Background/Objectives: Varicocele repair can improve semen parameters and pregnancy rates in appropriately selected men; however, persistence or recurrence remains a common cause of treatment failure with ongoing infertility or scrotal pain. Because mechanisms and definitions vary across studies, counseling and salvage selection can be challenging. This review synthesizes contemporary evidence on why varicocele recur and provides an anatomy-informed approach to evaluation and retreatment. Methods: A narrative evidence synthesis was performed using PubMed/MEDLINE, prioritizing clinical practice guidelines, systematic reviews, meta-analyses, and contemporary adult and adolescent clinical series addressing mechanisms of failure, diagnostic workup, and outcomes of salvage microsurgery and endovascular therapy. Results: Recurrence rates vary by technique and follow-up, with the lowest rates reported in contemporary microsurgical subinguinal series. The dominant drivers of failure are incomplete venous control and complex reflux pathways, including duplicated internal spermatic veins and missed collaterals such as cremasteric, external spermatic, gubernacular, and deferential veins. Clinical examination remains central; Doppler ultrasonography is most useful when pain persists or semen parameters and testicular growth do not improve. Venography can define culprit channels in complex or multiply treated cases and enables targeted embolization. Retreatment achieves high anatomic success with consistent improvements in semen parameters and meaningful pregnancy rates in available series, with modality-specific complication profiles. Conclusions: Recurrent varicocele should be managed with structured reassessment that links venous anatomy and the index procedure to the salvage option. Microsurgical redo is generally favored after non-microscopic repairs, whereas endovascular occlusion is often preferred after prior surgery or when venographic mapping is needed.

Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) is a high-risk disease state for which early radical cystectomy remains the guideline-supported oncologic reference in surgically fit patients. Bladder-sparing therapy is necessary for patients ineligible for or declining cystectomy, but it is a preference-sensitive trade-off rather than an equivalent alternative: failure may permit high-grade recurrence, progression, and loss of a curative window. This targeted narrative review synthesizes the evidence for intravesical gemcitabine monotherapy, sequential gemcitabine-docetaxel, and the sustained-release gemcitabine intravesical system TAR-200/INLEXZO, updated through 4 August 2026. Because the review is not systematic and the evidence is dominated by single-arm and retrospective studies, cross-study comparisons are descriptive and establish neither superiority nor equivalence; many gemcitabine studies enrolled mixed BCG-failure cohorts that do not satisfy the contemporary definition. Gemcitabine monotherapy is active but shows declining disease control over time. Sequential gemcitabine-docetaxel has accumulated substantial multicenter observational experience, yet a 2026 retrospective comparison did not demonstrate improved high-grade recurrence-free survival over gemcitabine alone. TAR-200 achieved a centrally confirmed complete response at any time in 82.4% of patients, with a median duration of response of 25.8 months in the single-arm phase 2b SunRISe-1 study and is approved in the United States as INLEXZO for BCG-unresponsive carcinoma in situ with or without papillary tumors; no approved agent holds a papillary-only indication. Comparative patient-reported outcome evidence remains limited, and molecular markers, urinary tumor DNA and transcriptomic subtypes remain investigational rather than validated selection tools. Bladder-sparing treatment should therefore be phenotype- and label-aware, time-limited, and coupled to intensive surveillance with predefined triggers for cystectomy.

Background/Objectives: Varicocele is usually clinically left-sided, but imaging and mechanistic studies suggest that contralateral venous reflux or bilateral testicular effects may be more common than physical examination indicates. This narrative review critically examines whether varicocele-associated infertility is better conceptualized as an asymmetric disorder with potential bilateral anatomical or functional involvement and considers the implications for diagnosis and treatment. Methods: PubMed/MEDLINE and Scopus were searched from inception to 21 June 2026 for studies on varicocele laterality, bilateral and subclinical disease, color Doppler ultrasonography, venography, and unilateral versus bilateral repair. Reference lists and contemporary clinical guidelines were also reviewed. Because the included studies differed substantially in patient selection, age, operator technique, diagnostic criteria, and reference standards, reported bilateral rates were not interpreted as head-to-head estimates of diagnostic sensitivity or as pooled prevalence estimates. Results: Physical examination identifies predominantly left-sided clinical disease. Bilateral involvement is reported more frequently when both sides are assessed using Doppler ultrasonography or venography, but estimates vary widely across referral-enriched and highly selected cohorts. Human and experimental evidence supports several mechanisms by which a clinically unilateral lesion may have bilateral functional effects, including shared scrotal hyperthermia, oxidative stress, endocrine disturbance, and venous cross-communication. Bilateral repair is consistent with standard treatment criteria when both varicoceles are clinically palpable. In men with a clinical left varicocele and non-palpable right-sided reflux, comparative evidence is mixed, and current guidelines do not support routine treatment of imaging-only disease. Conclusions: Varicocele is best viewed as an asymmetric disorder that may be anatomically or functionally bilateral in selected men, rather than as a universally bilateral disease. Deliberate bilateral clinical assessment and standardized bilateral ultrasonography when imaging is clinically indicated may improve phenotyping and operative planning. However, contralateral imaging abnormalities should not automatically be converted into a surgical indication.

Declining Leydig cell steroidogenesis contributes to late-onset hypogonadism and to age-associated impairment of male reproductive health. Determinants of dysfunction extend beyond chronological aging. This review synthesizes recent experimental and translational evidence on cellular and molecular processes that compromise Leydig cell endocrine output and the interstitial niche that supports spermatogenesis. Evidence spanning environmental endocrine-disrupting chemicals (EDCs), obesity and metabolic dysfunction, and testicular aging is integrated with emphasis on oxidative stress, endoplasmic reticulum stress, mitochondrial dysregulation, apoptosis, disrupted autophagy and mitophagy, and senescence-associated remodeling. Across model systems, toxicant exposure and metabolic stress converge on impaired organelle quality control and altered redox signaling, with downstream loss of steroidogenic capacity and, in some settings, premature senescence within the Leydig compartment. Aging further reshapes the testicular microenvironment through inflammatory shifts and biomechanical remodeling and may erode stem and progenitor Leydig cell homeostasis, thereby constraining regenerative potential. Single-cell transcriptomic atlases advance the field by resolving Leydig cell heterogeneity, nominating subsets that appear more vulnerable to stress and aging, and mapping age-dependent rewiring of interstitial cell-to-cell communication with Sertoli cells, peritubular myoid cells, vascular cells, and immune cells. Many mechanistic insights derive from rodent in vivo studies and in vitro platforms that include immortalized Leydig cell lines, and validation in human tissue and human clinical cohorts remains uneven. Together, these findings frame mechanistically informed opportunities to preserve endogenous androgen production and fertility through exposure mitigation, metabolic optimization, fertility-preserving endocrine stimulation, and strategies that target inflammation, senescence, and regenerative capacity.

Sickle cell disease (SCD) is an inherited hemoglobinopathy in which hemoglobin S polymerization drives hemolysis and vaso-occlusion with progressive organ morbidity. Male reproductive impairment is increasingly recognized but remains underreported. This narrative review summarizes mechanistic pathways, clinical manifestations, and fertility preservation options relevant to men with SCD. PubMed, the Cochrane Library, and Medscape were searched through 31 December 2025 for human studies addressing endocrine changes, semen quality, priapism and erectile dysfunction, oxidative stress, and treatment-related gonadotoxicity. Evidence supports converging mechanisms: recurrent vaso-occlusion and chronic hypoxia may injure the seminiferous epithelium and impair Leydig cell steroidogenesis; oxidative stress and inflammation contribute to sperm DNA and membrane damage; and disease-modifying or curative therapies such as hydroxyurea and hematopoietic stem cell transplantation can further compromise spermatogenesis. Clinically, men with SCD may present with oligozoospermia, azoospermia, hypogonadism, and sexual dysfunction, particularly after recurrent ischemic priapism. Fertility preservation should be discussed early, ideally before prolonged hydroxyurea exposure or transplantation, and may include semen cryopreservation and testicular sperm extraction (TESE) with assisted reproduction when needed. Prospective longitudinal studies are required to define reproductive trajectories and optimize counseling and management.

Male infertility contributes substantially to couple infertility, and a large proportion of cases remain idiopathic. Dysbiosis within the gut, seminal, and urinary microbiomes has been associated with impaired semen parameters, reproductive tract inflammation, and oxidative stress. This narrative review, informed by a structured literature search, summarizes current evidence for the gut-testis axis and the androbactome in male infertility and discusses mechanistic pathways linking microbial imbalance to sperm dysfunction. Proposed mechanisms include immune activation, increased oxidative stress, endocrine and metabolic perturbations, and disruption of epithelial barriers, including the blood-testis barrier. Early clinical trials report that selected probiotic or synbiotic formulations may be associated with improvements in one or more World Health Organization (WHO) semen parameters and with reductions in oxidative or inflammatory biomarkers (surrogate laboratory endpoints; pregnancy and live-birth outcomes are rarely reported and remain unproven) in selected populations, such as idiopathic infertility and the post-varicocelectomy setting. Given patient heterogeneity, a personalized approach requires prespecified clinical phenotypes and measurable monitoring targets, rather than indiscriminate supplementation. At present, probiotics should be considered an adjunct rather than a stand-alone therapy. Well-designed, contamination-aware microbiome studies and adequately powered randomized trials with clinically meaningful endpoints, including pregnancy and live birth, are required before routine clinical implementation. This synthesis is intended to support personalized counseling and trial design by clarifying candidate phenotypes, appropriate monitoring endpoints, and realistic limitations of current evidence.

Background and Objectives: Stress urinary incontinence (SUI) is a common condition among women and is frequently associated with impaired sexual function and increased sexual distress. Pelvic floor muscle training (PFMT) is considered a first-line conservative treatment for SUI; however, its effects on female sexual function remain incompletely understood. The present study aimed to evaluate the impact of PFMT on sexual function, sexual distress, and pelvic floor muscle performance in women with SUI. Materials and Methods: This prospective controlled observational study included sexually active women with clinically confirmed SUI and female sexual dysfunction. Participants were allocated either to a control group (Group A) or to a supervised 12-week PFMT program (Group B). Sexual function and distress were assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale–Revised (FSDS-R), respectively. Pelvic floor muscle performance was evaluated using Peritron perineometry, including peak vaginal squeeze pressure, endurance, and resting tone. Objective severity of SUI was assessed using the one-hour pad test. Results: A total of 102 women completed the study, including 44 in the control group and 58 in the PFMT group. After 12 weeks, women undergoing PFMT demonstrated significant improvements in urinary continence, pelvic floor muscle strength, and sexual function compared with controls (all p < 0.01). Mean FSFI total score increased from 21.5 ± 2.5 to 26.6 ± 3.3, while the proportion of women with clinically significant sexual distress decreased from 100% to 58.6%. Peak vaginal squeeze pressure and endurance also improved significantly following PFMT. Conclusions: PFMT significantly improves sexual function, reduces sexual distress, and enhances pelvic floor muscle performance in women with SUI. These findings support the integration of PFMT into the comprehensive management of women with SUI and associated sexual dysfunction.

Spermatogenesis is a tightly coordinated differentiation program that sustains male fertility while transmitting genetic and epigenetic information to the next generation. This review consolidates mechanistic evidence showing how RNA-centered regulation integrates with the epitranscriptome and three-dimensional (3D) genome architecture to orchestrate germ-cell fate transitions from spermatogonial stem cells through meiosis and spermiogenesis. Recent literature is critically surveyed and synthesized, with particular emphasis on human and primate data and on stage-resolved maps generated by single-cell and multi-omics technologies. Collectively, available studies support a layered regulatory model in which RNA-binding proteins and RNA modifications coordinate transcript processing, storage, translation, and decay; small and long noncoding RNAs shape post-transcriptional programs and transposon defense; and dynamic chromatin remodeling and 3D reconfiguration align transcriptional competence with recombination, sex-chromosome silencing, and genome packaging. Convergent nodes implicated in spermatogenic failure are highlighted, including defects in RNA metabolism, piRNA pathway integrity, epigenetic reprogramming, and nuclear architecture, and the potential of these frameworks to refine molecular phenotyping in male infertility is discussed. Finally, key gaps and priorities for causal testing in spatially informed, stage-specific experimental systems are outlined.

Psychological stress is increasingly investigated as a potentially modifiable factor in male infertility, in part through oxidative stress. This narrative review synthesizes mechanistic and translational evidence linking stress-related neuroendocrine activation and coping behaviors with redox imbalance in the male reproductive tract. Chronic activation of the hypothalamic-pituitary-adrenal axis and sympathetic outflow elevates glucocorticoids and catecholamines. In controlled animal stress paradigms, this is accompanied by suppression of the hypothalamic-pituitary-gonadal axis and by immune and metabolic changes that favor reactive oxygen species generation. The resulting oxidative stress may reduce Leydig cell steroidogenesis, impair testicular and epididymal function, and induce lipid peroxidation, mitochondrial dysfunction, and sperm DNA fragmentation. In such models, these lesions, together with apoptosis of germ and supporting cells, are associated with lower sperm concentration, reduced motility, compromised viability, and diminished fertilizing potential. Overall, preclinical animal studies using defined stress paradigms provide experimental evidence consistent with causal effects of stress on oxidative injury and reproductive impairment in preclinical settings. Human studies linking perceived stress, anxiety/depression, and disturbed sleep to adverse semen parameters and oxidative biomarkers are summarized. However, the human evidence is predominantly associative, and the available studies are cross sectional and remain vulnerable to residual confounding and reverse causality. Potential effect modifiers, including smoking, alcohol use, and circadian disruption, are also discussed as contributors to heterogeneity across clinical studies. Standardized assessment of stress biology and redox status, longitudinal designs aligned with spermatogenic timing, and well-powered intervention trials are needed to define dose-response relationships and support individualized prevention and care.

Background/Objectives: Hypogonadotropic hypogonadism (HH) is an uncommon but treatable cause of non-obstructive azoospermia (NOA). Fertility can often be restored with gonadotropin therapy. This study evaluated spermatogenic and reproductive outcomes in men with HH-related NOA managed by stepwise gonadotropin therapy, microdissection testicular sperm extraction (microTESE) for persistent azoospermia, and assisted reproduction when indicated. Methods: A retrospective cohort study included 35 men treated between 2010 and 2022. Human chorionic gonadotropin (hCG), with or without follicle-stimulating hormone (FSH), was administered to induce spermatogenesis. Outcomes included sperm appearance in the ejaculate, microTESE sperm retrieval rate in persistent azoospermia, and pregnancy and live birth outcomes after natural conception or in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI) when required. Results: Mean gonadotropin therapy duration was 12.0 months (range 6-24). Sperm appeared in the ejaculate in 27/35 men (77%). The remaining 8/35 (23%) underwent microTESE, with sperm retrieved in 7/8 (88%). Seven couples proceeded to IVF-ICSI, undergoing 11 cycles that yielded 6 clinical pregnancies (55% per cycle) and 5 live birth deliveries, including 2 twin pregnancies. Among responders, 13 natural pregnancies occurred, resulting in 13 live birth deliveries, including 2 twin pregnancies. Overall, 18/35 men (51%) achieved biological fatherhood, corresponding to 18 live birth delivery events (4 twin and 14 singleton deliveries) and 22 newborns. Conclusions: In men with HH-related NOA, exogenous gonadotropin therapy is expected to induce spermatogenesis in most patients. MicroTESE provides high sperm retrieval rates for those without ejaculatory sperm. Through an integrated approach of hormonal induction, microsurgical sperm retrieval, and assisted reproduction, approximately half of patients may ultimately achieve biological fatherhood in longer-term follow-up, depending on baseline severity and partner factors.

Prostatitis includes infectious and noninfectious inflammatory phenotypes that can impair male reproductive potential and may influence couple-level reproduction via seminal inflammatory and microbial exposure. This review summarizes mechanisms linking prostatic inflammation and dysbiosis to semen dysfunction and sperm DNA damage and proposes an infertility-oriented diagnostic and management framework. This is a narrative review of clinical and translational evidence addressing semen inflammation, oxidative stress, sperm DNA fragmentation (SDF), microbiome signatures, and reproductive outcomes in prostatitis (National Institutes of Health (NIH) categories I-IV). Across prostatitis phenotypes, leukocytospermia and elevated seminal cytokines (especially interleukin-8) are associated with impaired motility, altered viscosity and liquefaction, oxidative stress, and higher SDF. Persistent infection or dysbiosis may sustain immune activation and redox injury, while ductal remodeling and pain-related sexual dysfunction can further reduce natural conception. Seminal cytokines and microbes may affect female reproductive tract biology, although clinical outcome data remain limited. Prostatitis-related infertility requires evaluation beyond routine semen analysis. A biomarker-guided workup integrating inflammatory markers, oxidative stress testing, targeted microbiology (culture plus nucleic acid amplification tests when indicated), SDF testing in selected men, and imaging when obstruction is suspected can identify treatable drivers and guide timing and selection of assisted reproduction strategies. Future studies should standardize fertility endpoints and validate biomarker-guided and microbiome-directed interventions.

Testicular germ cell tumors (TGCTs) are the most common solid malignancy in young men and are highly curable, making reproductive and endocrine survivorship central concerns. Gonadal dysfunction is often attributed to orchiectomy and gonadotoxic therapy, yet semen and hormonal abnormalities may already be present at diagnosis. This narrative review synthesizes evidence obtained before orchiectomy and, where explicitly identified, broader pretreatment or pre-gonadotoxic evidence. Pre-orchiectomy studies generally report reduced sperm concentration, total sperm count, and progressive motility, together with impaired Sertoli and Leydig cell function. Tumor-derived human chorionic gonadotropin (hCG) can mask reduced Leydig reserve; in hCG-negative men, research-derived testosterone-to-luteinizing hormone and calculated free testosterone-to-luteinizing hormone ratios may aid risk stratification but lack standardized diagnostic cutoffs. Proposed contributors include testicular dysgenesis, contralateral impairment, germ cell neoplasia in situ, local tumor effects, and oxidative or proteomic alterations, although evidential support varies. These findings support fertility counseling at diagnosis, sperm cryopreservation before orchiectomy when feasible without delaying treatment, selected use of onco-microTESE when no usable ejaculate is available, and hCG-aware endocrine follow-up.

Non-coding RNAs (ncRNAs) are biologically plausible biomarkers in male infertility, but no assay is ready for routine use. This narrative review organizes human evidence by intended clinical decision and defines clinical actionability as a test’s ability to inform a specified decision through analytical reliability, clinical validity, incremental value, decision-level benefit, and feasible implementation. Evidence is most developed for obstructive versus non-obstructive azoospermia (NOA) classification and sperm-retrieval prognosis. Most reports, however, use selected case–control samples, single-center development cohorts, or same-program evaluations. Mixed biospecimens, incompletely specified RNA isoforms and normalization, uncertain cohort independence, imperfect diagnostic references, and protocol-dependent retrieval outcomes limit transportability. No independent geographic validation of a locked ncRNA assay or prospective evaluation of ncRNA-guided management was identified within the retrieved sources. Current guidelines do not recommend routine ncRNA testing. Progress requires prespecified intended uses, locked assays, representative multicenter validation, same-patient comparison with contemporary care, calibrated risk estimates, decision-curve analysis, and patient-important, couple-centered outcomes.

Female sexual dysfunction (FSD) is prevalent among women with multiple sclerosis (MS), leading to significant impairments in quality of life. Despite various available treatments, current approaches often fail to address the complex, multifactorial nature of FSD in this population. Transcutaneous tibial nerve stimulation (TTNS) has recently gained attention as a non-invasive neuromodulation therapy that has demonstrated potential benefits for neurogenic bladder dysfunction, with preliminary evidence suggesting overlapping improvements in sexual function. This narrative review synthesizes current evidence on the use of TTNS for managing FSD in women with MS. A comprehensive literature search of Medline, Web of Science, and Scopus was conducted, focusing on studies that explored TTNS interventions and outcomes in MS-related FSD. The findings indicate that TTNS likely modulates pelvic neural pathways, enhances genital blood flow, and improves key sexual function domains, including arousal, lubrication, and orgasm. Clinical studies using validated assessment tools, such as the Female Sexual Function Index (FSFI), have shown significant improvements in sexual outcomes, particularly when TTNS is combined with pelvic floor muscle training (PFMT). Experimental models further support the plausibility of these findings, linking TTNS to increased pelvic perfusion and more balanced neurogenic regulation of sexual response. Although initial evidence suggests that TTNS is safe, effective, and well-tolerated, limitations include small sample sizes, short follow-up periods, and variability in treatment protocols. Future research should focus on larger controlled trials, long-term follow-up studies, and standardized intervention parameters to optimize the application of TTNS for addressing FSD in women with MS.

Can abstinence from nicotine contribute to the recovery of the nicotine-induced damage in the male reproductive organs (MROs)? What are the effects on the offspring? Abstinence, by decreasing the nicotine-induced oxidative-stress(OS) in MROs, may contribute to production of sperm with better quality that can further affect the offspring development epigenetically. According to the WHO 1.3 billion people are tobacco-users worldwide (36.7% of men and 7.8% of women). Nicotine exposure can impair the steroidogenesis and spermatogenesis, resulting in decreased sperm concentration and motility. By increasing the OS nicotine may induce damage to the chromatin structure of sperm and impair the fertilizing capacity. In the present study, nicotine was selected as the primary addictive component in cigarettes and electronic cigarettes to investigate its effects in the MROs and to further identify the epigenetic impact of paternal exposure to nicotine on the offspring’s development. Additionally, the role of abstinence was investigated. Sixty male Wistar rats were separated equally into three groups: a) the Nico-group (n = 20) that was treated with nicotine (100 μg/ml) orally for 10 weeks, b) the Abstinence-group (n = 20) that was treated with nicotine (100 μg/ml) orally for 7 weeks followed by 3 weeks of abstinence from nicotine and c) the Control group (n = 20) that had free access to fresh water daily for the same period of time (10 weeks). Five days before the completion of the 10-week treatment, each male rat was placed in the same cage with two female rats and mating studies were performed. Subsequently all male rats were sacrificed and OS parameters were measured in MROs and histological evaluation was performed. Offspring-development was recorded up to the 28th day. Nicotine treatment significantly increased OS-markers levels and their expression in the testis, epididymis and seminal vesicles (SV) in Nico−group compared to Abstinence and Control groups. Total antioxidant capacity was significantly decreased both in the epididymal and testicular tissues of the Nico group compare to Abstinence or Control groups. Cotinine, the predominant metabolite of nicotine, was present at high levels in urine, serum and seminal vesicular fluid(SVF) of Nico−group compared to Abstinence-group (P<0.05). Testosterone levels were significantly lower in Nico-group compared to Control−group, while abstinence partially corrected this abnormality. Cytochrome P450(CYP2A6), the primary enzyme responsible for the oxidation of nicotine and cotinine was strongly expressed and localized in the epithelial cells of the epididymis in Nico−group. 8-hydroxy-2-deoxyguanosine (8-OHdG), one of the major products of DNA-oxidation was strongly expressed in the epididymal and seminal vesicular tissues of the Nico-group compared to the Abstinence and the Control group. The number of offspring in Nico-group was slightly decreased compared to the other two groups. The development of offspring and their body weights were recorded on 2nd, 3rd, 5th, 14th and 28th postnatal days. The body weight of offspring of the Nico-group was significantly lower compared to Abstinence or Control groups at all time-points measured. Extending the abstinence period up to one spermatogenic cycle could probably give better results in terms of tissue morphology, but even 3-week abstinence was beneficial. Nicotine exposure increases OS in MROs and creates a toxic environment in which spermatozoa are produced in the testis, become mature in the epididymis and are transported in the SVF until they reach the female reproductive system. Accumulated OS damages the sperm-DNA, which affects epigenetically the development of the offspring. No

Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating a growing cohort of younger survivors for whom post-treatment quality of life—notably reproductive function—is paramount. Curative treatments such as radical prostatectomy, pelvic radiotherapy, androgen-deprivation therapy (ADT), and chemotherapy often cause irreversible infertility via multiple mechanisms, including surgical disruption of the ejaculatory tract, endocrine suppression of spermatogenesis, direct gonadotoxic injury to the testes, and oxidative sperm DNA damage. Despite these risks, fertility preservation is frequently overlooked in pre-treatment counseling, leaving many patients unaware of their options. This narrative review synthesizes current evidence on how PCa therapies impact male fertility, elucidates the molecular and physiological mechanisms of iatrogenic infertility, and evaluates both established and emerging strategies for fertility preservation and restoration. Key interventions covered include sperm cryopreservation, microsurgical testicular sperm extraction (TESE), and assisted reproductive technologies (ART). Psychosocial factors influencing decision-making, novel biomarkers predictive of post-treatment spermatogenic recovery, and long-term offspring outcomes are also examined. The review underscores the urgent need for timely, multidisciplinary fertility consultation as a routine component of PCa care. As PCa increasingly affects men in their reproductive years, proactively integrating preservation into standard oncologic practice should become a standard survivorship priority.

BACKGROUND:Varicocoele represents the most common cause of male infertility, although most men with varicocoele remain fertile. Currently, no specific or sufficiently reliable criteria exist to identify patients who would benefit from varicocoele treatment to prevent impaired spermatogenesis. Emerging evidence suggests that magnetic resonance imaging (MRI) may provide valuable noninvasive insights into the mechanisms of testicular parenchymal damage in infertile men with clinical varicocoele. OBJECTIVES:The aim of this narrative review was to discuss the applications of advanced MRI techniques, including diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), dynamic contrast-enhanced MRI (DCE-MRI), and proton magnetic resonance spectroscopy (1H-MRS) in the assessment of testes in infertile men with clinical varicocoele and their role in uncovering the complex mechanisms impairing fertility. MATERIALS AND METHODS:PubMed database was searched for original articles published during 2010-2024. RESULTS:Advanced MRI techniques reveal alterations in apparent diffusion coefficient (ADC), fractional anisotropy (FA), intratesticular vasculature, and testicular metabolites in men with varicocoele compared to healthy controls. Decrease in testicular ADC and FA is detected in men with varicocoele, indicating microstructural abnormalities. Testes with varicocoele enhance fast and strongly during the early phases of dynamic imaging, providing a valuable insight into tissue perfusion. Proton MR spectra of infertile testes with varicocoele show a decrease in concentrations of choline, myoinositol, Glx complex, and lipids, signifying metabolic signatures of deranged spermatogenesis. CONCLUSIONS:Preliminary findings from advanced MRI techniques, including DWI, DTI, DCE-MRI, and 1H-MRS have demonstrated potential as noninvasive biomarkers of impaired spermatogenesis, by evaluating testicular microstructure, perfusion, and biochemical milieu.

Erectile dysfunction (ED) is a prevalent male sexual disorder characterized by the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. While its etiology is multifactorial, encompassing vascular, neurological, hormonal, and psychological components, emerging evidence suggests a significant role for gut microbiota dysbiosis in its development. The gut microbiota influences various metabolic, inflammatory, and neuropsychological processes critical to erectile function. Dysbiosis can lead to systemic inflammation, endothelial dysfunction, hormonal imbalances, and altered neurotransmitter production, all of which are key factors in ED pathogenesis. This narrative review synthesizes current research on the association between gut microbiota alterations and ED, highlighting specific bacterial taxa implicated in ED through mechanisms involving inflammation, metabolic disturbances, and hormonal regulation. This review explores potential mechanisms linking gut microbiota and ED, including pro-inflammatory cytokines, gut barrier integrity disruption, metabolic disorders, psychological factors via the gut–brain axis, and hormonal regulation. Furthermore, the gut microbiota offers promising avenues for developing non-invasive biomarkers and therapeutic interventions such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation. Future research should focus on longitudinal studies, mechanistic explorations, and clinical trials to validate these findings and translate them into clinical practice. Understanding the interplay between the gut microbiota and erectile function could unveil novel diagnostic biomarkers and pave the way for innovative treatments targeting the microbiota, ultimately improving men’s sexual and overall health.

Background/Objectives: Germ Cell Neoplasia In Situ (GCNIS) is considered the precursor lesion for the majority of testicular germ cell tumors (TGCTs). The aim of this study was to evaluate whether first-order radiomics features derived from volumetric diffusion tensor imaging (DTI) metrics—specifically apparent diffusion coefficient (ADC) and fractional anisotropy (FA) histogram parameters—can detect GCNIS. Methods: This study included 15 men with TGCTs and 10 controls. All participants underwent scrotal MRI, including DTI. Volumetric ADC and FA histogram metrics were calculated for the following tissues: group 1, TGCT; group 2: testicular parenchyma adjacent to tumor, histologically positive for GCNIS; and group 3, normal testis. Non-parametric statistics were used to assess differences in ADC and FA histogram parameters among the three groups. Pearson’s correlation analysis was followed by ordinal regression analysis to identify key predictive histogram parameters. Results: Widespread distributional differences (p < 0.05) were observed for many ADC and FA variables, with both TGCTs and GCNIS showing significant divergence from normal testes. Among the ADC statistics, the 10th percentile and skewness (p = 0.042), range (p = 0.023), interquartile range (p = 0.021), total energy (p = 0.033), entropy and kurtosis (p = 0.027) proved the most significant predictors for tissue classification. FA_energy (p = 0.039) was the most significant fingerprint of the carcinogenesis among the FA metrics. These parameters correctly characterized 88.8% of TGCTs, 87.5% of GCNIS tissues and 100% of normal testes. Conclusion: Radiomics features derived from volumetric ADC and FA histograms have promising potential to differentiate TGCTs, GCNIS, and normal testicular tissue, aiding early detection and characterization of pre-cancerous lesions.