A 31-year-old Nepalese American woman walked into Massachusetts General Hospital for unexplained infertility.(1) For the past two years, she struggled to conceive, undergoing two cycles of in vitro fertilization, only for the embryos to fail to implant. Infertility is a symptom of absence, the lack of viable pregnancy, and the causes of infertility range from genetic to hormonal to anatomic.(2) The patient had no salient medical issues, and thus underwent a battery of tests to figure out why she failed to get pregnant.
Finding the Cause
The tests included a pelvic exam, blood tests for hormone levels, cervical cultures for sexually transmitted diseases, an ultrasound, an X-ray of the uterus and fallopian tubes, and a hysteroscopy, which involves inserting a thin tube with a camera system into the uterus to visualize the inside. All her tests came back normal except for strange dilation of the fallopian tubes seen in the X-ray. After a litany of conventional tests, a biopsy of the uterus lining was performed. It showed peculiar scar tissue most often seen in lungs infected with tuberculosis.
The eventual, surprising diagnosis was endometrial tuberculosis, or infection of the uterine lining with tuberculosis bacteria. Tuberculosis is endemic in Nepal and North India, with up to 45% of the Nepalese population infected.(3) Unsurprisingly, endometrial tuberculosis is one of the leading causes of infertility in North India and Nepal, where it is endemic.(4,5) The peculiarity of endometrial tuberculosis is that infertility may be the only “silent” symptom(6) — quite a contrast to tuberculosis in the lungs, which may cause blood-streaked, hacking coughs. Pelvic pain or changes in menstrual cycles are seen in less than half the cases.(6) Diagnosis and detection of endometrial tuberculosis can therefore be a significant challenge.
Rotation Experience at JHBMC
During the summer months, I completed my women’s health (obstetrics-gynecology) rotation at Johns Hopkins Bayview Medical Center. One of the unique features of Hopkins Bayview is the large patient population of immigrants from Central America, where tuberculosis remains endemic. In fact, some of my patients had a history of tuberculosis infection. As part of the quintessential medical student experience, I spent time in the labor and delivery unit, assisting with the deliveries of many newborns. The labor and delivery unit was clearly the polar opposite of infertility, with vaginal deliveries and C-sections around the clock.
As I kept busy with countless birthdays, I could not help but wonder about the patients I hadn’t seen — those possibly carrying endometrial tuberculosis without any symptoms, except for years of infertility. To my knowledge, there is no systematic screening program for endometrial tuberculosis, unlike chest CT scans and T-SPOT blood tests for tuberculosis in the lungs. The only place for diagnosis is the reproductive endocrinology clinic for assisted reproductive services, which unfortunately remains a medical luxury. Given the immigrant population and disparities in health care access, I suspect there exists a Baltimore population of patients with endometrial tuberculosis, undetected by the health care system. Given that diagnosis of endometrial tuberculosis is very challenging, the prevalence of endometrial tuberculosis is very likely underestimated or even unknown. The irony is that the treatment is simple: the usual six-month course of anti-tuberculosis drugs.
The Medical and Socioeconomic Difficulties of Infertility
The difficult truth is that the distribution of assisted reproductive technologies remains unequal on a national and global scale. The overlap between those at risk for tuberculosis and those who can afford assisted reproductive technologies is practically nonexistent. The long and expensive process of assisted reproduction, starting from the battery of tests ruling out the diverse causes of infertility to the cycles of in vitro fertilization and embryo implantation, is simply out of reach for many for reasons of cost and access. The Affordable Care Act does not mandate coverage for infertility treatments, and a minority of states require insurers to cover infertility treatments. There is no simple answer for how to allocate the scarce resource of assisted reproductive technologies. As reproductive technologies advance, the question of distribution will always be at the forefront.
Spending time in Hopkins Bayview Gyn/Ob made me realize the medical and socioeconomic dimensions of fertility and childbearing. The issue of endometrial tuberculosis dovetails with the disparities in access to assisted reproductive technologies. The undetected cases of endometrial tuberculosis and silent infertility point out our own blind spots in treating infertility. As assisted reproductive technologies progress, it would be in our best interests to keep these blind spots in mind.
References
1. Legro RS, Hurtado RM, Kilcoyne A., and Roberts DJ. Case Records of the MGH: Case 28-2016 — A 31-Year-Old Woman with Infertility. N Engl J Med 2016; 375:1069-1077.
2. Infertility Workup for the Women's Health Specialist: ACOG Committee Opinion, Number 781. Obstet Gynecol. 2019; 133(6): e377-e384
3. Kulshrestha V, Kriplani A, Agarwal N, Singh UB, Rana T. Genital tuberculosis among infertile women and fertility outcome after antitubercular therapy. Int J Gynaecol Obstet 2011; 113:229-234
4. Mondal SK, Dutta TK. A ten year clinicopathological study of female genital tuberculosis and impact on fertility. JNMA J Nepal Med Assoc 2009; 48:52-57
5. Singh N, Sumana G, Mittal S. Genital tuberculosis: a leading cause for infertility in women seeking assisted conception in North India. Arch Gynecol Obstet 2008; 278:325-327
6. Visweswaran RK, Pais VM, Dionne-Odom J. Urogenital tuberculosis. UpToDate. May 7, 2021.
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