Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial
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- Individualized versus conventional ovarian stimulation for in vitro fertilization
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OBJECTIVE: 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.
DESIGN: Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1).
SETTING: Reproductive medicine clinics.
PATIENT(S): A total of 1,329 women (aged 18-40 years).
INTERVENTION(S): 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).
MAIN OUTCOMES MEASURE(S): Ongoing pregnancy and ongoing implantation rates; noninferiority margins -8.0%.
RESULT(S): 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).
CONCLUSION(S): 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.
CLINICAL TRIAL REGISTRATION NUMBER: NCT01956110.
|Journal||Fertility and Sterility|
|Publication status||Published - Feb 2017|
- Adolescent, Adult, Anti-Mullerian Hormone/blood, Biomarkers/blood, Body Weight/drug effects, Brazil, Canada, Embryo Implantation, Embryo Transfer, Europe, Female, Fertility/drug effects, Fertility Agents, Female/administration & dosage, Fertilization in Vitro/adverse effects, Follicle Stimulating Hormone, Human/administration & dosage, Humans, Infertility/diagnosis, Live Birth, Ovarian Hyperstimulation Syndrome/etiology, Ovulation/drug effects, Ovulation Induction/adverse effects, Pregnancy, Pregnancy Rate, Recombinant Proteins/administration & dosage, Treatment Outcome, Young Adult
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