Impact of antioxidant treatment on DNA fragmentation index: a double-blind placebo-controlled randomized trial.

BACKGROUND: Previous reports on effect of antioxidants on sperm DNA integrity were equivocal, and there is a lack of randomized, placebo-controlled studies. OBJECTIVES: To evaluate the efficacy of combined antioxidant treatment in subfertile men with normal reproductive hormone levels and high sperm DNA fragmentation index (DFI). MATERIALS AND METHODS: This placebo-controlled, double-blind, randomized study evaluated the effects of combined antioxidant treatment in 77 men from infertile couples, with normal testosterone, LH and FSH levels and DFI ≥25%. All participants were randomly assigned to receive combined antioxidant treatment (vitamins, antioxidants and oligoelements) or placebo for six months. The primary outcome measured was DFI. Secondary outcomes were standard semen parameters. DFI and other semen parameters were, at each time point (pre-treatment, and after three and six months of treatment), compared between the treatment and the placebo group using Mann-Whitney U-test. RESULTS: Antioxidant group had higher sperm concentration after three months of treatment (median: 24.4 × 106 /mL vs. 27.2 × 106 /mL; P = 0.028) and borderline statistically significant higher concentration after six months of treatment (median: 24.4 × 106 /mL vs. 33.3 × 106 /mL; P = 0.053) compared to pre-treatment values. The DFI did not change during the 6 months of antioxidant therapy. No statistically significant difference between the antioxidant and placebo group was seen for any of the semen parameters including sperm DFI at any of the three time points. DISCUSSION: The increase in sperm concentration was more pronounced in the antioxidant treated group but not statistically significantly higher than among controls, perhaps due to insufficient statistical power. Previous studies have shown positive effect of antioxidant treatment on DFI and other semen parameters. However, our findings indicate that men with normal reproductive hormone levels may not be the primary target group for such therapy. CONCLUSION: Six months treatment with antioxidants had no effect on sperm DFI.

Sperm chromatin structure assay in prediction of in vitro fertilization outcome.

Sperm DNA fragmentation index (DFI) assessed by sperm chromatin structure assay is a valuable tool for prediction of fertility in vivo. Previous studies on DFI as predictor of in vitro fertilization (IVF) outcome, based on relatively small materials, gave contradictory results. The present study examines, in a large cohort, the association between sperm DFI and the outcome of IVF/ICSI procedure. The study is based on 1633 IVF or ICSI cycles performed at the Reproductive Medicine Centre, Skåne University Hospital, Malmö, Sweden, between May 2007 and March 2013. DFI values were categorized into four intervals: DFI ≤ 10% (reference group), 10% < DFI ≤ 20%, 20% < DFI ≤ 30%, DFI > 30%. For the three latter intervals, the following outcomes of IVF/ICSI procedures were analyzed in relation to the reference group: fertilization, good quality embryo, pregnancy, miscarriage, and live births. In the standard IVF group, a significant negative association between DFI and fertilization rate was found. When calculated per ovum pick-up (OPU) Odds Ratios (ORs) for at least one good quality embryo (GQE) were significantly lower in the standard IVF group if DFI > 20%. OR for live birth calculated per OPU was significantly lower in standard IVF group if DFI > 20% (OR 0.61; 95% CI: 0.38-0.97; p = 0.04). No such associations were seen in the ICSI group. OR for live birth by ICSI compared to IVF were statistically significantly higher for DFI > 20% (OR 1.7; 95% CI: 1.0-2.9; p = 0.05). OR for miscarriage was significantly increased for DFI > 40% (OR 3.8; 95% CI: 1.2-12; p = 0.02). The results suggest that ICSI might be a preferred method of in vitro treatment in cases with high DFI. Efforts should be made to find options for pharmacologically induced reduction of DFI. The study was based on retrospectively collected data and prospective studies confirming the superiority of ICSI in cases with high DFI are warranted.

Prevalence of high DNA fragmentation index in male partners of unexplained infertile couples.

The sperm chromatin structure assay (SCSA) parameter DNA fragmentation Index (DFI) is a valuable tool for prediction of fertility in vivo. Clinical data show that a DFI above 30% is associated with very low chance for achieving pregnancy by natural conception or by insemination. Already when DFI is above 20% the chance of natural pregnancy is reduced, this despite normal conventional semen parameters. The aim of the present study was to investigate the prevalence of high DFI in male partners of unexplained infertile couples to further identification of male factors contributing to subfertility. Among 212 consecutive men under infertility investigation, 122 cases with the diagnosis 'unexplained infertility' were identified. For all but three, SCSA data were available. The percentage of couples with diagnosis 'unexplained infertility' in which the male partner has DFI >20% or DFI >30% was calculated. In the group diagnosed with 'unexplained infertility' 17.7% of the men (95% CI 10.8-24.5) presented with 20 ≤DFI <30 and 8.4% (95% CI 3.40-13.4) had DFI ≥30%. A significant part of men diagnosed as unexplained infertile according to traditional diagnostic methods has remarkably high degrees of fragmented sperm DNA. Apart from adding to our understanding of biology of infertility our finding has clinical implications. Couples in which the DFI of the male partner is high can avoid prolonged attempts to become spontaneously pregnant or referral for intrauterine insemination, both having low chances of leading to conception.

Intra-individual variation of the sperm chromatin structure assay DNA fragmentation index in men from infertile couples.

BACKGROUND: The sperm chromatin structure assay (SCSA) is a valuable tool for prediction of fertility in vivo, with DNA fragmentation index (DFI) of 30% as a clinically useful cut-off level. Previous studies on fertile men have shown a high level of repeatability, with an intra-individual variability in DFI of ≈ 10%. However, conflicting data on how much the DFI fluctuates within individuals exist. The aim of the present study was to investigate the intra-individual variation of DFI in order to further evaluate the clinical use of SCSA. METHODS: Among 2409 consecutive men under infertility investigation, repeated SCSA analyses were performed on 616 samples from men between 18 and 66 years of age. The coefficient of variation (CV) for DFI was calculated. For each patient, we also analyzed whether the DFI value in tests I and II switched the category from <30 to >30%, or vice versa. RESULTS: Mean CV for DFI for men with at least two SCSA analyses within a 30-month period was 30.1% (SD 21.5). Compared with the first test, 85% (95% confidence interval: 82-87%) of the men remained on the same side of the cut-off point of 30%. CONCLUSIONS: Despite showing a high intra-individual CV for DFI, 85% of the men from infertile couples did not change category between tests, with respect to the cut-off level of 30%. Thus, using the previously established DFI cut-off value of 30%, a single SCSA analysis has a high predictive value for assessing fertility in vivo.