Varicocele (VC), one of the most common correctable etiologies of male infertility, has long been pathophysiologically characterized by hemodynamic disturbances stemming from venous valvular incompetence and the consequent testicular insult. Yet this macrovascular perspective demonstrates limited explanatory power in accounting for the pronounced clinical heterogeneity of VC, the inter-individual variability in testicular impairment, and the nonlinear recovery of fertility following microsurgical repair. This review endeavors to present a propositional shift in perspective-one that warrants further empirical validation-drawn from vascular biology: between the inciting hemodynamic disturbance and the resultant testicular injury, an adaptive remodeling imbalance of the venous wall may occupy a position of considerable pathophysiological importance. Within this conceptual framework, the role of the spermatic vein might be extended from that of a passive conduit subjected to pressure toward that of a functional organ actively engaged in local microenvironmental regulation. This process involves a cascade of events, including endothelial dysfunction, phenotypic transition of vascular smooth muscle cells, progressive dysregulation of the collagen-to-elastin ratio within the extracellular matrix, and aberrant activation of pro-inflammatory and pro-fibrotic signaling within the vessel wall. Should this hypothesis prove tenable, such a paradigm transition would facilitate a reappraisal of VC-associated testicular damage through the microscopic lens of venous wall exhaustion, and offer a potential theoretical supplement and integrative framework for exploring disease-staging strategies and interventional timing that transcend conventional palpation-based grading, predicated instead upon vascular biological features of the venous wall.

Male factors account for approximately 50% of infertility cases; however, the mechanisms underlying sperm dysfunction remain unclear. Heat shock protein A2 (HSPA2) is a biomarker associated with sperm fertilization; however, few studies have examined changes in its localization in vitro. This study investigated the in vitro localization dynamics of HSPA2 in sperm and its association with male infertility. Fertility status was determined according to the 2021 World Health Organization criteria. Semen samples were collected from 28 men with normal findings and 57 men with varicocele or oligozoospermia. Samples were subjected to density gradient centrifugation and the swim-up procedure, followed by a 24 h incubation. HSPA2 protein levels were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting, and localization patterns were evaluated using immunofluorescence staining. Western blot analysis showed that HSPA2 levels were significantly lower in samples from men with oligozoospermia (P < 0.01) and varicocele (P < 0.05) than in those from men with normal findings. Moreover, HSPA2 levels were correlated with total motile sperm counts and sperm motility. The percentage of sperm with HSPA2 localized in the acrosomal region immediately after sperm processing was lower (P < 0.01) and peaked later in samples from men with oligozoospermia and varicocele than in those from men with normal findings. These findings indicate that the reduced acrosomal localization of HSPA2 and delayed acrosomal localization dynamics after sperm processing represent a shared feature of male infertility rather than condition-specific differences and may be linked to impaired sperm function.

Despite the recognized role of oxidative stress (OS) in sperm function, limited data exist on Nuclear factor-E2-related factor 2 (Nrf2) pathway modulation in relation to reliable oxidative damage markers in human semen. In this study, 79 semen samples were collected from men undergoing semen analysis and grouped as varicocele (V, no. 22), urogenital infections (UI, no. 23), unknown fertility status without pathologies (UFS, no. 15), and fertile controls (F, no. 19). After semen analysis, ELISA were used to quantify F2-Isoprostane (F2-IsoPs) level, a marker of lipid peroxidation, and Nrf2 in seminal plasma and spermatozoa. The Nrf2 pathway (Keap1, Nrf2, Bach1, HO-1) was assessed in spermatozoa by qRT-PCR. Seminal plasma and sperm Nrf2 positively correlated with F2-IsoPs (p < 0.001) and negatively with sperm vitality. Sperm Nrf2 also inversely correlated with progressive motility (p < 0.05). Seminal F2-IsoP levels were lower in F than in the other groups. Sperm Nrf2 was significantly lower in F versus V and UI (p < 0.001) and UFS (p < 0.05), while seminal plasma Nrf2 levels did not differ among groups. qRT-PCR suggested Nrf2 pathway activation mainly in V and UI, consistent with increased OS. Elevated F2-IsoPs, a marker of poor sperm quality, and sperm Nrf2 could suggest OS-driven Nrf2 activation, providing complementary biomarkers of oxidative status in male reproductive health.

Varicocele is a prevalent cause of male infertility and has been associated with erectile dysfunction in clinical and preclinical studies, characterized by a complex pathophysiological process involving immune-inflammatory responses. This review focuses on the preclinically supported immune-inflammatory interactions between the testicular and penile microenvironments in varicocele patients, systematically summarizing the plausible and partially validated molecular mechanisms mediating erectile dysfunction and spermatogenic impairment. We explore the network relationships among local and systemic inflammatory cytokines, immune cell infiltration, oxidative stress, endothelial dysfunction, and neurovascular injury. By integrating recent omics studies, animal models, and available clinical data, this article elucidates the hypothetical and mechanistically plausible pathological linkage from abnormal varicose veins in the pampiniform plexus to distal impairment of penile cavernous function. The review aims to synthesize and contextualize the systemic impact of varicocele and to establish a theoretical foundation for developing targeted therapies addressing immune-inflammatory pathways.

Testicular biopsy represents a crucial procedure in the management of non-obstructive azoospermia, though its success remains variable. [cite: 106] Identifying predictive factors for successful sperm retrieval is essential for patient selection. [cite: 107] Aim: To determine the clinical, hormonal and technical factors predictive of successful testicular biopsy in azoospermic patients [cite: 108] Methods: A retrospective analytical study was conducted over 5 years (2017-2021), including 28 patients. [cite: 109] Comparative analysis was performed between groups with successful (spermatozoa present) and failed biopsy. [cite: 110] Results: Significant predictive factors for successful biopsy included: testicular volume preservation (p=0.042), low FSH levels (p=0.002), low estradiol levels (p=0.018), excretory azoospermia type (p=0.023), and unilateral surgical approach (p=0.005). [cite: 111] Clinical varicocele and hydrocele showed no significant correlation. [cite: 112] Conclusion: Our study identifies a predictive profile for testicular biopsy success, enabling better patient selection and surgical strategy optimization in assisted reproductive technology. [cite: 113].

Polyorchidism, the presence of more than two testes, remains the rarest congenital anomaly of the male gonads, with fewer than 300 histologically or radiologically confirmed cases reported worldwide. Most supernumerary testes are discovered incidentally during imaging or surgery, yet their detection raises critical questions about malignancy risk, reproductive potential, and appropriate management. Current evidence indicates that approximately 90% of patients have three testes and two‑thirds show left‑sided duplication. About 75% of supernumerary testes are scrotal, roughly one‑fifth lie in the inguinal canal, and a small minority are abdominal or retroperitoneal. Inguinal hernia, cryptorchidism, and torsion are the most frequent associated anomalies, whereas hydrocele, varicocele, and renal agenesis occur less often. The pooled risk of neoplastic transformation ranges from 1% to 7% overall but climbs to 15% to 20% when the supernumerary testis is undescended. High‑resolution ultrasound is the diagnostic mainstay, while magnetic resonance imaging is indispensable for extrascrotal lesions and for clarifying drainage patterns. Contemporary practice increasingly favors surveillance of scrotal, anatomically normal, vas‑draining supernumerary testes, whereas extrascrotal, non‑draining, dysgenetic, or radiologically suspicious lesions warrant orchiectomy. Fertility outcomes remain poorly characterized. Isolated reports document both preserved spermatogenesis and severe oligoasthenoteratozoospermia, and endocrine profiles are usually normal. Advances in imaging have enabled conservative, fertility‑preserving management in many patients, but the absence of prospective registries, standardized follow‑up protocols, and molecular profiling limits reliable risk stratification. Multicenter collaborations are therefore essential to refine oncologic estimates, clarify reproductive implications, and establish evidence‑based guidelines for this exceptionally rare condition.

Liquid embolic agents (LEAs) have expanded the therapeutic options for complex vascular and non-vascular conditions. Tailored clinical assessment with dedicated procedure planning is critical in the selection of the most appropriate embolic to ensure procedural success and minimise complications. The LEAs, which range from sclerosant agents to glues and copolymers all have specific physical characteristics. Sclerosant agents are mainly selected for symptomatic vein diseases such as varicoceles and low-flow venous and lymphatic malformations (VM and LM), usually requiring multiple treatment sessions to achieve a satisfactory response. Glues and copolymers have completely different properties but may have overlapping indications ranging from haemorrhage control (gastrointestinal and solid-organ), treatment of visceral and renal aneurysms or pseudoaneurysms to type II endoleaks, arteriovenous malformations/fistulas, tumour devascularisation, and selective end-organ embolisation. The use of each agent varies according to the specific clinical scenario, and operator experience and preference. This review aims to provide a concise and practical overview of the use of LEAs.

Male infertility presents significant heterogeneity, yet traditional assessments primarily rely on semen parameters and endocrine, imaging, and genetic screening. Although these methods can identify some definitive etiologies, a mechanistic explanatory gap persists in large populations with mild to moderate oligoasthenoteratozoospermia, elevated sperm DNA fragmentation, or recurrent adverse reproductive outcomes. The testis maintains a dynamic immune-privileged balance by balancing infection defense against tolerance to post-pubertal germ cell antigens. In this context, infections, varicocele-induced hypoxia or thermal stress, metabolic abnormalities, and environmental factors, trigger innate immune recognition via PAMPs or DAMPs. Notably, most mechanistic insights discussed are derived from animal models and in vitro studies; direct high-level clinical evidence in humans remains limited, and the proposed framework requires prospective validation. This is proposed to drive myeloid amplification, complement cascades, and inflammasome activation, which may in turn mutually reinforce oxidative stress. Based on current evidence, this may consequently compromise blood-testis barrier integrity, cause immune tolerance thresholds to decline, and induce tissue remodeling, collectively impairing the spermatogenic microenvironment, sperm maturation, and DNA integrity. This article reviews these immunological mechanisms and proposes a hypothesis-driven intervention framework driven by immune endophenotypes, aiming to provide an actionable clinical roadmap for the precision management of male infertility.