Oocyte-Granulosa Cell Interactions

Abstract

The practice of Assisted Reproductive Technology (ART) over the past twenty years has sought to reduce the level of complexity of the human reproductive process into its essential elements, namely, follicular stimulation, antral growth, ovulation induction, fertilization in vitro, and embryo replacement into a properly prepared and receptive uterus. Successful outcome, measured by pregnancy rates and live births, has increased progressively and significantly over this period, and in current clinical in vitro fertilization (IVF) practice, experienced programs routinely report pregnancy and live birth rates in excess of 40-to-50%. While clinicians are primarily concerned with the production of fertilizable oocytes and embryos that can be transferred or cryopreserved, it is very apparent from the IVF experience that at follicular aspiration, a proportion of oocytes are meiotically immature or if mature, fail to fertilize. In the same respect, a significant proportion of the resulting embryos are developmentally incompetent despite normal morphology and apparently normal performance in vitro through the preimplantation stages. Because the primary emphasis of clinical IVF continues to focus on oocyte quantity rather than quality per cycle, the intricacies of molecular and cellular interactions that occur within each follicle between the oocyte and granulosa cell compartments are often not well understood or recognized as critical determinants of developmental competence. Therefore, by reducing “physiological” complexity for clinical purposes, the question of whether and how clinical procedures conform to or modify in vivo biology becomes central to understanding the unique potential of each oocyte and embryo generated by IVF. This question becomes of particular relevance in understanding whether current and largely unsuccessful attempts to produce viable human embryos after follicular and oocyte growth from cryopreserved ovarian biopsies, or by maturation in vitro of immature oocytes derived from preantral follicles, actually recognize or consider the physiological complexity of the oocyte growth and maturation process.