Perinatal and infant outcomes following ART treatment for endometriosis alone compared with other causes of infertility: a data linkage cohort study

Objective: To evaluate whether perinatal and infant outcomes differ between singleton births following 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 (ANZARD), hospital admissions and dispensed medication records. Cause of infertility was categorised as: 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 ICD-10 codes (N80.0-80.9) into superficial, ovarian, deep, and other endometriosis.

Main outcome measures: Perinatal and infant outcomes, including preterm birth (< 37 weeks), very preterm birth (< 32 weeks), small-for-gestational-age (SGA), large-for-gestational-age (LGA), admission to neonatal intensive care unit, perinatal death, and infant hospitalisation up to 2 years of age. Generalized estimating equations (GEE) 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) from mothers with an endometriosis alone diagnosis and 76.2% (4,427/5,806) from mothers with endometriosis plus other cause(s) of infertility. There were 74.8% (21,795/29,152) births from mothers without endometriosis and 5.3% (1,551/29,152) 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 to women without endometriosis, those with deep endometriosis had a higher risk of preterm birth (adjusted relative risk [aRR] 1.75, 95% confidence interval [CI] 1.12-2.75) and SGA (aRR=1.58, 95% CI 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 but for patients with deep endometriosis undergoing ART, the risks of preterm birth and SGA may be increased. Clinicians should be aware of the potential of these risks.