Endometriosis Linked to Adverse
Pregnancy Outcomes

Ricki Lewis, PhD

August 08, 2019

Endometriosis is associated with increased risk for specific adverse pregnancy outcomes, including spontaneous abortion, ectopic pregnancy, and preeclampsia, according to results of a study published today in Obstetrics and Gynecology.

Endometriosis is often associated with pelvic pain and infertility, but more than 80% of affected women do become pregnant. Leslie V. Farland, ScD, from the University of Arizona, Tucson, and colleagues investigated the association of endometriosis with adverse pregnancy outcomes.

Endometrial-like tissue growing outside the uterus has been hypothesized to compromise pregnancy in several ways: decreasing response to progesterone, damaging oocytes, reducing uterine contractility, interfering with placentation, and inducing inflammation. All are associated with increased risk for gestational diabetes, hypertensive disorders of pregnancy, and preterm birth. 

Small studies with participants from fertility clinics may have obscured the risk from endometriosis alone. Protocols that recruited women hospitalized with endometriosis may have overrepresented the most severe cases. Heterogeneous populations and differing definitions of endometriosis have also potentially compromised past investigations. The current study sought to avoid some of these potential flaws.

The researchers used the Nurses' Health Study II to investigate the relationship between endometriosis diagnosed laparoscopically and adverse pregnancy outcomes. The ongoing prospective cohort study follows 116,429 female US registered nurses aged 25 to 42 years when they enrolled in 1989. Questionnaires that probe lifestyle, reproductive information, and health were  self-administered at baseline and every 2 years. Beginning in 1993, the questionnaires asked women about laparoscopically-confirmed endometriosis.

Participants reported 196,722 pregnancies in a detailed questionnaire focused on pregnancy in 2009. The researchers compared pregnancy outcomes  among women with (8875 pregnancies; 4.5%) and without a history of confirmed endometriosis.

Outcomes were spontaneous abortion, ectopic pregnancy, stillbirth, gestational diabetes, hypertensive disorders of pregnancy (preeclampsia or gestational hypertension), preterm birth, and low birth weight.

Endometriosis was associated with elevated risk for spontaneous abortion (relative risk [RR], 1.40; 95% confidence interval [CI], 1.31 - 1.49); ectopic pregnancy (RR, 1.46; 95% CI, 1.19 - 1.80), gestational diabetes (RR, 1.35; 95% CI, 1.11 - 1.63), and hypertensive disorders (RR, 1.30; 95% CI, 1.16 - 1.45).

The researchers term the association with stillbirth "a suggestion" because it was not as strong as the other factors, and the sample size was smaller (RR, 1.27; 95% CI, 1.01 - 1.60). They defined stillbirth as fetal loss after 20 gestational weeks.

The covariates considered were age, parity, oral contraceptive use, infertility history, age at menarche, menstrual cycle characteristics, smoking status, and body mass index.

Supplemental analyses found that increased risk for spontaneous abortion associated with laparoscopically-diagnosed endometriosis was seen more in women younger than 35 years experiencing their first pregnancy; the relation with ectopic pregnancy was stronger for pregnancies in women without a history of infertility; the relation with ectopic pregnancy was stronger in pregnant women with no history of infertility; and relation with gestational diabetes was stronger among women who were multiparous, under age 35 years, and without infertility.

The researchers conclude by stating, "Women with endometriosis may represent a unique population of women at greater risk for adverse outcomes across pregnancy and birth." They suggest further investigation of the relationship between endometriosis and adverse pregnancy outcomes considering maternal age, parity, and infertility history, as revealed in the supplemental analyses.

"Elucidating mechanisms of association and possible pathways for intervention or screening procedures will be critical to improve the health of women with endometriosis and their children," the researchers add.

A limitation of the study is that the timing of endometriosis diagnosis in relation to pregnancy is not known for pregnancies before 1989. The investigation also did not consider placenta previa, placenta accreta, or cervical insufficiency ("incompetent cervix"), which may have affected pregnancy outcome.

The study was supported by the National Institutes of Health. Farland has disclosed no relevant financial relationships. Several authors have disclosed financial relationships with a variety of companies including UpToDate, the National Institutes of Health, UK MRC, NIHR, Wellbeing of Women, Roche Diagnostics, AstraZeneca, Ferring, AbbVie, Nordic Pharma, the Marriott Family Foundation, American Society for Reproductive Medicine, World Endometriosis Society, and the World Endometriosis Research Foundation. A complete list is available at the journal's website.

Obstet Gynecol. Published online August 8, 2019. Abstract

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