Relationship between sperm DNA fragmentation and sperm motility or abnormality. Comparison of FSH, LH, Testosterone, and prolactin before and after treatment with NAC. Red-staining sperm have intact DNA, while green-staining sperm have DNA fragmentation. Comparison of semen parameters before and after treatment with NAC. Comparison of age, duration of infertility, weight, height, and BMI before and after treatment with NAC. Seminal total antioxidant capacity (TAC) was measured using a commercially available kit (Zell Bio GmbH, Wurttemberg, Germany).
Based on the above, the present study was conducted to investigate the effects of daily oral NAC supplementation on the quality of semen parameters, chromatin integrity and reproductive hormones in asthenoteratozoospermic men. After NAC treatment, patients’ sperm count and motility increased significantly whereas abnormal morphology, DNA fragmentation and protamine deficiency showed significant decreases compared to pre-treatment levels (P P P The possible explanation is that the castrated condition and time course of castration in this study may induce only mild pathological condition in the brain, therefore the monotherapy by NAC and inulin can completely mitigate those deleterious effects. A previous study reported that 10% inulin improved cognitive performance in the light extinction test and the wellbeing of male rats using the functional observational battery assessment tool (FOB) . The underlying mechanisms of neuronal apoptosis in castrated rats may be due to increased oxidative stress and microglial hyperactivation, leading to releases several pro-inflammatory cytokines and brain inflammation . The present study and other also demonstrated an increase in hippocampal TUNEL positive cells of castrated male rats, resulting to cognitive decline. Moreover, our previous studies have shown that testosterone deprivation increased apoptosis, as measured by increasing levels of apoptotic proteins .
Performed pooled analyses on the number of follicles and endometrial thickness revealed that the effects of NAC on these variables were not in a dose-dependent manner. However, in a dose-dependent manner, its combination with acrylamide led to the significant elevation of the number of ovarian follicles and the levels of FSH, E2 and progesterone(Reference Naimi, Shariati and Naimi31). WMD, weighted mean difference; SMD, standardised mean difference; LH, luteinising hormone; FSH, follicle-stimulating hormone; E2, oestradiol; NR, not reported. Removing an individual research at a time by sensitivity analysis did not affect the results. There were no significant changes in results following subgroup analysis (Table 2). The blinding of subjects and researchers was reported in four studies(Reference Hashim, Anwar and El-Fatah22,Reference Nasr9,Reference Chandil, Pande and Sen27,Reference Gayatri, Kumar and Kumar28) . Overall, five studies were defined as high quality(Reference Hassan, Alalfy and Hassan18,Reference Badawy, El Nashar and El Totongy20,Reference El Sharkwy and Abd El Aziz24,Reference Kose and Naziroglu26,Reference Ghomian, Khadem and Moeindarbari5) .
Recent studies showed that BMI and E2 levels have positive association. In addition, NAC increases the cellular levels of antioxidants and reduces GSH at higher doses. Subgroup analysis based on the country showed that the improving effects of NAC on the endometrial thickness are more significant in some countries. Previous studies showed that with different doses of NAC, different effects could be observed(Reference Cavallini, Ferraretti and Gianaroli32). However, due to the limited range of administered dosages of NAC, subgroup analysis based on the dosage was not performed on LH, FSH and TT levels.
According to the inclusion criteria, 184 studies were excluded. The reviewers searched 219 studies in three databases. Two reviewers searched dependently for all randomized controlled trials (RCTs) published until August 31, 2020, involving the efficacy of LC/LAC and NAC in men with idiopathic asthenozoospermia. This meta-analysis strictly followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) list (Moher et al., 2010). Compared with placebo, NAC orally daily can significantly improve sperm motility (Safarinejad & Safarinejad, 2009). Among them, 44% of infertile men had no known disease that could explain infertility and these patients were assigned as idiopathic male infertility (Pierik et al., 2000). It is reported that about half of childless couples with infertility are not pregnant due to male factors (Gnoth et al., 2005).
High levels of LC in epididymal fluid plays an important role in sperm cell metabolism (Enomoto et al., 2002), and some studies report that the onset of sperm motility is related to the increase of LC in epididymal cavity and the concentration of L-acetyl-carnitine (LAC) in sperm cells (Radigue et al., 1996). 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. First, only a limited number of the studies have assessed the effects of NAC on progesterone and SHBG levels. Therefore, measuring GSH levels to determine the availability of cysteine as the limiting step must be considered in future studies. As well, NAC supplementation increased levels of GSH in individuals with low GSH levels and improved redox homoeostasis(Reference Paschalis, Theodorou and Margaritelis48).
On the other hand, the hormone status and other metabolites levels, such as serum 25(OH)D in women younger than 30 years, are lower than that in women 30 years and older(Reference Nakamura, Nashimoto and Matsuyama45). Similarly, our results suggested that improving the effects of NAC on FSH levels was more significant than l-carnitine. However, additional studies are needed to compare the effects of NAC with placebo on the number of follicles. However, the effects of NAC on the number of follicles, endometrial thickness, LH and FSH levels were not markedly different. In postmenopausal women, alcohol ingestion was related to increased plasma E2 and oestrone levels(Reference Ginsburg, Mello and Mendelson39). Indeed, increased E2 levels among overweight and obese postmenopausal women were due to the increased fat mass and E2 production in adipose tissue(Reference Gruber, Tschugguel and Schneeberger35).

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