Advanced Paternal Age: Implications on Fertility, Pregnancy Outcomes, and Offspring Health.
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AIM: To review associations between advanced paternal age (APA) and male reproductive health, assisted reproductive technology (ART) outcomes, pregnancy outcomes, and offspring health, to grade the evidence in each domain, and to address counseling implications. METHODS: Narrative review with a structured, reproducible search. PubMed/MEDLINE was searched from 1 January 1990 to 4 September 2026 using controlled-vocabulary and free-text terms for paternal age and for reproductive, pregnancy, perinatal, and offspring outcomes, limited to human studies in English (1975 records), supplemented by hand-searching, Cochrane reviews, and professional society guidance. Systematic reviews, randomized trials, and large cohorts were prioritized, and confidence in each association was graded qualitatively. RESULTS: APA (≥ 40 years) is consistently associated with lower semen volume, motility, and viability, higher sperm DNA fragmentation, and a linear increase in de novo mutations. Associations with reduced natural fecundability and modestly higher miscarriage risk are moderately consistent; ART outcomes are heterogeneous and largely attenuated once maternal age is controlled. Large registries show small but consistent associations with stillbirth, preterm birth, selected congenital anomalies, schizophrenia, and autism (relative effects mostly 1.1-3.0); associations with bipolar disorder, ADHD, childhood cancer, and cognitive outcomes are weaker or inconsistent. Because these outcomes are rare, absolute increments remain small. Paternal age alone is not an evidence-based indication for ICSI, sperm DNA fragmentation testing, preimplantation genetic testing, or other add-ons. CONCLUSIONS: APA is associated with measurable changes in sperm biology and modest increases in relative risk for several adverse outcomes, most evident beyond 40 years. Nearly all evidence is observational and should not be read as causal. Paternal age warrants inclusion in reproductive counseling, communicated in absolute terms and without alarm. ETHICAL ISSUE: Beyond biological risks, APA raises concerns about long-term child welfare, emotional well-being, and potential socio-economic implications due to a greater risk of early parental loss.