Sperm deoxyribonucleic acid fragmentation: predictors, fertility outcomes, and assays among infertile males.

OBJECTIVE

To examine the factors associated with increased deoxyribonucleic acid fragmentation index (DFI), evaluate the pregnancy outcomes of men with increased DFI, and compare three independent DFI assays.

DESIGN

Secondary analysis.

SETTING

Nine US-based fertility centers.

PATIENTS

Infertile men (N = 147) with sperm concentration ≤15 × 10/mL, motility ≤40%, or normal morphology ≤4% were enrolled. The female partners were ovulatory, ≤40 years old, and had documented tubal patency.

INTERVENTIONS

At a baseline visit, the men provided a semen sample. The couples attempted conception without assistance for 3 months and with ovarian stimulation and intrauterine insemination in the subsequent 3 months.

MAIN OUTCOME MEASURES

The DFI was analyzed using the sperm chromatin structure assay (SCSA) with increased DFI defined as >30%. The predictors of increased DFI were determined by a multivariable linear regression model. The pregnancy outcomes were compared using the χ test. The independent DFI assays (SCSA, deoxynucleotidyl transferase-mediated dUTP nick end labeling, and Comet) were compared with Pearson and Spearman correlations.

RESULTS

The 19% of men with increased DFI were older (36.0 vs. 33.0 years) and had lower total sperm motility (38.2% ± 20.5% vs. 45.2% ± 15.6%). Increased male age was found to be a significant predictor of DFI (0.75, 95% confidence interval [0.06, 1.45]). Increased DFI was not associated with conception or live birth. There was a modest correlation of the deoxynucleotidyl transferase-mediated dUTP nick end labeling assay with the SCSA (r = 0.34) and Comet assay (r = 0.19).

CONCLUSIONS

Older age was associated with increased DFI among infertile men. The DFI assays were only weakly correlated, indicating a standard definition of DFI is needed to truly interrogate how sperm deoxyribonucleic acid fragmentation impacts male fertility.