Female genital tuberculosis in an infertility patient resulting in destruction of ovarian tissue: A case report

A 30-year-old nulligravid woman presented for outpatient evaluation following a CT scan of the abdomen and pelvis and pelvic ultrasound that was notable for a 7.0 cm right adnexal cyst in the setting of right upper abdominal pain. The right ovary was not definitively visualized, and the left ovary was normal in appearance. On evaluation, the patient reported resolution of her abdominal pain although admitted to being unable to conceive for six months as well as new-onset amenorrhea for the last year. She denied any history of abnormal Papanicolaou smears or sexually transmitted infections. Her past medical and surgical history were otherwise unremarkable. There were no notable findings on her physical exam. The patient was consented for a diagnostic laparoscopy with possible ovarian cystectomy and hysteroscopy given her ultrasound findings and secondary amenorrhea. Laboratory investigations were also ordered to further investigate her secondary amenorrhea and infertility concerns. The results were unremarkable aside from a low anti-mullerian hormone (AMH) level (0.72 ng/mL). The patient underwent a diagnostic laparoscopy with findings concerning for sequelae of pelvic inflammatory disease. The liver and gallbladder had numerous thin adhesions to the anterior abdominal wall consistent with Fitz-Hugh-Curtis syndrome. Similar appearing adhesions were present throughout the pelvis ( Fig. 1 a and b) in addition to multiple subcentimeter nodules with yellow discoloration consistent with caseous nodules ( Fig. 2 a). The uterus was deviated to the right pelvic side wall due to dense adhesions, with additional adhesions from the uterine serosa to the posterior cul-de-sac and underlying colon. Both fallopian tubes were hyperemic and densely adhered to their respective pelvic side wall, and the tubal fimbriae had loss of their normal architecture ( Fig. 2 a and 3 a). On further examination of the left adnexa, the left ovary appeared to be densely adhered to the pelvic side wall with overlying adhesions making visualization difficult ( Fig. 2 a). The right adnexa was notable for a large, approximately 6 cm fluid-filled peritoneal inclusion cyst with multiple loculations and encased in adhesive tissue ( Fig. 2 a and b). The right ovary was not visualized in the right ovarian fossa even after extensive lysis of adhesions and attempts to restore normal anatomy ( Fig. 3 ). Hysteroscopic evaluation of the endometrium was limited due to diffuse synechiae and adhesive scarring. Fig. 1 (a) Evidence of perihepatic adhesions consistent with Fitz-Hugh-Curtis syndrome on laparoscopy. (b) Adhesions in the lower pelvis. Fig. 1 Fig. 2 (a) Uterus deviated to the right pelvic side wall. The left ovary is densely adhered to the left pelvic side wall with overlying adhesions (blue arrow). A caseous nodule is adjacent to the left ovary (white arrow). The peritoneal inclusion cyst visualized (green arrow). The left fallopian tube is notable for loss of normal architecture. (b) Peritoneal inclusion cyst (green arrow) with cloudy fluid in the posterior cul-de-sac. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) Fig. 2 Fig. 3 (a) Following removal of the peritoneal inclusion cyst, the right ovary cannot be definitively visualized in the ovarian fossa. The right fallopian tube is hyperemic with loss of normal architecture similar to the contralateral side (white arrow). (b) Global view of the pelvis following lysis of adhesions and removal of the peritoneal inclusion cyst. Significant scar tissue is still present. Fig. 3 (a) Evidence of perihepatic adhesions consistent with Fitz-Hugh-Curtis syndrome on laparoscopy. (b) Adhesions in the lower pelvis. (a) Uterus deviated to the right pelvic side wall. The left ovary is densely adhered to the left pelvic side wall with overlying adhesions (blue arrow). A caseous nodule is adjacent to the left ovary (white arrow). The peritoneal inclusion cyst visualized (green arrow). The left fallopian tube is notable for loss of normal architecture. (b) Peritoneal inclusion cyst (green arrow) with cloudy fluid in the posterior cul-de-sac. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) (a) Following removal of the peritoneal inclusion cyst, the right ovary cannot be definitively visualized in the ovarian fossa. The right fallopian tube is hyperemic with loss of normal architecture similar to the contralateral side (white arrow). (b) Global view of the pelvis following lysis of adhesions and removal of the peritoneal inclusion cyst. Significant scar tissue is still present. The diffuse damage to this patient's reproductive organs was thought to be secondary to pelvic inflammatory disease, but the patient denied any history of sexually transmitted infections and had recent negative testing. In further discussion with the patient following her surgery, she reported previously living in Cameroon, a region where tuberculosis is endemic. Subsequently a QuantiFeron-TB test was positive, raising concern for FGTB. Limited endometrial curettings from the patient's surgery were sent for TB-PCR, which was negative; however, this was suspected to be secondary to sample insufficiency. Given the likelihood of pelvic tuberculosis, a repeat endometrial biopsy was performed in the clinic to attempt to confirm the diagnosis. This biopsy had a positive TB-PCR as well as a positive acid-fast bacillus (AFB) culture, confirming the diagnosis of FGTB. The patient was promptly started on treatment with a multi-drug regimen of rifampin, isoniazid, ethambutol, and pyrazinamide, with the plan to proceed with intensive treatment for two months followed by at least four months of rifampin and isoniazid.

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Written informed consent was obtained from the patient for publication of the case report and the accompanying images.

This case demonstrates the devastating effects FGTB can have on the reproductive organs. FGTB is an important cause of infertility in endemic regions, where it is often first diagnosed at an infertility workup [ 5 ]. In contrast, its prevalence is rare amongst patients with infertility in the United States, though previous studies have noted that patients seeking infertility care who are originally from countries where the disease is endemic may benefit from screening for latent tuberculosis as part of their initial infertility workup [ 6 ]. FGTB can be difficult to diagnose due to the pauci-bacillary nature of the disease, and no single test has been shown to have adequate sensitivity and specificity to make a definitive diagnosis. The utilization of multiple diagnostic modalities has been proposed to avoid mis- and underdiagnosis. These include a positive AFB culture on endometrial biopsy; demonstration of acid fast bacilli on endometrial biopsy; positive gene Xpert test on endometrial or lesion biopsy, or peritoneal fluid; histopathological evidence of epithelioid granuloma on endometrial, peritoneal biopsy, or lesion biopsy; and definite or probable findings of disease on laparoscopy [ 2 , 3 , 7 ]. The use of TB-PCR alone to diagnose the disease and initiate treatment can be problematic due to its quoted high false positive rate, but it can be utilized in conjunction with other modalities, such as laparoscopy, to establish the diagnosis [ 3 ]. In the present case, affirming the diagnosis of FGTB was difficult, largely due to a low index of suspicion at the time of surgery. The patient's laparoscopic findings were initially attributed to pelvic inflammatory disease, given its greater prevalence, and as a result further testing of the patient's peritoneal fluid and other biopsies were not pursued. Only in retrospect did suspicion for FGTB increase, prompting further evaluation with an in-office endometrial biopsy. Although the diagnosis was eventually made by TB-PCR and affirmed by a positive AFB culture from the endometrial biopsy sample, this diagnosis might have been established sooner had it been considered during the initial surgical evaluation. The case thereby highlights how important it is to consider FGTB in patients from endemic regions or those with surgical findings consistent with the disease so that treatment can be promptly initiated. FGTB can lead to infertility in multiple ways. In most cases there is damage to both the fallopian tubes and uterine lining, which can appear as abnormal results on hysterosalpingogram and Asherman's syndrome on hysteroscopy [ 8 , 9 ]. FGTB has also been implicated in decreased ovarian reserve. Previous studies have noted that patients with FGTB have lower AMH levels and lower antral follicle counts (AFC) than unaffected patients. While the adverse effect on ovarian reserve is poorly understood, proposed mechanisms include decreased vascular flow to the ovary and the formation of ovarian cysts that impede upon normal ovarian tissue [ 4 , 10 , 11 ]. In this case, the right ovary appeared to be completely obliterated, as evidenced by the absence of any identifiable right ovarian tissue on laparoscopy or on preceding images. The complete destruction of normal ovarian tissue seen in this case is rare, but offers an additional pathophysiologic basis for diminished ovarian reserve in FGTB. Fertility in FGTB remains a challenge even following completion of treatment, and the use of assisted reproductive technology (ART) is often indicated. There is evidence that shows improvement in fertility parameters following 6–12 months of therapy. For instance, a prospective study on fifty patients with FGTB and infertility found an improvement in AFC and AMH levels following treatment for FGTB, which may translate into improved fertility treatment outcomes [ 4 ]. Another prospective study looking at laparoscopic findings before and after TB treatment in FGTB patients found a reduction in the presence of tubercles, caseous nodules, and encysted ascites following treatment. However, this study also found no improvement in advanced fibrotic lesions such as pelvic and perihepatic adhesions and found no improvement in tubal patency in patients with bilateral tubal blockage prior to treatment [ 12 ]. A systematic review found that pregnancy outcomes are overall uncertain following treatment for structural damage to reproductive organs from FGTB [ 13 ]. Therefore, the effect of anti-tuberculosis treatment alone on fertility and pregnancy outcomes in patients with FGTB is unknown and is likely related to the extent of disease. For patients with tubal disease from FGTB who are undergoing in-vitro fertilization (IVF), bilateral salpingectomy has been demonstrated to improve clinical pregnancy rates even after anti-tuberculosis treatment. However, patients with affected endometrium have reduced fertilization, implantation, cumulative pregnancy rates while undergoing ART compared to those with tubal tuberculosis even after treatment with ATT, suggesting these changes are more difficult to reverse or require further treatment [ 14 ]. In the present case, the extent of the patient's disease made spontaneous conception unlikely, and ART options might have been limited given the intrauterine scarring on hysteroscopy. However, the patient was potentially interested in egg retrieval in the future to pursue IVF with a pregnancy surrogate.

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FGTB is an important cause of infertility with detrimental impacts on pelvic organ function, including complete destruction of the ovary, as seen in this case. Therefore, this diagnosis should be considered in patients with concerning findings on imaging or laparoscopy, as well as patients from regions where TB is endemic. Further investigation in the relationship between FGTB and ovarian tissue damage is needed to understand its development and how these effects may be reversed or prevented.

Rachel Watkin contributed to patient care, conception of the case report, acquiring and interpreting the data, drafting the manuscript, undertaking the literature review and revising the article critically for important intellectual content. Kalen Hubbs contributed to patient care, conception of the case report, drafting the manuscript and revising the article critically for important intellectual content. Michael Clark contributed to patient care, conception of the case report, drafting the manuscript, and revising the article critically for important intellectual content. Shannon Wood contributed to patient care, conception of the case report, drafting the manuscript, and revising the article critically for important intellectual content. All authors approved the final submitted manuscript. The views expressed are those of the author(s) and do not reflect the official policy of the Department of the Army, the Department of Defense, or the U.S. Government.

Female genital tuberculosis (FGTB) is a form of extrapulmonary tuberculosis with consequential effects on pelvic health. The exact incidence of FGTB worldwide is unknown, as reported rates are likely underestimated due to underreporting, difficulty in diagnosis due to its paucibacillary nature, and asymptomatic illness [ [1] , [2] , [3] ]. The disease involves both fallopian tubes in over 90 % of cases, as well as the uterine endometrium (70 % of cases), ovaries (20–30 % of cases), and, more rarely, the cervix and vagina/vulva [ 1 ]. When it comes to ovarian function, previous studies have noted that FGTB can impact ovarian blood flow, ovarian volume, and function parameters such as anti-mullerian hormone level and antral follicle count [ 1 , 4 ]. While destruction of ovarian tissue has been previously described in FGTB, to our knowledge, a documented case resulting in the complete disappearance of the ovary has not yet been reported [ 1 , 4 ]. Though FGTB can present a diagnostic conundrum, prompt diagnosis and treatment are essential in preventing potentially irreversible damage to the pelvic organs. This case concerns an unexpected diagnosis of FGTB in a 30-year-old patient originally presenting for evaluation for a right adnexal mass, who ultimately had evidence of multi-pelvic organ involvement, including the complete destruction of her right ovary.

The authors declare that they have no competing interest regarding the publication of this case report.