A commentary on the article “Controlled Ovarian Stimulation (COS) with follitropin delta results in higher cumulative live birth rates compared with r-hFSH alfa/beta in a large retrospectively analysed real-world data set”

Follitropin delta, a recombinant human follicle-stimulating hormone (r-hFSH), is administered using an individualized dosing algorithm based on serum anti-Müllerian hormone (AMH) levels and body weight and offers a different pharmacokinetic (PK) and pharmacodynamic (PD) profile compared to conventional gonadotropins. The retrospective analysis by Eggersmann et al. aimed to compare the cumulative live birth rate (CLBR) of r-hFSH delta versus r-hFSH alfa/beta using data from the German In-vitro Fertilization (IVF) registry (D.I.R.^®; Deutsches IVF-Register), encompassing 113,936 stimulation cycles from women aged 24-45 years between 2017 and 2022. The authors found no statistical differences in oocyte yield, pregnancy rate (PR), and live birth rate (LBR), and an increase in cumulative live birth rate (CLBR) in the group stimulated with r-hFSH delta. The study presents several methodological challenges, such as differences in dose exposure, insufficient adjustment for confounding variables, and the inclusion of diverse patient groups, which may affect the clarity of the comparative effectiveness of the treatments. Additionally, the exclusion of patients who did not undergo frozen embryo transfer may limit the interpretability and generalizability of the findings. While Eggersmann et al. added valuable and meaningful insights into the real-world effectiveness of r-hFSH delta, its conclusions warrant thoughtful consideration. Undertaking a comprehensive methodological assessment strengthens causal inferences drawn from observational data, especially when intended to inform clinical decision-making. This real-world study serves as an important piece of the broader evidence base, contributing to our understanding of assisted reproductive technology (ART) outcomes.