Emerging therapeutic strategies to mitigate female and male reproductive aging

Abstract

People today are choosing to have children later in life, often in their thirties and forties, when their fertility is in decline. We sought to identify and compile effective methods for improving either male or female fertility in this context of advanced reproductive age. We found few clinical studies with strong evidence for therapeutics that mitigate reproductive aging or extend fertility; however, this Perspective summarizes the range of emerging experimental strategies under development. Preclinical studies, in mouse models of aging, have identified pharmaceutical candidates that improve egg and sperm quality. Further, a diverse array of medically assisted reproduction methodologies, including those that stimulate rare ovarian follicles and rejuvenate egg quality using mitochondria, may have future utility for older patients. Finally, we highlight the many knowledge gaps and possible future directions in the field of therapeutics to extend the age of healthy human reproduction. People now choose to start families in their 30s to 40s, when fertility is low owing to reproductive aging. In this Perspective, the authors highlight the absence of clinically confirmed therapeutics to mitigate reproductive aging or extend fertility, and they summarize the range of emerging strategies and point to knowledge gaps and future directions in the field.