Congenital heart disease in a singleton pregnancy conceived through assisted reproductive technology

To evaluate the risk of congenital heart disease (CHD) in offspring of singleton primiparous pregnancies conceived via assisted reproductive technology (ART).

Retrospective, nationwide cohort study.

Patients with singleton pregnancies who delivered between 2017 and 2021.

Singleton pregnancies conceived by natural conception, intrauterine insemination, fresh embryo transfer, and frozen embryo transfer were compared.

The primary outcome was the rate of CHDs among offspring. Secondary outcomes included CHD subtype distribution, sex differences, and perinatal outcomes.

Among 651,964 mother-child pairs, 6.19% were diagnosed with CHD, with the higher incidence in frozen embryo transfer (10.4%). Frozen embryo transfer, fresh embryo transfer and intrauterine insemination (IUI) exhibited 54.5%, 29.6%, and 21.5% increased risk of CHD compared with natural conception. Frozen embryo transfer was associated with an increased risk of right outflow malformations after adjusting for confounding factors. Septal defects and patent ductus arteriosus were increased in both the IUI and embryo transfer groups, with the highest prevalence observed in the frozen embryo transfer group. Findings within each sex subgroup were consistent with the overall trends. In natural conceptions, male fetuses showed a significantly higher risk of conotruncal defects and left ventricular outflow tract anomalies, but a lower risk of patent ductus arteriosus, compared with female fetuses. However, in IUI and embryo transfer pregnancies, no significant sex-specific differences were observed across the types of CHDs.

Singleton pregnancies achieved through IUI and ART, especially frozen embryo transfer, are associated with a higher incidence of CHD in offspring in this population-based study. Sex difference no longer had an impact on the CHD risk in IUI or ART. The findings should be communicated to patients undergoing pre-ART counseling. Because our outcome definition was based on claims data including mild lesions and early neonatal diagnoses, the absolute prevalence of CHD may appear higher than registry-based estimates.