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Objective: To investigate the relationship between sperm chromatin structure assay (SCSA) parameters, DNA fragmentation index (DFI) and high DNA stainability (HDS), and outcomes of IVF and intracytoplasmic sperm injection (ICSI)., Design: Retrospective review and prospective study., Setting: Academic human reproduction laboratory., Patient(s): Two hundred twenty-three couples undergoing conventional IVF (n = 137) and ICSI (n = 86)., Intervention(s): Testing with SCSA on a semen aliquot taken from ejaculate used for assisted reproductive technology (ART)., Main Outcome Measure(s): Conventional semen parameters, DFI, HDS, outcomes of IVF and ICSI., Result(s): There were no significant differences in IVF and ICSI fertilization rate, good embryo rate, and pregnancy rate (PR) between high, moderate, and low DFI or HDS groups. Men with HDS >15% had significantly higher IVF abortion rates. There was a statistically insignificant trend toward an increased abortion rate in the high DFI (>27%) group. The DFI correlated negatively with sperm motility, and HDS correlated negatively with sperm morphology and concentration., Conclusion(s): Neither DFI nor HDS scores can provide independent information about embryo quality, fertilization, and PRs for infertility patients undergoing ART. Sperm DNA fragmentation probably affects sperm motility. The relationship between HDS and IVF abortion rates provides preliminary evidence that ICSI may be indicated for men with HDS >15%. The potential adverse effect of sperm DNA damage on the quality of postimplantation embryo and spontaneous abortion should be a concern.