Cancer risk and male Infertility: Unravelling predictive biomarkers and prognostic indicators.

In recent years, there has been a global increase in cases of male infertility. There are about 30 million cases of male infertility worldwide and male reproductive health is showing rapid decline in last few decades. It is now recognized as a potential risk factor for developing certain types of cancer, particularly genitourinary malignancies like testicular and prostate cancer. Male infertility is considered a potential indicator of overall health and an early biomarker for cancer. Cases of unexplained male factor infertility have high levels of oxidative stress and oxidative DNA damage and this induces both denovo germ line mutations and epimutations due to build up of 8-hydroxy 2 deoxygunaosine abase which is highly mutagenic and also induces hypomethylation and genomic instability. Consequently, there is growing evidence to explore the various factors contributing to an increased cancer risk. Currently, the available prognostic and predictive biomarkers associated with semen characteristics and cancer risk are limited but gaining significant attention in clinical research for the diagnosis and treatment of elevated cancer risk in the individual and in offspring. The male germ cell being transcriptionally and translationally inert has a highly truncated repair mechanism and has minimal antioxidants and thus most vulnerable to oxidative injury due to environmental factors and unhealthy lifestyle and social habits. Therefore, advancing our understanding requires a thorough evaluation of the pathophysiologic mechanisms at the DNA, RNA, protein, and metabolite levels to identify key biomarkers that may underlie the pathogenesis of male infertility and associated cancer. Advanced methodologies such as genomics, epigenetics, proteomics, transcriptomics, and metabolomics stand at the forefront of cutting-edge approaches for discovering novel biomarkers, spanning from infertility to associated cancer types. Henceforth, in this review, we aim to assess the role and potential of recently identified predictive and prognostic biomarkers, offering insights into the success of assisted reproductive technologies, causes of azoospermia and idiopathic infertility, the impact of integrated holistic approach and lifestyle modifications, and the monitoring of cancer susceptibility, initiation and progression. Comprehending these biomarkers is crucial for providing comprehensive counselling to infertile men and cancer patients, along with their families.

Integrative Yoga and Ayurvedic Approach to Oligoasthenozoospermia: A Holistic Case Study on Fertility Enhancement.

Infertility is the failure to conceive after one or more years of regular, unprotected life for a fertile female. Around 45% of males are responsible for infertility worldwide. Research shows that nearly 50% of infertility in India is related to male reproductive factors or diseases. The male-carrying pathology in semen production includes low sperm count, volume, motility, abnormal forms, and sperm functional tests. This case presents a 31-year-old male with complaints of wanting issues after a complete year of regular, unprotected intercourse. He had undergone all the routine diagnostic investigations on his wife, which reported no issues and recorded regular ovulatory cycles with patent tubes. Then, progressing in the diagnosis, a semen analysis revealed a semen volume of 2 mL, a sperm concentration of 4 million/mL, progressive motility of 8%, non-progressive motility of 3%, and immotile sperm of 89%, with normal sperm morphology. Based on clinical examination, semen analysis, and investigation, the case was diagnosed as oligoasthenozoospermia. Oligozoospermia means low sperm count, and asthenozoospermia means low sperm motility. Oligoasthenozoospermia can be correlated to the Shukra Kshaya Lakshanas mentioned in Ashta Shukra Dushti. There is no satisfactory treatment in modern medicine for these conditions. Yoga and Ayurvedic intervention are the better options for these conditions. This case report focuses on the management of oligoasthenozoospermia through yoga and Ayurvedic medicines, Youvanamrit Vati and Shilajitrasayan Vati, given to the patient for four months.

Effects of Calorie Restriction on Preserving Male Fertility Particularly in a State of Obesity.

PURPOSE OF REVIEW: Highlight the importance of exploring nutritional interventions that could be applied as alternative or supplementary therapeutic strategies to enhance men's fertility. RECENT FINDINGS: Lifestyle choices have prompted extensive discussions regarding its implications and applications as a complementary therapy. The growing concern over the decline in sperm quality underscores the urgency of investigating these alternative interventions. Calorie restriction (CR) has emerged as a promising strategy to improve male fertility. The efficacy of CR depends on factors like age, ethnicity and genetics. Clinical studies, such as CALERIE, have shown an improvement in serum testosterone level and sexual drive in men with or without obesity. Additionally, CR has been shown to positively impact sperm count and motility; however, its effects on sperm morphology and DNA fragmentation remain less clear, and the literature has shown discrepancies, mainly due to the nature of technically dependent assessment tools. The review advocates a personalized approach to CR, considering individual health profiles to maximize its benefits. It underscores the need for routine, accessible diagnostic techniques in male reproductive health. It suggests that future research should focus on personalized dietary interventions to improve male fertility and overall well-being in individuals with or without obesity and unravel CR's immediate and lasting effects on semen parameters in men without obesity.

Beneficial effects of oral antioxidant supplementation on semen quality parameters, reproductive hormones, and sperm DNA integrity in men with idiopathic oligoasthenoteratozoospermia.

OBJECTIVE: Recently, oral antioxidants in combined forms have been used to treat men with idiopathic infertility. This study aimed to evaluate the effects of treatment with vitamin C, vitamin E, selenium, zinc, arginine, L-carnitine, and coenzyme Q10 on sperm quality parameters, DNA integrity, reproductive hormones, and pregnancy rates in men with infertility and idiopathic oligoasthenoteratozoospermia (OAT). METHODS: A prospective study was conducted on 420 men with infertility and idiopathic OAT who took an oral supplement of antioxidant SP-Power tablets twice daily for 6 months. Semen quality, reproductive hormones, and the DNA fragmentation index (DFI) were evaluated at baseline and at 3 and 6 months after supplementation, using the World Health Organization 2021 guidelines. RESULTS: No significant difference was observed in volume or the percentage of typical morphology during treatment. A significant improvement in sperm concentration was observed after supplementation (8.67±1.41, 12.17±1.91, and 19.01±0.86 at baseline, 3, and 6 months respectively, p<0.01). The total motility, progressive motility, and total motile sperm count also increased significantly (p<0.01), whereas the DFI decreased after 6 months. There was an increase in normal FSH levels and testosterone levels after 6 months of supplementation of antioxidant SP-Power but these differences were not statistically significant (p=not significant and p=0.06, respectively). CONCLUSION: Supplementation with SP-Power tablets improved sperm quality parameters, sperm DFI, some reproductive hormones, and pregnancy rates in men with infertility and idiopathic OAT, which could be attributed to the supplement's synergistic antioxidant action. Further studies are needed to determine the effects of supplementation on oxidative stress markers.

Effects of vitamin D on sex steroids, luteinizing hormone, and testosterone to luteinizing hormone ratio in 307 infertile men.

OBJECTIVE: Vitamin D status has been associated with sex steroid production. The question is whether vitamin D supplementation has an impact on sex steroid production in infertile men with vitamin D insufficiency? DESIGN: A single-center, double-blinded, randomized clinical trial. Differences in sex steroids and reproductive hormones were predefined secondary outcomes, vitamin D status at baseline was a predefined subgroup and the primary outcome was differences in semen quality. METHODS: A total of 307 infertile men were included and randomized 1:1 to active or placebo treatment for 150 days. Men in the active group initially received an oral bolus of 300,000 IU cholecalciferol, followed by daily supplementation with 1400 IU cholecalciferol and 500 mg calcium. RESULTS: After intervention, no differences were found in serum concentrations of sex steroids, luteinizing hormone, testosterone/luteinizing hormone ratio or SHBG between the vitamin D and placebo group. However, in a predefined subgroup analysis of men with serum 25OHD ≤ 50 nmol/L, men treated with vitamin D had a significantly higher testosterone/luteinizing hormone ratio [4.2 (3.8-4.4) vs. 3.7 (3.4-4.0); p = 0.033] compared with placebo treatment. In men with vitamin D deficiency, the difference between groups was larger but not significant due to few men with serum 25OHD < 25 nmol/L. CONCLUSION: Vitamin D + calcium supplementation did not alter sex steroid production in infertile men. However, vitamin D insufficient men treated with vitamin D supplementation had a significantly higher testosterone/LH ratio compared with placebo-treated men, suggesting that optimal Leydig cell function are dependent on adequate vitamin D status.

High-dose cholecalciferol supplementation to obese infertile men is sufficient to reach adequate vitamin D status.

Obesity is associated with low vitamin D status, and the optimal supplement and dosage of cholecalciferol (vitamin D3) or calcidiol (25OHD) for individuals with obesity have been debated. We aimed to determine the effect of high-dose vitamin D3 supplementation on achieving adequate vitamin D levels among infertile men with normal weight v. obesity. Here, we present secondary end points from a single-centre, double-blinded, randomised clinical trial, comprising 307 infertile men randomised to active or placebo treatment for 150 days. Men in the active group initially received an oral bolus of 300 000 mg of vitamin D3, followed by daily supplementation with 1400 mg of vitamin D3 and 500 mg of calcium. Baseline BMI was listed as a predefined subgroup. At baseline, serum 25OHD was significantly higher in men with normal weight (BMI < 25 kg/m2) compared with men with overweight (BMI 25-30 kg/m2) and obesity (BMI > 30 kg/m2) (48 nmol/l v. 45 nmol/l and 39 nmol/l, respectively; P = 0·024). After the intervention, men with normal weight, overweight and obesity treated with vitamin D3 had a significantly higher serum 25OHD compared with corresponding placebo-treated men (BMI < 25 kg/m2: 92 nmol/l v. 53 nmol/l, BMI = 25-30 kg/m2: 87 nmol/l v. 49 nmol/l and BMI > 30 kg/m2: 85 nmol/l v. 48 nmol/l; P < 0·001 for all, respectively). In conclusion, we show that high-dose vitamin D3 supplementation to infertile men with obesity and low vitamin D status is sufficient to achieve adequate serum 25OHD levels.

Effect of Medicago sativa seed powder (Plus vitamin E vs. vitamin E alone) on semen analysis in men with idiopathic infertility: A double blind randomized clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Different parts of the alfalfa plant (Medicago sativa L.), especially its seeds, have been introduced as a semen quality enhancer in the folk medicine of different regions of Iran as well as in the traditional Persian medicine (PM) books. The seeds of this plant are also used in many combined medicines to treat male infertility in PM. AIM OF THE STUDY: This study was designed to investigate the effect of M. sativa seed powder plus vitamin E vs. vitamin E alone on semen analysis of men with idiopathic infertility. MATERIALS AND METHODS: In this randomized clinical trial, 60 participants were randomly divided into two groups and then received M. sativa seed powder (6 g daily) or placebo for three months, as add-on to vitamin E (100 U). Results of semen analysis (sperm total count, motility, and morphology as well as semen volume) of these two groups and their changes were compared before and after treatment as the primary outcome. The number of pregnancies after one month and probable side effects were also assessed. RESULTS: After 12 weeks, sperm total count changed from 36.2 ± 21.8 × 106/ml to 48.5 ± 19.1 × 106/ml in M. sativa and from 39.5 ± 23.5 × 106/ml to 41.2 ± 20.9 × 106/ml in placebo, percentage of normal morphology changed from 1.8 ± 0.8% to 2.6 ± 1.2 % in M. sativa and from 2.0 ± 0.9% to 2.6 ± 1.2% in placebo and percentage of motile sperm changed from 36.5 ± 11.8 % to 39.7 ± 12.0% in M. sativa and from 39.3 ± 10.1 % to 38.1 ± 12.1% in placebo. The improvements in M. sativa group are significantly better than placebo group (P = 0.00, 0.01 and 0.04, respectively). However, semen volume decreased in both groups, but its changes were not significant. The number of pregnancies was four in the intervention and zero in placebo group. One case with abdominal bloating and one with respiratory allergy withdrew from the intervention group. No other adverse effect was reported. CONCLUSIONS: In this study, significant improvement was detected in sperm parameters (except semen volume) of men with idiopathic infertility in M. sativa plus vitamin E group in compare to vitamin E alone after 12 weeks. These findings suggest that the M. sativa, as a complementary therapy, may have a beneficial effect on semen quality. More clinical trials with larger sample size are needed.

Innocuité d'une recette médicinale traditionnelle utilisée pour l'infertilité masculine en Côte d'Ivoire / Safety of a traditional medicinal recipe used for male infertility in Ivory Coast

L'infertilité masculine est incriminée dans 50% des cas d'infertilité du couple. C'estun réel problème de santé publique en Afrique.Le présent travail avaitpour objectif d'évaluer l'innocuité et la tolérabilitéd'une recette médicinaletraditionnelle utilisée pour la prise en charge del'infertilité masculine dans le District Autonome d'Abidjan/Côte d'Ivoire. Cette étude a été réalisée dans le cadre de la valorisation de la pharmacopée africaine.Le matériel végétal était constitué de la recette médicinale et le matériel biologiquede 42 volontaires de sexe masculinsélectionnés sur une base raisonnée à postériori.Les volontaires ont été soumis à un traitement sur troismois. Lesvariables étudiées étaient: la glycémie,l'urée, la créatinine, les transaminases, les triglycérides et le cholestérol total. Leseffets secondaireset indésirablesont été notifiés.L'âge moyen de la populationd'étudeétait de 41,78 ans (± 7,73). Aux termes des trois mois d'utilisation de la recette médicinale, l'analyse statistiquedes variables biochimiquesa révélé: la glycémiep = 0,12; les transaminases p = 0,75; la créatinine p = 0,26; l'urée p = 0,04; les triglycérides p =0,95et le cholestérol total p = 0,64contre p< 0,05.Le principal effet secondaire notifié était la polyurie (97,5%).Ces résultatsaffirmentla sécurité de la recette médicinalepourl'utilisateur. Ils encouragentson utilisation chez les hommes infertileset un suivimédicaldespersonnes sous antihypertenseur.La recette médicinale présente une bonne innocuité et une bonne tolérabilité

Male infertility is incriminated in 50% of cases of couple infertility. This is a real public health problem in Africa.The present work aimed to evaluate the safety and tolerability of a traditional medicinal recipe used to treatmale infertilitMale infertility is incriminated in 50% of cases of couple infertility. This is a real public health problem in Africa.The present work aimed aimed to the safety and tMale infertility is incriminated in 50% of cases of couple infertility. This is a real public health problem in Africa.The present work aimed to evaluate the safety and tolerability of a traditional medicinal recipe used to treatmale infertility in the Autonomous District of Abidjan/Côte d'Ivoire. This study was carried out as part of the promotion of the African pharmacopoeia.The plant material consisted of the medicinal recipe and the biological material of 42 male volunteers selected purposively asposteriori. The volunteers underwent treatment over three months. The variables studied wereblood sugar, urea, creatinine, transaminases, triglycerides and total cholesterol. Side effects and undesirable effects were reported.The average age of the study population was 41.78 years (± 7.73). After three months of use of the medicinal recipe, the statistical analysis ofbiochemical variables revealedblood sugar p = 0.12; transaminases p = 0.75; creatinine p = 0.26; urea p = 0.04; triglycerides p = 0.95 and total cholesterol p = 0.64 versus p < 0.05. The main side effect reported was polyuria (97.5%).These results affirm the safety of the medicinal recipe for the user. They encourage its use in infertile men and medical monitoring of people on antihypertensive medication.The medicinal recipe isgood safety and tolerability.

Exploring the Potential of Plant Bioactive Compounds against Male Infertility: An In Silico and In Vivo Study.

Infertility is a well-recognized multifactorial problem affecting the majority of people who struggle with infertility issues. In recent times, among infertility cases, the male factor has acquired importance, and now it contributes to approximately half of the infertility cases because of different abnormalities. In the current study, we used natural phytochemicals as potential drug-lead compounds to target different receptor proteins that are involved in the onset of male infertility. A set of 210 plant phytochemicals were docked counter to active site residues of sex hormone-binding globulin, a disintegrin and metalloproteinase 17, and DNase I as receptor proteins. On the basis of binding scores and molecular dynamics simulation, the phytochemicals tricin, quercetin, malvidin, rhamnetin, isorhamnetin, gallic acid, kaempferol, esculin, robinetin, and okanin were found to be the potential drug candidates to treat male infertility. Molecular dynamics simulation showed tricin as a strong inhibitor of all selected receptor proteins because the ligand-protein complexes remained stabilized during the entire simulation time of 100 ns. Further, an in vivo study was designed to evaluate the effect of tricin in male rats with nicotine-induced infertility. It was explored that a high dose of tricin significantly reduced the levels of alanine transaminase, aspartate transaminase, urea, creatinine, cholesterol, triglyceride, and low-density lipoprotein and raised the level of high-density lipoprotein in intoxicated male rats. A high dose of tricin also increased the reproductive hormones (i.e., testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin) and reduced the level of DHEA-SO4. The phytochemical (tricin, 10 mg/kg body weight) also showed significant improvement in the histo-architecture after nicotine intoxication in rats. From the current study, it is concluded that the phytochemical tricin could serve as a potential drug candidate to cure male infertility.

The relationship between the intake of dietary fatty acids and minerals with sperm parameters in infertile men.

BACKGROUND & AIMS: Infertility has been increasing among Iranian couples. Some epidemiological studies have reported a relationship between infertility and lifestyle patterns, including dietary habits. Our objective was to evaluate the relationship between sperm parameters and the intake of dietary fatty acids and minerals among Iranian infertile men. METHODS: This cross-sectional was performed on 400 newly diagnosed infertile men at Yazd Reproductive Sciences Institute from July to December 2019. Men whose infertility was confirmed by an andrologist based on the World Health Organization (WHO) criteria were selected. They delivered a semen sample and answered a 168-item semi-quantitative food frequency questionnaire. All data were analyzed using SPSS and STATA software. A p-value of less than 0.5 was considered significant. RESULTS: In the adjusted model, a significant negative association between sperm motility and the 3rd quartile (Q) of poly-unsaturated fatty acids compared to the 1st quartile) P = 0.02). Also, in the adjusted model, total mobility was significantly increased in the second, third and last quartiles of omega-3 fatty acids compared to the first quartile (P < 0.001, P = 0.02, P < 0.001, respectively). Furthermore, omega-6 fatty acid intake in the last quartile were positively associated with sperm motility (P = 0.01). Moreover, there was a significant association between omega-3 fatty acid intake in the second, third, and last quartiles and sperm normal morphology (P = 0.003, P = 0.018, and P = 0.005, respectively) compared with the first quartile. Further, we observed a significant association between omega-6 fatty acid intake and sperm normal morphology in the last quartile compared with the reference quartile (P = 0.04). Also, the findings showed a significant negative association between the second quartile of sodium and calcium intake and sperm volume compared with the first quartile (P = 0.04, for both) in the adjusted model. CONCLUSIONS: We concluded that dietary polyunsaturated fatty acid, sodium, and calcium intake are related to sperm morphology, volume, and total motility in Iranian infertile men. However, more research is needed to confirm these relationships and provide evidence to exert these findings into clinical practice.

Therapeutic Effects of Low-Level Laser on Male Infertility: A Systematic Review.

Introduction: The objective of this study was to assess the effectiveness and safety of photobiomodulation (PBM) in the treatment of male infertility. Methods: We searched Google Scholar, PubMed, and the reference sections of relevant papers published from January 1, 2000 to September 23, 2022. We retrieved all publications related to the impact of PBM on male infertility. After reviewing the titles, abstracts, and full texts, we included fifteen papers in the research. The studies involved 477 semen samples (in vitro studies) and 70 male participants (randomized clinical trials). Results: All 14 in vitro studies that evaluated effectiveness reported that PBM was successful in increasing the proportion of progressive sperms in semen samples. Various methods were used to evaluate the safety. One study with a sample size of 58 concluded that PBM was not a safe treatment, whereas the other ten studies confirmed its safety. Only one clinical trial evaluated the effect of laser acupuncture on male infertility and found improvements in sperm progressive motility without any serious adverse effects. Conclusion: All 15 studies evaluating effectiveness reported that the low-level laser was effective for increasing the proportion of progressive sperm in semen samples and that it was safe to use. However, due to the heterogeneity of population characteristics, source characteristics, duration of exposure, sample size, and instruments for measuring safety and efficacy, we cannot conclude that the positive results obtained from the reviewed studies are solely attributable to the low-level laser on the sperm samples.

Micronutrient supplements as antioxidants in improving sperm quality and reducing DNA fragmentation.

BACKGROUND: Spermatogenesis and sperm quality may be negatively impacted by an increase in reactive oxygen species. This study investigates the efficacy of combined antioxidant therapy for treating male infertility, as measured by semen analyses and the sperm DNA fragmentation index (DFI). Infertile men with a high sperm DNA fragmentation index were instructed to take two oral micronutrient capsules daily for three months. Each antioxidant formulation contained 60 mg vitamin E, 400 µg folic acid, 30 mg selenium, 125 mg L-arginine, 220 mg L-carnitine, 7.5 mg coenzyme Q10, 40 mg L-glutathione, and 20 mg zinc citrate. At entry and post-treatment, the general characteristics, semen analysis, and sperm chromatin dispersion assays were recorded and compared. RESULTS: After three months of treatment with antioxidant compounds, the quality of spermatozoa improved significantly, as indicated by a decrease in the mean DNA fragmentation index from 45.6 ± 17.2% to 34.8 ± 20.3%; an increase in sperm concentration from 29.7 × 106/mL to 35.7 × 106/mL (p < 0.001), an increase in a total number of spermatozoa from 72.1 × 106 to 95.5 × 106 (p = 0.012), and an increase in the vitality from 75.5 ± 17.1 to 81.1 ± 14.4% viable forms (p < 0.001). CONCLUSIONS: Micronutrient supplementation can improve sperm quality and DNA integrity in infertile men. Men with infertility and significant sperm DNA fragmentation who take antioxidants for three months experience a reduction in DNA fragmentation index and an increase in sperm quality as measured by the semen analysis. TRIAL REGISTRATION: NCT04509583 . Registered 12 August 2020, Hue University of Medicine and Pharmacy Ethics Committee-Retrospectively registered.

RéSUMé: CONTEXTE: La spermatogenèse et la qualité du sperme peuvent être affectées négativement par une augmentation des espèces réactives de l'oxygène. La présente étude évalue l'efficacité d'une thérapie antioxydante combinée pour traiter l'infertilité masculine, telle que mesurée par les analyses du sperme et l'indice de fragmentation de l'ADN des spermatozoïdes (DFI). Les hommes infertiles avec un indice de fragmentation de l'ADN des spermatozoïdes élevé ont été invités à prendre, par voie orale, deux capsules de micronutriments par jour pendant trois mois. Chaque formulation antioxydante contenait 60 mg de vitamine E, 400 µg d'acide folique, 30 mg de sélénium, 125 mg de L-arginine, 220 mg de L-carnitine, 7,5 mg de coenzyme Q10, 40 mg de L-glutathion et 20 mg de citrate de zinc. À l'entrée et après le traitement, les caractéristiques générales, l'analyse du sperme et les tests de dispersion de la chromatine spermatique ont été enregistrés et comparés. RéSULTATS: Après trois mois de traitement avec des composés antioxydants, la qualité des spermatozoïdes s'est considérablement améliorée, comme l'indique une diminution de l'indice moyen de fragmentation de l'ADN de 45,6±17,2% à 34,8±20,3%; une augmentation de la concentration de spermatozoïdes de 29,7×106/mL à 35,7×106/mL (p<0,001), une augmentation du nombre total de spermatozoïdes de 72,1x106 à 95,5x106 (p=0,012), et une augmentation de la vitalité de 75,5±17,1 à 81,1±14,4% des formes viables (p<0,001). CONCLUSIONS: La supplémentation en micronutriments peut améliorer la qualité du sperme et l'intégrité de l'ADN chez les hommes infertiles. Les hommes souffrant d'infertilité et d'une fragmentation importante de l'ADN des spermatozoïdes qui prennent des antioxydants pendant trois mois subissent une réduction de l'indice de fragmentation de l'ADN et une augmentation de la qualité du sperme, mesurée par l'analyse du sperme.

L-Carnitine and Male Fertility: Is Supplementation Beneficial?

L-Carnitine, a natural antioxidant found in mammals, plays a crucial role in the transport of long-chain fatty acids across the inner mitochondrial membrane. It is used as a nutritional supplement by professional athletes, improving performance and post-exercise recovery. Additionally, its therapeutic applications, including those in male infertility, have been investigated, as it may act as a defense mechanism against the excessive production of reactive oxygen species (ROS) in the testis, a process that can lead to sperm damage. This effect is achieved by enhancing the expression and activity of enzymes with antioxidant properties. Nevertheless, the mechanisms underlying the benefits of L-Carnitine remain unknown. This review aims to consolidate the current knowledge about the potential benefits of L-Carnitine and its role in male (in)fertility. Considering in vitro studies with Sertoli cells, pre-clinical studies, and investigations involving infertile men, a comprehensive understanding of the effects of L-Carnitine has been established. In vitro studies suggest that L-Carnitine has a direct influence on somatic Sertoli cells, improving the development of germ cells. Overall, evidence supports that L-Carnitine can positively impact male fertility, even at a relatively low dose of 2 g/day. This supplementation enhances sperm parameters, regulates hormone levels, reduces ROS levels, and subsequently improves fertility rates. However, further research is needed to elucidate the underlying mechanisms and establish optimal doses. In conclusion, the role of L-Carnitine in the field of male reproductive health is highlighted, with the potential to improve sperm quality and fertility.

Understanding the Male Perspective: Evaluating Quality of Life and Psychological Distress in Serbian Men Undergoing Infertility Treatment.

The experience of an infertility diagnosis and treatment imposes a profound burden on affected individuals, encompassing not only physical and medical aspects but also a plethora of psychological, social, and emotional factors. By employing a multimodal assessment featuring validated self-report questionnaires, physical measurements, and clinical records, the present study aimed to explore the quality of life and psycho-emotional distress of men undergoing infertility treatment in Serbia, thereby addressing the dearth of research on the underrepresented male perspective in this domain. Findings revealed diverse semen abnormalities among participants (n = 96, average age 37.69 ± 5.72), with significant associations between longer treatment durations and reduced sperm motility. The observed rates of men surpassing predetermined DASS-42 questionnaire thresholds for depression, anxiety, and stress in the analyzed cohort were 13.54%, 11.46%, and 22.92%, respectively. Summary scores in conceptual areas comprised in the SF-36 questionnaire ranged from 49.00 ± 6.25 for the mental health dimension to 90.16 ± 17.75 obtained in the physical functioning subscale. Patients with a longer treatment duration demonstrated lower scores in the role emotional domain, indicative of a less favorable emotional state. Expectedly, inverse correlations were found between the SF-36 mental health score and DASS-42 subscales. By addressing the existing knowledge gap and highlighting the unique needs of infertile men, the finding of this study may contribute to a more inclusive and holistic approach to infertility research and management.

Effects of folic acid and folic acid plus zinc supplements on the sperm characteristics and pregnancy outcomes of infertile men: A systematic review and meta-analysis.

Background: Folic acid and zinc supplements have been used to treat male infertility, but their efficacy is still debated. Objective: To systematically evaluate the effects of folic acid and folic acid plus zinc supplements on sperm characteristics and pregnancy outcomes of infertile men. Methods: An online systematic search was performed using PubMed, Cochrane Library, and EMBASE databases from inception to August 1, 2022. The goal was to identify randomized controlled trials (RCTs) that used folic acid or folic acid plus zinc to improve sperm characteristics of infertile men. Data were extracted by two investigators who independently screened the literature and assessed for quality according to the criteria. The meta-analysis was performed using RevMan 5.4 software. Results: A total of 8 RCT studies involving 2168 patients were included. The results showed that compared with the controls, folic acid significantly increased sperm motility (MD, 3.63; 95% CI, -1.22 to 6.05; P = 0.003), but did not affect the sperm concentration (MD, 2.53; 95% CI, -1.68 to 6.73; P = 0.24) and sperm morphology (MD, -0.02; 95% CI, -0.29 to 0.24; P = 0.86) in infertile men. Folic acid plus zinc did not affect sperm concentration (MD, 1.87; 95% CI, -1.39 to 5.13; P = 0.26), motility (MD, 1.67; 95% CI, -1.29 to 4.63; P = 0.27), and morphology (MD, -0.05; 95% CI, -0.27 to 0.18; P = 0.69) in infertile men. Secondary results showed that compared with a placebo, folic acid alone had a higher rate of pregnancy in transferred embryos (35.6% vs. 20.4%, P = 0.082), but the difference was not significant. Folic acid plus zinc did not affect pregnancy outcomes. Conclusions: Based on the meta-analysis, no significant improvements in sperm characteristics with folic acid plus zinc supplements were seen. However, folic acid alone has demonstrated the potential to improve sperm motility and in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) outcomes. This indicates that folic acid supplements alone may be a viable treatment option for male infertility.

Guijiajiao (Colla Carapacis et Plastri, CCP) prevents male infertility via gut microbiota modulation.

Male infertility is a significant cause of psychosocial and marital distress in approximately 50% of couples who are unable to conceive, with male factors being the underlying cause. Guijiajiao (Colla Carapacis et Plastri, CCP) is a Traditional Chinese Medicine commonly used to treat male infertility. The present study aimed to investigate the potential mechanisms underlying the preventive effects of CCP on male infertility. An infertile male rat model was established using cyclophosphamide (CTX), and CCP was administered for both treatment and prevention. Fecal microbiota transplantation (FMT) was also performed to explore the role of gut microbiota in the CCP-mediated prevention of male infertility in rats. Sperm motility and concentration were determined using a semi-automatic sperm classification analyzer. Subsequently, histopathological analysis using HE staining was performed to examine the changes in the small intestine and testis. Moreover, the serum levels of lipopolysaccharide (LPS) and testosterone were measured by ELISA. In addition, immunohistochemistry was conducted to detect CD3 expression in the small intestine, while RT-qPCR was employed to assess the expressions of interleukin-1 beta (IL-1ß), cluster of differentiation 3 (CD3), Monocyte chemoattractant protein-1 (MCP-1), and C-X-C motif chemokine ligand 10 (CXCL-10) in the small intestine and epididymis. Finally, gut microbiota was analyzed by 16S rRNA sequencing. CCP improved sperm motility, number, and concentration in CTX-induced infertile male rats. CCP increased the serum testosterone level, inhibited the immune cell infiltration of the intestinal lamina propria, and promoted the aggregation of CD3+ T cells in CTX-induced male infertility rats. CCP also inhibited the expressions of MCP-1, CXCL-10, and IL-1ß in the epididymis of male infertility rats. At the genus level, CTX led to a reduction in the abundance of Lactobacillus, Clostridia_UCG.014, and Romboutsia in the intestinal tract of rats. In contrast, CCP decreased the abundance of Ruminococcus and increased the abundance of Romboutsia in infertile male rats. Additionally, FMT experiments proved that the gut microbiota of CCP-treated rats facilitated testicular tissue recovery and spermatogenesis while also reducing the serum LPS level in infertile male rats. CCP improves the spermatogenic ability of infertile male rats by restoring gut microbiota diversity and inhibiting epididymal inflammation.

[Treatment of infertility in men with pathospermia associated with oxidative stress].

INTRODUCTION: Oxidative stress considered to be the main cause of male infertility. Surgical treatment of varicocele and elimination of the inflammatory process in the male accessory glands can help reduce the level of oxidative stress, however, in most cases, antioxidant therapy is additionally prescribed. Currently, much attention is paid to regulatory peptides as a component of antioxidant therapy due to their antioxidant, anti-inflammatory and immunomodulatory properties. AIM: To evaluate the efficiency of a complex of antimicrobial peptides and cytokines Superlymph for the treatment of male infertility associated with oxidative stress. MATERIALS AND METHODS: A total of 30 patients with elevated levels of reactive oxygen species were recruited in the open, prospective, multicenter study. Ejaculate analysis (WHO-2010), MAR-test, sperm DNA damage testing and reactive oxygen species measurement were performed. All patients received Superlymph 25 IU/day for 60 days. Antibiotics and vitamin D were also prescribed if indicated. In addition, 12 patients took dietary supplements with antioxidant action. Laboratory tests were repeated after the completion of treatment. RESULTS: Superlymph therapy led to an improvement in standard semen parameters as well as decrease in sperm DNA fragmentation and oxidative stress. At the end of treatment, a significant increase in the sperm concentration was observed (46.8 [30; 87] vs. 62 [43-89], p=0.002). After treatment, there was also an increase in the median of sperm cells with normal morphology (3 [1; 7] vs. 4.5 [2; 9], p=0.002). The median sperm DNA fragmentation was lower compared to baseline, but this difference did not reach significant level (19 [14; 26] vs. 15 [10.5; 19.5], p=0.06). A significant decrease in the level of oxidative stress both in patients who took Superlymph as monotherapy (43 [27; 51] vs. 33 [22; 44], p=0.005), and as part of combination therapy with other antioxidants (31 [22; 54] vs. 21 [12; 36], p=0.009) was also observed. CONCLUSION: Superlymph contributes to the improvement of standard ejaculate parameters as well as decrease in the level of sperm DNA fragmentation and oxidative stress.

The lack of evidence behind over-the-counter antioxidant supplements for male fertility patients: a scoping review.

STUDY QUESTION: What is the evidence for over-the-counter antioxidant supplements for male infertility? SUMMARY ANSWER: Less than half of over-the-counter antioxidant supplements for male fertility patients have been tested in a clinical trial, and the available clinical trials are generally of poor quality. WHAT IS KNOWN ALREADY: The prevalence of male infertility is rising and, with this, the market for supplements claiming to improve male fertility is expanding. Up to now, there is limited data on the evidence for these over-the-counter supplements. STUDY DESIGN SIZE DURATION: Amazon, Google Shopping and other relevant shopping websites were searched on 24 June 2022 with the following terms: 'supplements', 'antioxidants', 'vitamins', AND 'male fertility', 'male infertility', 'male subfertility', 'fertility men', 'fertility man'. All supplements with a description of ingredients in English, Dutch, French, Spanish, or German were included. Subsequently, Pubmed and Google Scholar were searched for studies that included the supplements. PARTICIPANTS/MATERIALS SETTING METHODS: Inclusion criteria were supplements with antioxidant properties, of which the main purpose was to improve male fertility. Included supplements must be available without a doctor's prescription. Supplements containing plant extracts were excluded, as well as supplements of which the content or dosage was not clear. The ingredients, dosage, price and health claims of the supplements were recorded. We assessed whether substances in the supplements exceeded the recommended dietary allowance (RDA) or tolerable upper intake level (UL). All clinical trials and animal studies investigating included supplements were selected for this review. Clinical trials were assessed for risk of bias with a risk of bias tool appropriate for the study design. MAIN RESULTS AND THE ROLE OF CHANCE: There were 34 eligible antioxidant supplements found, containing 48 different active substances. The average price per 30 days was 53.10 US dollars. Most of the supplements (27/34, 79%) contained substances in a dosage exceeding the recommended daily allowance (RDA). All manufacturers of the supplements made health claims related to the improvement of sperm quality or male fertility. For 13 of the 34 supplements (38%), published clinical trials were available, and for one supplement, only an animal study was found. The overall quality of the included studies was poor. Only two supplements were tested in a good quality clinical trial. LIMITATIONS REASONS FOR CAUTION: As a consequence of searching shopping websites, a comprehensive search strategy could not be formulated. Most supplements were excluded because they contained plant extracts or because supplement information was not available (in an appropriate language). WIDER IMPLICATIONS OF THE FINDINGS: This is the first review that gives an insight into the market of male fertility supplements as available to infertility patients and other men seeking to improve their fertility. Earlier reviews have focused only on supplements with published clinical trials. However, we show that more than half of the supplements have not been tested in a clinical trial. To our knowledge, this review is the first to assess the dosage of supplements in relation to the RDA. In agreement with the literature, we found that the evidence on male fertility supplements is generally of poor quality. This review should urge pharmaceutical companies to evaluate their products in randomized controlled trials in order to provide people with substantiated information. STUDY FUNDING/COMPETING INTERESTS: The research position of W.R.d.L. is funded by an unrestricted grant from Goodlife Pharma. W.R.d.L., K.F., and J.P.d.B. are in the research team of a clinical trial on Impryl®, one of the supplements included in this review. REGISTRATION NUMBER: N/A.

Artemisia annua L. (Sweet wormwood) leaf extract attenuates high-fat diet-induced testicular dysfunctions and improves spermatogenesis in obese rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L., known as "sweet wormwood," is widely used in Egyptian folk medicine. Egyptians implement the aerial parts in the treatment of respiratory, digestive and sexual dysfunctions. However, the mechanism by which Artemisia annua improves testicular function is still being discovered. AIM OF THE STUDY: This study aimed to evaluate the modulatory effects of the crude leaf extract of Artemisia annua (AAE) on a high-fat diet induced testicular dysfunction in rats and compare it with the antilipolytic drug Orlistat. MATERIAL AND METHODS: Forty adult rats were randomly classified and assigned to four groups. The first group typically consumed a balanced diet and served as a negative control (GP1). A high-fat diet-induced obesity was applied to the other three groups for 12 weeks. A positive control remained on HFD for another 8 weeks, which is GP2. Other groups were administered for 8 consecutive weeks either with Orlistat (50 mg/kg body weight) or AAE (100 mg/kg body weight), which have been defined as GP3 and GP4, respectively. Testosterone (TST), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined in the sera of all groups. In addition, the oxidant/antioxidant biomarkers such as protein carbonyl, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) activities, lactate dehydrogenase (LDH) and creatine kinase isoenzyme-B (CK-MB) were determined. An immunohistochemical stain with the apoptotic marker caspase-3 and the proliferating cell nuclear antigen (PCNA) were also investigated. RESULTS: In the testes of the obese group, the results showed hormonal imbalance, an increase in oxidative stress biomarkers and apoptosis. In the group treated with orlistat (GP3), noticeably more perturbations were noted. The obese rats that had been treated with AAE (GP4) showed a significantly reduced level of oxidative stress, hormonal balance restoration and reduced apoptosis. CONCLUSIONS: The crude leaf extract of A. annua is a potential herbal therapeutic for the treatment of obesity-related testicular dysfunction and the restoration of hormonal imbalance in obese rats.

Effectiveness of non-pharmaceutical intervention on sperm quality: a systematic review and network meta-analysis.

Infertility affects about 10% of the world's population and has been recognized by the WHO as a global public health problem. The aim of this network meta-analysis was to investigate the efficacy of non-pharmaceutical interventions on sperm quality. All randomized clinical trials (RCTs) from the PubMed, MEDLINE, Embase, China national knowledge infrastructure (CNKI), Wanfang database, and Cochrane Library databases evaluating the effectiveness of non-pharmaceutical interventions on semen parameters using network meta-analyses. Results of the ω-3 fatty acid, lycopene, acupuncture, and vitamin suggested evident advantages in improving sperm concentration (MD, 9.93 (95% CI, 7.21 to 12.65)), (MD, 8.79 (95% CI, 2.67 to 14.91)), (MD, 5.40 (95% CI, 2.32 to 8.49)) and (MD, 3.82 (95% CI, 0.70 to 6.94) respectively). Acupuncture has a significant advantage over placebo in improving sperm total motility (MD, 17.81 (95% CI, 10.32 to 25.29)), and the effect of lycopene was obviously greater than that of placebo (MD, 19.91 (95% CI, 2.99 to 36.83)). Lycopene, Coenzyme Q10 (CoQ10), acupuncture, ω-3 fatty acid, and vitamin suggested significant advantages in improving sperm forward motility (MD, 8.64 (95% CI, 1.15 to 16.13), MD, 5.28 (95% CI, 2.70 to 7.86), MD, 3.95 (95% CI, 3.23 to 4.67), MD, 3.50 (95% CI, 2.21 to 4.79)) and (MD, 2.38 (95% CI, 0.96 to 3.80) respectively). This review establishes that non-pharmaceutical interventions, particularly acupuncture, exercise, lycopene, ω-3 fatty acids, CoQ10, zinc, vitamins, selenium, carnitine, or foods rich in these supplements, profitably improve sperm quality that may be used to treat male infertility.