Irregular cleavage divisions are expected to produce chromosomally deviant embryos. We investigated whether embryos from irregular cleavages could develop into euploid blastocysts, and, if so, whether any evidence existed of a self-correction mechanism of the embryo. We also investigated the role of different dynamic aspects of morula compaction in this process. A total of 791 embryos from 141 patients undergoing pre-implantation genetic screening were retrospectively analysed using a time-lapse imaging system, and multiple cell divisions were evaluated. A total of 276 embryos developed into blastocysts suitable for biopsy and chromosome screening through array-comparative genomic hybridization. As well as testing trophectoderm biopsy specimens for aneuploidy, excluded cells of 18 blastocysts, which developed from partially compacted morulas, were also analysed. Unique data on the developmental fate of embryos with cleavage abnormalities are presented, and a potential mechanism of 'aneuploidy rescue' is postulated through which mosaic embryos may form partially compacted morulas to exclude aneuploid cells. In addition, this process seems to be less efficient in older women. The data obtained also provide further evidence that excluded cells should not be used to infer the cytogenetic status of the embryo.

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RESULTS: 1108 blastocysts derived from 259 IVF/PGT-A cases were included in the study. The groups consisted of 126 cases (n¼ 543 embryos) with elevated DFI and 133 cases (n¼ 565 embryos) with normal DFI. Significant differences were found in mean male age (39.8 AE6, 37.8AE5,p¼0.004), female age (36.2AE4, 34.8AE4, p¼0.007) and cases with normal morphological sperm analysis (37%, 56.3%, p¼0.002) between cohorts. No differences were found in fertilization rate, zygotes achieving cleavage stage, and blastulation rates between study groups. Embryo euploidy rates were comparable (50.2% ( n¼273/543), 46.7%( n¼264/565), p¼0.24).After adjusting for female and male patient's age, BMI, AMH, normal semen analysis and number of biopsied embryos, there were no association with elevated DFI and lower odds of embryo euploidy (OR 1.39, CI95% 0.97-2.0, p¼0.07).CONCLUSIONS: Although multiple studies have reported poor outcomes in patients with elevated DFI, the exact mechanism of action is unclear. Our study analysis showed no correlation between high sperm DNA fragmentation and fertilization, blastulation, or embryo euploidy rates. Our study adds to the expanding body of evidence that shows no significant relationships between elevated DNA fragmentation, embryo development, or chromosomal composition. Future studies assessing the oocyte DNA-repair mechanism following fertilization should be performed to better understand the immediate impact of sperm chromatin damage during ART intervention.References: Zini A, Jamal W, Cowan L, Al-Hathal N (2011) Is sperm DNA damage associated with IVF embryo quality? A systematic review. J Assist Reprod Genet 28: 391AE397.Virro MR, Larson-Cook KL, Evenson DP. Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles.

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