Elevated sperm DNA fragmentation is associated with embryonic developmental attrition after fertilization in conventional IVF cycles.

Background: The influence of sperm DNA fragmentation on conventional Methods: This retrospective cohort study included 1,423 first eligible conventional IVF cycles selected from fresh oocyte-retrieval treatment cycles recorded between August 2021 and December 2025. Cycles involving intracytoplasmic sperm injection, rescue intracytoplasmic sperm injection, or mixed fertilization procedures were excluded. Sperm DFI was categorized using a primary threshold of 20%, with cycles classified as lower DFI (≤20%) or elevated DFI (>20%). Embryological development was assessed using stage-specific transition outcomes, including oocyte-to- two-pronuclear (2 P N) formation, 2 P N-to-day-3 good-quality embryo formation, blastocyst formation among embryos cultured for blastocyst development, and blastocyst-to-good-quality blastocyst formation. Binomial regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multivariable models were adjusted for female age, male age, female body mass index, and basal follicle-stimulating hormone. Additional analyses examined clinically interpretable DFI categories and alternative DFI thresholds. Results: Among the 1,423 cycles, 1,218 were classified as lower DFI and 205 as elevated DFI. Elevated DFI was not associated with the oocyte-to-2PN transition after adjustment (63.7% vs. 62.3%; adjusted OR, 0.96; 95% CI, 0.84-1.10; P = 0.523). In contrast, elevated DFI was associated with a lower probability of 2 P N-to-day-3 good-quality embryo formation (34.5% vs. 29.4%; adjusted OR, 0.71; 95% CI, 0.57-0.87; P = 0.001). Elevated DFI was also associated with reduced blastocyst formation among embryos cultured for blastocyst development (57.3% vs. 50.4%; adjusted OR, 0.80; 95% CI, 0.66-0.96; P = 0.018). Good-quality blastocyst formation among formed blastocysts was 34.4% in the lower-DFI group and 30.8% in the elevated-DFI group (adjusted OR, 0.87; 95% CI, 0.68-1.11; P = 0.267). Analyses using clinically interpretable DFI categories and alternative thresholds showed that the association was most consistently observed for post-fertilization developmental outcomes rather than normal fertilization. Conclusion: In this retrospective cohort of first eligible conventional IVF cycles, elevated sperm DFI was not independently associated with normal fertilization but was associated with modestly reduced post-fertilization embryological development, particularly 2 P N-to-day-3 good-quality embryo formation and blastocyst formation among embryos cultured for blastocyst development. These findings support a stage-specific developmental framework for evaluating the embryological relevance of paternal DNA integrity in conventional IVF, while suggesting that sperm DFI should not be interpreted as a stand-alone marker of fertilization potential.