Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial
Individualized follitropin delta was similar to conventional follitropin alfa in ongoing pregnancy and ongoing implantation rates but gave more targeted response and fewer ovarian hyperstimulation syndrome preventive measures.
Volume 107, Issue 2, Pages 387–396
Anders Nyboe Andersen, M.D., Ph.D., Scott M. Nelson, M.R.C.O.G., Ph.D., Bart C.J.M. Fauser, M.D., Ph.D., Juan Antonio García-Velasco, M.D., Ph.D., Bjarke M. Klein, Ph.D., Joan-Carles Arce, M.D., Ph.D., the ESTHER-1 study group
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).
Main Outcomes Measure(s)
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.