The peripheral blood sample was taken from each patient and was immediately centrifuged for 10 min at 3000 rpm (Hettich, EBA20, UK) and serum samples stored at − 70 °C for future evaluation and analysis. Sperm count was evaluated by a sperm counting chamber and expressed as million/ml. Normal morphology was assessed by Papanicolaou staining and subjects with less than 4% normal sperm morphology were considered as teratozospermic according to WHO criteria. Briefly, sperm motility was assessed by the Computer Aided Sperm Analysis (CASA) system (LABOMED, SDC313B, Germany), which defined sperm as progressive, non-progressive and immotile. Semen parameters (volume, sperm count, progressive and non-progressive motility and normal morphology) were evaluated according to WHO guidelines (2010). Variables including seminal parameters, DNA fragmentation index, chromatin maturity, total antioxidant capacity, lipid peroxidation and hormonal parameters (LH, FSH, Testosterone and Prolactin) were measured before and after the intervention. In addition, male height (m), weight (kg) and body mass index (BMI, kg/m3) were recorded and compared before and after intervention. After reviewing the full text and assessing potential records from databases, registries, and other sources, 16 21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36 studies were included in the systematic review (Figure 1). The literature search yielded 777 studies, 763 from the electronic databases WOS, SCOPUS, and PubMed, and 14 from other sources such as ResearchGate and reference lists of relevant studies. These parameters were included as outcomes because they are commonly investigated in health biomarker studies and sports science. We utilised a random-effects model to get the overall effect size if the amount of between-study heterogeneity was significant. If the trial had ‘low risk’ for all domains, a high-quality study was considered a low risk of bias. The Cochrane Collaboration’s risk of bias tool was employed to assess the risk of bias for each study(Reference Higgins, Altman and Gøtzsche19). Then, relevant studies were assessed to ensure the suitability of a study for full-text assessment. Numerous studies have indicated that NAC is effective for the induction of ovulation and pregnancy rates in PCOS patients. However, if the body experiences a deficiency in these precursor amino acids, cysteine becomes essential and must be obtained through dietary sources. This designation implies that the body can synthesize cysteine from two other amino acids, namely serine and methionine. Oxidative stress may lead to dysfunction in endocrine glands, contributing to hormone imbalances (13, 27). Excessive production of reactive oxygen species (ROS) can damage cells and impair the intricate signaling pathways that regulate hormone synthesis, secretion, and receptor binding. The results of evaluating the quality of the included studies are presented in online Supplementary Fig. Overall, eighteen clinical trials published between 2002 and 2021 were included in the meta-analysis. The sensitivity analysis was used to identify the dependence of overall effect size on a single study. NAC appears to be a more appropriate supplement than GSH or CySH administration to modulate OS induced by drugs (paracetamol) or diseases that occur with low GSH levels, such as chronic obstructive pulmonary disease (COPD), by increasing intra-tissue GSH 47,48. GSH is the most abundant non-protein thiol in the body and one of the major antioxidants against ROS, and GSH is a cofactor of GPx . The reduction in lipid peroxidation occurs as with other antioxidant supplements, such as vitamin C and/or E, and prevents OS 43,44. This is in line with Yalçin et al. who reported that oral supplementation with 100 mg/day of NAC blocked lipid peroxidation in chronic blepharitis. Exercise stimulates an increase in peroxidation that damages cell membranes, alters lipoproteins, and breaks down structures containing lipid conjugates . The concentration of NAC is considered to be a limiting factor in its direct antioxidant activity . The amino acid NAC can modulate OS through its actions as a cysteine donor in maintaining glutathione homeostasis and through a direct knockdown of ROS . In these cases, the administration of exogenous antioxidants seems necessary to alleviate oxidative damage . These factors can be considered oxidative risk co-factors, as they increase the risk of damage and OS due to their cumulative effect on the ROS sources of exercise . In addition, there are extrinsic factors to exercise that can increase and trigger more OS in the body or impair the effectiveness of the antioxidant defence system, such as environmental conditions and the athlete’s diet .
