Viable sperm DNA fragmentation index (SDF) provides better diagnostic accuracy than total SDF in male infertility: a...

Sperm DNA fragmentation index (SDF) is a key biomarker for male infertility; however, traditional SDF measurements include non-viable sperm, reducing clinical relevance. The viable SDF may provide greater diagnostic accuracy. This study aimed to explore the potential of viable SDF cutoff and assessed its predictive value for male fertility.

This cross-sectional study enrolled men undergoing reproductive evaluation at a tertiary reproductive medical center. Semen analysis followed the World Health Organization (WHO) 5th edition guidelines. Total and viable SDF were measured using the sperm chromatin structure assay, with viability assessed using Far Red staining. Spearman's correlation analysis examined relationships between viable SDF, total SDF, and standard semen parameters. Using the 25% total SDF cutoff, patients were grouped into high (≥25%, n=96) and low (<25%, n=131) categories. Receiver operating characteristic (ROC) curve analysis identified the optimal viable SDF cutoff. Multivariate logistic regression analysis determined independent influencing factors for viable SDF, and ROC curves assessed model performance.

A total of 227 men undergoing male reproductive evaluation were included in the study. The mean total and viable SDF were 21.89%±14.95% and 10.31%±12.21%, respectively. Viable SDF showed significant negative correlations with progressive and total motility and a strong positive correlation with total SDF. ROC analysis identified a viable SDF cutoff of 9.79% [area under the curve (AUC) =0.813; sensitivity =76%, specificity =66%]. Significant discrepancies were observed between groupings based on total and viable SDF thresholds. Notably, 23 men with total SDF ≥25% had viable SDF <9.79%, whereas 44 with total SDF <25% had viable SDF >9.79%. A clinical cutoff of 9.79% for viable SDF shows superior diagnostic performance over total SDF.

Viable SDF provides a more accurate assessment of clinically relevant (functional) sperm DNA damage because it evaluates DNA fragmentation specifically in membrane-intact, fertilization-competent sperm, rather than in the total sperm population.