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Tuberculosis and Infertility-pathophysiology & management
- 1. TB and Infertility Dr.DhwaniDesai Associate Professor,Obs & Gynec Dept. GMC,Surat.
- 2. Case 1 A 30year old nulliparous was referred to with a chief complaint of an irregular menstrual cycle. Patient had been married for 5 years and unable to conceive despite having a regular unprotected intercourse. Ultrasound examination identified a bilateral endometriotic cysts, thus she was immediately scheduled for laparoscopy. During surgery, bilateral pyosalpinx was visible. Patient was treated and discharged 1 week after surgery.
- 3. Case 2 Patient 2was a 28 years old nulliparous, who was admitted to our fertility clinic with a history of irregular menstrual cycle. Her last menstrual period was 1 year prior to her visit. Patient had been married for 5 years and unable to conceive.Patient was diagnosed with secondary amenorrhoea and infertility. Patient underwent laparoscopy and both of the fallopian tubes were severely damaged with adhesions to surrounding tissues. Patient was discharged 1 day after the surgery.
- 4. Case 3 A 26years old nulliparous came with chief complaint of inability to conceive after 3 years of marriage. Patient had regular menstrual cycle (30–31 days), with no other related complaints. During ultrasound examination, irregularity in uterine mucosa with bilateral tubal obstruction was observed. Patient was diagnosed with endometriotic cysts with bilateral tubal obstruction, thus she was admitted for laparoscopy,found proximal obstruction at both of the fallopian tubes and adhesion to the surrounding tissues.
- 5. Specimens were collectedfrom all three patients. Presence of caseating granulomas surrounded by epithelioid cells, lymphocytes, plasma cells and giant cells are diagnostic of TB
- 8. • Extra pulmonaryTB is being increasingly encountered and accounts for about 15-20% of all cases of tuberculosis. • Reportedly about 9 per cent of all extra-pulmonary tuberculosis are genital tract TB. • Incidence varies from 1 to 19 % in India. Prevalence of FGTB in women with infertility was 26% and incidence of infertility in FGTB, 42 % • REFERENCES 1) Global Report of WHO, 2016 2) National Strategic Plan for Tuberculosis Elimination- 2017–2025: March 2017 Central TB Division, Directorate General of Health Services, Ministry of Health with Family Welfare
- 9. Genital tuberculosis isalways secondary to tuberculosis else where in body, usually in lungs, GIT, kidneys, peritoneum, lymph glands, bones etc.
- 10. Hematogenous spread: seenin 90% of cases Descending infection (7%): direct or lymphatic spread from the peritoneum, bowel or mesenteric lymph nodes Ascending infection: rarely (1-2% cases) infection occurs from coitus with a male suffering from urogenital tuberculosis or by use of infected sputum as a lubricant for intercourse or in children who sit naked on infected sputum.
- 11. Involvement of organs---Norries (1)Fallopian tubes------85 to 100% (2) Endometrium--------35 to 50% (3) Ovaries----------------20% (4) cervix—----------------- 5% (5) Vagina & vulva -------2%
- 12. Factors responsible forinfertility • Inflammation • Fibrosis • Atrophy • Toxins • Mechanical obstruction • Inflammatory mediators
- 13. Causes for infertility a.Ovulation issues- anovulation , tubo-ovarian masses, decreased Ovarian reserve and volume b. Tuboperitoneal- Adhesions. Motility problems, mucosal blocks, tubal block at various sites, hydrosalpinx, kinking, salpingitis isthmica nodosa, etc., c. Endometrial- adhesions, atrophy, implantation problems, cornual lesions
- 14. Difficulty is facedin every aspect of diagnostic procedures :- • History • Clinical features • Investigations
- 15. Diagnostic dilemna Variedpresentations Subclinical presentations Battery of tests Newer tests BCG immunisation adds to confusion High index of suspicion
- 16. Symtoms • Asymptomatic • ConstitutionalSymptoms- Anorexia , Malaise, Evening Rise Of Temperature, Weight Loss • Infertility. Primary -75% Cases Secondary -14% cases following an abortion , ectopic or normal delivery.
- 17. Symtoms • Menstrual Disorders- •Normal menstruation in 50-85% early cases • Dysmenorrhoea • Menorrhagia, menometrorrhagia due to ulcerative • T.B. endometritis • Oligo-hypomenohea • Amenorrhoea- (7% cases ) • Due to destruction of endometrium & ovaries
- 18. Symtoms • Pain • BloodStained Vaginal Discharge • Post Coital Bleeding • Dyspareunia
- 19. Tripathi’s high-risk group •They are: • Women who have a family history of tuberculosis • Past history of tuberculosis • Chronic pelvic pain associated with infertility • Secondary amenorrhea associated with infertility • Women having an adnexal lump, alone or associated with infertility • Puberty menorrhagia not responding to the usual treatment • Primary amenorrhea with or with out an unilateral lump • Chronic pelvic inflammatory disease in an adolescent
- 21. Aim of theInvestigations • Confirmation of diagnosis • Activity of the disease assessment • Site of involvement • Assessment of damage and its extent • Formulating the best option to improve fertility
- 22. • The diagnosisis often a challenge, sensitivity of detection of acid- fast bacilli on microscopy or culture on endometrial biopsy or histopathological detection of epithelioid granuloma being low. • Though PCR for detection of mycobacterial DNA is a rapid, sensitive test, because of risk of false positivity as well as negativity, cannot be used alone to decide on treatment. • Most women with genital tuberculosis have poor prognosis for fertility in spite of ATT. • Recent evidence suggests that ATT improves ovarian function . • Therefore high index of suspicion, early diagnosis, timely and adequate treatment may limit the long term sequel including infertility.
- 23. DIAGNOSIS OF FEMALEGENITAL TB • Early diagnosis is crucial for timely treatment and prevention of fibrosis and long term sequel especially infertility. • A detailed history, general examination to identify signs of TB at any other site, chest, abdominal and pelvic examination helps in the diagnosis. • In a suspected case of tuberculosis, the purpose of various investigations is to directly isolate the organism, or indirectly look at the effects on the tissues, organs by haematological , histopathological or microbiological methods.
- 24. • All testsare not required for every case. Following are the various investigations that can be done. • 1. Blood and urine examination • 2. Chest X ray • 3. Mantoux Test and Interferon Gamma Release Assays(IGRA) • 4. Mycobacterial smear and Culture • 5. Histopathology • 6. PCR • 7. Identification by Accuprobe • 8. FAST plaque TB
- 25. HSG is agood and simple imaging technique and can identify the lesions in more than 70% of cases. The fallopiantube is affected in almost all patients with active genital tuberculosis. • Non specific findings like hydrosalpinx • Multiple constrictions along the whole length of the tube giving a beaded appearance • Most common finding of tubal occlusion either at the isthmus or ampulla • Multiple occlusions and scarring making the tube rigid and giving a pipestem appearance • Cobblestone appearance • Leopard skin appearance • Tubal calcifications • Golf club appearance- Bilateral distal isthmic obstruction • Healing process may produce dense tissue with scar around tubes with decreased tubes motility and makesthem fixed - peritubal adhesions • Caseous ulceration of the mucosa of the tube gives it an irregular contour and diverticular outpouchingsurround the ampulla giving it a tufted appearance • Same process in the isthmic region gives the typical appearance of salpingitis isthmica nodosa (SIN)
- 26. • Otherthan thechanges in the tubes, uterine changes that may be appreciated in HSG are. • a. Endometritis, Intrauterine adhesions and asymmetrical cavity- All non specific. • b. collar-stud abscess- Specific • c. Tuberculosis T-shaped uterus- TB’s scar cause triangular uterine cavity and make T-shape or septate appearance • d. Pseudounicornuate uterus- Unilateral obliteration followed by unilateral scar in uterine cavity • e. Small uterine cavity with irregular contour and resembling septate appearance • f. Complete obstruction of uterine cavity with glove’s finger appearance • g. Due to progressive endometrial lesion contrast medium may passed through lymphatic and venous systems- Dye extravasation to vascular channels • Pelvic node calcification also may be detected
- 29. USG Findings Suspiciousof Tuberculosis • Persistent Thin Endometrium • Chronic PID • Fluid in Endometrial cavity • calcifications in the endometrium • Encysted ascitis • Hydrosalpinx visible on ultrasound • T-O Mass • Restricted Mobility
- 31. ENDOMETRIAL HISTOLOGY • Endometrialtissue is obtained at D&C/hysteroscopy directed biopsy. The histologic examination of endometrial tissues removed by biopsy or curettage, especially from the cornual area, affords a rapid method of diagnosing genital TB. • The optimal time for sampling is at the end of the menstrual cycle or within 12 hours after the onset of menstrual flow to allow the endometrial granulomata maximal time to develop. • Tubercles are present in the superficial layers of endometrium and are shed during menstruation. Demonstration of granuloma with or without Langerhans giant cells on histopathology is diagnostic of genital TB. • A negative biopsy however does not rule out genital TB.
- 32.
- 33. • LAPAROSCOPIC FINDINGS •Diagnostic laparoscopy is currently the principle modality of diagnosing genital TB because many of the common findings can be seen during the procedure. • In addition, questionable lesions may be biopsied in an attempt to obtain a histopathologic diagnosis. • Tubal findings include hydrosalpinx, beading, tobacco pouch or Maltese cross appearance, and calcification, pyosalpinx, occlusion (by chromopertubation), Cornual block, Peritubal adhesions, Rigid tubes, Fimbrial phimosis, Granulomas,tubercules, delayed spill, Shortened tubes, Sacculations/beaded tubes are suggestive of GTB. • Ovary - ovarian tubercules, tubo-ovarian mass, Periovarian adhesions, Associated PCO. • Perihepatic adhesions (Fitz-Hugh-Curtis syndrome), ascites, and caseous or granulomatous nodules.
- 34. • Associated endometriosis,Bowel and omental adhesions and Isolated tubercles. • o High coloured copious peritoneal fluid (tending to become encysted) • o Periuteritis (non glistening uterine surface), with lepra patches or a thrush appearance • o Perisalpingitis, salpingitis Isthmica Nodosa, beaded tubes, rosary appearance, • o Tubercles, micro & macro caseation (on tube, pouch of Douglas, posterior part of broad ligament) • o Flimsy adhesions in right iliac fossa, pouch of Douglas, left iliac fossa, and the liver area. • o Fibrosis in posterior part of broad ligament, mimicking endometriosis because of breaking of fibrosis typically by ante-verting the uterus • o Smaller than normal size fibrous uterus • o Synechiae observed by vaginal assistant during elevation of the uterus
- 38. HYSTEROSCOPY • Distending thecavity may be difficult. • CERVIX - Cervical stenosis, Irregular and ulcerated endocervical canal, Fleshy and hyperplastic cervical erosion not bleeding on touch, and placed anteriorly. • UTERINE CAVITY - Irregular uterine cavity, Intrauterine adhesions, or (ASHERMAN SYNDROME), Synechiae and fibrosis in the uterine cavity. • ENDOMETRIUM - Scanty endometrium, Endometrial calcification, Caseation/ tubercles, Hyperplasia of endometrium with scanty periods (not bleeding to touch with hysteroscope). • OSTIA - Periosteal fibrosis, Caseous material coming out of ostia, Ostia not visualized, Microcaseation, Non-breathing tubal ostium, focusing as a blocked tube. • Hysteroscopic biopsy of sinister part of endometrium gives more positive histopathological results
- 41. Treatment • Mainstay OfTreatment Is Multiple Drugs Therapy In Adequate Doses For Adequate Duration Of Treatment. • Short course chemotherapy for 6 to 9mths is as effective.
- 43. Monitoring response totreatment • The response to therapy should be assessed by • Improvement in the constitutional symptoms and general health. • Change in the size of pelvic mass, ascites by clinical and USG assessment. • Change in the ESR. • Endometrial biopsy can be done 3 monthly • Decision to changeover to second line therapy and need for surgical intervention can be made on assessment of clinical response to treatment.
- 44. Surgical treatment • Needfor surgical intervention is limited as the medical therapy is highly effective in the treatment of FGTB. • Indications for surgical intervention are as follows • Diagnosis is in doubt • Drainage of large residual pelvic or tubo-ovarian abscesses, pyosalpinx. • Persistent symptoms of fever, pain, ascites. • Presence of fistulae. • Fertility evaluation after treatment. Surgical intervention required may be laparoscopy, laparotomy or hysteroscopy
- 45. • ART inFGTB Most women with genital TB present with infertility and have poor prognosis for fertility in spite of ATT. • The conception rate is low (19.2 %) with live birth rate being still low (7 %) • If after ATT their tubes are still damaged but their endometrium is receptive (no adhesions or mild adhesions which can be hysteroscopically resected), IVF–ET is recommended. • However, if they have endometrial TB causing damage to the endometrium with shrunken small uterine cavity with Asherman’s syndrome, adoption or gestational surrogacy is advised to them .
- 46. Pitfalls in diagnosisof GT • Many other organisms like gonorrhea and chlamydia can give features of PID on lap • In cases of endometritis, tubal peritoneum can look healthy • If we wait for definitive diagnosis with traditional methods, chances are we will diagnose the cases when irreversible damage already has taken place
- 47. CHALLENGES IN MANAGEMENTOF FGTB • The diagnostic dilemma arises because of the varied clinical presentation of the disease confounded • Diverse results on imaging, laparoscopy, histopathology and a mixed bag of bacteriological and serological tests, each of which has its limitation in diagnostic sensitivity and specificity. • Many other organisms like gonorrhea and chlamydia can give features of PID on lap • Nucleic acid amplification (NAA) tests are a reliable way to increase the specificity of diagnosis, but the sensitivity is too poor to rule out disease, especially in smear-negative (paucibacillary) disease where clinical diagnosis is equivocal and where the clinical need is greatest • If we wait for definitive diagnosis with traditional methods, chances are we will diagnose the cases when irreversible damage already has taken place
- 48. • Francis statedthat the incidence of genital TB varies not only with the prevalence of extragenital TB in the community but also with the physician’s interest in searching for the disease!
- 50. Female genital TB– referring to TB of the uterus, fallopian tubes and/or ovaries
- 57. Conclusion -FGTB is anendemic problem in India especially in the infertile population. Early diagnosis and appropriate treatment can result in successful pregnancies. In advanced stages, careful individualization, counseling and multidisciplinary approach will yield better results. ART should be offered to a select few after ensuring the quiescent nature of disease as hormonal treatment of ART can result in disease reactivation and is highly counterproductive.
- 58.