How Does the Exclusion of Blastomeres Affect the Outcome of Euploid Blastocysts?

Do euploid blastocysts with excluded blastomere(s) have the same probability of live birth when compared to euploid blastocysts without excluded blastomere(s)? Euploid blastocysts with excluded blastomere(s) have significantly worse pregnancy outcomes, with the live birth rate being 10% lower than those without any exclusion pattern. Blastomeres that have arisen at any time throughout cleavage-stage are sometimes excluded from the formation of the blastocyst and once isolated, those cells do not take further part in preimplantation development. Embryos harboring cell exclusion were found to have altered morphokinetic profiles; S2(second synchrony) and ECC3(embryonic cell cycle 3) were described as useful in identifying increased odds of FHB when a cell exclusion event was present (Kakulavarapua et al., 2023). Besides, pregnancy and live birth rates were reported to progressively decrease in a non-PGT-A (preimplantation genetic testing for aneuploidy) tested cohort with excluded or extruded blastomere(s) (Coticchio et al., 2021). This retrospective study included 667 euploid blastocysts with excluded blastomere(s) and 3830 euploid blastocysts without excluded blastomere(s). All were transferred between 2017 and 2023. No discrimination was made between cells failing to compact because of their exclusion from the compaction process (excluded from a partially compacted morula), and cells extruded after an initial inclusion in the compacted embryonic mass (extruded from a partially compacted morula). A total of 4497 IVF patients treated in a single private clinic were included in this retrospective study. Their blastocysts were subjected to PGT-A mainly for advanced maternal age. The analysis was done by next generation sequencing (NGS) (Ion Torrent S5, Thermo Fisher). Vitrified-warmed euploid blastocysts were then transferred in a next cycle. Pregnancy and miscarriage rates were compared between blastocysts with and without excluded blastomere(s) by chi-square test. The outcomes of euploid blastocysts with excluded blastomeres (n = 667) were compared to euploid blastocysts without excluded blastomeres (n = 3830). The biochemical pregnancy rate was 71.6% and 77%, respectively (p = 0.0026). The clinical pregnancy rate was 61.3% and 70.6%, respectively (p = 0.0001). The ongoing pregnancy rate was 53.7% and 63.3%, respectively (p = 0.0001). The biochemical miscarriage rate nearly doubled with the presence of excluded blastomere(s) (14% vs. 8.3%, respectively; p = 0.0001). The clinical miscarriage rate was 12.7% and 10.4%, respectively (ns). Ultimately, the live birth rate was 46.3% for the blastocysts with excluded blastomere(s), compared to 57.6% for the blastocysts without excluded blastomere(s) (p = 0.0001). No discrimination was made between cells excluded from a partially compacted morula and cells extruded after an initial inclusion in the compacted embryonic mass. Although blastocysts with excluded blastomere(s) are not the first choice for transfer, our results show that, although at lower rate, successful pregnancies and live births occur. A complete time-lapse culture evaluation not limited to cell division time points may propose indicators to identify higher implantation potential blastocysts with excluded blastomere(s). N/A