Associations Between Sperm DNA Fragmentation and Lifestyle Factors

Sperm DNA fragmentation index (DFI) has been proposed as a supplementary biomarker to traditional semen parameters in the evaluation of male infertility. However, its determinants and clinical relevance remain unclear, particularly regarding modifiable lifestyle factors. This study investigated associations between DFI, clinical characteristics, and lifestyle factors in comparison with conventional semen parameters.

This study included 172 men divided into three subgroups: (1) 68 men from couples undergoing intracytoplasmic sperm injection (ICSI) due to male infertility, (2) 49 men from couples undergoing in vitro fertilization/intrauterine insemination (IVF/IUI) attributable to female infertility, and (3) 55 fertile controls. DFI was assessed using sperm chromatin structure assay. Information on lifestyle, anthropometrics, and clinical history was collected through questionnaires and clinical examination. Associations with DFI were analyzed using multivariable linear regression with and without adjustment for treatment subgroup, and associations between DFI and semen parameters using Spearman's rank correlation.

Median DFI differed between groups (p < 0.001): 17.4% (ICSI), 10.8% (IVF/IUI), and 9.2% (fertile controls). DFI was inversely correlated with semen parameters, strongest for progressive motility (ρ = -0.61, p < 0.01). Varicocele, higher central adiposity (waist-to-height ratio [WtHR] ≥ 0.6), and smaller testis size were associated with higher DFI, although these associations disappeared after subgroup adjustment. In adjusted analysis, higher age was associated with higher DFI (3% increase per year), while lower central adiposity (WtHR < 0.4) was associated with 26% lower DFI. Smoking, alcohol intake, and BMI showed no consistent associations.

DFI was negatively associated with fertility potential and age; however, it was driven primarily by results from the IVF/IUI subgroup and WtHR, whereas BMI, smoking, and alcohol intake were not. Central adiposity and related metabolic or inflammatory burden may thus be more relevant for DFI than overall body mass. DFI largely paralleled conventional semen parameters and should not be interpreted as a stand-alone marker, although it may provide complementary information in male infertility evaluation.