To rescue or not to rescue immature oocytes: Prospects and challenges.

In vitro maturation (IVM) of immature oocytes has been explored for research and clinical purposes since the dawn of assisted reproduction technologies. Oocyte maturation is a highly specific process, based on complex mutual relationships between the germ and somatic cell compartments. The complexity of this relationship has made the quest for achieving oocyte maturation in vitro arduous. In its classical form, in which intact cumulus enclosed oocytes are collected without or with very mild ovarian stimulation, oocyte IVM is non-experimental and has been proposed as a more friendly treatment for PCO/PCOS patients. By contrast, rescue IVM, which is the maturation in vitro if immature oocytes collected in standard ovarian stimulation cycles, is an experimental procedure, proposed to mitigate the impact of low oocyte maturation rates in certain patients. Achieving effective rescue IVM has turned out to be an even more daunting task, as oocytes are cultured only after cumulus cell removal and therefore without the crucial somatic metabolic and regulative support. Immatures oocyte arrested at the germinal vesicle or metaphase I stage require different management for their maturation in vitro and exhibit different developmental and chromosomal competence. Therefore, their possible use for treatment suggests a personalized approach. Overall, rescue IVM has limited clinical efficacy due to suboptimal maturation and developmental competence of immature oocytes. This raises a cost/benefit question: i.e., the definition of appropriate clinical indications. Rescue IVM is probably irrelevant to treatment cycles in which the absolute number of mature oocytes is high. Conversely, specific poor prognosis cases, involving low maturation rates, low oocyte yield and/or low oocyte quality, could benefit from the contribution of even a single embryo generated from an in vitro matured oocyte. Future progress in this field will depend on our ability to mimic in vitro the support provided by cumulus cells to oocyte nuclear and cytoplasmic maturation.