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Corifollitropin Alfa

A Review of its Use in Controlled Ovarian Stimulation for Assisted Reproduction

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Abstract

Corifollitropin alfa (Elonva®) is a fusion product of human follicle-stimulating hormone (FSH) and the C-terminal peptide of the β-subunit of human chorionic gonadotropin (hCG) produced by recombinant DNA technology. It has the same pharmacologic activity as FSH and recombinant FSH (rFSH; follitropin alfa; follitropin beta), but with a slower absorption and a longer half-life. Corifollitropin alfa is indicated as a multifollicular stimulant for women undergoing controlled ovarian stimulation using gonadotropin-releasing hormone (GnRH) antagonist-assisted reproduction protocols.

In two large, randomized, double-blind, phase III trials, a single subcutaneous injection of corifollitropin alfa was no less effective as a multifollicular stimulant than seven once-daily injections of rFSH when used as part of a GnRH antagonist-assisted controlled ovarian stimulation cycle. With regard to primary endpoints, the mean number of retrieved oocytes per started cycle demonstrated that the two treatments were equivalent, and the ongoing pregnancy rate in recipients of corifollitropin alfa was noninferior to that in recipients of rFSH. The median duration of stimulation with FSH was 9 days in both treatment arms of both trials, which means that, on average, recipients of corifollitropin alfa required only 2 further days of stimulation with rFSH prior to triggering oocyte maturation with the administration of hCG. Fertilization rates were high, ranging from 66% to 68%, in recipients of corifollitropin alfa or rFSH in both trials.

When used as part of a GnRH antagonist-assisted reproduction protocol, corifollitropin alfa was generally well tolerated, with a tolerability profile similar to that of rFSH. In large, pooled analyses of clinical trials, the incidence of ovarian hyperstimulation syndrome in both the corifollitropin alfa and rFSH treatment arms was consistent with that expected in the relatively young patient population. Furthermore, there were no clinically relevant differences in pregnancy complications and the incidence of infant adverse events between treatment arms.

In conclusion, a single subcutaneous injection of corifollitropin alfa provides sustained multifollicular stimulation for up to a week in women undergoing controlled ovarian stimulation. Compared with seven once-daily injections of rFSH, a single injection of corifollitropin alfa achieves equivalent efficacy, and provides a well tolerated and more convenient treatment option to induce multiple follicular growth prior to assisted reproduction.

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References

  1. American Society for Reproductive Medicine. Infertility: an overview [online]. Available from URL: http://www.asrm.org/uploadedFiles/ASRM_Content/Resources/Patient_Resources/Fact_Sheets_and_Info_Booklets/infertility_overview.pdf [Accessed 2011 Jun 1]

  2. National Collaborating Centre for Women’s and Childrens Health. Fertility: assessment and treatment for people with fertility problems [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/10936/29269/29269.pdf [Accessed 2011 Jun 1]

  3. Human Fertilization and Embryology Authority. Long-term data: birth rates [online]. Available from URL: http://www.hfea.gov.uk/2588.html [Accessed 2011 Jun 1]

  4. Centers for Disease Control and Prevention. Assisted reproductive technology success rates: 2007 [online]. Available from URL: http://www.cdc.gov/art/ART2007/PDF/COMPLETE_2007_ART.pdf [Accessed 2011 Jun 1]

  5. Huirne J, Lambalk CB, van Loenen AC, et al. Contemporary pharmacological manipulation in assisted reproduction. Drugs 2004; 64 (3): 297–322

    Article  PubMed  CAS  Google Scholar 

  6. Daya S. Follicle-stimulating hormone in clinical practice: an update. Treat Endocrinol 2004; 3 (3): 161–71

    Article  PubMed  CAS  Google Scholar 

  7. Al-Shawaf T, Zosmer A, Dirnfeld M, et al. Safety of drugs used in assisted reproduction techniques. Drug Saf 2005; 28 (6): 513–28

    Article  PubMed  CAS  Google Scholar 

  8. Filicori M, Cognigni GE. Clinical review 126: roles and novel regimens of luteinizing hormone and follicle-stimulating hormone in ovulation induction. J Clin Endocrinol Metab 2001 Apr; 86 (4): 1437–41

    Article  PubMed  CAS  Google Scholar 

  9. Fauser BC, Mannaerts BM, Devroey P, et al. Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency. Hum Reprod Update 2009 May; 15 (3): 309–21

    Article  PubMed  CAS  Google Scholar 

  10. Pelinck MJ, Hoek A, Simons AH, et al. Efficacy of natural cycle IVF: a review of the literature. Hum Reprod Update 2002 Mar; 8 (2): 129–39

    Article  PubMed  CAS  Google Scholar 

  11. Papanikolaou E, Kolibianakis E, Devroey P. Emerging drugs in assisted reproduction. Expert Opin Emerg Drugs 2005; 10 (2): 425–40

    Article  PubMed  CAS  Google Scholar 

  12. Humaidan P, Quartarolo J, Papanikolaou EG. Preventing ovarian hyper-stimulation syndrome: guidance for the clinician. Fertil Steril 2010 Jul; 94 (2): 389–400

    Article  PubMed  Google Scholar 

  13. Al-Inany H, Abou-Setta A, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception. Cochrane Database Syst Rev 2006; (3): CD001750

  14. Reh A, Krey L, Noyes N. Are gonadotropin-releasing hormone agonists losing popularity? Current trends at a large fertility center. Fertil Steril 2010 Jan; 93 (1): 101–8

    Article  PubMed  CAS  Google Scholar 

  15. Huisman D, Raymakers X, Hoomans EH. Understanding the burden of ovarian stimulation: fertility expert and patient perceptions. Reprod Biomed Online 2009; 19Suppl. 2: 5–10

    Article  PubMed  Google Scholar 

  16. Fares FA, Suganuma N, Nishimori K, et al. Design of a long-acting follitropin agonist by fusing the C-terminal sequence of the chorionic gonadotropin beta subunit to the follitropin beta subunit. Proc Natl Acad Sci U S A 1992 May 15; 89 (10): 4304–8

    Article  PubMed  CAS  Google Scholar 

  17. European Medicines Agency. Elonva (corifollitropin alfa): summary of product characteristics [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001106/WC500074786.pdf [Accessed 2011 Jun 1]

  18. Ryan RJ, Charlesworth MC, McCormick DJ, et al. The glycoprotein hormones: recent studies of structure-function relationships. FASEB J 1988 Aug; 2 (11): 2661–9

    PubMed  CAS  Google Scholar 

  19. Stockell Hartree A, Renwick AG. Molecular structures of glycoprotein hormones and functions of their carbohydrate components. Biochem J 1992 Nov 1; 287 (Pt 3): 665–79

    PubMed  CAS  Google Scholar 

  20. Kohler PO, Ross GT, Odell WD. Metabolic clearance and production rates of human luteinizing hormone in pre- and postmenopausal women. J Clin Invest 1968 Jan; 47 (1): 38–47

    Article  PubMed  CAS  Google Scholar 

  21. Verbost P, Sloot WN, Rose UM, et al. Pharmacologic profiling of corifollitropin alfa, the first developed sustained follicle stimulant. Eur J Pharmacol 2011 Jan 25; 651 (1–3): 227–33

    Article  PubMed  CAS  Google Scholar 

  22. Duijkers IJ, Klipping C, Boerrigter PJ, et al. 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 Aug; 17 (8): 1987–93

    Article  PubMed  CAS  Google Scholar 

  23. de Greef R, Zandvliet AS, de Haan AF, et al. Dose selection of corifollitropin alfa by modeling and simulation in controlled ovarian stimulation. Clin Pharmacol Ther 2010 Jul; 88 (1): 79–87

    Article  PubMed  Google Scholar 

  24. Devroey P, Boostanfar R, Koper NP, et al. 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. Hum Reprod 2009 Dec; 24 (12): 3063–72

    Article  PubMed  CAS  Google Scholar 

  25. Fauser BC, Alper MM, Ledger W, et al. Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF. Reprod Biomed Online 2010 Nov; 21 (5): 593–601

    Article  PubMed  CAS  Google Scholar 

  26. The Corifollitropin Alfa Ensure Study Group. Corifollitropin alfa for ovarian stimulation in IVF: a randomized trial in lower-body-weight women. Reprod Biomed Online 2010 Jul; 21 (1): 66–76

    Article  Google Scholar 

  27. Devroey P, Fauser BC, Platteau P, et al. 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 May; 89 (5): 2062–70

    Article  PubMed  CAS  Google Scholar 

  28. The Corifollitropin Alfa Dose-Finding Study Group. A randomized dose-response trial of a single injection of corifollitropin alfa to sustain multi-follicular growth during controlled ovarian stimulation. Hum Reprod 2008 Nov; 23 (11): 2484–92

    Article  Google Scholar 

  29. Norman R, Zegers-Hochschild F, Salle B, et al. Repeated ovarian stimulation with corifollitropin alfa in patients in a GnRH antagonist protocol: no concern for immunogenicity. Hum Reprod. Epub 2011 May 27

  30. Van Schanke A, Van DW-KSFM, Bos E, et al. Absorption, distribution, metabolism and excretion of corifollitropin alfa, a recombinant hormone with a sustained follicle-stimulating activity. Pharmacology 2010; 85 (2): 77–87

    Article  PubMed  Google Scholar 

  31. Boostanfar R, Devroey P, Oberye J, et al. No difference in the cumulative pregnancy rates or live birth rates when comparing corifollitropin alfa with daily rFSH treatment for COS [abstract no. O-119]. Hum Reprod 2010 Jun; 25: i47

    Article  Google Scholar 

  32. Doody K, Devroey P, Leader A, et al. No association between endogenous LH and pregnancy in a GnRH antagonist protocol: part 1. Corifollitropin alfa. Reprod Biomed Online 2011. Epub 2011 Jul 8 [online]. Available from URL: http://www.rbmojournal.com/article/PIIS1472648311003592/abstract [Accessed 2011 Jul 11]

  33. Bonduelle M, Oberye J, Passier D, et al. Safety of corifollitropin alfa in controlled ovarian stimulation for assisted reproductive technology: pregnancy and infant follow-up data [abstract no. O-055]. Hum Reprod 2010 Jun; 25: i22–3

    Article  Google Scholar 

  34. Tarlatzis B, Witjes H, Mannaerts B. Combined incidence of OHSS in phase 3 trials of corifollitropin alfa for controlled ovarian stimulation [abstract no. P-323]. Hum Reprod 2010 Jun; 25: i242. Plus poster presented at the 26th Annual Meeting of the European Society of Human Reproduction and Embryology; 2010 Jun 27–30; Rome

    Google Scholar 

  35. Brod M, Verhaak CM, Wiebinga CJ, et al. Improving clinical understanding of the effect of ovarian stimulation on women’s lives. Reprod Biomed Online 2009 Mar; 18 (3): 391–400

    Article  PubMed  CAS  Google Scholar 

  36. Rajkhowa M, McConnell A, Thomas GE. Reasons for discontinuation of IVF treatment: a questionnaire study. Hum Reprod 2006 Feb; 21 (2): 358–63

    Article  PubMed  CAS  Google Scholar 

  37. Goa KL, Wagstaff AJ. Follitropin alpha in infertility: a review. Biodrugs 1998; 9 (3): 235–60

    Article  PubMed  CAS  Google Scholar 

  38. Ledger W, Fauser B, Devroey P, et al. Corifollitropin alfa doses based on body-weight: clinical overview of drug exposure and ovarian response. Reprod Biomed Online 2011. Epub Apr 18 [online]. Available from URL: http://www.rbmojournal.com/article/S1472-6483(11)00225-2/abstract [Accessed 2011 Jun 20]

  39. Balen AH, Mulders AG, Fauser BC, et al. Pharmacodynamics of a single low dose of long-acting recombinant follicle-stimulating hormone (FSH-carboxy terminal peptide, corifollitropin alfa) in women with World Health Organization group II anovulatory infertility. J Clin Endocrinol Metab 2004 Dec; 89 (12): 6297–6304

    Article  PubMed  CAS  Google Scholar 

  40. Fatemi HM, Oberye J, Popovic-Todorovic B, et al. Corifollitropin alfa in a long GnRH agonist protocol: proof of concept trial. Fertil Steril 2010 Feb 10; 94 (5): 1922–4

    Article  PubMed  CAS  Google Scholar 

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  1. Adis, a Wolters Kluwer Business, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Jamie D. Croxtall & Kate McKeage

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  1. Jamie D. Croxtall
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  2. Kate McKeage
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Correspondence to Jamie D. Croxtall.

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Croxtall, J.D., McKeage, K. Corifollitropin Alfa. BioDrugs 25, 243–254 (2011). https://doi.org/10.2165/11206890-000000000-00000

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