Female infertility

Dr. Ayesha Sherzada
FCPS Resident
The Indus hospital
Karachi, Pakistan.

 Epidemiology, aetiology and pathogenesis of infertility.
 Clinical management and prognosis of all aspects of female
fertility problems.
 Interpretation of relevant investigations in relation to
female infertility.
 Indications and limitation of treatments for female
infertility.

 Infertility is defined as the failure to conceive despite of
regular unprotected sexual intercourse over a specific
period of time, usually 1-2 years..
In the general population, spontaneous conception is
expected to occur in 85% of women after 1 year and in 93%
after 2 years.

 Primary:
 Couples who have had NO previous conception.
 Secondary:
 Difficulty conceiving after already having conceived (and
either carried the pregnancy to term or had a
miscarriage).

Data from population-based studies suggest that infertility
affects 9% of couples, of whom 70% suffer from primary
infertility, 30% from secondary infertility.

Approximately 50 per cent of couples will conceive after
receiving advice and simple treatment.
4% of couples will remain involuntarily childless.
Male factor is the reason for infertility in 35% of cases,
female factor is identified in 50% of couples and no cause in
the remainder.
Fertility reduces rapidly in women over 35 years of age.

 For a woman to conceive, certain things have to happen:
 Intercourse must take place around the time when an egg
is released from her ovary.
 The systems that produce eggs and sperm have to be
working at optimum levels.
 And her hormones must be balanced.

1. Ovulation Disorders
2. Tubal Damage
3. Age (>37 years) * Reduce chance of a spontaneous
conception.
4. Low coital frequency or inappropriate time of intercourse
to ovulation.
5. No previous pregnancy
6. Smoking
7. Malnutrition 1. Obesity 2. Underweight
8. Endometriosis, Fibroids, PID (Pelvic Inflammatory
Disease).

Table 45.1 Diagnostic categories in infertility
primary% secondary%
Male factor 25 20
Anovulation 20 15
Tubal 15 40
Endometriosis 10 05
Unexplained 30 20

 Arise due to defects in the hypothalamus, the pituitary or
the ovary.
 Classified into 3 categories:
 Group 1- hypothalamic pituitary failure 10%.
 Group 2- hypothalamic pituitary dysfunction 85%.
 Group 3- ovarian failure 4-5%.

 Group I ovulation disorders are caused by hypothalamic
pituitary failure.
 10% cases.
 Low basal gonadotrophins, normal prolactin, low estrogen.
 Failure of pituitary gland to produce gonadotrophins will
lead to lack of ovarian stimulation.
 Categories:
 Hypothalamic amenorrhea
 Hypogonadotrophic hypogonadism.

 Normogonadotrophic anovulation.
 85% cases.
 Gonadotrophins and estrogen levels in the normal range.
 Categories:
 PCOS
 Hyperprolactinaemia

 Group III ovulation disorders are caused by ovarian failure.
Around 5% of women with ovulation disorders have a group
III ovulation disorder.
 High gonadotrophins, low estrogen.
 Women with a group III ovulation disorder (‘ovarian
failure’) can only conceive through oocyte donation and
then IVF treatment

 Most commonest cause of anovulatory infertility accounts
for over 75% of all women with anovulation (Adams et al.
1986).
 Symptoms:
 Menstrual Cycle Disturbances.
 Obesity
 Hirsutism
 Acne and INFERTILITY!
 Diagnosis:
 Low Sex Hormone binding Globulins.
 Ultrasound Appearance of an enlarged ovary with multiple
sub capsular follicles and a dense stroma.

 Namely the presence of two out of the following three
criteria:
 1- Oligo- and/or anovulation;
 2- Hyperandrogenism (clinical and/or biochemical);
 3- Polycystic ovaries on U/S.
 The morphology of the polycystic ovary, has been
redefined as an ovary with 12 or more follicles measuring
2–9 mm in diameter and increased ovarian volume (>10
cm3) on transvaginal ultrasound.

 Total failure of the ovaries in women under the age of 40
years.
 Characterized by:
1- Amenorrhoea.
2-Raised FSH.
3- Decreased Estradiol.
 Linked to genetic causes.
1-Sex Chromosome abnormality.
 Acquired from damage by viruses and toxins.
 Pelvic Surgery, irradiation or autoimmune.

 Impaired oocyte pick-up mechanisms by the fimbriae or
damaged tubal epithelium.
 Tubal Damage following:
1-Pelvic Infection.
2-Endometriosis.
3-Pelvic Surgery
4-Pelvic sepsis following appendicitis or
peritonitis.
 STD’s – Leading to tubal damage.
1-Chlamydia trachomatis
2-Gonocci

 Defects related to endometrial development and
maintenance.
 Submucous Fibroids - benign or non-cancerous tumors
found in the muscular wall of the uterus distorting the
endometrial cavity.

 Endometriosis is most simply defined as the presence of
endometrial surface epithelium and/or the presence of
endometrial glands and stroma outside the lining of the
uterine cavity.
 It is estimated that between 30 and 40 per cent of patients
with endometriosis complain of difficulty in conceiving. In
many patients there is a multifactorial pathogenesis to this
subfertility.
 In the severe stages of endometriosis there is commonly
anatomical distortion, with peri-adnexal adhesions and
destruction of ovarian tissue .

 Unexplained infertility is diagnosed where routine
investigations including semen analyses, tubal evaluation
and tests of ovulation yield normal results.
 Intrinsic differences within populations and variations in
investigation protocols have led to a wide range in the
reported prevalence of unexplained infertility, but most
clinics now report incidences of 15-30%.
 Failure of routine tests to detect any obvious contributory
factors has led clinicians to speculate about numerous
factors contributing to a diagnosis of unexplained
infertility.

 Luteal phase deficiency
 Luteinized unruptured follicle (LUF) syndrome.
 Hyperprolactinemia
 Occult infection.
 Immunological cause
 Psychological factors

 Infertility: duration of infertility, length and type of
contraceptive use, fertility in previous relationship as well
as in current, previous investigations and treatment.
 Sexual: coital frequency & timing, including knowledge of
fertile period. Dyspareunia, PCB.
 Gynae: menarche, menstrual hx, cyclicity, pain, bouts of
amenorrhea, menorrhagia, IMB.
 Obs: parity, miscarriages, ectopic pregnancies, any
associated sepsis, time to initiate prev pregnancies.

 Medical: T.B, D.M, STD(past/present), thyroid disease,
hyperprolactinemia.
 Surgical: previous abdominal or pelvic surgery, in
particular gynae surgery.
 Drugs: dopamine antagonists, past cytotoxic treatment or
radiotherapy.
 Occupational: work patterns including separation from
partner.
 Family, addictions, socioeconomic history.

 General: height, weight, BMI, fat and hair distribution,
presence or absence of acne and galactorrhoea.
 Abdominal: check for abdominal masses or tenderness.
 Pelvis: assess state of hymen, normality of clitoris, labia,
assess vagina for infection, vaginal septa, endometriotic
deposits, check for cervical polyps, assess accessibility of
cervix for insemination, record uterine size, position,
mobility, tenderness.
 Then perform cervical smear if appropriate.

 Ultrasound pelvis on day 12 of cycle.
 FSH
 LH
 Prolactin
 TSH.
 Serum testosterone
 DHEA and DHEAS, 17–OH progesterone.

 progesterone tracking.
 Where the cycle length is either longer or shorter than 28
days a single day-21 progesterone level may be insufficient
to pinpoint ovulation and serial progesterone checks may
be needed (progesterone tracking). For example, in a 28–
35 day cycle progesterone tracking could be started from
day 21 and continued weekly until the next period begins.
 Where periods are either very irregular or absent it may be
impractical to estimate progesterone levels. Instead,
additional biochemical investigations are indicated to
establish a possible endocrine cause of oligo/anovulation

 Investigation for tubal factors.
 X-ray Hysterosalpingography
 Laparoscopy and dye hydrotubation
 Hysterosalpingo-contrast sonography

 Hysteroscopy for uterine factors.

 All couples trying for a pregnancy will benefit from some
general advice such as cessation of smoking and limiting
alcohol intake. Pre-treatment counselling should include
advice about general lifestyle measures including the need
to achieve an optimum BMI.

 Treatment of WHO Group I ovulation disorders depends on
the diagnosis. Treatment options include:
 lifestyle interventions (normalising weight and exercise)
 pulsatile gonadotrophin-releasing hormone (GnRH) (‘GnRH
pump’)
 gonadotrophins (human menopausal gonadotrophin [hMG]).

 Treatment of WHO Group I ovulation disorders depends on
the diagnosis. Treatment options include:
 weight loss
 medical treatment
 second-line treatments including laparoscopic ovarian
diathermy (LOD) and injectable gonadotrophin ovulation
induction
 assisted conception (usually in vitro fertilisation [IVF])
 dopamine agonists.(bromocriptine 2.5mg HS)

 Ovulation induction can be performed using antioestrogen
medication, including clomiphene citrate and tamoxifen or
exogenous gonadotrophin, to stimulate the development of
one or more mature follicles.
 Clomiphene citrate is administered during the follicular
phase of the menstrual cycle. It is thought to act by
increasing gonadotrophin release from the pituitary,
leading to enhanced follicular recruitment and growth. It
is effective at inducing ovulation in 85 per cent of women
and can be used for a maximum of a year.

 It is administered orally for 5 days from 2nd day of mc
50mg /d.
 Side effect:
 Hot flushes
 Bloating
 Multiple gestations
 Visual changes

 Ovulation can also be induced with exogenous
gonadotrophins given by daily injection from the beginning
of the cycle.
 The dose is titrated against the individual response and is
monitored by an ultrasound assessment of follicular
number and size.
 Ovulation is usually triggered with an injection of human
chorionic gonadotrophin (hCG, which binds to the LH
receptor) when 1-3 follicles are 18 mm in diameter.
 Clomiphene resistance was defined as failure to ovulate
during the treatment with a total dose of 200 mg of CC for
at least four cycles

 is a potentially serious side effect of ovulation induction
and is associated with large ovarian cysts.
 There is increased vascular permeability leading to ascites,
pleural effusions and intravascular hypovolaemia .
 Thrombosis may ensue. OHSS is found particularly in
patients with polycystic ovarian syndrome and older
women.
 The mild form found in approximately 30% of patients,
responds to conservative management and no further
ovarian stimulation .
 The severe form (found in < 2%) requires fluid replacement
,antithrombotic measures and bed rest.

 Weight loss alone may restore ovulation.
 Offer one of the following treatments.
 clomifene citrate or
 metformin* or
 a combination of the above
 Offer U/S monitoring during atleast 1st cycle of Rx.
 do not continue treatment for longer than 6 months
 Inform about side-effects of metformin.

 consider one of the following second-line treatments,
depending on clinical circumstances and the woman’s
preference:
 laparoscopic ovarian drilling or
 combined treatment with clomifene citrate and
metformin* if not already offered as first-line treatment or
 gonadotrophins.
 Do not offer gonadotrophins and GnRH agonists together.
 Growth hormone is not recommended with GnRH agonists
and/or hMG.
 The effectiveness of pulsatile gonadotrophin-releasing
hormone in women with clomifene citrate-resistant
polycystic ovary syndrome is uncertain

 Aim is to restore normal anatomy.
 In-vitro fertilization (IVF) is an alternative to surgery.
 Laparoscopic adhesiolysis.
 Fimbrioplasty.
 Although at least 5% of the resulting conceptions will be
ectopic, intrauterine pregnancy rates of 50% can be seen
after 6 months.

 Endometriosis: COCP, progestogens, danazol, gestrinone,
GnRH analogues.
Surgery may be helpful in cases of advanced disease.
Laproscopic or open surgical approaches may be used
dependent on the skill of the surgical team.
 Uterine fibroids: identify type of fibroid, degree of
myometrial penetration by hysteroscopy is essential if
surgery is contemplated.
Laproscopic or open myomectomy

 1-Gamete intrafallopian transfer(GIFT):
Extraction of the oocytes is followed by the transfer of
gametes(sperm & oocyte) into a normal fallopian tube by
laparoscopy.
 2-Zygote intarafallopian transfer(ZIFT):refers to the
placement of the embryos into the tube via laparoscopy after
oocyte retrieval and fertilization.
 3-Intracytoplasmic sperm injection( ICSI):a single
spermatozoon is injected microscopically in to each oocyte,
and the resulting embryos are transferred transcervically into
the uterus. The advent of ICSI has revolutionized fertility
treatment for male factor.
 4-In vitro fertilization(IVF):refers to controlled ovarian
hyperstimulation, ultrasonographically guided aspiration of
oocytes laboratory fertilization with prepared sperm, embryo
culture, and transcervical transfer of the resulting embryos
into the uterus.

 1-Tubal conditions like large hydrosalpinx, absence of
fimbria, sever adhesive disease, repeated ectopic
pregnancies or failed reconstructive surgical therapy.
 2-Endometriosis if treatment failed.
 3-Unexplained subfertility.
 4-Male type low sperm count and abnormal morphology.
 5-HIV positive males.
 6-Men and women seeking fertility preservation after
chemotherapy or irradiation of their pelvic regions.

 Dewhurst’s textbook of obstetrics and gynaecology.
 An evidence-based text for the MRCOG.
 Amin M, Abdel-Kareem O, Takekida S, Moriyama T, Abd el-
Aal G, Maruo T. Up-date management of non responder to
clomiphene citrate in polycystic ovary syndrome. Kobe J
Med Sci. 2003;49(3):59-73.
 Women's NCCf, Health Cs. Fertility: assessment and
treatment for people with fertility problems: RCOG press;
2004.

Female infertility

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