Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial
Anders Nyboe Andersen, Scott M Nelson, Bart C J M Fauser, Juan Antonio García-Velasco, Bjarke M Klein, Joan-Carles Arce, ESTHER-1 study group, Herman Tournaye, Petra De Sutter, Wim Decleer, Alvaro Petracco, Edson Borges, Caio Parente Barbosa, Jon Havelock, Paul Claman, Albert Yuzpe, Hana Višnová, Pavel Ventruba, Petr Uher, Milan Mrazek, Anders Nyboe Andersen, Ulla Breth Knudsen, Didier Dewailly, Anne Guivarc'h Leveque, Antonio La Marca, Enrico Papaleo, Waldemar Kuczynski, Katarzyna Kozioł, Margarita Anshina, Irina Zazerskaya, Alexander Gzgzyan, Elena Bulychova, Victoria Verdú, Pedro Barri, Juan Antonio García-Velasco, Manuel Fernández-Sánchez, Fernando Sánchez Martin, Ernesto Bosch, José Serna, Gemma Castillon, Rafael Bernabeu, Marcos Ferrando, Stuart Lavery, Marco Gaudoin, Scott M Nelson, Bart C J M Fauser, Bjarke M Klein, Lisbeth Helmgaard, Bernadette Mannaerts, Joan-Carles Arce, Anders Nyboe Andersen, Scott M Nelson, Bart C J M Fauser, Juan Antonio García-Velasco, Bjarke M Klein, Joan-Carles Arce, ESTHER-1 study group, Herman Tournaye, Petra De Sutter, Wim Decleer, Alvaro Petracco, Edson Borges, Caio Parente Barbosa, Jon Havelock, Paul Claman, Albert Yuzpe, Hana Višnová, Pavel Ventruba, Petr Uher, Milan Mrazek, Anders Nyboe Andersen, Ulla Breth Knudsen, Didier Dewailly, Anne Guivarc'h Leveque, Antonio La Marca, Enrico Papaleo, Waldemar Kuczynski, Katarzyna Kozioł, Margarita Anshina, Irina Zazerskaya, Alexander Gzgzyan, Elena Bulychova, Victoria Verdú, Pedro Barri, Juan Antonio García-Velasco, Manuel Fernández-Sánchez, Fernando Sánchez Martin, Ernesto Bosch, José Serna, Gemma Castillon, Rafael Bernabeu, Marcos Ferrando, Stuart Lavery, Marco Gaudoin, Scott M Nelson, Bart C J M Fauser, Bjarke M Klein, Lisbeth Helmgaard, Bernadette Mannaerts, Joan-Carles Arce
Abstract
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.
Keywords: Antimüllerian hormone; OHSS; follitropin delta; ovarian response; pregnancy.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed