The Science behind 25 Years of Ovarian Stimulation for in Vitro Fertilization

To allow selection of embryos for transfer after in vitro fertilization, ovarian stimulation is usually carried out with exogenous gonadotropins.To compensate for changes induced by stimulation, GnRH analog cotreatment, oral contraceptive pretreatment, late follicular phase human chorionic gonadotropin, and luteal phase progesterone supplementation are usually added.These approaches render ovarian stimulation complex and costly.The stimulation of multiple follicular development disrupts the physiology of follicular development, with consequences for the oocyte, embryo, and endometrium.In recent years, recombinant gonadotropin preparations have become available, and novel stimulation protocols with less detrimental effects have been developed.In this article, the scientific background to current approaches to ovarian stimulation for in vitro fertilization is reviewed.After a brief discussion of the relevant aspect of ovarian physiology, the development, application, and consequences of ovarian stimulation strategies are reviewed in detail.(Endocrine Reviews 27: 170 -207, 2006) I. Introduction II.Physiology of Ovarian Function Relevant to Ovarian Stimulation A. Endocrine control of follicular development B. Intraovarian modulators of steroidogenesis C. Control of corpus luteum function D. Control of endometrial function E. Ovarian aging III.The Development of Ovarian Stimulation Agents A. Background B. The discovery of clomiphene citrate C. Gonadotropins D. GnRH agonists E. GnRH antagonists IV.Ovarian Stimulation Regimens A. Clomiphene citrate B. Gonadotropins C. The role of LH D. GnRH agonists E. GnRH antagonists V. Adjuvant Therapies A. Oral contraceptive pretreatment B.