Could this treatable infection be related to recurrent pregnancy loss?

In the spring of 2020, Molly Sohr and her husband Andrew had been trying for a baby for four years. “We tried every fertility treatment under the sun,” she tells Motherly. Sohr was eventually diagnosed with polycystic ovary syndrome (PCOS), but the traditional PCOS treatments still didn’t help. Nothing was working, from hormone protocols to more invasive fertility processes, like in vitro fertilization (IVF) and embryo transfers. 

In April that year, Sohr had her fourth miscarriage. “Our fourth loss led us to interview surrogates while also diving deeper into why I would have lost a genetically tested, ‘great quality’ embryo,” she recalls. After a specialist requested that her fertility doctor run a slew of new tests looking for the cause of her recurrent pregnancy loss (RPL), only one came back positive, offering a clue as to what was going on: Ureaplasma.

Related: Here’s why we need an expanded definition of infertility

What is ureaplasma?

Ureaplasma spp. is a group of microscopic bacteria that colonize the urinary and reproductive tracts. They’re typically harmless, but an overgrowth can inflame healthy tissues like the endometrial lining, making pregnancy much more difficult. Ureaplasma infection may also play a role in preterm delivery. Infections may often be asymptomatic, but are generally treated with common antibiotics such as azithromycin or doxycycline. 

Ureaplasma is highly common. So why don’t more doctors routinely test for it?

“It was the only test that came back positive as to why I would have lost all of these babies—and possibly the reason why it was hard for me to conceive in the first place!” Sohr shares. She and her husband both took antibiotics for two weeks, tested again for ureaplasma to ensure the infection had cleared, and then transferred another embryo. She delivered a healthy baby boy 10 months later. 

Some statistics estimate that ureaplasma can be found in anywhere from 40% to 80% of women who are asymptomatic and sexually active. Ureaplasma is usually harmless in a large percentage of people who have the bacteria. But ureaplasma has also been identified as a potential contributor to chronic endometritis (an inflammation of the endometrial lining, which differs from endometriosis), and has been examined for its relationship to recurrent miscarriage. 

“I remember my doctor [the specialist, William Kutteh, MD, PhD, at Fertility Associates of Memphis] at the time telling me that 90% of patients he tests and finds [positive for ureaplasma] go on to have a healthy pregnancy. It was the only test that gave any indication to what my issue may be,” Sohr says. So why don’t more doctors routinely test for ureaplasma? 

Related: 12 signs you might be having fertility struggles

Recurrent pregnancy loss is relatively rare

For one, recurrent pregnancy loss is both rare and an incredibly challenging diagnosis, and there’s a dearth of evidence regarding treatment at this time, notes Sarah Hartwick Bjorkman, MD, an OB-GYN and Motherly’s Medical Advisor.

The American Society for Reproductive Medicine (ASRM) defines recurrent pregnancy loss as two or more failed clinical pregnancies. “Best estimates suggest that less than 5% of women will experience two consecutive miscarriages, and only 1% experience three or more,” says Dr. Bjorkman.

But if you’re part of that 5%, those recurrent losses can be devastating, regardless of how rare they are, and will probably send you searching for answers, like Sohr. While several different causes can be attributed to or correlated with RPL, many others are still unknown. One condition that’s considered a potential—though somewhat controversial—cause of RPL is chronic endometritis, which may also be related to ureaplasma infection. 

What is chronic endometritis?

Defined as chronic inflammation of the endometrial lining, chronic endometritis differs from endometriosis and has been shown to be fairly common in women with RPL. As many as 10% to 27% of those with RPL may have this condition. 

Chronic endometritis is most likely the result of an infection (from a variety of potential sources), and can usually be treated with antibiotics in most cases. Like ureaplasma infection, the condition is also usually without symptoms, but can present with low-grade inflammation. While there’s some evidence that chronic endometritis is related to ureaplasma infection, no direct causal link exists—yet. That’s the primary reason why routine testing or even prophylactic treatment with antibiotics isn’t widely recommended.

“No randomized trials have been published to date, and controversies remain concerning the impact of [chronic endometritis] on reproductive outcome, the patient population to screen, the treatment regimen, and the need for a biopsy to confirm resolution. Given the lack of conclusive evidence, several international societies do not include screening for [chronic endometritis] in their recommendations,” writes Hady El Hachem and colleagues in a 2017 article on RPL. 

“There may be some utility in treating [chronic endometritis], but this is not the standard of care and there is still a lot to learn about RPL and chronic endometritis,” Dr. Bjorkman shares.

Should you get tested for ureaplasma?

Because ureaplasma is just one of several potential causes of both chronic endometritis and RPL, without direct evidence supporting the link, it’s not high on most doctors’ lists to routinely test for. It also tends to be harmless in most cases—the majority of people who harbor the bacteria do not go on to develop disease, which means general screening likely isn’t warranted.

“It potentially falls under the umbrella of testing for chronic endometritis, but looking for soley ureaplasma isn’t something routinely done,” Dr. Bjorkman notes. “Those with recurrent pregnancy losses should talk with their OB provider and even ask for a referral to a reproductive endocrinology and infertility specialist, who can help guide them to pursue the best options for work-up and treatment that are available.”

If you’ve had recurrent losses or an especially tough time getting pregnant, it could be worth bringing up chronic endometritis and ureaplasma with your doctor. “This test brought us not only answers but our baby,” Sohr shares. “The process of trying to conceive [TTC] is a lonely, hard road, but I learned you have to be your own advocate and never give up hope.” 

Sources:

Cicinelli E, Matteo M, Tinelli R, et al. Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment. Reprod Sci. 2014;21(5):640-647. doi:10.1177/1933719113508817

El Hachem H, Crepaux V, May-Panloup P, Descamps P, Legendre G, Bouet PE. Recurrent pregnancy loss: current perspectives. Int J Womens Health. 2017;9:331-345. doi:10.2147/IJWH.S100817

Horner P, et al. Should we be testing for urogenital Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum in men and women? – a position statement from the European STI Guidelines Editorial Board [Abstract]. 2018. doi:10.1111/jdv.15146

Park HJ, Kim YS, Yoon TK, Lee WS. Chronic endometritis and infertility. Clin Exp Reprod Med. 2016;43(4):185-192. doi:10.5653/cerm.2016.43.4.185

Rittenschober-Böhm J, et al. First trimester vaginal Ureaplasma biovar colonization and preterm birth: Results of a prospective multicenter study. 2017. doi:10.1159/000480065