Older paternal age linked to higher miscarriage risk and lower live birth rates in donor egg IVF cycles, new study finds

A new international study presented today at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) reveals that IVF cycles involving male partners over the age of 45 carry significantly increased miscarriage risks and lower live birth rates – even when young donor eggs are used.

By isolating paternal age from female reproductive factors through the exclusive use of donor eggs from young women, the study provides robust evidence that male age plays a critical role in reproductive success, challenging the common assumption that sperm age has little impact once fertilisation occurs.

The retrospective study analysed 1,712 first oocyte donation cycles conducted between 2019 and 2023 across six IVF centres in Italy and Spain. All cycles used fresh donor oocytes (mean donor age 26.1 years) and frozen sperm from male partners, with only the first single blastocyst transfer included. Female recipients had a mean age of 43.3 years.

Participants were divided into two groups: men aged 45 or younger (n=1,066) and those over 45 (n=646). While fertilisation rates and embryo development were comparable between groups, significant differences emerged in clinical outcomes.

Miscarriage rates were notably higher among couples where the male partner was over 45, reaching 23.8% compared to 16.3% in the younger paternal age group. Similarly, live birth rates were significantly lower in the older paternal age group, at 35.1% versus 41% for men aged 45 or younger.

Discussing the findings, Dr. Maria Cristina Guglielmo, Embryologist at Eugin Italy, said, “Traditionally, maternal age has been the central focus in reproductive medicine, but our results show that the age of the male partner also plays a crucial and independent role. Even when using eggs from young, healthy donors and transferring only a single, high-quality embryo, we observed poorer outcomes in men over 45.”

Explaining the potential underlying mechanisms, Dr. Guglielmo elaborated, “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.”

She continued, “Together, these factors affect both the genetic integrity and the functional quality of sperm, which can impair embryo development and contribute to a higher risk of miscarriage.”

Highlighting the clinical implications, Dr. Guglielmo stated, “Our findings underscore the need for fertility clinics to adopt a more balanced approach that recognises the role of paternal age, even in donor egg cycles where maternal factors are controlled”, she said. “Clinics should ensure that male patients are fully informed about how advancing paternal age can impact fertility potential, pregnancy success, and miscarriage risk.”

Looking ahead, Dr. Guglielmo outlined the research priorities: “Our future studies will aim to deepen understanding of the biological mechanisms behind the impact of paternal age, focusing on sperm DNA damage, oxidative stress, and epigenetic changes.”

She also emphasised the importance of examining how paternal age affects the health of offspring. “There is growing evidence linking advanced paternal age to an increased risk of neurodevelopment disorders in children. Our future work will investigate the long-term health and developmental outcomes of children conceived through donor egg cycles with older fathers, where maternal factors are minimised, to isolate paternal effects more clearly.”

Professor Dr. Carlos Calhaz-Jorge, Immediate Past Chair of ESHRE, said, “This is an important paper that draws attention to an often-overlooked factor in the IVF field. Although it might be interesting to further subdivide the ‘older paternal age’ group (for instance, would men over 55 show even poorer outcomes?), the results presented should be seriously considered during the counselling process for couples in which the male partner is over 45.”

Reference:

Older paternal age linked to higher miscarriage risk and lower live birth rates in donor egg IVF cycles, new study finds, European Society of Human Reproduction and Embryology, Meeting: ESHRE 41st Annual Meeting.