Clinical Context

Endometriosis is an inflammatory disease with heterogeneous presentations affecting 10% to 15% of women of reproductive age. Findings of previous studies are conflicting regarding implications of endometriosis for pregnancy outcomes. A recent multicenter cohort study by Marcellin and colleagues evaluated over 1300 women with singleton pregnancies in France from February 4, 2016 to June 28, 2018, with final follow-up in July 2019. This study was published in the February 1, 2021 issue of JAMA Network Open.^[1]

Using non-modifiable risk factors, researchers found that modifying pregnancy monitoring strategies beyond the normal protocols or may not be warranted in cases of endometriosis. Additionally, there was no correlation discovered between a mother's endometriosis phenotype and preterm birth rate.

These novel results by Marcellin and colleagues have incited a potential interest in further studies related to pregnancy risk and endometriosis that would be valuable to the healthcare team.

Study Synopsis and Perspective

Researchers evaluating whether endometriosis is linked with preterm birth found no such association in a multicenter cohort study of more than 1300 women.

These new findings, which were published February 1 in JAMA Network Open,^[1] suggest that changing monitoring strategies to prevent preterm birth for women with the disease may not be necessary.

The research team, led by Louis Marcellin, MD, PhD, with the department of obstetrics and gynecology at Université de Paris, in Paris, France, also found that disease phenotype or whether the preterm birth was induced or spontaneous did not appear to alter the result.

Those results differ from previous research. Data on the phenotypes and their link with preterm birth have been scarce, but previous studies have shown the risk for preterm birth is more pronounced in women who have deep endometriosis than in women with ovarian endometriosis.

Marcellin told Medscape Medical News, "Little is known about the impact of endometriosis on obstetric outcomes. In contrast to previous studies, we reported no differences in the risk for preterm delivery between women with endometriosis (34 of 470 [7.2%]) and those without endometriosis (53 of 881 [6.0%]), even when adjusted for multiple factors."

The authors accounted for mother's age, body mass index (BMI) before pregnancy, birth country, number of times the woman had given birth, previous cesarean delivery, and history of preterm birth. After adjusting for potential confounders, endometriosis was not associated with preterm birth (adjusted odds ratio [aOR] 1.07 [95% CI: 0.64, 1.77]).

The researchers found no differences among preterm births based on a mother's endometriosis phenotype. Those phenotypes include isolated superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), and deep endometriosis (DE).

"Monitoring pregnancy beyond the normal protocols or changing management strategies may not be warranted in cases of endometriosis," Marcellin said.

More research on endometriosis' potential link to birth outcomes is needed.

An expert not involved with the study said the new paper highlights important new avenues of research but should not be seen as the final word on the connection between endometriosis and preterm birth.

Of the 1351 study participants (mean age, 32.9 ± 5 years) who had a singleton delivery after 22 weeks of gestation, 470 were assigned to the endometriosis group, and 881 were assigned to the control group.

The authors concluded, "Pregnant women with endometriosis should not be considered to have an exceptionally high risk for preterm birth. However, further studies are needed to examine the potential for other adverse perinatal outcomes or specific but rare complications."

Daniela Carusi, MD, said the difficulty with the study's design is that "premature birth is not one problem or one disease."

Many very different problems can all end with premature birth. Sometimes it's an infection or inflammation or bleeding in the uterus or hypertension in the mother, for example, and all those things can lead to a preterm birth, she explained.

"This study inherently lumps all those things together," said Carusi, who is director of surgical obstetrics and placental abnormalities in the department of obstetrics and gynecology at Brigham and Women's Hospital in Boston, Massachusetts. "It's quite possible endometriosis can have a big impact in one of those areas and no impact in the other areas, but the study design wouldn't be able to pick that up."

In an accompanying commentary,^[2] Liisu Saavalainen, MD, PhD, and Oskari Heikinheimo, MD, PhD, both with the department of obstetrics and gynecology, and Helsinki University Hospital, in Helsinki, Finland, wrote that several previous studies have suggested that women with endometriosis have a slightly higher risk for preterm birth.

Those studies were mostly retrospective and differed in the way they classified endometriosis and the way they selected patients, the editorialists wrote. Also, most women in these studies typically had subfertility, they added.

The study by Marcellin and colleagues differs from previous related research in that it was prospective and assessed the risk for preterm delivery in women with endometriosis and women without endometriosis from several maternity centers in France. The women with endometriosis were classified according to the severity of their disease.

The editorialists wrote, "[T]he novel results by Marcellin et al challenge the findings of most previous studies on this topic. These results are valuable and comforting. However, they are also likely to trigger new studies on the pregnancy risks associated with different types of endometriosis That is good news."

Carusi said the study was well done and included a notably large size. Further complimenting the research, she said it is important to talk about this little-discussed pregnancy complication.

There has been much more focus for women with endometriosis and their physicians on getting pregnant and on talking about the length of their term, she said.

The study leaves some things unanswered.

The study was funded by research grants from the French Ministry of Health and was sponsored by the Département de la Recherche Clinique et du Développement de l'Assistance Publique–Hôpitaux de Paris. Carusi reports no relevant financial relationships. A coauthor of the study reports personal fees from Bioserinity and Ferring outside the submitted work. No other disclosures were reported.

Clinical Implications

• After adjusting for risk factors, endometriosis was not associated with preterm birth, overall or based on disease phenotype.
• For women with endometriosis, monitoring pregnancy beyond normal protocols or changing management strategies may not be warranted.
• Implications for the Healthcare Team: Further studies are needed to examine the potential for other adverse perinatal outcomes or specific but rare complications.

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