BACKGROUND:Vasectomy reversal is the primary method of fertility restoration for men who wish to pursue natural conception following vasectomy. The existing body of literature evaluating vasovasostomy (VV) success is primarily focused on endpoints that capture the presence or absence, rather than the quantity and quality, of sperm in postoperative semen analyses (SAs). OBJECTIVES:To identify reproductive and surgical factors associated with favorable postoperative semen parameters in men who underwent bilateral VV. MATERIALS AND METHODS:We performed a retrospective study of men meeting strict inclusion criteria who underwent bilateral VV at a large academic center. Postoperative semen parameters, operative findings, and clinical characteristics were analyzed. Associations between predictors and semen outcomes were evaluated using univariate linear and logistic regression models. RESULTS:One hundred men who underwent bilateral VV were included in the final analysis. The median age was 39.9 years, and the median obstructive interval was 8.6 years. Those with motile sperm on initial postoperative SA had shorter mean obstructive intervals (8.1 vs. 11.0 years, p = 0.04) and had a higher proportion of motile sperm in vasal fluid during intraoperative assessment (51.1 vs. 8.1%, p = 0.01). Fifty-eight percent of men (n = 44/76) exhibited a TMSC > 4.55 million, the lowest TMSC with a confirmed spontaneous pregnancy in our cohort. Motile sperm on postoperative SA were best predicted by the intraoperative presence of motile sperm in vasal fluid (OR: 11.51, 95% CI: 1.43-93.01, p = 0.02) and shorter obstructive intervals (OR: 0.87, 95% CI: 0.76-0.99, p = 0.04) on univariate regression. Postoperative normozoospermia was associated with shorter obstructive intervals (OR: 0.80, 95% CI: 0.69-0.92, p = 0.002) but was not statistically associated with the intraoperative presence of motile sperm. DISCUSSION:These findings highlight the utility of intraoperative vasal fluid evaluations for postoperative prognostication. CONCLUSION:Intraoperative sperm motility and obstructive interval duration are predictive of postoperative semen quality.

Background/Objectives: Male infertility, including primary and secondary infertility, is significantly influenced by oxidative stress, which disrupts sperm function and fertility. Seminal plasma, a protein-rich fluid essential for sperm protection and function, represents a valuable source for identifying biomarkers through proteomic analysis. While previous studies have explored seminal plasma proteins in fertility, the specific proteomic changes associated with oxidative stress in secondary infertility remain unclear. This study aimed to characterize these alterations by analyzing seminal plasma from three groups: men with secondary infertility, fertile donors with high oxidative stress, and fertile donors without oxidative stress. Methods: Pooled semen samples from each group underwent quantitative proteomics analysis using advanced mass spectrometry, with subsequent bioinformatic analysis using tools like DAVID, STRING, and IPA for identifying differentially expressed proteins (DEPs). Results: Quantitative proteomic analysis identified 377 DEPs in secondary infertility and 523 DEPs in fertile donors with high oxidative stress compared to controls. Bioinformatic analysis revealed seven shared pathways, including acute-phase response signaling, organismal injury, cellular movement, cell-to-cell signaling, free radical scavenging, immune cell trafficking, and Hematological system development. Notably, C3 and SERPINA3 exhibited significant alterations, along with proteins involved in sperm motility, capacitation, and fertilization, suggesting their potential roles in impaired fertility. Conclusions: These findings underscore the link between oxidative stress and secondary infertility and highlight specific seminal plasma proteins as potential biomarkers and therapeutic targets for diagnosing and treating male infertility.

Stimulant medications are increasingly prescribed for attention-deficit/hyperactivity disorder (ADHD) in men of reproductive age, yet their impact on semen quality remains poorly characterized. We aimed to evaluate whether recent stimulant exposure would negatively affect semen parameters in reproductive-age men with ADHD. We performed a multi-center retrospective analysis of 2039 men aged 18-40 years with a diagnosis of ADHD and available semen volume data between 1995-2025. We excluded men with diagnoses or treatments known to affect spermatogenesis or ejaculatory function. Exposure was defined as an active outpatient prescription for methylphenidate, amphetamine, lisdexamfetamine, dextroamphetamine, or methamphetamine within 90 days prior to semen testing. Exposed patients were matched 2:1 by age (±4 years) to stimulant-unexposed controls with ADHD. The final cohort included 388 exposed and 776 matched controls, with median ages of 33 (IQR 30-37) and 33 (IQR 29-37) years, respectively. Stimulant exposure was associated with lower semen volume (median 2.70 mL [IQR 1.9-3.7] vs. 2.95 mL [IQR 2.0-4.1], p = 0.02). No significant differences were observed between groups in other semen parameters (p > 0.25). On univariable regression, stimulant exposure was associated with a 5.7% decrease in semen volume (p = 0.02). After adjustment in multivariable regression, stimulant exposure remained associated with an 8.4% lower semen volume (p = 0.01). Among reproductive-age men with ADHD, recent stimulant use was associated with a modest decrease in semen volume, while other semen parameters remained unchanged. Importantly, preserved sperm quality suggests that stimulant use during attempts at conception is unlikely to significantly impair fertility.

This review evaluates global trends, economic considerations, and recent innovations in penile prosthesis surgery for erectile dysfunction (ED). It aims to examine rising procedural costs, disparities in accessibility, and strategies to enhance affordability particularly in low- and middle-income countries (LMICs). Despite its cost-effectiveness and high patient satisfaction, penile prosthesis surgery remains underutilized due to increasing costs and inconsistent insurance coverage. In the U.S., a shift toward ambulatory surgical centers may help reduce procedural costs. Low-cost devices like the Shah Malleable Prosthesis have improved accessibility in LMICs but face limited global adoption due to regulatory and evidence gaps. Broader health system reforms and novel tools such as predictive digital models may further mitigate economic barriers. Penile prosthesis implantation is a durable and effective treatment for ED but remains financially inaccessible to many patients worldwide. Reducing costs through outpatient surgery, insurance expansion, and validated low-cost devices can improve global access. Future progress requires coordinated policy reform and investment in scalable, equitable care pathways.

BACKGROUND:Vasectomy is the most common non-diagnostic procedure performed by urologists and the only permanent form of sterilization routinely offered to men. Though vasal fluid has been estimated to represent less than 10% of seminal volume, studies describing the effect of vasectomy on semen volume remain limited. OBJECTIVE:To describe the effect of vasectomy on semen volume compared to controls independent of changes with time/aging. MATERIALS AND METHODS:Men undergoing vasectomy between January 2015 and December 2024, who underwent a pre-vasectomy semen analysis (SA) with volume ≥ 1.5 mL and sperm concentration ≥ 15.0 M/mL, and post-vasectomy SA, were identified and included in this single-center retrospective case-control study. Non-vasectomized men with normal semen parameters and two SAs were identified as controls. Cases were matched to controls in a 1:2 ratio regarding patient age at the time of initial SA. RESULTS:A total of 957 patients were included in the analysis cohort, including 319 vasectomized men and 638 controls. Mean age (33.3 ± 5.1 vs. 33.4 ± 5.0 years, p = 0.80) and sperm concentration on initial SA (69.2 ± 50.5 vs. 75.5 ± 54.7 M/mL, p = 0.08) did not differ between cases and controls, nor did mean volume on initial (3.51 ± 1.51 vs. 3.51 ± 1.51 mL, p = 0.98) or subsequent SA (3.07 ± 1.42 vs. 3.19 ± 1.60 mL, p = 0.22). Semen volume decreased slightly in both groups between measurements (cases: -0.44 mL; controls: -0.32 mL; both p < 0.0001), but the between-group difference was not statistically significant (p = 0.19). Vasectomy status was not associated with volume change in the univariate (β = 0.06 mL, p = 0.19) or multivariable models (β = 0.04 mL, p = 0.50) adjusted for time between SAs. A sensitivity analysis among matched groups from whom initial and subsequent SA volumes ≥1.5 mL echoed these findings. DISCUSSION AND CONCLUSION:Vasectomy does not result in a significant change in semen volume when SA parameters are compared between cases and controls. Patients should be counseled that vasectomy itself does not change semen volume, but that volume might subtly decrease with aging.

OBJECTIVE:To evaluate whether varicocele modifies the relationship between hypogonadism and incident prostate cancer. Venous shunting of testosterone-enriched blood from the testicle to the dorsal venous complex occurs in ∼20% of men and has been linked to prostate cancer progression. Although hypogonadism has been inconsistently associated with prostate cancer risk, the influence of varicocele remains unexplored. MATERIALS AND METHODS:Using the Merative MarketScan database, we identified men >40 years with varicocele and matched them by age and follow-up interval to 2 cohorts as follows: (1) a general population cohort and (2) men with benign scrotal pathology associated with urological assessment. Time to prostate cancer was assessed using Cox proportional hazards models adjusted for age, obesity, rurality, family history, hypogonadism status, testosterone therapy, and varicocele status. An interaction term between varicocele and hypogonadism was included. RESULTS:Among 149,848 men (75,673 varicocele and 74,175 scrotal pathology controls), varicocele was associated with a higher incidence of prostate cancer (4.4 vs 3.8%, P<.01) and hypogonadism (13.3 vs 11.2%, P<.01). In adjusted models, varicocele alone was not associated with prostate cancer risk (HR: 1.04, P = .18), whereas untreated hypogonadism was associated with a modest but statistically signifiant increase in incident prostate cancer risk (HR: 1.27, P<.01). Men with both varicocele and untreated hypogonadism experienced the highest hazard of incident prostate cancer (HR: 1.31, P<.001). CONCLUSION:Varicocele amplifies the risk of prostate cancer associated with untreated hypogonadism. Testosterone therapy and possibly varicocelectomy mitigate this effect, supporting the notion that venous testosterone shunting to the prostate occurs in a subset of men.

IMPORTANCE:One in six couples worldwide experience infertility, and male factors contribute to at least half of these cases. The pathophysiology of male infertility is complex and often multifactorial, and the male reproductive microbiome has now been implicated as a potentially critical component in male reproductive health and disease. OBJECTIVE:To summarize the emerging evidence describing the male reproductive microbiome with a focus on clinically relevant aspects within spermatogenesis and reproductive outcomes. EVIDENCE REVIEW:We performed a librarian-led search of MEDLINE, Embase, and Web of Science and a targeted PubMed search for antibiotic and probiotic trials, focusing on human studies that reported male reproductive microbiome data together with semen parameters, oxidative, deoxyribonucleic acid (DNA)-damage, or inflammatory indices, or assisted reproduction outcomes. Given heterogeneity in design and laboratory methods, we conducted a narrative synthesis and integrated relevant mechanistic animal work. FINDINGS:Across heterogeneous cohorts, anaerobe-leaning seminal profiles (often with Prevotella or Atopobium) are more often linked to higher oxidative stress, greater sperm DNA fragmentation, and lower motility or total motile count. In contrast, Lactobacillus-rich profiles more often align with better redox status and DNA integrity. Couple-level data show rapid and robust partner microbiome exchange that can shift semen over short periods. Work on the gut-testis axis has identified a link between gut dysbiosis and systemic inflammation with semen quality via the gut-testis axis. Proposed mechanisms underlying the effect of the microbiome on fertility include local inflammation, oxidative injury, altered seminal rheology (e.g., viscosity/viscoelastic properties of seminal plasma), adherence/biofilms, and immune-metabolic crosstalk. Small trials to date using antibiotics and/or probiotics show variable benefits; durability and reproductive endpoints remain limited. CONCLUSION AND RELEVANCE:Emerging evidence supports a role for the male reproductive microbiome in sperm function and fertility and highlights it as a potential target for clinical intervention. However, predominantly small, cross-sectional studies and methodological heterogeneity limit causal inference and immediate translation, underscoring the need for longitudinal, couple-integrated cohorts and adequately powered randomized trials of targeted microbiome modulation.

Male factor infertility acts as a contributing or sole cause in approximately half of all infertility cases, with autoimmunity against spermatozoa-manifested as antisperm antibodies (ASA)-affecting 5%-12% of infertile men. The ASA formation typically results from a disruption of the blood-testis barrier because of trauma, obstruction, or inflammation, leading to the exposure of immunogenic sperm antigens to the systemic immune system. These antibodies, predominantly of the immunoglobulin G and immunoglobulin A classes, impair fertility by hindering sperm motility, preventing cervical mucus penetration, and blocking gamete interaction. Diagnostic evaluation primarily relies on direct assays such as the mixed antiglobulin reaction and immunobead test; however, in the era of intracytoplasmic sperm injection, the utility of ASA testing has evolved from routine screening to a targeted triage tool. Contemporary guidelines discourage universal testing, reserving it for ‟gray zone" clinical scenarios, such as unexplained infertility or isolated asthenozoospermia, where results directly influence the decision between intrauterine insemination (IUI) and in vitro fertilization. Therapeutically, historical reliance on systemic immunosuppression has been largely abandoned because of inefficacy and adverse effects. Instead, management is now stratified by the degree of autoimmunity: although IUI remains a viable option for lower levels of antibody binding, high levels of sperm autoimmunization (>80%) render IUI ineffective, necessitating intracytoplasmic sperm injection to mechanically bypass the immune barrier. This views and reviews article summarizes current evidence on pathophysiology and diagnostic methodologies, providing a pragmatic, management-oriented algorithm to guide urologists and reproductive specialists in optimizing outcomes for couples with immunologic infertility.

With increasing cancer incidence among individuals of reproductive age, preserving fertility has become a critical aspect of cancer care. This narrative review explores the impact of contemporary cancer therapies, including immunotherapies and targeted agents, on reproductive health, highlighting clinical fertility outcomes and underlying biological mechanisms. We outline the epidemiology and treatment strategies for malignancies common in adolescents and young adults (AYAs), including breast, melanoma, lung, gynaecologic, colorectal cancers and haematologic malignancies. Basic reproductive physiology in males and females is reviewed, including the hypothalamic–pituitary–gonadal axis, ovarian follicle and oocyte development, and spermatogenesis. Clinical data related to fertility and reproductive outcomes in patients receiving immunotherapy or targeted therapy are summarised, along with proposed mechanisms of gonadotoxicity from both conventional chemotherapy and newer drug classes. Special emphasis is placed on immunotherapy, such as checkpoint inhibitors, cell-based therapies (eg, chimeric antigen receptor T cells, tumour-infiltrating lymphocytes) and monoclonal antibodies, and small-molecule inhibitors, including kinase inhibitors (eg, BRAF, MEK, epidermal growth factor receptor), poly (ADP-ribose) polymerase inhibitors, epigenetic modifiers and apoptosis promoters (eg, BCL-2 inhibitors). Despite their growing use, these therapies are poorly studied in terms of reproductive safety, with available evidence being limited, heterogeneous and often lacking baseline fertility assessments or long-term follow-up. This uncertainty complicates counselling and decision-making, requiring a precautionary approach to fertility preservation. Multidisciplinary collaboration incorporating oncology, reproductive medicine, psychology and ethics is essential for individualised, ethically sound care. Emerging technologies such as organ-on-chip systems and induced pluripotent stem cell models offer promising avenues for mechanistic insight. To advance the field, future efforts must focus on prospective cohort studies, robust preclinical models and interim clinical guidelines to support informed fertility-related care for cancer patients.

To identify the principal cost drivers in U.S. management of NOA and evaluate evidence-based strategies—particularly the sequencing of mTESE and the surgical venue—that can lower out-of-pocket spending without compromising success mTESE provides ≈10

Advances in hematopoietic stem cell transplantation (HSCT) and other cellular therapies have continued to improve the long-term outcomes for pediatric patients undergoing these treatments. However, treatment impacts on future fertility can have a substantial impact on the patient's quality of life. Concurrent with improvements in transplantation, fertility preservation (FP) options and outcomes have also evolved. Options such as ovarian tissue cryopreservation and testicular tissue cryopreservation are now more widely available and can be considered for very young patients. The timing and choice of FP to be offered can be complex, and many considerations must be made when counseling patients and families. Cost and access are also variable depending on the country and region in which a patient resides. The aim of this paper is to provide an updated overview of the current strategies and recommendations for FP that should be offered to all children and adolescents undergoing an allo-HSCT. By summarizing contemporary evidence and practices, this paper may provide support to clinicians in delivering equitable, informed, and accessible FP counseling and care for all eligible patients.