Cohort study reaffirms link between endometriosis and pregnancy loss

Published 07 February 2023

A large Danish population study of almost 30,000 women diagnosed with endometriosis between 1977 and 2017 (and matched with 300,000 controls) has found an association with pregnancy loss and recurrent pregnancy loss, but also that the association strengthened with the increasing number of miscarriages.

Women with endometriosis are not only less likely to get pregnant and more likely to experience pregnancy loss, but their chance of losing a baby also increases for each subsequent pregnancy, according to data from a large nationwide historical cohort study. These findings, reported by a group from the University of Copenhagen, are from the first study of its size to investigate the number of pregnancy losses linked to endometriosis.(1)

Based on data from more than 29,000 women with this chronic inflammatory disease, the authors found endometriosis to be associated with pregnancy loss and recurrent pregnancy loss, a link which strengthened with an increasing number of miscarriages.

The authors report that many previous studies have found associations between pregnancy loss and endometriosis. However, follow-up periods in these studies were short, the focus was usually pregnancy outcomes after medical/surgical therapy, and overall findings were inconsistent – indeed, some studies failed to find an association. For example, a large meta-analysis from 2017 did identify an increased risk of pregnancy loss in women with the disease, but none of the studies analysed investigated an association with more than one miscarriage.(2)

This new Danish study was thus designed to establish if endometriosis was associated with both pregnancy loss and recurrent pregnancy loss. Data used was from national health registers in Denmark and based on 29,563 women born between 1957 and 1997 and diagnosed with endometriosis between 1977 and 2017. All were age-matched with 295,630 women a diagnosis of endometriosis. Primary outcomes were the number of pregnancy loss events (0, 1, 2 and 3 or more), secondary outcomes were predefined types of pregnancy loss, and number of events was defined as the spontaneous demise of a pregnancy prior to 22 weeks’ gestation.

In addition, the researchers created seven endometriosis subgroups to explore if these drove any potential association. The groups were women diagnosed in each of the four decades between 1977 and 2017, women with severe endometriosis, those with adenomyosis, and with adenomyosis only.

Results first demonstrated that there were more never-pregnant women among those with endometriosis than among those without the disease (19.8% vs 17.5%). A total of 18.9% of ever-pregnant women with endometriosis had one pregnancy loss vs 17.3% of women without the disease; and the more babies they lost, the more the odds increased in comparison with women without endometriosis - with 3.9% vs 3.5% experiencing two events, and 2.1% vs 1.5% experiencing three or more (OR: 1.13; 1.18 and 1.44 respectively). When adjusted for the number of times a woman had been pregnant, the corresponding results were even higher (1.37; 1.75; and 2.57 respectively).

The authors write that a strength of their study is its longitudinal design over decades of observation, which makes it ‘superior to previous studies’, and that it includes women who’ve never given birth. They add that the theory that immunological factors might influence the association between endometriosis and pregnancy loss appears confirmed by this study. Recently published data have suggested one possible explanation in that each pregnancy loss might increase the likelihood of a maternal immune defect.(3)

The indication that adenomyosis on its own was strongly linked to pregnancy loss (especially with two and three/or more losses) shows that adenomyosis is an important factor, report the authors, who add that future studies should distinguish between adenomyosis and endometriosis.

1. Boje AD, Egerup P, Westergaard D, et al. Endometriosis is associated with pregnancy loss: A nationwide historical cohort study. Fertil Steril 2023;
2. Zullo F, Spagnolo E, Saccone G, et al. Endometriosis and obstetrics complications: a systematic review and meta-analysis. Fert Steril 2017; 108; 667-672. https://doi.org/10.1016/j.fertnstert.2017.07.019
3. Bortoletto P, Lucas ES, Melo P, et al. Miscarriage syndrome: Linking early pregnancy loss to obstetric and age-related disorders. EBio Medicine 2022; 81. doi.org/10.1016/j.ebiom.2022.104134

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