In briefWhether sperm DNA fragmentation (SDF) affects embryo development and clinical outcomes is still controversial, which limits the utility of SDF testing in assisted reproductive technology management. This study demonstrates that high SDF is associated with the incidence of segmental chromosomal aneuploidy and increased paternal whole chromosomal aneuploidies.AbstractWe aimed to investigate the correlation of sperm DNA fragmentation (SDF) with the incidence and paternal origin of whole and segmental chromosomal aneuploidies of embryos at the blastocyst stage. A retrospective cohort study was conducted with a total of 174 couples (women aged 35 years or younger) who underwent 238 cycles (including 748 blastocysts) of preimplantation genetic testing for monogenic diseases (PGT-M). All subjects were divided into two groups based on the sperm DNA fragmentation index (DFI) level: low DFI (<27%) and high DFI (≥27%). The rates of euploidy, whole chromosomal aneuploidy, segmental chromosomal aneuploidy, mosaicism, parental origin of aneuploidy, fertilization, cleavage, and blastocyst formation were compared between low- and high-DFI groups. We found no significant differences in fertilization, cleavage, or blastocyst formation between the two groups. Compared to that in the low-DFI group, segmental chromosomal aneuploidy rate was significantly higher in the high-DFI group (11.57% vs 5.83%,P= 0.021; OR: 2.32, 95% CI: 1.10–4.89,P= 0.028). The whole chromosomal embryonic aneuploidy of paternal origin was significantly higher in cycles with high DFI than in cycles with low DFI (46.43% vs 23.33%,P= 0.018; OR: 4.32, 95% CI: 1.06–17.66,P= 0.041). However, the segmental chromosomal aneuploidy of paternal origin was not significantly different between the two groups (71.43% vs 78.05%,P= 0.615; OR: 1.01, 95% CI: 0.16–6.40,P= 0.995). In conclusion, our results suggested that high SDF was associated with the incidence of segmental chromosomal aneuploidy and increased paternal whole chromosomal aneuploidies in embryos.