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 - Tournaye, Herman

AU - De Sutter, Petra

AU - Decleer, Wim

AU - Petracco, Alvaro

AU - Borges, Edson

AU - Barbosa, Caio Parente

AU - Havelock, Jon

AU - Claman, Paul

AU - Yuzpe, Albert

AU - Višnová, Hana

AU - Ventruba, Pavel

AU - Uher, Petr

AU - Mrazek, Milan

AU - Andersen, Anders Nyboe

AU - Knudsen, Ulla Breth

AU - Dewailly, Didier

AU - Leveque, Anne Guivarc h.

AU - La Marca, Antonio

AU - Papaleo, Enrico

AU - Kuczynski, Waldemar

AU - Kozioł, Katarzyna

AU - Anshina, Margarita

AU - Zazerskaya, Irina

AU - Gzgzyan, Alexander

AU - Bulychova, Elena

AU - Verdú, Victoria

AU - Barri, Pedro

AU - García-Velasco, Juan Antonio

AU - Fernández-Sánchez, Manuel

AU - Martin, Fernando Sánchez

AU - Bosch, Ernesto

AU - Serna, José

AU - Castillon, Gemma

AU - Bernabeu, Rafael

AU - Ferrando, Marcos

AU - Lavery, Stuart

AU - Gaudoin, Marco

AU - Fauser, Bart C.J.M.

AU - Klein, Bjarke M.

AU - Helmgaard, Lisbeth

AU - Mannaerts, Bernadette

AU - Arce, Joan Carles

N1 - Publisher Copyright: © 2016 The Authors Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2017/2/1

Y1 - 2017/2/1

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 - Antimüllerian hormone

KW - follitropin delta

KW - OHSS

KW - ovarian response

KW - pregnancy

UR - http://www.scopus.com/inward/record.url?scp=85007296368&partnerID=8YFLogxK

U2 - 10.1016/j.fertnstert.2016.10.033

DO - 10.1016/j.fertnstert.2016.10.033

M3 - Article

C2 - 27912901

AN - SCOPUS:85007296368

VL - 107

SP - 387-396.e4

JO - Fertility and Sterility

JF - Fertility and Sterility

SN - 0015-0282

IS - 2

ER -