TY - JOUR

T1 - Individualized versus conventional ovarian stimulation for in vitro fertilization

T2 - a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

AU - Nyboe Andersen, Anders

AU - Nelson, Scott M

AU - Fauser, Bart C J M

AU - García-Velasco, Juan Antonio

AU - Klein, Bjarke M

AU - Arce, Joan-Carles

AU - ESTHER-1 study group

N1 - Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2017/2

Y1 - 2017/2

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Anti-Mullerian Hormone/blood

KW - Biomarkers/blood

KW - Body Weight/drug effects

KW - Brazil

KW - Canada

KW - Embryo Implantation

KW - Embryo Transfer

KW - Europe

KW - Female

KW - Fertility/drug effects

KW - Fertility Agents, Female/administration & dosage

KW - Fertilization in Vitro/adverse effects

KW - Follicle Stimulating Hormone, Human/administration & dosage

KW - Humans

KW - Infertility/diagnosis

KW - Live Birth

KW - Ovarian Hyperstimulation Syndrome/etiology

KW - Ovulation/drug effects

KW - Ovulation Induction/adverse effects

KW - Pregnancy

KW - Pregnancy Rate

KW - Recombinant Proteins/administration & dosage

KW - Treatment Outcome

KW - Young Adult

U2 - 10.1016/j.fertnstert.2016.10.033

DO - 10.1016/j.fertnstert.2016.10.033

M3 - Journal article

C2 - 27912901

VL - 107

SP - 387-396.e4

JO - Sexuality, Reproduction and Menopause

JF - Sexuality, Reproduction and Menopause

SN - 1546-2501

IS - 2

ER -