In Vitro Activation: A Possible New Frontier for Treatment of Primary Ovarian Insufficiency.

In vitro activation (IVA) represents a new frontier in the treatment of women with primary ovarian insufficiency as well as patients with cancer desiring fertility preservation. Here, we review the biological basis of IVA and the recent translation of IVA to humans by targeting Hippo and Akt-signaling pathways. We then provide a new integrated viewpoint on IVA, highlighting basic science research on the aspects of follicular development and ovarian tissue transplantation which may potentially optimize future translational research on IVA. Specific topics discussed include cryopreservation techniques, additional IVA pathway targets, the roles of actin polymerization, paracrine and endocrine factors, and the role of mechanical signaling and associated tissue rigidity in controlling ovarian follicular activation. Further research and improved understanding is needed to optimize success of IVA.