Human sperm RNA in male infertility.

The function and value of specific sperm RNAs in apparently idiopathic male infertility are currently poorly understood. Whether differences exist in the sperm RNA profile between patients with infertility and fertile men needs clarification. Similarly, the utility of sperm RNAs in predicting successful sperm retrieval and assisted reproductive technique (ART) outcome is unknown. Patients with infertility and fertile individuals seem to have differences in the expression of non-coding RNAs that regulate genes controlling spermatogenesis. Several RNAs seem to influence embryo quality and development. Also, RNA types seem to predict successful sperm retrieval in patients with azoospermia. These findings suggest that sperm RNAs could influence decision-making during the management of patients with infertility. This evidence might help to identify possible therapeutic approaches aimed at modulating the expression of dysregulated genes in patients with infertility. Performing prospective studies with large sample sizes is necessary to investigate cost-effective panels consisting of proven molecular targets to ensure that this evidence can be translated to clinical practice.

Predictability of varicocele repair success: preliminary results of a machine learning-based approach.

Varicocele is a prevalent condition in the infertile male population. However, to date, which patients may benefit most from varicocele repair is still a matter of debate. The purpose of this study was to evaluate whether certain preintervention sperm parameters are predictive of successful varicocele repair, defined as an improvement in total motile sperm count (TMSC). We performed a retrospective study on 111 patients with varicocele who had undergone varicocele repair, collected from the Department of Endocrinology, Metabolic Diseases and Nutrition, University of Catania (Catania, Italy), and the Unit of Urology at the Selcuk University School of Medicine (Konya, Türkiye). The predictive analysis was conducted through the use of the Brain Project, an innovative tool that allows a complete and totally unbiased search of mathematical expressions that relate the object of study to the various parameters available. Varicocele repair was considered successful when TMSC increased by at least 50% of the preintervention value. For patients with preintervention TMSC below 5 × 106, improvement was considered clinically relevant when the increase exceeded 50% and the absolute TMSC value was >5 × 106. From the preintervention TMSC alone, we found a model that predicts patients who appear to benefit little from varicocele repair with a sensitivity of 50.0% and a specificity of 81.8%. Varicocele grade and serum follicle-stimulating hormone (FSH) levels did not play a predictive role, but it should be noted that all patients enrolled in this study were selected with intermediate- or high-grade varicocele and normal FSH levels. In conclusion, preintervention TMSC is predictive of the success of varicocele repair in terms of TMSC improvement in patients with intermediate- or high-grade varicoceles and normal FSH levels.

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

ABSTRACT: 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.

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.

Lifestyle and sexual habits of students in a Southern Italian region.

BACKGROUND: Incorrect or harmful lifestyle during youth may impact negatively gonadal function later in life. To reduce the development of risky behaviors a series of health prevention and intervention campaigns have been conducted in Italy. The present study is part of a Sicily Region (Italy) health surveillance program that was carried out on a sample of late adolescents. METHODS: Between March 2022 to December 2022, we enrolled 718 adolescents (15-26 years old) attending the last two years of high school (278 males and 440 females) in the districts of Syracuse, Ragusa, Catania, and Agrigento (Sicily, Italy). All adolescents were invited to complete a questionnaire that explored their lifestyles and the student's knowledge of sexually transmitted diseases (STDs) and the main andrological diseases. RESULTS: Our analysis revealed that 43% of students smoke cigarettes, with a similar gender distribution; one-third of the students use illicit drugs, with a higher prevalence of males than females. More than two-thirds of youngsters reported drinking alcohol with a statistically significant difference between genders. 68.2% of students do not have sexual difficulties and males have a greater tendency to sexual promiscuity than females and only about half of them use condoms. 92% of students surf the Internet every day; boys tend to visit pornographic sites more often than girls. CONCLUSIONS: This survey revealed statistically significant differences between the two genders in terms of lifestyle and sexual habits. In particular, the survey shows that the prevalence of risky behaviour is still extremely high among late adolescents and young adults and that much still needs to be done in terms of prevention and information. Adequate prevention campaigns, to be proposed in the early years of adolescence, should be initiated in order to provide youngsters with adequate preparation in terms of healthy lifestyle habits.

DNA Methylation in Offspring Conceived after Assisted Reproductive Techniques: A Systematic Review and Meta-Analysis.

Background: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate whether ART is associated with epigenetic dysregulation in the offspring. Methods. To accomplish this, we collected all available data on methylation patterns in offspring conceived after ART and in spontaneously conceived (SC) offspring. Results. We extracted 949 records. Of these, 50 were considered eligible; 12 were included in the quantitative synthesis. Methylation levels of H19 CCCTC-binding factor 3 (CTCF3) were significantly lower in the ART group compared to controls (SMD -0.81 (-1.53; -0.09), I2 = 89%, p = 0.03). In contrast, H19 CCCTC-binding factor 6 (CTCF6), Potassium Voltage-Gated Channel Subfamily Q Member 1 (KCNQ1OT1), Paternally-expressed gene 3 (PEG3), and Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) were not differently methylated in ART vs. SC offspring. Conclusion: The methylation pattern of the offspring conceived after ART may be different compared to spontaneous conception. Due to the lack of studies and the heterogeneity of the data, further prospective and well-sized population studies are needed to evaluate the impact of ART on the epigenome of the offspring.

The Use of Ellagic Acid and Annona Muricata Improves Semen Quality in Men with High-Risk Papillomavirus Infection.

Background: Few data are currently available on the treatment of patients with HPV infection. In particular, there is no agreement on the use of antioxidants in these patients. Ellagic acid and annona muricata appear to improve HPV clearance in infected women. However, it is presently unknown whether they could enhance the clearance of HPV infection in infertile male patients. Aim: To evaluate the effects of a commercially available combined compound containing ellagic acid and annona muricata on semen quality in patients with documented papillomavirus (HPV) infection, and on the frequency of HPV DNA detection in seminal fluid after treatment. In addition, anti-sperm antibodies and the percentage of spermatozoa with fragmented DNA were evaluated. Materials and methods: This was a retrospective case-control study including patients attending our center for infertility. Fifty selected patients who were positive for high risk (HR)-HPV with available semen analysis results were consecutively enrolled. Patients were classified into two groups, according to the clinician's decision to either administer ellagic acid 100 mg and annona muricata 100 mg (combined tablet formulation) for a period of three months (Group A; 25 patients), or to re-evaluate HPV DNA after a period of active surveillance only (protected sexual intercourse) (Group B; 25 patients). Results: Group A patients had a mean age of 31.0 ± 11.0 years, while Group B was 33.0 ± 8.0 years old (p > 0.05). After three months of treatment with ellagic acid and annona muricata, all conventional seminal parameters improved more significantly in Group A than in Group B patients: sperm concentration = 45 mil/mL vs. 20 mil/mL (p < 0.05); sperm progressive motility = 45% vs. 18% (p < 0.05); and normal sperm morphology = 18% vs. 6% (p < 0.05). After the treatment, the frequency of persistence of HPV DNA in the seminal fluid was significantly lower in Group A patients compared to those in Group B (12/25 = 48% vs. 22/25 = 88%; p < 0.05). Finally, after 3 months, Group A showed a significant reduction in anti-sperm antibodies and in the percentage of spermatozoa with fragmented DNA. Conclusion: The results of this study demonstrate, for the first time, the effects of a commercially available combined compound containing ellagic acid and annona muricata on semen quality in patients with HR-HPV infection, and that this therapy is also associated with a significant reduction in the persistence of HPV DNA in the seminal fluid.

Examples of Inverse Comorbidity between Cancer and Neurodegenerative Diseases: A Possible Role for Noncoding RNA.

Cancer is one of the most common causes of death; in parallel, the incidence and prevalence of central nervous system diseases are equally high. Among neurodegenerative diseases, Alzheimer's dementia is the most common, while Parkinson's disease (PD) is the second most frequent neurodegenerative disease. There is a significant amount of evidence on the complex biological connection between cancer and neurodegeneration. Noncoding RNAs (ncRNAs) are defined as transcribed nucleotides that perform a variety of regulatory functions. The mechanisms by which ncRNAs exert their functions are numerous and involve every aspect of cellular life. The same ncRNA can act in multiple ways, leading to different outcomes; in fact, a single ncRNA can participate in the pathogenesis of more than one disease-even if these seem very different, as cancer and neurodegenerative disorders are. The ncRNA activates specific pathways leading to one or the other clinical phenotype, sometimes with obvious mechanisms of inverse comorbidity. We aimed to collect from the existing literature examples of inverse comorbidity in which ncRNAs seem to play a key role. We also investigated the example of mir-519a-3p, and one of its target genes Poly (ADP-ribose) polymerase 1, for the inverse comorbidity mechanism between some cancers and PD. We believe it is very important to study the inverse comorbidity relationship between cancer and neurodegenerative diseases because it will help us to better assess these two major areas of human disease.

Advances in non-hormonal pharmacotherapy for the treatment of male infertility: the role of inositols.

INTRODUCTION: Several antioxidants are available for the treatment of male infertility. Although the benefit of myo-inositol (MYO) and D-chiro-inositol (DCI) for female infertility is recognized, their role in male infertility is a matter of debate. AREAS COVERED: The authors review the impact that treatment with MYO and/or DCI may have on conventional and bio-functional sperm parameters [mitochondrial membrane potential (MMP), sperm chromatin compactness, and sperm DNA fragmentation (SDF)], seminal oxidative stress (OS), and pregnancy, miscarriage, and live birth rates, and the possible mechanisms involved. Furthermore, the authors gather evidence on the effects of MYO and/or DCI on sperm function in vitro. EXPERT OPINION: MYO can improve sperm count, motility, capacitation, acrosome reaction, and MMP. No data are currently available on the effects of DCI in vivo. Both MYO and DCI ameliorate sperm motility and MMP in vitro. Therefore, the use of inositols should be preferred in patients with idiopathic asthenozoospermia, especially in case of impaired sperm mitochondrial function. Due to their insulin-sensitizing action, a role for these molecules may be envisaged for the treatment of infertility caused by carbohydrate metabolism derangement.

Beneficial Effects of the Very-Low-Calorie Ketogenic Diet on the Symptoms of Male Accessory Gland Inflammation.

Introduction. Obesity exposes individuals to the risk of chronic inflammation of the prostate gland. Aim and design of the study. A longitudinal clinical study was conducted on selected overweight/obese patients with male accessory gland inflammation (MAGI) to evaluate the effects of body weight loss on their urogenital symptoms. Materials and methods. One hundred patients were selected and assigned to two groups undergoing two different nutritional programs. The first group (n = 50) started a Mediterranean diet (MedDiet) and the second (n = 50) a very-low-calorie ketogenic diet (VLCKD). Before and after three months on the diet, each patient was evaluated for body weight, waist circumference, and MAGI symptoms. The MAGI was assessed using the Structured Interview about MAGI (SI-MAGI), a questionnaire previously designed to assess the symptoms of MAGI. The questionnaire explores four domains, including urinary symptoms, ejaculatory pain or discomfort, sexual dysfunction, and impaired quality of life. Finally, in the two groups, the frequency of an α-blocker used to treat urinary tract symptoms was also evaluated. Results. Patients on MedDiet experienced significant amelioration in urinary symptoms and quality of life. Patients under VLCKD reported not only significant improvement of the same parameters, but also in ejaculatory pain/discomfort and sexual dysfunction. Finally, the percentage of patients on VLCKD taking the α-blocker decreased significantly. Moreover, patients under VLCKD showed a greater loss of body weight than those following the MedDiet. Discussion. The results of this study support the effectiveness of VLCKD in improving the symptoms of patients with MAGI. This improvement involved all of the domains of the SI-MAGI questionnaire and became manifest in a relatively short time. We suggest that a ketogenic nutritional approach can be used in overweight/obese patients with MAGI.

Obesity and Male Reproduction: Do Sirtuins Play a Role?

Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years.

Testosterone replacement therapy in hypogonadal male patients with hypogonadism and heart failure: a meta-analysis of randomized controlled studies.

INTRODUCTION: The recently published guidelines of the European Academy of Andrology (EAA) recommended not to prescribe testosterone replacement therapy (TRT) in male patients with hypotestosteronemia and severe heart failure (HF) [New York Hearth Association (NYHA) class III and IV] since the risk in these patients has not been formally documented. Therefore, the aim of this study was to systematically evaluate the risk of TRT on the cardiac function and angina, in male patients with hypotestosteronemia and HF or coronary heart disease. EVIDENCE ACQUISITION: Randomized controlled trials (RCTs) on male patients with hypotestosteronemia and chronic HF (ejection fraction <40%) or stable angina documenting the effect of TRT on NYHA class, left ventricular ejection fraction (LVEF), adverse events, ST depression and other indexes of cardiovascular function. EVIDENCE SYNTHESIS: Seven articles were included, for a total of 140 participants with HF (71 on TRT and 69 on placebo or no treatment). Included patients were of NYHA class II and III. TRT had no effect on death and rehospitalization rates of patients with HF and significantly delayed the time to ischemia in patients with chronic angina. TRT had no effect on the NYHA class, the LVEF, and on the Minnesota Living with Heart Failure questionnaire. Although a significant increase of oxygen consumption was found in the TRT group, no improvement to the physical exercise tolerance tests was observed. TRT showed no effect on systolic nor diastolic blood pressure, but it significantly ameliorated the heart rate. It significantly decreased the insulin serum levels and the HOMA index. CONCLUSIONS: These results suggest the safety of TRT, in patients with hypotestosteronemia and severe HF (class NYHA II and III). Although deriving from a limited number of studies, these data could prompt to perform other RCTs on the effects of TRT in patients with hypotestosteronemia and severe HFrEF (NYHA class III).

Molecular Mechanisms Underlying the Relationship between Obesity and Male Infertility.

In recent decades, the worldwide prevalence of obesity has risen dramatically and is currently estimated to be around 20%. Obesity is linked to an increased risk of comorbidities and premature mortality. Several studies have shown that obesity negatively impacts male fertility through various mechanisms. This review aims to investigate the molecular mechanisms through which obesity impairs male reproduction, including obesity-associated hypogonadism and its effects on spermatogenesis, chronic inflammation, and oxidative stress. Obesity negatively impacts both conventional and biofunctional sperm parameters, and it also induces epigenetic changes that can be transferred to offspring. Moreover, obesity-related diseases are linked to a dysregulation of adipocyte function and micro-environmental inflammatory processes. The dysregulated adipokines significantly influence insulin signaling, and they may also have a detrimental effect on testicular function. Sirtuins can also play an important role in inflammatory and metabolic responses in obese patients. Understanding the molecular mechanisms that are involved in obesity-induced male infertility could increase our ability to identify novel targets for the prevention and treatment of obesity and its related consequences.

Corrigendum to: Influence of 25­hydroxy-cholecalciferol levels on SARS-CoV-2 infection and COVID-19 severity: A systematic review and meta-analysis [EClinicalMedicine 37 (2021) 100,967].

[This corrects the article DOI: 10.1016/j.eclinm.2021.100967.].

Very-low-calorie ketogenic diet: An alternative to a pharmacological approach to improve glycometabolic and gonadal profile in men with obesity.

Obesity and metabolic diseases have become a worrying reality, especially in more developed societies. They are associated with the development of many comorbidities, such as type 2 diabetes mellitus, hypogonadism, hypertension, cerebrovascular and cardiovascular diseases, neoplasia, obstructive sleep apnea, and non-alcoholic fatty liver disease. Therefore, weight loss is of paramount importance. A promising therapeutic option to achieve this goal is the very-low-calorie ketogenic diet. This review aims to summarize the main effects of very-low-calorie-ketogenic diet on the glycometabolic and gonadal profiles of men with overweight/obesity.

The Burden of Hormonal Disorders: A Worldwide Overview With a Particular Look in Italy.

Endocrine diseases have a considerable impact on public health from an epidemiological point of view and because they may cause long-term disability, alteration of the quality-of-life of the affected patients, and are the fifth leading cause of death. In this extensive review of the literature, we have evaluated the prevalence of the different disorders of endocrine interest in the world and Italy, highlighting their epidemiological, clinical, and economic impact.

Retrospective Monocentric Clinical Study on Male Infertility: Comparison between Two Different Therapeutic Schemes Using Follicle-Stimulating Hormone.

Follicle-stimulating hormone (FSH) is a therapeutic option in patients with idiopathic oligozoospermia and normal FSH serum levels. However, few studies have evaluated which dose of FSH is more effective. The aim of this study was to compare the clinical efficacy of the two most frequently used FSH treatment regimens: 75 IU daily vs. 150 IU three times a week. Patients were retrospectively assigned to two groups. The first group (n = 24) was prescribed highly purified FSH (hpFSH) 75 IU/daily (Group A), and the second group (n = 24) was prescribed hpFSH 150 IU three times a week (Group B) for three months. Before and after treatment, each patient underwent semen analysis, evaluation of the percentage of DNA-fragmented spermatozoa, assessment of testicular volume (by ultrasonography), and measurement of FSH and total testosterone (TT) serum levels. Treatment with hpFSH significantly improved conventional sperm parameters. In detail, sperm concentration increased significantly after treatment only in Group A, whereas total sperm count, percentage of spermatozoa with progressive motility, normal morphology, or alive improved significantly in both groups. Interestingly, the percentage of sperm DNA fragmentation decreased significantly in both groups after treatment with hpFSH. FSH serum levels were expectably higher at the end of the treatment than before hpFSH was administered to both groups. Remarkably, TT serum levels only increased significantly in Group A. Finally, testicular volume was significantly higher in Group A after treatment, while it did not change significantly compared to baseline in Group B. The percentage of FSH responders did not differ significantly between the two groups (8/24 vs. 6/24). The daily administration of hpFSH 75 IU seems more effective than using 150 IU three times a week. However, this therapeutic scheme implies a higher number of injections and slightly higher costs.

Influence of 25-hydroxy-cholecalciferol levels on SARS-CoV-2 infection and COVID-19 severity: A systematic review and meta-analysis.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 19 (COVID-19), a respiratory infection that, starting from December 2019, has spread around the world in a few months, becoming a pandemic. The lack of initial knowledge on its management has led to a great effort in developing vaccines and in finding therapeutic weapons capable of improving the clinical outcome of the affected patients. In particular, the possible role of vitamin D status in the management of COVID-19 has been widely analysed, resulting in a great amount of data. This systematic review and meta-analysis aimed to assess whether hypovitaminosis D is a risk factor for developing SARS-CoV-2 infection and whether it affects the worsening of the clinical course of COVID-19. METHODS: Data were extracted through extensive searches in the Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases from December 2019 to January 2021, using the keywords: "Vitamin D", "25 hydroxy Vitamin D", "25 hydroxycholecalciferol", "cholecalciferol", "COVID 19″, "SARS-CoV-2″. We included observational cohort, cross-sectional, and case-control studies that evaluated differences in serum levels of 25­hydroxy-cholecalciferol [25(OH)D] in patients who were positive or negative for SARS-CoV-2, in patients with mild or severe forms of COVID-19, and in patients who died or were discharged from the hospital. Finally, studies that evaluated the risk of developing severe illness or death in patients with vitamin D deficiency (VDD), defined as levels of 25(OH)D <20 ng/ml, were also included. We calculated the mean difference (MD) and the 95% confidence intervals (CI) for quantitative variables such as 25(OH)D levels in patients with or without SARS-CoV-2 infection, in those with mild vs. severe COVID-19, or those who have died vs. those who have been discharged. Instead, we calculated odds ratios and 95% CI for qualitative ones, such as the number of patients with severe illness/death in the presence of VDD vs. those with normal serum 25(OH)D levels. A p-value lower than 0.05 was considered statistically significant. The study was registered on PROSPERO (CRD42021241473). FINDINGS: Out of 662 records, 30 articles met inclusion criteria and, therefore, were included in the meta-analysis. We found that the serum levels of 25(OH)D were significantly lower in patients with SARS-CoV-2 infection than in negative ones [MD -3.99 (-5.34, -2.64); p <0.00001; I2= 95%]. Furthermore, its levels were significantly lower in patients with severe disease [MD -6.88 (-9.74, -4.03); p <0.00001; I2=98%] and in those who died of COVID-19 [MD -8.01 (-12.50, -3.51); p = 0.0005; I2=86%]. Finally, patients with VDD had an increased risk of developing severe disease [OR 4.58 (2.24, 9.35); p <0.0001; I2=84%] but not a fatal outcome [OR 4.92 (0.83, 29.31); p = 0.08; I2=94%]. INTERPRETATION: This meta-analysis revealed a large heterogeneity of the studies included due to the different enrolment criteria of patient samples (age, body mass index, ethnicity, comorbidities), the country where they live, all factors influencing serum 25(OH)D levels, and the different criteria used to define the severity of COVID-19. Furthermore, the observational nature of these studies does not allow to establish a cause-effect relationship, even taking into account that 25(OH)D represents a marker of acute inflammation. Treatment with vitamin D might be considered for the primary prevention of SARS-CoV-2 infection and the management of patients with COVID-19. However, further intervention studies are needed to prove this hypothesis.

Relevance of sperm imprinted gene methylation on assisted reproductive technique outcomes and pregnancy loss: a systematic review.

Recent evidence suggests that gamete-imprinted genes play a role in embryo and placenta development and growth. This systematic review aimed to evaluate whether altered methylation of sperm-imprinted genes associates with sperm DNA fragmentation (SDF), pregnancy loss rate and assisted reproductive technique (ART) outcome. To accomplish this, Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases were used for search strategy from each database inception until December 2020. Specific keywords were used. Studies satisfying the PECOS (Population, Exposure, Comparison/Comparator, Outcomes, Study design) model were retrieved. Ten studies could be included in the qualitative analysis. A significant association was reported between increased SDF rate and aberrant methylation of H19/IGF2 and KCNQ1 genes by two studies. A significantly lower H19 methylation was found in patients with idiopathic recurrent pregnancy loss (RPL) and in infertile patients compared to fertile men. Methylation of GLT2, PEG1/MEST, and ZAC/PLACL1 were similar in patients with RPL and controls. The ART outcome was similar in patients with aberrant and normal methylation of H19, SNRPN, KCNQ1OT1, PEG1/MEST, LIT1, PEG3, NESPAS, and GLT2. By contrast, a study showed an association between altered GLT2 methylation and more inferior ART results. If further confirmed by well-sized studies, these data might be helpful to identify possible epigenetic predictors of ART outcome. Particularly, aberrant methylation of H19/IGF2 and KCNQ1 genes might represent interesting targets that deserve further investigation.

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.