Clinical applications of in vitro primordial follicle activation

With advances in our understanding of the mechanisms behind the activation of primordial follicles, clinical in vitro activation (IVA) of human primordial follicles has become a viable technology for treating decreased ovarian reserve (DOR) and primary ovarian insufficiency (POI) patients. In this review, we provide an updated picture of how phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-kinase (PI3K) signaling, Hippo signaling, and mTORC1 signaling are involved in primordial follicle activation and how these pathways can be targeted for IVA. We also review the basic methods and current clinical results from the use of IVA, and we discuss how IVA can potentially be optimized for future use as a new treatment for POI and DOR patients.