title: Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial.
abstract: To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF.
  
  
  
  Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1).
  
  
  
  Reproductive medicine clinics.
  
  
  
  A total of 1,329 women (aged 18-40 years).
  
  
  
  Follitropin delta (AMH <15 pmol/L: 12 μg/d; AMH ≥15 pmol/L: 0.10-0.19 μg/kg/d; maximum 12 μg/d), or follitropin alfa (150 IU/d for 5 days, potential subsequent dose adjustments; maximum 450 IU/d).
  
  
  
  Ongoing pregnancy and ongoing implantation rates; noninferiority margins -8.0%.
  
  
  
  Ongoing pregnancy (30.7% vs. 31.6%; difference -0.9% [95% confidence interval (CI) -5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; -0.6% [95% CI -6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; -0.9% [95% CI -5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8-14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH <15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (≥15 or ≥20 oocytes in patients with AMH ≥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6 μg).
  
  
  
  Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation.
  
  
  
  NCT01956110.
authors.affiliation: Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Nyboe Andersen
authors.affiliation: School of Medicine, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Nelson
authors.affiliation: Division Woman & Baby, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
authors.affiliation: IVI Madrid, Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: García-Velasco
authors.affiliation: Biometrics, Ferring Pharmaceuticals, Copenhagen, Denmark.
authors.forename: Bjarke M
authors.initials: BM
authors.lastname: Klein
authors.affiliation: Reproductive Health, Ferring Pharmaceuticals, Copenhagen, Denmark. Electronic address: jca@ferring.com.
authors.forename: Joan-Carles
authors.initials: JC
authors.lastname: Arce
mesh_terms: D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D001938:Brazil; D002170:Canada; D010064:Embryo Implantation; D004624:Embryo Transfer; D005060:Europe; D005260:Female; D005298:Fertility / Q000187:drug effects; D005300:Fertility Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects; D005307:Fertilization in Vitro / Q000009:adverse effects; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007246:Infertility / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D050498:Live Birth; D016471:Ovarian Hyperstimulation Syndrome / Q000209:etiology / Q000517:prevention & control; D010060:Ovulation / Q000187:drug effects*; D010062:Ovulation Induction / Q000009:adverse effects / Q000379:methods*; D011247:Pregnancy; D018873:Pregnancy Rate; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005300:Fertility Agents, Female; D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; C571801:follitropin alfa; C000620228:follitropin delta; D054304:Anti-Mullerian Hormone
keywords: Antimüllerian hormone; OHSS; follitropin delta; ovarian response; pregnancy