Preventing blastocyst culture failure risk in IVF cycles merits a strategy of cleavage backup combined with blastocyst culture

Abstract Background Blastocyst transfer is associated with a high cycle cancellation rate due to more early embryo arrest. However, cleavage backup combined with blastocyst culture maybe merit prevention blastocyst culture failure. Methods We retrospectively analyzed 7026 cycles between October 2017 and August 2020 in our center for reproductive medicine. Two day-3 embryos were transferred or cryopreserved in addition to at least 1 surplus embryo extended the culture for blastocysts. The primary objective was to analyze the factors of influencing blastocyst formation. The secondary objective was to study the fate of sibling cleavage embryos after sparing the embryo culture for blastocysts. Results In all included cycles, there was 12.43% occurrence without blastocyst formation (CNB), 5.19% of nonavailable blastocysts (NAB), and 82.38% cycles with at least 1 valuable blastocyst (CHB). The number of day-3 embryos was associated with blastocyst formation outcome (adjusted odds ratio [aOR] 1.71), and older women and short agonist ovary stimulation decreased the odds of blastocyst formation (aOR 0.97 and 0.18, respectively). Female age and numbers of embryos for blastocyst culture were related to blastocyst quality (aOR 0.98 and 1.36, respectively). Some couples underwent fresh cleavage transfer (CNB 453, NAB 203, CHB 2341), and the pregnancy rate was significantly higher with positive culture results (CHB 47.97%, NAB 34.48%, CNB 34.88%, P = 0.001). There was a lower chance of being pregnant for advanced aged women (aOR 0.94). Compared with mild ovary stimulation, the long stimulation protocol and modified ultralong protocol were beneficial for pregnancy after day-3 embryo transfer (aOR 1.62 and 2.77, respectively). Cleavage of embryos from cycles with available blastocysts increased the odds of implantation (CHB 35.25%, CNB 23.40%, NAB 24.88%, P < 0.001). Pregnancy from cycles of no available blastocyst was associated with higher odds of miscarriage (NAB 19.10%, CNB 9.84%, CHB 10.70%). Outcome of blastocyst formation had no influence on preterm birth rate (CNB 12.03%, NAB 18.21%, CHB 18.45%, respectively, P = 0.139), birth defects (CNB 1.05%, NAB 1.09% CHB 0.89% P = 0.966), or sex ratio of male proportion (CNB 0.57, NAB 0.55, CHB 0.53, P = 0.669). Conclusions The pregnancy outcome of sibling cleavage transfer is related to blastocyst formation of spare embryos. For negative blastocyst culture patients, there is a lower but acceptable live birth rate from sibling cleavage transfer. Cleavage backup combined with blastocyst culture may prevent blastocyst formation failure risk.