Polycystic Ovary Syndrome and Oocyte Developmental Competence

Abstract

Folliculogenesis is a complex process, in which multiple endocrine and intraovarian paracrine interactions create a changing intrafollicular microenvironment for appropriate oocyte development. Within this microenvironment, bidirectional cumulus cell-oocyte signaling governs the gradual acquisition of developmental competence by the oocyte, defined as the ability of the oocyte to complete meiosis and undergo fertilization, embryogenesis, and term development. These regulatory mechanisms of follicle growth, controlled in part by the oocyte itself, are susceptible to derangement in polycystic ovary syndrome (PCOS), a heterogeneous syndrome characterized by ovarian hyperandrogenism, insulin resistance, and paracrine dysregulation of follicle development. Consequently, only a subset of PCOS patients experience reduced pregnancy outcome after ovarian stimulation for in vitro fertilization. Recent data implicate functional associations between endocrine/paracrine abnormalities, metabolic dysfunction, and altered oocyte gene expression with impaired oocyte developmental competence in women with PCOS. Therefore, an understanding of how developmentally relevant endocrine/paracrine factors interact to promote optimal oocyte developmental is crucial to identify those PCOS patients who might benefit from long-term correction of follicle growth to improve fertility, optimize follicular responsiveness to gonadotropin therapy, and enhance pregnancy outcome by in vitro fertilization. Editor’s Note: Dr. Dumesic, the first author of the insightful and informative overview of the molecular and pathologic abnormalities underpinning the varying degrees of severity of polycystic ovary syndrome, presented a lecture on this topic at the annual meeting of the Endocrine Society in Toronto in June, 2007. I was so stimulated by his presentation that I asked him to write this review for the SURVEY. I hope that our readers find it as thoughtful and perceptive as I did—RBJ. (As a disclaimer: Dr. Dumesic was a postdoctoral reproductive endocrinology fellow in my laboratory from 1985 to 1987.) Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to explain that oocyte developmental competence in patients with polycystic ovary syndrome (PCOS) is very complicated, with multiple interactions between endocrine, metabolic, and altered gene expression, and recall that it is related to a syndrome of ovarian hyperandrogenism, insulin resistance, and paracrine dysregulation of follicle development.