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Background: Varicocele represents the most common correctable cause of male infertility. The presence of non-invasive imaging parameters providing evidence as to which patients with varicocele are at risk for infertility would be important. Purpose: To explore the role of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) using semi-quantitative parameters in the assessment of testicular perfusion in infertile men with clinical varicocele. Material and Methods: The study cohort included 11 infertile men with clinical varicocele and six controls, with prior paternity. Subtraction DCE-MRI was performed after gadolinium administration, using a three-dimensional fast field-echo sequence. Time-signal intensity curves were created and semi-quantitative parameters were calculated. The independent samples t -test was used to compare basic T1 perfusion parameters between infertile testes with clinical varicocele and normal testes. Logistic regression analysis was performed to assess the most significant predictor of the diagnosis of clinical varicocele. Results: Both testes with clinical varicocele and normal testes enhanced moderately and homogeneously, with a linear increase of enhancement throughout the examination. Higher mean values of maximum enhancement (P = 0.026), maximum relative enhancement (P = 0.024), and wash-in rate (P = 0.013) were detected in the testes of infertile men with clinical varicocele, compared to the normal population. The wash-in rate proved the most significant predictor of the diagnosis of clinical varicocele (P = 0.013). Conclusion: DCE-MRI may provide a valuable insight into the testicular perfusion of infertile men with clinical varicocele. The wash-in rate proved a strong and independent predictor of the diagnosis of clinical varicocele. [ABSTRACT FROM AUTHOR]

Simple Summary: Although conventional ultrasonography remains the primary imaging modality for the assessment of testicular tumors, multiparametric MRI of the scrotum, which combines morphologic and functional data, serves as a powerful adjunct. Based on the recommendations issued by the Scrotal and Penile Imaging Working Group of the European Society of Urogenital Radiology, scrotal MRI is strongly recommended after equivocal US findings. In cases of testicular masses, the main clinical indications are as follows: lesion characterization when sonographic findings are non-diagnostic, discrimination between germ-cell and non-germ-cell testicular tumors, local staging of testicular tumors in patients who are candidates for testis-sparing surgery, and preoperative histological characterization of testicular germ-cell tumors in selected cases. This article aims to provide an overview of the role of multiparametric MRI in the investigation of testicular tumors. Conventional ultrasonography represents the mainstay of testis imaging. In cases in which ultrasonography is inconclusive, scrotal MRI using a multiparametric protocol may be used as a useful problem-solving tool. MRI of the scrotum is primarily recommended for differentiating between benign and malignant testicular masses when sonographic findings are ambiguous. This technique is also accurate in the preoperative local staging of testicular tumors and, therefore, is recommended in patients scheduled for testis-sparing surgery. In addition, MRI may provide valuable information regarding the histological characterization of testicular germ-cell tumors, in selected cases. Scrotal MRI may also help in the differentiation between testicular germ-cell neoplasms and non-germ-cell neoplasms. Axial T1-weighted imaging, axial and coronal T2-weighted imaging, axial diffusion-weighted imaging, and coronal subtracted dynamic contrast-enhanced imaging are the minimum requirements for scrotal MRI. A variety of MRI techniques—including diffusion tensor imaging, magnetization transfer imaging, proton MR spectroscopy, volumetric apparent diffusion coefficient histogram analysis, and MRI-based radiomics—are being investigated for testicular mass characterization, providing valuable supplementary diagnostic information. In the present review, we aim to discuss clinical indications for scrotal MRI in cases of testicular tumors, along with MRI findings of common testicular malignancies. [ABSTRACT FROM AUTHOR]

Background: Testicular magnetic resonance imaging parameters, including apparent diffusion coefficient, fractional anisotropy, magnetization transfer ratio, and normalized metabolite concentrations represent useful noninvasive fingerprints of nonobstructive azoospermia. Nonobstructive azoospermia etiology might correlate with the spermatogenesis status. Objectives: To assess the possible association between apparent diffusion coefficient, fractional anisotropy, magnetization transfer ratio, and normalised metabolite concentrations with nonobstructive azoospermia etiology. Materials and methods: This retrospective study included 48 consecutive men with nonobstructive azoospermia and 18 age‐matched controls. All participants underwent scrotal magnetic resonance imaging. The testicular apparent diffusion coefficient, fractional anisotropy, magnetization transfer ratio, and normalized metabolite concentrations were calculated. nonobstructive azoospermia men were classified into three groups, based on etiology: group 1, idiopathic; group 2, genetic causes; and group 3, non‐genetic causes. Parametric and nonparametric statistical tests were used to evaluate differences in magnetic resonance imaging parameters between nonobstructive azoospermia groups and normal testes (group 4). Regression analysis was performed to assess the most predictive magnetic resonance imaging factor of nonobstructive azoospermia etiology. Results: Differences in mean apparent diffusion coefficient (p <.001), fractional anisotropy (p <.001), magnetization transfer ratio (p <.001), and normalized concentrations of total choline (p =.005), glucose (p =.012), myo‐inositol (p =.024), and lipids (p =.010) were observed among groups. Regression analysis failed to identify the most discriminating magnetic resonance imaging feature for nonobstructive azoospermia etiology. Discussion and conclusion: Apparent diffusion coefficient, fractional anisotropy, magnetization transfer ratio, and normalized concentrations of total choline, glucose, myo‐inositol, and lipids are helpful in discriminating nonobstructive azoospermia etiology. Magnetic resonance imaging may provide useful, noninvasive information on the microstructural and biochemical milieu of nonobstructive azoospermia testes. [ABSTRACT FROM AUTHOR]

Although testicular carcinoma represents approximately only 1% of solid neoplasms in men, it is the most common malignancy between young men. The two main histologic categories are testicular germ cell tumors (TGCTs), including seminomas and nonseminomas, accounting for 90-95% of testicular neoplasms and sex cord-stromal tumors. Scrotal MRI, including a multiparametric protocol, has been proposed as a valuable supplemental imaging technique in the investigation of testicular pathology. Recently, the Scrotal and Penile Imaging Working Group appointed by the board of the European Society of Urogenital Radiology has produced recommendations on when to perform scrotal MRI. Regarding intratesticular masses, MRI of the scrotum may be used for their characterization, when US findings are indeterminate and for local staging of TGCTs, when organ-sparing surgery is planned. Differentiation between seminomas and nonseminomas is possible based on MRI features, when clinically needed. Scrotal MRI may also help in differentiating between TGCTs and nongerm cell tumors. Functional information based on diffusion-weighted imaging and dynamic contrast-enhanced MRI data improve testicular mass lesion characterization. Preliminary observations on diffusion tensor imaging, magnetization transfer imaging, and proton MR spectroscopy bring about new data in the understanding of testicular microstructure and pathophysiology. [ABSTRACT FROM AUTHOR]

Development of varicocele in the human has been associated with reduced male reproductive potential. Induction of left experimental varicoceles in the rat, rabbit, and monkey results in a bilateral detrimental effect on testicular endocrine and exocrine function. This review discusses mechanisms mediating the consequences of varicocele on male reproductive potential, indications for the treatment of varicocele, and techniques for varicocelectomy and reviews the difficulties in the interpretation of studies evaluating the effect of varicocele reversal on semen parameters and male reproductive potential. [ABSTRACT FROM AUTHOR]

Abstract: Normal testicular function is dependent upon hormones acting through endocrine and paracrine pathways both in vivo and in vitro. Sertoli cells provide factors necessary for the successful progression of spermatogonia into spermatozoa. Sertoli cells have receptors for follicle stimulating hormone (FSH) and testosterone which are the main hormonal regulators of spermatogenesis. Hormones such as testosterone, FSH and luteinizing hormone (LH) are known to influence the germ cell fate. Their removal induces germ cell apoptosis. Proteins of the Bcl-2 family provide one signaling pathway which appears to be essential for male germ cell homeostasis. In addition to paracrine signals, germ cells also depend upon signals derived from Sertoli by direct membrane contact. Somatostatin is a regulatory peptide playing a role in the regulation of the proliferation of the male gametes. Activin A, follistatin and FSH play a role in germ cell maturation during the period when gonocytes resume mitosis to form the spermatogonial stem cells and differentiating germ cell populations. In vitro cultures systems have provided evidence that spermatogonia in advance stage of differentiation have specific regulatory mechanisms that control their fate. This review article provides an overview of the literature concerning the hormonal pathways regulating spermatogenesis. [Copyright &y& Elsevier]

Cystinuria is a complex genetic disorder. In the present study, we report on the strict linkage disequilibrium of SLC7A9 mutations with the wild type SLC7A9 haplotype of 15 single nucleotide polymorphisms (SNPs) and their effect on cystinuria manifestation and classification. Specifically, screening for mutations and polymorphisms was performed in the family members of ten cystinuric patients with SLC7A9 gene mutations. The molecular genetic and clinical data of cystinuric patients and their relatives were combined to construct the SLC7A9 SNP haplotypes and evaluate the manifestation of the disorder in carriers for a SLC7A9 gene mutation. It was found that all carriers of a SLC7A9 mutation manifested cystinuria if their normal allele had non-wild type nucleotides in two or more of the identified polymorphic sites. Subsequently, the polymorphic background of the SLC7A9 gene probably affects the expression of the disorder in SLC7A9 mutation carriers and points to a revised genetic classification of cystinuric patients. [ABSTRACT FROM AUTHOR]

Phosphodiesterases, particularly the type 5 isoform (PDE5), have gained recognition as pivotal regulators of male reproductive physiology, exerting significant influence on testicular function, sperm maturation, and overall fertility potential. Over the past several decades, investigations have expanded beyond the original therapeutic intent of PDE5 inhibitors for erectile dysfunction, exploring their broader reproductive implications. This narrative review integrates current evidence from in vitro studies, animal models, and clinical research to clarify the roles of PDEs in effecting the male reproductive tract, with an emphasis on the mechanistic pathways underlying cyclic nucleotide signaling, the cellular specificity of PDE isoform expression, and the effects of PDE5 inhibitors on Leydig and Sertoli cell functions. Although certain findings suggest potential improvements in sperm motility, semen parameters, and a more favorable biochemical milieu for spermatogenesis, inconsistencies in study design, limited sample sizes, and inadequate long-term data temper definitive conclusions. Addressing these gaps through standardized protocols, larger and more diverse patient cohorts, and explorations of mechanistic biomarkers could pave the way for incorporating PDE5 inhibitors into evidence-based fertility treatment strategies. In the future, such targeted approaches may inform individualized regimens, optimize male reproductive outcomes, and refine the clinical application of PDE5 inhibitors as part of comprehensive male fertility management. [ABSTRACT FROM AUTHOR]

Male reproductive health is governed by an intricate interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms—encompassing DNA methylation, histone modifications, and non-coding RNA activity—are crucial both for spermatogenesis and sperm maturation. However, oxidative stress, driven by excessive reactive oxygen species, disrupts these processes, leading to impaired sperm function and male infertility. This disruption extends to epigenetic modifications, resulting in abnormal gene expression and chromatin remodeling that compromise genomic integrity and fertilization potential. Importantly, oxidative-stress-induced epigenetic alterations can be inherited, affecting the health and fertility of offspring and future generations. This review investigates how oxidative stress influences epigenetic regulation in male reproduction by modifying DNA methylation, histone modifications, and non-coding RNAs, ultimately compromising spermatogenesis. Additionally, it discusses the transgenerational implications of these epigenetic disruptions and their potential role in hereditary infertility and disease predisposition. Understanding these mechanisms is vital for developing therapeutic strategies that mitigate oxidative damage and restore epigenetic homeostasis in the male germline. By integrating insights from molecular, clinical, and transgenerational research, this work emphasizes the need for targeted interventions to enhance male reproductive health and prevent adverse outcomes in progeny. Furthermore, elucidating the dose–response relationships between oxidative stress and epigenetic changes remains a critical research priority, informing personalized diagnostics and therapeutic interventions. In this context, future studies should adopt standardized markers of oxidative damage, robust clinical trials, and multi-omic approaches to capture the complexity of epigenetic regulation in spermatogenesis. Such rigorous investigations will ultimately reduce the risk of transgenerational disorders and optimize reproductive health outcomes. [ABSTRACT FROM AUTHOR]

Background/Objectives: Beta-thalassemia (BTH), a genetic disorder resulting from beta-globin gene mutations, affects over 1.5 million people globally. The disorder's multifactorial impact on male fertility, particularly through oxidative stress (OS), warrants focused study. This review examines the mechanisms of OS in TM, its implications for male infertility, and the potential of antioxidant therapies to mitigate fertility challenges. Methods: A non-systematic review was conducted using the PubMed, Cochrane, and Medscape databases, focusing on studies on beta-thalassemia (BTH), erectile dysfunction (ED), hormonal alterations, and OS. Studies were screened based on relevance, language, and topic, with 71 articles meeting the inclusion criteria after removing duplicates. Results: The findings reveal that OS, exacerbated by iron overload from regular blood transfusions, is significantly associated with impaired sperm quality and fertility in patients with TM. Iron toxicity affects gonadotropin levels, reduces sperm quality, and contributes to hypogonadism. Additionally, antioxidant therapies show promise in reducing OS-induced sperm damage, though efficacy is limited by a lack of robust clinical trials. Conclusions: OS plays a considerable role in male infertility among patients with TM, primarily through iron-induced sperm damage and hormonal disruptions. While antioxidant therapies may offer a partial remedy, further research is necessary to understand OS's mechanisms in TM and develop effective fertility treatments. This review highlights the need for personalized antioxidant approaches to improve reproductive outcomes in this population. [ABSTRACT FROM AUTHOR]

Background/Objectives: Varicoceles are a common contributor to male infertility, significantly impacting male-factor infertility cases. Traditional diagnostic methods often lack the sensitivity to detect the molecular and cellular disruptions caused by varicoceles, limiting the development of effective, personalized treatments. This narrative review aims to explore the advancements in proteomics and metabolomics as innovative, non-invasive diagnostic tools for varicocele-associated male infertility and their potential in guiding personalized therapeutic strategies. Methods: A comprehensive literature search was conducted using databases such as PubMed, Scopus, and Web of Science up to October 2024. Studies focusing on the application of proteomic and metabolomic analyses in varicocele-associated male infertility were selected. The findings were critically analyzed to synthesize current knowledge and identify future research directions. Results: Proteomic analyses revealed differentially expressed proteins in the sperm and seminal plasma of varicocele patients, revealing disruptions in pathways related to oxidative stress, mitochondrial dysfunction, apoptosis, and energy metabolism. Key proteins such as heat shock proteins, mitochondrial enzymes, and apoptotic regulators were notably altered. Metabolomic profiling uncovered specific metabolites in seminal plasma—such as decreased levels of lysine, valine, and fructose—that correlate with impaired sperm function and fertility potential. The integration of proteomic and metabolomic data provides a comprehensive molecular fingerprint of varicocele-induced infertility, facilitating the identification of novel biomarkers for early diagnosis and the development of personalized therapeutic interventions. Conclusions: Advances in proteomics and metabolomics have significantly enhanced our understanding of the molecular mechanisms underlying varicocele-associated male infertility. These "omics" technologies hold great promise for improving diagnostic accuracy and personalizing treatment, ultimately leading to better outcomes for affected men. Future large-scale clinical trials and validations are essential to confirm these biomarkers and facilitate their integration into routine clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To assess the role of 3.0 T Diffusion Tensor Imaging (DTI) and Fiber Tractography (FT) of the testes in the work-up of nonobstructive azoospermia (NOA). Methods: This prospective study included consecutive NOA men and controls. A 3.0 T scrotal MRI was performed, including DTI. The testicular apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were calculated. FT reconstructions were created. The Kruskal–Wallis test, followed by pairwise comparisons, assessed differences in testicular ADC and FA between NOA histologic phenotypes (group 1: hypospermatogenesis; group 2: maturation arrest; and group 3: Sertoli cell-only syndrome) and normal testes. The Mann–Whitney-U test compared ADC and FA between NOA testes with positive and negative sperm retrieval. Visual assessment of the testicular fiber tracts was performed. Fiber tracts fewer in number, of reduced thickness, disrupted and/or disorganized were considered "abnormal". Chi-square tests and binary logistic regression analysis assessed variations in testicular fiber tracts morphology. Results: Twenty-nine NOA men (mean age: 39 ± 5.93 years) and 20 controls (mean age: 26 ± 5.83 years) were included for analysis. Higher ADC (p < 0.001) and FA (p < 0.001) was observed in NOA testes compared to controls. Differences in FA were found between groups 1 and 3 (0.07 vs 0.10, p = 0.26) and groups 2 and 3 (0.07 vs 0.10, p = 0.03), but not between groups 1 and 2 (p = 0.66). An increase in FA was observed in NOA testes with Sertoli cell-only syndrome compared to hypospermatogenesis and maturation arrest. FA was higher in NOA testes with negative results for the presence of sperm compared to those with positive results (0.09 vs 0.07, p = 0.006). FT showed "abnormal" fiber tracts in NOA testes (p < 0.001). Conclusion: 3.0 T DTI and FT provide an insight into deranged spermatogenesis in NOA testes. [ABSTRACT FROM AUTHOR]

Applies ooplasmic round spermatid nuclear injections for the treatment of nonobstuctive azoospermia. Includes the outcome of human ooplasmic round spermatid nuclear injections; Identification of cells isolated as round spermatids of stages 2 to 7 of spermiogenesis using electron microscopy and confocal scanning laser.

Background/Objectives: Multiple sclerosis (MS) frequently results in both urinary and sexual dysfunction, which significantly impairs quality of life. Conventional treatments for bladder dysfunction often prove insufficient, leading to the exploration of alternative therapies such as percutaneous tibial nerve stimulation (PTNS). This study aimed to assess the impact of PTNS on sexual function and bladder symptoms in female MS patients with neurogenic detrusor overactivity (NDO) and female sexual dysfunction (FSD). Methods: A total of 65 female MS patients with NDO were evaluated and underwent 12 weeks of standardized PTNS treatment. Sexual function was assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R), while bladder symptoms were evaluated using the OAB-v8 questionnaire. Participants were grouped based on the presence of sexual dysfunction and distress and compared to a control group of 20 patients who declined PTNS. Results: Significant improvements were observed in FSFI scores across multiple domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) in the treatment groups (p < 0.05). Additionally, 58.46% of patients showed positive responses to PTNS regarding overactive bladder symptoms (OAB-v8 score), while the control group showed no significant changes. Conclusions: PTNS appears to be an effective therapeutic option for improving sexual function and urinary symptoms in female MS patients with NDO and FSD, offering a promising non-invasive alternative for managing these conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is one of the most common cancers in men worldwide, and its causes are influenced by both genetic and lifestyle factors. One lifestyle factor that has shown mixed evidence is alcohol consumption. While some studies suggest that heavy drinking increases prostate cancer risk, others show little to no connection. This research aims to clarify the relationship between alcohol consumption and prostate cancer by reviewing and analyzing global studies. By exploring how different types of alcohol and drinking patterns may influence cancer risk, the goal is to provide more precise guidance for healthcare providers and patients. These findings can help inform public health recommendations and future research on cancer prevention strategies, especially for higher-risk populations. Background/Objectives: Prostate cancer (PCa) is a significant global health issue. The relationship between alcohol consumption and PCa risk has been the subject of extensive research, yet findings remain inconsistent. This review aims to clarify the association between alcohol intake and PCa risk, its aggressiveness, and the potential metabolic pathways involved in PCa onset. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed and MEDLINE, focusing on epidemiological studies, meta-analyses, cohort studies, and case–control studies. Studies evaluating alcohol consumption, prostate-specific antigen (PSA) levels, and PCa risk were included. The review also explored the roles of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in alcohol metabolism. Results: The analysis reveals a complex relationship between alcohol consumption and PCa. Heavy alcohol intake is associated with an increased risk of PCa, particularly more aggressive forms, and higher mortality rates. However, studies also show weak or no association between moderate alcohol consumption and PCa. The variability in findings may be attributed to differences in alcohol types, regional factors, and study methodologies. Conclusions: The link between alcohol consumption and PCa risk is multifaceted. While heavy drinking appears to increase the risk of aggressive PCa, the overall relationship remains unclear. Further research is needed to better understand these associations and inform public health recommendations and cancer prevention strategies. [ABSTRACT FROM AUTHOR]

A noninvasive imaging technique providing information about testicular dysfunction in testes with varicocele would be useful. The aim is to measure the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in testes of infertile men with varicocele and to assess interobserver agreement. Sixteen infertile men with varicocele and 14 age‐matched controls underwent 1.5 T diffusion tensor imaging (DTI) MRI. Testicular ADC and FA were measured by two radiologists independently. Parametric and nonparametric statistical tests were applied to compare between the ADC and FA of testes with varicocele and normal testes. Interobserver agreement was evaluated. The interobserver variability for ADC (0.915) and FA (0.948) was very good. No differences in ADC (p = 0.294) were found between the two groups. FA was significantly lower in testes with varicocele compared to age‐matched controls (p < 0.001). An optimal cut‐off of FA 0.08 was found for the diagnosis of varicocele (sensitivity = 88%, specificity = 93.5%, positive predictive value = 91.6% and negative predictive value = 90.6%). Based on our results, FA is useful for the diagnosis of testes in infertile men with varicocele, with very good interobserver agreement. Therefore, DTI may be used as a noninvasive imaging tool in the work‐up of varicocele. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility of diffusion tensor imaging (DTI) and fiber tractography (FT) of the normal epididymis and to determine normative apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values. Methods: Twenty-eight healthy volunteers underwent MRI of the scrotum, including DTI on a 3.0 T system. For each anatomic part of the epididymis (head, body and tail) free-hand regions of interest were drawn and the mean ADC and FA were measured by two radiologists in consensus. Parametric statistical tests were used to determine intersubject differences in ADC and FA between the anatomic parts of each normal epididymis and between bilateral epididymides. Fiber tracts of the epididymis were reconstructed using the MR Diffusion tool. Results: The mean ADC and FA of the normal epididymis was 1.31 × 10–3 mm2/s and 0.20, respectively. No differences in ADC (p = 0.736) and FA (p = 0.628) between the anatomic parts of each normal epididymis were found. Differences (p = 0.020) were observed in FA of the body between the right and the left epididymis. FT showed the fiber tracts of the normal epididymis. Main study's limitations include the following: small number of participants with narrow age range, absence of histologic confirmation and lack of quantitative assessment of the FT reconstructions. Conclusion: DTI and FT of the normal epididymis is feasible and allow the noninvasive assessment of the structural and geometric organization of the organ. [ABSTRACT FROM AUTHOR]

Infertility represents a significant global health challenge impacting millions of couples worldwide. Approximately half of all infertile couples exhibit compromised semen quality, indicative of diminished male fertility. While the diagnosis of male infertility traditionally relies on semen analysis, its limitations in providing a comprehensive assessment of male reproductive health have spurred efforts to identify novel biomarkers. Seminal plasma, a complex fluid containing proteins, lipids, and metabolites, has emerged as a rich source of such indicators. Reproduction depends heavily on seminal plasma, the primary transporter of chemicals from male reproductive glands. It provides a non-invasive sample for urogenital diagnostics and has demonstrated potential in the identification of biomarkers linked to illnesses of the male reproductive system. The abundance of seminal proteins has enabled a deeper understanding of their biological functions, origins, and differential expression in various conditions associated with male infertility, including azoospermia, asthenozoospermia, oligozoospermia, teratozoospermia, among others. The true prevalence of male infertility is understated due to the limitations of the current diagnostic techniques. This review critically evaluates the current landscape of seminal plasma biomarkers and their utility in assessing male infertility. Βy bridging the gap between research and clinical practice, the integrative assessment of seminal plasma biomarkers offers a multimodal approach to comprehensively evaluate male infertility. [ABSTRACT FROM AUTHOR]

Bilateral normal testes asymmetry represents an interesting phenomenon. The aim was to assess possible differences in the biochemical profile of bilateral normal testes by 3.0 T proton magnetic resonance spectroscopy (1H‐MRS). Twenty‐one men were examined with scrotal 3.0 T MRI, including a single‐voxel point‐resolved spectroscopy sequence. MR spectra were obtained by placing a volume of interest in the middle of each normal testis. Normalised metabolite concentrations, defined as ratios of the calculated metabolite concentrations relative to creatine (Cr) concentration, were compared between bilateral normal testes using Mann–Whitney U test. 1H‐MRS allowed the detection of certain testicular metabolites, including total choline, Cr, myo‐inositol, Glx, total lipids and macromolecules resonating at 0.9, 1.3 and 2.0 ppm. Normal left testis had higher median normalised concentrations of Glx (p =.002) and lactate (p =.041) compared with the normal right testis. Differences in concentrations of Glx were attributed to differences in glutamate (p =.020). Normal testes asymmetry is confirmed in this study by differences in the biochemical testicular profile, as assessed by 3.0 T 1H‐MRS. Increase in levels of glutamate and lactate in normal left testis should be correlated with changes in metabolic pathways, specifically glycometabolism and amino acid metabolism. [ABSTRACT FROM AUTHOR]

As global demographics shift toward increasing paternal age, the realm of assisted reproductive technologies (ARTs), particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), faces new challenges and opportunities. This study provides a comprehensive exploration of the implications of advanced paternal age on ART outcomes. Background research highlights the social, cultural, and economic factors driving men toward later fatherhood, with a focus on the impact of delayed paternity on reproductive outcomes. Methods involve a thorough review of existing literature, centering on changes in testicular function, semen quality, and genetic and epigenetic shifts associated with advancing age. Study results point to intricate associations between the father's age and ART outcomes, with older age being linked to diminished semen quality, potential genetic risks, and varied impacts on embryo quality, implantation rates, and birth outcomes. The conclusions drawn from the current study suggest that while advanced paternal age presents certain risks and challenges, understanding and mitigating these through strategies such as sperm cryopreservation, lifestyle modifications, and preimplantation genetic testing can optimize ART outcomes. Future research directions are identified to further comprehend the epigenetic mechanisms and long-term effects of the older father on offspring health. This study underscores the need for a comprehensive approach in navigating the intricacies of delayed fatherhood within the context of ART, aiming for the best possible outcomes for couples and their children. [ABSTRACT FROM AUTHOR]

Purpose: To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high level of interest in this disease. Methods: A comprehensive and exhaustive review of the literature was performed, identifying hundreds of articles on the topic. Results: Peyronie's disease is a condition that has been recognized, studied, and treated for centuries; despite this, if one excludes surgery in cases in which the deformity is stable, no clear treatment (or line of treatment) is available for complete relief of signs and symptoms. Treatment options were divided into local, oral, and injection therapy, and a wide variety of drugs, remedies, and options were identified. Conclusions: Low-intensity extracorporeal shock wave therapy, vacuum therapy, penile traction therapy, phosphodiesterase type 5 inhibitors, hyaluronic acid, and collagenase of Clostridium histolyticum may be recommended only in specific contexts. Further studies on individual options or potential combinations are required. [ABSTRACT FROM AUTHOR]

Bladder dysfunction, particularly neurogenic detrusor overactivity (DO), poses a substantial challenge in multiple sclerosis (MS) patients, detrimentally impacting their quality of life (QoL). Conventional therapies often fall short, necessitating alternative approaches like posterior tibial nerve stimulation (PTNS) for effective management. This narrative review critically examines the application of PTNS in treating DO among MS patients, aiming to provide a comprehensive synthesis of its efficacy, underlying mechanisms, and clinical outcomes. By evaluating a spectrum of studies, including randomized controlled trials and long-term follow-up research, the review elucidates PTNS's role in enhancing bladder control and ameliorating symptoms of urgency and incontinence, thereby improving patient well-being. Despite its potential, the review acknowledges the limited scope of existing research specific to MS-induced neurogenic DO and calls for further investigation to optimize PTNS protocols and understand its long-term benefits. Highlighting PTNS's minimal invasiveness and favorable safety profile, the review advocates for its consideration as a viable third-line treatment option in MS-related bladder dysfunction management. Through this analysis, the review contributes to the broader narrative of seeking effective, patient-centered therapeutic strategies for MS-related complications, underscoring the importance of personalized care in improving patient outcomes. [ABSTRACT FROM AUTHOR]

This study investigates the impact of pelvic floor muscle training (PFMT) on sexual function and distress in women with multiple sclerosis (MS), a prevalent chronic nervous system disorder associated with sexual dysfunction. This study's primary aim was to assess the effectiveness of PFMT at improving sexual function and alleviating sexual distress in this population. In a randomised controlled trial, 82 women with MS were divided into two groups: Group A (41 women) underwent 12 weeks of PFMT, while Group B (41 women) served as a control group with no intervention. Both groups were assessed at the beginning and end of this study using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R). Statistical analysis, including Chi-square tests, was employed to compare the outcomes between the two groups, with a p-value of less than 0.05 considered significant. The results revealed no significant differences in baseline sexual function and distress between the groups. However, at the conclusion of the 12-week period, Group A exhibited statistically significant improvements in nearly all domains of FSFI and FSDS-R compared to Group B, except in the pain domain. This study concludes that PFMT can effectively enhance sexual function and reduce sexual distress in women suffering from MS. These findings underscore the potential of PFMT as a therapeutic intervention in managing sexual dysfunction associated with MS. [ABSTRACT FROM AUTHOR]

Presents research which used ooplasmic injections of secondary spermatocytes in men with non-obstructive azoospermia. Some men with non-obstructive azoospermia having testicular foci of spermatids or spermatozoa; Methods; Results; Usefulness of ooplasmic injections of secondary spermatocytes.

The human microbiota in the genital tract is pivotal for maintaining fertility, but its disruption can lead to male infertility. This study examines the relationship between microbial dysbiosis and male infertility, underscoring the promise of precision medicine in this field. Through a comprehensive review, this research indicates microbial signatures associated with male infertility, such as altered bacterial diversity, the dominance of pathogenic species, and imbalances in the genital microbiome. Key mechanisms linking microbial dysbiosis to infertility include inflammation, oxidative stress, and sperm structural deterioration. Emerging strategies like targeted antimicrobial therapies, probiotics, prebiotics, and fecal microbiota transplantation have shown potential in adjusting the genital microbiota to enhance male fertility. Notably, the application of precision medicine, which customizes treatments based on individual microbial profiles and specific causes of infertility, emerges as a promising approach to enhance treatment outcomes. Ultimately, microbial dysbiosis is intricately linked to male infertility, and embracing personalized treatment strategies rooted in precision medicine principles could be the way forward in addressing infertility associated with microbial factors. [ABSTRACT FROM AUTHOR]

Background: Non-obstructive azoospermia (NOA) presents a challenge in male infertility management. This study aimed to assess the efficacy of diagnostic testicular biopsy (DTB) in predicting sperm retrieval success via therapeutic testicular biopsy (TTB) and to understand the role of systemic inflammation in microdissection testicular sperm extraction (mTESE) outcomes. Methods: A retrospective analysis was conducted on 50 NOA males who underwent mTESE at the University of Ioannina's Department of Urology from January 2017 to December 2019. All participants underwent thorough medical evaluations, including semen analyses and endocrinological assessments. Results: DTB did not detect spermatozoa in half of the patients who later showed positive sperm findings in TTB. Preoperative variables, such as age, plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), prolactin (PRL), estradiol (E2), and inflammation biomarkers (neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–eosinophil ratio (MER)), were not consistently predictive of sperm retrieval success. Notably, TTB-negative patients had elevated NLR and PLR values, suggesting a possible link between systemic inflammation and reduced sperm retrieval during mTESE. Conclusions: The findings question the necessity of an initial DTB, which might provide misleading results. A negative DTB should not deter further TTB or intracytoplasmic sperm injection (ICSI) attempts. The study emphasizes the need for further research to refine diagnostic approaches and deepen the understanding of factors influencing sperm retrieval in NOA patients, ultimately enhancing their prospects of biological parenthood. [ABSTRACT FROM AUTHOR]

The average age of fathers at first pregnancy has risen significantly over the last decade owing to various variables, including a longer life expectancy, more access to contraception, later marriage, and other factors. As has been proven in several studies, women over 35 years of age have an increased risk of infertility, pregnancy problems, spontaneous abortion, congenital malformations, and postnatal issues. There are varying opinions on whether a father's age affects the quality of his sperm or his ability to father a child. First, there is no single accepted definition of old age in a father. Second, much research has reported contradictory findings in the literature, particularly concerning the most frequently examined criteria. Increasing evidence suggests that the father's age contributes to his offspring's higher vulnerability to inheritable diseases. Our comprehensive literature evaluation shows a direct correlation between paternal age and decreased sperm quality and testicular function. Genetic abnormalities, such as DNA mutations and chromosomal aneuploidies, and epigenetic modifications, such as the silencing of essential genes, have all been linked to the father's advancing years. Paternal age has been shown to affect reproductive and fertility outcomes, such as the success rate of in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and premature birth rate. Several diseases, including autism, schizophrenia, bipolar disorders, and paediatric leukaemia, have been linked to the father's advanced years. Therefore, informing infertile couples of the alarming correlations between older fathers and a rise in their offspring's diseases is crucial, so that they can be effectively guided through their reproductive years. [ABSTRACT FROM AUTHOR]

Introduction: Erectile dysfunction is associated with diabetes mellitus with an estimated prevalence of 52.5% in the diabetic population. The first-line therapy for erectile dysfunction is phosphodiesterase type 5 inhibitors, but data suggest that diabetic men may be less responsive than non-diabetic men. Thus, other treatments, including intracavernosal injections, intraurethral prostaglandin, vacuum erection devices and penile prosthetic surgery, should be considered in management of diabetic men with erectile dysfunction refractory to phosphodiesterase type 5 inhibitors. Furthermore, combination therapy of phosphodiesterase type 5 inhibitors and other oral treatments such as arginine or L-carnitine may have synergistic effects resulting in better outcomes. In addition, there are novel therapies such as low-intensity shockwave therapy and stem-cell therapy, which may also be effective in targeted treatment modalities. Furthermore, studies suggest that erectile dysfunction can be improved by targeting concurrent comorbidities or metabolic diseases such as depression, hypertension, hypogonadism, and dyslipidaemia. We present an evidence-based narrative review focusing on the management of erectile dysfunction in diabetic men who have not responded to phosphodiesterase type 5 inhibitors. Conclusions: Both clinicians and patients should be aware of the different management options in diabetic patients who have not responded to phosphodiesterase type 5 inhibitors. [ABSTRACT FROM AUTHOR]

The objective of this review study is to evaluate the therapeutic role of PDE5 inhibitors (PDE5is) in the amelioration of oligoasthenospermia in infertile males. PDE5is have a beneficial influence on the secretory function of the Leydig and Sertoli cells, the biochemical environment within the seminiferous tubule, the contractility of the testicular tunica albuginea, and the prostatic secretory function. In several studies, the overall effect of sildenafil and vardenafil increased quantitative and qualitative sperm motility. Furthermore, some studies indicate that PDE5is influence positively the sperm capacity to undergo capacitation under biochemical conditions that are known to induce the sperm capacitation process. Additional research efforts are necessary in order to recommend unequivocally the usage of sildenafil, vardenafil, or avanafil for the alleviation of male infertility. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer is a malignancy that predominantly affects male patients. Surgical treatment is the first option for clinical management and cancer cell characterization is critical for tumor margin detection and complete tumor removal. We developed a specialized intraoperative flow cytometry (iFC) methodology for bladder cancer cell detection. Our study, including 52 individuals, reveals that iFC is highly specific, sensitive and accurate in detecting cancer cells, based on the quantification of cell proliferation and the presence of tumor aneuploidy. The results of this study advocate further research on the utility of iFC as a next-generation malignancy evaluation technique during transurethral resections. Bladder cancer represents a major health issue. Transurethral resection is the first line treatment and an accurate assessment of tumor margins might warrant complete tumor removal. Genomic instability and proliferative potential are common hallmarks of cancer cells. We have previously demonstrated the utility of intraoperative flow cytometry (iFC), a next-generation margin evaluation methodology for assessment of DNA content, in the detection of several types of malignancy. In the current study we investigated the possible value of iFC in the characterization of bladder cancer during surgery. Samples from a population of 52 people with urothelial cancer were included in the study. The total time for iFC evaluation is 3–5 min per sample and included a two-step analysis, including DNA-index and Tumor-index calculation. First, DNA-index calculation revealed 24 hyperploid and one hypoploid tumor. Second, cell cycle analysis and Tumor-index calculation revealed that tumor samples are distinguished from normal cells based on their significantly higher proliferative potential. The standard for iFC evaluation was pathology assessment and revealed that our protocol exhibits an accuracy of 98% in defining the presence of cancer cells in a given sample. Our results support the further assessment of iFC value towards its use as a novel malignancy evaluation tool in transurethral resections. [ABSTRACT FROM AUTHOR]

Objectives: To explore the association between testicular volumetric apparent diffusion coefficient (ADC) histogram analysis metrics and histologic categories in nonobstructive azoospermia (NOA). The role of ADC histogram analysis in predicting the presence of spermatozoa, prior to testicular sperm extraction (TESE), was also investigated. Methods: Forty-one NOA men and 17 age-matched controls underwent scrotal MRI with diffusion-weighted imaging. Histogram analysis of ADC data of the whole testis was performed. Metrics including mean, standard deviation, median, mode, 25th percentile, 75th percentile, skewness, kurtosis, and entropy of volumetric ADC histograms were calculated. Nonparametric statistical tests were used to assess differences in ADC histogram parameters between NOA histologic categories (hypospermatogenesis, severe hypospermatogenesis, early maturation arrest, and Sertoli cell-only syndrome) and normal testes and, between NOA with positive and negative sperm retrieval. Results: Normal testes had a lower mean, median, mode, 25th percentile (p < 0.001), and 75th percentile of ADC (p = 0.001), compared to NOA histologic phenotypes. NOA with hypospermatogenesis had a lower 25th percentile of ADC compared to NOA with severe hypospermatogenesis. Regression analysis revealed that the 25th percentile of ADC had a moderately negative correlation with NOA histologic phenotype. The median ADC proved the most significant metric (p = 0.007) to predict the presence of sperm. Conclusions: Testicular volumetric ADC histogram parameters may contribute in the identification of the subpopulation of NOA men with a specific type of spermatogenic arrest. Key Points: • Volumetric ADC histogram analysis metrics may be used as noninvasive markers of impaired spermatogenesis in nonobstructive azoospermia. • The 25th percentile of ADC proved useful in discriminating between NOA testes with hypospermatogenesis and severe hypospermatogenesis. • The median ADC proved the most significant parameter to predict the presence of viable spermatozoa prior to TESE. [ABSTRACT FROM AUTHOR]

Background: The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates.Objective and Rationale: The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men.Search Methods: A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated.Outcomes: A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias.Wider Implications: This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings. [ABSTRACT FROM AUTHOR]

The potential renoprotective effects of vardenafil (VAR) have been evaluated in a very limited number of studies using acute kidney injury animal models other than contrast-induced nephropathy (CIN) with promising results, while avanafil (AVA) has not been evaluated in this respect before. The purpose of this study was to evaluate for the first time the potential renoprotective effect of VAR and AVA in a rat model of CIN. Twenty-five male Wistar rats were equally assigned into five groups: control, CIN, CIN+N-acetyl cysteine (NAC) (100 mg/kg/day) as a positive control, CIN+VAR (10 mg/kg/day) and CIN+AVA (50 mg/kg/day). CIN was induced by dehydration, inhibition of prostaglandin and nitric oxide synthesis as well as exposure to the contrast medium (CM). Serum Cr (sCr) levels were measured at 24 and 48 h after CIN induction. At 48 h of CM exposure, animals were sacrificed. Matrix metalloproteinase (MMP) 2 (MMP-2) and MMP-9, kidney injury molecule 1 (KIM-1) and cystatin-C (Cys-C) were measured on renal tissue. Histopathological findings were evaluated on kidney tissue. All treatment groups had close to normal kidney appearance. sCr levels subsided in all treatment groups compared to CIN group at 48 h following CIN induction. A significant decline in the levels of MMP-2, MMP-9, KIM-1 and Cys-C compared to CIN group was observed. These results provide emerging evidence that VAR and AVA may have the potential to prevent CIN. [ABSTRACT FROM AUTHOR]

Mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) are post‐translational modifiers that regulate energy production, body homeostasis and mitochondrial activities via different substrates in response to environmental stressors. The present study aimed at assessing the expression of SIRT3, SIRT4, and SIRT5 in the semen of infertile men. Expression analysis was performed using q‐RT PCR. All mitochondrial sirtuin genes were significantly down‐regulated in the semen of infertile men compared to fertile men. Mitochondrial sirtuin genes expression levels were correlated with mitochondrial HSP90 expression. HSP90 expression was positively correlated with SIRT3, SIRT4 and SIRT5 expression in the semen of fertile men, while a negative correlation was observed between HSP90 in the semen of infertile men and mitochondrial sirtuin genes in the semen of fertile men. These data suggest that dysregulation of mitochondrial sirtuin genes causes mitochondrial dysfunction due to stress, which appears to be associated with human male infertility by compromising functional and structural sperm integrity. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate the sensitivity of male testis parenchyma cells to chemotherapy agents and the protective effects and mechanisms of Morinda citrifolia (Noni) administration against structural and functional changes before and after chemotherapy (Paclitaxel (PTX)). For this purpose, rats were randomly assigned into four groups (Control = G1, PTX 5 mg/kg = G2; PTX + Noni 10 mg/kg = G3, PTX + Noni 20 mg/kg = G4). PTX was injected intraperitoneally for 4 consecutive weeks, at a dose of 5 mg/kg to all groups except the control group. Then noni was administrated in 10 (G3) and 20 (G4) mg/kg groups orally (gavage) for 14 days. Biochemical analyses, Real-Time Polymerase Chain Reaction (PCR), and immunohistochemical analyses were performed. According to our results, Total Oxidative Stress (TOS) and Malondialdehyde (MDA) were significantly increased in the PTX group (P < 0.01). Superoxide Dismutase (SOD) enzyme activity and Total Antioxidant Capacity (TAC) levels were decreased (P < 0.01). The changes in the rats treated with PTX + Noni 20 mg/kg were noteworthy. The increased levels of IL1-β (Interleukin 1 beta) and TNFα (tumor necrosis factor-alpha) with PTX were down-regulated after treatment with PTX + Noni 20 mg/kg (P < 0.01) (9 % and 5 % respectively). In addition, Noni restored the testicular histopathological structure by reducing caspase-3 expression and significantly (61 %) suppressed oxidative DNA damage and apoptosis (by regulating the Bax (bcl-2-like protein 4)/Bcl-2 (B-cell lymphoma gene-2) ratio). In conclusion, Noni reduced cellular apoptosis and drastically changed Caspase 8 and Bax/Bcl-2 levels. Furthermore, it considerably decreases oxidative damage and can be used in testicular degeneration. • PTX-induced toxicity was established in male germ cell Sprague Dawley. • Oxidative stress levels in germ cells and testis tissue were very high. • Noni increased TAC level and decreased SOD and MDA level. • Noni restored the testicular histopathological structure by reducing caspase-3 expression. • Noni significantly (61 %) suppressed oxidative DNA damage and apoptosis by regulating the Bax/Bcl-2 ratio. [ABSTRACT FROM AUTHOR]

Preliminary published data depict a much greater prevalence of males with laboratory‐confirmed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) referred for intensive care unit admission and severe sequelae in several countries. In this context, males seem to not only be more susceptible to the infection compared to female subjects, at least in Western countries, but their case fatality rate attributable to SARS‐CoV‐2 infection is also highest. Therefore, we may speculate that the different hormonal milieu could have a more profound pathophysiological role in association with SARS‐CoV‐2, with endogenous testosterone leaving men more prone to develop more serious complications related to the SARS‐CoV‐2 infection. Another option is that SARS‐CoV‐2 infection per se causes an acute stage of male hypogonadism, the depletion of androgenic action triggering serious or an even fatal course of the disease. Therefore, we strongly advocate the development of a prospective multidimensional andrological translational research project in men, which we called the PROTEGGIMI study. In this Opinion Article, we will not only highlight novel research activity in this area but also invite other researchers and learned scientific societies to join us in our efforts to understand an important and very newly discovered gap in knowledge, which may have serious implications for the lives of millions of men. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the biochemical milieu in testes with nonobstructive azoospermia (NOA) by using proton MR spectroscopy (1H-MRS) in detecting differences in testicular metabolites between histological stages of NOA and in assessing the possible presence of spermatozoa before microdissection testicular sperm extraction (mTESE).Methods: Forty-nine NOA men and fifty age-matched controls were included in this prospective study. A single-voxel point-resolved spectroscopy sequence with TR/TE (2000/25 ms) was used. NOA testes were classified using the higher Johnsen score (hJS) (group 1, hJS ≥ 8; and group 2, hJS < 8). Nonparametric statistical tests were used to assess differences in normalized metabolite concentrations, defined as ratios of the metabolite concentrations versus creatine concentration between (a) NOA and controls, (b) NOA groups, and (c) NOA with positive and negative sperm retrieval.Results: Normalized concentrations of total choline (median 0.396 vs 1.09 mmol/kg, p = 0.002), myo-inositol (median 1.985 vs 3.19 mmol/kg, p = 0.002), and total lipids and macromolecules (TLM) resonating at 0.9 ppm (median 0.962 vs 2.43 mmol/kg, p = 0.024), 1.3 ppm (median 4.88 vs 10.7 mmol/kg, p = 0.043), and 2.0 ppm (median 2.33 vs 5.96 mmol/kg, p = 0.007) were reduced in NOA testes compared with controls. Decreased concentrations of TLM 2.0 (median 3.755 vs 0.436 mmol/kg, p = 0.043) were found in group 2 compared with group 1. Increased normalized concentrations of glutamate were observed in NOA testes with failed sperm retrieval (median 0.321 vs 0.000 mmol/kg, p = 0.028).Conclusions: 1H-MRS provides metabolic information about the testis in NOA patients and assesses spermatogenic status before mTESE.Key Points: • NOA testes differed from age-matched controls, in terms of reduced normalized concentrations of tChol, mI, and lipids. • TLM 2.0 peaks were found useful in the identification of NOA testes with the presence of foci of advanced spermatogenesis up to the haploid gamete stage. • Glu proved a reliable metabolic signature of spermatogenesis in NOA population by assessing the possible presence of sperm after mTESE. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. Health systems across the world are struggling to manage it. Added to this struggle are the effects of social confinement and isolation. This brings into question whether the latest guidelines are relevant in this crisis. We aim to support urologists in this difficult situation by providing tools that can facilitate decision making, and to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible. We hope that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic. The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. As a scientific society, the European Association of Urology, via the guidelines, section offices, and the European Urology family of journals, we believe that it is important that we try to support urologists in this difficult situation. We aim to do this by providing tools that can facilitate decision making with the goal to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible, although it is clear that it is not always possible to mitigate them entirely. We hope that these revised recommendations will fill an important urological practice void and assist urologist surgeons across the globe as they do their very best to deal with the crisis of our generation. [ABSTRACT FROM AUTHOR]

Background: Factor affecting sperm retrieval rate (SRR) or pregnancy rates (PR) after testicular sperm extraction (TESE) in patients with non-obstructive azoospermia (NOA) have not been systematically evaluated. In addition, although micro-TESE (mTESE) has been advocated as the gold standard for sperm retrieval in men with NOA, its superiority over conventional TESE (cTESE) remains conflicting.Objective and Rationale: The objective was to perform a meta-analysis of the currently available studies comparing the techniques of sperm retrieval and to identify clinical and biochemical factors predicting SRR in men with NOA. In addition, PRs and live birth rates (LBRs), as derived from subjects with NOA post-ICSI, were also analysed as secondary outcomes.Search Methods: An extensive Medline, Embase and Cochrane search was performed. All trials reporting SRR derived from cTESE or mTESE in patients with NOA and their specific determinants were included. Data derived from genetic causes of NOA or testicular sperm aspiration were excluded.Outcomes: Out of 1236 studies, 117 studies met the inclusion criteria for this study, enrolling 21 404 patients with a mean age (± SD) of 35.0 ± 2.7 years. cTESE and mTESE were used in 56 and 43 studies, respectively. In addition, 10 studies used a mixed approach and 8 studies compared cTESE with mTESE approach. Overall, a SRR per TESE procedure of 47[45;49]% (mean percentage [95% CI]) was found. No differences were observed when mTESE was compared to cTESE (46[43;49]% for cTESE versus 46[42;49]% for mTESE). Meta-regression analysis demonstrated that SRR per cycle was independent of age and hormonal parameters at enrolment. However, the SRR increased as a function of testis volume. In particular, by applying ROC curve analysis, a mean testis volume higher than 12.5 ml predicted SRR >60% with an accuracy of 86.2% ± 0.01. In addition, SRR decreased as a function of the number of Klinefelter's syndrome cases included (S = -0.02[-0.04;-0.01]; P < 0.01. I = 0.12[-0.05;0.29]; P = 0.16). Information on fertility outcomes after ICSI was available in 42 studies. Overall, a total of 1096 biochemical pregnancies were reported (cumulative PR = 29[25;32]% per ICSI cycle). A similar rate was observed when LBR was analysed (569 live births with a cumulative LBR = 24[20;28]% per ICSI cycle). No influence of male and female age, mean testis volume or hormonal parameters on both PR and LBR per ICSI cycle was observed. Finally, a higher PR per ICSI cycle was observed when the use of fresh sperm was compared to cryopreserved sperm (PR = 35[30;40]%, versus 20[13;29]% respectively): however, this result was not confirmed when cumulative LBR per ICSI cycle was analysed (LBR = 30[20;41]% for fresh versus 20[12;31]% for cryopreserved sperm).Wider Implications: This analysis shows that cTESE/mTESE in subjects with NOA results in SRRs of up to 50%, with no differences when cTESE was compared to mTESE. Retrieved sperms resulted in a LBR of up to 28% ICSI cycle. Although no difference between techniques was found, to conclusively clarify if one technique is superior to the other, there is a need for a sufficiently powered and well-designed randomized controlled trial to compare mTESE to cTESE in men with NOA. [ABSTRACT FROM AUTHOR]

Abstract: The main objective of this study was to evaluate the effects of a micronutrient supplementation (MS) combined with avanafil on sperm function. Oligoasthenospermic men (n = 217) were treated daily for 90 days with either an MS (45 men, Group A), l‐carnitine (44 men, Group B), MS plus avanafil (43 men, Group C) or avanafil (43 men, Group D); another group of 42 men with oligoasthenospermia (Group E) received no treatment. Sperm parameters were evaluated before and after the end of treatment in each Group A, B, C and D respectively. The same sperm parameters were measured in each participant of Group E before and at the 90‐day experimental period. Within Groups A, C or D, the total percentage of motile spermatozoa, the hypoosmotic swelling test (HOST) result and the percentage of hyperactivated spermatozoa after incubation under conditions known to induce sperm capacitation were significantly greater after MS or MS plus avanafil treatment, or avanafil treatment than before the respective treatment. We suggest that MS or MS plus avanafil combined administration or avanafil alone improves sperm membrane permeability with an overall result improvement in sperm motility, outcome of HOST and increase in the percentage of hyperactivated spermatozoa. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to test platelet function pre- and peri-operatively in clopidogrel-treated patients undergoing transurethral resection of the prostate. Methods: This was a pilot study involving 20 male patients treated with clopidogrel (75 mg/day) for the secondary prevention of cardiovascular disease and scheduled for elective transurethral resection of the prostate. Platelet function testing with light transmittance aggregometry in platelet-rich plasma of four samples (T0, T1, T2, and T3 drawn on the same day, 3 and 7 days of clopidogrel cessation and 24-h post-operatively, respectively) was performed and evaluated in each patient. P-selectin membrane expression was evaluated using monoclonal antibodies. Results: The platelet response to adenosine diphosphate 5 µΜ and 20 µΜ at T0 were 42 ± 15 and 60 ± 14%, respectively. After discontinuation of clopidogrel, corresponding maximum aggregation values at T1 were 60 ± 16 and 74 ± 14%, and increased to 69 ± 16 and 79 ± 18% at T2. No significant difference in platelet aggregation values were noted between T1 and T2, while similar aggregation values were recorded at T3. Conclusions: Our findings indicate that in patients undergoing transurethral resection of the prostate, platelet activation is similar 3 and 7 days from clopidogrel cessation. These results may be of relevance in subjects at increased thrombotic risk prior to a surgical procedure carrying a high-bleeding risk. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the feasibility of testis diffusion tensor imaging (DTI), to determine normative apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values and to assess the efficacy of DTI in characterizing testicular pathology.Materials and Methods: Fifty-six men underwent MRI of the scrotum, including DTI. Parametric and non-parametric statistical tests were used to compare the ADC and FA between the cranial, middle and lower thirds of normal testis and between the bilateral testicular thirds. Comparison between the ADC and FA of normal testis, malignant and benign testicular lesions was performed.Results: No significant differences of the ADC and FA in normal testis between the cranial, middle and lower thirds and between the bilateral testicular thirds were found. ADC was significantly lower in malignancies compared to normal testis (P=0.006) and benign testicular lesions (P=0.006). FA was significantly higher both in malignancies (P=0.001) and benign lesions (P<0.001) compared to normal testis. FA in malignancies did not differ from FA in benign lesions (P=0.221) CONCLUSIONS: This study shows the feasibility of testis DTI. Both ADC and FA significantly differ between testicular lesions and normal testis, although FA did not show an incremental diagnostic value compared to ADC in lesion differentiation. [ABSTRACT FROM AUTHOR]

Background In humans, the left testis generally hangs lower than the right and the right is larger than the left. Magnetic resonance imaging (MRI) represents an important adjuvant modality in the investigation of testicular diseases. Purpose To assess if normal testes asymmetry is related to apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR). Material and Methods The normal testes from 106 men were included. Testicular volume (TV) was calculated by using the ellipsoid formula: length × width × height × 0.52. Diffusion-weighted imaging was performed using a SS EPI diffusion pulse sequence and b-values of 0 and 900 s/mm-2. Magnetization transfer imaging was obtained using a 3D GRE sequence both with and without an off-resonance radiofrequency pulse. MTR maps were obtained by the following formula: (SIo-SIm) / (SIo) × 100%, where SIo and SIm represent the signal intensity in the baseline image and that in the corresponding image acquired with an off-resonance MT pulse, respectively. The mean and standard deviation of testicular volume (TV), ADC, and MTR of both testes was calculated and compared using a paired sample t-test. Results The mean TV (mL) was greater ( P = 0.006) for the right testis (16.77 ± 4.84) compared to the left (15.97 ± 4.45). ADC of the right testis (1.09 ± 0.12 × 10 - 3 mm2 s-1) was not different ( P = 0.064) from that of the left testis (1.07 ± 0.12 × 10-3 mm2 s-1). Differences ( P = 0.032) were observed between MTR of the right (46.6 ± 2.1%) and left testis (46.0 ± 2.2%). Conclusion The reported differences in paired testes size was confirmed, introducing a possible relationship with structural and functional asymmetry of normal testes, based on MTR. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the difference in apparent diffusion coefficient (ADC) measurements at diffusion-weighted (DW) magnetic resonance imaging of differently shaped regions-of-interest (ROIs) in testicular germ cell neoplasms (TGCNS), the diagnostic ability of differently shaped ROIs in differentiating seminomas from nonseminomatous germ cell neoplasms (NSGCNs) and the interobserver variability.Materials and Methods: Thirty-three TGCNs were retrospectively evaluated. Patients underwent MR examinations, including DWI on a 1.5-T MR system. Two observers measured mean tumor ADCs using four distinct ROI methods: round, square, freehand and multiple small, round ROIs. The interclass correlation coefficient was analyzed to assess interobserver variability. Statistical analysis was used to compare mean ADC measurements among observers, methods and histologic types.Results: All ROI methods showed excellent interobserver agreement, with excellent correlation (P<0.001). Multiple, small ROIs provided the lower mean ADC in TGCNs. Seminomas had lower mean ADC compared to NSGCNs for each ROI method (P<0.001). Round ROI proved the most accurate method in characterizing TGCNS.Conclusion: Interobserver variability in ADC measurement is excellent, irrespective of the ROI shape. Multiple, small round ROIs and round ROI proved the more accurate methods for ADC measurement in the characterization of TGCNs and in the differentiation between seminomas and NSGCNs, respectively. [ABSTRACT FROM AUTHOR]

Objectives: The aim was to determine the proton MR (1H-MR) spectra of normal adult testes and variations with age.Methods: Forty-one MR spectra of normal testes, including 16 testes from men aged 20-39 years (group I) and 25 testes from men aged 40-69 years (group II), were analyzed. A single-voxel point-resolved spectroscopy sequence (PRESS), with TR/TE: 2000/25 ms was used. The volume of interest was placed to include the majority of normal testicular parenchyma. Association between normalized metabolite concentrations, defined as ratios of the calculated metabolite concentrations relative to creatine concentration, and age was assessed.Results: Quantified metabolites of the spectra were choline (Cho), creatine (Cr), myo-inositol (mI), scyllo-inositol, taurine, lactate, GLx compound, glucose, lipids, and macromolecules resonating at 0.9 ppm (LM09), around 20 ppm (LM20), and at 13 ppm (LM13). Most prominent peaks were Cho, Cr, mI, and lipids. A weak negative correlation between mI and age (P = 0.015) was observed. Higher normalized concentrations of Cho (P = 0.03), mI (P = 0.08), and LM13 (P = 0.05) were found in group I than in group II.Conclusions: 1H-MR spectra of a normal adult testis showed several metabolite peaks. A decrease of levels of Cho, mI, and LM13 was observed with advancing age.Key Points: • Single-voxel PRESS MRS of a normal testis is feasible. • 1H-MR spectra of a normal testis showed several metabolite peaks. • Most prominent peaks were Cho, Cr, mI, and lipids. • A decrease of Cho, mI, and LM13 was seen with advancing age. [ABSTRACT FROM AUTHOR]

Background: Cellular angiofibroma represents a rare mesenchymal tumor typically involving the inguinoscrotal area in middle-aged men. Although the origin of this benign tumor is unknown, it is histologically classified as an angiomyxoid tumor. Cellular angiofibroma is characterized by a diversity of pathological and imaging features. An accurate preoperative diagnosis is challenging. Magnetic resonance imaging examination of the scrotum has been reported as a valuable adjunct modality in the investigation of scrotal pathology. The technique by providing both structural and functional information is useful in the differentiation between extratesticular and intratesticular diseases and in the preoperative characterization of the histologic nature of various scrotal lesions. There are few reports in the English literature addressing the magnetic resonance imaging findings of cellular angiofibroma of the scrotum and no reports on functional magnetic resonance imaging data. Here we present the first case of a cellular angiofibroma arising from the tunica vaginalis of the testis and we discuss the value of a multiparametric magnetic resonance protocol, including diffusion-weighted imaging, magnetization transfer imaging and dynamic contrast-enhanced magnetic resonance imaging in the preoperative diagnosis of this rare neoplasm. Case Presentation: A 47-year Greek man presented with a painless left scrotal swelling, which had gradually enlarged during the last 6 months. Magnetic resonance imaging of his scrotum displayed a left paratesticular mass, in close proximity to the tunica vaginalis, with heterogeneous high signal intensity on T2-weighted images and no areas of restricted diffusion. The tumor was hypointense on magnetization transfer images, suggestive for the presence of macromolecules. On dynamic contrast-enhanced magnetic resonance imaging the mass showed intense heterogeneous enhancement with a type II curve. Magnetic resonance imaging findings were strongly suggestive of a benign paratesticular tumor, which was confirmed on pathology following lesion excision. Conclusions: Magnetic resonance imaging of the scrotum by combining conventional and functional magnetic resonance data provides useful diagnostic information in the preoperative characterization of scrotal masses. A possible diagnosis of a benign paratesticular tumor based on magnetic resonance imaging features may improve patient care and decrease the number of unnecessary radical surgical explorations. [ABSTRACT FROM AUTHOR]

Objectives: The aim was to determine the magnetization transfer ratio (MTR) of normal testes, possible variations with age and to assess the feasibility of MTR in characterizing various testicular lesions.Methods: Eighty-six men were included. A three-dimensional gradient-echo MT sequence was performed, with/without an on-resonance binomial prepulse. MTR was calculated as: (SIo-SIm)/(SIo) × 100 %, where SIm and SIo refers to signal intensities with and without the saturation pulse, respectively. Subjects were classified as: group 1, 20-39 years; group 2, 40-65 years; and group 3, older than 65 years of age. Analysis of variance (ANOVA) followed by the least significant difference test was used to assess variations of MTR with age. Comparison between the MTR of normal testis, malignant and benign testicular lesions was performed using independent-samples t testing.Results: ANOVA revealed differences of MTR between age groups (F = 7.51, P = 0.001). Significant differences between groups 1, 2 (P = 0.011) and 1, 3 (P < 0.001) were found, but not between 2, 3 (P = 0.082). The MTR (in percent) of testicular carcinomas was 55.0 ± 3.2, significantly higher than that of benign lesions (50.3 ± 4.0, P = 0.02) and of normal testes (47.4 ± 2.2, P < 0.001).Conclusions: MTR of normal testes decreases with age. MTR might be helpful in the diagnostic work-up of testicular lesions.Key Points: MTR of normal testes shows age-related changes. Testicular carcinomas have high MTR values. MTR may be useful in the diagnostic work-up of testicular lesions. [ABSTRACT FROM AUTHOR]

Introduction The aim of this study is to investigate the role of apparent diffusion coefficient (ADC) values and dynamic contrast enhancement (DCE) patterns in differentiating seminomas from nonseminomatous germ cell tumors (NSGCTs). Materials and methods The MRI examinations of the scrotum of 26 men with histologically proven testicular GCTs were reviewed. DWI was performed in all patients, using a single shot, multi-slice spin-echo planar diffusion pulse sequence and b -values of 0 and 900 s/mm 2 . Subtraction DCE-MRI was performed in 20 cases using a 3D fast-field echo sequence after gadolinium administration. Time-signal intensity curves were created and semi-quantitative parameters (peak enhancement, time to peak, wash-in and wash-out rate) were calculated. The Student's t -test was used to compare the mean values of ADC, peak enhancement, time to peak, wash-in and wash-out rate between seminomas and NSGCTs. ROC analysis was also performed. Results Histopathology disclosed the presence of 15 seminomas and 11 NSGCTs. The mean ± s.d. of ADC values (× 10 −3 mm 2 /s) of seminomas (0.59 ± 0.009) were significantly lower than those of NSGCTs (0.90 ± 0.33) ( P = 0.01). The optimal ADC cut-off value was 0.68 × 10 −3 mm 2 /s. No differences between the two groups were observed for peak enhancement ( P = 0.18), time to peak ( P = 0.63) wash-in rate ( P = 0.32) and wash-out rate ( P = 0.18). Conclusions ADC values may be used to preoperatively differentiate seminomas from NSGCTs. [ABSTRACT FROM AUTHOR]