Comparative study on complications and difficulties in laparoscopy in female genital tuberculosis cases versus non-tuberculosis cases.

BACKGROUND AND OBJECTIVE: Female genital tuberculosis (FGTB) is an important type of extrapulmonary tuberculosis (TB) associated with morbidity especially infertility in developing countries. Laparoscopy may be difficult and hazardous in FGTB. The aim of the study was to observe the difficulties and complications of laparoscopy in FGTB cases. MATERIALS AND METHODS: It was a prospective study over 12 years' period on 412 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling for acid-fast bacilli (AFB) microscopy, culture, polymerase chain reaction (PCR), gene Xpert (last 212 cases) and histopathological evidence of epithelioid granuloma. Another 412 cases of diagnostic laparoscopy in the absence of FGTB performed during same time were taken as controls from the pool of non-TB cases. Various difficulties and complications were noted in both groups and statistical analysis was done. RESULTS: Mean age, parity, body mass index and duration of infertility were 26.8 versus 25.4 years, 0.32 versus 0.28, 23.15 versus 25.28 Kg/m 2 and 4.15 versus 5.12 years, respectively. Primary and secondary infertility was seen in 78.6% and 20.38% of cases in the study group and 74.75% and 25.24% in the control group, respectively. Endometrial biopsy showed AFB microscopy in 5.3%, culture in 6.3%, epithelioid granuloma in 15.77% and on peritoneal biopsy granuloma in 6.55%, positive PCR in 368 (89.32%) and positive gene Xpert in 38 out of 212 (17.92%, out of last 212 cases). Definite findings of FGTB were seen in 171 (41.50%) cases. Probable findings of FGTB were seen in 241 (58.49%) cases. Various complications were difficulty in the creation of pneumoperitoneum or insertion of trocar and cannula in 16.74% and 13.10% of cases as compared to 1.94% and 1.69% in the control group. Excessive bleeding was seen in 5.09% versus 0.97% cases, respectively. Various injuries observed were bowel injury in 1.69% versus 0.24% cases (small bowel in 1.21% vs. 0.24%, large bowel in 0.48% vs. 0.1%), while bladder injury was seen in 0.97% versus 0.24% cases, subacute intestinal obstruction was seen in 5.8% versus 0.72% cases respectively while flare up of TB was seen in 5.09% versus 0% in cases and controls, respectively. Wound infection was seen in 8.48% versus 1.25% cases, respectively. INTERPRETATION AND CONCLUSION: FGTB is associated with increased complications and difficulties as compared to laparoscopy in other cases.

To Study the Efficacy and Safety of Diosmin with Tranexamic Acid and Mefenamic Acid Versus only Tranexamic Acid and Mefenamic Acid in Medical Management of Abnormal Uterine Bleeding: A Randomized Controlled Trial.

Background: Abnormal uterine bleeding (AUB) is a common problem in reproductive age group and perimenopausal age group being responsible for many outpatient visits. Traditional management of AUB consists of giving mefenamic acid, tranexamic acid, or their combination with progestogens or hormonal intrauterine deviced levonorgestrel intrauterine system (LNG-IUS) for severe or nonresponsive cases. The objective of the current study was to study the efficacy and safety of adding diosmin along with tranexamic acid and mefenamic acid in reducing menstrual blood loss in AUB patients. Materials and Methods: It was a prospective double-blind randomized controlled trial in which 900 mg of diosmin was given once daily along with 500 mg tranexamic acid and 250 mg mefenamic acid during menstruation (Group I-92 patients), or only tranexamic acid and mefenamic acid during menstruation (Group II-92 patients). Results: Mean age, parity, body mass index, and socioeconomic status were similar in the two groups. It was 35.68 years versus 36.78 years, 2.2 versus 2.3, 23.68 kg/m2 versus 24.62 kg/m2 respectively. Mean days of bleeding before this treatment were 6.8 versus 6.6 (P = 0.33) and were 3.5 versus 5.2 (P = 0.02) after treatment. There was a significant reduction in both groups as compared to before treatment (P = 0.021 in Group I, 0.027 in Group II) but the reduction was greater in Group I (P = 0.02). The amount of blood loss was 385 ml versus 390 ml (P = 0.7) before treatment which was significantly reduced in both groups to 68 ml versus 112 ml (P = 0.02 in Group I, 0.03 in Group II) with more decrease in Group I than in Group II (P = 0.01). Mean hemoglobin at beginning of the study was 8.4 versus 8.5 g/dl in Group I and Group II (P = 0.02) and significantly increased in both groups posttreatment to 10.9 and 9.8 g/dl in Group I and Group II (P = 0.012 in Group I, 0.011 in Group II) with increase being more in Group I than Group II (P = 0.03). Pictorial blood assessment chart score was 398 versus 406 (P = 0.35) before treatment and decreased significantly to 86.5 and 110.5 (P = 0.001 in Group I, 0.001 in Group II) with more decrease being in Group I than II (P = 0.01). There was significant decrease in dysmenorrhea with both treatments with no difference in the two groups. Various adverse effects such as nausea, vomiting, abdominal pain, diarrhea, constipation, and headache were equal in the two groups. Conclusion: Both the group's diosmin with tranexamic acid and mefenamic acid (Group I) and tranexamic acid and mefenamic acid (Group II) were efficacious in reducing menstrual blood loss, number of menstrual days and dysmenorrhea with effect being more by addition of diosmin. Adverse effects were equal in both the two groups.

Laparoscopic evaluation of female genital tuberculosis in infertility: An observational study.

Background & objectives: Female genital tuberculosis (FGTB) is an important variety of extrapulmonary TB causing significant morbidity, especially infertility, in developing countries like India. The aim of this study was to evaluate the laparoscopic findings of the FGTB. Methods: This was a cross-sectional study on 374 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling/biopsy for acid-fast bacilli, microscopy, culture, PCR, GeneXpert (only last 167 cases) and histopathological evidence of epithelioid granuloma. Diagnostic laparoscopy was performed in all the cases to evaluate the findings of FGTB. Results: Mean age, parity, body mass index and duration of infertility were 27.5 yr, 0.29, 22.6 kg/m2 and 3.78 years, respectively. Primary infertility was found in 81 per cent and secondary infertility in 18.18 per cent of cases. Endometrial biopsy was positive for AFB microscopy in 4.8 per cent, culture in 6.4 per cent and epithelioid granuloma in 15.5 per cent. Positive peritoneal biopsy granuloma was seen in 5.88 per cent, PCR in 314 (83.95%) and GeneXpert in 31 (18.56%, out of last 167 cases) cases. Definite findings of FGTB were seen in 164 (43.86%) cases with beaded tubes (12.29%), tubercles (32.88%) and caseous nodules (14.96%). Probable findings of FGTB were seen in 210 (56.14%) cases with pelvic adhesions (23.52%), perihepatic adhesions (47.86%), shaggy areas (11.7%), pelvic adhesions (11.71%), encysted ascites (10.42%) and frozen pelvis in 3.7 per cent of cases. Interpretation & conclusions: The finding of this study suggests that laparoscopy is a useful modality to diagnose FGTB with a higher pickup rate of cases. Hence it should be included as a part of composite reference standard.

An evaluation of Composite Reference Standard (CRS) for diagnosis of Female Genital Tuberculosis.

BACKGROUND: Female genital tuberculosis (FGTB) is a common cause of infertility in developing countries. Its diagnosis is difficult due to its paucibacillary nature, with no single test having high sensitivity and specificity. This study is to share the experience of using Composite Reference Standard (CRS) for the diagnosis of FGTB. METHODS: This is a prospective study conducted between September 2017 to June 2019, over 100 infertile females found to have FGTB on composite reference standard which consisted of acid-fast bacilli on microscopy or culture, histopathological evidence of epithelioid granuloma, positive gene Xpert on endometrial sample or definite or probable finding of FGTB on laparoscopy. RESULTS: A total of 100 infertile women (78% primary, 22% secondary) found to have FGTB on CRS were enrolled in this study. Mean age, body mass index, parity and duration of infertility were 28.2 years, 23.17 kg/m2, 0.24 ± 0.12 and 2.41 years respectively. Various symptoms were scanty menses (16%), irregular cycle (7%), dysmenorrhea (11%), pelvic pain (11%). Various signs were vaginal discharge (65%), adnexal mass (6%), tubo-ovarian mass on ultrasound (15%), abnormal hysterosalpingography findings (57.14%), positive polymerase chain reaction test (65%) and abnormal hysteroscopy (82.2%). The positive findings on CRS were positive AFB on microscopy or culture (3%), positive gene Xpert (28%) (done in some cases), epithelioid granuloma on histopathology (13%), definite findings on laparoscopy like tubercles, caseous nodules and beaded tubes in (57.19%) patients while probable findings of FGTB like straw colored fluid in POD, extensive dense pelvic, peri-tubal, peri-ovarian adhesions; hydrosalpinx; tubo-ovarian mass; thick fibrosed tubes; mid tubal block; peri hepatic adhesions (Fitz Hugh Curtis Syndrome); hyperemia of tubes/blue uterus on chromotubation were seen in (48.8%) patients. All patients found to be positive on CRS were given 6 months of anti-tubercular therapy. CONCLUSION: This study demonstrates the high reliability of use of composite reference standard for diagnosis of FGTB.

Immune disturbances in female genital tuberculosis and latent genital tuberculosis.

BACKGROUND: Female genital tuberculosis (FGTB), an important clinical sub-type of extra-pulmonary tuberculosis (EPTB) is responsible for about 10% cases of infertility in India. Both FGTB and latent genital tuberculosis (LGTB) can cause infertility through blockage of fallopian tubes and through altered uterine endometrial receptivity. AIMS: This review tries to elucidates the role of various immune factors in FGTB and LGTB. CONTENT: Various immune disturbances are observed in FGTB and LGTB like growth factors and cytokines which inhibit implantation and several inflammatory signaling pathways like mitogen activated protein kinase (MAPK), natural killer (NK) cells, nuclear factor kappa-B (NF-KB), tumor necrosis factor (TNF), and toll like receptors (TLR) signaling are dysregulated. These altered immune factors and pathways may be detected in the endometrial biopsies at the early stages of disease before permanent damage. Prompt and adequate treatment with the four anti-tubercular drugs (rifampicin [R], isoniazid [H], pyrazinamide [Z], and ethambutol [E]) can increase pregnancy rates in some of these women. Assisted reproduction especially in-vitro fertilization and embryo transfer may be required for some women. IMPLICATIONS: Inflammatory pathways identified from the gene profiling have enabled development of potential biomarkers for early diagnosis of FGTB. Immunomodulation and novel biotechniques like stem cell transplantation, nanoparticles and host directed therapies are being tried in selected patients of FGTB and LGTB with promising results.

Role of Magnetic Resonance Imaging in evaluation of tuberculous tubo ovarian mass.

OBJECTIVE: Role of Magnetic Resonance Imaging (MRI) in diagnosis of tuberculous tubo-ovarian (TO) mass. METHODS: MRI was performed on 33 patients of tuberculous TO mass of female genital tuberculosis (FGTB). RESULTS: Mean age, BMI, and parity was 27.5 ± 4.2 years, 22.7 ± 3.6 kg/m2, and 0.27 ± 0.13. All patients (100%) had infertility; primary infertility (72.72%) and secondary infertility (27.23%) with mean 5.8 years. Abdominal/pelvic pain 33 (100%) cases, abdominal lump 4 (12.12%), adnexal mass 33 (100%). MRI findings showed pelvic masses 33 (100%), bilateral TO masses 11 (33.33%), cystic lesion 4 (12.12%), solid cystic lesion 3 (9.09%) with bilateral pyosalpinx 1 (3.3%), homogeneous content with ascites 1 (3.03%), rim enhancing lesion abutting pelvic wall in 1 (3.03%). Right adnexal mass 11 (33.33%), right adnexal cyst 2 (6.06%), right adnexal cystic mass in 1 (3.03%), right sided complex TO mass 1 (3.03%), right sided hydrosalpinx in 1 (3.03%) case, right sided TO mass in 4 (12.12%) cases and right sided para-ovarian cyst in 2 (6.06%). Left sided adnexal mass was seen in 11 (33.33%), cystic lesion in 1 (3.03%), ovarian cyst in 3 (9.09%) cases, left sided hydrosalpinx in 2 (6.06%), left ovarian cyst 2 (6.06%) cases, left sided ovarian cyst with encysted ascites 1 (3.03%) case and with left sided paraovarian cyst 2 (6.06%) case. Miscellaneous finding were generalised ascites (6.06%), encysted ascites (3.03%), pelvic (1; 3.03%) and mesenteric lymphadenopathy 1 (3.03%). Incidental finding were fibroid 3 (9.09%) and adenomyosis 1 (3.03%) case. CONCLUSION: MRI appears to be useful diagnostic modality for tuberculous TO masses where differential diagnosis is malignancy but molecular diagnosis remains the gold standard.

Hysteroscopic observations in 348 consecutive cases of female genital tuberculosis: A prospective study.

STUDY OBJECTIVE: To evaluate the hysteroscopic findings in female genital tuberculosis. DESIGN: It was a prospective study of hysteroscopic findings performed on 348 cases of female genital tuberculosis (FGTB). SETTING: It was a prospective cross-sectional study in a tertiary referral centre. PATIENTS: A total of 348 patients with infertility with FGTB on various tests. INTERVENTION: A total of 348 patients of infertility found to have FGTB on various investigations were enrolled in the study. A detailed history was taken. Clinical examination, endometrial sampling and diagnostic laparoscopy were performed was also performed in selected cases. All patients underwent hysteroscopy as part of evaluation for infertility and tuberculosis (TB) findings. MEASUREMENTS AND MAIN RESULTS: The mean age, parity, body mass index and duration of infertility was 28.2 years, 0.31,23.1kg/m2 and 3.44 years respectively. Infertility was primary in 81.03% and secondary in 18.96% cases. Diagnosis of FGTB was made by endometrial aspirate findings of positive AFB on microscopy (4.02%), positive culture (4.88%), positive PCR (83.90%), epithelioid granuloma (14.65%), positive AFB on microscopy or culture of peritoneal cytology (1.14%) or epithelioid granuloma on peritoneal biopsy (1.72%), definitive findings of TB on laparoscopy (41.95%) or probable findings of TB on laparoscopy (58.05%). Various hysteroscopic findings observed were normal findings (28.16%), pale endometrial cavity (54.31%), features of active TB (7.47%), features of chronic TB (19.54%), features of TB sequelae like obstructed ostia (both ostia in 13.79%, one ostia 14.94%, periostial fibrosis; (bilateral 4.59%, unilateral 5.17%), endometrial glands atrophy (12.35%), small shrunken cavity (6.32%), distorted cavity (5.17%), various grades of intrauterine adhesions (29.88%). Hysteroscopy in FGTB was associated with increased difficulties and complications like failed procedures, difficult visualisation, false passage and uterine perforation. CONCLUSION: Hysteroscopy is useful modality to detect endometrial TB but is associated with increased difficulty and complications.

Computed tomographic findings in female genital tuberculosis tubo-ovarian masses.

Female genital tuberculosis (FGTB) is a common cause of infertility in developing countries. It can manifest as menstrual disturbances, infertility and pelvic masses. OBJECTIVE: To evaluate the role of computed tomography in diagnosis of female genital tuberculosis with tubo-ovarian (adnexal) masses. METHODS: It was a prospective study over a four year period (July 2015 to August 2019) in a tertiary referral centre over 33 patients presenting with tuberculosis and tubo ovarian masses only. 75 total cases of FGTB diagnosed on composite reference standard (evaluation of AFB bacilli in microscopy or culture or endometrial biopsy, gene expert, epitheloid granulomas on endometrial biopsy or definitive or possible findings of FGTB on laparoscopy). Detailed history taken, clinical examination, baseline investigations and endometrial biopsy were done in all cases. Computed tomography was performed in women presenting with infertility, tubo ovarian masses on clinical examination and laboratory investigations. A total of 33 cases were evaluated. RESULTS: Mean age, body mass index, parity and history of TB contact were 27.5 ± 4.2 year, 22.7 ± 3.6 kg/m2, 0.27 ± 0.13 and 44.4% respectively. Infertility was primary in 72.72% and secondary in 27.23%. Case wise mean duration being 5.8 years, menstrual dysfunction was seen in 45.45% cases. Abdominal discomfort with pain and lump were seen in all 33 (100%) cases. Abdominal lumps were felt in 4 (12.12%) cases while adnexal mass was seen in all 33 (100%) cases being unilateral in 18 (54.54%) and bilateral in 15 (45.45%). Mean ESR was 33.4mm in first hour while mean leucocyte count was 6128 ± 2854 per cubic mm. Infectious mantoux test (>10mm) was seen in 14 (42.82%) cases while abnormal X ray chest was seen in 9 (27.27%) cases. Diagnosis of FGTB was made by positive AFB n microscopy or culture of endometrial biopsy in 5 (15.15%) cases, positive gene expert in 6 (18.18%) cases, positive polymerase chain reaction in 32 (96.96%) cases, epitheloid granulomas on histopathology of endometrial biopsy in 7 (21.21%) cases, definitive findings of tuberculosis in 15 (45.45%) cases and a possible findings of tuberculosis inn 18 (54.54%) cases. Various CT findings were pelvic mass (100%), unilateral pelvic mass in 18 (54.54%), bilateral pelvic mass in 15 (45.45%), cystic mass (24.2%), solid mass (21.2%), mixed mass (54.54%), mass showing multilocular caseous necrotic enhancements (12.12%), ascites (42.4%), thickening and enhancement of peritoneum in 14 (42.42%), nodules in 24.2%, smooth in 18.8%, pelvic adhesion in 6 (18.18%), lymphadenopathy in 8 (24.3%) with calcifications (9.09%) and central necrosis (52.5%). Other CT findings were thickening and enhancement of bowel wall (12.12%), hepatic TB (3.03%), splenic TB (3.03%), omental thickening (9.09%) and omental calcification (3.03%) cases. CONCLUSION: Computed tomography appears to be a useful diagnostic modality in diagnosis of tuberculosis tubo ovarian masses and may help avoid unnecessary surgery.

Hysterosalpingography Observations in Female Genital Tuberculosis with Infertility.

Background: Hysterosalpingography (HSG) is radiographic evaluation of uterine cavity and tubal patency. Aims: The aim of this study was to evaluate the safety and utilisation of HSG in female genital tuberculosis (FGTB) with infertility. Settings and Design: The study was conducted in a tertiary referral centre of North India. Materials and Methods: It was a prospective study on 87 cases of FGTB with infertility. Diagnosis of FGTB was made by composite reference standard using the presence of acid-fast bacilli on microscopy/culture or positive GeneXpert, positive polymerase chain reaction or epithelioid granuloma on endometrial biopsy or definitive or probable findings on laparoscopy or hysteroscopy. Statistical Analysis Used: Suitable statistical methods were used with STATA software version 12.0. Results: HSG findings were normal in 49 (56.32%) cases. There were filling defects in 14 (16.09%), short and shrunken cavity in 4 (4.49%), intrauterine synechiae in 14 (16.09%), T-shaped cavity in 3 (3.44%) and deformed uterine cavity in 5 (5.74%) cases. Fallopian tube findings were hydrosalpinx in 12 (13.79%) and 11 (12.64%) cases, beading of tube in 4 (4.59%) and 2 (2.29%) cases, pipestem appearance in 2 (2.29%) cases each and Maltese cross appearance in 3 (3.44%) and 2 (2.29%) cases, respectively. Tubal blockage was seen in 69 (79.31%) and 67 (77.01%) cases being cornual block in 28 (32.18%) and 26 (29.88%) cases, mid-tubal block in 16 (18.39%) and 15 (17.24%) cases, multiple blocks in 10 (11.49%) and 12 (13.79%) cases and fimbrial block in 15 (17.24%) and 14 (16.09%) cases. None of the cases had flare-up of the disease after HSG in the current study. Conclusion: HSG is a useful modality in FGTB with infertility.

Evaluation of Role of Transabdominal and Transvaginal Ultrasound in Diagnosis of Female Genital Tuberculosis.

BACKGROUND: Female genital tuberculosis (FGTB) is a common problem in developing countries causing significant morbidity, especially infertility. Radiological imaging, especially ultrasound, can help in diagnosis of FGTB with tubo-ovarian masses. AIMS: The present study was performed to evaluate the role of ultrasound in diagnosis of FGTB and to see various findings of FGTB on ultrasound. STUDY SETTING AND DESIGN: It was a prospective cross-sectional study over 4-year period between August 2015 and August 2019 in a tertiary referral center. SUBJECTS AND METHODS: One hundred and seventy-five patients of infertility diagnosed to have FGTB on composite reference standard (CRS) of positive acid-fast bacilli on microscopy or culture of endometrial biopsy, positive polymerase chain reaction, positive GeneXpert, epithelioid granuloma on histology of endometrial biopsy, or definite or probable finding of FGTB on laparoscopy were subjected to transvaginal ultrasound by an experienced sonographer for various findings of FGTB. STATISTICAL ANALYSIS: Data analysis was carried out using STATA software 12.0. Comparison of categorical values was tested using Chi-square Fisher's exact test, with P < 0.05 being taken as significant. RESULTS: Mean age, body mass index, parity, and duration of infertility were 28.9 years, 22.9 kg/m2, 0.26, and 6.06 years, respectively. Menstrual dysfunction was common (44%). Diagnosis of FGTB was made by CRS. Ultrasound was normal in 112 (64%) cases and was abnormal in 63 (36%) cases. Various ultrasound findings were ovarian cyst (23.42%), tubo-ovarian masses (15.42%), unilateral or bilateral hydrosalpinx (13.71%), pyosalpinx (0.57%), adhesion (1.14%), adnexal fixity (6.28%), thin endometrium (24.57%), endometrial fluid (12.57%), endometrial calcification (1.7%), endometrial synechiae (4.57%), cornual synechiae (2.28%), impaired endometrial vascularity (21.71%), ascites (6.85%), and peritoneal or omental thickening (1.75%). CONCLUSION: Carefully performed ultrasound is a useful modality in diagnosis of FGTB, especially in adnexal masses.

Recent Advances in Diagnosis and Management of Female Genital Tuberculosis.

Female genital tuberculosis (FGTB) is an important cause of significant morbidity and infertility. Gold-standard diagnosis by demonstration of acid fast bacilli on microscopy or culture or detection of epithelioid granuloma on histopathology of endometrial or peritoneal biopsy is positive in only small percentage of cases due to its paucibacillary nature. Use of gene Xpert on endometrial or peritoneal biopsy has improved sensitivity of diagnosis. Composite reference standard (CRS) is a significant landmark in its diagnosis in which combination of factors like AFB on microscopy or culture, positive gene Xpert, epithelioid granuloma on endometrial or peritoneal biopsy, demonstration of definite or probable findings of FGTB on laparoscopy or hysteroscopy. There have been many advances and changes in management of FGTB recently. The program is now called National Tuberculosis Elimination Program (NTEP), and categorization of TB has been stopped. Now, patients are divided into drug-sensitive FGTB for which rifampicin (R), isoniazid (H), pyrazinamide (Z) and ethambutol (E) are given orally daily for 2 months followed by three drugs (rifampicin, isoniazid and ethambutol (RHE) orally daily for next 4 months. Multi-drug-resistant FGTB is treated with shorter MDR TB regimen of 9-11 months or longer MDR TB regimen of 18-20 months with reserved drugs. In vitro fertilization and embryo transfer have good results for blocked tubes and receptive endometrium, while surrogacy or adoption is advised for severe grades of Asherman's syndrome.

Pre treatment and post treatment positron emission tomography-computed tomography (PET-CT) to evaluate treatment response in tuberculous Tubo-Ovarian masses.

PURPOSE: Female genital Tuberculosis (FGTB) causes infertility and formation of Tubo-ovarian (TO) masses. The study showed treatment response of PET-CT in evaluation of anti-tubercular treatment response in patients of infertility with tuberculous TO masses. METHOD: It's a Prospective study on 47 confirmed cases of FGTB with infertility having TO masses. All patients were subjected to 18F-FDGPET/CT to see the glucose uptake by the TO mass and extent of the disease. Category I treatment under DOTS was given for 6 months. All underwent follow-up of PET/CT to see the response to ATT. Results of pre ATT PET/CT were compared with post ATT PET/CT. RESULTS: TO masses was in 42 (89.36%); bilateral in 18 (38.29%) FDG uptake in 14 (29.78%) and without FDG uptake in 4 (8.51%) cases. Right sided mass in 13 (27.65%) FDG uptake in 9 (19.14%) and without FDG uptake in 4 (8.51%) cases. Left sided mass in 11 (23.40%) FDG uptake in 7 (14.89%) and without FDG uptake in 4 (8.51%) cases. Post ATT, there was significant decrease in most parameters. Repeat PET-CT done in 44 cases showed TO mass in 9 (20.45%); bilateral in 4 (9.09%) (FDG uptake in 2.27%) (p < 0.001), right sided in 3 (6.85%) (FDG uptake in 2.27%) (p < 0.002) and left side in 2 (2.27%) FDG uptake in 1 case (p < 0.004). Pelvic and mesenteric lymphadenopathy without FDG uptake was in 1 case (p value = 0.03) while omental and peritoneal deposits without FDG uptake in 1 and 2 cases, respectively. CONCLUSION: PET-CT is useful in treatment response evaluation of tubercular TO masses.

Evaluation of Gene Xpert as compared to conventional methods in diagnosis of Female Genital Tuberculosis.

To evaluate Gene Xpert for diagnosis of Female Genital Tuberculosis (FGTB) as compared to conventional methods. STUDY DESIGN: It was a prospective study conducted over 167 cases of infertile female genital tuberculosis (FGTB) diagnosed on composite reference standard (CRS) (smear for AFB, histopathological evidence of epithelioid granuloma or definite or possible findings of tuberculosis on laparoscopy). All women underwent endometrial biopsy for AFB microscopy, culture, gene Xpert, PCR and histopathology) and laparoscopy and hysteroscopy for diagnosis and prognostication of disease. The results of Gene Xpert were compared with conventional methods in detection of FGTB. All patients were treated with 6 months course of rifampicin (R), isoniazid (H), pyrazinamide (Z) and ethambutol (E) (RHZE for 2 months, RHE for 4 months) using directly observed treatment short course strategy. RESULTS: Mean age, parity, body mass index and history of contact was 28.3 years, 0.28, 22.9 Kg/m2 and 38.92% respectively. Primary infertility was seen in 87.42% cases with mean duration of 2.42 years. Menstrual dysfunctions, abdominal or pelvic pain and lump were seen in 38.92%, 14.37% and 10.77% cases. Abnormal vaginal discharge and adnexal mass were seen in 28.14% and 13.17 % cases. On diagnostic laparoscopy, definite findings of tuberculosis (beaded tubes, tuebrcles and caseous nodules) were seen in 96 (57.48%) women while probable findings of tuberculosis (pelvic or abdominal adhesions, hydrosaplinx, tubo-ovarian mass, pyosalpinx) were seen in 81 (48.50%) women. On laboratory investigations, positive AFB on microscopy or culture was seen in 2.99% casess, PCR was positive in 47.90% gene Xpert was positive in 18.56% cases while epitheloid granuloma was seen on histopathology in 16 (9.58%) cases. Gene Xpert had sensitivity of 35.63%, specificity of 100%, positive predictive value of 100% and negative predictive value of 58.82% and diagnostic accuracy of 66.47% in the present study. CONCLUSION: Gene Xpert is a very useful test to rule in tuberculosis whereas when it is negative it is not a good test to rule out tuberculosis.

Female genital tuberculosis: Revisited.

Female genital tuberculosis (FGTB) is caused by Mycobacterium tuberculosis (rarely Mycobacterium bovis and/or atypical mycobacteria) being usually secondary to TB of the lungs or other organs with infection reaching through haematogenous, lymphatic route or direct spread from abdominal TB. In FGTB, fallopian tubes are affected in 90 per cent women, whereas uterine endometrium is affected in 70 per cent and ovaries in about 25 per cent women. It causes menstrual dysfunction and infertility through the damage of genital organs. Some cases may be asymptomatic. Diagnosis is often made from proper history taking, meticulous clinical examination and judicious use of investigations, especially endometrial aspirate (or biopsy) and endoscopy. Treatment is through multi-drug antitubercular treatment for adequate time period (rifampicin, isoniazid, pyrazinamide, ethambutol daily for 60 days followed by rifampicin, isoniazid, ethambutol daily for 120 days). Treatment is given for 18-24 months using the second-line drugs for drug-resistant (DR) cases. With the advent of increased access to rapid diagnostics and newer drugs, the management protocol is moving towards achieving universal drug sensitivity testing and treatment with injection-free regimens containing newer drugs, especially for new and previously treated DR cases.

Multi drug resistant female genital tuberculosis: A preliminary report.

OBJECTIVE: Evaluation of 6 patients presenting with tubo-ovarian mass or infertility with multi drug resistant (MDR) female genital tuberculosis (FGTB). STUDY DESIGN: It was an observational study in a tertiary referral centre, India on subjects with MDR FGTB on clinical examination and investigations. All patients were given category IV drugs using kanamycin (intramuscular), levofloxacin, pyrazinamide, cycloserine, ethionamide and ethambutol (or para aminosalicylic acid [PAS] for ethambutol resistant cases) for 6 months intensive phase followed by oral levofloxacin, cycloserine, ethionamide and ethambutol (or PAS for ethambutol resistant cases) for 18 months continuation phase. Patients were evaluated for primary end points (complete cure, partial response, no response, treatment completed) and secondary end points (recurrence rate, pregnancy rate) during treatment. RESULTS: There were 2 (33.3%) primary MDR FGTB patients and 4 (66.6%) secondary MDR FGTB (three pulmonary MDR and one MDR lymphadenitis) patients. Mean age was 23.6 years. Presenting features were menstrual dysfunction in all patients (100%) especially oligomenorrhea in 3 (50%) patients, weight loss in all the patients (100%), cough with expectoration in three patients (50%), tubo-ovarian masses in five (83.3%) patients. Endometrial biopsy showed positive culture for AFB with rifampicin and isoniazid (INH) resistance in both primary MDR FGTB patients and in two secondary MDR FGTB patients who were sexually active. In secondary MDR FGTB, three pulmonary MDR patients had positive sputum AFB smear and culture, while the patient with MDR lymphadenitis had lymph node aspirate for AFB smear and culture positive with all showing resistance to rifampicin and isoniazid. Gene Xpert on endometrial biopsy or sputum was positive in 5 (83.3%) patients. Three (50%) patients (one primary and two secondary) have completed therapy while other 3 (50%) are in continuation phase. All patients are asymptomatic with one having 12 weeks ongoing successful pregnancy. CONCLUSION: MDR FGTB should be thought of in women of FGTB with tubo- ovarian masses who are not responding to first line drugs. Gene Xpert can be used in early diagnosis of MDR FGTB.

Effect of antitubercular treatment on ovarian function in female genital tuberculosis with infertility.

AIM: To evaluate the effect of antitubercular therapy (ATT) on an ovarian function such as ovarian reserve, ovarian dimensions, and ovarian stromal blood flow. SETTINGS AND DESIGN: Prospective study design. MATERIALS AND METHODS: Fifty infertile women with female genital tuberculosis (FGTB) without tubo-ovarian masses diagnosed by positive acid-fast bacilli culture or epithelioid granuloma on endometrial aspirate or positive polymerase chain reaction with positive findings on laparoscopy or hysteroscopy were recruited. The ovarian function tests were performed on day 2/3 as follicle-stimulating hormone (FSH) levels and anti-Mullerian hormone (AMH) levels. Ovarian dimensions (length, width, and depth) were measured using a transvaginal ultrasound. Mean antral follicle count (AFC) and ovarian stromal blood flow (peak systolic velocity [PSV], pulsatility index (PI), and resistive index [RI]) were measured using a transvaginal ultrasound. All women were started on ATT for 6 months by directly observed treatment strategy. After completion of ATT, all the parameters were repeated. RESULTS: There was a significant increase in AMH (2.68 ± 0.97 ng/ml to 2.8 ± 1.03 ng/ml) pre- to post-ATT, nonsignificant increase in FSH (7.16 ± 2.34 mIU/ml to 7.26 ± 2.33 mIU/ml) post-ATT, significant increase in mean AFC (7.40 ± 2.12-8.14 ± 2.17), PSV in the right ovary (6.015-6.11 cm/s) and left ovary (6.05-6.08 cm/s), PI in the right ovary (0.935-0.951 cm/s) and left ovary (0.936-0.957 cm/s), and RI in the right ovary (0.62 ± 0.01-0.79 ± 0.02) and left ovary (0.65 ± 0.02-0.84 ± 0.01) with ATT. There was no significant change in mean ovarian dimensions (ovarian length, breadth, and width) and summed ovarian volume with ATT. On laparoscopy, tubercles were seen in 27 (54%) women. Caseous nodules and encysted ascites were seen in 8% cases each. CONCLUSION: ATT improves the ovarian function (AMH and AFC) and ovarian blood flow in women with FGTB.

Six months versus nine months anti-tuberculous therapy for female genital tuberculosis: a randomized controlled trial.

OBJECTIVE: To compare six months versus nine months anti-tuberculous therapy in patients of female genital tuberculosis. STUDY DESIGN: It was a randomized controlled trial in a tertiary referral center teaching institute on 175 women presenting with infertility and found to have female genital tuberculosis on clinical examination and investigations. Group I women (86 women) were given 9 months of intermitted anti-tuberculous therapy under directly observed treatment short course (DOTS) strategy while Group II (89 women) were given 6 months of anti-tuberculous therapy under DOTS. Patients were evaluated for primary end points (complete cure, partial response, no response) and secondary end points (recurrence rate, pregnancy rate) during treatment. All patients were followed up further for one year after completion of therapy to assess recurrence of disease and further pregnancies. RESULTS: Baseline characteristics were similar between two randomized groups. There was no difference in the complete clinical response rate (95.3% vs 97.7%, p=0.441) between 9-months and 6-months groups. Four patients in 9-months group and two patients in 6-months group had recurrence of disease and required category II anti tuberculous therapy (p=0.441). Pregnancy rate during treatment and up to one year follow up was also similar in the two groups (23.2% vs 21.3%, p=0.762). Side effects occurred in 27(31.4%) and 29(32.6%) in 9-months and 6-months of therapy and were similar (p=0.866). CONCLUSIONS: There was no difference in complete cure rate, recurrent rate and pregnancy rate for either 6-months or 9-months of intermittent directly observed treatment short course anti-tuberculous therapy in female genital tuberculosis. CLINICAL TRIAL REGISTRATION: The trial was registered in clinicaltrials.gov with registration no: CTRI/2009/091/001088.

Comparative Study of Laparoscopic Abdominopelvic and Fallopian Tube Findings Before and After Antitubercular Therapy in Female Genital Tuberculosis With Infertility.

STUDY OBJECTIVE: To study the effect of antitubercular treatment (ATT) on the laparoscopic abdominopelvic and fallopian tube findings in female genital tuberculosis (FGBT). DESIGN: Prospective cohort (Canadian Task Force classification II2). SETTING: Tertiary referral center in northern India. PATIENTS: Fifty women with infertility and diagnosed with FGTB on laparoscopy, histopathology findings, or endometrial sampling (acid-fast bacilli culture, granuloma on histopathology, positive polymerase chain reaction). INTERVENTIONS: Diagnostic laparoscopy in all women diagnosed with FGTB before and after a 6-month course of ATT (2 months of rifampicin, isoniazid, pyrazinamide, and ethambutol, followed by 4 months of rifampicin and isoniazid). All procedures were performed by the same surgeon between June 2012 and May 2014. MEASUREMENTS AND MAIN RESULTS: The mean patient age was 28.7 years, mean parity was 0.9, and mean body mass index was 23.6 kg/m(2). Infertility was seen in all 50 women (66% primary infertility, 34% secondary infertility), with a mean duration of 6.06 years. Abnormal laparoscopic findings of FGTB included tubercles in the pelvic peritoneum, fallopian tube, and ovary in 27 women (54%) before ATT and in only 1 (2.04%) woman after ATT (p < .001). Caseous nodules and encysted ascites were seen in 4 women (8%) before ATT, and in no women after ATT (p < .001); however, there was no change from before ATT to after ATT in the rate of pelvic adhesions (42% vs 42.5%) and perihepatic adhesions (56% vs 58%). Laparoscopic findings in fallopian tubes included hydrosalpinx (32%), pyosalpinx (4%), beaded tubes (12%), nonvisualization of tube (20%), and tubal blockage on the right side (56%), left side (50%), and both sides (38%) before ATT. Hydrosalpinx, beaded tubes, and nonvisualized tube were seen in 33.4%, 4.1%, and 20.8% cases, respectively, after ATT; however, free spill increased to 52% on the right side and 50% on left side after ATT. CONCLUSION: ATT improves laparoscopic findings in FGTB with infertility. However, advanced fibrotic lesions (eg, pelvic and perihepatic adhesions, bilateral blocked tubes) do not improve with ATT.

Effect of Antitubercular Therapy on Endometrial Function in Infertile Women with Female Genital Tuberculosis.

OBJECTIVE: Evaluation of anti-tubercular therapy on endometrium in Female Genital Tuberculosis. METHOD: Total of 50 women having FGTB on endometrial aspirate (positive AFB, epithelioid granuloma, positive PCR, laparoscopy or hysteroscopy findings) were enrolled. Ultrasound was performed for endometrial thickness, mean resistive index and pulsatility index before and after anti-tubercular therapy (ATT). Diagnostic hysteroscopy was performed for intra-uterine adhesions and to visualise cavity before and after ATT. RESULTS: Menstrual cycle improved after anti-tubercular therapy (ATT). Endometrial aspirate findings improved with disappearance of AFB, epithelioid granuloma and decrease in PCR (94%vs 33%). After ATT, ultrasound examination of endometrial thickness improved from 7.01±1.48 mm to 7.51±1.48 mm while mean resistive index and pulsatility index decreased from 0.729±0.304 to 0.692±0.399 and 1.180 to 1.138. With ATT, improvement was seen in hysteroscopic findings with normal looking cavity increasing from 18(36%) to 34(72.1%) and pale looking cavity decreasing from 20(42.5%) to 8(16.8%). Before ATT, prevalence of intrauterine adhesions was 62% which decreased to 28.7% after ATT. Improvement was significant only in grade I adhesions from 34% to 2.1%, (p<0.001). There was no improvement in higher grade of intrauterine adhesions with ATT with grade II (6% vs 4.2%) and grade 2a (4% vs 2.1%), grade III being (2% vs 2.1%), grade II a (4% vs 4.2%), grade Va (4% vs 4.2%) and grade Vb (8% vs 10.6%) before and after ATT respectively. CONCLUSION: Early ATT improved menstrual cycle, endometrial thickness and reduced incidence of grade I adhesions. Advanced stages did not show any improvement.

Autologous stem cell transplantation in refractory Asherman's syndrome: A novel cell based therapy.

BACKGROUND: There is substantial evidence that adult stem cell populations exist in human endometrium, and hence it is suggested that either endogenous endometrial stem/progenitor cells can be activated or bone marrow derived stem cells can be transplanted in the uterine cavity for endometrial regeneration in Asherman's syndrome (AS). AIMS AND OBJECTIVES: The objective was to evaluate the role of sub-endometrial autologous stem cell implantation in women with refractory AS in attaining menstruation and fertility. SETTING: Tertiary care referral center. DESIGN: Prospective case series. MATERIALS AND METHODS: Six cases of refractory AS with failed standard treatment option of hysteroscopic adhesiolysis in the past were included. Mononuclear stem cells (MNCs) were implanted in sub-endometrial zone followed by exogenous oral estrogen therapy. Endometrial thickness (ET) was assessed at 3, 6, and 9 months. RESULTS: Descriptive statistics and statistical analysis of study variables was carried out using STATA version 9.0. The mean MNC count was 103.3 × 106 (±20.45) with mean CD34+ count being 203,642 (±269,274). Mean of ET (mm) at 3 months (4.05 ± 1.40), 6 months (5.46 ± 1.36) and 9 months (5.48 ± 1.14) were significantly (P < 0.05) increased from pretreatment level (1.38 ± 0.39). Five out of six patients resumed menstruation. CONCLUSION: The autologous stem cell implantation leads to endometrial regeneration reflected by restoration of menstruation in five out of six cases. Autologous stem cell implantation is a promising novel cell based therapy for refractory AS.