Efforts to optimize oocyte quality as a result of in vitro maturation (IVM) are critical to achieving patient-specific success in assisted reproductive techniques. Traditional approaches to human IVM have been replaced by methodologies aimed at recapitulating the changing milieu of the ovulatory follicle following reception of signals initiated by LH. These include the deployment of sequential media changes that more accurately reflect the temporal shift in balance between biosynthetic and metabolic alterations that occur within the cumulus cells and their enclosed oocytes. Distinctions in cumulus cell physiology and gene expression in an in vivo and in vitro context are likely to serve as useful noninvasive biomarkers for the developmental potential of human oocytes that complete nuclear and cytoplasmic maturation under ex vivo conditions.