title: The science behind 25 years of ovarian stimulation for in vitro fertilization.
abstract: 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.
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. n.s.macklon@umcutrecht.nl
authors.forename: Nick S
authors.initials: NS
authors.lastname: Macklon
authors.forename: Richard L
authors.initials: RL
authors.lastname: Stouffer
authors.forename: Linda C
authors.initials: LC
authors.lastname: Giudice
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
mesh_terms: D000375:Aging; D000728:Androgens; D047072:Aromatase Inhibitors; D006063:Chorionic Gonadotropin; D002996:Clomiphene; D003276:Contraceptives, Oral; D003338:Corpus Luteum / Q000502:physiology; D004624:Embryo Transfer; D004717:Endometrium / Q000502:physiology; D005260:Female; D005307:Fertilization in Vitro; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors; D006062:Gonadotropins; D049673:History, 20th Century; D019382:Human Growth Hormone; D006801:Humans; D007328:Insulin; D007986:Luteinizing Hormone / Q000502:physiology; D010053:Ovary / Q000502:physiology; D010062:Ovulation Induction / Q000009:adverse effects / Q000266:history / Q000379:methods; D013256:Steroids / Q000096:biosynthesis
chemical_list: D000728:Androgens; D047072:Aromatase Inhibitors; D006063:Chorionic Gonadotropin; D003276:Contraceptives, Oral; D006062:Gonadotropins; D007328:Insulin; D013256:Steroids; D019382:Human Growth Hormone; D002996:Clomiphene; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone