Comparative analysis of sperm preparation techniques on DNA fragmentation and clinical outcomes: a network meta-analysis
In brief
Adding magnetic-activated cell sorting to density gradient doubles pregnancy odds in IVF
In a network meta-analysis of 15 randomized trials, combining magnetic-activated cell sorting with density-gradient centrifugation yielded roughly twice the clinical pregnancy rate and a modestly lower miscarriage risk compared with density gradient alone. Microfluidic sorting cut DNA fragmentation the most, but the data were highly heterogeneous and of low certainty, so routine use remains unproven.
- Journal
- Frontiers in endocrinology (Q1)
- Published
- 13 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Linlin Wang, Jingjing Xu, Yaman Guo, Xintao Wang, Meng Jia
- PMID
- 42516744
- DOI
- 10.3389/fendo.2026.1817587
Why clinicians should know about it
- Picked for Obstetrics and Gynecology (top studies of the week, 2 August 2026).
Abstract
INTRODUCTION: Elevated sperm DNA fragmentation negatively affects assisted reproductive technology outcomes. Although multiple sperm preparation techniques are used, existing evidence is largely limited to pairwise comparisons. We performed a systematic review and network meta-analysis to investigate the most effective technique for reducing sperm DNA fragmentation and improving clinical outcomes. METHODS: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to July 26, 2025. Due to the limited randomized studies for sperm DNA fragmentation (N=2), both randomized and non-randomized studies comparing at least two preparation techniques were included for sperm DNA fragmentation analyses, while only randomized controlled trials were included for clinical outcomes to ensure the highest stringency for treatment efficacy. Data were synthesized using frequentist random-effect network meta-analysis. RESULTS: Forty-two studies (2697 semen samples) were included for sperm DNA fragmentation. Despite high heterogeneity (I2 =96.1%), network estimates indicated that microfluidic sperm sorting (MFSS) was associated with a significant showed the greatest reduction in DNA fragmentation (SMD -2.64; 95%CI -3.53 to -1.75), followed by magnetic-activated cell sorting (MACS) combined with density gradient centrifugation (DGC; SMD, -1.53; 95%CI -2.93 to -0.12). Fifteen randomized controlled trials reported clinical outcomes. Magnetic-activated cell sorting combined with density gradient centrifugation was associated with a higher clinical pregnancy rate compared with density gradient centrifugation alone (OR1.93; 95% CI 1.23 --3.02), and pairwise meta-analysis showed a lower miscarriage rate (OR 0.65; 95% CI 0.46 -0.91). DISCUSSION: While MFSS and MACS-based combinations showed the greatest numerical reduction in sperm DNA fragmentation, these findings are characterized by high heterogeneity and low certainty of evidence. Although some improvements in clinical pregnancy and miscarriage rates were observed with the combination of MACS and DGC, the lack of robust, large-scale data prevents a definitive clinical recommendation outcomes. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251181955, identifier CRD420251181955.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.