Hum. Reprod. Advance Access published online on August 14, 2009
Human Reproduction, doi:10.1093/humrep/dep291
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A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol
1 Center for Reproductive Medicine, UZ Brussel, Brussels, Belgium 2 Huntington Reproductive Center, Westlake Village, CA, USA 3 Global Clinical Research, Schering-Plough Research Institute, Molenstraat 110, PO Box 20, Oss, The Netherlands 4 Research Data and Quantitative Sciences, Schering-Plough Research Institute, Oss, The Netherlands 5 Department of Reproductive Medicine and Gynecology, University Medical Center, Utrecht, The Netherlands
6 Correspondence address. E-mail: b.mannaerts{at}spcorp.com
BACKGROUND: Corifollitropin alfa, a fusion protein lacking LH activity, has a longer elimination half-life and extended time to peak levels than recombinant FSH (rFSH). A single injection of corifollitropin alfa may replace seven daily gonadotrophin injections during the first week of ovarian stimulation.
METHODS: In this large, double-blind, randomized, non-inferiority trial the ongoing pregnancy rates were assessed after one injection of 150 µg corifollitropin alfa during the first week of stimulation and compared with daily injections of 200 IU rFSH using a standard GnRH antagonist protocol.
RESULTS: The study population comprised 1506 treated patients with mean age of 31.5 years and body weight of 68.6 kg. Ongoing pregnancy rates of 38.9% for the corifollitropin alfa group and 38.1% for rFSH were achieved, with an estimated non-significant difference of 0.9% [95% confidence interval (CI): –3.9; 5.7] in favor of corifollitropin alfa. Stratified analyses of pregnancy rates confirmed robustness of this primary outcome by showing similar results regardless of IVF or ICSI, or number of embryos transferred. A slightly higher follicular response with corifollitropin alfa resulted in a higher number of cumulus–oocyte-complexes compared with rFSH [estimated difference 1.2 (95% CI: 0.5; 1.9)], whereas median duration of stimulation was equal (9 days) and incidence of (moderate/severe) ovarian hyperstimulation syndrome was the same (4.1 and 2.7%, respectively P = 0.15).
CONCLUSION: Corifollitropin alfa is a novel and effective treatment option for potential normal responder patients undergoing ovarian stimulation with GnRH antagonist co-treatment for IVF resulting in a high ongoing pregnancy rate, equal to that achieved with daily rFSH.
The trial was registered under ClinicalTrials.gov identifier NTC00696800.
Key words: corifollitropin alfa/sustained follicle stimulant/FSH/ovarian stimulation/IVF
ENGAGE investigators: Belgium: Devroey, UZ Brusssel, Center for Reproductive Medicine, Brussels; Dhont, University Hospital Ghent, Department of Gynecology. Canada: Leader, The Ottawa Fertility Center, Ottawa, Ontario. Czech Republic: Mardesic, Sanatorium Pronatal, Prague; Mrázek, ISCARE IVF a.s., Prague. Denmark: Blaabjerg, Herlev Hospital, Fertility Clinic, Herlev. Finland: Tapanainen, Naistentautien klinikka, Oulun yliopistollinen sairaala (OYS), Oulu; Varila, Väestöliitto, Tampereen klinikka, Tampere. France: Barrière, Hôpital de la mère et de l'enfant, Nantes; Hedon, Hôpital Arnaud de Villeneuve, Montpellier. The Netherlands: Fauser and Sterrenburg, University Medical Center, Department of Reproductive Medicine & Gynecology, Utrecht. Norway: Kahn, Sykehuset Telemark HF, Skien; Von Düring, St. Olavs Hospital HF, Trondheim. Spain: Bajo Arenas, Ginefiv, Madrid; Barri, Institut Universitari Dexeus, Barcelona; Fernández-Sánchez, IVI Sevilla, Sevilla. Sweden: Bergh, Kvinnokliniken, Sahlgrenska Universitetssjukhuset, Göteborg; Hillensjö, Fertilitetscentrum, Carlanderska Sjukhuset, Göteborg. United Kingdom: Balen, Assisted Conception Unit, Leeds General Infirmary; Ledger, Assisted Conception Unit, Jessop Wing, The Halllamshire Hospital, Sheffield; Matthews, Bourn Hall Clinic, Cambridge. United States of America: Abuzeid, IVF Michigan, Rochester Hills (MI), Alper, Boston IVF, Waltham (MA); Boostanfar, Huntington Reproductive Center, Westlake Village (CA); Doody, Center for Assisted Reproduction, Bedford (TX); Frattarelli, Reproductive Medicine Associates of New Jersey, Morristown (NJ); Grunfeld, Reproductive Medicine Associates of New York, New York (NY); Karande, Karande and Associates SC, Hoffman Estates (IL); Kort, Reproductive Biology Associates, Atlanta (GA); Levy, Shady Grove Fertility Reproductive Science Center, Rockville (MD); Lifchez, Fertility Centers of Illinois, Chicago (IL); Pang, Reproductive Science Center of Boston, Lexington (MA); Schoolcraft, Colorado Center for Reproductive Medicine, Englewood (CO); Yeko, The Reproductive Medicine Group, Tampa (FL). Submitted on February 17, 2009; resubmitted on July 14, 2009; accepted on July 20, 2009.