Sex-specific differences in head circumference of term singletons after assisted reproductive technology: a multicentre study in Japan

Research question: Does fertility treatment, specifically assisted reproductive technology (ART), affect head circumference in term singletons?Design: A total of 32,651 women who delivered at term at 12 maternity hospitals in Japan between 2010 and 2018 were included in the analysis; of these, 1941 (5.9%) and 2984 (9.1%) women conceived through ART and non-ART fertility treatments (timed intercourse, ovulation induction or artificial insemination), respectively. The study evaluated the adjusted odds ratios of head circumference >= 90th percentile stratified by infant sex and type of ART procedure after adjusting for covariates, with natural conception as the reference group.Results: ART significantly increased the risk of head circumference >= 90th percentile (adjusted odds ratio 1.56 [95% confidence interval 1.25-1.96]), whereas non-ART fertility treatment did not increase the risk (1.14 [0.92-1.42]). This increased risk of head circumference >= 90th percentile was observed exclusively in male neonates (1.73 [1.33-2.26]) and not in female neonates (1.18 [0.76-1.85]) in the ART group. Frozen embryo transfer (FET), FET in a hormone replacement cycle (HRC-FET) and blastocyst-stage embryo transfer were significantly associated with head circumference >= 90th percentile (1.60 [1.26-2.02], 1.70 [1.30-2.22] and 1.72 [1.33-2.24], respectively).Conclusions :The use of ART, particularly FET, HRC-FET or blastocyst-stage embryo transfer, was linked with a heightened risk of head circumference >= 90th percentile compared with non-ART fertility treatment or natural conception. The increased risk was observed only in male neonates.

Automated summary

This study found that assisted reproductive technology (ART), especially frozen embryo transfer, hormone replacement cycle frozen embryo transfer, or blastocyst-stage embryo transfer, was associated with an increased risk of head circumference ≥ 90th percentile compared to non-ART fertility treatment or natural conception. This increased risk was observed only in male neonates.