A groundbreaking international study unveiled at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) has illuminated a critical yet often underestimated factor influencing reproductive success: paternal age. Contrary to longstanding assumptions in reproductive medicine that sperm quality remains largely unaffected by age once fertilisation is achieved, this study compellingly demonstrates that male partners over 45 experience markedly increased rates of miscarriage and significantly lower live birth outcomes, even when the youngest and healthiest donor eggs are utilized. This insight challenges the prevailing focus on maternal age as the primary determinant of IVF success and calls for a paradigm shift in reproductive counselling and clinical practice.
The robust nature of this research owes much to its design, which uniquely isolates paternal influence by employing donor eggs exclusively from young women, with a mean donor age of just 26.1 years. By controlling for female reproductive variables, the team was able to precisely assess the impact of paternal factors on IVF outcomes. The retrospective analysis encompassed 1,712 first-time oocyte donation cycles conducted between 2019 and 2023 at six leading IVF centers across Italy and Spain, ensuring a diverse and representative sample.
Participants were classified into two distinct cohorts based on paternal age: those 45 years or younger, and those older than 45. Fertilisation rates and early embryo developmental milestones did not differ significantly between these age groups, underscoring that initial conception potential may not be impaired by male age. However, pronounced disparities emerged during the subsequent clinical stages. Miscarriage incidences soared to 23.8% in the advanced paternal age group, markedly higher than the 16.3% observed in the younger cohort. Correspondingly, live birth rates plummeted to 35.1% amongst fathers over 45, contrasting with a more favourable 41% in younger men.
Delving into the biological underpinnings, Dr. Maria Cristina Guglielmo, Laboratory Director at Eugin Italy and the study’s lead embryologist, elucidates the mechanisms driving these outcomes. She highlights the relentless mitotic activity of spermatogonial stem cells throughout a man’s reproductive lifespan, which paradoxically increases the likelihood of DNA replication errors. Such errors can result in de novo mutations, chromosomal aneuploidies in spermatozoa, and elevated levels of DNA fragmentation, all of which compromise the genetic fidelity essential for healthy embryo development.
Beyond genetic mutations, advanced paternal age also induces profound epigenetic alterations within sperm cells. These changes, such as aberrant DNA methylation patterns, can modulate gene expression without altering the underlying DNA sequence. Such epigenetic dysregulation has been implicated in impaired embryo implantation and increased susceptibility to miscarriage, highlighting a multifaceted assault on reproductive potential tied to male aging.
The study’s meticulous focus on donor egg cycles is particularly crucial, as it effectively eliminates confounding maternal factors. By ensuring that the oocytes used originated from young, healthy donors, the research confirms that poorer reproductive outcomes are attributable predominantly to sperm quality diminished by paternal aging rather than egg-related variables. This methodological rigor adds unprecedented clarity to the discourse on male fertility and its clinical significance.
Clinically, these findings demand a reevaluation of current fertility counselling protocols. Dr. Guglielmo advocates for a more holistic approach that places paternal age alongside maternal age as a vital consideration in IVF treatment planning. Fertility clinics should strive to inform male patients candidly about how their advancing age may compromise not only embryo viability but also the broader trajectory of pregnancy success and offspring health.
Looking forward, the research team plans to expand investigations into the molecular pathways linking paternal age to reproductive failures. Special emphasis will be placed on quantifying sperm DNA damage, elucidating the role of oxidative stress in germ cell integrity, and mapping the intricate landscape of epigenetic modifications. Such detailed mechanistic studies promise to uncover potential biomarkers for sperm quality and novel therapeutic targets to enhance fertility outcomes.
The broader implications of paternal age on offspring health also remain a critical concern. Emerging evidence associates advanced paternal age with an increased risk of neurodevelopmental disorders and other long-term health issues in children. By isolating paternal effects in donor egg cycles, future longitudinal studies led by Dr. Guglielmo’s team aim to disentangle these paternal contributions from maternal influences, potentially informing public health strategies and clinical guidelines.
Professor Dr. Carlos Calhaz-Jorge, Immediate Past Chair of ESHRE, emphasizes the clinical relevance of these results. He notes the necessity of acknowledging the substantial impact of paternal age during patient counselling and suggests that further subdivision of the older age bracket, such as isolating men over 55, could yield even more nuanced insights. Such stratified data would be invaluable in tailoring fertility advice and managing patient expectations more effectively.
The publishing of the study’s abstract today in Human Reproduction, a preeminent journal in the field, underscores the significance of these revelations within the scientific community. This research not only pushes the boundaries of our understanding of male fertility but also serves as a clarion call for clinicians and researchers alike to integrate paternal age as a cornerstone variable in reproductive medicine.
In summary, the study affirms that paternal age profoundly affects miscarriage risk and live birth success in IVF cycles, even when young donor eggs are used. By shedding light on the genetic and epigenetic deterioration occurring in sperm over time, it challenges entrenched assumptions and advances the discourse toward more comprehensive and inclusive fertility care. This milestone investigation paves the way for a future where both maternal and paternal factors are equally prioritized to optimize reproductive outcomes and offspring well-being.
Subject of Research: Advanced paternal age effects on IVF outcomes using donor egg cycles
Article Title: Advanced Paternal Age Linked to Increased Miscarriage Risk and Lower Live Birth Rates Despite Young Donor Eggs
News Publication Date: 30 June 2025
References:
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.
Keywords: Human reproduction, reproductive biology, pregnancy, IVF, in vitro fertilization, embryo implantation, birth control, human fertilization
