Couple age interaction and cumulative live birth rate after IVF/ICSI: a large cohort study

Does maternal age modify the association between paternal age and cumulative live birth rate (CLBR) after IVF/intracytoplasmic sperm injection (ICSI)?

This retrospective cohort study included 22,013 first oocyte retrieval cycles using autologous oocytes and non-donor spermatozoa at a tertiary reproductive centre between 2016 and 2024. The primary outcome was CLBR within the first three embryo transfer attempts from a single retrieval. Paternal age was analysed per 5-year increase, and interaction with maternal age was tested formally. Multivariable models adjusted for female body mass index, duration of infertility, type of infertility, fertilization method, and major infertility aetiologies. Sensitivity analyses used CLBR within the first five embryo transfer attempts.

Among women aged <40 years, paternal age was not associated with CLBR within three embryo transfer attempts [adjusted OR (aOR) per 5-year increase 0.98, 95% CI 0.94-1.02]. Among women aged ≥40 years, increasing paternal age was associated with lower CLBR (aOR 0.78, 95% CI 0.75- 0.81), with a significant paternal age × maternal age interaction (P for interaction < 0.001). In the older maternal age group, increasing paternal age was also associated with a lower cumulative clinical pregnancy rate and higher risk of miscarriage, whereas fertilization rate and high-quality embryo rate did not decline. Results were consistent when CLBR was defined within the first five embryo transfer attempts.

Paternal age was not uniformly associated with CLBR after IVF/ICSI. Its adverse association became clinically evident mainly among couples in which the female partner was aged ≥40 years. These findings support joint consideration of paternal and maternal age when counselling couples about cumulative reproductive prognosis after assisted reproduction.