Anoscrotal distance and urogenital anomalies in ART-conceived male infants: a retrospective cohort study

Abstract

Background: Assisted reproductive technology (ART) is widely used, yet potential effects on androgen-sensitive male genital development remain a concern. Anoscrotal distance (ASD), a validated marker of prenatal androgen exposure, may differ in ART-conceived infants. This study compared ASD and urogenital anomalies among male newborns conceived via frozen-thawed embryo transfer (FET) using natural-cycle (tNC) or hormone-replacement therapy (HRT) protocols versus natural conception (NC). Methods: In this retrospective cohort of 432 singleton male births (156 NC, 132 FET-tNC, 144 FET-HRT) delivered between 2021 and 2023, neonatal outcomes, including ASD, hypospadias, and undescended testes (UDT), were assessed. Group comparisons were performed using standard statistical tests, and exploratory modelling was conducted to identify variables most strongly distinguishing conception groups. Results: Median ASD was significantly longer in NC infants (26.2 mm) than in FET-tNC (24.9 mm) and FET-HRT (24.6 mm) infants (p < 0.001), with no difference between FET protocols. Hypospadias was less frequent in FET-HRT than FET-tNC infants (p = 0.031), while UDT was more common in NC than FET-tNC infants (p = 0.041). Exploratory modelling identified ASD as the strongest discriminator across conception groups. Conclusions: Male infants conceived via FET consistently exhibited shorter neonatal ASD than naturally conceived infants, suggesting subtle alterations in androgen-sensitive genital development. These findings underscore the importance of incorporating careful genital assessment and ART-specific counseling into neonatal care.