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Study question What is the embryo survival rate when combining freezing and warming media from different manufacturers. Summary answer Vitrification protocol with DMSO in freezing medium and 4-step warming at room temperature resulted in highest implantation and high embryo survival rates. What is known already Cryopreservation media containing 7,5% and 15% DMSO in a two-steps protocol are widely used for vitrification of human embryos. Studies with the data on safety, survival rates, cellular structures integrity and the warmed embryo's implantation potential confirm efficiency of DMSO as cryoprotectant. However, questions remain on whether DMSO have any negative impact, thus interest to DC. Likewise with the choice of cryoprotectant, more data is needed to determine which temperature corresponds to better survival rates. Study design, size, duration This retrospective cohort study covered the period from January 2019 till November 2021. A total of 834 consecutive cycles of frozen/warmed embryo transfers were included in the study. Inclusion criteria were: women's age below 40 years, cryopreservation on the day 5 of embryo culture. Exclusion criteria were: donor oocyte cycles, cycles with pre-implantation genetic testing for aneuploidies and cycles with severe male factor after surgical sperm retrieval. Participants/materials, setting, methods Following groups were compared using Rapid-i carrier device: 1 - Kitazato vitrification/warming protocol, 2 - Kitazato vitrification and Vitrolife's Omni warming, 3 - Vitrolife's Omni vitrification/warming, 4 - Vitrolife's Omni vitrification and Kitazato warming, 5 - Kitazato vitrification/Vitrolife's Omni warming media used in accordance with Kitazato protocol (ambient temperature, Reproplate dish). Efficiency was evaluated comparing embryo survival, implantation, clinical pregnancy and early pregnancy termination rates. Mann-Whitney and Pearson's Chi-square tests were used for statistical analysis. Main results and the role of chance The average patient age in assigned groups was: group 1: 32,5±3,6 years (n = 569); 2:32,2±3,5 years (n = 47); 3:30,4±3,5 years (n = 15); 4:32,3±3,5 years (n = 74); 5:32,7±3,4 years (n = 129). Average number of transferred embryos: 1,3±0,5; 1,2±0,4; 1,1±0,3; 1,3±0,4 and 1,2±0,4 per group, respectively. Embryo survival rates were: 97%, 96%, 100%, 97% and 100% in each group, respectively. Group 5 was significantly different from other groups (p < 0,05; group 3 had too small sample size for an adequate comparison). Implantation rates per group: 43%, 57%, 44%, 40% and 49%, respectively (p > 0,05). Clinical pregnancy rates were not different between groups. The early pregnancy termination rates were: 18,1%, 20,7%, 33,3%, 14,7% and 8,9% per group, respectively (p > 0,05). Therefore, group 2 resulted in a best clinical outcomes. Limitations, reasons for caution The present study is a retrospective cohort study and it has a limited number of patients in compared groups. Additionally, live births and health of newborn children was not taken into account. Wider implications of the findings Freezing medium from one manufacturer can be combined with warming medium from another manufacturer and result in a good clinical outcome. Furthermore, this study sheds the light that there is still a room for the improvement of existing cryopreservation media and protocols. Trial registration number not applicable

Study question To investigate the therapeutic efficacy of follitropin alpha biosimilar therapy in nonselected patients undergoing IVF. Summary answer This large retrospective study demonstrated similar therapeutic efficacy for follitropin alpha biosimilar therapy in women who underwent ovarian stimulation (OS) using different protocols. What is known already Based on data from the last meta-analyses (Budani et al., 2020), follitropin alpha biosimilars showed similar efficacy and safety in randomized controlled trials aimed at proving the therapeutic equivalence in terms of oocytes retrieved in women undergoing OS. In most cases, normogonadotrophic patients were enrolled in such studies without any endocrine or ovarian disturbances. The absence of real-world data can be compensated by additional post-marketing studies aimed at investigating the efficacy of biosimilars in different OS protocols using antagonists and agonists of GnRH and OS with mixed gonadotropins. Study design, size, duration A retrospective, observational, anonymized cohort study conducted at 35 IVF clinics in Russia, named “FOLLITROPIN”, compared the efficacy of OS in 2020. The OS protocols analysed where follitropin alpha biosimilar (Primapur®) was applied for at least 5 days. All of the analysed subjects underwent OS using GnRH antagonist/agonist protocols, with no restrictions on the OS protocol or food supplements/vitamins. No inclusion or exclusion criteria were applied. Overall, 5484 OS protocols were analysed. Participants/materials, setting, methods The efficacy of 5484 OS protocols was calculated, and two subgroups were extracted: (1) mixed gonadotropin OS protocols (N = 2625) vs monotherapy with Primapur® (N = 2859); (2) GnRH antagonist OS (N = 2183) vs GnRH agonist (N = 676) using only Primapur®. Demographic and clinical characteristics: (1) Age 34.9±4.8 vs 32.9±4.7 (p Main results and the role of chance The total efficacy of OS with Primapur®: oocytes retrieved: 9.5±7.2, MII: 6.8±6.6, 2PN: 6.1±5.8, clinical pregnancy per ET (PR) 6 weeks after ET: 38.4%. Subgroup 1 analysis: oocytes retrieved: 8.6±6.8 vs 10.3±7.4 (p Limitations, reasons for caution The real-world patient data analysed in this study were representative, showing the ability of follitropin biosimilars to develop both folliculogenesis and clinical pregnancy in a nonselected population. Additional comparative studies are needed to confirm the efficacy of the biosimilars in patients with classified types of infertility causes, including unexplained infertility. Wider implications of the findings: In this study, we demonstrated the therapeutic efficacy of biosimilars in terms of oocyte yield and clinical pregnancy development in women undergoing different OS protocols. Further large-scale studies with known hormonal levels before and during OS, as well as the micro- and macronutrient status of both parents, are needed. Trial registration number None