Real-World Effectiveness and Safety of Recombinant Human Follicle-Stimulating Hormone (rhFSH) in Infertile Women undergoing Assisted Reproductive Technology (ART): A Korean Nationwide Cohort Study

Abstract

Despite widespread rhFSH use in infertile women undergoing ART, real-world comparative data on its effectiveness and safety across different rhFSH types remain limited. Using the HIRA claims database, we included 10,684 women aged 20-39 with infertility (2016-2021) who used only rhFSH in their first in vitro fertilization-embryo transfer (IVF-ET). Outcome variables comprised effectiveness (>= 11 oocytes retrieved, pregnancy rates and live birth rate) and safety (ectopic pregnancy, miscarriage, preterm birth and ovarian hyperstimulation syndrome [OHSS]) in the whole cohort, further categorized into follitropin and other rhFSH. Baseline characteristics were described, and relative risks (RR) with 95% confidence intervals (CI) were estimated using a generalized linear model, adjusting for age and imbalanced variables. Of 10,684 patients prescribed rhFSH, 7.1% were aged 20-29, 41.6% were 30-34, and 51.3% were 35-39. ICSI was utilized in 57.7% of cycles, and 76.8% used the GnRH antagonist protocol. The live birth rate was 38.8%, and the OHSS rate was 5.9%. Comparing baseline characteristics of the follitropin (n = 2,594) and other rhFSH group (n = 8,090), ICSI (62.2% vs. 56.3%) and GnRH antagonist protocol (81.3% vs. 75.3%) were more common in the follitropin group. Women who received follitropin were more likely to have >= 11 oocytes retrieved (adjusted RR, 1.09; 95% CI: 1.02-1.16) and less likely to have OHSS (adjusted RR, 0.73; 95% CI: 0.60-0.90). These findings provide real-world evidence supporting rhFSH effectiveness and safety in fresh IVF cycles, with follitropin potentially offering advantages in oocyte retrieval and reduced OHSS rates.