In 2009, Safarinejad evaluated the effect of CoQ10 on semen parameters in 212 infertile men with idiopathic oligoasthenoteratospermia (iOAT). In a subsequent randomized, double-blind, placebo-controlled study, the same group studied the effect of daily administration of 200 mg of CoQ10 for 6 months in 28 subjects and 27 control subjects. Coenzyme Q10 and male fertility (mixed compounds), characteristics of suitable studies. Coenzyme Q10 and male fertility (monotherapy), characteristics of suitable studies. Coenzyme Q10 is an obligatory co-factor with strong antioxidant properties that counteract OS by reducing ROS production in mitochondria and protect spermatozoa membranes from lipid peroxidation. Seminal fluid and sperm cells are rich in antioxidant molecules (superoxide dismutase -SOD-, catalase -CAT- and glutathione peroxidase 4—Gpx4), which counterbalance the effect of ROS. Coenzyme Q10 (CoQ10) is an obligatory co-factor with strong antioxidant properties involved in mitochondrial energy production, which is essential in maintaining the efficient energy system of spermatozoa and protecting their membranes from lipid peroxidation.
The study by Kopets et al. (2020) showed low RoB in all domains, with the exception of the "incomplete outcome data" domain, where the RoB was unclear. With regard to the RoB, the studies by Balercia et al. (2009) and Gopinath et al. (2013) showed low RoB in all domains except for the domain "random sequence generation", where the RoB was unclear. Arm 1 subjects received 2 tablets of FDC antioxidants twice daily, arm 2 subjects received 1 FDC tablet +1 placebo tablet twice daily and arm 3 subjects received 2 tablets of placebo twice daily. Arm denotes the treatment groups as stated by the authors (Gopinath et al., 2013). The age of the participants ranged from 18 to 50 years, and the duration of intervention was between 12 weeks and 26 weeks (3–6.5 months) (Table 1). The studies were from India (1), Iran (4), Italy (1), Sweden (1), and Ukraine (1). PRISMA flowchart for the identification, screening, and inclusion of eligible studies.
In the idiopathic infertility group, supplementation showed a significant decrease in seminal ORP and SDF levels. Arafa et al. have recently evaluated the effect of antioxidant supplementation on conventional semen parameters and advanced sperm function tests in a population of infertile men. Sperm analysis and LH, FSH and testosterone serum concentrations were performed before and after 3 months of treatment. No significant difference between the antioxidant and the placebo group was seen for any of the semen parameters or for sperm DNA fragmentation index (DFI) after treatment . After 3 months, all studied sperm parameters significantly improved, but the relative change of sperm density and progressive motility was higher in the combined micronutrient treatment group . Treatment with CoQ10 for 3 months resulted in a significant increase in sperm concentration, progressive motility and total motility in both groups, but changes in the kinetic parameters were greater in the 400 mg CoQ10 group. In a prospective uncontrolled study published in 2015, 60 oligospermic patients received 150 mg ubiquinol daily supplementation for 6 months.
Several clinical studies have reported beneficial effects of CoQ10 supplementation on sperm parameters of infertile patients 21,37,38. Antioxidant therapy has been considered for supplementation and has been introduced into routine clinical practice for the treatment of male infertility . Despite the recognition of ROS and OS as a factor contributing to male infertility, antioxidant use for treatment is still debatable. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Coenzyme Q10 Supplementation enhances testicular volume and hemodynamics, reproductive hormones, sperm quality, and seminal antioxidant capacity in goat bucks under summer hot humid conditions. Interpretation of the semen quality improvement in the present study, especially before the end of the spermatogenesis (47 days) is complex.
CoQ10 and α-tocopherol concentrations increased significantly whereas the levels of thiobarbituric acid reactive substances (an oxidative stress parameter) decreased significantly . Levels of nitric oxide and peroxynitrite in seminal plasma decreased, whereas SOD activity increased. After a 3-month treatment period, there was a significant improvement in sperm kinetics, but not in sperm count or in the number of atypical sperm cells. The ongoing pregnancy rate, calculated 3 months after treatment by telephone interview, was 15% .
This demonstrates that CoQ10 enhances sperm count, at least in part, through a testosterone-dependent mechanism. The improvement is likely due to the ability of CoQ10 to promote testosterone production, accompanied by an increase in inhibin B levels, which exerts a negative feedback effect on LH and FSH release. The HPT axis operates through a negative feedback loop, wherein optimal levels of testosterone suppresses LH and FSH secretion. LH activated the Leydig cells to produce testosterone, while FSH promote spermatogenesis by activating the Sertoli cells. It is likely that a higher dose of CoQ10 is required to achieve a beneficial effect on semen quality. However, noteworthy inter-study heterogeneity is observed in some analyses, and there are insufficient data for sensitivity analysis across all parameters.

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