Nutcracker syndrome (NCS) refers to symptomatic compression of the left renal vein (LRV), most commonly between the aorta and superior mesenteric artery (anterior nutcracker) or, less frequently, between the aorta and vertebral column in the presence of a retro-aortic LRV (posterior nutcracker). This venous entrapment elevates renal venous pressure and promotes drainage through the gonadal and pelvic venous networks. Clinical manifestations typically include haematuria, left flank or abdominal pain, orthostatic proteinuria, and features of gonadal or pelvic venous congestion such as varicocele. Diagnosis relies on careful clinical evaluation, exclusion of alternative aetiologies, and targeted imaging modalities including Doppler ultrasonography, computed tomography, magnetic resonance angiography, venography, and intravascular ultrasound. Despite increasing recognition of NCS, standardized diagnostic criteria and imaging thresholds remain lacking. Management strategies range from conservative treatment to endovascular interventions and open or laparoscopic surgical procedures. Optimal care requires a multidisciplinary approach involving urology, radiology, nephrology, and vascular surgery to ensure accurate diagnosis and individualized treatment planning.

Vascular malformations are abnormalities of the vascular tree, either congenital or acquired, which may involve arteries, veins, capillaries, or lymphatic vessels. Congenital malformations, such as patent ductus arteriosus, may persist into adulthood, resulting in abnormal vascular communications. Acquired vascular communications may occur following trauma, such as gunshot or stab injuries, or after surgical procedures. Arteriovenous malformations are congenital disorders affecting the circulatory system during early developmental stages. Renal vascular variations are also relatively common, usually silent (asymptomatic) and often diagnosed incidentally during surgical or radiological procedures. Renal artery variations occur in approximately 30% of the population. Renal vein variations are also frequent but are always overlooked than their arterial counterpart. In this case study, we report an abnormal communication along with multiple urogenital vascular anomalies and discuss their genetic and developmental perspectives. Recognition of such anomalies helps establish safety guidelines for the diagnosis and management of renal and gonadal disorders.

Male infertility is an increasingly serious global health problem. As an organ with immune privilege, the testis possesses a unique immune microenvironment that shapes normal spermatogenesis. Distinct from the testicular microenvironment, the epididymis plays a critical role in both sperm maturation and immune regulation. This review aims to systematically describe the regulatory mechanisms of the testicular and epididymal immune microenvironment and, using various diseases as examples (varicocele, testicular torsion, prostatitis, orchitis, viral infections, environmental toxicant exposure, aging and obesity), to explore in depth how disruption of this balance leads to male infertility through immunological pathways. Targeted antioxidant and anti-inflammatory interventions on specific immune pathways currently represent major therapeutic directions. Although many precision interventions and other emerging therapies remain at the experimental stage, they provide broad prospects for the development of novel treatment paradigms.

To evaluate seminal oxidative stress, antioxidant defense, apoptosis-related activity, and Sertoli cell biomarkers in infertile men with grade 3 varicocele versus normozoospermic controls, and to assess postoperative changes after varicocelectomy. This prospective observational case-control study included 39 infertile men with grade 3 clinical varicocele and 44 normozoospermic controls. Seminal plasma levels of Malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), superoxide dismutase (SOD), glutathione peroxidase-1 (GPx-1), reduced glutathione (GSH), nuclear factor erythroid 2-related factor 2 (NRF2), Kelch-like ECH-associated protein 1 (KEAP1), caspase-3, anti-Müllerian hormone (AMH), and inhibin B were measured by ELISA. Testicular volume, semen parameters, and diagnostic performance were also evaluated. Compared with controls, patients with varicocele had lower testicular volumes and impaired semen parameters. Seminal 8-OHdG and caspase-3 levels were higher, whereas SOD and inhibin B levels were lower. Baseline MDA, GPx-1, GSH, NRF2, KEAP1, and AMH levels did not differ significantly. After varicocelectomy, sperm concentration, total sperm count, progressive and total motility, total motile sperm count, morphology, and round cell count improved significantly. Postoperatively, caspase-3, MDA, and KEAP1 decreased, whereas SOD, GPx-1, GSH, NRF2, and inhibin B increased significantly. 8-OHdG showed a borderline decrease, and AMH remained unchanged. SOD showed the best diagnostic performance. Grade 3 varicocele is associated with oxidative DNA damage, impaired antioxidant defense, increased apoptotic signaling, and altered Sertoli cell-related seminal biomarkers. Varicocelectomy partially restores redox homeostasis, which may contribute to improved spermatogenic function.

Adolescent varicocele is a common yet clinically complex condition, affecting up to 15% of post-pubertal boys. The natural history and long-term reproductive implications in adolescents are not as well understood as the association of varicocele with infertility in the adult population. As such, the primary challenge in the management of adolescent varicocele lies in identifying the subset of boys at risk for impaired spermatogenesis while avoiding unnecessary intervention in those who may normalize testicular development as puberty progresses. The pathophysiology of varicocele-related testicular dysfunction is thought to be multifactorial, involving increased scrotal temperature, oxidative stress, and associated germ cell apoptosis. There is also an element of genetic factors that may have implications in the development of varicocele and susceptibility to spermatogenic injury. Regardless of history, we have taken an institutional algorithmic approach whereby boys are evaluated at the time of initial presentation using a longitudinal, biologically informed process incorporating physical exam, serial assessment of total and relative testicular volume, scrotal ultrasound, endocrine evaluation, and semen analysis in appropriate Tanner V patients. Indications for surgical intervention in adolescents are guided by surrogate markers of testicular dysfunction such as persistent testicular volume asymmetry, abnormal semen parameters, and hormonal abnormalities. The preferred technique for intervention when indicated is a subinguinal microsurgical varicocele repair as this is associated with low recurrence and few complications. Surgical repair has been shown to improve testicular growth and semen parameters. However, the long-term impact of surgical repair on paternity is particularly challenging to assess in the adolescent population and requires continued long-term study. An algorithmic, longitudinal approach to the evaluation and management of adolescent varicocele that allows for the early identification of at-risk patients and avoidance of overtreatment is presented. Ultimately, management should be individualized, with the goal of preserving testicular function and optimizing future reproductive potential.

Varicocele is a common cause of male infertility, but the mechanisms by which it disrupts testicular homeostasis and impairs spermatogenesis remain incompletely elucidated. This article reviews current evidence on the multifactorial disturbances in the testicular microenvironment induced by varicocele, with a focus on hemodynamic, biochemical, and structural abnormalities. Anatomical predisposition, venous valve incompetence, and impaired venous return collectively lead to chronic venous hypertension, causing progressive dilation of the pampiniform plexus and severe hemodynamic dysregulation. These primary vascular abnormalities subsequently establish a foundation for downstream cellular damage, including testicular hyperthermia, hypoxia, and metabolic stress. Among these pathological processes, oxidative stress is widely recognized as a central mediator of testicular injury. Excessive reactive oxygen species overwhelm intrinsic antioxidant defenses, disrupt mitochondrial function, damage germ cell DNA, and impair epididymal sperm maturation, ultimately leading to reduced sperm concentration, motility, and viability. Simultaneously, elevated inflammatory cytokines and immune dysregulation further compromise Sertoli and Leydig cell function, activate inflammasome signaling and amplify inflammatory injury. These inflammatory signals also synergize with oxidative damage to disrupt the blood-testis barrier, resulting in increased permeability, autoimmune activation, and accelerated loss of germ cells. Structural impairment of the seminiferous epithelium, mitochondrial dysfunction, and the activation of intrinsic and extrinsic apoptotic pathways further exacerbate spermatogenic failure. Ultimately, varicocele induces a multifaceted and sustained cycle of testicular microenvironment disruption, impairing spermatogenesis at multiple levels-from Sertoli cell function and blood-testis barrier integrity to germ cell survival and sperm DNA stability.

Sperm DNA fragmentation (SDF) represents strand breaks that may compromise embryo development, reproductive outcomes, and offspring health, particularly when the oocyte's repair capacity is limited. This mini-review provides a clinically pragmatic framework addressing how to test, when to test, and whom to test for SDF, translating biological and laboratory insights into actionable andrology practice. The mechanistic basis of SDF is summarized, including the two-step hypothesis linking defective chromatin packaging to oxidative stress, and the combined influence of paternal and maternal aging on the creation and repair of DNA lesions. Contemporary methods for detecting both single- and double-strand breaks (DSBs), as well as DSB-specific platforms, are reviewed with emphasis on assay-specific cut-offs and clinical indications. Management strategies are outlined, prioritizing andrological optimization through lifestyle modification, antioxidant supplementation, treatment of genital tract infection, varicocele repair, and selected hormonal therapy, followed by retesting after one spermatogenic cycle. For persistently high SDF, selective use of testicular sperm for ICSI (Testi-ICSI) and laboratory adjuncts is discussed, supported by evidence of lower miscarriage and higher live-birth rates in defined high-SDF phenotypes. The limitations of the existing observational evidence base-particularly the paucity of phenotype-targeted randomized controlled trials-are highlighted. The review also underscores the value of embedding SDF testing within quality-managed programs and incorporating systematic audits of indications, treatment effects, and ART outcomes. Beyond ART, SDF assessment is positioned within preconception care, recognizing sperm chromatin integrity as a determinant of reproductive and intergenerational health. Future priorities include randomized trials comparing testicular and ejaculated sperm for ICSI in high-SDF cohorts, validation of DSB-specific assays, and longitudinal offspring follow-up to clarify intergenerational effects. This integrative approach promotes precision rather than proliferation of testing, aligning molecular insight with clinical prudence to improve reproductive and generational outcomes.

Male infertility accounts for nearly half of all infertility cases, yet standard semen analysis often fails to reflect sperm's functional competence or fertilization potential. Sperm DNA fragmentation (SDF) has emerged as a potential biomarker of sperm quality, with elevated levels frequently associated with reduced fertilization rates, lower IVF/ICSI success, and an increased risk of recurrent pregnancy loss (RPL). Meta-analyses suggest an inverse relationship between SDF and both clinical pregnancy and live birth rates, particularly in IVF/ICSI cycles; however, assay variability limits the interpretability of SDF testing. Varicocele has been implicated as a contributor to elevated SDF, with several studies indicating an association. However, causality and clinical implications remain under investigation. While varicocelectomy may reduce SDF, its effect on reproductive outcomes remains uncertain. Adjunctive strategies, such as antioxidant therapy, microfluidic sperm selection, and testicular sperm retrieval, have been explored in cases of elevated SDF; however, supporting evidence remains limited. A shortened ejaculatory abstinence interval, typically 24 h or less, has been proposed as a non-invasive strategy to reduce SDF, though its efficacy remains to be fully elucidated. The American Urological Association (AUA) regards SDF testing as investigational. While the AUA discourages its routine use, it permits consideration in select cases, such as RPL or unexplained IVF/ICSI failure. Due to methodological inconsistencies and the lack of standardized thresholds, SDF testing is best applied within an individualized, evidence-informed clinical framework.

One of the most promising markers in the evaluation of male infertility is sperm DNA fragmentation. Studies have shown that the etiology of sperm DNA fragmentation is multifactorial, and includes genetic and developmental abnormalities, ageing, gonadotoxins, hyperthermia, varicocele, medications, and endocrine abnormalities. Clinical studies have demonstrated that sperm DNA damage is associated with poor reproductive outcomes and based on these observation investigators have proposed that tests of sperm DNA fragmentation be used in the evaluation of infertile couples, particularly in those with recurrent pregnancy loss, failed ICSI cycles, and unexplained infertility. An abnormal sperm DNA test in these couples should prompt a thorough evaluation as it may help the clinician uncover the etiology of DNA damage and initiate cause-specific treatment to optimize reproductive outcomes.