Infertility and Risk of Congenital Anomalies: A Population‐Based Cohort Study

BACKGROUND: Fertility treatments have been associated with an increased risk of congenital anomalies. Most studies have compared births conceived through fertility treatment with unassisted conceptions; consequently, these estimates reflect the combined effects of fertility treatment and the underlying infertility, potentially resulting in confounding by indication. OBJECTIVES: To estimate the association between infertility, independent of fertility treatment, and the risk of congenital anomalies. METHODS: This population-based cohort study included all live births and stillbirths at ≥ 20 weeks' gestation to women aged 15-50 in Ontario, Canada, 2006-2021. Infertility without treatment was defined as a history of one or more infertility consultations with a physician within 2 years before conception, in the absence of fertility treatment. Modified Poisson regression generated relative risks (RR) adjusted for maternal age, income quintile, rurality, pre-existing comorbidities, and smoking, alcohol use, and substance use during pregnancy. RESULTS: Of the 1,415,324 deliveries, the prevalence of congenital anomalies was 5.3% in unassisted conception and 5.9% among births to women with infertility who did not use fertility treatment. A small increase in risk was observed for any congenital anomaly (RR 1.12, 95% confidence interval CI 1.09, 1.14). Among organ system anomalies, the highest relative risks were observed for eye anomalies (0.11% vs 0.14%; RR 1.22, 95% CI 1.03, 1.45) and ear, face, and neck anomalies (0.06% vs 0.08%; RR 1.19, 95% CI 1.05, 1.35). Among specific anomalies, the highest relative risk was observed for other penile malformations (0.03% vs 0.04%; RR 1.41, 95% CI 1.09, 1.83). CONCLUSIONS: Although the overall risk of congenital anomalies was low, infants born to women with infertility who did not use fertility treatment had small increased risks of any congenital anomaly, selected organ system anomalies, and specific anomalies compared with infants born from unassisted conceptions.