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.”
The study abstract will be published today in Human Reproduction, one of the world’s leading reproductive medicine journals.
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Notes to editors:
A reference to the ESHRE Annual Meeting must be included in all coverage and/or articles associated with this study.
For more information or to arrange an expert interview, please contact the ESHRE Press Office at: press@eshre.eu
About the study author:
Maria Cristina Guglielmo, PhD, is Laboratory Director at Eugin Taranto and a senior clinical embryologist specialising in assisted reproductive technologies. She earned her degree in Medical Biotechnologies and a PhD in Science and Cellular Technologies from the University of Rome “La Sapienza” where her doctoral research investigated the regulatory mechanisms of follicle development and oocyte maturation. Dr. Guglielmo’s current research is dedicated to translational clinical studies aimed at improving IVF success rates and advancing novel technologies to enhance outcomes in reproductive medicine.
About the European Society of Human Reproduction and Embryology
The main aim of ESHRE is to promote interest in infertility care and to aim for a holistic understanding of reproductive biology and medicine.
ESHRE collaborates world-wide and advocates universal improvements in scientific research, encourages and evaluates new developments in the field, and fosters harmonisation in clinical practice. It also provides guidance to enhance effectiveness, safety and quality assurance in clinical and laboratory procedures, psychosocial care, and promotes ethical practice. ESHRE also fosters prevention of infertility and related educational programmes and promotes reproductive rights regardless of the individual’s background. ESHRE’s activities include teaching, training, professional accreditations, mentoring and career planning for junior professionals, as well as developing and maintaining data registries. It also facilitates and disseminates research in human reproduction and embryology to the general public, scientists, clinicians, allied personnel, and patient associations.
Website: https://www.eshre.eu/
About Human Reproduction
Human Reproduction is a monthly journal of ESHRE and is one of the top three journals in the world in the field of reproductive biology, obstetrics and gynaecology. It is published by Oxford Journals, a division of Oxford University Press.
References:
[1] Guglielmo, M.C., et al. (2025). Advanced paternal age affects miscarriage and live birth outcomes following the first transfer in oocyte donation cycles. Human Reproduction.
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