Abstract

Abstract Study question Whether slow developing expanded day 6 (D6) blastocysts should be either transferred during fresh cycle or systematically vitrified at D6 Summary answer Fresh D6 blastocyst transfer is independently associated with reduced live birth rate compared to frozen thawed D6 transfer What is known already Live birth rate (LBR) after D5 blastocyst transfers are significantly higher when compared with D6 embryos in both fresh and frozen-vitrified embryo transfer cycles according to the last published meta-analyses. Therefore, for women obtaining only D6 blastocysts, chances of pregnancy may be lower but still persist and these embryos should be transferred. The question of the best strategy for transfer (i.e. in fresh or frozen cycles) remains unclear while data on this subject are scarce. Study design, size, duration Retrospective observational cohort study. Patients having only embryos reaching blastocyst stage at D6 were included between January 2018 and May 2021. Two groups were compared : patients having a fresh D6 transfer (D6 fresh transfer group) and patients having a frozen thawed D6 transfer ( D6 frozen transfer group). Participants/materials, setting, methods 830 D6 single blastocyst transfers (736 frozen blastocysts and 94 fresh blastocysts) were analyzed. LBR and neonatal outcome were compared between groups, as well as the influence of clinical characteristics and data related to COS protocols. Correlation between D6 blastocyst morphology according to Gardner’s classification and livebirth occurrence was also evaluated. Statistical analysis of the data was carried out using univariate and multivariate logistic regression models. Main results and the role of chance LBR was significantly lower after D6 fresh blastocyst transfer compared to D6 frozen thawed blastocyst transfer [5.3% (5/96) vs 12.2% (90/736), p < 0.05]. Moreover, when comparing a subgroup of 68 first D6 frozen embryo transfers (1st D6 frozen transfer group) to the 94 fresh D6 blastocyst transfers (D6 fresh elective group), the superiority of D6 frozen blastocyst transfers regarding LBR was also confirmed (17.6% vs 5.3% p < 0.001, respectively). Concerning neonatal outcomes, the mean birth weight was comparable between the two groups. Univariate logistic regression analysis taking into account blastocyst morphology parameters showed that TE grade was the only parameter significantly associated with LBR after D6 embryo transfer (p < 0.001). Multiple logistic regression revealed that D6 embryo fresh transfer was independently associated with reduced LBR compared to frozen thawed D6 transfer (OR 0.367; 95%IC 0.143-0.945; p = 0.038). Moreover, our results showed that transferring a good or top quality D6 blastocyst increases 3 fold chances of live birth. Limitations, reasons for caution The number of fresh cycles seems relatively small, but the consistency of our results was guaranteed by the homogeneity of the 2 subgroups, standardization of all biological and clinical procedures and the robust statistical analysis methodology used in this study. Wider implications of the findings Despite their lower potential, D6 blastocysts have to be transferred with the objective to improve LBR, especially in women obtaining only these type of embryos. Our results recommend to transfer D6 blastocysts in frozen cycles. However, these findings have to be confirmed on larger series in prospective randomized trials. Trial registration number not applicable

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