Density Gradient Centrifugation Versus Swim‐Up for Cumulative Live Birth in IVF/ICSI Cycles With High Sperm DNA Fragmentation: A Propensity Score Matching Analysis

BACKGROUND: A high sperm DNA fragmentation index (DFI) has been found to be associated with male infertility and suboptimal outcomes in assisted reproductive technology (ART). Although sperm preparation techniques can reduce DFI following processing, it is unclear whether density gradient centrifugation (DGC) or swim-up (SU) achieves better clinical outcomes, particularly in terms of cumulative live birth rates (cLBR), for patients with elevated DFI. OBJECTIVE: Using a propensity score-matched statistical approach, this study aims to compare the clinical effectiveness of DGC versus swim-up sperm preparation in male infertility patients with elevated sperm DFI. The primary objective is to determine which technique is associated with a higher cLBR following ART. Secondary objectives include evaluating post-processing DFI reduction, fertilization rates, embryo quality, high quality blastocyst rate, and other relevant laboratory and clinical outcomes. MATERIALS AND METHODS: This study was a retrospective design conducted at a single-center reproductive center. A total of 1769 couples were included in the study. They were receiving their first autologous IVF/ICSI cycle with a male partner who had a DFI of ≥ 20%. Following matching for propensity, 279 cycles were allocated to each of the DGC and SU groups. The primary outcome was cLBR per oocyte retrieval. RESULTS: The SU group had a longer duration of abstinence and a higher proportion of conventional IVF cycles, while the DGC group included more ICSI cycles. There were no significant differences observed in cLBR (adjusted odds ratio [OR] = 1.06, 95% confidence interval [CI]: 0.76-1.49) or live birth rate per transfer (adjusted OR = 1.16, 95% CI: 0.89-1.52). The absolute difference in cLBR between groups was small. Laboratory outcomes, including fertilization rate, high-quality embryo rate, high-quality blastocyst rate, and blastocyst formation rate, showed similar point estimates, with no statistically significant differences. Results were broadly consistent across subgroups stratified by abstinence duration (less than 3 days, 3-5 days, or more than 5 days) and baseline semen parameter status (normal or abnormal). DISCUSSION AND CONCLUSION: Among patients with DFI ≥ 20% undergoing IVF/ICSI, no statistically significant differences in cLBRs or laboratory outcomes were observed between DGC and SU. The effect estimates were close to the null and consistent across analyses; however, confidence intervals were wide, indicating limited precision. These findings suggest no clear evidence of a difference under the conditions studied. Further adequately powered prospective studies are warranted to more precisely estimate potential differences between these techniques.