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

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.