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Endometriosis and Risk of Adverse Pregnancy Outcomes

Farland, Leslie V. ScD; Prescott, Jennifer PhD; Sasamoto, Naoko MD, MPH; Tobias, Deirdre K. ScD; Gaskins, Audrey J. ScD; Stuart, Jennifer J. ScD; Carusi, Daniela A. MD, MPH; Chavarro, Jorge E. MD, ScD; Horne, Andrew W. MB ChB, PhD; Rich-Edwards, Janet W. ScD; Missmer, Stacey A. ScD

doi: 10.1097/AOG.0000000000003410
Contents: Endometrioisis: Original Research
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OBJECTIVE: To investigate the relationship between endometriosis and adverse pregnancy outcomes.

METHODS: Women between ages 25 and 42 years in 1989 (n=116,429) reported detailed information on pregnancies and reproductive health at baseline and every 2 years thereafter in the Nurses' Health Study II, a cohort study. In 2009, they completed a detailed, pregnancy-focused questionnaire. A total of 196,722 pregnancies were reported. Adverse pregnancy outcomes included spontaneous abortion, ectopic pregnancy, stillbirth, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (preeclampsia or gestational hypertension), preterm birth, and low birth weight. We estimated the relative risks (RRs) and 95% CIs of adverse pregnancy outcomes comparing pregnancies in women with and without a history of laparoscopically confirmed endometriosis using multivariable log-binomial regression, with generalized estimating equations to account for multiple pregnancies per woman.

RESULTS: Endometriosis was associated with a greater risk of pregnancy loss (spontaneous abortion: RR 1.40, 95% CI 1.31–1.49; ectopic pregnancy: RR 1.46, 95% CI 1.19–1.80). Endometriosis was also associated with a greater risk of GDM (RR 1.35, 95% CI 1.11–1.63) and hypertensive disorders of pregnancy (RR 1.30, 95% CI 1.16–1.45).

CONCLUSIONS: We observed an association between laparoscopically confirmed endometriosis and several adverse pregnancy outcomes. Future research should focus on the potential biological pathways underlying these relationships to inform screening or preventive interventions.

Women with laparoscopically confirmed endometriosis had greater risk of adverse pregnancy outcomes.

Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona; the Channing Division of Network Medicine, the Department of Obstetrics, Gynecology, and Reproductive Biology, the Division of Preventive Medicine, and the Division of Women's Health, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, and the Department of Nutrition and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; the MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, Scotland; and the Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, Michigan.

Corresponding author: Leslie V. Farland, ScD, University of Arizona, Tucson, AZ; email:

Supported by grants from the National Institutes of Health [UM1 CA176726, HD52473, T32DK007703, T32HD060454, K01DK103720, K99ES026648]. The authors assume full responsibility for analyses and interpretation of these data.

Financial Disclosure Daniela A. Carusi has received money paid to her from UpToDate. Jorge E. Chavarro received money paid to his institution from the National Institutes of Health. Andrew W. Horne receives grant funding from the UK MRC, NIHR, Wellbeing of Women, Roche Diagnostics, Astra Zeneca, and Ferring. He has carried out consultancy work for AbbVie, Ferring, Roche Diagnostics, and Nordic Pharma. Stacey A. Missmer has received money paid to her institution from the NIH: two R01-funded grants; one focused on endometriosis but unrelated to the data or project presented in this manuscript; one focused on infertility (again, unrelated to this manuscript). She has received a consulting fee for service as an Advisory Board member for the Endometriosis Disease Burden and Endometriosis International Steering Committee working groups of AbbVie, Inc. No connection with the data or project presented in this manuscript. The Marriott Family Foundation Funding supports the research core of the Boston Center for Endometriosis, for which she is the Scientific Director. No connection with the data or project presented in this manuscript. As the Chair of the Endometriosis SIG for ASRM, Treasurer of the World Endometriosis Society, and Secretary of the World Endometriosis Research Foundation, she has attended many professional meetings for which her registration was either paid or forgiven and/or for which travel to provide lectures as an invited speaker was either paid de novo or reimbursed to her institution. These talks/responsibilities at professional meetings was not related to this project presented in this manuscript. The other authors did not report any potential conflicts of interest.

Presented at the American Society for Reproductive Medicine, October 6–10, 2018, Denver, Colorado.

The authors thank the participants of the Nurses' Health Study II for their valuable contributions and participation in research for the past 30 years.

Each author has confirmed compliance with the journal's requirements for authorship.

Peer reviews and author correspondence are available at

© 2019 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.