To compare the effectiveness of various sperm preparation techniques, including microfluidic sperm sorting (MFSS) and magnetic-activated cell sorting (MACS) combined with density gradient centrifugation (DGC), in reducing sperm DNA fragmentation and improving clinical outcomes.
Approach:
Study Design: Systematic review and network meta-analysis of randomized and non-randomized studies comparing sperm preparation techniques, including both randomized controlled trials and observational studies.
Data Sources: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched until July 26, 2025, for studies comparing at least two sperm preparation techniques.
Analysis Method: Frequentist random-effect network meta-analysis was employed to synthesize data from the included studies.
Key Findings:
Microfluidic sperm sorting (MFSS) showed the greatest reduction in DNA fragmentation (SMD -2.64; 95%CI -3.53 to -1.75).
Magnetic-activated cell sorting (MACS) combined with density gradient centrifugation (DGC) was associated with a higher clinical pregnancy rate (OR 1.93; 95% CI 1.23–3.02).
The combination of MACS and DGC showed a lower miscarriage rate (OR 0.65; 95% CI 0.46–0.91).
Interpretation:
MFSS and MACS-based combinations demonstrated significant reductions in sperm DNA fragmentation; however, high heterogeneity and low certainty of evidence limit definitive conclusions. Improvements in clinical pregnancy and miscarriage rates with MACS and DGC combinations were noted.
Limitations:
High heterogeneity in studies (I2=96.1%) may affect the reliability of findings.
Limited number of randomized studies for sperm DNA fragmentation (N=2) restricts the strength of conclusions.
Conclusion:
The analysis highlights the need for further robust, large-scale studies to establish definitive clinical recommendations regarding sperm preparation techniques.
