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Abstract Study question Does the type of FSH preparation used for ovarian stimulation, recombinant human FSH (r-hFSH) or biosimilar, influence reproductive success in oocyte donation and autologous cycles? Summary answer Ovarian response and reproductive outcomes, including live birth rates, are comparable in oocyte donation and autologous cycle, irrespective of the type of r-hFSH preparation used. What is known already Exogenous gonadotrophins, particularly FSH, have long been used in assisted reproduction, evolving from urinary to recombinant forms. The first generation of r-hFSH, including Puregon® and Gonal-f®, became available in the 1990s. However, interest in biosimilar FSH products has grown globally following the expiry of original patents. Approved by the European Medicines Agency, two r-hFSH biosimilars, Ovaleap® and Bemfola®, offer cost-effective alternatives for infertility treatments. Regulatory guidelines emphasize non-inferiority to the originator product, with clinical trials showing comparable outcomes between biosimilar and reference FSH preparations. However, debates persist regarding the efficacy and safety of r-hFSH biosimilars, particularly in achieving live births. Study design, size, duration In this retrospective cohort study, we compared reproductive outcomes following 8,429 controlled ovarian stimulations (COS) using r-hFSH Gonal-f® (n = 5,059) or the biosimilar FSH Bemfola® (n = 3,370), performed between January 2015 and December 2022 at a single fertility center. Overall, 242,978 mature (MII) oocytes were retrieved, utilized in 12,952 ICSI cycles (n = 11,421 heterologous and n = 1,531 autologous). We primarily evaluated ovarian response, measured by oocyte retrieval and maturation rates. Secondary outcomes included ongoing pregnancy and live birth rates. Participants/materials, setting, methods Participants included both oocyte donors (6,895 COS, 18-35 years) and patients using autologous oocytes (1,534 COS, 20-46 years). Univariate and multivariate analyses were performed separately across oocyte donor and patient groups. Outcomes in autologous cycles were further stratified by age. Regressions were adjusted for r-hFSH dose, antral follicle count (AFC), days of stimulation, age, BMI, use of menotropins, fertilization rates and number of embryos transferred, as appropriate. All p-values 0.05 were considered statistically significant. Main results and the role of chance Oocyte donors exhibited similar demographics (age, BMI, days of stimulation), however AFC was significantly higher in the biosimilar group compared to donors stimulated with Gonal-f® (11.31 ± 9.72 vs 7.63 ± 7.5). In patients, we observed no difference in demographic variables between study groups. A mean of 20.5 cumulus-oocyte complexes (COCs) and 15.7 MII oocytes were obtained across all COS. In oocyte donation cycles, the number of COCs retrieved was comparable between groups (22.6, Gonal-f®, 22.3, Bemfola®), however stimulation with Gonal-f® led to a slightly higher number of MII oocytes (17.6 vs 16.9, t-test p 0.0001). Nevertheless, adjusted analyses revealed improved oocyte retrieval rates with Bemfola® (coeff 0.12, 95% CI: (0.05-0.18), p = 0.0006), while oocyte maturity rates were equivalent amongst the two groups (80% Gonal-f®, 77%, Bemfola®). Comparable results were observed in autologous cycles in terms of COCs (13.7, Gonal-f®, 12.7, Bemfola®) and number of MII oocytes (9.6, Gonal-f®, 9.0, Bemfola®). In autologous cycles, r-hFSH choice did not affect oocyte retrieval rates (coeff -3.3x10-04, 95% CI (-0,09-0,09), p 0.05) nor oocyte maturation rates (coeff -2.7x10-04, 95% CI (-0,02-0,02), p 0.05). Our adjusted analysis revealed comparable ongoing pregnancy and live birth rates between the study groups across all 12,952 ICSI cycles (p 0.05 in all cases). Limitations, reasons for caution The main limitation of this study is its non-interventional retrospective cohort design, impacting generalizability to broader populations and diverse clinical settings. Despite its exploratory nature, the study’s scale, encompassing over 8,000 COS and close to 13,000 ICSI cycles, offers valuable insights into routine clinical care. Wider implications of the findings Comparable ovarian response, pregnancy and live birth rates following COS with Gonal-f® and Bemfola®, in both heterologous and autologous cycles, underscore the utility of biosimilars in ART. Our findings support the broader implications of EU’s policy on biosimilar interchangeability, ultimately enhancing patient access to a wider range of treatment options. Trial registration number not applicable
Abraham-Zadeh et al. (Mon,) studied this question.