title: Corifollitropin alfa compared with follitropin beta in poor responders undergoing ICSI: a randomized controlled trial.
abstract: OBJECTIVE
  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)?
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  Seventy-nine women with previous poor ovarian response undergoing ICSI treatment were enrolled in this open label, non-inferiority, randomized clinical trial (RCT).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece stratis.kolibianakis@gmail.com.
authors.forename: E M
authors.initials: EM
authors.lastname: Kolibianakis
authors.affiliation: Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece School of Women's and Children's Health, UNSW Medicine, University of New South Wales, Sydney, Australia.
authors.forename: C A
authors.initials: CA
authors.lastname: Venetis
authors.affiliation: Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: J K
authors.initials: JK
authors.lastname: Bosdou
authors.affiliation: Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: L
authors.initials: L
authors.lastname: Zepiridis
authors.affiliation: Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Chatzimeletiou
authors.affiliation: Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Makedos
authors.affiliation: Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Masouridou
authors.affiliation: Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Triantafillidis
authors.affiliation: Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Mitsoli
authors.affiliation: Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: B C
authors.initials: BC
authors.lastname: Tarlatzis
mesh_terms: D000328:Adult; D001723:Birth Rate; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004351:Drug Resistance / Q000187:drug effects*; D004477:Ectogenesis / Q000187:drug effects; D005191:Family Characteristics; D005240:Feasibility Studies; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006115:Greece / Q000453:epidemiology; D006801:Humans; D007247:Infertility, Female / Q000628:therapy*; D007248:Infertility, Male; D007279:Injections, Subcutaneous; D008297:Male; D054315:Oocyte Retrieval; D010062:Ovulation Induction / Q000009:adverse effects*; D011247:Pregnancy; D018873:Pregnancy Rate; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D020554:Sperm Injections, Intracytoplasmic
chemical_list: D005300:Fertility Agents, Female; D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; C437186:follicle stimulating hormone, human, with HCG C-terminal peptide; C571802:follitropin beta
keywords: corifollitropin alfa; follitropin beta; in vitro fertilization; poor ovarian response; recombinant FSH