The antioxidant N-acetyl cysteine ​​improves sperm quality

Relation

Jannatifar R, Parivar K, Roodbari NH, Nasr-Esfahani MH. Effects of N-acetyl-cysteine ​​supplementation on sperm quality, chromatin integrity and levels of oxidative stress in infertile men. (Link removed). 2019;17(24).

Study objective

To determine the effects of supplementation with the antioxidant N-acetyl-cysteine ​​(NAC) on sperm quality, chromatin integrity and levels of oxidative stress in infertile men with abnormal semen parameters

Draft

Three-month prospective, randomized, blinded clinical trial

Participant

Fifty men aged 25 to 40 years with asthenoteratozoospermia determined according to WHO criteria. Participants reported no previous impregnations and had partners without fertility problems.

Patients with medical conditions and/or risk factors known to affect fertility (hormonal abnormalities, Klinefelter syndrome, varicocele, cryptorchidism, vasectomy, leukospermia, sperm antibodies, anatomical diseases, cancer, abnormal liver function, cigarette smoking, alcohol consumption, fever within 90 days after semen analysis) were excluded.

intervention

All participants received oral NAC supplementation of 600 mg daily for 3 months.

Study parameters assessed

Semen analysis was used to assess the following semen parameters: volume, sperm concentration, total motility, progressive motility, non-progressive motility, immotile sperm and abnormal morphology. Other data recorded included DNA fragmentation index, protamine deficiency levels, total antioxidant capacity (TAC), seminal malondialdehyde (MDA) levels and hormonal parameters including serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone and Prolactin. Assessments were conducted at baseline and 3 months.

Primary outcome measures

Results after 3 months were compared with those at baseline.

Key insights

After 3 months of NAC, significant improvements were noted in all semen parameters evaluated: volume (P=0.01), sperm concentration (P=0.02), total mobility (P=0.01), progressive motility (P=0.001), non-progressive mobility (P=0.01), immotile sperm (P=0.01) and abnormal morphology (P=0.001).

There were also significant reductions in the percentages of DNA fragmentation (P=0.001) and sperm with protamine deficiency (P=0.009). Oxidative stress levels improved from baseline, as evidenced by a decrease in MDA (P=0.01) and an increase in TAC (P=0.01). All hormonal parameters except prolactin showed statistically significant differences with decreases in FSH (P=0.01) and LH (P=0.04) and an increase in testosterone (P=0.01).

Practice implications

Male infertility accounts for a significant percentage of infertility cases, with a prevalence approximately equal to that of female infertility.¹Multiple etiologies have been identified, including congenital anomalies, genetic inheritance, poor lifestyle, environmental influences, and iatrogenic conditions. If no cause is identified, a diagnosis of unexplained or idiopathic infertility is made.²While the terms “unexplained” and “idiopathic” are often used interchangeably, there is an important difference. Patients with true unexplained infertility are presented with a normal examination, including semen analysis. In contrast, those with idiopathic infertility have a normal workup, with the exception of suboptimal semen analysis findings.³The participants in this study were classified as the latter because poor motility and morphology were noted (asthenoteratozoospermia).

After 3 months of NAC, significant improvements were noted in all semen parameters evaluated.

Idiopathic male infertility is a current topic of interest among researchers, with particular emphasis on the relationship between oxidative stress and abnormal semen parameters. Oxidative stress occurs when there is an excess of reactive oxygen species (ROS) with insufficient antioxidant stores.⁴Under normal physiological conditions, sperm produce small amounts of ROS, which are required for prefertilization events (sperm hyperactivation, capacitation, acrosome reaction).⁵When ROS are present in excess, they impair spermatogenesis and threaten overall sperm quality.⁶Male idiopathic infertility often presents abnormalities in both ROS and antioxidants, suggesting that these individuals carry a greater burden of oxidative stress.^4.7

In the present study, malondialdehyde (MDA) and total antioxidant capacity (TAC) served as biomarkers of oxidative stress. MDA is produced when ROS initiate lipid peroxidation of polyunsaturated fatty acids (PUFAs). Since the plasma membranes of spermatozoa contain PUFAs, MDA levels in semen serve as an indicator of lipid peroxidation.⁸Several studies have shown higher MDA levels in infertile men compared to fertile men.^9.10These findings suggest that seminal lipid peroxidation and subsequent oxidative stress contribute to the seminal abnormalities associated with idiopathic male infertility.

While the mechanism by which oxidative stress alters normal sperm physiology is unknown, recent research has shown that it affects DNA integrity. DNA fragmentation index and protamine content are considered promising markers of DNA damage. They appear to predict fertility results better than semen analysis.¹¹In 2019, Borges et al. statistically significant correlations between high levels of sperm DNA fragmentation and poor embryo development, low implantation rate and high miscarriage rate.¹²Participants in this study were initially thought to have unexplained infertility. However, almost 10% were found to have sperm abnormalities in the form of DNA fragmentation. These results suggest that DNA fragmentation is a valuable marker of sperm abnormalities for some men and could be used in combination with semen analysis to strengthen the diagnostic workup of male infertility.¹³

The connection between oxidative stress, DNA damage and poor sperm quality appears to be well documented. What is less clear is whether oxidative stress causes the DNA damage associated with semen abnormalities. The present study demonstrated remarkable improvements in oxidative stress, DNA integrity and sperm quality with antioxidant supplementation in the form of NAC. Other studies of antioxidant therapy for male infertility have reported similar results. However, rigorous studies showing clear clinical outcomes are limited, and most research concludes that further investigation is warranted.¹⁴In the meantime, it seems reasonable to target oxidative stress in the treatment of male idiopathic infertility, whether through antioxidant supplementation or otherwise. Current options for providers are extensive, with a growing list of antioxidant supplements including Selenium, L-Carnitine, Acetyl-L-Carnitine, Coenzyme Q10, Zinc, Folic Acid, Myo-Inositol, Vitamin E, Vitamin C, Docosahexaenoic Acid (DHA). , eicosapentaenoic acid (EPA) and now NAC.^15-20