Endometriosis poses increased risk of preterm birth

Women with endometriosis at first singleton pregnancy are about 1.5 times more likely to have a preterm birth (PTB), according to a meta-analysis in Obstetrics & Gynecology Science.

The investigators, led by Sun-Gyeong Kim, MD, of the Department of Obstetrics and Gynecology at the University of Soonchunhyang College of Medicine in Cheonan, Korea, identified six studies published between March 1994 and February 2016 that met inclusion criteria. Among 50,472 pregnancies, 39,659 had endometriosis.

The odds ratio for PTB was 1.473 (95% confidence interval, 1.216 to 1.785).

Based on the findings, “it is worthy for obstetrics to increase the careful inspection in women with endometriosis,” the authors state.

Because abnormal endometrium may cause decidual impairment and atypical placentation during pregnancy, pregnancy outcomes may be adversely impacted.

Expression of local and systemic inflammatory cytokines, such as interleukin 6, interleukin 1 beta and tumor necrosis factor alpha, is also implicated in the endometrium of endometriosis and trophoblast in PTB.

The 6 studies for meta-analysis were a Japanese retrospective study from 1995-2011 with 108 patients; a Canadian cohort study from 1997-2008 comprising 31,068 patients; a Swedish population-based prospective cohort from 1992-2006 of 13,090 patients; an Italian multicenter, observational and cohort study from 2010-2013 of 1,550 patients; a Chinese retrospective cohort study 1995-2013 of 498 patients; and a US retrospective cohort study from 2004-2008 with 4,098 patients.  

Four of the 6 trials that assessed the adverse effect of endometriosis on pregnancy outcome by comparing women with endometriosis with women without endometriosis concluded that pregnant women with endometriosis are significantly linked with increased risk of PTB (< 37 weeks’ gestation).

Some of the studies considered included women with clinical endometriosis for whom a definitive diagnosis was not determined, while other studies encompassed women who were pregnant via assisted reproductive technology (ART), “which in itself is a risk factor for preterm birth,” the authors note.

However, the included Swedish studies found an increased risk of PTB in women with endometriosis concluded that the relative risk remained unchanged when taking into account ART: 1.24 with ART and 1.37 without ART.

The Italian study found that prior to their first pregnancy, all women had a confirmed pathologic diagnosis of endometriosis by surgical removal of the lesions, characterized as ovarian (35%), mixed ovarian and peritoneal (25%), mixed ovarian and deep (21%) and deep lesions (19%). But data as to the interval between surgery and first pregnancy, as well as any additional treatment, were not collected.

The US study concluded that the rate of obstetric complications was dramatically higher during first pregnancy compared to subsequent pregnancy. This finding suggests “a protective role of pregnancy in endometriosis towards second pregnancies, perhaps through immunological and hormonal modification,” the authors of the meta-analysis commented.

Still, ART and subsequent multiple pregnancies associated with endometriosis are risk factors for PTB. The authors also pointed out that removal and simultaneous additional treatment for endometriosis may improve pregnancy outcomes.

A study limitation, however, is that ART adjustment was not performed.

To clarify the effects of endometriosis on PTB, the authors advocate more subspecialized classification of the chronic disease: removal and simultaneous additional treatment, order of diagnosis, availability and methods of ART, primiparous versus multiparous, and the time interval between surgery and first pregnancy.

Also needed is an accelerated international effort to understand the etiology of endometriosis, which afflicts roughly 6% to 10% of women of reproductive age, explore preventative methods of PTB, and offer personalized treatment options.