Advanced paternal age, infertility, and reproductive risks: A review of the literature

Advanced paternal age (APA) is associated with infertility and other reproductive risks. Studies looking at APA and outcomes have used different paternal age cut-offs, which has complicated systematic evaluations of reproductive risk associated with paternal aging. This review of the literature suggests that the impact of paternal aging on adverse reproductive outcomes is small, but significant. Studies suggest the incidence of paternal age effect disorders attributed to de novo autosomal dominant mutations is less than 0.5%. Other risks associated with APA include infertility, miscarriage, birth defects, poor neurodevelopmental outcomes, and childhood cancer. Although the increasing prevalence of APA has mirrored the rise in maternal age, this topic has not received similar attention. In this review, we summarize the available literature on the reproductive risks associated with APA to provide a framework for comprehensive genetic counseling and evidence-based management of APA pregnancies.