93 Gynecological Endocrinology, 2013; 29(2): 93–97 © 2013 Informa UK, Ltd. ISSN 0951-3590 print/ISSN 1473-0766 online DOI: 10.3109/09513590.2012.730577 Background: A randomized controlled trial (RCT) comparing highly purified human Choriogonadotrophin (HP-hCG) and recombinant hCG (r-hCG) both administered subcutaneously for triggering ovulation in controlled ovarian stimulation (COS) for Assisted Reproductive Technology (ART). Methods: Multi-centre (n = 4), prospective, controlled, randomized, non-inferiority, parallel group, investigator blind design, including 147 patients. The trial was registered with www.clinicaltrials.gov, using the identifier: NCT00335569. The primary endpoint is the number of oocytes retrieved, while the secondary endpoints include embryo implantation, pregnancy and delivery rates as well as safety parameters. Results: The number of retrieved oocytes was not inferior when HP-hCG was used as compared to r-hCG: the mean number was 13.3 (6.8) in HP-hCG and 12.5 (5.8) in the r-hCG group (p = 0.49) with a 95% CI (-1.34, 2.77). Regarding the secondary outcomes, there were also no differences in fertiliza- tion rate at 57.3% (467/815) vs. 61.3% (482/787) (p = 0.11), the number of embryos available for transfer and cryopreservation (2PN stage) and implantation, pregnancy and delivery rates. Furthermore, there were no differences in the number and type of adverse events reported. HP-hCG was therefore not inferior to r-hCG. Conclusions: HP-hCG and r-hCG are equally efficient and safe for triggering ovulation in ART and, both being admin- istered subcutaneously, equally practical and well tolerated by patients. Keywords: COH, hCG, highly purified, triggering ovulation Introduction Inducing multiple ovulation through controlled ovarian stimula- tion (COS) has been instrumental in improving the outcome of assisted reproductive technologies (ART) [1–3]. As previously determined when inducing ovulation, 5,000–10,000 IU of hCG are needed for triggering the inal stages of oocyte maturation [4,5]. Over the years, the sources of gonadotropins and hCG were diversiied. In pre-IVF days, products obtained from pregnant women urine (u-hCG) replaced the non-human preparations used before [4]. Today, hCG is also produced by recombinant techniques (r-hCG) [6]. In a comparison of u-hCG et r-hCG [6], the authors concluded that r-hCG (0.250 mg) is as efective and well tolerated as the existing reference, 10,000 IU of u-hCG, for inducing inal follic- ular maturation in women undergoing ART [7]. In parallel u-hCG was further puriied using nano-iltration techniques, which yielded highly puriied (HP) hCG (HP-hCG, Gonasi® HP, IBSA Italia, Roma, Italy) [8]. Like their recombinant counterparts, HP products are administered subcutaneously. A study comparing HP-hCG and r-hCG showed that the overall purity of the two products was comparable [9], with similar eletrophoretic proiles. Yet, HP-hCG contained lower concentra- tions of urinary contaminants such as epidermal growth factor (EGF) than other urinary hCG preparations (u-hCG) [10]. he reported concentrations of eosinophil derived neurotoxin (EDN) in HP-hCG are suspicious however, as its measurement was 1,000 less sensitive than that of EGF [9]. he recent availability of HP-hCG (IBSA Institut Biochimique SA) motivated the present RCT for comparing its safety and ei- cacy to r-hCG. HP-hCG and r-hCG were studied in the context of COS conducted in ART, for either IVF or ICSI. he higher degree of purity of HP-hCG, as compared to classical u-hCG, obtained through nano-iltration rendered s.c. administration possible, which was tested in the present trial. Methods General information A multi-centre single blind randomized controlled non-inferi- ority trial was conducted in four centers in Switzerland between 8/2005 and 10/2007. he trial, approved by each institution’s internal review board and the health authorities of Switzerland, was registered with www.clinicaltrials.gov with the identiier: NCT00335569. Reporting of this study follows the recommen- dations of the CONSORT 2010 statement [11]. he study was monitored by a Contract Research Organization appointed by the Sponsor. Studied population Participation in the study was ofered to regular ART patients (IVF or ICSI), aged 18–39 years whose BMI was between 18 and ART Randomized controlled trial comparing highly purified (HP-hCG) and recombinant hCG (r-hCG) for triggering ovulation in ART Marina Bellavia 1 , Christian de Geyter 2 , Isabelle Streuli 3,4 , Victoria Ibecheole 4 , Martin H. Birkhäuser 5 , Barbara P. S. Cometti 6 & Dominique de Ziegler 1,3,4 1 Department of Obstetrics & Gynecology, Reproductive Endocrinology and Infertility, CHUV, Lausanne, Switzerland, 2 Division of Gynecology Endocrinology and Reproductive Medicine, Women’s Hospital, University of Basel, Basel, Switzerland, 3 Department of Obstetrics & Gynecology II, Reproductive Endocrinology and Infertility, Université Paris Descartes, Hôpital Cochin, Paris, France, 4 Department of Obstetrics and Gynecology, University Hospital Geneva, Geneva, Switzerland, 5 Department of Obstetrics and Gynecology, University of Berne, Inselspital, Bern, Switzerland, and 6 IBSA Institut Biochimique SA, Pambio-Noranco, Switzerland Correspondence: Dr. Barbara Cometti, Ph.D., Clinical Research Manager, R&D Department, IBSA Institut Biochimique SA, Via del Piano, P.O. Box 266, CH-6915 Pambio-Noranco. E-mail: barbara.cometti@ibsa.ch Gynecol Endocrinol Downloaded from informahealthcare.com by Medizinbibliothek im Kantonsspital on 02/03/13 For personal use only.