Older paternal age a risk factor for poor reproductive outcomes after ICSI

Paternal age appears to independently factor in the success of intracytoplasmic sperm injection (ICSI), with sperm from men over 45 years of age being associated with increased risk of miscarriage and lower live birth rates, according to a retrospective study.

The study included 1,712 first oocyte donation cycles performed across six IVF centres. These cycles involved fresh donor oocytes injected with frozen sperms from normospermic men and limited to single blastocyst transfers. The mean recipient age was 43.3 years, the mean oocyte donor age was 26.1 years, and the mean paternal age was 43.5 years.

In an analysis stratified by paternal age, laboratory outcomes did not significantly differ between the ≤45- and >45-year-old age groups, including fertilization rate (80.1 percent vs 80.4 percent; p=0.353), number of viable blastocysts (mean, 3.5 vs 3.5; p=0.199), and blastocyst utilization rate (63.8 percent vs 65 percent; p=0.122). [ESHRE 2025, abstract deaf097.015]

However, in the >45-year-old age group, miscarriage rate was significantly higher (23.8 percent vs 16.3 percent; p=0.006), while live birth rate was significantly lower (35.1 percent vs 41 percent; p=0.009).

These results were confirmed in the adjusted analysis, where advanced paternal age (>45 years) was associated with 61-percent greater odds of miscarriage (odds ratio [OR], 1.61, 95 percent confidence interval [CI], 1.10–2.35; p=0.014) and 23-percent reduced odds of live birth (OR, 0.77, 95 percent CI, 0.62–0.96; p=0.022).

This study points to advanced paternal age as an important factor that can negatively affect pregnancy success, even when using eggs from young, healthy donors and transferring only a single, high-quality embryo, said lead researcher Dr Maria Cristina Guglielmo from Eugin Taranto, IVF Center, Taranto, Italy.

Guglielmo explained that the ageing process in men leads to a decline in sperm quality. “As men age, the continuous division of spermatogonial stem cells increases the chance of DNA replication errors. This results in a greater number of new genetic mutations and a higher rate of sperm aneuploidy, where sperm carry abnormal chromosomes. Older paternal age is also linked to increased sperm DNA fragmentation and changes in the epigenetic profile of sperms, such as DNA methylation.”

The age-related decline in sperm quality can impair embryo development and contribute to a higher risk of miscarriage, she added.

“Male patients must be fully informed about how advancing paternal age can impact fertility potential, pregnancy success, and miscarriage risk. And for younger men who plan to delay parenthood, sperm cryopreservation can be recommended,” according to Guglielmo.

She acknowledged that the study was limited by its retrospective nature and the lack of data on the chromosomal status of the embryos. Caution is advised when generalizing results to different embryo transfer strategies or other patient populations.

Looking ahead, Guglielmo shared that they are planning to conduct further studies that will investigate the long-term health and developmental outcomes of children conceived through donor egg cycles with older fathers, where maternal factors are controlled, to isolate paternal effects more clearly. She also noted that future work will help deepen understanding of the biological mechanisms underlying the impact of paternal age, focusing on sperm DNA damage, oxidative stress, and epigenetic changes.