Perinatal and infant outcomes after assisted reproductive technology treatment for endometriosis alone compared with other causes of infertility: a data linkage cohort study
- PMID: 39672363
- DOI: 10.1016/j.fertnstert.2024.12.007
Perinatal and infant outcomes after assisted reproductive technology treatment for endometriosis alone compared with other causes of infertility: a data linkage cohort study
Abstract
Objective: To evaluate whether perinatal and infant outcomes differ between singleton births after assisted reproductive technology (ART) in women with endometriosis alone and those with other causes of infertility.
Design: Population-based data linkage cohort study.
Subjects: A total of 29,152 ART-conceived singleton births from 24,116 mothers, 2010-2017, New South Wales, Australia.
Exposure: Endometriosis, identified from the Australian and New Zealand Assisted Reproduction Database, hospital admissions, and dispensed medication records. The causes of infertility were categorized as follows: endometriosis alone; endometriosis plus other cause(s) of infertility; infertility other than endometriosis; and unstated cause of infertility. The endometriosis alone group was further classified using International Classification of Diseases, Tenth Revision, codes (N80.0-N80.9) into superficial, ovarian, deep, and other endometriosis.
Main outcome measures: Perinatal and infant outcomes, included preterm birth (<37 weeks), very preterm birth (<32 weeks), small for gestational age (SGA), large for gestational age, admission to neonatal intensive care unit, perinatal death, and infant hospitalization up to 2 years of age. Generalized estimating equations were used to investigate independent associations between endometriosis and study outcomes.
Results: Of the 29,152 ART-conceived singleton births, 19.9% (5,806/29,152) were from mothers with a diagnosis of endometriosis. Among these, 23.8% (1,379/5,806) were from mothers with an endometriosis alone diagnosis, and 76.2% (4,427/5,806) were from mothers with endometriosis plus other cause(s) of infertility. Three quarters (21,795/29,152) of births were from mothers without endometriosis and 5.3% (1,551/29,152) were from mothers with an unstated cause of infertility. After adjusting for maternal age at the time of birth, parity, ART treatment characteristics, gestational hypertension and diabetes, smoking, and socioeconomic status, there was no overall association between endometriosis and perinatal and infant outcomes. However, compared with women without endometriosis, those with deep endometriosis had a higher risk of preterm birth (adjusted relative risk, 1.75; 95% confidence interval, 1.12-2.75) and SGA (adjusted relative risk, 1.58; 95% confidence interval, 1.05-2.37).
Conclusion: Reassuringly, perinatal and infant outcomes are generally comparable for ART-conceived infants born to mothers with endometriosis alone and those with other causes of infertility when considered as a singular disease entity. Larger studies are needed to confirm the differential risk associated with endometriosis phenotypes; however, for patients with deep endometriosis undergoing ART, the risks of preterm birth and SGA may be increased. Clinicians should be aware of these potential risks.
Keywords: Assisted reproductive technology; data linkage study; endometriosis; infant outcomes; perinatal outcomes.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of Interests X.Z. has nothing to disclose. G.M.C. reports funding from the Australian National Health and Medical Research Council (NHMRC) Project Grant APP1127437 for the submitted work (the Fertility Society of Australia and New Zealand contracts the National Perinatal Statistics and Epidemiology and Statistics Unit [NPESU], University of New South Wales [UNSW], to prepare annual reports and benchmarking reports from the Australian and New Zealand Assisted Reproductive Technology Database; this is one of the data sets used in this study) and is the Director of the NPESU, UNSW, outside the submitted work. C.V. is an employee of Aristotle University of Thessaloniki (Greece) and affiliated with the University of New South Wales and the NPESU, UNSW (the NPESU manages the Australian and New Zealand Assisted Reproduction Database with funding support from the Fertility Society of Australia and New Zealand); reports honoraria and travel support from Merck Ltd, Merck Sharpe & Dohme, Ferring, Organon, and Gedeon-Richter; Fertility Society of Australia and New Zealand (since, 2019 member of the Board of Directors of the Fertility Society of Australia and New Zealand [unpaid role]); and “Doctors in ART” subcommittee of the Fertility Society of Australia and New Zealand (since, 2019 member of the Executive Board of the “Doctors in ART” subcommittee of the Fertility Society of Australia and New Zealand [unpaid role]); and is Shareholder of Virtus Health Ltd (a company providing ART services in multiple countries) until June 2022, outside the submitted work. S.K.Y.C. is an employee of Sanofi. B.G. reports funding from the Medical Research Future Fund outside the submitted work. C.H.M.N. reports funding from Commonwealth Department of Health and Aged Care, paid to institution (UNSW; salary) and Medical Research Future Fund paid to institution (Jean Hailes for Women’s Health; salary) for the submitted work; funding from Medical Research Future Fund paid to institution (UNSW); Chair of Special Interest Group for Clinical Trial Network Managers (SIGNet) Australian Clinical Trials Alliance (ACTA) (Unpaid); and CSL Vifor (formerly Vifor Pharma) previous employee, 2014–2018, outside the submitted work. J.A.A. reports funding from MRFF – Australian government, MSD, AGES, and Country Women’s Association of NSW; consulting fees Hologic, Vifor, and Gideon Richter; honoraria from MSD, Hologic, and Organon; travel support from Hologic and Gideon Richter; advisory board from Hologic, Vifor, and Gideon Richter; Past President of the Australasian Gynaecological Endoscopy & Surgery Society; Chair of the Australian Endometriosis Guideline Committee; and Past Chair and Medical Director of Endometriosis Australia outside the submitted work.
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