - anal sphincter, LA muscle contraction ,
spread and dorsiflex the toes
• Incotenience at any stage ( check for potential SI – valsalva
wit prolapse reduced)
GONDER

POP Classification
POP-Q System
• This system contains a series of site-specific measurements of
a woman's pelvic organ support.
• Prolapse in each segment is measured relative to the HYMEN,
which is a fixed anatomic landmark that can be identified
consistently.
• Six points are located with reference to the plane of the
hymen: two on each of the following
– the anterior vaginal wall (points Aa and Ba),
– the apical vagina (points C and D), and
– the posterior vaginal wall (points Ap and Bp) .
• All POP-Q points, except total vaginal length (tvl), are
measured during patient Valsalva and should reflect
maximum protrusion.
GONDER

ANATOMIC LANDMARKS USED DURING POP-Q.
GONDER
•Aa-3cm proximal to urethral meatus on anterior vaginal wall
•Ap-3cm proximal to hymen on posterior vaginal wall
•Ba and Bp –maximum prolapse excursions on A and P Vaginal wall

The Pelvic Organ Prolapse Quantification (POP-Q)
Staging System of Pelvic Organ Support (Williams)
Stage 0:
• No prolapse is demonstrated.
– Points Aa, Ap, Ba, and Bp are all at –3 cm
– and either point C or D is b/n – (TVL)cm and – (TVL–2) cm
(i.e., the quantitation value for point C or D is –[TVL – 2] cm
Stage I:
• The criteria for stage 0 are not met, but the most distal
portion of the prolapse is >1 cm above the level of the
hymen (i.e., its quantitation value is < – 1 cm).
Stage II:
• The most distal portion of the prolapse is < 1 cm
proximal to or distal to the plane of the hymen (i.e., its
quantitation value is > –1 cm but < 1 cm).
GONDER

POP (Williams)
• Stage III:
The most distal portion of the prolapse is >1 cm below the
plane of the hymen but protrudes no further than 2 cm
less than the total vaginal length in centimeters (i.e., its
quantitation value is > + 1 cm but < + [TVL–2] cm).
Fig. 24–4A represents stage III Ba and Fig. 24–4B represents stage III
Bp prolapse.
• Stage IV:
Essentially, complete eversion of the total length of the
lower genital tract is demonstrated. The distal portion of
the prolapse protrudes to at least (TVL–2) cm (i.e., its
quantitation value is >/= +[TVL–2] cm). In most instances,
the leading edge of stage IV prolapse will be the cervix or
vaginal cuff scar.
Fig. 24–3A represents stage IV C prolapse.
GONDER

Mediscape
Most clinicians routinely use the ICS classification
(POP-Q) system, which is classified as follows:
– Stage 0 - No prolapse
– Stage I - Descent of the most distal portion of prolapse
is more than 1 cm above the level of the hymen.
– Stage II - Maximal descent of prolapse is between 1
cm above and 1 cm below the hymen.
– Stage III - Prolapse extends more than 1 cm beyond
the hymen, but no more than within 2 cm of the total
vaginal length.
– Stage IV - Total or complete vaginal eversion
GONDER

Baden-Walker Halfway System
Will Gyn.
• This descriptive tool is also used to classify
prolapse on physical examination and is in
widespread clinical use.
• Although not as informative as the POP-Q, it
is adequate for clinical use if each
compartment (anterior, apical, and posterior)
is evaluated
GONDER

Baden-Walker Halfway System -Telinde
• Two anatomic points to be assesed for prolapse
(Grade 0-4) on each compartment (total 6)
– Urethral and vesical - anterior
– Uterine and Culdesac- superior
– Rectal and perineal- posterior
+Levator strength graded subjectively out of 4
• Example: 12/44/32.
– A dominant complete apical prolapse is with
enterocele,
– significant cystocele and rectocele, and
– perineal attenuation to the level of the external anal
sphincter
• 2/4 levator strength is present.
GONDER

Primary and Secondary Symptoms at Each Site Used in
the Baden-Walker Halfway System-Telinde
Anatomic site Primary symptoms Secondary symptoms
Urethral Urinary incontinence Falling out
Vesical Voiding difficulties Falling out
Uterine Falling out Heaviness and so forth
Cul-de-sac Pelvic pressure
(standing)
Falling out
Rectal True bowel pocket Falling out
Perineal Anal incontinence Too loose (gas/feces)
GONDER

Table 24-3 Baden-Walker Halfway System for the Evaluation of Pelvic
Organ Prolapse on Physical Examinationa
• Grade 0
– Normal position for each respective site
• Grade 1
– Descent halfway to the hymen
• Grade 2
– Descent to the hymen
• Grade 3
– Descent halfway past the hymen
• Grade 4
– Maximum possible descent for each site
GONDER

GONDER
B-W Halfway System Telinde

POP (Telinde)
LUMBOSCRAL LORDOSIS
partially vertical pelvic inlet posterior aspect
is ~60⁰ higher than the anterior  downard
pressure deflected from pelvic outlet and UGH
onto superior symphysis Pubis partial
shielding of the PO & UGH from downward
stress
GONDER

Pelvic Diaphragm (Telinde)
Muscles-collectively named Levator ani/ sling
• These muscles form a basin or covering of the pelvic outlet and
are often grouped together as the levator ani or levator sling
– Puborectalis
– Pubococcygeous
– Iliococcygeous
– Coccygeous
– Piriformis
• The levator ani muscles are fused posteriorly to the rectum and
attach to the coccyx
• Lavator Plate/Sacrococcygeal Raphae - strong band of fibrous
CT due to midline confluence of lavator muscles b/n coccyx
and anus
• Vagina and anus are suspended by EP fascia directly over
lavator plate
GONDER

Telinde
• This plate is oriented horizontally in the standing patient.
• The vagina and the rectum are suspended by the
endopelvic fascia directly over the levator plate.
• Myopathies or neuropathies cause weakness of the
pubococcygeus and iliococcygeus muscles and may allow
the levator plate to sag and descend permanently.
• This descent causes the genital hiatus to remain open as
it does during defecation.
• This increased opening changes the normal horizontal
axis of the proximal vagina to a vertical orientation and
predisposes the central pelvic organs to prolapse.
GONDER

Pelvic Diaphragm WILL GYN.
• The muscles that span the pelvic floor are collectively
known as the pelvic diaphragm. This diaphragm consists of
the levator ani and coccygeus muscles along with their
superior and inferior investing layers of fasciae.
• Levator Ani-a critical component of pelvic organ support .
– Physiologically, normal levator ani muscles maintain a constant
state of contraction. (Basal Tonicity)
– They provide a solid floor that supports the weight of the
abdominopelvic contents against intra-abdominal forces.
• Inferior to the pelvic diaphragm, the perineal membrane
and perineal body also contribute to the pelvic floor
GONDER

• The levator plate is the region between the anus
and the coccyx formed primarily by the insertion
of the iliococcygeus muscles (see Figs. 38-7 and 38-9).
• This portion of the levator muscles forms a
supportive shelf on which the rectum, upper
vagina, and uterus rest.
• In a woman with normal support, the levator
plate lies almost parallel to the horizontal plane
in the standing position (Berglas, 1953).
• One theory suggests that levator plate support
prevents excessive tension or stretching of the
connective tissue pelvic ligaments and faciae
(Paramore, 1908)
GONDER

• Accordingly, neuromuscular injury to the levator
muscles may lead to eventual sagging or vertical
inclination of the levator plate and of the urogenital
hiatus.
• Consequently, the vaginal axis becomes more vertical,
and the cervix is oriented over the opened hiatus.
• The mechanical effect of this change is to increase
strain on connective tissues that support the pelvic
viscera.
• Increased urogenital hiatus size has been shown to
correlate with increased severity of pelvic organ
prolapse (DeLancey, 1998).
GONDER

View of lateral pelvic sidewall-Will Fig 38-7
GONDER

Pelvic Diaphragm Vs Floor-Telinde
• The term pelvic diaphragm refers to the
levator ani muscle and its covering fasciae,
both the superior fascia and the inferior
fascia.
• The term pelvic floor refers to all of the
supportive structures that are involved with
pelvic organ support.
• Sometimes the term pelvic floor and pelvic
diaphragm can be used interchangeably,
especially in the British literature
GONDER

Inferior view of pelvic floor muscles.
Will Fig 38-8
GONDER

The pelvic diaphragm viewed from above
GONDER

(Telinde)
Archus Tendinus Levator ani ( Muscular Arches)/ATLA
– Superior insertions of iliococcygeous- =>pelvic side wall
parietal fascia thickenings from ischial spines to pubic
tubercle
• ATLA -a condensation of fascia covering the medial
surface of the obturator internus muscle, serves as the
point of origin for parts of the very important levator ani
muscles.( WILL GYN)
Arcus tendineus fasciae pelvis (fascial arches) white lines
/ATFP:
– thickenings of the parietal fascia of the bellies of the
ileococcygeus muscles immediately inferior to the muscular
arches
• ATFP-a condensation of fascia covering the medial
aspect of the obturator internus and levator ani muscles.
It represents the lateral point of attachment of the
anterior vaginal wall. ( WILL GYN)
GONDER

The lateral attachments of the pubocervical fascia (PCF) and the
rectovaginal fascia (RVF) to the pelvic sidewall. Also shown are
the arcus tendineus fascia pelvis (ATFP), arcus tendineus fasciae
rectovaginalis (ATFRV), and ischial spine (IS).
GONDER

(Telinde)
• In the standing patient, the white line is nearly
horizontal; in the lithotomy position, it is nearly
vertical
• The ATFP are the lateral attachment points for the
pubocervical fascia and proximal rectovaginal
septum.
• The white line serves the function of midvaginal
lateral support.
• Paravaginal and proximal pararectal defects are
located immediately medial to the white line
GONDER

Pelvic CTs (Telinde)
• The connective tissues of the pelvis are
collectively known as the endopelvic fascia.
• This fibroelastic CT matrix contains varying
amounts of smooth muscle.
• It supports and invests all the midline organs
and structures of the pelvis.
• Only the ovaries and fallopian tubes lie outside
this investment.
GONDER

• In the central pelvis, the visceral peritoneum
drapes over the midline structures, dipping
into recesses but not descending into direct
contact with the muscular pelvic floor.
• The irregular space between the pelvic
diaphragm, the muscular pelvic sidewall, and
the visceral peritoneum is the location of the
endopelvic fascia (Tables
•
GONDER

• At various locations, the endopelvic fascia manifests
different characteristics.
• These forms include
– loose areolar tissue capable of distention,
– neurovascular sheaths,
– septa and ligaments that support, suspend, and
separate organs, and
– dense skeletal muscle investments
GONDER

PELVIC CTS (Telinde)
• The endopelvic fascia may be divided into
three parts:
I. parietal fasciae,- invest straited muscles
II. visceral fasciae, and
III. deep endopelvic connective tissue
GONDER

Parietal Faciae (Telinde)
• Obturator facia
• Levator ani facia( superio pelvic diaphragm
facia)
• Coccygeous faciae (sacrospinous
ligament)
• Piriformis facia
Pelvic parietal fascia provides muscle
attachment to the bony pelvis and serves as
anchoring points for visceral fascia,
GONDER

Visceral Faciae (Telinde)
Organs invested by VF
– Vagina
– Uterus
– Bladder
– Rectum
Not invested by VF
– Fallopian tubes
– ovaries
GONDER

DEEP ENDOPELVIC CONNECTIVE TISSUE
(Telinde)
GONDER

Deep Endopelvic Connective Tissue (Telinde)
1.UTEROSACRLA LIGAMENTS (RECTAL PILLARS)
• Origin-S2,S3,S4 pereostium
• Insertion- 5 &7 oclock position of the supravaginal
cervix posteriorly and laterally
• Contents: US autonomic N plexus, Rectouterine
muscles
• Function: proximal suspension of the uterovaginal
complex
• They hold the cervix behind the urogenital hiatus in
the posterior pelvis at the ischial spines level with the
uterus in anteflexion and the vagina suspended over
the levator plate
GONDER

2.Cardinal ligaments (Mackenrodt's ligament /lateral cervical
ligament/proper cervical ligament)
Origin
• The hypogastric root with fibrous connections to the lateral
abdominal and pelvic walls
Insertion
on the lateral supravaginal cervix at the 3-o'clock and 9-o'clock
positions,continuous with and forms part of the pericervical ring.
Cntents
• Portions of the uterosacral plexus.
• Uterine artery and veins, Minimal smooth muscle content with no
named component.
• The distal ureter passes under the uterine artery within the
superior portion of the cardinal ligament
Function
the primary vascular conduits of the uterus and vagina, providing
lateral stabilization to the cervix at the level of the ischial spines.
They are similar in structure, content, and function to the
mesenteries of the abdomen
GONDER

3. Pubocervical Ligaments
(Bladder pillar)
Origin
Inferior surface of the superior pubic ramus medially
and the arcus tendineus fascia pelvis laterally
Insertion
The points of insertion are on the anterior and lateral
supravaginal cervix at the 11-o'clock and 1-o'clock
positions. This insertion is continuous with and forms
part of the pericervical ring.
Vascular component
Artery and veins of the bladder pillar
Function
These ligaments are the least well developed of the
pericervical ligaments, serving as a vascular conduit
and for a minimal degree of cervical stabilization
GONDER

4: Pubocervical Septum or Fascia (Vesicovaginal septum /fascia,
pubovesicocervical septum/ fascia)
Shape:Trapezoidal with the narrow end located distally
Contents:Fibroelastic connective tissue and smooth
muscle
Function:Anterior vaginal support, including support of
the bladder
Boundaries
Distal: Pubic tubercles laterally and the pubic arch
centrally fusing with the urogenital diaphragm
Lateral: Arcus tendineus fascia pelvis or white line.
Proximal: Pericervical ring centrally and both
pubocervical and cardinal ligaments laterally
Superior: Visceral fascia of the bladder
Inferior: Epithelium of the vagina
GONDER

Pubocervical fascia-TELINDE
• A trapezoid-shaped fascia that provides
support for the anterior vagina under the
bladder.
• It is attached
– superiorly to the pericervical ring,
– distally to the pubic ramus, and
– laterally to the arcus tendineus fascia pelvis (white
line).
GONDER

5: Rectovaginal Septum or Fascia
(Denonvilliers' fascia)
Shape:Trapezoidal with the narrow end located distally
Contents: Fibroelastic connective tissue and smooth
muscle
Function
• Posterior vaginal support and suspension,
• stabilization of the rectum, and perineal suspension.
The vaginal suspensory axis consists of the perineum,
rectovaginal septum, pericervical ring, uterosacral
ligaments, and presacral periosteum.
• The RVS also guides the leading edge of a descending
bowel movement into the anus.
GONDER

Rectovaginal Septum or Fascia-Boundaries
(Denonvilliers' fascia)
Distal: Fusion with the proximal perineal body at
the central tendon of the perineum.
Lateral:
– In the distal half of the vagina- the arcus tendineus
fasciae rectovaginalis;
– in the proximal half of the vagina- the arcus tendineus
fascia pelvis
Proximal: Uterosacral ligaments laterally and the
pericervical ring centrally.
Superior: Epithelium of the vagina
Inferior: Visceral fascia of the rectum
GONDER

6-Pericervical Ring (Supravaginal septum)
Shape Collar of connective tissue encircling the supravaginal cervix
Contents Fibroelastic connective tissue
Function
Cervical stabilization within the interspinous diameter by
connecting with all other named components of the deep
endopelvic connective tissue
Connections
Anterior: The PC ring is located between the base of the bladder and
the anterior cervix, where it connects with the pubocervical
ligaments at the 11-o'clock and 1-o'clock positions and the
proximal pubocervical septum centrally.
Lateral: Cardinal ligaments at the 3-o'clock and 9-o'clock positions
Posterior: The pericervical ring is located between the rectum and
the posterior cervix, where it connects with the uterosacral
ligaments at the 5-o'clock and 7-o'clock positions and the proximal
rectovaginal septum centrally.
GONDER

Avascular Spaces
• Outside the confines of the named condensations of
endopelvic fascia are avascular potential spaces.
• When properly used, these spaces give the surgeon access to
important support structures deep within the pelvis.
-Prevesical
-Paravesical
-Vesicovaginal
-Vesicocervical
-Rectovaginal
-Pararectal
-Retrorectal
• These spaces are not only available to the vaginal
reconstructive surgeon, but they are also critical in
identification of pelvic support landmarks.
GONDER

The avascular spaces of the female pelvis.
GONDER

Delancey’s Division of vaginal support levels
(Telinde)
LEVEL I (Proximal vaginal support)
Due to suspension by paracolpic ligaments(Involves
mainly USL and to a lesser extent cardinal ligaments )
Defect of support at or above IS resulting in
UVP, Post hysterectomy vaginal prolapse, enterocele
GONDER

Delancey’s Division of vaginal support levels (Telinde)
Level II support (midvaginal)-lateral support
 Due to lateral attachment of the facial septa (pubocervical and
rectovaginal septa to the pelvic side walls
 the septa attach to the ATFP(anteriorly) and
ATFRV(posteriorly)
Damage results in paravaginal and pararectal defects
 Cystocel and rectocele - central defects in pubocervical and
rectovaginal septa SAMUEL BEZABIH MESKEREM 2004 EC
GONDER

Delancey’s Division of vaginal support levels
(Telinde)
Level III support (distal fusion)
Due to fusion to urogenital diaphragm anteriorly and
proximal perineum posteriorly
Damage results in urinary incontenience anteriorly
and perineal body deficits posteriorly(.. Damage to level
III support contributes to anterior and posterior vaginal wall
prolapse, gaping introitus, and perineal descent-Williams)
GONDER

Three-dimensional view of the endopelvic fascia. Notice the location of
the cervix in the proximalanterior vaginal segment. (From DeLancey
JO. Anatomic aspects of vaginal eversion after hysterectomy. Am J
Obstet Gynecol 1992;166:1717.)
GONDER

DeLancey's biomechanical levels of The endopelvic fascia of a
posthysterectomy patient
• level I”proximal suspension;
• level II lateral attachment;
• level III distal fusion. (From DeLancey JO. Anatomic aspects of vaginal eversion after hysterectomy. Am J Obstet Gynecol
1992;166:1717.)
GONDER

UPTODATE
• Level 1 – Uterosacral/cardinal ligament complex, which suspends the uterus and upper
vagina to the sacrum and lateral pelvic side wall.
• Loss of level 1 support contributes to the prolapse of the uterus
and/or vaginal apex.
• Level 2 – Paravaginal attachments along the length of the vagina to the superior
fascia of the levator ani muscle and the arcus tendineus fascia pelvis (also
referred to as the “white line”). Loss of level 2 support contributes to anterior
vaginal wall prolapse (cystocele).
• Level 3 – Perineal body, perineal membrane, and superficial and deep perineal muscles,
which support the distal one third of the vagina.
GONDER

Will. Gyn.
LEVEL I SUPPORT
• consists of the cardinal and uterosacral ligaments
attachment to the cervix and upper vagina.
• The CLs fan out laterally and attach to the parietal fascia
of the obturator internus and piriformis muscles, the
anterior border of the greater sciatic foramen, and the
ischial spines.
• TheUSLs are posterior fibers that attach to the presacral
region at the level of S2 through S4.
• Together, this dense visceral CT complex maintains
vaginal length and horizontal axis. It allows the vagina to
be supported by the levator plate and positions the
cervix just superior to the level of the ischial spines.
• Defects in this support complex may lead to apical
prolapse. This is frequently associated with small bowel
herniation into the vaginal wall, that is, enterocele.
GONDER

Will. Gyn.
LEVEL II SUPPORT
• consists of the paravaginal attachments that are contiguous with
the cardinal/uterosacral complex at the ischial spine.
• These are the CT attachments of the lateral vagina anteriorly to the
ATFP and posteriorly to the ATRV. Detachment of this connective
tissue from the ATFP leads to lateral or paravaginal anterior vaginal
wall prolapse.
LEVEL III SUPPORT
• The perineal body, superficial and deep perineal muscles, and
fibromuscular CT comprise level III. Collectively, these support the
distal1/3rd of the vagina and introitus.
• The perineal body is essential for distal vaginal support as well as
proper function of the anal canal.
• Damage to level III support contributes to anterior and posterior
vaginal wall prolapse, gaping introitus, and perineal descent
GONDER

Will Gyn.
• The parametria continues down the vagina as the
paracolpium (see Fig. 38-11). This tissue attaches
the upper vagina to the pelvic wall, suspending it
over the pelvic floor. These attachments are also
known as level I support or the suspensory axis.
They provide connective tissue support to the
vaginal apex after hysterectomy. In the standing
position, level I support fibers are vertically
oriented. Clinical manifestations of level I support
defects include posthysterectomy vaginal vault
prolapse
GONDER

Level II –Will Gyn.
• Midvaginal Support -The lateral walls of the
midportion of the vagina are attached to the
pelvic walls on each side by visceral connective
tissue known as endopelvic fascia. These lateral
attachments of the vaginal walls blend into the
arcus tendineus fascia pelvis and the medial
aspect of the levator ani muscles. In doing so,
these lateral attachments create the anterior and
posterior lateral vaginal sulci. These sulci run
along the vaginal sidewalls and give the vagina
an H shape when viewed in cross section
GONDER

Level II- Will Gyn.
• Attachment of the anterior vaginal wall to the
levator ani muscles is responsible for the bladder
neck elevation noted with cough or Valsalva (see
Fig. 38-8). Therefore, these attachments may
have significance for stress urinary continence.
The midvaginal attachments are referred to as
level II support or the attachment axis. Clinical
manifestations of level II support defects include
anterior and posterior vaginal wall prolapse and
stress urinary incontinence.
GONDER

Level III- Will Gyn.
Distal Vaginal Support -The distal third of the vagina is
attached directly to its surrounding structures
• Anteriorly, the vagina is fused with the urethra,
• laterally it attaches to the pubovaginalis muscle and
perineal membrane, and
• posteriorly it attaches to the perineal body.
• These vaginal attachments are referred to as level III
support or the fusion axis. They are considered the
strongest of the vaginal support components. Failure of this
level of support can result in distal rectoceles or perineal
descent. Anal incontinence also may result if the perineal
body is absent, as may follow obstetric trauma.
GONDER

UPTODATE
GONDER

Preventive measures/
Conservative Mg’t (Telinde)
considerations in the conservative treatment
of pelvic organ prolapse are:
– Pelvic floor exercises,
– weight loss,
– treatment of chronic disease(cough)
– physical therapy,
– cessation of smoking,
– estrogen therapy
GONDER

Kegel’s Exercise- Telinde
• Pelvic floor strengthening by voluntary contraction of the
muscles innervated by the pudendal nerve was popularized
by Arnold Kegel.
• Pelvic diaphragm (10 ly Puborectalis) and anal sphincte
• Several different strategies help to remind patients to do
their Kegel exercises. One of the most effective techniques
is briefly outlined below.
• The Kegel contraction should be confirmed during a pelvic
examination to ensure that the patient understands the
correct muscles to contract
• Frequently, patients will either perform a Valsalva
maneuver or tighten the gluteus maximus muscle instead
of the external anal sphincter and levator ani muscles
GONDER

Kegles Exercise- Telinde
• The proper time to Kegel is after micturition.
• After the bladder is emptied, the patient is instructed to lean as far
forward as her stability allows.
• While leaning forward, she performs three or more isometric Kegel
exercises by tightening the muscles until they voluntarily relax on
their own.
• The dependent portion of a cystocele is below the level of the
internal urethral orifice.
• The forward tilt physically elevates the bladder floor and allows for
more complete emptying. The muscular action of the Kegel
contractions also aids the process of emptying
• Coupling this activity with voiding habituates the patient to perform
the exercises several times a day.
• The result is the combination of more complete emptying and a
strengthened pelvic floor, both of which are advantageous for the
patient. The patient may then be able to use the Kegel contraction
during physical stress to prevent incontinence or to protect against
the pelvic floor impact of sudden increases in abdominal pressure
GONDER

Surgical management (Telinde)
• Regardless of the degree of prolapse, no
surgery should be done unless the patient
experiences a sufficient degree of morbidity.
• Most symptoms relate to quality-of-life issues
• The management of advanced and
symptomatic prolapse is primarily surgical
GONDER

Surgical management
• 1 obliterative procedures-colpocleisis-
removing vaginal epithelium
GONDER

Surgical management
Apical descent
• Abdominal sacropoplexy
• Sacrospinal ligament suspension
• Uterosacral ligament vaginal cuff
suspension
Paravaginal defect
• Reattachment of vagianl connective tissue
to ATFP
GONDER

PELVIC ORGAN PROLAPSE(POP)
Birhanu Sendek(MD, MPH, OB/GYN)
April 2012
05/04/2012 1
Birhanu sendek (MD, MPH)

Objectives
• Describe POP
• Explain factors involved in the pathogenesis
• Describe the clinical presentation of POP
• Describe complications of POP
• Describe current management principles
05/04/2012 2

INTRODUCTION
• Pelvic Organ Prolapse (POP) is the downward
displacement of the structures that are
normally located adjacent to the vaginal vault.
• Protrusion of the pelvic organs into or out the
vaginal canal
• Defects in the pelvic supporting structures
result in a variety of clinically evident pelvic
relaxation abnormalities
05/04/2012 3

Introduction...
• It's estimated that half of women who have
children will experience some form of
prolapse in later life, but because many
women don't seek help , the actual number of
women affected by prolapse is unknown.
• POP occurs when the pelvic floor muscles
become weak or damaged and can no longer
support the pelvic organs.
05/04/2012 4

History of prolapse
• Prolapse was clearly known to the ancients as
mentioned in the writings of Hippocrates and
Galen
• Vaginal packing, tampons, massages, and
exercises were used with some success
• Suspended from their feet for a period of 24
hours to treat prolapse
• Prolapse should be attacked with a red hot iron
as if to burn it
• Various caustics were used, including silver
nitrate, nitric acid, acid nitrate of mercury, hot
metal, and sulfuric acid
05/04/2012 5

Epidemiology
• Most are parous, older women
• History of increased intra-abdominal pressure
• Postmenopausal
• History of trauma to pelvic supporting
structures
• 11% of women up to the age of 80 in USA
have surgery for POP &/or Incontinence
05/04/2012 6

Elements comprising the Pelvis
• Bones
– Ilium, ischium and pubis fusion
• Ligaments
• Muscles
– Obturator internis muscle
– Arcus tendineus levator ani or white line
– Levator ani muscles
– Urethral and anal sphincter muscles
05/04/2012 7

Elements comprising the Pelvis…
• Endopelvic fascia
– Meshwork of collagen, elastin and smooth muscle
– Extends from the level of uterine artery to the
fusion of the vagina and levator ani
– Attached to uterus is parametrium – cardinal-
uterosacral ligament complex
– Attached to vagina is paracolpium – pubocervical
and rectovaginal fasciae
05/04/2012 8

De Lancey’s three levels of vaginal
support
• Apical suspension
– Upper paracolpium suspends apex to pelvic walls and
sacrum
– Damage results in prolapse of vaginal apex
• Midvaginal lateral attachment
– Vaginal attachment to arcus tendineus fascia and
levator ani muscle fascia
– Pubocervical and rectovaginal fasciae support bladder
and anterior rectum
– Avulsion results in cystocele or rectocele
• Distal perineal fusion
– Fusion of vagina to perineal membrane, body and
levators
– Damage results in deficient perineal body or
urethrocele
05/04/2012 9

Fascial and Muscular layers of the
Pelvic Floor
05/04/2012 10

Attachments of cardinal/Utero-sacral
ligaments
05/04/2012 11

Schematic diagram of the striated musculature of the pelvic floor. PR, puborectalis; PC,
pubococcygeus; IC, iliococcygeus; O, obturator muscle; TA, tendinous arc of the obturator
muscle
05/04/2012 12

Pelvic Relaxation
• Cystocele
• Stress urinary incontinence
• Rectocele
• Enterocele
• Uterine and vaginal prolapse
Result of weakness or defect in supporting tissues-
endopelvic fascia and neuromuscular damage
05/04/2012 13

Boat in dock analogy
• Boat- pelvic organs
• Water- levator muscles
• Moorings- Endopelvic fascial ligaments
• Problem is with the water or moorings or both
• Result is sinking of the boat
• Really the boat itself is fine
05/04/2012 14

Pathognesis
• Mutifactorial involving both neuromuscular
and endopelvic fascial damage
• Relaxation of the tissues supporting the pelvic
organs may cause downward displacement of
one or more of these organs into the vagina,
which may result in their protrusion through
the vaginal introitus.
05/04/2012 15

Factors promoting prolapse
• Erect posture causes increased stress on muscles,
nerves and connective tissue
• Acute and chronic trauma of vaginal delivery
• Aging
• Estrogen deprivation
• Intrinsic collagen abnormalities
• Chronic increase in intraabdominal pressure
– heavy lifting
– coughing
– constipation
05/04/2012 16

Clinical Presentation
• Variable & not associated with degrees
• Feeling of something coming down
• Complain as they are sitting on a ball/egg
• Back ache or dragging sensation
• Urinary symptoms like difficulty in passing urine,
frequency, etc
• Bowel symptoms like constipation
• Excessive white or blood stained discharge
05/04/2012 17

Clinical Evaluation
• Composite examination needed
• Straining & different positions
• Prolapsed uterus with cervix as leading point
• Prolapse of one organ is associated with other
prolapses
05/04/2012 18

Clinical Evaluation…
• Hormonal and neurologic evaluation
– Level of estrogenization
– Sensory and sacral reflex activity
• Quantitative site-specific assessment of pelvic floor
components
– in lithotomy position, patient sitting, standing
– at rest and with valsalva
– ability to contract levator and anal sphincter
muscles
05/04/2012 19

Patient position for evaluating pelvic
floor defects
05/04/2012 20

Investigations
• Hct(Hgb), blood group & Rh status
• U/A, culture & sensitivity
• RBS(FBS)
• RFT
• IVU
• Ultrasound
• Urodynamic studies
• CXR, etc
05/04/2012 21

Complications
1.Vaginal mucosa: keratinization & decubitus ulcer
2.Cervix: hypertrophied & elongated
3.Urinary symptom:
-Bladder: cystitis, trabeculation, incomplete
evacuation
-Ureters: hydroureter, pyelonephritis
4. Incarceration
5. Peritonitis
6. Carcinoma: rarely develops on decubitus ulcer
05/04/2012 22

DDX
• Cystocele versus Gartner’s cyst(wolffian remnant)
• Congenital elongation of the cervix
• Chronic uterine inversion
• Fibroid or polyp
• Tumors
05/04/2012 23

What is it?
05/04/2012 24

What is it?
05/04/2012 25

Anterior compartment defects
• Urethral hypermobility
– Distal 4 cm of anterior vaginal wall
– Cotton swab test
– If describes an arc greater than 30 degrees from
horizontal with valsalva
– Results in genuine stress incontinence
• Cystocele
05/04/2012 26

Cystocele
• Main support of urethra and bladder is the pubo-vesical-
cervical fascia
• Essentially a hernia in the anterior vaginal wall due to
weakness or defect in this fascia
– Midline weakness allows bladder to descend causing
central cystocele
– Tearing of endopelvic fascial connections from lateral
sulci to arcus tendinii causes lateral or displacement
cystocele
– Detachment of pubocervical fascia from pericervical
ring causes a transverse or apical cystocele
• Symptoms include pelvic pressure and bulge or mass in
the vagina
05/04/2012 27

Cystocele
• Classified as Grade I, II, or III
• Grade III is prolapse outside the introitus
• Surgical repair is treatment of choice
– Anterior Colporrhaphy
– Paravaginal repair
– Colpocleisis
• Vaginal pessary
05/04/2012 28

Evaluation of a cystourethrocele
05/04/2012 29

05/04/2012 30

Posterior compartment defects
• Rectocele
• Perineal descent
– Sagging and funneling of the levator ani
around the perineum such that anus becomes
most dependent
– Difficulty with defecation
05/04/2012 31

Rectocele
• Chiefly a hernia in the posterior vaginal wall
secondary to weakness or defect in the
rectovaginal septum or fascia of Denonvilliers
• Symptoms include difficulty evacuating stool,
a vaginal mass, and fullness sensation
• Rectovaginal exam confirms diagnosis
05/04/2012 32

Rectocele
• Damage generally due to excessive pushing in
childbirth or chronic constipation
• Surgical treatment if symptomatic
– Posterior Colporrhaphy, defect repair
– Laxatives and stool softeners
• Temporary relief
• Pessary not helpful
05/04/2012 33

Evaluation of a rectocele
05/04/2012 34

Apical defects
• Uterine prolapse
– Normal cervix located in upper third of vagina
– Degree of prolapse measured by position of cervix
at maximum intraabdominal pressure, without
traction
– Complete uterovaginal prolapse is called
procidentia
• Vault prolapse
• Enterocele
05/04/2012 35

Uterine prolapse
• Weakness of endopelvic fascia and detachment of
cardinal and uterosacral ligaments
• Complains of severe pelvic or abdominal pressure,
bulge or mass, and low back pain
• Surgical management includes hysterectomy and
vaginal cuff or apex suspension
05/04/2012 36

Complete Uterovaginal procidentia
05/04/2012 37

Grading/staging/degrees of POP
• Three systems
• Degree system: three degrees
1. 1st degree: external cervical os below the
ischial spines but within the vagina
2. 2nd degree: external os protrudes out of the
interoitus but fundus inside the vagina
3. 3rd degree: uterine body outside of the
interoitus. It is also called as PROCEDENTIA
05/04/2012 38

• Baden-Walker half way system:
1. Grade 0: normal position
2. Grade 1: Halfway between ischial spine to
hymen
3. Grade 2: In to hymen
4. Grade 3: halfway past hymen to maximal
descent
5. Grade 4: Maximal descent past hymen
05/04/2012 39

Pelvic organ prolapse quantification system
(POP-Q)
• Four stages
• brought by ICS and adopted by different
societies
1. Stage 0: no prolapse
2. Stage 1: maximal descent is 1cm above
hymenal ring
3. Stage 2: up to 1cm beyond the hymenal ring
4. Stage 3: up to (TVL-2cm) from hymenal ring
5. Stage 4: beyond the hymenal ring to the
extent of total vaginal length
05/04/2012 40

05/04/2012 41

Enterocele
• A true hernia of the rectouterine or cul-de-sac pouch
(pouch of Douglas) into the rectovaginal septum
• Descent of bowel in a peritoneum-lined sac between
posterior vaginal apex and anterior rectum
– Pulsion enterocele is filled with bowel and
distended by abdominal pressure
• Can occur anteriorly as well
– Generally after a surgical change in vaginal axis
• Symptoms of fullness and vaginal pressure or
palpable mass
• Bowel peristalsis confirms diagnosis
05/04/2012 42

Enterocele…
• Commonly found in association with other defects
• Surgical approach
– Vaginal
– Abdominal
• Laparoscopic
• Ligation of hernia sac and obliteration of the pouch
of Douglas
05/04/2012 43

Principles of reconstructive pelvic
surgery
• Site-specific repair
– Rebuild weakened endopelvic fascia, repair fascial
tears, and reattach prolapsed tissues to stronger
sites
– Goal is a vagina of normal depth, width and axis:
function follows form
– Denervation or muscle trauma cannot be
corrected surgically
05/04/2012 44

Conservative treatments
• Pessary
• Obstetric care to protect pelvic floor
– Decreased pushing times
– Avoid forceps, major lacerations
– Permit passive descent
• General lifestyle changes
– Smoking cessation and cough cessation
– Routine use of Kegel pelvic floor exercises
– Regular physical activity
– Proper nutrition
– Weight loss
– Avoid constipation and repetitive heavy lifting
– Hormone replacement therapy
05/04/2012 45

05/04/2012 46

Will 24th
Obstetrics is concerned with human reproduction
and as such is always a subject of considerable
contemporary relevance.
The specialty promotes health and well-being of
the pregnant woman and her fetus through
quality of perinatal care. Such care entails
• Appropriate recognition and treatment of
complications,
• Supervision of labor and delivery,
• Ensuring care of the newborn and
• Management of the puerperium.

Postpartum care promotes health and provides
family planning options.
The importance of obstetrics is reflected by the
use of maternal and neonatal outcomes as an
index of the quality of health and life among
nations.
Intuitively, indices that reflect poor obstetrical and
perinatal outcomes would lead to the assumption
that medical care for the entire population is
lacking.

Obstetric facts (CURRENT)
• Pregnancy (gestation) is the maternal
condition of having a developing fetus in the
body.
• Embryo-the human conceptus from
fertilization (beginning of 3rd week from
fertilization) through the eighth week of
pregnancy
• Fetus -from the eighth week until delivery,
• For obstetric purposes, the duration of
pregnancy is based on gestational age(GA):

• GA -the estimated age of the fetus
calculated from the first day of the last
(normal) menstrual period (LMP), assuming
a 28-day cycle.
• GA is expressed in completed weeks.
• Developmental age (fetal age) is the age of
the offspring calculated from the time of
implantation (Ovulation, Fertilization).

NCHS and CDC Definitions-Will 24th
• Perinatal period.
–The interval b/n the birth of an infant
born after 20 weeks’ gestation and the 28
completed days after that birth. ???????
–When perinatal rates are based on birth
weight, rather than GA, it is
recommended that the perinatal period
be defined as commencing at 500 g

• Birth
– The complete expulsion or extraction
from the mother of a fetus after 20
weeks’ gestation.
–In the absence of accurate dating criteria,
fetuses weighing < 500 g are usually not
considered as births but rather are
termed abortuses for purposes of vital
statistics.

Will 24th
• The National Vital Statistics Reports tabulates
fetal deaths from > 20 weeks of GA (CDC, 2009).
• This is problematic because the 50th percentile
for fetal weight at 20 weeks approximates 325 to
350 g—considerably < the 500-g definition.
• Indeed, a birth weight of 500 g corresponds
closely with the 50th percentile for 22 weeks.

• Live birth is the term used to record a birth
whenever the newborn at or sometime after
birth breathes spontaneously or shows any other
sign of life such as a heartbeat or definite
spontaneous movement of voluntary muscles.
–Heartbeats are distinguished from transient
cardiac contractions, and
–respirations are differentiated from fleeting
respiratory efforts or gasps.

• Stillbirth / Fetal Death
–the absence of signs of life at or afterbirth.
• Early neonatal death
–death of a live born neonate during the first 7
days after birth.
• Late Neonatal Death
–death after 7 days but before 29 days

• Birth Rate-the number of live births per 1000
population.
• Fertility Rate-the number of live births per
1000 females aged 15 through 44 years.

• Stillbirth rate or fetal death rate. The number of
stillborn neonates per 1000 neonates born,
including live births and stillbirths.
• Neonatal mortality rate. The number of neonatal
deaths per 1000 live births.
• Perinatal mortality rate. The number of
stillbirths plus neonatal deaths per 1000 total
births.
• Infant death. All deaths of live born infants from
birth through 12 months of age.
• Infant mortality rate. The number of infant
deaths per 1000 live births

• Low birth weight.
–A newborn whose weight is < 2500 g.
• Very low birth weight.
– A newborn whose weight is < 1500 g.
• Extremely low birth weight.
– A newborn whose weight is < 1000 g.

• Term neonate.
– A neonate born any time after 37 completed weeks of
gestation and up until 42 completed weeks of gestation
(260 to 294 days).
• ACOG(2013b) and the SMFM endorse and
encourage specific GA designations.
• Early term refers to
– neonates born at 37 completed wks up to 38 6/7 wks.
• Full term denotes
– those born at 39 completed wks up to 40 6/7 wks.

• Late term describes
– neonates born at 41 completed wks up to 41 6/7 wks.
• Preterm neonate.
– A neonate born before 37 completed wks (the 259th
day).
• Post term neonate.
– A neonate born anytime after completion of the 42nd
week, beginning with day 295.

• Abortus.
– A fetus or embryo removed or expelled from the
uterus during the first half of gestation— ≤ 20 wks or
– in the absence of accurate dating criteria, born
weighing < 500 g.
• Induced termination of pregnancy.
– The purposeful interruption of an intrauterine
pregnancy that has the intention other than to
produce a live born neonate and that does not result
in a live birth.
– This definition excludes retention of products of
conception following fetal death

Definition of maternal death
The death of a woman while pregnant or
within 42 days of termination of pregnancy,
irrespective of the duration and site of the
pregnancy, from any cause related to or
aggravated by the pregnancy or its
management but not from accidental or
incidental causes.
=> WHO International Statistical Classification of Diseases and
Related Health Problems, Tenth Revision, 1992 (ICD-10),

• Direct maternal death.
–The death of the mother that results from
obstetrical complications of pregnancy,
labor, or the puerperium and from
interventions, omissions, incorrect
treatment, or a chain of events resulting
from any of these factors.
• Eg maternal death from exsanguinations after
uterine rupture.

• Indirect maternal death.
–A maternal death that is not directly due to an
obstetrical cause.
– Death results from previously existing disease
or a disease developing during pregnancy,
labor, or the puerperium that was aggravated
by maternal physiological adaptation to
pregnancy.
• Eg. is maternal death from complications of mitral
valve stenosis

• Non maternal death-
– Death of the mother that results from
accidental or incidental causes not
related to pregnancy.
• An example is death from an automobile
accident or concurrent malignancy

• Pregnancy-associated death
– the death of a woman, from any cause, while
pregnant or within 1 calendar year of termination
of pregnancy, regardless of the duration and the
site of pregnancy.
• Pregnancy-related death-
– a pregnancy-associated death that results from:
1. complications of pregnancy itself,
2. the chain of events initiated by pregnancy that led to
death, or
3. aggravation of an unrelated condition by the
physiological or pharmacological effects of pregnancy
and that subsequently caused death.

• Maternal mortality ratio.” The number of maternal
deaths that result from the reproductive process per
100,000 live births.”
• “maternal mortality rate” or “maternal death rate”
are more commonly but less accurately, Used terms,
• The term ratio is more accurate because it includes
in the numerator the number of deaths regardless of
pregnancy outcome—for example, live births,
stillbirths, and ectopic pregnancies—whereas the
denominator includes the number of live births.
MMratio denominator is no of live birth
MMrate- denomiator no of women of Rep. Age

MM Rate Vs MM Ratio
• MM rate- no of maternal deaths per
100000/??1000 women of rep age
– Precise determination of denominator is difficult
• MM ratio- no of maternal death per 100000
live birth
– preferable

Denominators of MM- PPH
• Denominator Definition Advantages and
disadvantages
• Live births: Number of pregnancies that result in a
live birth at any gestation
– Easier to collect than maternities
• Maternities:
– Number of pregnancies that result in a live birth at any
gestation or
– stillbirths occurring at or after 24 weeks of completed
gestation and required to be notified by law Includes
the majority of women at risk from

• death from obstetric causes but requires
infrastructure for notification of stillbirths
Women aged 15–44 years
• Number of women of reproductive age in a
given population
• Lacks rigor of confining rate to women who were
pregnant
• Enables comparison with other causes of death

MDG
MDG 5- Improve maternal health
Indicators:
– ↓MMR by 75%
– Proportion of births attended by skilled birth attendant
MDG Target 5. A: Reduce by three-quarters,
between 1990 and 2015, the maternal mortality
ratio at the rate of 5,5% decline /year
 current rate of decline is 2.3% to date (2010)
World wide MMR
– 1990 MMR: 400 per 100,000 live births
– 2008 MMR: 260
– 2010 MMR: 210 47% decrease from 1990 (WHO,2012
MMTrends)

MM- WHO 210
• Low MM: 20- 99/100,000 LBs
• Moderate MM: 100- 299/100,000LBs
• High MM: > 300/ 100,000LBs
– Toally 40 Cs in 2010,
• Extremely high MM- ≥1000
– Chad and Somalia 1100 and 1000 resp.

 Maternal Death-Medical Factors
DOC – Account for 80% of MDs
Hemorrhage-Leading cause of MD in
developing world, accounting for 30%.( Jimma-
43% ). Rate slow to decline.
Sepsis - 2nd most important cause of MD in
dev’ing countries, accounting 20%. 1st cause of
death to decline.
HDP – 3rd most important cause of death in
dev’ing countries, accounting for 10-15%.
(Jimma-3.8% ). Relatively slow to decline.
Prolonged or obstructed labor-account for 8%.
Complications of abortion- account for 13%.

Maternal Death-Medical Factors
 IOC – Account for 20% of MDs
 Anemia
α Developing countries-2/3 of pregnant women
α Developed countries-14%
α Highest rates are found in Asia, followed by Oceania and Africa.
 Malaria –Resistance to malaria breaks down from the 14th week of gestation.
 Viral hepatitis
αSerious with case fatality rate up to 3.5 higher than the non-pregnant women.
αReported to be the 3rd most important cause of MD in 1983.
 Heart diseases
 HIV/AIDS

Route of delivery and MM-Will 24th
• MM in a review of nearly 1.5 million
pregnancies Clark and colleagues (2008)
– 2.2/ 100,000 CD
– 0.2/100,000 VB
• MM in a Meta analysis of 203 studies (Guise etal
2010)
– 13/100,000 RECS
– 4/100,000 TOLACs

Maternal Near Miss (MNM)-WHO
DEFINITION
• WHO defines a maternal near miss case as
 “ A woman who nearly died but survived a
complication that occurred during pregnancy,
birth or within 42 days after termination of
pregnancy
Declining MM ratio in the west led to
switching attention to MNMs and their causes

MNM Identification criteria
According to WHO ,women with the following
conditions , but survived in the aforementioned
periods are considered MNM Cases
 CVS
–shock,
–cardiac arrest,
–marked hypo perfusion (lactate>45mg/dl),
–severe acidosis ( PH< 7.1),
–continuous use of vasoactive substances, CPR

MNM Identification Criteria
Respiratory Dysfunction-
• acute cyanosis,
• gasping
• severe tachypnoea (> 40)/ bradypnoea(<6),
• severe hypoxemia (O2 saturation< 90%)
• intubation and ventilation not related to
anesthesia

Renal Dysfunction
• Oliguria not responsive to fluids or diuretics,
• Severe acute azetomia (Creat> 3.5mg/dl) ,
• Dyalisis for AR
• Coagulation Disorders-
• failure to form clots,
• severe acute thrombocyttope nia (<50,000),
• massive transfusion of RBC (> 5mg/dl)

MNM Identification Criteria
• Hepatic Dysfunction-
– jaundice with PE,
– Acute severe hyperbilirubinemia ( Bil > 6mg/dl),
• Neurological Dysfunction-
– prolonged unconsciousness/ comma (>12hrs),
– Stroke,
– uncontrollable fits/status epilepticus,
– global Paralysis
• Uterine Dysfunction-
– Hysterectomy due to hemorrhage or infection

OB facts
• The neonatal interval is from birth until 28 days of
life.(the infant is referred to as a newborn). The
interval may be divided into 3 periods:
• Neonatal period I: birth through 23 hours, 59
minutes.
• Neonatal period II: 24 hours of life through 6 days,
23 hours, 59 minutes.
• Neonatal period III: seventh day of life through 27
days, 23 hours, 59 minutes
• The perinatal period - from 28 weeks of completed
gestation to the first 7 days of life, spanning the
fetal and early neonatal interval

PRECONCEPTIONAL EDUCATION-Gabbe
• The best time to see a woman for prenatal care is
when she is considering pregnancy.
• At routine gynecologic visits and especially infertility
visits, patients should be asked about their plans for
pregnancy.
• At that time, much of the risk assessment can be
performed, as well as the basic physical and
laboratory evaluations.
• If there are questions about the history, such as
family history of fetal anomaly, or previous cesarean
delivery, further details can be obtained from family
members or the appropriate medical facility.

At this time
• a rubella titer is drawn and immunize the
susceptible patient.
• HBV immunization to appropriate patients
• HIV testing can be offered.
• Varicella titers or immunization is recommended
in women with no history of chickenpox. Patients
need to use contraception for up to 3 months
following immunizations.

• Toxoplasmosis screening based on risk factors
may be indicated and Patients who have
negative screens are at risk for congenital
toxoplasmosis and should be counseled to avoid
risks such as contact with wild felines and
ingestion of raw or undercooked meat.
• Immunocompetent patients who screen positive
can be reassured of lack of risk with regard to
fetal loss, or stillbirth; albeit rare reports of
congenital infection after previous infection have
been described.

• screen appropriate populations for genetic disease
carrier states such as Tay-Sachs disease, Canavan's
disease, cystic fibrosis, or hemoglobinopathies.
• Medical conditions such as anemia or hypothyroidism
can be fully evaluated and the woman medically
treated before pregnancy.
• If the patient is obese, weight reduction should be
attempted before pregnancy.
• Patients in whom risks are very serious should be so
counseled, and every attempt should be made to let
them make a fully informed decision about
pregnancy.
• Often, significant risk factors can be treated or
managed so as to reduce risk during pregnancy

Dx of pregnancy
SS of pregnancy may appear as early as 6 weeks
Manifestations of pregnancy may be
– presumptive,
– probable
– positive

Dx of pregnancy
Presumptive symptoms
• Amenorrhea,
• Nausea and vomiting
• Breast changes
– tenderness ,enlargement, colostrum
– Montgomenary T.
– 2⁰ breasts prominence
• Quickening(18 -20 wks primis, 14-16wk multis)
• Frequency+ nocturia ( bladder irritation)
• UTI ( bacteruria in preg woman ~7% vs 3% in non-
preg)*
*Bacteruria may be asymptomatic but leads to serious complications
(pyelonephritis, which is associated with miscarriage, preterm birth,
and intrauterine fetal demise) if left untreated

OB facts
Presumptive Signs
Skin changes
• Chloasma ( mask of pregnancy), is darkening of
the skin over the forehead, bridge of the nose, or
cheekbones . It usually occurs after 16 weeks'
gestation and is intensified by exposure to
sunlight.
• Linea Nigra is darkening of the nipples and lower
midline of the abdomen from the umbilicus to the
pubis (darkening of the linea alba) due to
stimulation of the melanophores by an increase in
melanocyteSH.

Presumptive signs- contd.
• Stretch Marks - striae of the breast and abdomen
are caused by separation of the underlying
collagen tissue and appear as irregular scars. This
is probably an adrenocorticosteroid response.
These marks generally appear later in pregnancy
when the skin is under greater tension.
• Spider Telangiectases are common skin lesions
that result from high levels of circulating
estrogen.
These vascular stellate marks blanch when
compressed. Palmar erythema is often an
associated sign. Both of these signs are also seen
in patients with liver failure.

Probable Manifestations
Probable Symptoms are the same as the Presumptive ones, above.
Probable Signs
• Pelvic organ changes
- Chadwick’s sign
- lukorrhea
-Hegar’s sign(by 6–8 weeks)
-Relaxation of pelvic joints(pronounced on SP)
• Abdominal Enlargement
There is progressive abdominal enlargement from 7–28 weeks.
At 16–22 weeks, growth may appear more rapid as the uterus rises out
of the pelvis and into the abdomen
• Painless uterine contractions (Braxton Hicks contractions) are felt
as tightening or pressure usually disappear with walking or exercise.
They usually begin at about 28 weeks' gestation and increase in
regularity.

Pregnancy – Positive manifestations
The various signs and symptoms of pregnancy are often
reliable, but none is diagnostic.
A positive diagnosis must be made on objective findings,
many of which are not produced until after the first
trimester. However, more methods are becoming
available to diagnose pregnancy at an early stage.
• Fetal Heart Tones (FHTs) detected by
– hand held Doppler as early as 10 weeks' and
– fetoscope at 18–20 weeks'.
The normal fetal heart rate is 120–160 bpm.
• Palpation of Fetus: Fetal outline after 22 wks
Fetal movement after 18 wks

• Ultrasound Examination of Fetus
– Cardiac activity- 5-6 wks
– limb buds- 7-8wks
– Fingers & limbs mov’t- 9-10 wk
– Human appearance after 10 wk

Positive manifestations-US Will 24th
• A Gestational Sac—the first sonographic evidence of pregnancy -a small anechoic
fluid collection within the endometrial cavity – seen by TVUS at 4 to 5 Wks GA.
• A fluid collection, however, can also be seen within the endometrial cavity with an
EP and is termed a pseudogestational sac or pseudosac (Fig. 19-5, p. 382).
• Thus, further evaluation may be warranted if this is the only sonographic finding,
particularly in a patient with pain or bleeding.
• A normal GS implants eccentrically in the endometrium, whereas a pseudosac is
seen in the midline of the endometrial cavity.
• Other potential indicators of early intrauterine pregnancy are—
• The Intradecidual Sign—an anechoic center surrounded by a single echogenic rim
or
• Double Decidual Sign-two concentric echogenic rings surrounding the gestational
sac ( Dparietalis and D Capsularies)
• yolk sac—a brightly echogenic ring with an anechoic center—and can normally be
seen by the middle of the fifth week-.confirms with certainty an Iux pregnancy
• Embryo is seen after 6 weeks, an as a linear structure immediately adjacent to the
yolk sac, and cardiac motion is typically noted at this point.
• Up to 12 weeks’ gestation, the CRL is predictive of GA within 4 days

• pregnancy of unknown location- equivocal
sonography finding
• With PUL -serial serum hCG levels can help
differentiate a normal intrauterine pregnancy
from an extrauterine pregnancy or an early
miscarriage

Positive manifestations-contd.
• Pregnancy Tests –
• Sensitive, early pregnancy tests measure changes in levels
of BhCG.
hCG is produced by the syncytiotrophoblast 8 days after
fertilization and may be detected in the maternal serum
after implantation occurs, 8–11 days after conception.
hCG levels peak at approximately 10–12 weeks of gestation.
Levels gradually decrease in the second and third trimesters
and increase slightly after 34 weeks.
The half-life of hCG is 1.5 days
Normally, serum and urine hCG levels return to nonpregnant
values (<5mIU/mL) 21–24 days after delivery

Pregnancy-positive manifestations
Urine Pregnancy Test (the level of hCG detection ranging
between 5 and 50 mIU/mL, depending on the kit used.)
Home Pregnancy tests first voided morning urine( low
sensitivity)
Serum Pregnancy test: hCG can be detected in the serum as
early as a week after conception. The serum pregnancy
test can be quantitative or qualitative with a threshold as
low as 2–4 mIU/mL, depending on the technique used.
The serum pregnancy test is a reliable method to
diagnose an early pregnancy; it is widely used in the
evaluation of threatened abortion, ectopic pregnancy,
and other conditions

HCG ( WILLIAMS)
• HCG prevents involution of the corpus luteum, the principal
site of progesterone formation during the first 6 weeks.
• Trophoblast cells produce hCG in amounts that increase
exponentially following implantation.
• With a sensitive test, the hormone can be detected in
maternal plasma or urine by 8 to 9 days after ovulation.
• The doubling time of plasma hCG concentration is 1.4 to 2.0
days.
• serum hCG levels increase from the day of implantation and
reach peak levels at 60 to 70 days.
• Thereafter, the concentration declines slowly until a nadir is
reached at about 16 weeks.
• Serum total hCG concentration peaks at 93,598 mIU/mL (range 27,300 to 233,000
mIU/mL) at 8 to 11 weeks of gestation -Uptodate

hCG Types- Uptodate
• Regular
• Hypergycosylated

hCG Tests Will 24th
• Several Immunoassays-
‘Sandwitch Immunoassay’ – Immunometric assay- all comm assays
– Monoclonal Ab against B subunit
– 2 antibodies –
– capture (1st)—bound and immobilize hCG
– tracer (2nd) – lable the immobilized hCG by radioactive or Enzyme label
– hCG is sandwithced b/n Abs ( 1st on solid phase support, second added
subsequently)
Amount of immobilized label measyred proportional to the
amount of hCG in the sandwitch
Enzyme linked
• 2nd Ab is E linked (eg ALPase)
• After 2nd Ab, E substrate is added, bind to E and color change is
produced
– Intense color high E conc High amount of bound 2nd Ab High hCG
conc
– Can detect as low as 1miu/ml hCG

hCG tests-Home Pregnancy tests
• HPTs are Less accurate than advertisement
– Only 1 brand detected 95% of hCG +ves at
12mu/ml
– 44% of brands +VE at 100Miu/ml
only 15% are dxed at time of missed menses
Cole and ASS 2011

• Although all assays detect regular hCG, they do not necessarily
detect all hCG variants [40]. For example, many over-the-counter
pregnancy tests do not measure hyperglycosylated hCG, which
accounts for most of the total hCG at the time of missed menses
when these tests are typically performed.
• At a minimum, testing for total hCG should detect both regular
and hyperglycosylated hCG. The hCG variants detected depends
upon the only commercial assay used;
• the only commercial assay that detects all hCG variants is the
Siemen's Immulite Series. It is also important to know the
sensitivity of the test.
• Clinical tests for pregnancy may only detect total hCG levels ≥20
mIU/mL. Therefore, when following hCG levels to negative (<1
mIU/mL) in women with gestational trophoblastic disease, it is
important to use a sensitive hCG test that detects both regular and
hCG-H.
• Testing for pregnancy — The clinical use of this test for diagnosis of
pregnancy (intrauterine or ectopic) is reviewed separately:

False negative test - hook effect
• At levels of hCG > 500,000 mIU/mL, a "hook effect" can
occur resulting in an artifactually low value for hCG (ie,
1 to 100 mIU/mL) [23].
• This is because the sensitivity of most hCG tests is set
to the pregnancy hCG range (ie, 27,300 to 233,000
mIU/mL at 8 to 11 weeks of gestation); therefore,
when an extremely high hCG concentration is present,
both the capture and tracer antibodies used in
immunoradiometric assays become saturated,
preventing the binding of the two to create a sandwich
[23,41]. Since the nonsandwiched tracer antibodies are
washed away with the excess material, the test result
will be negative. For this reason, a suspected diagnosis
of gestational trophoblastic disease must be
communicated to the laboratory so that the hCG assay
will also be performed at 1:1000 dilution.

False-positive hCG values
• “phantom hCG,”- a false +ve serum hCG result due to nonspecific
heterophilic antibodies in the serum and this often results in
inappropriate intervention (chemorx, Hysterectomy---).
– Seen in people who are close to animals
– Abs against Ags of animal origin bind to the animal derived test abs
• These false-positive levels are usually low (10 mIU/mL) but have
been reported at levels > 300 mIU/mL.
• This situation should be suspected when hCG levels plateau at a
low concentration and do not respond to further therapeutic
attempts, such as methotrexate for a persistent EP or molar gest.
• Since the H Abs are not secreted in the urine, one should measure
a urinary hCG level if suspicious.
• Also, a serial dilution of the patient’s serum can be performed, as
the false-positive test is not affected by the dilution

How to RO Phantom hCG?
• Urinary test –VE
– Hetrophilic Abs are not excreted by the kidney
• Serial dilution of serum sample
– True hCG conc decreases with dilution while that
of the phantom is not affected
• Alternate assay which blocks hetrophilic Abs
Will Gyn 2nd Ed

False hCG +VES
• Exogenous hCG-Injection for wt loss
• Tumors-
– GI,Ovary, Bladder, Lung
– hCG may hve angiogenic role for the tumors
• Renal Failure- impaired clearance
• Physiologic Pitutary hCG
• One possible explanation is that a small amount of hCG is
produced along LH because the single LH beta-subunit gene is
buried among the seven back-to-back hCG beta-subunit gene
• Usualy 1-32mu/ml
• Pituitary production of hCG is most notable around the time of
menopause (natural or surgical) and prior to ovulation, which
are times when LH levels peak

Components of Standard Ultrasound Examination by
Trimester (WILLIAMS)
First Trimester
• Gestational sac location
• Embryo and/or yolk sac identification
• CRL
• Cardiac activity
• Fetal number, including amnionicity and chorionicity of
multiples when possible
• Assessment of embryonic/fetal anatomy appropriate
for the first trimester
• Evaluation of the uterus, adnexa, and cul-de-sac
• Assessment of the fetal nuchal region if possible

Components of Standard Ultrasound
Examination by Trimester(WILLIAMS)
Second and Third Trimester
• Fetal number; multifetal gestations: amnionicity,
chorionicity, fetal sizes, amnionic fluid volume, and fetal
genitalia, if visualized
• Presentation
• Placental location and its relationship to the internal cervical
os
• Amnionic fluid volume
• Gestational age
• Fetal weight
• Evaluation of the uterus, adnexa, and cervix
• Fetal anatomical survey, including documentation of
technical limitations

GA Clinical Dating
• Comparison of the various clinical estimators shows a
known LMP date to be the most precise predictor. The
clinical estimators can be ranked according to
decreasing order of accuracy as follows:
(1) LMP
(2) the uterus reaching umbilicus; and
(3) fetal heart tone documentation, fundal height
measurements, and quickening.
• Because of inherent biologic variability and differences
in the examiner acuity, the estimated date of
confinement can be predicted with 90 percent certainty
only within ± 3 weeks by even the best single estimator.

GA dating
• Ultrasonography may be considered to confirm
menstrual dates if there is a GA agreement
– within 1 week by CRL obtained in the 1st trimester
or
– within 10 days by an average of multiple fetal
biometric measurements (eg,CRL, BPD, HC, AC,FL)
obtained in the 2nd (up to 20 weeks GA) .
ACOG-2008

US Dating- Uptodate
• , the optimal time to obtain an estimate of
GA is during the first trimester when biologic
variation in size from fetus to fetus is minima

US Dating-indications, Uptodate
Sonographic estimation is particularly important
• when menstrual cycles are irregular,
• the last menstrual period is unknown, and
• in patients who conceive while using hormonal
contraception.
• Ultrasound is also used to establish a pregnancy's
duration when the uterine size estimated on
physical examination differs from that predicted
by menstrual dating.

US - Uptodate
• Several studies have demonstrated that ultrasound estimation of
EDD in the first half of pregnancy is superior to dating based on
the last menstrual period or physical examination
• sonographic dating resulted in a small downward estimation of
GA more often than an upward estimation [3]. This finding is
consistent with other series showing that delayed ovulation (after
day 14) occurs more often than early ovulation.
• Because routine US examination has the net effect of reducing the
estimated GA, populations assigned an EDD by routine US
examination have a lower rate of induction for postterm birth than
those assigned an EDD by menstrual dating (2 versus 3 percent);

SIGNS OF AN ABNORMAL GESTATION

Wt gain in pregnancy(NMS)
• Pregnancy-induced changes account for about 9
to 10 kg (20 to 22 lb) of the weight gain in normal
conditions in the following approximate
distributions:
– Fetus: 3.4 kg (7.5 lb)
– Placenta plus membranes: 0.7 kg (1.5 lb)
– Amniotic fluid: 0.9 kg (2 lb)
– Increase in weight of the uterus: 1.1 kg (2.5 lb)
– Increase in blood volume: 1.6 kg (3.5 lb)
– Breasts: 0.45 kg (1lb)
– Lower extremity fluid: 1.1 kg (2.5 lb)

Weight Gain Based on Pregnancy-RelatedComponents

WT. GAIN IN PREGNANCY (UPTODATE)
On average, weight gain at term is distributed as follows:
• Fetus: 7 to 8 pounds (3.2 to 3.6 kg)
• Fat stores: 6 to 8 pounds (2.7 to 3.6 kg)
• Increased blood volume: 3 to 4 pounds (1.3 to 1.8kg)
• Increased fluid volume: 2 to 3 pounds (0.9 to 1.3 kg)
• Amniotic fluid: 2 pounds (0.9 kg)
• Breast enlargement: 1 to 3 pounds (0.9 to 1.3 kg)
• Uterine hypertrophy: 2 pounds (0.9 kg)
• Placenta: 1.5 pounds (0.7 kg)

Recommended Total Weight Gain Ranges for Pregnant(UPTODATE)
Twin pregnancy — For twin pregnancies that go
to term, the recommendations are:
• BMI <18.5 kg/m2 (underweight) — no
recommendation due to insufficient data
• BMI 18.5 to 24.9 kg/m2 (normal weight) —
weight gain 37 to 54 lbs (16.8 to 24.5 kg)
• BMI 25.0 to 29.9 kg/m2 (overweight) —
weight gain 31 to 50 lbs (14.1 to 22.7 kg)
• BMI ≥30.0 kg/m2 (obese) — weight gain 25 to
42 lbs (11.4 to 19.1 kg)

Recommended Total Weight Gain Ranges for Pregnant Women
(UPTODATE)
• These recommendations for the general obstetrical
population in the United States also apply to short
women, women of different ethnic groups, and
teenagers, but may not apply to women in other
countries.
• For underweight and normal weight women, these
guidelines translate to about one pound (0.4 kg) weight
gain per week in the second and third trimesters;
• for overweight and obese women, the guidelines
translate to about one-half pound (0.2 kg) weight gain
per week in the second and third trimesters

Weight Gain (ACOG 2006)
• Height and weight should be recorded for all
women at the initial prenatal visit to allow
calculation of the BMI.
• Recommendations for prenatal weight gain
should be made based on the Institute of
Medicine (IOM) guidelines,which suggest a gain
of
– 25-35 lb for women of normal weight,
– 15-25 lb for overweight women,and
– 15 lb for obese women .

ACOG perinatal care guideline 2012

Recommended Total Weight Gain Ranges for
Pregnant(UPTODATE)
Singleton pregnancy:
• BMI <18.5 kg/m2 (underweight) —
28 to 40 lbs (12.5 to 18.0 kg)
• BMI 18.5 - 24.9 kg/m2 (normal weight) —
25 to 35 lbs (11.5 to 16.0 kg)
• BMI 25.0 to 29.9 kg/m2 (overweight) —
15 to 25 lbs (7.0 to 11.5 kg)
• BMI ≥30.0 kg/m2 (obese) —
11 to 20 lbs (5 to 9.0 kg)
NB.Prepregnancy BMI is an important predictor
of birth weight

NMS
• A normal fetus weighs approximately
– 1000 g (more than 2 lb) at 26 to 28 weeks,
– 2500 g (5.5 lb) at 36 weeks, and
– 3300 g (7.0 to 7.5 lb) at 40 weeks.
The fetus gains weight at a rate of approximately
224 g (0.5 lb) per week for the last 4 weeks
and weighs an average of 3300 g (7.0 to 7.5 lb)
at term

Clinical Parameters of GA(CURRENT)
Ultrasonography
Ultrasound is used to measure fetal growth parameters,
to estimate fetal weight, to access fetal anatomy, and
to measure amniotic fluid volume. Fetal well-being can
also be evaluated by measuring biophysical
characteristics
CRL 5-13 wks( most accurate to detemine GA with 3-5 days
descrepancy)
BPD, FL, AC- beyond 13wks*
Beyond 30 weeks, the accuracy of gestational age assessment by
ultrasound is much less.
*BPD at 13-20 wks- 1week descrepancy
20-30 wks-2wk
beyond 30wk- 3weeks

MSD Measurement
Measurement of the mean sac diameter (MSD). The distances measured by the
calipers in the longitudinal axis (A, number one) and the depth (A, number two) and
the transverse diameter measured in (B) are added together and divided by three to
produce the MSD. Some authors use only the sum of the longitudinal and depth
measurements divided by two.

Assessment of gestational age-Uptodate
Parameter GA weeks Accuracy, days
Mean sac diameter 4.5 to 6 ± 5 to 7
Crown-rump length 7 to 10 ± 3
10 to 14 ± 5
15 ± 8.4
BPD, HC, FL 14 to 20 ± 7
21 to 30 ± 14
over 30 ± 21 to 28
ACOG suggest using the US derived GA to calculate EDD if it differs from
that calculated using the LMP by more than seven days in the first
trimester and by more than 10 days in the second trimester but before 20
weeks of gestation.

GA- Clinical
Uterine Size
• An early first-trimester examination usually correlates well
with the estimated gestational age.
• at 8 weeksThe uterus is palpable just at the pubic
symphysis.
• At 12 weeks, the uterus becomes an abdominal organ and
• at 16 weeks is usually at the midpoint between the pubic
symphysis and the umbilicus.
• The uterus is palpable at 20 weeks at the umbilicus.
• Fundal height (determined by measuring the distance in
centimeters from the pubic symphysis to the curvature of
the fundus) correlates roughly with the estimated
gestational age at 26–34 weeks .
• After 36 weeks, the fundal height may decrease as the
fetal head descends into the pelvis

GA-clinical
Quickening
• The first fetal movement is usually
appreciated at 17 weeks in the average
multipara and at 18 weeks in the average
primipara.
Fetal Heart Tones
• FHTs may be heard by fetoscope at 20 weeks,
whereas Doppler ultrasound usually detects
heart rates by 10 weeks.

Fetal Maturity- ACOG Criteria (2008)
• Ultrasound measurement at less than 20 weeks
of gestation supports gestational age of 39 weeks
or greater.℗
• Fetal heart tones have been documented as
present for 30 weeks by Dopplerultrasonography.
• It has been 36 weeks since a positive serum or
urine HCG pregnancy test result
If any of these criteria confirms a gestational age of 39 weeks or
more, it is appropriate to schedule delivery at that time

Contd.
℗ Ultrasonography may be considered to
confirm menstrual dates if there is a GA
agreement :
– within 1 week by Crown-rump measurements
obtained in the first trimester or
– within 10 days by an average of multiple fetal
biometric measurements (eg, crown rump length,
biparietal diameter, head and abdominal
circumference, and femur length) obtained in the
second trimester (up to 20 weeks of gestation

Diagnosis of Fetal Death
US
• The accepted method of diagnosing pregnancy failure early
is ultrasound.
• Early in pregnancy, failure to visualize a fetal pole with
cardiac activity at the appropriate gestational age suggests
fetal death.
• Serial measurements of serum -hCG may be helpful when
the ultrasound findings are equivocal.
• In late pregnancy, the first sign of fetal death is usually
absence of fetal movement noted by the mother. This is
followed by absence of FHTs. Real-time ultrasonography is
virtually 100% accurate in determining the absence of fetal
heart motion.

Fetal Death
Hypofibrinogenemia may rarely develop 4–5 weeks
after fetal death as thromboplastic substances
are released from the degenerating products of
conception.
Coagulation studies should be started 2 weeks after
intrauterine death, and delivery should be
attempted by 4 weeks or if serum fibrinogen falls
below 200 mg/mL.
This is only clinically applicable in the case of death
of one of twins; otherwise, the singleton demise
would be delivered promptly.

Data from ACOG, 2013a; Cahill, 2010b; Chauhan, 2002; Landon, 2006;
Macones, 2005; Martin, 1997; Miller,1994; Sciscione, 2008; Society for
Maternal-FetalMedicine, 2012; Tahseen, 2010

Complications in Women with a Prior Cesarean Delivery
Enrolledin the NICHD Maternal-Fetal Medicine Units
Network, 1999–2002

Neonatal morbidity and mortality rates seen with 13,258 elective
repeat cesarean deliveries. Any adverse outcome includes death.
Sepsis includes suspected and proven. RDS = respiratory distress
syndrome; TTN = transient tachypnea of the newborn. (From Tita,
2009.) Will 24th

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