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.

Effects of alpha-lipoic acid on sperm quality in patients with varicocele-related male infertility: study protocol for a randomized controlled clinical trial.

BACKGROUND: Varicocele is a high incidence and is considered to be the most common and correctable cause of male infertility. Oxidative stress (OS) plays a central role in the pathogenesis of varicocele-related male infertility. In addition to varicocelectomy, antioxidant supplementation seems to be an effective scheme for the treatment of varicocele-related male infertility, but it is still controversial. The purpose of this study is to determine the effects of alpha-lipoic acid (ALA) supplementation on sperm quality in patients with varicocele-related male infertility. METHODS: In this randomized controlled clinical trial, we will randomize 80 patients with varicocele-related male infertility from Guilin People's Hospital. The non-surgical observation group (n = 20) will receive ALA, the non-surgical control group (n = 20) will receive vitamin E, the surgical observation group (n = 20) will receive ALA after the operation, and the surgical control group (n = 20) will receive vitamin E after the operation. The course of treatment will be 3 months. The results will compare the changes in semen parameters, sex hormones, testicular volume, sperm DNA fragment index (DFI), seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) between the groups at baseline and after 3 months of antioxidant supplementation. DISCUSSION: Whether it is necessary to use antioxidants in varicocele-related male infertility, how potent antioxidants should be used, postoperative application or non-surgical independent application still needs to be explored. This study attempts to compare the effects of two antioxidants (ALA and vitamin E) on sperm quality in patients with varicocele-related male infertility (surgical or non-surgical) and attempted to answer the above questions. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100054958. Registered on 29 December 2021.

Vitamin D Supplementation Improves Fasting Insulin Levels and HDL Cholesterol in Infertile Men.

CONTEXT: Vitamin D has been linked with glucose and lipid metabolism. Men with impaired gonadal function have a higher risk of metabolic syndrome and mortality, and vitamin D status may be a reversible modulator. OBJECTIVE: This work aimed to determine the effect of daily vitamin D and calcium supplementation for 150 days on glucose and lipid homeostasis in infertile men. METHODS: A single-center, double-blinded, randomized clinical trial (NCT01304927) was conducted. A total of 307 infertile men were randomly assigned (1:1) to a single dose of 300 000 IU cholecalciferol followed by 1400 IU cholecalciferol + 500 mg of calcium daily (n = 151) or placebo (n = 156) for 150 days. Reported metabolic parameters including fasting plasma glucose, glycated hemoglobin A1c, fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma cholesterols, and triglycerides were secondary end points. The primary end point semen quality has previously been reported. RESULTS: Men receiving vitamin D supplementation improved their vitamin D status, whereas vitamin D status was aggravated in the placebo group characterized by higher serum parathyroid hormone. At the end of the trial, men receiving vitamin D supplementation had 13% lower fasting serum insulin concentrations compared with the placebo-treated group (65 vs 74 pmol/L, P = .018) and 19% lower HOMA-IR (2.2 vs 2.7, P = .025). Moreover, men in the vitamin D group had higher high-density lipoprotein (HDL) cholesterol levels (1.38 vs 1.32 mmol/L, P = .008) compared with the placebo group. CONCLUSION: High-dose vitamin D supplementation has beneficial effects on glucose homeostasis and HDL cholesterol levels in infertile men.

Male vitamin D status and male factor infertility.

OBJECTIVE: To determine the association between vitamin D levels in the male partner and fertility outcomes in couples with mild male factor infertility. DESIGN: Secondary analysis of a randomized, controlled trial. SETTING: Nine fertility centers in the United States. PATIENT(S): Men (n = 154) with sperm concentration between 5 and 15 million/mL, motility ≤40%, or normal morphology ≤4% were eligible. Female partners were ovulatory, ≤40 years old, and had documented tubal patency. INTERVENTION(S): Men provided semen and blood at baseline for semen analysis and 25-hydroxyvitamin D (25(OH)D) levels. They were randomly assigned to receive a vitamin formulation including vitamin D 2,000 IU daily or placebo for up to 6 months. Couples attempted to conceive naturally during the first 3 months and with clomiphene citrate with intrauterine insemination of the female partner in months 4 through 6. MAIN OUTCOME MEASURE(S): Primary: sperm concentration, motility, morphology, and DNA fragmentation at baseline. Secondary: cumulative pregnancy, miscarriage, and live birth rates. RESULT(S): Semen parameters and sperm DNA fragmentation were not statistically significantly different between men with vitamin D deficiency and men with 25(OH)D levels ≥20 ng/mL. In addition, clinical pregnancy and live birth rates were similar. Male 25(OH)D level <20 ng/mL was associated with a higher rate of pregnancy loss (adjusted odds ratio 9.0; 95% confidence interval 1.3 to 61.3). CONCLUSION(S): Vitamin D deficiency in the male partner did not significantly impact semen parameters or treatment outcomes. Further study is warranted to better characterize the rate of miscarriage in couples with male vitamin D deficiency.

The effects of Vitamin D3 supplementation on Spermatogram and endocrine factors in asthenozoospermia infertile men: a randomized, triple blind, placebo-controlled clinical trial.

OBJECTIVE: Evaluate the effects of vitamin D3 (VD3) on sperm parameters and endocrine markers in infertile men with asthenozoospermia. MATERIALS AND METHODS: This randomized, triple-masking, placebo-controlled clinical trial conducted on 86 asthenozoospermia infertile men with serum 25 hydroxy vitamin D3 (25(OH)VD3) < 30 ng/ml in the infertility clinic of Ahvaz Jahad daneshgahi, Iran. Patients were randomly allocated to groups A and B, who received daily 4000 IU VD3 and matching placebo respectively for 3 months. Demographic data, dietary intake, physical activity, sun exposure, anthropometric indices, serum 25(OH)VD3, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (T), estradiol (E2),, sex hormone-binding globulin (SHBG), free androgen index (FAI = T/SHBG. 100), T/LH and T/E2 ratios, prolactin (PRO), parathyroid hormone (PTH), osteocalcin (OCN), phosphorus and sperm parameters were assessed. RESULTS: Three months VD3 supplementation with 4000 IU/day had no significant effects body weight, body mass index (BMI), waist circumference (WC), body fat (BF), serum, OCN, LH, FSH, T, E2, SHBG, PRO, T/E2 ratio, FAI, semen volume, sperm count and normal sperm morphology. It increases serum 25(OH)VD3, PTH and phosphorus and seminal and serum calcium, T/LH ratio and total and progressive sperm motility and decreased significantly compared to the baseline and placebo group. CONCLUSION: VD3 supplementation may affect sperm motility in men with asthenozoospermia and serum 25(OH)VD3 < 30 ng/ml. TRIAL REGISTRATION: Iran Clinical Trials Registry, ID: IRCT20151128025274N4, registered on 28 March 2018, URL of trial registry record: https://www.irct.ir/trial/29983.

Treatment With Cholecalciferol Leads to Increase Of Selected Semen Parameters in Young Infertile Males: Results of a 6-month Interventional Study.

High incidence of infertility along with low vitamin D levels was detected in otherwise healthy young men. The aim is to observe the effect of vitamin D supplementation on semen parameters as assessed by semen analysis in infertile men. In total, 45 men (mean age 36.6 years) in consecutive order were included, of whom 34 finished the study. Subjects were supplemented by vitamin D (cholecalciferol) 2500 IU/day. Vitamin D levels were assessed by HPLC. Semen analysis was performed strictly following 2010 WHO guidelines. Study periods were baseline and month 6. During follow-up, 20 %, 7.4 %, 22 % and 0.7 % increase in serum vitamin D levels, progressive sperm motility, sperm concentration and sperm morphology, respectively, were observed (all p<0.05). At follow-up end, 9 patients (26 %) reached normal sperm parameters of whom 2 fertilized their partner. There was no correlation between vitamin D and semen parameters observed. This study proves that vitamin D supplementation is possibly a modulator of sperm parameters in vitamin D deficient, otherwise healthy men. Although a direct relationship between vitamin D and sperm parameters was not observed obtaining adequate vitamin D levels could likely play a role in the male factor of infertility.

Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline PART II.

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

Three hour abstinence as a treatment for high sperm DNA fragmentation: a prospective cohort study.

PURPOSE: This study sought to compare sperm DNA fragmentation (SDF) in semen specimens after 3 days and then after 3 h of abstinence in men presenting for initial infertility evaluation. METHODS: A prospective cohort study of 112 men undergoing their first semen analysis as part of an infertility work-up was conducted. All participants presented with 3 days of abstinence for a semen analysis and DNA-fragmentation test. Both tests were repeated on a second sample collected 3 h after the first ejaculation. DNA-fragmentation was evaluated with the halo test by one of two technicians blinded to duration of abstinence. Variables analyzed include ejaculate volume, sperm concentration and motility, smoking status, cannabis use, initial specimen DNA fragmentation, and use of sperm-directed anti-oxidant formulations. RESULTS: Among all subjects, DNA fragmentation improved in the 3-h abstinence specimen (34.6 ± 19.4% vs. 23.7 ± 16.0%, p = 0.0001). Among subjects with high DNA fragmentation (> 35%) on the initial specimen, 55% improved into the normal range. Semen volume and sperm concentration decreased (3.1 ± 3.3 ml vs. 1.9 ± 0.8 ml, p < 0.01 and 41 ± 39 vs. 32 ± 31 (millions/ml), p = 0.01), while progressive motility tended to increase. Fifty-eight subjects demonstrated ≥ 30% improvement in SDF in the second specimen as compared to the first. Factors found to correlate with > 30% improvement in DNA fragmentation in the 3-h abstinence specimen compared to 3 days were younger age and use of anti-oxidants. CONCLUSION: High SDF can often be managed with a second ejaculation 3 h after the first in infertile couples, including in males with abnormal semen analyses per the 2010 WHO guide. Apart from SDF levels, changes in sperm quality were not clinically significant in the second specimen and did not increase rates of ICSI. However, a second ejaculation after 3 h probably may reduce the necessity of costly and/or invasive ART strategies.

[Distribution of TCM syndrome types and their correlation semen parameters in infertility patients with varicocele].

OBJECTIVE: To explore the distribution of Traditional Chinese Medicine (TCM) syndrome types and their relationship with semen parameters in infertility male patients with varicocele (VC). METHODS: Using Questionnaire on Clinical Symptoms of Varicocele-Caused Male Infertility, we made an investigation among 147 infertility male patients with VC, determined the types of their TCM syndromes, obtained their semen parameters, and analyzed the distribution of the TCM syndrome types and their correlation with semen parameters. RESULTS: Of the TCM syndrome types identified, kidney deficiency and stagnated heat constituted the largest proportion (34.7%), and the mixed type accounted for a significantly higher percentage than the simple type (P < 0.05). The patients with kidney deficiency and stagnated heat, compared with those with other syndrome types, had a dramatically lower sperm concentration (ï¼»21.62 ± 9.25ï¼½ vs ï¼»28.88 ± 12.92ï¼½ ×106/ml, P < 0.01), but a higher percentage of morphologically abnormal sperm (ï¼»98.33 ± 0.15ï¼½% vs ï¼»96.27 ± 0.18ï¼½%, P < 0.05) and DNA fragmentation index (ï¼»19.72 ± 3.17ï¼½% vs ï¼»10.96 ± 3.82ï¼½%, P < 0.01). No statistically significant differences were observed in the percentage of progressively motile sperm among different TCM syndrome types. CONCLUSIONS: Kidney deficiency and stagnated heat is a main TCM syndrome type in infertility male patients with varicocele and correlated with sperm concentration, the percentage of morphologically abnormal sperm and DNA fragmentation index.

IMPORTANCE OF ZINC CONCENTRATION IN SEMINAL FLUID OF MEN DIAGNOSED WITH INFERTILITY.

The prevalence and importance of male infertility make it a serious worldwide medical and social problem. The aim of this study was to determine if there were any significant differences in zinc concentrations in seminal fluid in men diagnosed with infertility compared to control group, and if there were, to determine how it affected the number and percentage of sperm cells with normal motility and morphology. A case-control study was conducted in the Osijek-Baranja County from January 2014 to June of 2015. The study included 276 subjects referred to biochemistry laboratory of the Osijek University Hospital Centre, 100 (36.2%) of them with low sperm count confirmed by spermiogram after 3 months. Semen samples were processed according to the World Health Organization criteria, and zinc concentrations were determined using spectrophotometry and direct colorimetry without deproteinization on a chemistry analyzer (Olympus AU 680, Beckman Coulter, Tokyo, Japan). Study results showed the men with low sperm count to be significantly older (Mann Whitney U test: p=0.013) and to have lower zinc levels (χ2-test: p<0.001). Further analysis included 100 (36.2%) patients with low sperm count. In the group of infertile men, those with low sperm count had higher zinc levels compared to men with azoospermia (Mann Whitney U test: p=0.036), suggesting a connection between lower zinc level in seminal fluid and male fertility. Zinc as a biological marker and an antioxidant affects sperm count, motility and morphology. Zinc supplemental therapy could improve seminal parameters in patients diagnosed with low sperm count. Dietary habits of the subjects differ regionally, and future research could make a solid foundation for complementary approach to treatment of male infertility.

Photobiomodulation therapy for male infertility.

Male infertility is a worldwide critical condition that affects about the 7.5% of males in Europe leading to an increment of the couples referring to reproductive medicine units to achieve pregnancy. Moreover, in the recent years, an increased number of patients have required to freeze their gametes in order to preserve their fertility. Photobiomodulation (PBM) therapy is a potential treatment that has been used for different clinical application basically aimed at biostimulating cells and tissues. Here, we report a deep overview of the published studies, focusing on PBM mechanism of action, with the aim of expanding the knowledge in the field of laser light for a rational utilization of irradiation in the clinical practice. In the field of reproductive science, PBM was employed to increment spermatozoa's metabolism, motility, and viability, due to its beneficial action on mitochondria, leading to an activation of the mitochondrial respiratory chain and to the ATP production. This treatment can be particularly useful to avoid the use of chemicals in the spermatozoa culture medium as well as to promote the spermatozoa survival and movement especially after thawing or in largely immotile sperm samples.

Distribution of TCM syndrome types and their correlation semen parameters in infertility patients with varicocele / 中华男科学杂志

Objective@#To explore the distribution of Traditional Chinese Medicine (TCM) syndrome types and their relationship with semen parameters in infertility male patients with varicocele (VC).@*METHODS@#Using Questionnaire on Clinical Symptoms of Varicocele-Caused Male Infertility, we made an investigation among 147 infertility male patients with VC, determined the types of their TCM syndromes, obtained their semen parameters, and analyzed the distribution of the TCM syndrome types and their correlation with semen parameters.@*RESULTS@#Of the TCM syndrome types identified, kidney deficiency and stagnated heat constituted the largest proportion (34.7%), and the mixed type accounted for a significantly higher percentage than the simple type (P < 0.05). The patients with kidney deficiency and stagnated heat, compared with those with other syndrome types, had a dramatically lower sperm concentration (［21.62 ± 9.25］ vs ［28.88 ± 12.92］ ×10⁶/ml, P < 0.01), but a higher percentage of morphologically abnormal sperm (［98.33 ± 0.15］% vs ［96.27 ± 0.18］%, P < 0.05) and DNA fragmentation index (［19.72 ± 3.17］% vs ［10.96 ± 3.82］%, P < 0.01). No statistically significant differences were observed in the percentage of progressively motile sperm among different TCM syndrome types.@*CONCLUSIONS@#Kidney deficiency and stagnated heat is a main TCM syndrome type in infertility male patients with varicocele and correlated with sperm concentration, the percentage of morphologically abnormal sperm and DNA fragmentation index.

A double-blinded, randomized placebo-controlled trial on the effect of traditional Chinese medicine formula Wuzi Yanzong pill on improving semen qualities in men with suboptimal parameters.

BACKGROUND: In Hong Kong, one of six couples is affected by subfertility problems. Male infertility contributes to half of the infertility cases. In male infertility, there is no effective treatment for patients with idiopathic infertility/poor semen parameters. Recent meta-analysis results suggest that a traditional Chinese medicine (TCM) formula - Wuzi Yanzong pill - showed a curative effect on male fertility. However, the heterogeneity of the studies could not draw a definitive conclusion on the therapeutic effect of this formula. The aim of this study is to conduct a well-designed randomized controlled trial to investigate the effect of TCM formula Wuzi Yanzong pill on improving semen qualities in men with suboptimal parameters. METHODS: This study is a double-blinded, randomized placebo-controlled trial conducted in a public hospital in Hong Kong. Participants will be randomized, using computer-generated random numbers, with a 1:1 ratio to either the Wuzi Yanzong pill formula group or the placebo group. Both groups will be administered the drugs for 12 weeks. Participants will have a total of four visits for their semen and blood assessments for a 6-month period, and we will follow up for another 6 months to record their conception outcome. The primary outcome is to compare the total motile sperm count, natural conception rate, and pregnancy outcome to those under placebo treatment. Secondary objectives are sperm functions and assisted reproductive technology outcome. DISCUSSION: To date, there are no studies using the disclosed Wuzi Yanzong formula or double-blinded, randomized trials. The Wuzi Yanzong TCM formula may provide a good clinical solution for subfertile males for which contemporary western medicine has no cure. Therefore, a well-designed randomized trial for evaluating the effect of Wuzi Yanzong TCM formula is urgently needed. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR-INR-17010790 . Registered on 27 February 2017. Centre for Clinical Research and Biostatistics - Clinical Trials Registry, CUHK_CCRB00548 . Registered on 27 February 2017.

Non-hormonal treatment for male infertility: the potential role of Serenoa repens, selenium and lycopene.

OBJECTIVE: Male infertility is a wide spread disease among couple of childbearing age. Spermatozoa are highly susceptible to oxidative stress. Reactive oxygen species (ROS) are capable of damaging the sperm membrane and DNA, inducing lipid peroxidation and sperm DNA fragmentation (SDF). Antioxidant supplementation is currently suggested after a complete diagnostic work-up, as recognized by the Italian Society of Andrology and Sexual Medicine (SIAMS). Indeed, it has been showed to improve sperm quality, DNA fragmentation and pregnancy rate. The administration of Serenoa repens extracts (SrE), including free fatty acids (FFA), methyl and ethyl esters, glycerides, flavonoids and sterols, has never been investigated for male infertility. However, their antioxidant and anti-inflammatory properties provide the rational for their possible effectiveness. The aim of this review was to collect all the evidence supporting the potential usefulness of SrE, alone or in combination with other molecules with proven antioxidant effects, like selenium and lycopene (along with which they are often commercialized), to improve sperm parameters. MATERIALS AND METHODS: A systematic search was performed using Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar and Scopus databases. The search strategy included the following key words: Serenoa repens, selenium, lycopene, oligozoospermia, oxidative stress, DNA fragmentation, male infertility, pregnancy rate. CONCLUSIONS: By triggering multiple inflammatory and oxidative pathways, the combined administration of SrE, selenium and lycopene might likely improve the sperm quality. Proper studies are needed to test this hypothesis. Finally, since prostatitis can affect the sperm quality and considering the anti-estrogenic properties of SrE, we speculate about a possible specific indication in those patients with male infertility and "metabolic" prostatitis (where obesity and abnormal androgen/estrogen ratio concomitantly occur).

Correlation of oxidation-reduction potential with hormones, semen parameters and testicular volume.

Seminal oxidative stress (OS) is a major cause of male factor infertility and can be measured as oxidation-reduction potential (ORP). Studies showed significant negative relationships of ORP with sperm count, motility or DNA integrity. Since these parameters are also positively or negatively associated with reproductive hormones follicle-stimulating hormone (FSH), luteinising hormone (LH), testosterone, testicular volume and the occurrence of varicocele, it is important to understand the mechanistic relationship between ORP and hormonal and/or testicular parameters. Therefore, we studied the relationship between ORP levels, standard hormone profiles and testicular volume in infertile men with and without varicocele. Results show a highly significant negative relationship of ORP with testicular volume and significantly positive correlations with FSH and LH. Yet, when adding varicocele as covariate, the relationship with FSH/LH became nonsignificant. Contrary, the presence of varicocele had only a contributing influence on the association of ORP with the testis volume. No association was found with estradiol. We propose that since OS causes degeneration of Sertoli cell with testicular shrinkage, such negative effect would result in a negative feedback on the hypothalamus with less inhibin secretion. This may result in increased secretion of LH and FSH. Thus, systemic and/or local OS may be responsible for smaller testis volumes.

Benefits of Empiric Nutritional and Medical Therapy for Semen Parameters and Pregnancy and Live Birth Rates in Couples with Idiopathic Infertility: A Systematic Review and Meta-analysis.

CONTEXT: Empiric use of medical and nutritional supplements to improve semen parameters and pregnancy rates in couples with idiopathic infertility has reached global proportions, although the evidence base for their use in this setting is controversial. OBJECTIVE: We systematically reviewed evidence comparing the benefits of nutritional and medical therapy on pregnancy rates and semen parameters in men with idiopathic infertility. EVIDENCE ACQUISITION: A literature search was performed using MEDLINE, Embase, LILACS, and the Cochrane Library (searched from January 1, 1990 to September 19, 2017). using the methods detailed in the Cochrane Handbook. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence. EVIDENCE SYNTHESIS: The literature search identified 5663 citations, and after screening of abstracts and full texts, 61 studies (59 randomised controlled trials and two nonrandomised comparative studies) were included. Pooled results demonstrated that pentoxyfylline, coenzyme Q10, L-carnitine, follicle-stimulating hormone, tamoxifen, and kallikrein all resulted in improvements in semen parameters. Individual studies identified several other medical and nutritional therapies that improved semen parameters, but data were limited to individual studies with inherent methodological flaws. There were limited data available on live birth and pregnancy rates for all interventions. The GRADE certainty of evidence for all outcomes was very low mainly owing to methodological flaws and inconsistencies in study design. Some outcomes were also downgraded owing to imprecision of results. CONCLUSIONS: There is some evidence that empiric medical and nutritional supplements may improve semen parameters. There is very limited evidence that empiric therapy leads to better live birth rates, spontaneous pregnancy, or pregnancy following assisted-reproductive techniques. However, the findings should be interpreted with caution as there were some methodological flaws, as a number of studies were judged to be either at high or unclear risk of bias for many domains. PATIENT SUMMARY: This review identified several medical and nutritional treatments, such as pentoxyfylline, coenzyme Q10, L-carnitine, follicle-stimulating hormone, tamoxifen, and kallikrein, that appear to improve semen parameters. However, there are limited data suggesting improvements in pregnancy and live birth rates. The lack of evidence can be attributed to methodological flaws in studies and the low number of pregnancies reported.

Steroid profiles in both blood serum and seminal plasma are not correlated and do not reflect sperm quality: Study on the male reproductive health of fifty young Swiss men.

Steroids play an important role in sperm production and quality. These hormones have been extensively studied in blood, but poorly investigated in semen. The purpose of our study was to evaluate the relationship between sperm quality and steroid profiles in blood and semen in a small cohort of young Swiss men. Another objective was to determine whether the presence of xenobiotics or drugs could influence these profiles. Semen analysis was performed according to WHO guidelines, and steroid profiles in blood serum and seminal plasma were determined by two complementary approaches: a targeted investigation involving the quantification of a limited number of relevant steroids for testing putative correlations with sperm parameters and a global "steroidomic" analysis highlighting their complex metabolic relationship. Results showed that steroid profiles are distinct within blood and seminal fluid. No significant correlation was found between individual steroids measured in blood and in semen, demonstrating the relevance of assessing hormone levels in both fluids. Moreover, testosterone and androstenedione levels were significantly correlated in semen but not in blood. None of the evaluated spermiogram parameters was linked to steroid levels measured in any medium. The steroidomic analyses confirmed that the steroids present in both fluids are different and that there is no correlation with spermiogram parameters. Finally, upon toxicological screening, we observed that all the three samples positive for tetrahydrocannabinol, which is known to act as an endocrine disruptor, displayed low seminal testosterone concentrations. In conclusion, we did not find any evidence suggesting using steroid profiles, neither in blood nor in semen, as surrogates for sperm analyses. However, steroid profiles could be useful biomarkers of individual exposure to endocrine disruptors.

Traditional Chinese Medicine syndrome elements of male infertility revealed by latent tree model analysis.

OBJECTIVE: To explore the features of Traditional Chinese Medicine (TCM) syndromes in male infertility using computer-based analyses. METHODS: Latent class analysis was used to analyze the TCM syndrome data from 813 patients with male infertility and establish a latent tree model. RESULTS: A latent tree model with a Bayesian information criterion score of -11 263 was created. This model revealed that the characteristics of basic TCM syndromes in patients with male infertility were kidney Yang deficiency, kidney Qi deficiency, spleen Yang deficiency, liver Qi stagnation, Qi stagnation and blood stasis, and dump-heat; moreover, most patients with male infertility had complex syndromes (spleen-kidney Yang deficiency and liver Qi stagnation) rather than simple single syndromes. CONCLUSION: The hidden tree model analysis revealed the objective and quantitative complex relationships between the TCM symptoms of male infertility, and obtained the quantification and objective evidence of TCM syndromes in male infertility.

Oxidative stress and male infertility.

DNA damage, largely owing to oxidative stress, is a leading cause of defective sperm function. High levels of oxidative stress result in damage to sperm DNA, RNA transcripts, and telomeres and, therefore might provide a common underlying aetiology of male infertility and recurrent pregnancy loss, in addition to congenital malformations, complex neuropsychiatric disorders, and childhood cancers in children fathered by men with defective sperm cells. Spermatozoa are highly vulnerable to oxidative stress owing to limited levels of antioxidant defence and a single, limited DNA-damage detection and repair mechanism. Oxidative stress is predominantly caused by a host of lifestyle-related factors, the majority of which are modifiable. Antioxidant regimens and lifestyle modifications could both be plausible therapeutic approaches that enable the burden of oxidative-stress-induced male factor infertility to be overcome. Lifestyle interventions including yoga and meditation can substantially improve the integrity of sperm DNA by reducing levels of oxidative DNA damage, regulating oxidative stress and by increasing the expression of genes responsible for DNA repair, cell-cycle control and anti-inflammatory effects. Oxidative stress is caused by various modifiable factors, and the use of simple interventions can decrease levels of oxidative stress, and therefore reduce the incidence of both infertility and complex diseases in the resultant offspring.