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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., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. Springer Nature Limited.)

Abstract: 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 × 10 6 , improvement was considered clinically relevant when the increase exceeded 50% and the absolute TMSC value was >5 × 10 6 . 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., (Copyright ©The Author(s)(2024).)

Affecting up to 15% of men worldwide, varicocele has been recognized as a cause of infertility, and its repair is associated with an improvement in conventional and bio-functional sperm parameters. Various surgical and radiological techniques exist for varicocele repair. However, it is unclear which technique is associated with greater clinical efficacy. This retrospective, single-center study aimed to compare the effectiveness of surgical treatment (Ivanissevich technique) versus radiological treatment (sclerotherapy) in a cohort of 94 patients with varicocele. After varicocele repair, a significant increase in sperm concentration was observed only in the group of patients treated with sclerotherapy. A significant reduction in the percentage of patients with oligozoospermia was found in the group of patients treated surgically. Patients undergoing surgical varicocelectomy had increased serum luteinizing hormone (LH) levels, decreased spermatid concentration, and increased percentage of spermatozoa in late apoptosis, probably as a result of surgical traumatism. In conclusion, the results of this study did not show a clear benefit of one technique over the other and confirm the findings of the current literature. However, it remains one of the few on the topic that also considers sperm bio-functional parameters among its outcomes and opens the research up to new considerations on the bio-functional sperm parameters.

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., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

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.

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.

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), I 2 = 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.

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.

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).

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.

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.

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 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.

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.

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., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The ultrasound (US) evaluation of the male sex accessory gland inflammation (MAGI) helps the clinicians to understand the severity of this condition, allowing them to distinguish the uncomplicated form (prostatitis) from the complicated ones (prostate-vesiculitis and prostate-vesiculitis-epididymitis), as well as the unilateral from the bilateral forms, the fibrosclerotic and the hypertrophic-congestive form., Objective: This retrospective study aimed to evaluate the US features of MAGI patients with active symptoms compared to patients without sexual, voiding, and ejaculatory dysfunction., Materials/methods: To achieve this aim, an analysis of the prevalence of MAGI US criteria was carried out on a very large series of over 500 patients diagnosed with MAGI classified according to the different symptom profile evaluated through a dedicated questionnaire (previously conceived and published by our group) arbitrarily named "structured interview about MAGI" (SI-MAGI) for sexual, voiding, and ejaculatory disorders reported by these patients., Results: The results of this study revealed that US criteria most frequently detected in patients with severe urinary symptoms were the presence of areas of high echogenicity (almost exclusively in the periurethral prostatic zone) together with the presence of single or multiple areas of acinar ectasia of the prostate. The presence of seminal vesicles with polycyclic areas within the glandular lumen separated by hyperechoic septa represented US criterion most frequently detected in patients with severe spontaneous or post-ejaculate pain. Finally, US criterion most frequently detected in patients with severe sexual dysfunction was the dilation of the periprostatic venous plexus, suggesting the hypothesis of a possible alternative therapeutic approach., Conclusion: The data of the present study suggest that symptoms may associate with US signs in patients with MAGI. Also, specific US signs may associate with specific symptoms. Further studies are needed to understand whether patients with specific US signs may in turn benefit from a personalized therapeutic choice., (© 2021 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Male accessory gland infection/inflammation (MAGI) is a major cause of male infertility. The importance of ultrasound evaluation in these patients is highly controversial, although evidence of its relevance has increased in recent years. Ultrasound criteria are an important element for confirming the clinical diagnosis. Furthermore, they help to localize the anatomical site or sites of the inflammatory process and in assessing its extension which, in turn, have different consequences on the seminological and symptomatic aspects. This article summarizes the clinical interpretations related to ultrasound aspects in patients with MAGI and the possible effects on the seminological, microbiological, endocrinologic, urological, sexological, and internist aspects., (© 2021 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

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.

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 25‑hydroxy-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; I 2 = 95%]. Furthermore, its levels were significantly lower in patients with severe disease [MD -6.88 (-9.74, -4.03); p <0.00001; I 2 =98%] and in those who died of COVID-19 [MD -8.01 (-12.50, -3.51); p  = 0.0005; I 2 =86%]. Finally, patients with VDD had an increased risk of developing severe disease [OR 4.58 (2.24, 9.35); p <0.0001; I 2 =84%] but not a fatal outcome [OR 4.92 (0.83, 29.31); p  = 0.08; I 2 =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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2021 The Author(s).)

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.

Background: Exposure to metals/metalloids, including essential and nonessential elements, has been associated to male reproductive health in animals. However, findings from human studies are inconsistent., Objectives: To investigate the impact of exposure to multiple metals/metalloids at environmental levels on the conventional human semen-quality parameters., Materials and Methods: Men living in rural or industrial areas were recruited by personalized letters. No exclusion criteria were applied. Each man provided one semen sample and one blood sample. We analyzed the semen sample both to determine conventional sperm parameters (concentration, progressive motility and normal forms) and to quantify lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), vanadium (V) and selenium (Se) levels. The levels of these metals/metalloids were also quantified in venous blood and spermatozoa samples. Associations between the blood/seminal plasma metal/metalloid levels and semen quality parameters were assessed using confounder adjusted logistic regression models. Correlation and interactions between blood/seminal plasma and semen metal/metalloid levels were investigated using the Spearman's correlation., Results: We found a positive association of seminal plasma cadmium level with lower Total count (OR = 4.48, 95%CI 0.25-80); whereas lead (OR = 4.51, 95%CI 0.86-23) and cadmium (OR = 3.45, 95%CI 0.77-16) seminal plasma levels had a positive association with progressive sperm motility. Overall, these associations remained suggestive after adjustment, though statistically unstable risks. Finally, we found weak interactions between beneficial effects of Se and detrimental ones only for Cd and Pb blood level on sperm concentration, total sperm count and progressive sperm motility., Conclusions: Our findings suggest that environmental exposure to Pb and Cd contributes to a decline in human semen quality, whereas Se can have beneficial effects. Measurements of metals/metalloids in the seminal fluid may be more predictable of semen quality than conventional blood measurements., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Overweight and obesity are increasingly spread in our society. Low testosterone levels are often present in these patients, the so-called metabolic hypogonadism, that further alters the metabolic balance in a sort of vicious cycle. Very low-calorie ketogenic diet (VLCKD) has been reported to efficiently reduce body weight, glycaemia, and the serum levels of insulin, glycated hemoglobin, but its effects on β-cell function and total testosterone (TT) levels are less clear., Aim: To evaluate the effects of VLCKD on markers suggested to be predictive of β-cell dysfunction development, such as proinsulin or proinsulin/insulin ratio, and on TT values in a cohort of overweight or obese nondiabetic male patients with metabolic hypogonadism., Methods: Patients with overweight or obesity and metabolic hypogonadism underwent to VLCKD for 12 weeks. Anthropometric parameters, blood testing for the measurement of glycaemia, insulin, C-peptide, proinsulin, TT, calculation of body-mass index (BMI), and HOMA index were performed before VLCKD and after 12 weeks., Results: Twenty patients (mean age 49.3 ± 5.2 years) were enrolled. At enrollement all patients presented increased insulin, HOMA index, C-peptide, and proinsulin levels, whereas the proinsulin/insulin ratio was within the normal values. After VLCKD treatment, body weight and BMI significantly decreased, and 14.9 ± 3.9% loss of the initial body weight was achieved. Glycaemia, insulin, HOMA index, C-peptide, and proinsulin significantly decreased compared to pre-VLCKD levels. Serum glycaemia, insulin, C-peptide, and proinsulin levels returned within the normal range in all patients. No difference in the proinsulin/insulin ratio was observed after VLCKD treatment. A mean increase of 218.1 ± 53.9% in serum TT levels was achieved and none of the patients showed TT values falling in the hypogonadal range at the end of the VLCKD treatment., Conclusions: This is the first study that evaluated the effects of VLCKD on proinsulin, proinsulin/insulin ratio, and TT levels. VLCKD could be safely used to improve β-cell secretory function and insulin-sensitivity, and to rescue overweight and obese patients from β-cell failure and metabolic hypogonadism.

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.

Obesity is a widespread disease that is associated with numerous and serious comorbidities. These include metabolic syndrome, diabetes mellitus, cardiovascular-cerebrovascular disease, hypertension, obstructive sleep apnea syndrome, cancer, and sexual and hormonal disorders. The treatment of obesity has therefore become a goal of great clinical and social relevance. Among the therapeutic strategies against obesity, resveratrol has aroused great interest. This polyphenol has anticancer and antioxidant properties and cytoprotective and anti-inflammatory effects. Other favorable effects attributed to resveratrol are anti-lipid, anti-aging, anti-bacterial, anti-viral, and neuroprotective actions. Administration of resveratrol appears to improve the metabolic profile in obese and/or insulin-resistant patients. This article aims to review the main results of clinical studies evaluating the effects of administering resveratrol alone in overweight/obese patients.

The evaluation of biofunctional sperm parameters can explain some cases of idiopathic male infertility. Among these, sperm DNA fragmentation (fDNA) is the most studied biofunctional sperm parameter. Mitochondrial membrane potential (MMP) correlates positively with sperm motility, the evaluation of sperm apoptosis by flow cytometry allows us to identify a population of spermatozoa not recognizable at the optical microscopy and finally, lipid peroxidation (LP) and mitochondrial superoxide levels measurements are rational oxidative stress indices. Male age seems to affect sperm concentration and sperm fDNA. For these reasons, this study was undertaken to evaluate the correlation, if any, between male age and biofunctional sperm parameters evaluating their possible impact on fDNA. To accomplish this, MMP, degree of chromatin compactness, sperm apoptosis/vitality, fDNA, LP, and mitochondrial superoxide levels were evaluated by flow cytometry in a cohort of 874 men. A significant negative correlation was found between age and the percentage of alive spermatozoa (r = -0.75, p < 0.05). The percentage of spermatozoa with low MMP (L-MMP) correlated positively with the percentage of spermatozoa with abnormal chromatin compactness (r = 0.24, p < 0.05). Spermatozoa with abnormal chromatin compactness and L-MMP correlated negatively with the percentage of alive spermatozoa (r = 0.83, p < 0.05) and positively with spermatozoa with PS externalization (r = 0.13, p < 0.01). The percentage of alive spermatozoa correlated negatively with both the percentage of spermatozoa with PS externalization (r = 0.24, p < 0.01) and of the spermatozoa with fDNA (r = 0.10, p < 0.05). Spermatozoa with PS externalization correlated positively with the percentage of spermatozoa with fDNA (r = 0.09, p < 0.05). Spermatozoa with LP correlated positively with the percentage of spermatozoa with increased mitochondrial superoxide (r = 0.11, p < 0.01) In conclusion, these findings in a large number of men suggest that age, mitochondrial damage, and alteration of chromatin compactness could activate the apoptotic cascade which could result in an increased fDNA rate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Condorelli, La Vignera, Barbagallo, Alamo, Mongioì, Cannarella, Aversa and Calogero.)

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., Competing Interests: The authors declare no conflict of interest.

Background: Obesity has become an increasingly worrisome reality. A very-low-calorie ketogenic diet (VLCKD) represents a promising option by which to achieve significant weight loss. This study sought to evaluate the effectiveness of VLCKD on metabolic parameters and hormonal profiles of obese male patients., Methods: We enrolled 40 overweight/obese men who consumed VLCKD for at least eight weeks. Body weight, waist circumference, fasting glucose, insulin, total cholesterol, high-density lipoprotein, triglycerides, creatinine, uric acid, aspartate aminotransferase, alanine aminotransferase, vitamin D, luteinizing hormone (LH), total testosterone (TT), and prostate-specific antigen (PSA) were calculated before and after VLCKD consumption. We additionally determined the homeostasis model assessment index and low-density lipoprotein (LDL) values., Results: After VLCKD (13.5 ± 0.83 weeks), the mean body weight loss was 21.05 ± 1.44 kg; the glucose homeostasis and lipid profile were improved significantly; serum vitamin D, LH, and TT levels were increased and the PSA levels were decreased significantly as compared with pretreatment values. These results are of interest since obesity can lead to hypogonadism and in turn, testosterone deficiency is associated with impaired glucose homeostasis, metabolic syndrome, and diabetes mellitus. Moreover, a close relationship between obesity, insulin resistance, and/or hyperinsulinemia and increased prostate volume has been reported, with a consequent greater risk of developing lower urinary tract symptoms., Conclusions: VLCKD is an effective tool against obesity and could be a noninvasive, rapid, and valid means to treat obese patients with metabolic hypogonadism and lower urinary tract symptoms.

Cardiovascular diseases are the main cause of mortality in the Western population, so the attempt to find a marker capable of predicting their early onset is not surprising. It is known that arteriogenic erectile dysfunction (ED) precedes the onset of a major coronary event by several years. However, a marker that is able to early identify those patients who should undergo further diagnostic investigations is, to date, missing. Recent research on this topic has focused on the role of the mean platelet volume (MPV), a marker of platelet activity that is high in most vascular diseases, such as coronary artery disease (CAD), stroke, peripheral artery disease (PAD), and ED. The basic pathophysiological mechanism of all these clinical conditions is atherosclerosis. Platelets play a central role in amplifying this process both indirectly by stimulating endothelial cells to produce inflammatory cytokines and chemokines, and directly through the expression of membrane receptors and the release of molecules that contribute to the formation of atherosclerotic plaque. The objective of this review is to critically analyze the evidence on the role of MPV in predicting the diagnosis and severity of vasculogenic ED and the possibility of using this simple marker as a first step to start a diagnostic process aimed at assessing the cardiovascular risk in these patients.

The evaluation of conventional and biofunctional sperm parameters is of fundamental importance for assessing male reproductive function. Among these, sperm motility is one of the most important parameters. Indeed, asthenozoospermia is a frequent cause of male infertility. Sperm motility depends on mitochondrial function and the measurement of mitochondrial membrane potential (MMP) better accounts for the function of this intracellular organelle. On the basis of these premises, the present study assessed whether the MMP predicts sperm motility at 4 h in patients with low or normal MMP. To accomplish this, 31 men were enrolled. Sperm analysis was conducted according to the WHO 2010 criteria. Particular attention was paid to the evaluation of MMP after liquefaction (T0) using JC-1 staining by flow cytometry. Sperm total and progressive motility were measured at T0 and after 4 h from seminal fluid collection (T4). Patients were divided into two groups based on their sperm mitochondrial function at T0. Group A ( n = 18) was composed of men with normal mitochondrial function since they had a percentage of spermatozoa with low MMP (L-MMP) below the normal reference value of our laboratory (<36.5%). In contrast, group B ( n = 13) was made up of men with impaired sperm mitochondrial function (L-MMP > 36.5%). Group A had a slight but not significant reduction in total and progressive sperm motility at T4 compared with the values recorded at T0. In contrast, patients in group B showed a significant decline in both total and progressive sperm motility at T4 compared with T0 ( p < 0.05). The results of this study showed that worse mitochondrial function, assessed by staining with JC1, is associated with a significant decline in sperm motility over time. These findings may be of clinical relevance in programs of assisted reproduction techniques. Based on our knowledge, there is no other evidence in the literature that has shown this relationship in healthy men with low MMP of idiopathic etiology, but normozoospermics according to the WHO 2010 criteria.

Over the last decades, the adverse effects of human exposure to the so-called "endocrine disruptors" have been a matter of scientific debate and public attention. Bisphenols are synthetic chemicals, widely used in the manufacture of hard plastic products. Bisphenol A (BPA) is one of the best-known environmental toxicants proven to alter the reproductive function in men and to cause other health problems. Consumer concern resulted in "BPA free" products and in the development of bisphenol analogs (BPA-A) to replace BPA in many applications. However, these other bisphenol derivatives seem to have effects similar to those of BPA. Although a number of reviews have summarized the effects of BPA on human reproduction, the purpose of this article is to review the effects of bisphenols on testicular steroidogenesis and to explore their mechanisms of action. Testicular steroidogenesis is a fine-regulated process, and its main product, testosterone (T), has a crucial role in fetal development and maturation and in adulthood for the maintenance of secondary sexual function and spermatogenesis. Contradictory outcomes of both human and animal studies on the effects of BPA on steroid hormone levels may be related to various factors that include study design, dosage of BPA used in in vitro studies, timing and route of exposure, and other confounding factors. We described the main possible molecular target of bisphenols on this complex pathway. We report that Leydig cells (LCs), the steroidogenic testicular component, are highly sensitive to BPA and several mechanisms concur to the functional impairment of these cells., (Copyright © 2020 Barbagallo, Condorelli, Mongioì, Cannarella, Aversa, Calogero and La Vignera.)

Scientific evidence shows that the administration of follicle-stimulating hormone (FSH) to infertile patients with normal serum FSH concentrations improves sperm parameters in oligozoospermic men. The aim of this study was to evaluate the effects of highly purified urofollitropin (hpFSH) on conventional and bio-functional sperm parameters and on oxidative stress indices in patients with idiopathic infertility. We also evaluated the response to hpFSH on these parameters in relationship to FSHR c. 2039 A/G and FSHR c. -29 G/A genotypes. A prospective longitudinal study was conducted on 42 patients with idiopathic male infertility, 23 of whom underwent to FSHR c. 2039 A/G and FSHR c. -29 G/A genotyping. Each patient was asked to collect two semen samples before and after administration of 150 IU hpFSH three times a week for 16 weeks. Patients were divided into responders or non-responders based on whether their total sperm count had at least doubled or was less than double at the end of treatment, respectively. Responders showed a significantly higher semen volume, sperm concentration, spermatids, and leukocytes. Non-responders had a significant decrease of the percentage of spermatozoa in early apoptosis after hpFSH administration. Oxidative stress indexes did not differ significantly after FSH administration in both groups. Conventional and bio-functional sperm parameters did not differ in patients with FSHR c. 2039 GG and AA genotypes, and FSHR c. -29 GG genotype both before and after FSH administration. The FSHR c. 2039 and FSHR -29 G/A genotypes and allelic distribution did not differ between responders and non-responders. FSH showed to be capable of ameliorating sperm parameters in about half patients treated, therefore it may be helpful in patients with idiopathic infertility.

Follicle-stimulating hormone (FSH) represents a therapeutic option in normogonadotropic patients with idiopathic oligozoospermia. The aim of this review was to evaluate the possible dose- and drug-dependent efficacy of FSH treatment on conventional sperm parameters. We performed a comprehensive systematic review via a meta-analysis of all available randomized controlled trials, in which FSH administration was compared with placebo or no treatment when administered to normogonadotropic patients with idiopathic oligozoospermia. Of the 971 articles that were retrieved, 5 were finally included, including a total of 372 patients and 294 controls. Overall, FSH treatment was effective in ameliorating the sperm concentration, total count, progressive motility, but not normal forms. On the basis of the weekly dosage, the studies were classified into those using low (175-262.5 IU per week), intermediate (350-525 IU per week), and high (700-1050 IU per week) doses. At low doses, FSH improved only sperm motility. At intermediate doses, FSH ameliorated sperm concentration and morphology. Total sperm count and progressive motility showed a trend toward the increase. At high doses, FSH increased sperm concentration, total sperm count, and progressive motility. Sperm morphology showed a trend toward the increase. Finally, both highly purified FSH (hpFSH) and recombinant human FSH (rhFSH) improved sperm concentration, total sperm count, progressive motility, but not morphology. No different efficacy was observed between these two preparations. This meta-analysis provides evidence in favor of high FSH doses. The FSH efficacy was not related to the preparation type (recombinant vs highly purified). Further studies are needed to evaluate the effectiveness of long-standing treatment regimes., Competing Interests: None

Male infertility affects half of infertile couples and, currently, a relevant percentage of cases of male infertility is considered as idiopathic. Although the male contribution to human fertilization has traditionally been restricted to sperm DNA, current evidence suggest that a relevant number of sperm transcripts and proteins are involved in acrosome reactions, sperm‒oocyte fusion and, once released into the oocyte, embryo growth and development. The aim of this review is to provide updated and comprehensive insight into the molecular biology of spermatogenesis, including evidence on spermatogenetic failure and underlining the role of the sperm-carried molecular factors involved in oocyte fertilization and embryo growth. This represents the first step in the identification of new possible diagnostic and, possibly, therapeutic markers in the field of apparently idiopathic male infertility.

Dual-release hydrocortisone is a new hydrocortisone formulation developed to improve the pharmacokinetic and the pharmacodynamic profiles and patient compliance. The aim of this review is to summarize the main knowledge on dual-release hydrocortisone, with particular attention to pharmacokinetics, metabolic and health-related quality-of-life aspects, bone health and drug safety.

Background: Increased dehydroepiandrosterone sulfate (DHEAS) levels have been reported in men with early-onset (<35 years) androgenetic alopecia (AGA). It has been suggested that a male polycystic ovarian syndrome- (PCOS-) equivalent, defined as an endocrine syndrome with a metabolic background and a PCOS-like hormonal pattern, predisposing to type II diabetes mellitus (DM II), cardiovascular and prostate diseases later in life, may occur in at least a part of these men. The gonadal function, including sperm parameters and total testosterone (TT) levels, has been investigated in a low number of these men., Objective: The aim of the study was to assess gonadal and adrenal function in a subset of men with early-onset AGA and controls., Methods: 43 men with early-onset AGA and 36 controls were screened for DHEAS, TT, glycaemia, insulin, gonadotropins, 17 α -hydroxyprogesterone (17 α -hydroxyprogesterone (17 n  = 21), as those with at least one of the following parameters: body mass index (BMI) >25 kg/m 2 , insulin resistance (IR), and/or SHBG <25 nmol/l., Results: Patients with early-onset AGA had higher mean (±SD) BMI (25.5 ± 3.8 vs. 23.7 ± 3.0 kg/m 2 ; P < 0.05) and 17 α -hydroxyprogesterone (17 P < 0.05) and 17 P < 0.05) and 17 P < 0.05) and 17 P < 0.05) and 17 μ g/dl; P < 0.05) and 17 P < 0.05) and 17 P < 0.05) and 17 P < 0.05) and 17., Conclusion: Men with early-onset AGA and at least one among BMI >25 kg/m 2 , IR, and SHBG <25 nmol/l have increased DHEAS levels and a worse gonadal steroidogenesis. They might have a greater risk to develop gonadal dysfunction later in life. These criteria may be used to define male PCOS-equivalent., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Rossella Cannarella et al.)

Air pollution has been suggested to affect semen quality, but the evidence is still contradictory. To assess whether any differences occur in conventional sperm parameters of men life-long resident in low, middle-low, middle, and high industrial density zones in the province of Messina. We retrospectively analyzed the conventional sperm parameters of patients to whom the sperm analysis was requested during their female partner counseling for infertility in an assisted reproductive technique (ART) center. A total of 184 men were enrolled. Total sperm count was higher in patients living in low and middle-low industrial density areas compared with that of men living in middle and high ones (123.5 ± 146.8 vs. 80.7 ± 92.7 mil/ejaculate, p < 0.05). No difference was found for sperm concentration (37.2 ± 49.7 vs. 30.5 ± 37.2 mil/mL), progressive motility (15.4 ± 19.8% vs. 14.2 ± 18.4%), total motility (62.3 ± 20.5 vs. 58.4 ± 19.9 mil/mL), and normal forms (2.7 ± 1.5 vs. 2.3 ± 3.0 mil/mL). These results add further evidence to findings from Sicilian population. Effective control of air pollution should be accomplished to prevent its negative impact on human reproductive health.

Background : Selective estrogen receptor modulators (SERMs) represent a poorly investigated class of drugs for the treatment of male infertility. The aim of this study was to assess the effects of SERMs on conventional sperm parameters, serum gonadotropin and testosterone levels, and pregnancy rate in patients with idiopathic infertility. Methods : The authors performed a comprehensive systematic review with meta-analysis of all available controlled and not-controlled studies of the literature reporting sperm conventional parameters, gonadotropin and testosterone levels, and/or the pregnancy rate following SERM administration in normogonadotropic patients with idiopathic oligozoospermia. Results : From the 418 papers retrieved, 16 controlled and not-controlled trials were lastly included. SERM administration increased significantly sperm concentration, total sperm count, and serum luteinizing hormone, follicle-stimulating hormone, and total testosterone levels compared with baseline values. In contrast, SERMs did not have any significant effect on sperm concentration and progressive and total motility, but improved total sperm count, sperm morphology, and increased the pregnancy rate compared to the control group, which included studies done with placebo or other treatments. Conclusions : The results of this meta-analysis suggest that SERMs may be effective in the treatment of infertile patients with idiopathic infertility. However, the paucity of data does not allow to draw a definitive conclusion.