Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

Nyboe Andersen, A, Nelson, S M, Fauser, B C, Garcia-Velasco, J A, Klein, B M, Arce, J C, group, Esther- study,
Fertil Steril. Feb. 2017 doi: 10.1016/j.fertnstert.2016.10.033


OBJECTIVE: To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimullerian 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 mug/d; AMH >/=15 pmol/L: 0.10-0.19 mug/kg/d; maximum 12 mug/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 mug). 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.