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

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-M & uuml;llerian 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 & micro;g/day; AMH >= 15 pmol/l: 0.10-0.19 & micro;g/kg/day; minimum 6 & micro;g/day; maximum 12 & micro;g/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 (& minus;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 & minus;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.

Automated summary

The individualized fixed-dose regimen of follitropin delta for ovarian stimulation in Japanese women is just as effective as conventional follitropin beta dosing in terms of number of oocytes retrieved, while significantly reducing the incidence of ovarian hyperstimulation syndrome (OHSS).