Shetty A*, Pardeshi S**, Gupta AS***
(* Third year Resident, ** Assistant Professor, *** Professor, Department of Obstetrics and Gynecology, Seth GS Medical College and KEM Hospital, Mumbai, India..)
Genital tuberculosis is one of the important cause of infertility in India. Apart from concerns of drug toxicity, this may be a contributing factor in the increasing incidence of multi-drug resistant tuberculosis. Female genital tuberculosis (FGTB) is an important cause of significant morbidity, short term and long term sequelae especially infertility. We present a case of confirmed genital tuberculosis and a discussion on the various tests that are available for diagnosis of FGTB.
Genitourinary Tuberculosis (GUTB) is the second most common extra pulmonary manifestation of tuberculosis (TB). Lack of an accurate diagnostic test has led to rampant use of anti-tubercular treatment in infertile women. FGTB is an important cause of significant morbidity, short term and long term sequelae especially infertility; the incidence of which varies from 3 to 16 % cases in India. An isolated involvement of genital organs is reported in 5-30 % of the cases. Disease usually severely affects the fallopian tubes leading to infertility. Diagnosis is usually difficult because of the asymptomatic nature of the disease or atypical clinical presentation. 
A twenty-six-year-old woman with a prior 1 abortion came with the chief complaints of oligomenorrhea of 3 years duration and secondary amenorrhea of 1 year duration for evaluation of infertility. She had no history of tuberculosis, thyroid dysfunction or galactorrhea. Her cycles previously have been regular, with moderate amount of flow. She also gave history of missed abortion a year back, no curettage was done. Her general and systemic examinations were normal. On local speculum examination, cervix had an erosion that did not bleed on touch, vagina was healthy, uterus was normal in size, anteverted, and fornices were normal. Urine pregnancy test was negative. Serological, biochemical, and hormonal profile were advised. Progesterone challenge test with oral medroxyprogesterone acetate was given. She had no withdrawal bleeding with progesterone, and was advised estrogen challenge test. She received conjugated equine estradiol for 21 days but had no withdrawal bleeding. Her hormonal profile that included TSH, serum LH and FSH levels were all within normal limits. Semen analysis was within normal limits. Ultrasonography showed sub endometrial calcification with endometrial thickness of 3.6 mm. A colposcopy, diagnostic hystero-laparoscopy and endometrial curettage was performed. Colposcopy was negative. On hysteroscopy right ostia was visualized, left ostia was not visualised and left uterine wall was irregular with multiple transverse bands of adhesions. On laparoscopy bilateral tubes were rigid, and both ovaries were obscured due to dense adhesions. Multiple tubercles were seen. Peritoneal and endometrial samples were collected and sent for smear, staining and isolation of AFB (acid fast bacilli), Gene Xpert, MGIT (mycobacterium growth indicator tube), TB PCR (tuberculosis polymerase chain reaction) and histopathology. MGIT showed growth of mycobacterium tuberculosis complex. Endometrial PCR was negative. Histopathology showed evidence of necrotising granulomatous endometritis possibly of tuberculous etiology. She was started on anti-tuberculous therapy (AKT). After 6 months of AKT she remained amenorrhoeic. She was started on cyclical conjugated equine estrogens in the dose of 1.25 mg twice daily for 21 days. She had no withdrawal bleeding even after 2 cycles of estrogen therapy. A second look hysteroscopy showed an irregular left uterine wall was with multiple transverse bands of adhesions. Curettage was done and endometrial samples were send for repeat Kochs’ cultures and histopathology to assess the need for further continuation of anti-tuberculous treatment. There was no evidence of tuberculosis on histopathology. She was counseled regarding IVF embryo transfer, surrogacy and adoption options.
Female genital tuberculosis is a common cause of infertility. It usually has mild clinical picture and usually detected with high index of clinical suspicion. Incidence of female genital tuberculosis is 27% worldwide. Incidence is increased to about 58% in endemic country like India. About 27 % of patients with genital tuberculosis present with menstrual irregularities.
Four clinical criteria are established by Klein et al. These are 1) There are irregular calcifications in adnexal area. 2) Tubal obstruction in zone of transition between isthmus and ampulla. 3) Multiple constrictions in tube. 4) Endometrial adhesions or obliteration in absence of history of curettage.
In study conducted by Kapoor et al it is reported that only 25 % of the cases of tuberculous endometritis are detected on histopathology as involvement of endometrium is usually focal and due to cyclical shedding of endometrium, evidence of tuberculosis may not be picked up in all cycles. However in our case histopathology showed evidence of tuberculosis.
Polymerase chain reaction (PCR) test in the endometrial tissue has been used for identification of tuberculous bacilli. Endometrial scrapped samples are sent in normal saline. The DNA samples are amplified using primer. MGIT test works on the principle that fluorescent compound in the broth is sensitive to the dissolved oxygen which is released by the actively respiring tuberculous bacteria. This fluorescence can be recorded by automated instruments. This test can also be used to detect culture and sensitivity pattern of the bacilli.
In our case mycobacterium growth indicator tube (MGIT) showed growth of mycobacterium tuberculosis but TB PCR was negative, probably because of the sampling error that occurs as there is only a focal area of endometrial lesions or bacterial load is less as tuberculosis has a paucibacillary nature. Moreover, endometrial samples are always admixed with blood and presence of inhibitors can also be possibility for false negative results. A negative PCR results may be misleading, so when GTB is clinically suspected and PCR tests are negative further testing should be gone to confirm the diagnosis.
In study conducted by Sharma et al, starting of anti-tuberculosis therapy in early disease improved the clinical outcome whereas advanced disease had poorer outcomes.
Infertility management for these patients is usually multidrug anti-tuberculous therapy. In case of presence of synechiae, hysteroscopy with adhesiolysis and with insertion of intrauterine device for short periods is recommended. Conjugated sstrogens can be used for rapid growth of endometrium. Spontaneous pregnancy after the diagnosis of genital tuberculosis is rare and if it occurs it usually results is an abortion or ectopic pregnancy. Frydman et al reported about 25% pregnancy rate per transfer in tuberculous infertility. In vitro fertilisation presents the only treatment for tubal and possibly endometrial tubercular infertility and improves the chances of fertility in what was earlier considered a desperate situation.
In this era of multi drug resistant tuberculosis it is essential for all clinicians especially those treating extra pulmonary tuberculosis to ensure that all diagnostic modalities that are available for diagnosing pulmonary tuberculosis and used to confirm extra pulmonary tuberculosis like genital Kochs’.
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Shetty A, Pardeshi S, Gupta AS. Infertility Due To Genital Tuberculosis. JPGO 2018. Volume 5 No.1. Available from: http://www.jpgo.org/2018/01/infertility-due-to-genital-tuberculosis.html