Baseline Levels of Seminal Reactive Oxygen Species Predict Improvements in Sperm Function Following Antioxidant Therapy in Men With Infertility

Wayne Vessey; Shaghayegh Saifi; Aditi Sharma; Cassandra McDonald; Paula Almeida; Monica Figueiredo; Suks Minhas; Ashraf Virmani; Waljit S. Dhillo; Jonathan W. Ramsay; Channa N. Jayasena

Disclosures

Clin Endocrinol. 2021;94(1):102-110. 

In This Article

Results

Baseline Characteristics

Forty-four infertile men with reduced sperm function were included in the study. The mean age of participants was 40 ± 1 years. Baseline semen parameters are summarized in Table 1. Fifteen of the 44 patients had abnormally elevated semen ROS levels (>10 RLU/SEC/106 sperm). No significant differences in baseline characteristics were observed between men with elevated ROS levels ('High ROS' group) and normal ROS levels ('Normal ROS' group).

Effects of Antioxidant Treatment on Sperm Function in Men With Infertility

We investigated whether sperm function, measured by the WHO 2010[14] criteria, changed following a 3-month course of daily LAL administration in infertile men with at least one abnormal semen analysis parameter with either normal or elevated baseline semen ROS levels.

Normal ROS Group. LAL administration had no significant effect on semen volume, sperm count, total and progressive sperm motility or sperm morphology in men with reduced sperm function and normal baseline ROS levels (Figure 2A-E). Semen ROS levels increased nearly twofold higher post-treatment when compared to pretreatment, but this increase was nonsignficant (mean semen ROS in RLU/SEC/106 sperm: 1.4 ± 0.3, baseline: 2.6 ± 1.0, post-treatment, P = .22 vs. baseline) (Figure 2F).

Figure 2.

Sperm characteristics of infertile patients with normal baseline ROS (ROS ≤ 10). Bar graphs compare semen volume (A), sperm count (B), total sperm motility (C), progressive sperm motility (D), sperm morphology (E) semen ROS (F) at baseline versus after 3 months of L-carnitine and acetyl-L-carnitine (LAL) therapy. Data are mean ± SEM. ROS: Reactive oxygen species [Colour figure can be viewed at wileyonlinelibrary.com]

High ROS Group. Semen volume and sperm morphology did not change significantly following LAL treatment when compared with baseline in men with reduced sperm function and High ROS (Figure 3A and E). However, mean levels of sperm count increased by approximately 50% following 3 months of LAL treatment in men with reduced sperm function and High ROS (mean count in mill/ml: 21.5 ± 7.2, baseline; 32.6 ± 9.5, post-treatment, P = .0005 vs. baseline) (Figure 3B). Mean total and progressive sperm motility also increased significantly following 3 months of LAL treatment in men with reduced sperm function and High ROS (mean total sperm motility in % 29.8 ± 5.0, baseline: 39.4 ± 6.2, post-treatment, P = .004 vs. baseline; mean progressive sperm motility in % 23.1 ± 4.6, baseline: 30.0 ± 5.5, post-treatment, P = .014 vs. baseline) (Figure 3C&D). Furthermore, mean semen ROS levels reduced significantly by approximately fivefold, after 3 months of LAL therapy in men with reduced sperm function and High ROS (mean semen ROS in RLU/SEC/106 sperm 55.2 ± 14.3, baseline; 10.6 ± 2.5, post-treatment, P = .0001 vs baseline) (Figure 3F).

Figure 3.

Sperm characteristics of patients with elevated baseline ROS (ROS > 10). Bar graphs compare semen volume (A), sperm count (B), total sperm motility (C), progressive sperm motility (D), sperm morphology (E) and semen ROS (F) at baseline versus after 3 months of L-carnitine and acetyl-L-carnitine (LAL) therapy. Data are mean ± SEM. ROS: Reactive oxygen species. **P < .01; ***P < .001; ****P < .0001 [Colour figure can be viewed at wileyonlinelibrary.com]

Comparing how Semen ROS Levels Influence the Response of Men With Reduced Sperm Function to Antioxidant Treatment

Sperm count increased in 13/15 (86.7%) men in the high ROS group which was significantly higher when compared with the normal ROS group (14/29 (48.3%, P < .05) (Figure 4B). Total sperm motility increased in 12/14 (85.77%) men in the high ROS group which was significantly higher when compared with the normal ROS group (12/29 (41.4%, P < .01) (Figure 4C). Progressive sperm motility increased in 12/15 (80%) men in the high ROS group which was significantly higher when compared with the Normal ROS group (11/29 (37.9%, P < .05) (Figure 4D). Furthermore, semen ROS levels reduced in all (14/14; 100%) men in the high ROS group which was significantly lower when compared with the Normal ROS group (11/29 (42.3%, P < .001) (Figure 4E). No significant difference was noted in sperm volume (Figure 3A) or sperm morphology (Figure 4E).

Figure 4.

Proportion of infertile men with improvements in sperm function. Bar graphs present the percentage of infertile men with increases of semen volume (A), sperm count (B), total sperm motility (C), progressive sperm motility (D, sperm morphology (E) and reduction in semen reactive oxygen species (ROS) (F) following 3 months of L-carnitine and acetyl-L-carnitine (LAL) therapy. The Normal ROS group (grey bars) had semen ROS ≤ 10 RLU/SEC/106 sperm at baseline. The High ROS group (red bars) had semen ROS > 10 RLU/SEC/106 sperm at baseline. *P < .05; **P < .01; ***P < .001. Proportions were compared using Fisher's exact test [Colour figure can be viewed at wileyonlinelibrary.com]

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