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The purpose of ubiquinol allocation is hypothetically in the electron transport chain and an excess would act as antioxidents in the sperm cytoplasm and membrane. Sperm cells uptake ubiquinol and ubiquinol precursors from their environment, which are converted to ubiquinol by enzymatic changes in the sperm cytoplasm or mitochondrial inner membranes (Hughes et al., 2023). Apart from the hormonal mechanism through which CoQ10 may exert its effect, it also exerts antioxidant activities. Furthermore, inhibin B plays a crucial role in the negative regulation of FSH secretion, (Ajayi and Akhigbe, 2020) establishing an inverse relationship between inhibin B and FSH, and a positive relationship between inhibin B and sperm count (Meachem et al., 2001). The male reproductive function is regulated by the hypothalamic-pituitary-testicular (HPT) axis, which involves the pulsatile release of gonadotropin-releasing hormone. This disparity may be due to the low doses of CoQ10 administered in the older studies.
The elevated TAC and CAT activities and decreased MDA and ALT concentrations noted in the present study inferred the role of CoQ10 in amelioration of heat stress in the perspective of semen quality via enhancement of seminal plasma antioxidant defense systems and lowering sperm membrane lipid peroxidation. Moreover, compared to fertile men, the seminal plasma of infertile men has lower levels of CoQ10 which could be increased via dietary supplementation and improved semen density and quality (Ghanbarzadeh et al. 2014; Nadjarzadeh et al. 2014). Lafuente et al. in 2013 conducted a meta-analysis to evaluate the effect of CoQ10 treatment on live birth, pregnancy rate, level of Q10 in seminal plasma, sperm concentration and total sperm motility. This systematic review aims to elucidate the usefulness of CoQ10 supplementation in the treatment of male infertility, particularly with regard to semen quality assessed by conventional and advanced methods, and pregnancy rates.
Interestingly, there was no significant inter-study heterogeneity in the hormonal studies. Nonetheless, there was a significant inter-study heterogeneity in these studies. Seminal oxidative stress has been shown to be a key factor in the development of male infertility. No studies confirm direct testosterone elevation in healthy men. Improved sperm quality correlates with hormonal regulation. For fertility, sperm DNA fragmentation improves by 25% after six months.
However, other studies (Safarinejad et al., 2012; Balercia et al., 2009; Gopinath et al., 2013; Nadjarzadeh et al., 2014; Safarinejad, 2009; Stenqvist et al., 2018) showed a high certainty of evidence (Table 2). In two of the studies (Kopets et al., 2020; Nadjarzadeh et al., 2011), a moderate certainty of evidence was observed. In addition, 100% low risk was observed in performance bias, detection bias, reporting bias, and other bias, while about 82.5% of the studies had low risk for attrition bias (Figure 2B). Overall, considering all eligible studies, the selection bias was 62.5% and 100% low risk in "random sequence generation" and "allocation concealment" respectively. In the remaining studies (Safarinejad et al., 2012; Nadjarzadeh et al., 2014; Nadjarzadeh et al., 2011; Safarinejad, 2009; Stenqvist et al., 2018) a low RoB was measured in all domains.
Moreover, CoQ10 supplementation seems to correlate with a significant increase in serum inhibin B levels. Sensitivity analysis was not performed due to limited data on the effect of CoQ10 on serum inhibin B levels (Figure 12). Two studies measured circulating FSH level in men after 26 weeks of treatment with CoQ10 or placebo.
Further studies are clearly needed to determine whether CoQ10 has a merely "cosmetic" effect or whether it can have a real impact on the treatment of male infertility. On the other hand, the only study evaluating two different treatment regimens showed a greater improvement in seminal parameters in the group treated with 400 mg CoQ10 than in the group treated with 200 mg CoQ10 . CoQ10 supplementation significantly increases seminal coQ10 levels 14,15 and improves the antioxidant capacity of seminal fluid 13,17,18,20,21,23, improving both enzymatic and non-enzymatic germ cell protection systems. On the other hand, supplementation with compound mixes (including 20–200 mg CoQ10) showed similar effects on sperm density 11,12,24,26,27,29,31,32, motility 10,11,24,25,27,29,30,31 and morphology 11,29,30,31,32. As regards CoQ10 monotherapy, sperm motility significantly increased in all the studies evaluated 9,13,14,15,16,18,19,20,21,22,23 except one . In a recent systematic review, Majzoub et al. reported a beneficial effect of antioxidant therapy in reversing OS-induced sperm dysfunction, but the heterogeneous nature of the study designs prevented the recognition of an optimal treatment regimen . In a recent open study by Nazari et al., 180 male patients with iOAT received an antioxidant mix including 40 mg CoQ10 daily for 3 months.
In an attempt to answer this question, evidence from clinical trials and meta-analyses on the impact of CoQ10 treatment in male infertility revealed that oral supplementation with CoQ10 raised seminal CoQ10 levels, sperm motility, and spermatozoa concentration 32,42. The qualitative analysis of available studies has shown that supplementation with CoQ10, alone or in combination with other antioxidant molecules, has a beneficial effect on seminal quality, especially regarding sperm motility. Terai et al. (2020) reported that supplementation with a combination of antioxidants (L-carnitine, zinc, astaxanthin, coenzyme Q10, vitamin C, vitamin B12, and vitamin E) increased total sperm motility but did not significantly improve ejaculate volume, sperm count, or testosterone levels. The aim of the present study was to assess the effects of CoQ10 supplementation on semen quality, i.e., semen volume, total sperm number, sperm concentration, total sperm motility, percentage of progressive sperm motility and sperm morphology.
Indirect indications derive from an improvement in the antioxidant capacity of the seminal fluid and the chromatin integrity of spermatozoa. First, studies with uncontrolled design do not allow excluding the influence of lifestyle modifications on semen quality. In any case, the beneficial effects on semen parameters seem to decrease after treatment discontinuation 14,16,18,19 The positive effect of CoQ10 supplementation on spermatogenesis has also been confirmed by the reduction of FSH levels and the increase of inhibin B levels 16,18,19. DFI improvement provides further evidence of the usefulness of antioxidant therapy in male infertility, but further work is required. This appears critical in protecting sperm DNA from ROS damage, as demonstrated by some authors 11,25,28,29, who reported a significant reduction in the DFI after antioxidant treatment. However, compared to selenium supplementation, CoQ10 supplementation seems to provide better results both in terms of seminal parameters and of antioxidant capacity of seminal fluid .
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