Gonadotropin-releasing hormone antagonists (GnRH-nt) available for clinical use are GnRH molecules with amino acid modifications in positions 1, 2, 3, 6, and 10. They are not associated with the histaminic-release effects of previous compounds (1). These compounds immediately block GnRH receptor in a competitive fashion (2). They decrease the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion within a period of eight hours. Inhibition of LH secretion is more important than FSH. This is probably due to the different forms of gonadotropin regulation, the prolonged FSH half-life, or the immunoactive and bioactive forms of FSH (3,4). . | _5_ Gonadotropin-Releasing Hormone-Antagonist in Human In Vitro Fertilization F. Olivennes Department of Obstetrics and Gynecology Hospital Cochin Paris France INTRODUCTION Gonadotropin-releasing hormone antagonists GnRH-nt available for clinical use are GnRH molecules with amino acid modifications in positions 1 2 3 6 and 10. They are not associated with the histaminic-release effects of previous compounds 1 . These compounds immediately block GnRH receptor in a competitive fashion 2 . They decrease the luteinizing hormone LH and follicle-stimulating hormone FSH secretion within a period of eight hours. Inhibition of LH secretion is more important than FSH. This is probably due to the different forms of gonadotropin regulation the prolonged FSH half-life or the immunoactive and bioactive forms of FSH 3 4 . Administered during the follicular phase GnRH-nt can prevent or interrupt LH surges 5 . In addition their use has been proposed in in vitro fertilization IVF -embryo transfer ET cycles to obtain results similar to those obtained with GnRH-a however with the simplest protocol and fewer side effects 6 . Two different compounds are available the Cetrorelix Cetrotide formerly ASTA Medica now Serono and the Ganirelix Antagon or Orgalutran Organon . Two different protocols of administration Fig. 1 have been proposed in the literature for using GnRH-nt in controlled 67 68 Olivennes Figure 1 Gonadotropin-releasing hormone antagonist multiple- and single-dose protocols. Fixed day regimens. Abbreviations FSH follicle-stimulating hormone hMG human menopausal gonadotropin hCG human chorionic gonadotropin. ovarian stimulation COH . In the multiple-dose protocol small doses mg of the GnRH-nt are injected in the middle of the follicular phase 7-9 . In the single-dose protocol a higher dose 3 mg is injected during the late follicular phase when the LH surge is most feared 10 11 . PHASE II DOSE-FINDING STUDIES Single-Dose .
