1. In a prospective cohort, a diagnosis of endometriosis was associated with a higher risk of subsequent infertility.
2. This association was only statistically significant for women under 35 years old.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Endometriosis, a condition in which endometrial tissue exists outside of the uterus and affects pain and scarring, affects an estimated 5-10 percent of women. Endometriosis is the leading cause of missed work in reproductive-age women and is associated with a range of morbidities, including pelvic pain, ovarian cysts and an increased risk of infertility. The prevalence of endometriosis is higher (20-30%) among infertile women and represents the most common pathologic finding among infertile women who undergo laparoscopic exam. Possible mechanisms through which endometriosis might affect infertility include impairment in endometrial receptivity, oocyte function or tubal disease from scarring. However, a causal, temporal link between endometriosis and infertility has not been established. In this study, researchers used prospective data from the Nurses Health II cohort study to better evaluate the temporal relationship between a history of confirmed endometriosis and infertility.
Women with a history of laparoscopically confirmed endometriosis experienced a two-fold increased risk for subsequent infertility compared to women without endometriosis, although this risk was only significant for women under the age of 35. Strengths of this study included prospective data collection and large, well-characterized cohort. This study was unable to assess intention to conceive, and therefore may have missed some cases of infertility, however this would not be expected to result in systematic bias or confounding. Replication of findings in additional prospective investigations would support the temporal relationship between endometriosis and infertility risk and further qualify the endometriosis-associated risk of infertility.
Relevant Reading: Endometriosis and Infertility: A Cause-Effect Relationship?
Stacey Missmer, PhD, talks to 2 Minute Medicine: Division of Reproductive Medicine, Brigham & Women’s Hospital, Harvard Medical School and Harvard School of Public Health, Boston, MA
“As we’ve known for many years, women with endometriosis are at greater risk for infertility compared to women without endo. What this new study confirms, however, is that endometriosis and infertility should not be conflated. The majority of women with endometriosis do not experience infertility and the majority do become pregnant and are able to build the families that they desire. The key next step in endometriosis discovery is identifying that minority of women with endometriosis who are at higher risk of infertility. We can then target treatments directly to the biology causing infertility in women with endometriosis. We can also attempt to identify the women at risk early so that they can access fertility treatment and perhaps fertility preservation early.”
In-Depth [prospective cohort]: Researchers used data from the Nurses’ Health Study II, a prospective cohort of 58 427 married, premenopausal female nurses <40 years old. The incidence of infertility, defined as inability to conceive after >12 months of unprotected intercourse, was compared between women with laparoscopically confirmed endometriosis (n=3537) and controls who did not have a diagnosis of endometriosis. Multivariate-adjusted Cox proportional hazards regression models were used to calculate risk.
In multivariate-adjusted models, women with a history of endometriosis were more likely to be subsequently diagnosed with infertility compared to controls (HR = 2.11, 95%CI= 0.74-2.54). The relationship between endometriosis and infertility was modified by age and BMI whereby the association of endometriosis with infertility was not evident in women >35 years of age after adjusting for parity (p-interaction < 0.01) or in obese women (p-interaction = 0.02).
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