title: Ovarian response to recombinant human follicle-stimulating hormone: a randomized, antimüllerian hormone-stratified, dose-response trial in women undergoing in vitro fertilization/intracytoplasmic sperm injection.
abstract: OBJECTIVE
  To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrations.
  
  
  METHODS
  Randomized, controlled, assessor-blinded, AMH-stratified (low: 5.0-14.9 pmol/L [0.7-<2.1 ng/mL]; high: 15.0-44.9 pmol/L [2.1-6.3 ng/mL]) trial.
  
  
  METHODS
  Seven infertility centers in four countries.
  
  
  METHODS
  Two hundred sixty-five women aged ≤37 years.
  
  
  METHODS
  Controlled ovarian stimulation with either 5.2, 6.9, 8.6, 10.3, or 12.1 μg of rhFSH, or 11 μg (150 IU) of follitropin alfa in a GnRH antagonist cycle.
  
  
  METHODS
  Number of oocytes retrieved.
  
  
  RESULTS
  The number of oocytes retrieved increased in an rhFSH dose-dependent manner, from 5.2 ± 3.3 oocytes with 5.2 μg/d to 12.2 ± 5.9 with 12.1 μg/d. The slopes of the rhFSH dose-response curves differed significantly between the two AMH strata, demonstrating that a 10% increase in dose resulted in 0.5 (95% confidence interval 0.2-0.7) and 1.0 (95% confidence interval 0.7-1.3) more oocytes in the low and high AMH stratum, respectively. Fertilization rate and blastocyst/oocyte ratio decreased significantly with increasing rhFSH doses in both AMH strata. No linear relationship was observed between rhFSH dose and number of blastocysts overall or by AMH strata. Five cases of ovarian hyperstimulation syndrome were reported for the three highest rhFSH doses and in the high AMH stratum.
  
  
  CONCLUSIONS
  Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner. The availability of blastocysts is less influenced by the rhFSH dose and AMH level.
  
  
  BACKGROUND
  NCT01426386.
authors.affiliation: Reproductive Health, Ferring Pharmaceuticals, Copenhagen, Denmark. Electronic address: jca@ferring.com.
authors.forename: Joan-Carles
authors.initials: JC
authors.lastname: Arce
authors.affiliation: Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Anders Nyboe
authors.initials: AN
authors.lastname: Andersen
authors.affiliation: IVI Sevilla, Seville, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Fernández-Sánchez
authors.affiliation: IVF CUBE SE, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Visnova
authors.affiliation: IVI Valencia, Valencia, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Bosch
authors.affiliation: IVI Madrid, Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: García-Velasco
authors.affiliation: Obstetrics, Gynecology & Reproduction, IU Dexeus, Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Barri
authors.affiliation: Reproductive Medicine, Universitair Ziekenhuis, Ghent, Belgium.
authors.forename: Petra
authors.initials: P
authors.lastname: de Sutter
authors.affiliation: Global Biometrics, Ferring Pharmaceuticals, Copenhagen, Denmark.
authors.forename: Bjarke M
authors.initials: BM
authors.lastname: Klein
authors.affiliation: Division Woman & Baby, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
mesh_terms: D000328:Adult; D054304:Anti-Mullerian Hormone / Q000008:administration & dosage*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage*; D006801:Humans; D054315:Oocyte Retrieval; D010062:Ovulation Induction / Q000379:methods; D011994:Recombinant Proteins / Q000008:administration & dosage; D020554:Sperm Injections, Intracytoplasmic / Q000379:methods; D016896:Treatment Outcome
chemical_list: D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; C571801:follitropin alfa; D054304:Anti-Mullerian Hormone
keywords: Antimüllerian hormone; blastocyst; in vitro fertilization; oocyte; ovarian response; recombinant FSH