The combined effect of lifestyle intervention and antioxidant therapy on sperm DNA fragmentation and seminal oxidative stress in IVF patients: a pilot study

Abstract

Purpose: Sperm DNA fragmentation (SDF) and seminal oxidative stress are emerging measurable factors in male factor infertility, which interventions could potentially reduce. We evaluated (i) the impact of lifestyle changes combined with oral antioxidant intake on sperm DNA fragmentation index (DFI) and static oxidation-reduction potential (sORP), and (ii) the correlation between DFI and sORP.

Materials and methods: We conducted a prospective study involving 93 infertile males with a history of failed IVF/ICSI. Ten healthy male volunteers served as controls. Semen analysis was carried out according to 2010 WHO manual, whereas seminal sORP was measured using the MiOXSYS platform. SDF was assessed by sperm chromatin structure assay. Participants with DFI >15% underwent a three-month lifestyle intervention program, primarily based on diet and exercise, combined with oral antioxidant therapy using multivitamins, coenzyme Q10, omega-3, and oligo-elements. We assessed changes in semen parameters, DFI, and sORP, and compared DFI results to those of volunteers obtained two weeks apart. Spearman rank correlation tests were computed for sORP and DFI results.

Results: Thirty-eight (40.8%) patients had DFI >15%, of whom 31 participated in the intervention program. A significant decrease in median DFI from 25.8% to 18.0% was seen after the intervention (P <0.0001). The mean DFI decrease was 7.2% (95% CI: 4.8-9.5%; P <0.0001), whereas it was 0.42% (95%CI; -4.8 to 5.6%) in volunteers (P <0.00001). No differences were observed in sperm parameters and sORP. Based on paired sORP and DFI data from 86 patients, no correlation was observed between sORP and DFI values (rho=0.03).

Conclusion: A 3-month lifestyle intervention program combined with antioxidant therapy reduced DFI in infertile men with elevated SDF and a history of failed IVF/ICSI. A personalized lifestyle and antioxidant intervention could improve fertility of subfertile couples through a reduction in DFI, albeit controlled trials evaluating reproductive outcomes are needed before firm conclusions can be made. Trial registration number and date: clinicaltrials.gov NCT03898752, April 2, 2019.

Keywords: DNA Fragmentation; Infertility; Reproductive Techniques, Assisted.

Figure 1. Flow diagram showing total patient breakdown.

Figure 2. Boxplots showing the difference between sperm DNA fragmentation (DFI) measurements of 10 healthy controls who delivered two semen specimens within a 14-day interval and 31 IVF patients with baseline DFI >15% who had lifestyle intervention and antioxidant therapy for 3 months. The boxplot includes the median (horizontal line in the box), 25-75% interquartile range box (i.e., representing 50% of the data), minimum and maximum values excluding outliers (whiskers extending outside of the box), and outlier (blue dot). The DFI differences between the groups were significant (P <0.0001).

Figure 3. Scatterplot of the correlation between Sperm DNA Fragmentation and Seminal Oxidation Reduction Potential, excluding patients with sperm concentration below 1 million/mL. A total of 86 patients was included. As raw data did not meet the assumptions to fit a linear model, a Spearman's rank correlation was run to test the overall hypothesis of monotonic correlation between sORP and DFI (A), and sORP normalized for motility and DFI (B). The test indicated a very weak correlation: rho=0.03 and -0.09, respectively.