Multimodal biomarker profiling in varicocele predicts surgical recovery

Varicocele (VC) remains a leading correctable cause of male infertility, yet standardized multimodal biomarkers are lacking for clinical stratification and outcome prediction.

This prospective observational study enrolled 131 primary VC patients and 20 healthy controls, evaluating semen parameters, sperm DNA fragmentation index (DFI), testicular shear wave elastography (SWE), hormonal profiles, and inflammatory/metabolic markers.

VC patients showed reduced sperm progressive motility (sperm PM) (p < 0.001), elevated DFI (p = 0.002), increased abnormal sperm morphology (p < 0.001); smaller left (p = 0.002) and right (p = 0.029) testis, volume difference (p = 0.030); bilateral testicular stiffness (left p < 0.001, right p < 0.001); higher homocysteine (p = 0.001); and a lower T/E2 ratio (p = 0.030). DFI correlated negatively with sperm PM (r = -0.367, p < 0.001). Postoperative improvements were observed in sperm PM (p < 0.001), sperm morphology (p < 0.001), DFI (p < 0.001), left testicular elasticity (p < 0.001), right testicular elasticity (p < 0.001), homocysteine (p = 0.001), testosterone (p = 0.011), and the T/E2 ratio (p = 0.011). Preoperative DFI (OR =1.045), abnormal sperm morphology rate (OR =1.604), and sperm PM (OR =0.951) independently predicted complete semen parameter recovery at 3 months (AUC = 0.863, sensitivity 67.9%, specificity 89.5%).

An integrated multimodal framework incorporating imaging, molecular, and functional biomarkers facilitates prognostic stratification and personalized management of varicocele-associated infertility.