Advancing paternal age: Effects on sperm quality and offspring health

Over recent decades, socioeconomic and cultural changes have led to a progressive increase in paternal age at conception, prompting growing concern regarding its potential effects on male reproductive function, pregnancy outcomes, and offspring health. In contrast to the extensive literature on female reproductive aging, the biological and clinical consequences of paternal aging have received less attention.

This narrative review summarizes and critically discusses current evidence on the impact of advanced paternal age on conventional and biofunctional sperm parameters, sperm epigenetic modifications, reproductive outcomes, and offspring health.

A comprehensive literature review was conducted, encompassing clinical, epidemiological, and experimental studies investigating the association between paternal age and semen quality, sperm DNA integrity and epigenetic alterations, pregnancy outcomes in natural and assisted reproduction settings, and long-term neurodevelopmental and metabolic consequences in the offspring.

Advanced paternal age is associated with progressive alterations in semen volume, sperm motility, morphology, vitality, and biofunctional parameters, including increased sperm DNA fragmentation, chromatin instability, and structural chromosomal abnormalities. Growing evidence further indicates that advanced paternal age is linked to age-related epigenetic sperm remodeling, involving alterations in DNA methylation patterns and non-coding RNA expression, particularly in genes implicated in neurodevelopment and metabolic regulation. Clinically, advanced paternal age has been associated with reduced pregnancy and implantation rates, an increased risk of miscarriage, and abnormal embryo development, especially in the context of assisted reproductive technologies. Moreover, epidemiological and experimental data suggest that paternal aging contributes to a higher risk of neuropsychiatric and metabolic disorders in the offspring.

Paternal aging represents a relevant and multifaceted determinant of reproductive outcomes and offspring health. Integrating paternal age and male-specific factors into infertility assessment and counseling may improve clinical decision-making and support preventive strategies aimed at optimizing reproductive success and long-term health consequences.