Cumulative live birth rate after IVF: trend over time and the impact of blastocyst culture and vitrification.

study questionHas cumulative live birth rate (CLBR) improved over time and which factors are associated with such an improvement? SUMMARY ANSWER: During an 11-year period, 2007-2017, CLBR per oocyte aspiration increased significantly, from 27.0% to 36.3%, in parallel with an increase in blastocyst transfer and cryopreservation by vitrification. WHAT IS KNOWN ALREADY: While it has been shown that live birth rate (LBR) per embryo transfer (ET) is higher for fresh blastocyst than for fresh cleavage stage embryo transfer, CLBR per oocyte aspiration, including one fresh ET and all subsequent frozen embryo transfers (FET), does not seem to differ between the two culture strategies. STUDY DESIGN SIZE DURATION: A national register study including all oocyte aspirations performed in Sweden from 2007 to 2017 (n = 124 700 complete IVF treatment cycles) was carried out. Oocyte donation cycles were excluded. PARTICIPANTS/MATERIALS SETTING

methodsData were retrieved from the Swedish National Registry of Assisted Reproduction (Q-IVF) on all oocyte aspirations during the study period where autologous oocytes were used. CLBR was defined as the proportion of deliveries with at least one live birth per oocyte aspiration, including all fresh and/or frozen embryo transfers within 1 year, until one delivery with a live birth or until all embryos were used, whichever occurred first. The delivery of a singleton, twin, or other multiples was registered as one delivery. Cryopreservation of cleavage stage embryos was performed by slow freezing and of blastocyst by vitrification. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 124 700 oocyte aspirations were performed (in 61 313 women), with 65 304 aspirations in women <35 years and 59 396 in women ≥ 35 years, resulting in 38 403 deliveries with live born children. Overall, the CLBR per oocyte aspiration increased significantly during the study period, from 27.0% to 36.3% (odds ratio (OR) 1.039, 95% CI 1.035-1.043) and from 30.0% to 43.3% if at least one ET was performed (adjusted OR 1.055, 95% CI 1.050-1.059). The increase in CLBR was independent of maternal age, number of oocytes retrieved and number of previous IVF live births. The CLBR for women <35 and ≥35 years both increased significantly, following the same pattern. During the study period, a substantially increasing number of blastocyst transfers was performed, both in fresh and in FET cycles. Other important predicting factors for live birth, such as number of embryos transferred, could not explain the improvement. An increased single embryo transfer rate was observed with time. LIMITATIONS REASONS FOR CAUTION: The retrospective design implicates that other confounders of importance for CLBR cannot be ruled out. In addition, some FET cycles might be performed later than 1 year post oocyte aspiration for the last year (2017) and are, thus, not included in this study. In addition, no data on 'dropouts', i.e. patients that do not continue their treatment despite having cryopreserved embryos, are available, or if this drop-out rate has changed over time. WIDER IMPLICATIONS OF THE

findingsThe results suggest that blastocyst transfer, particularly when used in FET cycles and in combination with vitrification, is an important contributor to the improved live birth rates over time. This gives a possibility for a lower number of oocyte aspirations needed to achieve a live birth and a shortened time to live birth. STUDY FUNDING/COMPETING INTERESTS: The study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70940) and by Hjalmar Svensson's research foundation. None of the authors declares any conflict of interest.