Article
Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF

https://doi.org/10.1016/S1472-6483(11)60006-0Get rights and content

Abstract

A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. This double-blind randomized controlled trial assessed the pharmacokinetics and pharmacodynamics of 150 μg corifollitropin alfa versus daily 200 IU rFSH in 1509 patients. Comparative analyses were performed on serum concentrations of FSH immunoreactivity (pharmacokinetics), and the number and size of growing follicles, and inhibin B and oestradiol concentrations as biomarkers of ovarian response (pharmacodynamics). The rate of follicular development was similar in both treatment groups. By stimulation day 8, 33% of patients treated with corifollitropin alfa reached the criterion for human chorionic gonadotrophin (HCG) injection. The number of follicles ≥11 mm was slightly higher after corifollitropin alfa compared with daily rFSH at stimulation day 8 (difference, 1.2; 95% confidence interval (Cl) 0.5−1.8; P < 0.01) and on the day of HCG injection (difference, 2.1; 95% Cl 1.4−2.8; P < 0.01). The rise of inhibin B and oestradiol concentrations was similar in both treatment groups. Although the pharmacokinetics of corifollitropin alfa and rFSH are quite different their pharmacodynamic profiles at the dosages used are similar.

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      However, corroborative studies comparing the DuoStim protocol with conventional stimulation protocols are needed to draw firm conclusions. Corifollitropin alfa is used in the DuoStim protocol due to its long-lasting profile, with a half-life of 68 h and a maximal serum concentration after 44 h (Fauser et al., 2011). This pharmacokinetic profile showed its advantage compared with daily-administered rFSH in a study including Bologna POR only.

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    Bart CJM Fauser, MD, PhD, is Professor of Reproductive Medicine, University of Utrecht and Chair of the Woman & Baby Division at the University Medical Center, Utrecht. Previously, he was Fulbright post-doctoral scholar at the University of California, San Diego (1987-1988), Visiting Professor at Stanford School of Medicine, Palo Alto (1993-1995), Professor of Reproductive Endocrinology and director of the Center of Reproductive Medicine, Erasmus Medical Center, Rotterdam (1996-2003), editor-in-chief of Molecular Biology in Reproductive Medicine and Human Reproduction Update (2001-2007) and Saal van Zwanenberg Professor, Centre for Reproductive Medicine, Free University of Brussels (2003-2008).

    Declaration: Financial support for this study was provided by Schering-Plough, now Merck, Sharp and Dohme. Editorial support was provided by P Milner, PhD, of PAREXEL and funded by Schering-Plough. BCJMF has received fees and grant support from the following companies (in alphabetical order); Andromed, Ardana, Ferring, Genovum, Glycotope, Merck Serono, Organon, Pantharei Bioscience, Philips, PregLem, Schering and Schering-Plough. MMA has received honoraria and research support from Ferring, Merck-Serono, and Schering-Plough. WL has received fees and grants from the following companies: Akzo Nobel, Ferring, Ipsen and Almirall, Merck Serono, Organon, Schering-Plough, Serono and Wyeth. WBS has received honoraria and research support from Ferring, Merck-Serono and Schering-Plough. AZ and BMJLM are employed by Schering-Plough.

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    Engage investigators Belgium: Devroey, UZ Brussel, 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 IVFa.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 and Gynecology, Utrecht. Norway: Kahn, Sykehuset Telemark HF, Skien; Von During, 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. UK: Balen, Assisted Conception Unit, Leeds General Infirmary; Ledger, Assisted Conception Unit, Jessop Wing, The Halllamshire Hospital, Sheffield; Matthews, Bourn Hall Clinic, Cambridge. USA: Abuzeid, IVF Michigan, Rochester Hills, Ml; 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.

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