Identifying fertilization-ready metaphase II stage oocytes beyond the microscope: a proposed molecular path forward

One key variable in the success of in vitro fertilization (IVF) cycles is the maturation of oocytes for fertilization. Current practices of both conventional IVF and intracytoplasmic sperm injection do not evaluate the maturity of eggs immediately at the time of oocyte retrieval. In conventional IVF, all retrieved eggs are inseminated with sperm without further evaluation of their maturity. With conventional IVF, immature oocytes are not identified and are inseminated with resulting poor outcomes. In intracytoplasmic sperm injection, retrieved eggs are denuded of cumulus cells (CCs) for evaluation of maturity before insemination. Immature oocytes are identified after denudation and may not reach their full maturation potential because of the loss of surrounding CCs. Both approaches can benefit from an early noninvasive evaluation of oocyte maturity. Cumulus cells are physically and biochemically connected to oocytes and could serve as a window to look into oocyte maturity. This study reviews current literature on processes essential in oocyte maturation involving CCs as well as messenger RNA (mRNA), microRNA (miRNA), and protein biomarkers of metaphase II (MII) stage oocytes identified in CCs. We use this information as a starting point to propose a path forward in the molecular analysis of CCs as a tool of MII oocyte selection. With future studies proposed in this review, we envision a clinically useful approach of selected mRNA, miRNA, and protein marker analysis and eventually a transition to mRNA–miRNA–protein expression correlation analysis and pathway analysis of CC markers to identify MII oocytes at the time of retrieval and enable metaphase I and germinal vesicle oocytes to be further matured in vitro with intact supporting CCs.