In vitro maturation 2.0: a new era for an underdog in ART

In vitro maturation (IVM) of human oocytes, once a pioneering concept predating conventional IVF, has long remained an underutilized technique in assisted reproduction. Despite early promise, clinical adoption of IVM has been limited due to lower embryo developmental competence and live birth rates compared to IVF. However, recent advances in the understanding of oocyte physiology, including cumulus-oocyte communication, the regulatory roles of cAMP/cGMP signaling pathways, and endocrine modulation of meiotic resumption, have reignited interest in optimizing IVM protocols. Innovations such as biphasic Capacitation (CAPA) IVM systems and the use of ovarian somatic support cells (OSCs) derived from induced pluripotent stem cells (iPSCs) aim to replicate the dynamic follicular environment more accurately and enhance oocyte competence. Clinical studies suggest that, while IVM still results in modestly lower cumulative live birth rates compared to conventional IVF, it offers significant advantages for selected patient populations, particularly women with polycystic ovary syndrome (PCOS), high ovarian reserve, or those requiring fertility preservation. Importantly, current evidence supports the genetic and epigenetic safety of IVM-derived offspring. As technical refinements continue and professional education expands, IVM is poised to fulfill its potential as a safer, less invasive, and more accessible alternative within the landscape of assisted reproductive technologies.