A comparison of live birth rates and cumulative ongoing pregnancy rates between Europe and North America after ovarian stimulation with corifollitropin alfa or recombinant follicle-stimulating hormone


      To compare live birth rates after fresh embryo transfer (ET) and cumulative ongoing pregnancy rates after fresh ET and frozen-thawed (ET) between continents and overall after one treatment cycle with corifollitropin alfa or recombinant FSH.


      Double-blind, multicenter, randomized controlled trial.


      Fourteen centers in North America (NA); 20 in Europe (EU).


      804 NA patients and 702 EU patients.


      Patients >60 kg received a single dose of corifollitropin alfa or daily rFSH for the first 7 days of controlled ovarian stimulation.

      Main Outcome Measure(s)

      Live birth rates.


      Within each continent no differences were noted between the two treatment groups; however, between continents, the cumulative ongoing pregnancy rate and live birth rate were considerably higher in NA than in EU. The live birth rate in NA was 39.2% in both treatment groups compared with 31.5% and 28.8% in EU after corifollitropin alfa and rFSH treatment, respectively. Considering the number of embryos transferred, the live birth rate per ET was still higher in NA than in EU (42.7% v.s 36.8% with corifollitropin alfa and 41.6% vs. 30.9% with rFSH). Overall live birth rates after fresh ET were 35.6% and 34.4% (estimated difference 1.1% [95% confidence interval −3.7–5.8]), and the estimated cumulative live birth rates were 43.4% and 41.3% with corifollitropin alfa and rFSH, respectively.


      Live birth rates and cumulative pregnancy rates were higher in NA than in EU after treatment with either corifollitropin alfa or daily rFSH; both treatment protocols provided equal success rates. Identifiers

      Key Words

      To read this article in full you will need to make a payment


      Subscribe to Fertility and Sterility
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Thurin-Kjellberg A.
        • Carlsson P.
        • Bergh C.
        Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis.
        Hum Reprod. 2006; 21: 210-216
        • Devroey P.
        • Boostanfar R.
        • Koper N.P.
        • Mannaerts B.M.J.L.
        • Ijzerman-Boon P.C.
        • Fauser B.C.J.M.
        • Engage Investigators
        A double-blind, noninferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol.
        Hum Reprod. 2009; 24: 3063-3072
        • Min J.K.
        • Breheny S.A.
        • MacLachlan V.
        • Healy D.L.
        What is the most relevant standard of success in assisted reproduction? The singleton, term gestation, live birth rate per cycle initiated: the BESST endpoint for assisted reproduction.
        Hum Reprod. 2004; 19: 3-7
        • Arce J.C.
        • Nyboe Andersen A.
        • Collins J.
        Resolving methodological and clinical issues in the design of efficacy trials in assisted reproductive technologies: a mini-review.
        Hum Reprod. 2005; 20: 1757-1771
        • Fauser B.C.J.M.
        • Mannaerts B.M.J.L.
        • Devroey P.
        • Leader A.
        • Boime I.
        • Baird D.T.
        Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency.
        Hum Reprod Update. 2009; 15: 309-321
        • Fauser B.C.
        • Alper M.M.
        • Ledger W.
        • Schoolcraft W.B.
        • Zandvliet A.
        • Mannaerts B.M.
        • Engage Investigators
        Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF.
        Reprod Biomed Online. 2010; 21: 593-601
        • Gleicher N.
        • Weghofer A.
        • Barad D.
        A formal comparison of the practice of assisted reproductive technologies between Europe and the USA.
        Hum Reprod. 2006; 21: 1945-1950
        • Gleicher N.
        • Weghofer A.
        • Barad D.
        Update on the comparison of assisted reproduction outcomes between Europe and the USA: the 2002 data.
        Fertil Steril. 2007; 87: 1301-1305
        • Baker V.L.
        • Jones C.E.
        • Cometti B.
        • Hoehler F.
        • Salle B.
        • Urbancsek J.
        • et al.
        Factors affecting success rates in two concurrent clinical IVF trials: an examination of potential explanations for the difference in pregnancy rates between the United States and Europe.
        Fertil Steril. 2010; 94: 1287-1291
        • Gerris J.M.
        Single embryo transfer and IVF/ICSI outcome: a balanced appraisal.
        Hum Reprod Update. 2005; 11: 105-121
        • Scotland G.
        • McLernon D.
        • Kurinczuk J.
        • McNamee P.
        • Harrild K.
        • Lyall H.
        • et al.
        Minimising twins in in vitro fertilisation: a modelling study assessing the costs, consequences and cost-utility of elective single versus double embryo transfer over a 20-year time horizon.
        Br J Obstet Gynecol. 2011; 118: 1073-1083
        • Connolly M.P.
        • Hoorens S.
        • Chambers G.M.
        • ESHRE Reproduction and Society Task Force
        The costs and consequences of assisted reproductive technology: an economic perspective.
        Hum Reprod Update. 2010; 16: 603-613
        • Duijkers I.J.
        • Klipping C.
        • Boerrigter P.J.
        • Machielsen C.S.
        • de Bie J.J.
        • Voortman G.
        Single dose pharmacokinetics and effects on follicular growth and serum hormones of a long-acting recombinant FSH preparation (FSH-CTP) in healthy pituitary-suppressed females.
        Hum Reprod. 2002; 17: 1987-1993
        • Devroey P.
        • Fauser B.C.
        • Platteau P.
        • Beckers N.G.
        • Dhont M.
        • Mannaerts B.M.
        Induction of multiple follicular development by a single dose of long-acting recombinant follicle-stimulating hormone (FSH-CTP, corifollitropin alfa) for controlled ovarian stimulation before in vitro fertilization.
        J Clin Endocrinol Metab. 2004; 89: 2062-2070
        • Mannaerts B.M.J.L.
        • Fauser B.
        • Lahlou N.
        • Harlin J.
        • Shoham Z.
        • Coelingh Bennink H.
        • et al.
        Serum hormone concentrations during treatment with multiple rising doses of recombinant follicle stimulating hormone (rFSH; Puregon): relationship between serum FSH and efficacy.
        Hum Reprod Update. 1996; 2: 153-161
        • Macklon N.S.
        • Stouffer R.L.
        • Giudice L.C.
        • Fauser B.C.J.M.
        The science behind 25 years of ovarian stimulation for IVF.
        Endocr Rev. 2006; 27: 170-207
        • Shoham Z.
        The clinical therapeutic window for luteinizing hormone in controlled ovarian stimulation.
        Fertil Steril. 2002; 77: 1170-1177
        • Griesinger G.
        • Shapiro D.B.
        Luteinizing hormone add-back: is it needed in controlled ovarian stimulation, and if so, when?.
        J Reprod Med. 2001; 56: 279-300
      1. Nyboe Andersen A, Pellicer A, Devroey P, Arce JC. A randomized trial (MEGASET) comparing highly purified menotropin and recombinant FSH in a GnRH antagonist cycle with single blastocyst transfer. 27th annual meeting of the European Society for Human Reproduction and Embryology, July 3-6, 2011; Stockholm, Sweden: O-296.

        • Doody K.J.
        • Devroey P.
        • Leader A.
        • Witjes H.
        • Mannaerts B.M.
        No association between endogenous LH and pregnancy in a GnRH antagonist protocol: part 1, corifollitropin alfa.
        Reprod Biomed Online. 2011; 23: 449-456
        • Griesinger G.
        • Shapiro D.B.
        • Kolibianakis E.M.
        • Witjes H.
        • Mannaerts B.M.
        No association between endogenous LH and pregnancy in a GnRH antagonist protocol: part II, recombinant FSH.
        Reprod Biomed Online. 2011; 23: 457-465
        • Mardešič T.
        • Abuzeid M.
        • Witjes H.
        • Mannaerts B.
        • Engage Investigators
        Success rates of early responders to corifollitropin alfa or daily rFSH in a large, randomized, double-blind trial.
        Hum Reprod. 2011; 26 ([abst.]): P469
        • Norman R.J.
        • Zegers-Hochschild F.
        • Salle B.S.
        • Elbers J.
        • Heijnen E.
        • Marintcheva-Petrova M.
        • et al.
        • Trust Investigators
        Repeated ovarian stimulation with corifollitropin alfa in patients in a GnRH antagonist protocol: no concern for immunogenicity.
        Hum Reprod. 2011; 26: 2200-2208
        • Henman M.
        • Catt J.W.
        • Wood T.
        • Bowman M.C.
        • de Boer K.A.
        • Jansen R.P.S.
        Elective transfer of single fresh blastocysts and later transfer of cryostored blastocysts reduces the twin pregnancy rate and can improve the in vitro fertilization live birth rate in younger women.
        Fertil Steril. 2005; 84: 1620-1627
        • Selman H.
        • Brusco G.F.
        • Fiorini F.
        • Barnocchi N.
        • Mariani M.
        • El-Danasouri I.
        Vitrification is a highly efficient method to cryopreserve human embryos in in vitro fertilization patients at high risk of developing ovarian hyperstimulation syndrome.
        Fertil Steril. 2009; 91: 1611-1613