Relationship between degree of methylation of sperm long interspersed nuclear element-1 (LINE-1) gene and alteration of sperm parameters and age: a meta-regression analysis.

INTRODUCTION: The long interspersed nuclear element-1 (LINE1) gene is a retrotransposon whose methylation status appears to play a role in spermatogenesis, the outcome of assisted reproductive techniques (ART), and even in recurrent pregnancy loss (RPL). Advanced paternal age appears associated with altered sperm parameters, RPL, poor ART outcomes, and compromised offspring health. The methylation status of LINE1 has been reported to be affected by age. The latest meta-analysis on the LINE1 methylation pattern in spermatozoa found no significant differences in methylation levels between infertile patients and fertile controls. However, to the best of our knowledge, no updated meta-analysis on this topic has been published recently. Furthermore, no comprehensive meta-regression analysis was performed to investigate the association between sperm LINE1 methylation pattern and age. OBJECTIVES: To provide an updated and comprehensive systematic review and meta-analysis on sperm LINE1 gene methylation degree in patients with abnormal sperm parameters compared to men with normal sperm parameters and to probe the association between sperm LINE1 methylation status and age and/or sperm concentration. METHODS: This meta-analysis was registered in PROSPERO (registration n. CRD42023397056). It was performed according to the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating LINE1 gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included. RESULTS: Of 192 abstracts evaluated for eligibility, only 5 studies were included in the quantitative synthesis, involving a total of 340 patients and 150 controls. Our analysis showed no significant difference in LINE1 gene methylation degree in patients with infertility and/or abnormal sperm parameters compared to fertile controls and/or men with normal sperm parameters, although there was significant heterogeneity across studies. No significant evidence of publication bias was found, and no study was sensitive enough to alter the results. In meta-regression analysis, we found that the results were independent of both ages and sperm concentration. A sub-analysis examining patients and controls separately was also conducted and we found a trend for a positive correlation between LINE1 methylation and sperm concentration in the control group only. CONCLUSIONS: The results of this systematic review and meta-analysis do not suggest a determining role of sperm LINE1 gene methylation degree in patients with infertility and/or abnormal sperm parameters. Therefore, we do not suggest including LINE1 in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART cycles.

H19 Sperm Methylation in Male Infertility: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis summarize the difference in the methylation of the H19 gene in patients with abnormal versus normal conventional sperm parameters. It also evaluates the effects of age and sperm concentration on H19 methylation in spermatozoa using meta-regression analysis. It was performed according to the MOOSE guidelines for meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The quality of the evidence reported in the studies included was assessed using the Cambridge Quality Checklists. A total of 11 articles met our inclusion criteria. Quantitative analysis showed that H19 methylation levels were significantly lower in the group of infertile patients than in fertile controls. The reduction in methylation was much more pronounced in patients with oligozoospermia (alone or associated with other sperm parameter abnormalities) and in those with recurrent pregnancy loss. Meta-regression analysis showed the results to be independent of both patient age and sperm concentration. Therefore, the H19 methylation pattern should be evaluated among couples accessing assisted reproductive techniques (ART), in order to gain prognostic information on ART outcome and offspring health.

The Role of Resveratrol in Human Male Fertility.

Resveratrol (RSV) (3,4',5 trihydroxystilbene) is a natural non-flavonoid polyphenol widely present in the Mediterranean diet. In particular, RSV is found in grapes, peanuts, berries, and red wine. Many beneficial effects of this molecule on human health have been reported. In fact, it improves some clinical aspects of various diseases, such as obesity, tumors, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, and diabetes mellitus. However, little is known about the relationship between this compound and male fertility and the few available results are often controversial. Therefore, this review evaluated the effects of RSV on human male fertility and the mechanisms through which this polyphenol could act on human spermatozoa.

Complete Androgen Insensitivity Syndrome: From the Relevance of an Accurate Genetic Diagnosis to the Challenge of Clinical Management. A Case Report.

Introduction: Androgen insensitivity syndrome (AIS), an X-linked recessive disorder of sex development (DSD), is caused by variants of the androgen receptor (AR) gene, mapping in the long arm of the X chromosome, which cause a complete loss of function of the receptor. Case presentation: We report a patient diagnosed with complete AIS (CAIS) at birth due to swelling in the bilateral inguinal region. Transabdominal ultrasound revealed the absence of the uterus and ovaries and the presence of bilateral testes in the inguinal region. The karyotype was 46,XY. She underwent bilateral orchiectomy at 9 months and was given estrogen substitutive therapy at the age of 11 years. Genetic analysis of the AR gene variants was requested when, at the age of 20, the patient came to our observation. Methods: The genetic testing was performed by next-generation sequence (NGS) analysis. Results: The genetic analysis showed the presence of the c.2242T>A, p.(Phe748Ile) variant in the AR gene. To the best of our knowledge, this variant has not been published so far. Furthermore, the patient has a heterozygous c.317A>G, p.(Gln106Arg) variation of the gonadotropin-releasing hormone receptor (GNRHR) gene, a heterozygous c.2273G>A, p.Arg758His variation of the chromodomain helicase DNA binding protein 7 (CHD7) gene, and compound heterozygous c.875A>G, p.Tyr292Cys, and c.8023A>G, p.Ile2675Val variations of the Dynein Axonemal Heavy Chain 11 (DNAH11) gene. Conclusions: The case herein reported underlines the importance of an accurate genetic analysis that has to include karyotype and AR gene variant analysis. This is useful to confirm a clinical diagnosis and establish the proper management of patients with CAIS. Numerous variants of the AR gene have not yet been identified. Moreover, several pitfalls are still present in the management of these patients. More studies are needed to answer unresolved questions, and common protocols are required for the clinical follow-up of patients with CAIS.

Seminal Plasma Transcriptome and Proteome: Towards a Molecular Approach in the Diagnosis of Idiopathic Male Infertility.

As the "-omic" technology has largely developed, its application in the field of medical science seems a highly promising tool to clarify the etiology, at least in part, of the so-called idiopathic male infertility. The seminal plasma (SP) is made-up of secretions coming from the male accessory glands, namely epididymis, seminal vesicles, and prostate. It is not only a medium for sperm transport since it is able to modulate the female reproductive environment and immunity, to allow the acquisition of sperm competence, to influence the sperm RNA content, and even embryo development. The aim of this systematic review was to provide an updated and comprehensive description of the main transcripts and proteins reported by transcriptome and proteome studies performed in the human SP of patients with idiopathic infertility, in the attempt of identifying possible candidate molecular targets. We recurrently found that micro RNA (miR)-34, miR-122, and miR-509 are down-regulated in patients with non-obstructive azoospermia (NOA) and oligozoospermia compared with fertile controls. These molecules may represent interesting targets whose predictive role in testicular sperm extraction (TESE) or assisted reproductive techniques (ART) outcome deserves further investigation. Furthermore, according to the available proteomic studies, ECM1, TEX101, lectingalactoside-binding andsoluble 3 binding protein (LGALS3BP) have been reported as accurate predictors of TESE outcome. Interestingly, ECM1 is differently expressed in patients with different ART outcomes. Further prospective, ample-sized studies are needed to validate these molecular targets that will help in the counseling of patients with NOA or undergoing ART.

Seminal Plasma Proteomic Biomarkers of Oxidative Stress.

The prevalence of idiopathic male infertility is high, up to 75% of patients with abnormal sperm parameters. Hence, the research of its causes is mandatory. Oxidative stress (OS) can be responsible for male infertility in 30-80% of cases. In recent years, seminal plasma (SP) proteomics has developed as a useful tool to provide biomarkers of specific diseases. This systematic review aims to collect the available evidence on the changes of SP proteome in patients exposed to OS to provide possible SP biomarkers of sperm OS. To accomplish this, the following keyterms "seminal fluid proteome", "seminal plasma proteome", "oxidative stress", and "sperm oxidative stress" were used and 137 records were found. Among these, 17 were finally included. Nine proteins involved with OS were found overexpressed in patients with OS. Twenty-three proteins were found differentially expressed in patients with clinical conditions associated with OS, such as varicocele, male accessory gland infection/inflammation, cigarette smoke, and obesity. These proteins do not seem to overlap among the clinical conditions taken into account. We speculate that specific SP proteins may mediate OS in different clinical conditions. Altogether, these results suggest that proteomics could help to better understand some of the molecular mechanisms involved in the pathogenesis of infertility. However, further studies are needed to identify potential biomarkers of male infertility with valuable clinical significance.

Impact of COVID-19 on testicular function: a systematic review and meta-analysis.

INTRODUCTION: Studies investigating the effects of SARS-CoV-2 on male reproductive function are few and heterogeneous, and results are often conflicting. This systematic review and meta-analysis was carried out on studies conducted in men with active or anamnestic SARS-CoV-2 infection to evaluate its consequences on the male sex hormone profile and semen parameters. MATERIALS AND METHOD: This meta-analysis follows the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. PubMed, Scopus, Cochrane, and Embase databases were searched to identify relevant studies. We originally selected 3553 articles. After the eligibility phase, 16 articles met our inclusion criteria encompassing 11 case-control studies and 5 cohort studies (2 prospective and 3 retrospective studies). We performed the quantitative analysis with Comprehensive Meta-Analysis Software. Cochran-Q and heterogeneity (I2) indexes were used to assess statistical heterogeneity. Sensitivity analysis and publication bias tests were also performed. RESULTS: Overall, 1250 patients with active or recent (up to 80 days before) COVID-19 infection and 1232 matched healthy controls were included. Sperm concentration, total sperm count, and total motility were significantly lower in patients compared with controls. Patients also showed lower levels of total testosterone and follicle-stimulating hormone, and higher levels of luteinizing hormone, 17ß-estradiol, and prolactin compared with healthy controls. None of the included studies found the presence of SARS-CoV-2 mRNA in the semen of infected patients. CONCLUSION: The present systematic review and meta-analysis suggests the presence of an association between SARS-CoV-2 infection and primary testicular damage manifested with a picture of altered steroidogenesis and worsening spermatogenesis. The absence of the virus in the seminal fluid indicates a low possibility of sexual transmission of the infection to partners and offspring. However, our findings mostly show short-term follow-up, while few studies have considered the long-term consequences of the viral infection, thus further studies are needed to evaluate the long-term consequences on male reproductive health.

Obesity and male fertility disorders.

Often associated with obesity, male infertility represents a widespread condition that challenges the wellbeing of the couple. In this article, we provide a comprehensive and critical analysis of studies exploring the association between obesity and male reproductive function, to evaluate the frequency of this association, and establish the effects of increased body weight on conventional and biofunctional sperm parameters and infertility. In an attempt to find possible molecular markers of infertility in obese male patients, the numerous mechanisms responsible for infertility in overweight/obese patients are reviewed in depth. These include obesity-related functional hypogonadism, insulin resistance, hyperinsulinemia, chronic inflammation, adipokines, irisin, gut hormones, gut microbiome, and sperm transcriptome. According to meta-analytic evidence, excessive body weight negatively influences male reproductive health. This can occurr through a broad array of molecular mechanisms. Some of these are not yet fully understood and need to be further elucidated in the future. A better understanding of the effects of metabolic disorders on spermatogenesis and sperm fertilizing capacity is very useful for identifying new diagnostic markers and designing therapeutic strategies for better clinical management of male infertility.

New Insights of Target Therapy: Effects of Tyrosine Kinase Inhibitors on Male Gonadal Function: A Systematic Review.

The number of cancer patients undergoing chronic treatment with target therapy is increasing. Although much is known about the toxicity of conventional anticancer therapies, evidence on the effects of tyrosine kinase inhibitors (TKIs) on fertility is still lacking. Therefore, this review was undertaken to evaluate the effects of TKIs on male gonadal function. A comprehensive search of PubMed and Scopus databases was conducted, focusing on the effects of TKIs on spermatogenesis and testicular endocrine function. We included animal studies, observational studies, and case reports published up to December 31, 2023. Identified articles were reviewed and analyzed to evaluate the impact of TKIs on the male gonad. Their long-term effects, the reversibility of the observed changes, and the underlying molecular mechanisms involved were recorded. The findings emerging on the effects of TKIs on male gonadal function are conflicting. Although specific TKIs (imatinib, gefitinib, sorafenib, sunitinib, quizartinib, dasatinib, and nilotinib) have been identified as potentially as potential interfering with spermatogenesis and hormone production, the extent and severity of these effects may vary from patient to patient and between different drugs within this drug class. Experimental studies on mouse models have suggested a potential interference with spermatogenesis. Evidence also suggests that TKIs affects the hypothalamic-pituitary-testicular axis, decreasing serum testosterone and gonadotropin levels. The effects of TKIs on male gonadal function highlight the need for personalized treatment choices. Potential fertility concerns can help minimize adverse effects and improve patient outcomes. Addressing the potential impact of TKIs on male fertility helps optimize cancer treatment and survival outcomes.

Predictive parameters of the efficacy of varicocele repair: a review.

ABSTARCT: Varicocele has a prevalence of 15% in the population and represents a primary cause of infertility in 40% of cases and a secondary cause in approximately 80% of cases. It is considered the major correctable cause of male infertility. Despite its high prevalence in the infertile population, a large number of patients with varicocele do not experience reproductive difficulties. For this reason, it is still highly debated which parameters could be used to predict which patients with varicocele will be most likely to benefit from its repair. The main international and European guidelines state that treatment should only be considered in infertile patients with abnormal sperm quality. However, these guidelines do not help physicians to identify which of these patients may benefit from the treatment. Therefore, this narrative review collects the evidence in the literature on the usefulness of some factors as predictors of improvement, highlighting how some of them may be effective in an initial selection of patients to be treated, while others are promising but further studies are needed. Finally, a brief consideration on the possible role of artificial intelligence is proposed.

In-Vitro Effects of Perfluorooctanoic Acid on Human Sperm Function: What Are the Clinical Consequences?

Background: Lifestyle and environmental pollution harm male fertility. Perfluoroalkyl substances (PFAS) are bio-accumulates in the environment as well as in several human tissues, and one of the most common PFAS is perfluorooctanoic acid (PFOA). Therefore, this study aimed to evaluate the in vitro effects of PFOA with hydrophobic and waterproofing properties on motility and bio-functional sperm parameters. Methods: To accomplish this, 50 healthy men with normozoospermia and not exposed to high doses of PFAS were enrolled. Their spermatozoa were incubated for 3 h with increasing concentrations of PFOA (0, 0.01, 0.1, and 1 mM) to evaluate its effects. In particular, we evaluated the effects of PFOA on total and progressive sperm motility and, by flow cytometry, on the following bio-functional sperm parameters: degree of chromatin compactness, viability, early and late apoptosis, mitochondrial membrane potential, the degree of lipoperoxidation, and concentrations of mitochondrial superoxide anion. Results: The results showed that PFOA decreased both total and progressive sperm motility, impaired chromatin compactness, and increased sperm lipid peroxidation and mitochondrial superoxide anion levels. Conclusions: This study showed that PFOA alters several sperm parameters and thus it may play a negative role in male fertility.

Antioxidants for male infertility: therapeutic scheme and indications. A retrospective single-center real-life study.

BACKGROUND: This single-center real-life study was conducted to evaluate the most effective combination of nutraceuticals and the most appropriate indications for the treatment of male infertile patients. METHODS: Infertile patients aged 20-55 years were treated with a combination of antioxidants (Androlen®; Enfarma, Misterbianco, Catania, Italy) (group A), with Androlen® (Enfarma) and a mixture of fibrinolytic molecules (Lenidase®, Enfarma) (group B), or Androlen® (Enfarma) and other molecules different from those used for the patients of the group B (group C). Patients were also subdivided according to the presence of varicocele, mild testicular hypotrophy, idiopathic infertility, and chronic male accessory gland infection. RESULTS: Forty-three patients were enrolled. In the overall analysis, only progressive motility significantly improved after therapy. Subgroup analysis showed a significant increase in progressive motility, total motile sperm count (TMSC), and in the percentage of alive spermatozoa after treatment in the group A. Progressive motility improved significantly in patients with varicocele, while the TMSC in patients with varicocele and those with idiopathic infertility. The percentage of alive spermatozoa increased in patients with testicular hypotrophy. CONCLUSIONS: Treatment with antioxidants increased progressive sperm motility, especially in patients with varicocele or idiopathic infertility.

Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study of Before-After Data.

PURPOSE: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. MATERIALS AND METHODS: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). RESULTS: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864. CONCLUSIONS: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele.

Globozoospermia: A Case Report and Systematic Review of Literature.

PURPOSE: Globozoospermia is a genetic syndrome characterized by the presence of round-headed spermatozoa and infertility due to the inability of these spermatozoa to fertilize the oocyte. In this article, we present the clinical case of a young globozoospermic patient with a new, not yet described mutation of the DPY19L2 gene. We also performed a systematic review of the literature on gene mutations, the outcome of assisted reproductive techniques, and the risk of transmission of abnormalities to the offspring in patients with globozoospermia and made recommendations to offer a more appropriate clinical management of these patients. MATERIALS AND METHODS: We performed a systematic search in the PubMed, Google Scholar, and Scopus databases from their inception to December 2021. The search strategy included the combination of the following Medical Subjects Headings (MeSH) terms and keywords: "globozoospermia", "round-headed spermatozoa", "round head spermatozoa", "intracytoplasmic sperm injection", "ICSI", "offspring", "child health", "assisted reproductive technique outcome". All the eligible studies were selected following the PECOS (Population, Exposure, Comparison/Comparator, Outcomes, Study design) model. The quality of included studies was assessed by applying the "Cambridge Quality Checklists". RESULTS: The main genes involved in the pathogenesis of globozoospermia are DPY19L2, SPATA16, PICK1, GGN, SPACA1, ZPBP, CCDC62, and CCNB3 genes. Other genes could also play a role. These include C2CD6, C7orf61, CCIN, DNH17, DNH6, PIWIL4, and CHPT1. Globozoospermic patients should undergo ART to achieve fertility. In particular, intracytoplasmic sperm injection with assisted oocyte activation or intracytoplasmic morphologically-selected sperm injection appears to be associated with a higher success rate. Patients with globozoospermia should also be evaluated for the high rate of sperm aneuploidy which appears to influence the success rate of ART but does not appear to be associated with an increased risk of transmission of genetic abnormalities to offspring. CONCLUSIONS: This systematic review summarizes the evidence on the gene panel to be evaluated, ICSI outcomes, and the health of the offspring in patients with globozoospermia. Evidence-based recommendations on the management of patients with globozoospermia are provided.

Productivity Index in Clinical Andrology: Research Directions on High-Impact Topics and in Particular on Male Infertility.

PURPOSE: Andrological diseases have an important social and economic impact as they cause a serious impairment of the quality of life of the affected patient. Epidemiologically, the impact of these disorders is progressively increasing, as demonstrated by the ever-growing prevalence of male infertility. This evidence justifies the rapid development of research in andrology that the scientific community has undertaken in recent decades. This study aims to evaluate the productivity index of the main andrological topics studied and reported in the literature. METHODS: The total number of published articles was extracted from the Scopus database by entering the following keywords and mesh terms: "Male Infertility", "Erectile Dysfunction", "Premature Ejaculation", "Male Hypogonadism", "Testicular Tumors", "Prostate Cancer", "Prostatic hyperplasia", "Prostate hyperplasia", "Prostatitis", "Prostate inflammation", and "Male Accessory Gland Infections". Furthermore, a list of the top 50 researchers sorted by productivity was created for each topic. For male infertility, a further search was performed by combining the search term "male infertility" with the above-mentioned terms. Thus, a list of the top 30 authors in order of productivity was also extracted. The graphs were created using Excel. RESULTS AND CONCLUSIONS: As could be expected, we observed that prostate cancer and male infertility were the two most investigated topics, followed by benign prostatic hyperplasia and erectile dysfunction, whose prevalence is set to increase given the progressive aging of the population. Less investigated is the inflammation of the accessory sexual glands. In conclusion, this study provides a ranking of the main andrological topics investigated in the literature, also presenting the top list of the most productive authors for each one.

Mechanisms Suggesting a Relationship between Vitamin D and Erectile Dysfunction: An Overview.

Vitamin D deficiency (VDD) and erectile dysfunction (ED) heavily burden the male population. The higher prevalence of both conditions in the elderly suggests a possible relationship between the two conditions. In addition, in vitro, animal, and human studies have revealed several mechanisms that may relate VDD to ED. The main mechanism by which vitamin D might exert its action on sexual function appears to be through the regulation of endothelial function. Indeed, VDD correlates with several markers of endothelial function. The action of vitamin D on the endothelium would be exercised both indirectly through its intervention in inflammatory processes and through the production of oxygen free radicals, and directly through the regulation of vascular stiffness, the production of nitric oxide, and the regulation of vessel permeability. Furthermore, the ubiquitous distribution of the vitamin D receptor in the human body means that this hormone can also exert a beneficial effect on erectile function by interfering with those comorbidities significantly associated with ED, such as hypertension, diabetes mellitus, hypercholesterolemia, chronic kidney disease, and hypogonadism. In this review, we thoroughly and carefully presented the evidence and mechanisms that would appear to relate vitamin D levels to erectile function. Furthermore, we have summarized the meta-analytic evidence for and against this association to provide a true representation of this topic. Data published to date suggest that low levels of vitamin D could contribute to worsening erectile function through several mechanisms. Therefore, vitamin D levels should be measured in patients with ED and maintained at adequate levels by specific supplementation in case of deficiency. However, the low quality and heterogeneity of clinical trials evaluating the effects of vitamin D administration on erectile function and ED-associated comorbidities do not allow for a univocal conclusion, and indicate the need for further studies to analyze these aspects.

Red Wine and Sexual Function in Men: An Original Point of View.

Red wine is a rich source of nutrients whose biological properties have inspired numerous scientific studies. Indeed, it has been widely reported that there is a correlation between the positive health effects of moderate consumption of red wine and its phenolic content, which, due to its antioxidant activity, has proved to be useful in the improvement of various diseases, such as cardiovascular diseases, metabolic syndrome, cognitive disorders, depression, and cancer. It is a common opinion that the antioxidant activity of red wine is to be ascribed to its entire content of polyphenols, which act synergistically and not as a single component. Furthermore, this health-promoting effect of red wine can also be linked to its ethanol content, which has shown a wide array of biological properties. Beyond this evidence, very little is known about a possible correlation between moderate consumption of red wine and male sexual function. This brief review aimed to evaluate the effects of moderate consumption of red wine on erectile function. To accomplish this, Pubmed and Google Scholar databases were searched to retrieve the most relevant studies on this topic. The evidence so far collected has shown that red wine, if consumed in moderation, can be potentially beneficial for patients with erectile dysfunction as well as can positively influence reproductive function through mechanisms that depend on the vasorelaxant properties of red wine and its antioxidant properties.

The Impact of a Very Short Abstinence Period on Assisted Reproductive Technique Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous studies supported the beneficial effects of a very short abstinence period on sperm quality. This systematic review and meta-analysis aimed to evaluate the effects of a very short abstinence period (within 4 h) on assisted reproductive technique (ART) outcomes. METHODS: A literature search was performed using the Pubmed, Scopus, Web of Science, and Cochrane databases. A meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) for randomized controlled trials (RCTs). All eligible studies were selected following the PICOS (Population, Intervention, Comparison/Comparator, Outcomes, Study type) model. The following pregnancy outcomes after ART were considered: fertilization rate (FR), implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate (MR). This study was registered on PROSPERO (CRD42023396429). RESULTS: We evaluated 414 records for eligibility, and 7 studies were ultimately included. Our analysis showed that a very short abstinence period significantly increased the IR, CPR, and LBR after ART. No significant differences were found for the FR and MR. CONCLUSIONS: A second ejaculation collected very shortly after the first one could represent a simple strategy to improve the results of ART, especially in couples including patients with abnormal sperm parameters.

Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis.

ABSTRACT: To evaluate the relationship between testosterone replacement therapy (TRT) and arterial and/or venous thrombosis in patients with pre-treatment total testosterone (TT) <12 nmol l-1, we performed a meta-analysis following the Population Intervention Comparison Outcome model. Population: men with TT <12 nmol l-1 or clear mention of hypogonadism in the inclusion criteria of patients; intervention: TRT; comparison: placebo or no therapy; outcomes: arterial thrombotic events (stroke, myocardial infarction [MI], upper limbs, and lower limbs), VTE (deep vein thrombosis [DVT], portal vein thrombosis, splenic thrombosis, and pulmonary embolism), and mortality. A total of 2423 abstracts were assessed for eligibility. Twenty-four studies, including 14 randomized controlled trials (RCTs), were finally included, with a total of 4027 and 310 288 hypotestosteronemic male patients, from RCTs and from observational studies, respectively. Based on RCT-derived data, TRT did not influence the risk of arterial thrombosis (odds ratio [OR] = 1.27, 95% confidence interval [CI]: 0.47-3.43, P = 0.64), stroke (OR = 1.34, 95% CI: 0.09-18.97, P = 0.83), MI (OR = 0.51, 95% CI: 0.11-2.31, P = 0.39), VTE (OR = 1.42, 95% CI: 0.22-9.03, P = 0.71), pulmonary embolism (OR = 1.38, 95% CI: 0.27-7.04, P = 0.70), and mortality (OR = 0.70, 95% CI: 0.20-2.38, P = 0.56). Meanwhile, when only observational studies are considered, a significant reduction in the risk of developing arterial thrombotic events, MI, venous thromboembolism, and mortality was observed. The risk for DVT remains uncertain, due to the paucity of RCT-based data. TRT in men with TT <12 nmol l-1 is safe from the risk of adverse cardiovascular events. Further studies specifically assessing the risk of DVT in men on TRT are needed.