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

Department of Reproductive Medicine and Gynecology (N.S.M., B.C.J.M.F.), University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands; Division of Reproductive Sciences (R.L.S.), Oregon National Primate Research Center, Oregon Health & Science University, Portland, Oregon 97239-3098; and Department of Obstetrics and Gynecology (L.C.G.), Stanford University School of Medicine, Stanford, California 94305

Correspondence: Address all correspondence and requests for reprints to: N. S. Macklon, Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. E-mail: n.s.macklon{at}umcutrecht.nl

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.

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