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BACKGROUND. Several studies have already investigated the relationship between IGF1 and semen parameters. However, clinical studies rarely concluded on the existence of a relationship between IGF1 and the sperm number, and whether the IGF1 serum levels have a practical value in the diagnostic work-up of patients with oligozoospermia is still unclear. OBJECTIVE. Molecular evidence reported that IGF1 and FSH belongs to the same molecular pathway. The aim of this study is to assess whether insulin-like growth factor-1 (IGF1)/follicle-stimulating hormone (FSH) ratio has an impact on testicular function and, specifically, on sperm number and testicular volume in a cohort of unselected men. METHODS. This is a cross-sectional study on 59 patients who attended the Seminology laboratory of the Division of Endocrinology of the University of Catania (Catania, Italy) for semen analysis. Data were analyzed to evaluate the relationships between IGF1 or IGF1/FSH ratio and sperm concentration, total sperm count (TSC), and testicular volume (TV). We also evaluated the occurrence of any difference in IGF1 and FSH serum levels and the IGF1/FSH ratio in patients with oligozoospermia and those with a TSC > 39 million/ejaculate. MAIN RESULTS AND ROLE OF CHANGE. Patients had a mean age of 31.0 ± 8.5 years. The mean FSH and IGF1 levels were 3.95 ± 2.55 mIU/mL and 232.59 ± 65.13 ng/mL, respectively. IGF1 serum levels did not correlate with sperm concentration, TSC, and TV. The IGF1/FSH ratio showed a positive correlation with sperm concentration (r = 0.408; p = 0.004), TSC (r = 0.468; p = 0.001), and TV (0.463; p = 0.002). Patients with oligozoospermia (Group 1, 23.7%, n = 14) had a significant lower IGF1/FSH ratio (57.9 ± 9.5 vs. 94.1 ± 8.7; p = 0.03) compared to those with TSC > 39 million/ejaculate (Group 2, 76.3%, n = 45). They did not differ significantly for neither IGF1 nor FSH serum levels. CONCLUSION. We found a positive correlation between the IGF1/FSH ratio and sperm concentration, TSC and TV. Furthermore, patients with oligozoospermia showed a significantly lower ratio compared to those with a normal TSC, while neither IGF1 nor FSH differed significantly in the two groups. Our results may reflect the existence of a molecular pathway to which IGF1 and FSH belongs. However, further studies are needed.

The spread of severe acute respiratory syndrome—Coronavirus 2 (SARS-CoV-2) around the world has rapidly sparked the interest of the scientific community to discover its implications in human health. Many studies have suggested that SARS-CoV-2 is directly or indirectly involved in the male reproductive tract impairment. Some evidence supports the possible role of the virus in male infertility. Therefore, this review aims to summarize the relationship between the male urogenital tract, male fertility, and the gonadal hormone profile. The testis is one of the organs with the highest expression of the angiotensin-converting enzyme (ACE) 2-receptor that allows the virus to penetrate human cells. Orchitis is a possible clinical manifestation of COVID-19 and testicular damage has been found on autopsy in the testes of patients who died from the disease. SARS-CoV-2 infection can compromise the blood-testis barrier, favoring testicular damage and the production of anti-sperm autoantibodies. Some studies have detected the presence of SARS-CoV-2 in semen and a high percentage of patients with COVID-19 have altered sperm parameters compared to controls. Finally, lower testosterone levels, higher luteinizing hormone (LH) levels, and decreased follicle-stimulating (FSH)/LH and testosterone/LH ratios suggest primary testicular damage. In conclusion, further studies are needed to evaluate the exact mechanisms by which SARS-CoV-2 affects the male reproductive system and fertility and to evaluate the reversibility of its long-term effects.

Transrectal ultrasound (TRUS) parameters are not standardized, especially in men of reproductive age. Hence, the European Academy of Andrology (EAA) promoted a multicenter study to assess the TRUS characteristics of healthy-fertile men (HFM) to establish normative parameters.To report and discuss the prostate and seminal vesicles (SV) reference ranges and characteristics in HFM and their associations with clinical, seminal, biochemical parameters.188 men (35.6 ± 6.0 years) from a cohort of 248 HFM were studied, evaluating, on the same day, clinical, biochemical, seminal, TRUS parameters following Standard Operating Procedures.TRUS reference ranges and characteristics of the prostate and SV of HFM are reported herein. The mean PV was ∼25 ml. PV lower and upper limits were 15 and 35 ml, defining prostate hypotrophy and enlargement, respectively. PV was positively associated with age, waistline, current smoking (but not with T levels), seminal volume (and negatively with seminal pH), prostate inhomogeneity, macrocalcifications, calcification size and prostate arterial parameters, SV volume before and after ejaculation, deferential and epididymal size. Prostate calcifications and inhomogeneity were frequent, while midline prostatic cysts were rare and small. Ejaculatory duct abnormalities were absent. Periprostatic venous plexus size was positively associated with prostate calcifications, SV volume and arterial peak systolic velocity. Lower and upper limits of SV anterior-posterior diameter after ejaculation were 6 and 16 mm, defining SV hypotrophy or dilation, respectively. SV total volume before ejaculation and delta SV total volume (DSTV) positively correlated with ejaculate volume, and DSTV correlated positively with sperm progressive motility. SV total volume after ejaculation was associated negatively with SV ejection fraction and positively with distal ampullas size. SV US abnormalities were rare. No association between TRUS and time to pregnancy, number of children or history of miscarriage was observed.The present findings will help in better understanding male infertility pathophysiology and the meaning of specific TRUS findings.

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. Infertile patients aged 20–55 years were treated with a combination of antioxidants (Androlen®) (Group 1), with Androlen® and a mixture of fibrinolytic molecules (Lenidase®) (Group 2), or Androlen® and other molecules different from those used for the patients of the Group 2 (Group 3). Patients were also subdivided according to the presence of varicocele, mild testicular hypotrophy, idiopathic infertility, and chronic male accessory gland infection (MAGI). 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. The percentage of alive spermatozoa increased in patients with testicular hypotrophy. Treatment with antioxidants increases progressive sperm motility. The association of fibrinolytic or other nutraceuticals does not improve the efficacy of the treatment with antioxidants alone. The treatment was effective in patients with varicocele or idiopathic infertility.

To evaluate whether the follicle-stimulating hormone (FSH) receptor (FSHR) is expressed in human spermatozoa and the effects of FSH incubation on sperm function. Twenty-four Caucasian men were recruited. Thirteen patients had asthenozoospermia, and the remaining 11 had normal sperm parameters (controls). After confirming FSHR expression, spermatozoa from patients and controls were incubated with increasing concentrations of human purified FSH (hpFSH) to reassess FSHR expression and localization and to evaluate progressive and total sperm motility, the mitochondrial membrane potential, and protein kinase B (AKT) 473 and 308 phosphorylation. FSHR is expressed in the post-acrosomal segment, neck, midpiece, and tail of human spermatozoa. Its localization does not differ between patients and controls. Incubation with hpFSH at a concentration of 30 mIU/mL appeared to increase FSHR expression mainly in patients. Incubation of human spermatozoa with hpFSH overall resulted in an overall deterioration of both progressive and total motility in patients and controls and worse mitochondrial function only in controls. Finally, incubation with FSH increased AKT473/tubulin phosphorylation to a greater extent than AKT308. FSHR is expressed in the post-acrosomal region, neck, midpiece, and tail of human spermatozoa. Contrary to a previous study, we report a negative effect of FSH on sperm motility and mitochondrial function. FSH also activates the AKT473 signaling pathway.

PURPOSE: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. MATERIALS AND METHODS: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. RESULTS: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. CONCLUSIONS: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.

Graves’ disease (GD) is an autoimmune disease considered the most common cause of hyperthyroidism. Some studies have investigated its relationship with the risk and prognosis of developing thyroid cancer. Considering that there is no consensus on the relationship between GD and thyroid cancer risk, this umbrella review aimed to summarize the epidemiologic evidence and evaluate its strength and validity on the associations of GD with thyroid cancer risk and its prognosis. This umbrella review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched PubMed and Scopus from January 2012 to December 2022. The strength of the epidemiological evidence was graded as high, moderate, or weak by the Measurement Tool to Assess Systematic Reviews (AMSTAR-2). “Strong” evidence was found for the risk of thyroid cancer in GD patients with thyroid nodular disease (OR: 5.30; 95% CI 2.43–12) and for the risk of mortality from thyroid cancer in these patients (OR 2.93, 95% CI 1.17–7.37, p = 0.02), particularly in Europe (OR 4.89; 95% CI 1.52–16). The results of this umbrella review should be interpreted with caution; as the evidence comes mostly from retrospective studies, potential concerns are selection and recall bias, and whether the empirically observed association reflects a causal relationship remains an open question.

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.

We thank our French colleagues for commenting [...].

Diabetes mellitus (DM) is a widespread chronic disease with a prevalence that is expected to further increase in the near future. The classical management of DM includes the normalization of the glycometabolic profile and the evaluation of cardiac and cerebral vascular health by the intervention of an array of different specialists. However, so far, sexual dysfunctions are still a neglected complication in patients with DM, although there is an elevated prevalence of this long-term complication in male and female patients. Furthermore, some of them may represent a sign of vascular alteration and/or hypogonadism and require timely management to prevent the onset of major adverse cardiac events. This narrative review briefly summarizes the current evidence on epidemiology, pathogenesis, diagnosis, and therapy of erectile dysfunction in male patients with DM to support diabetologists in clinical practice.

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.

Glucagon‐like peptide‐1 receptor agonists (GLP1‐RAs) are novel anti‐hyperglycemic drugs efficacious on glucose control, weight loss, and cardiovascular prevention. These drugs may also be effective in modulating testicular function. In fact, they increase serum testosterone levels in diabetic and/or obese patients with functional hypogonadism on a dysmetabolic basis. Although part of this effect can be ascribed to weight loss, some evidence suggests that there is a direct effect at the testicular level. Indeed, human Leydig, Sertoli, and germ cells express GLP1 receptors. GLP1‐RAs improve sperm metabolism, motility, and insulin secretion in vitro. Likewise, GLP1‐RAs exert positive effects on the metabolism of human Sertoli cells in vitro. Finally, GLP1 is secreted by mouse Leydig cells and this suggests the presence of a paracrine mechanism by which these cells could support the metabolism of Sertoli cells. Therefore, the widespread use of GLP1‐RAs in clinical practice may reveal an important role in the management of male infertility in obese and/or diabetic patients given the negative impact of these diseases on testicular steroidogenesis and spermatogenesis. This should suggest the design of randomized controlled studies aimed at evaluating the effects of these drugs on testicular function.

Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying mechanism of idiopathic male infertility, the specific treatment of OS-mediated male infertility requires further investigation. Coenzyme Q10 (CoQ10), a vitamin-like substance, has been found in measurable levels in human semen. It exhibits essential metabolic and antioxidant functions, as well as playing a vital role in mitochondrial bioenergetics. Thus, CoQ10 may be a key player in the maintenance of biological redox balance. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Seminal CoQ10 concentrations have been shown to be altered in various male infertility states, such as varicocele, asthenozoospermia, and medical or surgical regimens used to treat male infertility. These observations imply that CoQ10 plays an important physiological role in the maintenance and amelioration of semen quality. The present article thereby aimed to review the possible mechanisms through which CoQ10 plays a role in the regulation of male reproductive function, and to concisely discuss its efficacy as an ameliorative agent in restoring semen parameters in male infertility, as well as its impact on OS markers, sperm DNA fragmentation, pregnancy, and assisted reproductive technology outcomes.

Objective: Oxidative stress (OS) plays a key role in the etiology of unexplained male infertility. Coenzyme Q10 (CoQ10) is a potent antioxidant that may improve semen quality and OS in infertile men with idiopathic oligoasthenoteratospermia (OAT), but the underlying mechanism is unknown. Therefore, the present study was undertaken to investigate the effect of CoQ10 on OS markers and sperm DNA damage in infertile patients with idiopathic OAT. Methods: This prospective controlled study included 50 patients with idiopathic OAT and 50 fertile men who served as controls. All patients underwent a comprehensive medical assessment. Patients and controls received 200 mg of oral CoQ10 once daily for 3 months. Semen and blood were collected and analyzed for sperm parameters, seminal CoQ10 levels, reactive oxygen species (ROS) levels, total antioxidant capacity, catalase, sperm DNA fragmentation (SDF), and serum hormonal profile. Results: The administration of CoQ10 to patients with idiopathic OAT significantly improved sperm quality and seminal antioxidant status and significantly reduced total ROS and SDF levels compared to pre-treatment values. Conclusion: CoQ10, at a dose of 200 mg/day for 3 months, may be a potential therapy for infertile patients with idiopathic OAT, as it improved sperm parameters and reduced OS and SDF in these patients.

Scarce data are available about the impact of natalizumab (NTZ) and ocrelizumab (OCR) on male fertility in relapsing-remitting multiple sclerosis (RRMS). In this case–control prospective study, the gonadal steroids and the sperm parameters have been analysed at the time of the RRMS diagnosis and after 12 months from the beginning of the investigated therapies. Sixteen men with RRMS and sixteen matched healthy controls were included. At enrolment and after 12 months on therapy, the gonadal steroids and the sperm parameters of men with RRMS did not differ from the healthy controls. In conclusion, therapy with NTZ and OCR had no impact on fertility status in our cohort of men with RRMS. Further randomized and prospective studies are needed.

Metformin appears to reduce TSH levels in untreated hypothyroid patients. In contrast, in euthyroid patients with type 2 diabetes mellitus (T2DM), metformin is initially devoid of effects on TSH. However, it is followed by a significant reduction in TSH level after twelve months of treatment. Additionally, some evidence suggests that metformin may also improve thyroid morphological abnormalities. This study aimed to evaluate the effects of metformin not only on TSH and thyroid hormone values, but also on thyroid volume and nodules. A total of 50 patients (mean age: 36.9 ± 12.8 years) with insulin resistance (homeostatic model assessment (HOMA) index ≥2.5) and with thyroid uninodular disease were recruited for this study. They were prescribed slow-acting metformin at a daily dose of 500 mg for six months. Treatment with metformin in euthyroid patients with uninodular thyroid disease and insulin resistance reduces TSH levels, increases FT4 and FT3 values, and decreases thyroid and nodule volumes. These data suggest that metformin may be an effective drug not only for the treatment of T2DM and metabolic syndrome, but also for thyroid disease.

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.

Neuroactive steroids may have a role in regulating sexual function. This case-control study assessed whether dutasteride, a 5α-reductase inhibitor used for treatment of patients with benign prostate hyperplasia (BPH), impacts on the levels of neuroactive steroids, leading to erectile dysfunction (ED) and/or hypoactive sexual desire (HSD). Forty patients with BPH and moderate-to-severe lower urinary tract symptoms (LUTS), pre-scheduled for prostate transurethral resection or open prostatectomy were enrolled. Twenty of these patients with prostate volume ≤40 mL were treated with α-blockers (Group A) and the remaining 20, with prostate volume >40 mL, with dutasteride plus α-blockers (Group B) for at least 6 months before surgery. Serum sex steroids and gonadotropin levels were measured the day before surgery, and the neuroactive steroid levels were assessed in the cerebrospinal fluid (CSF) collected during spinal anesthesia, at the day of surgery. Before surgery, the International Index of Erectile Function 5-item score was higher in Group A that Group B (18.8 ± 4.8 vs. 15.1 ± 5.4, p

SommarioIl volume piastrinico medio (VPM) è un parametro che sta acquisendo sempre maggiore importanza nella stratificazione del rischio vascolare sistemico dal momento che è in grado di predire il grado di attività piastrinica. Piastrine più attive sono infatti più trombogeniche e contribuiscono al processo di aterosclerosi che, a sua volta, è la principale causa della disfunzione vascolare. La disfunzione erettile (DE) è una condizione che impatta notevolmente sulla qualità della vita di un uomo e, tra le varie cause, la DE su base vascolare arteriosa è quella che ha la prevalenza maggiore. Per questo motivo, alcuni studi hanno cercato di valutare la relazione tra i valori di VPM nei pazienti con DE, suggerendo che questo parametro può essere considerato uno strumento per la diagnosi precoce della DE oltre che un possibile nuovo bersaglio terapeutico, facilmente valutabile.

Diabetes mellitus (DM) is one of the most common chronic diseases worldwide and its prevalence is expected to increase in the coming years. Therefore, updated knowledge of all diabetic complications and their management is essential for the proper treatment of these patients. Sexual dysfunctions are one of the long-term complications of DM in both genders. However, female sexuality is still a taboo and sexual concerns are often overlooked, underdiagnosed, and untreated. The aim of this review is to summarize the current knowledge on the relationship between sexual function and DM in women. In particular, we evaluated the prevalence, etiology, diagnostic approaches, and current treatment options of female sexual dysfunction (FSD) in diabetic patients.

The evidence on the role of obstructive sleep apnea (OSA) in the pathogenesis of hypogonadism and the impact of testosterone replacement therapy (TRT) in OSA patients are still contradictory. OSA i...

A large proportion of patients with idiopathic spermatogenic failure (SPGF; oligozoospermia or nonobstructive azoospermia [NOA]) do not receive a diagnosis despite an extensive diagnostic workup. Recent evidence has shown that the etiology remains undefined in up to 75% of these patients. A number of genes involved in germ-cell proliferation, spermatocyte meiotic divisions, and spermatid development have been called into play in the pathogenesis of idiopathic oligozoospermia or NOA. However, this evidence mainly comes from case reports. Therefore, this study was undertaken to identify the molecular causes of SPGF. To accomplish this, 15 genes (USP9Y, NR5A1, KLHL10, ZMYND15, PLK4, TEX15, TEX11, MEIOB, SOHLH1, HSF2, SYCP3, TAF4B, NANOS1, SYCE1, and RHOXF2) involved in idiopathic SPGF were simultaneously analyzed in a cohort of 25 patients with idiopathic oligozoospermia or NOA, accurately selected after a thorough diagnostic workup. After next-generation sequencing (NGS) analysis, we identified the presence of rare variants in the NR5A1 and TEX11 genes with a pathogenic role in 3/25 (12.0%) patients. Seventeen other different variants were identified, and among them, 13 have never been reported before. Eleven out of 17 variants were likely pathogenic and deserve functional or segregation studies. The genes most frequently mutated were MEIOB, followed by USP9Y, KLHL10, NR5A1, and SOHLH1. No alterations were found in the SYCP3, TAF4B, NANOS1, SYCE1, or RHOXF2 genes. In conclusion, NGS technology, by screening a specific custom-made panel of genes, could help increase the diagnostic rate in patients with idiopathic oligozoospermia or NOA.

Background Infertility is a disorder of the male and/or female reproductive system, characterized by failure to establish a clinical pregnancy after 12 months of regular unprotected sexual intercourse. On a world basis, about one in six couplesare affected by infertility during their reproductive lifespan. Despite a comprehensive diagnostic work-up, infertility in about 50% of couples remains idiopathic. In this context, a next-generation sequencing (NGS) approach has been suggested to increase diagnostic yield. Accordingly, this study aimed to evaluate the effectiveness of a custom-made NGS gene panel for the simultaneous genetic diagnosis of both partners of a large population of infertile couples. Methods We developed a custom-made NGS panel for 229 genes associated with male and female infertility. The panel targeted exons and their flanking regions and was used to screen 99 couples with idiopathic infertility. Results NGS sequencing revealed five pathogenic variants in six couples and 17 likely pathogenic variants or variants with uncertain significance (VUS). The pathogenic variants were identified in the following genes: GNRHR, CCDC39, DNAH5, and CCDC103; likely pathogenic variants were identified in TAC3, PROKR2, and CFTR; VUS were identified in CATSPER2, FGFR1, LRRC6, DNAH5, DNAH11, TGFBR3, and DNAI1. Conclusions The panel of genes designed for this study allowed the identification of pathogenetic gene mutations and the presence of VUS in 6.1% and 17.2%, respectively, of couples with idiopathic infertility. This is the first study to successfully apply an NGS-based genetic screening including 229 genes known to play a role in both male and female infertility.

Congenital hypogonadotropic hypogonadism (cHH)/Kallmann syndrome (KS) is a rare genetic disorder with variable penetrance and a complex inheritance pattern. Consequently, it does not always follow Mendelian laws. More recently, digenic and oligogenic transmission has been recognized in 1.5–15% of cases. We report the results of a clinical and genetic investigation of five unrelated patients with cHH/KS analyzed using a customized gene panel. Patients were diagnosed according to the clinical, hormonal, and radiological criteria of the European Consensus Statement. DNA was analyzed using next-generation sequencing with a customized panel that included 31 genes. When available, first-degree relatives of the probands were also analyzed to assess genotype–phenotype segregation. The consequences of the identified variants on gene function were evaluated by analyzing the conservation of amino acids across species and by using molecular modeling. We found one new pathogenic variant of the CHD7 gene (c.576T>A, p.Tyr1928) and three new variants of unknown significance (VUSs) in IL17RD (c.960G>A, p.Met320Ile), FGF17 (c.208G>A, p.Gly70Arg), and DUSP6 (c.434T>G, p.Leu145Arg). All were present in the heterozygous state. Previously reported heterozygous variants were also found in the PROK2 (c.163del, p.Ile55*), CHD7 (c.c.2750C>T, p.Thr917Met and c.7891C>T, p.Arg2631*), FLRT3 (c.1106C>T, p.Ala369Val), and CCDC103 (c.461A>C, p.His154Pro) genes. Molecular modeling, molecular dynamics, and conservation analyses were performed on three out of the nine variants identified in our patients, namely, FGF17 (p.Gly70Arg), DUSP6 (p.Leu145Arg), and CHD7 p.(Thr917Met). Except for DUSP6, where the L145R variant was shown to disrupt the interaction between β6 and β3, needed for extracellular signal-regulated kinase 2 (ERK2) binding and recognition, no significant changes were identified between the wild-types and mutants of the other proteins. We found a new pathogenic variant of the CHD7 gene. The molecular modeling results suggest that the VUS of the DUSP6 (c.434T>G, p.Leu145Arg) gene may play a role in the pathogenesis of cHH. However, our analysis indicates that it is unlikely that the VUSs for the IL17RD (c.960G>A, p.Met320Ile) and FGF17 (c.208G>A, p.Gly70Arg) genes are involved in the pathogenesis of cHH. Functional studies are needed to confirm this hypothesis.

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

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.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 functionMYO can improve sperm count, motility, capacitation, acrosome reaction, and MMP. No data are currently available on the effects of DCI

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.

A physical examination represents a fundamental step in diagnosing diseases. Due to the role that hormones play in the regulation of numerous biological processes in various organs and systems, endocrine diseases cause a variety of clinical manifestations that can be easily identified with a careful physical examination and can guide the clinician to specific diagnoses. Furthermore, the presence of specific clinical signs in various endocrine-metabolic diseases can predict the risk of developing comorbidities and serious adverse events. In this article, we present some of the main clinical signs of endocrine-metabolic diseases and the risk of comorbidities, summarizing the pathogenetic mechanisms that lead to their formation. The aim is to highlight how the identification of these specific signs can reduce the number of dynamic tests and the costs necessary to reach the diagnosis and allow the early identification of any complications associated with these diseases, improving the clinical management of affected patients.