Intracytoplasmic sperm injection is associated with a shift in the human secondary sex ratio at birth

Abstract Human sex ratios at birth are remarkably stable, yet may be sensitive to events during fertilisation and early embryo development. Intracytoplasmic sperm injection (ICSI) bypasses sperm-zona interaction by injecting a selected sperm directly into the oocyte and is increasingly used beyond severe male-factor infertility. We analysed anonymised UK Human Fertilisation and Embryology Authority registry data for 2005–2018 to test whether fertilisation method is associated with the secondary sex ratio among singleton live births. The cohort included 164,684 singleton live births after conventional IVF or ICSI with recorded infant sex. Multivariable logistic regression adjusted for maternal age, treatment year, number of embryos transferred, and fresh or frozen embryo transfer. The adjusted proportion of male live births was 52.6% after IVF and 49.2% after ICSI, an absolute difference of 3.4 percentage points (95% CI 2.8–3.9); the adjusted odds ratio for male live birth after ICSI versus IVF was 0.88 (95% CI 0.86–0.89). The association was consistent across single-embryo transfers, fresh and frozen cycles, cycles without recorded male-factor infertility, and analyses excluding preimplantation genetic testing and donor-gamete cycles. These data identify a small association between fertilisation method and the proportion of male singleton live births within this ART cohort. They do not establish that ICSI causes a shift in the secondary sex ratio in the wider population and should not alter individual counselling, but support deeper study of sex-specific selection across fertilisation, embryo culture, transfer, and early survival.