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Human Reproduction Update Advance Access originally published online on January 30, 2009
Human Reproduction Update 2009 15(3):309-321; doi:10.1093/humupd/dmn065
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency

B.C.J.M. Fauser1,7, B.M.J.L. Mannaerts2, P. Devroey3, A. Leader4, I. Boime5 and D.T. Baird6

1 Department of Reproductive Medicine and Gynecology, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands 2 Clinical Development Department, Schering-Plough, Oss, The Netherlands 3 Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Brussels, Belgium 4 The Ottawa Fertility Centre, Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Ottawa, Ontario, Canada 5 Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO, USA 6 Division of Reproductive and Developmental Sciences, University of Edinburgh Centre for Reproductive Biology, The Queen's Medical Research Institute, Edinburgh, UK

7 Correspondence address. Tel: +31-88-7557524; Fax: +31-88-7555433; E-mail: b.c.fauser{at}umcutrecht.nl

BACKGROUND: Recombinant DNA technologies have been used to develop longer-acting therapeutic proteins. One approach is to introduce sequences containing additional glycosylation sites. Using this technique, a new chimeric gene has been developed containing the coding sequences of the FSH β-subunit and the C-terminal peptide of the hCG β-subunit, which bears four O-linked oligosaccharide binding sites. Co-expression of the {alpha}-subunit and the chimeric FSH β-subunit produces a new recombinant molecule, named corifollitropin alfa, with a prolonged elimination half-life and enhanced in vivo bioactivity compared with wild-type FSH.

METHODS: Medline searches by subject and additional searching by hand.

RESULTS: Initial studies in pituitary suppressed female volunteers confirmed the extended half-life of the compound. Phase II studies have shown that corifollitropin alfa is able to induce and sustain multi-follicular growth for an entire week in women undergoing ovarian stimulation using GnRH antagonist co-treatment for IVF. Corifollitropin alfa regimens have been developed with dosages of 100 and 150 µg, for patients with body weight ≤60 and >60 kg, respectively.

CONCLUSIONS: Corifollitropin alfa is the first long-acting hybrid molecule with sustained follicle-stimulating activity developed for the induction of multi-follicular growth along with GnRH antagonist co-treatment for IVF. This new treatment option may be simpler and more convenient for patients compared with conventional long protocols of daily FSH injections in combination with GnRH agonist co-treatment. The safety and efficacy of such regimens is currently being evaluated in large comparative phase III clinical trials. The development of corifollitropin alfa is the first step towards a new generation of recombinant gonadotrophins.

Key words: corifollitropin alfa / ovarian stimulation / FSH / IVF

Received on September 26, 2008; revised November 26, 2008; accepted on December 29, 2008


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