The impact of sperm DNA fragmentation index levels on embryo development potential and clinical outcomes in infertile couples undergoing IVF/ICSI treatment

The sperm DNA fragmentation (SDF) impact on embryo development, particularly regarding the fertilization methods and female age, remains incompletely defined. This study evaluated the effect of the sperm DNA fragmentation index (DFI) on embryo quality and development and examined whether this effect was modified by insemination method or maternal age. This retrospective cohort study included 3567 infertility treatment cycles at The Third Affiliated Hospital of Zhengzhou University (Zhengzhou, China) between January 2019 and April 2025. The DFI was measured using the Sperm Chromatin Structure Assay (SCSA), and patients were stratified into low, moderate, and high DFI groups. The embryo quality was assessed morphokinetically on day 3 and days 5-7. Generalized estimating equations (GEEs) were employed to account for multiple embryos per patient, with adjustments for female age, body mass index (BMI), infertility cause, and insemination method. A high DFI was significantly associated with reduced good-quality blastocysts rate (P < 0.001). Stratified analyses revealed that the adverse effects of a high DFI were most pronounced in ICSI cycles and among women aged ≥35 years, where it correlated with markedly lower usable and good blastocyst rates (adjusted Exp[β] = 0.99 and 0.98, respectively; P = 0.002 and 0.008, respectively). In conclusion, an elevated DFI is negatively associated with embryo developmental potential in a dose-dependent manner, particularly in cycles involving ICSI and among couples with advanced maternal age. However, when the analysis was restricted to fresh embryo transfer, high DFI levels did not result in worse reproductive outcomes.