Endometriosis, especially mild disease: a risk factor for miscarriages

Alexandra Sabrina Kohl Schwartz; Monika Martina Wölfler; Vera Mitter; Martina Rauchfuss; Felix Haeberlin; Markus Eberhard; Stephanie von Orelli; Bruno Imthurn; Patrick Imesch; Daniel Fink; Brigitte Leeners

doi:10.1016/j.fertnstert.2017.08.025

Endometriosis, especially mild disease: a risk factor for miscarriages

Kohl Schwartz AS, Wölfler MM, Mitter V, Rauchfuss M, Haeberlin F, Eberhard M, von Orelli S, Imthurn B, Imesch P, Fink D, Leeners B

Published November 2017 Fertility and Sterility, 108(5), 806-814.e2

DOI 10.1016/j.fertnstert.2017.08.025 PMID 29079275

RRM Academy Synopsis

Endometriosis linked to more miscarriages, especially mild disease

Women with surgically confirmed endometriosis had more miscarriages than matched women without it, in a cross-sectional study of 143 women in each group who had been pregnant. Miscarriage ended about 36 of 100 pregnancies with endometriosis and 22 of 100 without. The gap held in women with trouble conceiving and grew in mild disease.

Miscarriage: Women with endometriosis, 35.8 in 100; Women without endometriosis, 22.0 in 100. Source: Kohl Schwartz AS et al., 2017, PMID 29079275.

Study at a glance, cross-sectional study: Women with endometriosis had more miscarriages than matched women without it — Study at a glance, cross-sectional study of 143 women in each group: Women with endometriosis had more miscarriages than matched women without it. Source: Kohl Schwartz AS et al., 2017, PMID 29079275.

Key Findings

Miscarriage rates were 35.8% (95% CI 29.6%–42.0%), 86 of 240 pregnancies, in women with endometriosis and 22.0% (16.7%–27.0%), 59 of 268 pregnancies, in control women.
After adjustment for age, BMI, smoking and subfertility, the incidence rate ratio for miscarriage was 1.97 (95% CI 1.41–2.75) in women with endometriosis versus control women.
Among subfertile women, miscarriage rates were 50.0% (40.7%–59.4%) with endometriosis and 25.8% (8.5%–41.2%) in controls. Among fertile women, they were 24.5% (16.3%–31.6%) and 21.5% (15.9%–26.8%).
Stage I and II disease carried a miscarriage rate of 42.1% (32.6%–51.4%), stage III and IV 30.8% (22.6%–38.7%), and control women 22.0% (16.7%–27.0%).
Three or more miscarriages occurred in 7 of 143 women with endometriosis (4.9%) and 4 of 143 control women (2.8%), P = .874.

Interpretation

This retrospective cohort study compared women who had been pregnant, with and without surgically confirmed endometriosis. Researchers recruited the women from hospitals and private practices in Switzerland, Germany and Austria. Women with endometriosis had fewer births overall. They had 152 children, against 204 among control women. The authors adjusted for age, weight, smoking and trouble getting pregnant. The authors note that undiagnosed endometriosis in some control women could have led to an overestimate of the difference. The findings support larger studies of miscarriage risk in endometriosis.

RRM Context

Restorative reproductive medicine looks for a cause when a pregnancy ends in miscarriage. The study links surgically confirmed endometriosis with miscarriage. The link was strongest in mild disease. A Canadian registry study the authors cite found a similar pattern, with an odds ratio of 1.89 (95% CI 1.23–2.93) in 784 women with endometriosis and 30,284 control women. The authors point to inflammation and progesterone resistance as possible causes.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

To investigate the prevalence of miscarriage in women with endometriosis (WwE) compared with disease-free control women (CW).

Design

Cross-sectional analysis nested in a retrospective observational study (n = 940).

Setting

Hospitals and associated private practices.

Patients

Previously pregnant women (n = 268) within reproductive age in matched pairs.

Interventions

Retrospective analysis of surgical reports and self-administered questionnaires.

Main Outcome Measures

Rate of miscarriage, subanalysis for fertility status (≤12 vs. >12 months' time to conception), endometriosis stages (revised American Society of Reproductive Medicine classification [rASRM] I/II vs. III/IV) and phenotypic localizations (superficial peritoneal, ovarian, and deep infiltrating endometriosis).

Results

The miscarriage rate was higher in WwE (35.8% [95% confidence interval 29.6%-42.0%]) compared with CW (22.0% [16.7%-27.0%]); adjusted incidence risk ratio of 1.97 (95% CI 1.41-2.75). This remained significant in subfertile WwE (50.0% [40.7%-59.4%]) vs. CW (25.8% [8.5%-41.2%]) but not in fertile WwE (24.5% [16.3%-31.6%]) vs. CW (21.5% [15.9%-26.8%]). The miscarriage rate was higher in women with milder forms (rASRM I/II 42.1% [32.6%-51.4%] vs. rASRM III/IV 30.8% [22.6%-38.7%], compared with 22.0% [16.7%-27.0%] in CW), and in women with superficial peritoneal endometriosis (42.0% [32.0%-53.9%]) compared with ovarian endometriosis (28.6% [17.7%-38.7%]) and deep infiltrating endometriosis (33.9% [21.2%-46.0%]) compared with CW (22.0% [16.7%-27.0%]).

Conclusions

Mild endometriosis, as in superficial lesions, is related to a great extent of inflammatory disorder, possibly leading to defective folliculogenesis, fertilization, and/or implantation, presenting as increased risk of miscarriage.

Trial Registration

NCT02511626.

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Topics

Endometriosis › Fertility and Outcomes › Conception After Excision · Pregnancy › Early Pregnancy › Miscarriage · Infertility › Recurrent Pregnancy Loss › Anatomic Causes

Alexandra Sabrina Kohl Schwartz, Monika Martina Wölfler, Vera Mitter, Martina Rauchfuss, Felix Haeberlin, Markus Eberhard, Stephanie von Orelli, Bruno Imthurn, Patrick Imesch, Daniel Fink, Brigitte Leeners

Alex Schwartz, A Schwartz, M Wölfler, V Mitter, M Rauchfuss, F Haeberlin, M Eberhard, S Orelli, B Imthurn, Pat Imesch, P Imesch, Dan Fink, Danny Fink, D Fink, B Leeners

PMID 29079275 29079275 DOI 10.1016/j.fertnstert.2017.08.025 10.1016/j.fertnstert.2017.08.025 Kohl Schwartz et al. 2017, Kohl Schwartz 2017

Endometriosis, especially mild disease: a risk factor for miscarriages

Endometriosis linked to more miscarriages, especially mild disease

Key Findings

Interpretation

RRM Context

Abstract

Read the guides

Topics

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