Randomized, assessor-blind, antimüllerian hormone–stratified, dose-response trial in Japanese in vitro fertilization/intracytoplasmic sperm injection patients undergoing controlled ovarian stimulation with follitropin delta
Article In Press
Published
Authors:
Osamu Ishihara, M.D., Ph.D., Bjarke M. Klein, Ph.D., Joan-Carles Arce, M.D., Ph.D. for the Japanese Follitropin Delta Phase 2 Trial Group
Abstract:
Objective
To establish the relationship between follitropin delta doses (recombinant follicle-stimulating hormone produced from the human cell line PER.C6) and ovarian response in Japanese women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment and to evaluate the influence of initial antimüllerian hormone (AMH) levels.
Design
Randomized, controlled, assessor-blind, AMH-stratified (low 5.0–14.9 pmol/L; high 15.0–44.9 pmol/L) dose-response trial.
Setting
Reproductive medicine clinics.
Patient(s)
A total of 158 Japanese women (20–39 years of age).
Intervention(s)
Controlled ovarian stimulation with 6, 9, or 12 μg/d of follitropin delta or 150 IU/d follitropin beta as a reference arm in a gonadotropin-releasing hormone antagonist cycle.
Main Outcome Measure(s)
Number of oocytes retrieved.
Result(s)
Among all women who started stimulation, the mean number (± standard deviation) of oocytes retrieved in the 6 μg/d, 9 μg/d, and 12 μg/d follitropin delta groups was 7.0 ± 4.1, 9.1 ± 5.6, and 11.6 ± 5.6, respectively, and a significant dose-relation was established, which also remained significant within each AMH strata. Significant dose-responses also were observed for serum estradiol, inhibin A, and progesterone at end-of-stimulation with follitropin delta. The vital pregnancy rate per started cycle with follitropin delta was 19% for 6 μg/d, 20% for 9 μg/d, and 25% for 12 μg/d. The rate of early moderate/severe ovarian hyperstimulation syndrome with follitropin delta was 8% for 6 μg/d, 8% for 9 μg/d, and 13% for 12 μg/d, with 82% of the cases in the high AMH stratum.
Conclusion(s)
This trial establishes the dose-response relationship between follitropin delta and ovarian response in Japanese women.
Clinical Trial Registration Number
NCT02309671.
