Reductive Stress and Male Infertility.

Male infertility research and clinical advances had vast progress in the last few decades. Strong research evidence underpinned the concepts of oxidative stress (OS)-mediated male reproductive disruptions, which bear answers to several cases of idiopathic male infertility. Antioxidant treatment held the prime solution for OS-mediated male infertility. But excess use of antioxidants is challenged by the research breakthrough that reductive stress also predisposes to male infertility, resolutely instituting that any biological extremes of the redox spectrum are deleterious to male fertility. Superfluity of reducing agents may hinder essential oxidation mechanisms, affecting physiological homeostasis. These mechanisms need to be explicated and updated time and again to identify the fine thread between OS-mediated male infertility treatment and induction of reductive stress. This chapter thus presents the evidence-based concepts pertaining to the antioxidants actions to combat OS-induced male infertility, the mechanism of induction of reductive stress and its impact on male reproduction.

Predictors of pregnancy and time to pregnancy in infertile men with idiopathic oligoasthenospermia pre- and post-coenzyme Q10 therapy.

Different antioxidants including coenzyme Q10 (CoQ10) have been tried to treat idiopathic male infertility (IMI) with variable results. Therefore, this study aimed to determine the clinical and biochemical predictors of pregnancy outcome and time to pregnancy (TTP) in infertile men with idiopathic oligoasthenospermia (OA) pre- and post-CoQ10 therapy. This prospective controlled clinical study included 178 male patients with idiopathic OA and 84 fertile men (controls). Patients received 200 mg of oral CoQ10 once daily for 6 months. Demographics, semen parameters, seminal CoQ10 levels, reactive oxygen species (ROS) levels, total antioxidant capacity (TAC), catalase (CAT), glutathione peroxidase (GPx), sperm DNA fragmentation (SDF) and body mass index were measured and compared at baseline and after 6 months. All participants were followed up for another 18 months for pregnancy outcome and TTP. CoQ10 therapy for 6 months significantly improved semen parameters, antioxidant measures and reduced SDF. The pregnancy rate was 24.2% and TTP was 20.52 ± 6.72 months in patients as compared to 95.2% and 5.73 ± 6.65 months in fertile controls. After CoQ10 therapy, CoQ10 level, sperm concentration, motility and ROS were independent predictors of pregnancy outcome and CoQ10 level, male age, sperm concentration, motility, ROS and GPx were independent predictors of TTP in patients. In conclusion, CoQ10 therapy of 6 months is a potential treatment for men with idiopathic OA. CoQ10 level, male age, semen parameters, ROS and GPx could potentially be used as diagnostic biomarkers for male fertility and predictors for pregnancy outcome and TTP in these patients.

Coenzyme Q10 effect on semen parameters: Profound or meagre?

Coenzyme Q10 has shown promise in treating male infertility; however, there are inconsistencies across the published data. We undertook a quantitative meta-analysis by pooling data from three placebo-controlled randomised clinical trials (RCTs) in order to evaluate the efficacy of CoQ10 in improving semen parameters. Sperm count, sperm motility, sperm forward motility, sperm morphology and CoQ10 level in the seminal plasma were measured and quantitatively correlated with CoQ10 oral administration. Pooled analysis showed a significant impact of CoQ10 in improving sperm motility and forward motility, without a significant impact on sperm count, sperm morphology, ejaculate volume or seminal plasma level of CoQ10. Efficacy assessment suggested that CoQ10 shows better results at higher doses and when administered for a period of more than 3 months but not longer than 6 months. We conclude that CoQ10 has a profound effect on sperm motility and a meagre effect on all other parameters. Therefore, CoQ10 can be used for treating asthenozoospermic infertility with the dosage and duration depending upon the severity of the disorder and the patient's response to the treatment.

The Effect of Selenium Therapy on Semen Parameters, Antioxidant Capacity, and Sperm DNA Fragmentation in Men with Idiopathic Oligoasthenoteratospermia.

Idiopathic male infertility (IMI) remains challenging as the etiology of semen abnormalities is still unidentified. Sperm DNA fragmentation (SDF) has been suggested as a potential mechanism. Oral antioxidants including selenium have been tried for IMI with variable results. This study was undertaken to explore the effect of selenium therapy on semen parameters, antioxidant capacity, and SDF in infertile patients with idiopathic oligoasthenoteratospermia (OAT). Sixty-five infertile men with idiopathic OAT and fifty fertile controls were included in this prospective clinical study. Patients received selenium (200 µg/day) orally for 6 months. Seminal fluid parameters (WHO 5th criteria), total antioxidant capacity (TAC), catalase (CAT), and seminal SDF levels were assessed for all participants at the start of the study and after 6 months. Sperm concentration (P < 0.001), progressive motility (P < 0.001), and total motility (P < 0.01) significantly increased in patients after selenium therapy. Seminal TAC and CAT increased in patients post-therapy as compared to baseline values (P < 0.01). SDF levels significantly decreased (P < 0.001) in patients following selenium treatment in comparison to baseline values. SDF levels also correlated negatively with sperm progressive motility (r = - 0.44, P = 0.003) and total motility (r = - 0.48, P = 0.001). In conclusion, selenium therapy (200 µg/day) for 6 months increases sperm concentration, motility, seminal antioxidant capacity, and reduces SDF in patients with idiopathic OAT. Thus, selenium could be a promising therapy for men with IMI and may boost their fertility and fertility treatment outcomes.

Coenzyme Q10 improves sperm motility and antioxidant status in infertile men with idiopathic oligoasthenospermia.

OBJECTIVE: Oxidative stress is a key player in the development of idiopathic male infertility (IMI), and various antioxidants have been used for the treatment of IMI with inconsistent results. Coenzyme Q10 (CoQ10) is a cofactor and an antioxidant that may improve semen parameters and reduce oxidative stress in patients with idiopathic oligoasthenospermia (OA). Therefore, this study aimed to explore the effect of CoQ10 on semen parameters and antioxidant markers in patients with idiopathic OA. METHODS: Fifty patients with idiopathic OA and 35 fertile controls were enrolled in this prospective controlled study. All participants underwent a comprehensive fertility assessment. All patients received CoQ10 (300 mg/day) orally once daily for 3 months. Semen parameters, seminal CoQ10 levels, reactive oxygen species (ROS) levels, total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured in patients and controls at the start of the study and after 3 months. RESULTS: Treatment with CoQ10 resulted in increased sperm progressive motility (p<0.05), total motility (p<0.01), seminal TAC (p<0.01), SOD (p<0.05), GPx (p<0.001), and seminal CoQ10 (p<0.001) levels and reduced ROS (p<0.01) in patients as compared to baseline. Sperm concentration and motility were also significantly correlated with antioxidant measures and seminal CoQ10 levels (r=0.38-0.57). CONCLUSION: CoQ10 therapy (300 mg/day for 3 months) improved sperm motility and seminal antioxidant markers in patients with idiopathic OA. Therefore, CoQ10 could be a promising treatment for patients with idiopathic infertility and may improve their fertility potential.

Comparison of the effects of coenzyme Q10 and Centrum multivitamins on semen parameters, oxidative stress markers, and sperm DNA fragmentation in infertile men with idiopathic oligoasthenospermia.

OBJECTIVE: Oxidative stress and sperm DNA fragmentation (SDF) have been linked to idiopathic male infertility (IMI). Various antioxidants have been tried to improve semen parameters and fertility potential in IMI patients, but with inconsistent results. The study aimed to compare the effects of coenzyme Q10 (CoQ10) and Centrum multivitamins on semen parameters, seminal antioxidant capacity, and SDF in infertile men with idiopathic oligoasthenospermia (OA). METHODS: This prospective controlled clinical study involved 130 patients with idiopathic OA and 58 fertile controls. The patients were divided randomly into two groups: the first group received CoQ10 (200 mg/day orally) and the second group received Centrum multivitamins (1 tablet/day) for 3 months. Semen parameters, CoQ10 levels, reactive oxygen species (ROS), total antioxidant capacity (TAC), catalase, SDF, and serum hormone levels (follicle-stimulating hormone, luteinizing hormone, testosterone, and prolactin) were compared at baseline and after 3 months. RESULTS: Both CoQ10 and Centrum improved sperm concentration and motility, but the improvement was greater with Centrum therapy (p<0.05). Similarly, both therapies improved antioxidant capacity, but TAC and catalase improvement was greater (p<0.01 and p<0.001 respectively) with CoQ10, whereas ROS (p<0.01) and SDF (p<0.001) improvements were greater with Centrum administration. Centrum therapy was associated with reduced serum testosterone (p<0.05). CONCLUSION: In conclusion, both CoQ10 and Centrum were effective in improving semen parameters, antioxidant capacity, and SDF, but the improvement was greater with Centrum than with CoQ10. Therefore, Centrum-as a source of combined antioxidants-may provide more effective results than individual antioxidants such as CoQ10 in the treatment of infertile men with idiopathic OA.

Sperm DNA Fragmentation in Reproductive Medicine: A Review.

Approximately 15% of the world's couples suffer from infertility during their reproductive period of which the male factor is responsible for 50% of cases. Male factor infertility is multifactorial in origin, and sperm DNA fragmentation (SDF) has also been linked to male infertility including idiopathic male infertility. Some degree of controlled DNA nicking is essential for adequate DNA compaction, but excessive SDF is usually associated with reduced male fertility potential, reduced fertilisation, poor embryo quality, recurrent pregnancy loss and poor assisted reproductive techniques (ARTs) outcomes. Although semen analysis remains the gold standard for diagnosis of male factor infertility worldwide, its limitations motivated the search and the development of complementary tests of sperm function and integrity. SDF assay is an emerging diagnostic tool in infertile men, and several indications for SDF testing in infertile couples have also been proposed. The use of SDF in routine male infertility assessment is, however, still controversial. Furthermore, both direct and indirect SDF tests are now available. Hence, the present review was conducted to summarise the recent evidence of SDF, underlying mechanisms, clinical indications, diagnostic tests, as well as the role of SDF in male factor infertility, pregnancy and ART outcomes.

Impact of Coenzyme Q10 and Selenium on Seminal Fluid Parameters and Antioxidant Status in Men with Idiopathic Infertility.

Oxidative stress (OS) is a key contributing factor in 30-80% of male infertility cases. To date, several antioxidant treatments have been put forth to manage OS-induced male infertility. This study intended to elucidate the impact of coenzyme Q10 (CoQ10) and selenium on seminal fluid parameters and antioxidant status in infertile men with idiopathic oligoasthenoteratospermia (OAT). In this prospective study, 70 patients with idiopathic OAT were randomly allocated to receive CoQ10 (200 mg/day) or selenium (200 µg/day) for 3 months. Semen quality parameters (following WHO guidelines, 5th edition), total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD) activities were compared before and after the treatment. The results of the study showed an increase in sperm concentration with CoQ10 treatment (p < 0.01) as well as increased progressive sperm motility (p < 0.01 and p < 0.05) and total sperm motility (p < 0.01 and p < 0.05) with CoQ10 and selenium treatment respectively. There was also a significant improvement in TAC (p < 0.01 and p < 0.05) and SOD (p < 0.01 and p < 0.05) following treatment with CoQ10 and selenium respectively while CAT improved only with CoQ10 therapy (p < 0.05). Sperm concentration, motility, and morphology also correlated significantly with TAC, SOD, and CAT (r = 0.37-0.76). In conclusion, treatment with CoQ10 (200 mg) or selenium (200 µg) could improve sperm concentration, motility, and antioxidant status in infertile men with idiopathic OAT with CoQ10 providing the higher improvement.

Coenzyme Q10, oxidative stress markers, and sperm DNA damage in men with idiopathic oligoasthenoteratospermia.

OBJECTIVE: Oxidative stress (OS) plays a key role in the etiology of unexplained male infertility. Coenzyme Q10 (CoQ10) is a potent antioxidant that may improve semen quality and OS in infertile men with idiopathic oligoasthenoteratospermia (OAT), but the underlying mechanism is unknown. Therefore, the present study was undertaken to investigate the effect of CoQ10 on OS markers and sperm DNA damage in infertile patients with idiopathic OAT. METHODS: This prospective controlled study included 50 patients with idiopathic OAT and 50 fertile men who served as controls. All patients underwent a comprehensive medical assessment. Patients and controls received 200 mg of oral CoQ10 once daily for 3 months. Semen and blood were collected and analyzed for sperm parameters, seminal CoQ10 levels, reactive oxygen species (ROS) levels, total antioxidant capacity, catalase, sperm DNA fragmentation (SDF), and serum hormonal profile. RESULTS: The administration of CoQ10 to patients with idiopathic OAT significantly improved sperm quality and seminal antioxidant status and significantly reduced total ROS and SDF levels compared to pretreatment values. CONCLUSION: CoQ10, at a dose of 200 mg/day for 3 months, may be a potential therapy for infertile patients with idiopathic OAT, as it improved sperm parameters and reduced OS and SDF in these patients.

Coenzyme Q10 Improves Sperm Parameters, Oxidative Stress Markers and Sperm DNA Fragmentation in Infertile Patients with Idiopathic Oligoasthenozoospermia.

PURPOSE: Oxidative stress and sperm DNA fragmentation (SDF) are potential contributing factors for idiopathic male infertility. Coenzyme Q10 (CoQ10) have been reported to be effective in the treatment of idiopathic male infertility, in general, owing to its antioxidant properties. Thus, the present study intends to investigate the effects of CoQ10 therapy on semen parameters, oxidative stress markers and SDF in infertile men, specifically with idiopathic oligoasthenozoospermia (OA). MATERIALS AND METHODS: In this case-control study, sixty-five infertile patients with idiopathic OA and forty fertile men (control) were included. All participants underwent semen analysis based on the World Health Organization guidelines (5th edition, 2010). Patients received CoQ10 at the dose of 200 mg/d orally for three months. Seminal plasma CoQ10, total antioxidant capacity (TAC), total reactive oxygen species (ROS), glutathione peroxidase (GPx), and SDF levels were measured in controls (baseline) and infertile patients pre- and post-CoQ10 treatment. RESULTS: CoQ10 treatment for three months significantly improved sperm concentration (p<0.05), progressive motility (p<0.05), total motility (p<0.01), seminal fluid CoQ10 concentration (p<0.001), TAC (p<0.001), and GPx (p<0.001) levels in infertile men with OA. Further, ROS level (p<0.05) and SDF percentage (p<0.001) were reduced in OA patients as compared to the baseline. CoQ10 levels also correlated positively with sperm concentration (r=0.48, p=0.01) and total motility (r=0.59, p=0.003) while a negative correlation was recorded between SDF and sperm motility (r=-0.54, p=0.006). CONCLUSIONS: CoQ10 supplementation for three months could improve semen parameters, oxidative stress markers and reduce SDF in infertile men with idiopathic OA.

Coenzyme Q10, oxidative stress, and male infertility: A review.

Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying mechanism of idiopathic male infertility, the specific treatment of OS-mediated male infertility requires further investigation. Coenzyme Q10 (CoQ10), a vitamin-like substance, has been found in measurable levels in human semen. It exhibits essential metabolic and antioxidant functions, as well as playing a vital role in mitochondrial bioenergetics. Thus, CoQ10 may be a key player in the maintenance of biological redox balance. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Seminal CoQ10 concentrations have been shown to be altered in various male infertility states, such as varicocele, asthenozoospermia, and medical or surgical regimens used to treat male infertility. These observations imply that CoQ10 plays an important physiological role in the maintenance and amelioration of semen quality. The present article thereby aimed to review the possible mechanisms through which CoQ10 plays a role in the regulation of male reproductive function, and to concisely discuss its efficacy as an ameliorative agent in restoring semen parameters in male infertility, as well as its impact on OS markers, sperm DNA fragmentation, pregnancy, and assisted reproductive technology outcomes.

Role of Oxidative Stress in Male Infertility: An Updated Review.

Current evidence links oxidative stress (OS) to male infertility, reduced sperm motility, sperm DNA damage and increased risk of recurrent abortions and genetic diseases. A review of PubMed, Medline, Google Scholar, and Cochrane review databases of published articles from years 2000-2018 was performed focusing on physiological and pathological consequences of reactive oxygen species (ROS), sperm DNA damage, OS tests, and the association between OS and male infertility, pregnancy and assisted reproductive techniques outcomes. Generation of ROS is essential for reproductive function, but OS is detrimental to fertility, pregnancy, and genetic status of the newborns. Further, there is a lack of consensus on selecting OS test, type, and duration of antioxidants treatment as well as on the target patients group. Developing advanced diagnostic and therapeutic options for OS is essential to improve fertility potential and limit genetic diseases transmitted to offspring.

The impact of two doses of coenzyme Q10 on semen parameters and antioxidant status in men with idiopathic oligoasthenoteratozoospermia.

OBJECTIVE: Oxidative stress contributes to male infertility, and antioxidants have been recommended for treating idiopathic oligoasthenoteratozoospermia (OAT). There is, however, a lack of agreement on the type, dosing, and use of individual antioxidants or combinations thereof. The purpose of this study was to compare the effects of two doses of coenzyme Q10 (CoQ10) on semen parameters and antioxidant status in men with idiopathic OAT. METHODS: In this prospective study, patients with idiopathic OAT received 200 mg/day (n = 35) or 400 mg/day (n = 30) of CoQ10 orally for 3 months. All patients underwent semen analysis according to the fifth editions of the World Health Organization criteria. Total antioxidant capacity (TAC), catalase (CAT) activity, and superoxide dismutase (SOD) activity were measured both before and after treatment. RESULTS: Treatment with CoQ10 (200 mg/day or 400 mg/day) resulted in a significant increase in sperm concentration from baseline (8.22 ± 6.88 to 12.53 ± 8.11 million/mL, p= 0.019; 7.58 ± 5.41 to 12.33 ± 6.1 million/mL, p= 0.002, respectively), progressive motility (16.54% ±9.26% to 22.58% ±10.15%, p=0.011; 14.22% ±12.85% to 26.1% ±14.52%, p= 0.001, respectively), and total motility (25.68% ± 6.41% to 29.96% ± 8.09%, p= 0.016; 23.46% ± 12.59% to 34.82% ± 14.17%, p= 0.001, respectively). CoQ10 therapy also increased TAC (p= 0.009, p= 0.001, respectively), SOD activity (p= 0.004, p= 0.001, respectively), and CAT activity (p= 0.039, p= 0.024, respectively). Furthermore, antioxidant measures correlated significantly with seminal fluid parameters (r = 0.36-0.76). CONCLUSION: CoQ10 supplementation improved semen parameters and antioxidant status in men with idiopathic OAT, with a greater improvement shown in men who took 400 mg/day than in those who took 200 mg/day.

The effects of oral antioxidants on the semen of men with idiopathic oligoasthenoteratozoospermia.

It has been estimated that approximately 15% of reproductive-age couples suffer from infertility. Male factors contribute to almost half of infertility cases, and in many patients the underlying cause of oligoasthenoteratozoospermia is unknown. Accumulating evidence suggests that oxidative stress plays a role as a contributing factor to male infertility, and reactive oxygen species have been shown to impair sperm function and motility and to damage sperm membrane and DNA. Therefore, this review explored the evidence provided by studies published from 2002 to 2017 on the impact of oral antioxidants (vitamin C, vitamin E, L-carnitine, coenzyme Q10, zinc, selenium, and pentoxifylline) on seminal fluid parameters in men with idiopathic oligoasthenoteratozoospermia. Most of the studies were randomized controlled studies that investigated the effect of single or combined antioxidants and reported improvements in at least one semen parameter. The most noteworthy effect that was found was that the use of multiple antioxidants increased sperm motility and concentration. Nonetheless, there is a lack of agreement on the dose, the duration of treatment, and whether individual or combined oral antioxidants should be used. Therefore, the current review provides evidence supporting the use of oral antioxidants in the treatment of infertile men with idiopathic oligoasthenoteratozoospermia.