Individualized follitropin delta dosing reduces OHSS risk in Japanese IVF/ICSI patients: a randomized controlled trial

Reprod Biomed Online. 2021 May;42(5):909-918. doi: 10.1016/j.rbmo.2021.01.023. Epub 2021 Feb 9.

Abstract

Research question: This study aimed to establish the efficacy and safety of ovarian stimulation with a follitropin delta individualized fixed-dose regimen based on serum anti-Müllerian hormone (AMH) concentration and body weight versus conventional follitropin beta dosing in Japanese women.

Design: This randomized, controlled, assessor-blind, multicentre, non-inferiority trial was conducted in 347 Japanese IVF/intracytoplasmic sperm injection patients. They were randomized to individualized follitropin delta (AMH <15 pmol/l: 12 µg/day; AMH ≥15 pmol/l: 0.10-0.19 µg/kg/day; minimum 6 µg/day; maximum 12 µg/day) or conventional follitropin beta (150 IU/day for the first 5 days, with potential subsequent dose adjustments). The primary end-point was the number of oocytes retrieved with a pre-specified non-inferiority margin (-3.0 oocytes).

Results: The primary trial objective was met, as non-inferiority was established for number of oocytes retrieved for individualized follitropin delta dosing compared with conventional follitropin beta dosing (9.3 versus 10.5; lower boundary of 95% confidence interval -2.3). The occurrence of ovarian hyperstimulation syndrome (OHSS) was reduced to approximately half with individualized compared with conventional dosing, with an incidence of 11.2% versus 19.8% (P = 0.021) for OHSS of any grade and 7.1% versus 14.1% (P = 0.027) for moderate/severe OHSS. The live birth rate per started cycle was 23.5% for individualized dosing and 18.6% for conventional dosing.

Conclusions: Dosing with individualized follitropin delta in Japanese women is non-inferior to conventional dosing with follitropin beta for number of oocytes retrieved. The individualized approach shows a favourable benefit-risk profile, providing a statistically significant and clinically relevant reduction in the incidence of OHSS, without compromising live birth rates.

Keywords: Anti-Müllerian hormone; Follitropin delta; Individualized dosing; Japan; Live birth; Ovarian hyperstimulation syndrome.

Publication types

  • Equivalence Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Anti-Mullerian Hormone / blood
  • Birth Rate
  • Female
  • Follicle Stimulating Hormone, Human / administration & dosage*
  • Follicle Stimulating Hormone, Human / adverse effects*
  • Humans
  • Ovarian Hyperstimulation Syndrome / blood
  • Ovarian Hyperstimulation Syndrome / etiology
  • Ovarian Hyperstimulation Syndrome / prevention & control*
  • Ovary / drug effects*
  • Ovulation Induction / adverse effects
  • Ovulation Induction / methods
  • Ovulation Induction / statistics & numerical data*
  • Pregnancy
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects

Substances

  • Follicle Stimulating Hormone, Human
  • Recombinant Proteins
  • follitropin beta
  • follitropin delta
  • Anti-Mullerian Hormone