Abstract Study question Is it possible to estimate the trend in the cumulative rate of live births in IVF over 12 years, using data from the Spanish Registry? Summary answer With the proposed formula, a constant increase of 1.7% in the cumulative live birth rate is verified throughout the 12 years of study. What is known already The progressive increase in elective freeze-all cycles no longer allows the use of live birth data by fresh transfer, especially in time series. Cumulative live birth rate (CLBR) has been proposed as an appropriate way of reporting success of an IVF program, incorporating both, fresh and frozen embryos. Nevertheless, views on the most appropriate parameters required to calculate such an outcome have been inconsistent and difficult for national aggregate registries. Furthermore, there is not unanimous definition for its calculation and although IVF Register is mandatory in Spain, an analysis of the CLBR has not been carried out. Study design, size, duration Data from the Spanish National Register of Assisted Reproduction including 456302 women undergoing IVF/ICSI (563000 ovarian stimulation cycles started, 359587 fresh transfers, and 36400 cryotransfer) using autologous gametes performed in Spain from 2009 to 2021 were analyzed. Oocyte donation and PGT-a cycles were excluded. Participants/materials, setting, methods The main outcomes of present study were live birth rate per cycle (LBR) and cumulative live birth rate (CLBR). To obtain the CLBR, the probability of achieving at least one live birth for each cycle started was calculated. This includes both live births after fresh transfer and those achieved after cryotransfer of the embryos obtained from each cycle until they have run out, or a full-term pregnancy is obtained. Main results and the role of chance The live birth rate (LBR) per fresh transfer remains steady (around 24%) throughout the period analyzed. However, LBR for started cycle, which remains constant (17%) until 2013, shows a marked decline since then at a rate of 1% per year. In this same period was observed: a progressive increase in the percentage of cycles with frozen embryos (from 29% to 48%), a greater number of cryopreserved embryos (from 0.9 to 1.6 embryos per started cycle), and a constant decrease in the number of embryos in each cryotransfer (from 2.39 to 1.42). LBR after cryotransfer per started cycle has increased exponentially from 4% to 24%. It was also found a steady increase of the percentage of births after a cryotransfer cycle (from 19 to 70%), surpassing since 2017 those obtained after fresh transfer. To calculate the cumulative live birth rate (CLBR), an algorithm has been developed including all pregnancies that can be achieved with the use of all the embryos obtained after each cycle started until alive child is born. CLBR shows a constant increase in the cumulative delivery rate of 1.7% annually since 2012, rising from 22 % to 35% of births per cycle started. Limitations, reasons for caution One of the main weaknesses of the study is that some patients have not attempted a second or third cryotransfer during the timeframe (for unknown reasons), though they had supernumerary embryos available. However, this model reflects the potential capacity to have at least one living child for each cycle started. Wider implications of the findings The LBR per cycle based only on fresh transfers is not useful for a historical analysis of the effectiveness of the technique. Only the calculation of the CLBR per cycle allows us to understand the real progress of IVF effectiveness in recent years. Trial registration number not applicable
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