Value of sperm DNA fragmentation (SDF) in predicting reproductive outcomes - a systematic review and meta-analysis

Male infertility is commonly diagnosed by semen analysis, but it often fails to distinguish fertile from infertile men unless abnormalities are marked. Sperm DNA fragmentation (SDF) testing is becoming a diagnostic aid. High SDF-defined as values higher than assay-specific cut-offs-predicts adverse reproductive outcomes in natural conception and after IUI, IVF, and ICSI, as shown in this systematic review and meta-analysis. From inception to March 2025, we searched MEDLINE, EMBASE, CINAHL, Google Scholar, Web of Science, and SCISEARCH for COMET, SCSA, TUNEL, or SCD studies that reported pregnancy or miscarriage. Assay cut-offs were used to extract data into 2x2 tables. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios were evaluated using random-effects HSROC models following PRISMA and QUADAS-2 guidelines. In 52 trials with 19,930 subjects, all reported pregnancies and 41 reported miscarriages. High SDF had low sensitivity and higher specificity across natural and assisted conception, with modest likelihood and diagnostic odds ratios indicating limited discrimination. With significant heterogeneity, HSROC curves showed poor-to-moderate discrimination. High SDF had low sensitivity and high specificity for miscarriage, indicating poor prediction. Evaluating high SDF alone to predict pregnancy or miscarriage is limited. Its clinical value needs to be determined through well-designed trials.