Introduction: It has been observed that there is an increased incidence of total fertilization failure (TFF) and a low fertilization rate (LFR, <25 %) during conventional in vitro fertilization (IVF) treatments involving men with poor sperm motility. These men also exhibit a high sperm DNA fragmentation index (DFI), which has adverse effects on various IVF outcomes. However, the relationship between a high DFI and an increased TFF or LFR during IVF cycles has not been elucidated. Here, we aimed to investigate the association between the sperm DFI and TFF or LFR in IVF cycles involving men with mild-to-moderate asthenozoospermia and normozoospermia. Materials and methods: This retrospective study included 116 men diagnosed as mild-to-moderate asthenozoospermia, and 407 men with normozoospermia. The sperm DFI was assessed using the sperm chromatin dispersion (SCD) test. Results: Men in the asthenozoospermia group had a significantly higher incidence of cycles with a TFF or LFR (9.5 % vs 2.7 %, P = 0.01), and these were associated significantly with an increased DFI (P < 0.01). After adjustment for confounding factors, a TFF or LFR was to correlate significantly with the DFI (odds ratio: 1.188; 95 % confidence interval, 1.035–1.363; P = 0.014). Area under the receiver operating characteristic curve was 0.772. No similar relationships between the DFI and IVF outcomes were observed in the normozoospermia group. Conclusions: For men with mild-to-moderate asthenozoospermia, a high sperm DFI is associated with a decreased fertilization rate and an increased risk of a TFF or LFR. Additional prospectively-designed studies are warranted to confirm our results. © 2020 Elsevier Masson SAS