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

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.

• Authors: Osamu Ishihara, Joan-Carles Arce, Japanese Follitropin Delta Phase 3 Trial (STORK) Group
• Journal: Reproductive biomedicine online (Reprod Biomed Online) Vol. 42 Issue 5 Pg. 909-918 (May 2021) ISSN: 1472-6491 [Electronic] Netherlands
• PMID: 33722477 (Publication Type: Equivalence Trial, Journal Article, Multicenter Study)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Chemical References

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

Topics

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