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    Does substituting 150 µg corifollitropin alfa for 450 IU follitropin beta during the first 7 days of ovarian stimulation in proven poor responders, result in retrieval of a non-inferior number (<1.5 fewer) of cumulus oocyte complexes (COCs)? A single s.c. dose of 150 µg corifollitropin alfa on the first day of ovarian stimulation, followed if necessary, from Day 8 onwards, with 450 IU of follitropin beta/day, is not inferior to daily doses of 450 IU follitropin beta. The 95% CI of the difference between medians in the number of oocytes retrieved was -1 to +1 within the safety margin of 1.5. Recent data from retrospective studies suggest that the use of corifollitropin alfa in poor responders is promising since it could simplify ovarian stimulation without compromising its outcome. Seventy-nine women with previous poor ovarian response undergoing ICSI treatment were enrolled in this open label, non-inferiority, randomized clinical trial (RCT). Inclusion criteria were: previous poor response to ovarian stimulation (≤4 COCs) after maximal stimulation, age <45 years, regular spontaneous menstrual cycle, body mass index: 18-32 kg/m(2) and basal follicle stimulating hormone ≤20 IU/l. On Day 2 of the menstrual cycle, patients were administered either a single s.c dose of 150 µg corifollitropin alfa (n = 40) or a fixed daily dose of 450 IU of follitropin beta (n = 39). In the corifollitropin alfa group, 450 IU of follitropin beta were administered from Day 8 of stimulation until the day of human chorionic gonadotrophin (hCG) administration, if necessary. To inhibit premature luteinizing hormone surge, the gonadotrophin releasing hormone antagonist ganirelix was used. Triggering of final oocyte maturation was performed using 250 µg of recombinant hCG, when at least two follicles reached 17 mm in mean diameter. The number of COCs retrieved was not statistically different between the corifollitropin alfa and the follitropin beta groups [Median 3 versus 2, 95% CI 2-4, 2-3, respectively, P = 0.26]. The 95% CI of the difference between medians in the number of oocytes retrieved was -1 to +1. A multivariable analysis adjusting for all the potential baseline differences confirmed this finding. No significant difference was observed regarding the probability of live birth between the corifollitropin alfa and the follitropin beta group (live birth per patient reaching oocyte retrieval: 7.9 versus 2.6%, respectively, difference +5.3%, 95% CI: -6.8 to +18.3). The present study was not powered to test a smaller difference (e.g. 1 COC) in terms of COCs retrieved as well as to show potential differences in the probability of pregnancy. Moreover, it would be interesting to assess whether the continuation of stimulation in the long acting FSH arm, where necessary, with 200 IU instead of 450 IU of follitropin beta would have altered the direction or the magnitude of the effect of the type of FSH, observed on the number of COCs retrieved. Corifollitropin alfa simplifies IVF treatment because it is administered in a GnRH antagonist protocol and replaces seven daily FSH injections with a single one of a long acting FSH without compromising the outcome. It could greatly reduce the burden of treatment for poor responders and this deserves further investigation. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email:


    E M Kolibianakis, C A Venetis, J K Bosdou, L Zepiridis, K Chatzimeletiou, A Makedos, S Masouridou, S Triantafillidis, A Mitsoli, B C Tarlatzis. Corifollitropin alfa compared with follitropin beta in poor responders undergoing ICSI: a randomized controlled trial. Human reproduction (Oxford, England). 2015 Feb;30(2):432-40

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    PMID: 25492411

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