The small-study effect was evaluated by the formal tests of Egger’s and Begg’s. To detect potential sources of heterogeneity, subgroup analyses were performed according to the predefined variables, including duration of the intervention, NAC dosage, study location and the type of control. If heterogeneity was not significant, the fixed-effects model was employed to estimate the overall effect size. Risk bias assessments were conducted independently by two reviewers. If the study contains a methodological defect that may affect its findings, the study was given a ‘high risk’ score; if there was no defect for that domain, a ‘low risk’ score; if the information was insufficient to determine the effect, an ‘uncertain risk’ score. The tool consists of seven domains, including random sequence generation, allocation concealment, performance bias, reporting bias, detection bias, attrition bias and other sources of bias.
There are deficiencies in the quality of the trials used for analysis, mainly including fewer trials included and inconsistent basic indicators of various studies. Jannatifar et al. (2019) reported that the concentration of seminal malondialdehyde (MDA) decreased significantly, and MDA was a specific marker of lipid peroxidation, while TAC increased significantly after NAC treatment. Khan et al. (2013) reported that the level of total antioxidant capacity (TAC) in seminal plasma of patients with asthenospermia was significantly lower than that of healthy men. Thus, these antioxidants should be received cautiously and patients should take necessary tests for their redox status prior to the treatment with a supplement of specific formulation. This study reported the positive effects of the use of the LC/LAC and NAC for treating male infertility caused by oxidative stress on the semen parameters. Different from the results of this study, an RCT found that sperm motility was improved after NAC treatment. Besides, NAC had a significantly greater increase in sperm concentration and ejaculate volume compared with the placebo group, and there was no significant difference in LC/LAC.
NAC may help improve insulin sensitivity, which could support balanced glucose and androgen levels in women with PCOS (34). It is characterized by a range of symptoms, including irregular menstrual cycles, ovarian cysts, and elevated levels of androgens. Due to its antioxidant properties, NAC has emerged as a promising intervention to influence hormonal regulation in a variety of endocrine conditions. Glutathione protects liver cells from oxidative damage, preserving their structural and functional integrity.
N-acetyl-cysteine (NAC) as a derivative of L-cysteine is frequently regarded as antioxidant (Zafarullah et al., 2003). Moreover, NAC has a positive effect on sperm concentration and ejaculate volume, whereas no obvious effect was observed in serum hormones. However, this conclusion should be with precaution as the other sex hormones and ovulation parameters were not influenced by NAC supplementation, significantly.
Carnitine can not only protect cell membrane and DNA from oxygen free radical damage but can also prevent protein oxidation and pyruvate and lactate oxidative damage (Arduini, 1992). Among them, the treatment of idiopathic male infertility is still controversial, and most of the clinical treatment still depends on empirical methods (Agarwal et al., 2020). Forest plots showing results in sperm parameters on the normal morphology. Forest plots showing results in sperm parameters on the sperm motility. Forest plots showing results in sperm parameters on the sperm volume. Forest plots showing results in sperm parameters on the sperm concentration. Table 1 presents the basic characteristics of each study.
However, due to the limited number of conducted studies, more conclusions must be declared with precaution. These factors have been ignored in the relationship between NAC and E2 levels. These pathways could contribute to a synergistic effect of metformin and NAC on sex hormones profile. Cigarette smoking is related to increase in 2-hydroxylation pathway of E2 and decrease in bio-availability of oestrogen(Reference Michnovicz, Hershcopf and Naganuma40). It has been shown that BMI, alcohol use and smoking influence E2 serum levels(Reference Sriprasert, Kono and Karim34). However, due to the limited number of countries in which studies have been performed, exact interpretation of this issue must be with precaution.
Comparison of age, duration of infertility, weight, height, and BMI before and after treatment with NAC. Five hundred sperm per slide were evaluated under a fluorescence microscope (BX51, Olympus, Japan). Five hundred sperms per slide were assessed under a fluorescence microscope (BX51, Olympus, Japan) at 100x magnification. Seminal total antioxidant capacity (TAC) was measured using a commercially available kit (Zell Bio GmbH, Wurttemberg, Germany).
Two RCTs including 139 patients were included in the analysis. Two RCTs including 86 patients were included in the analysis. Three RCTs including 431 patients were included in the analysis. Four RCTs including 190 patients were included in the analysis. All included studies were randomized controlled design with specific randomized protocols, and three study described the calculation of sample size. The meta-analysis was performed to access efficacy of L-carnitine/L-acetyl-carnitine (LC/LAC) and N-acetyl-cysteine (NAC) in men with idiopathic asthenozoospermia. Overall, this study supports the efficacy and favourable effects of NAC supplementation on improvement of reproductive system function.

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