Research productivity is a key indicator of academic performance and is shaped by access to resources, collaborative engagement, and effective communication. This study aimed to evaluate the impact of resource availability, research collaboration, and the use of digital communication tools (DCTs) on researchers' productivity. This cross-sectional study used an online questionnaire to evaluate the influence of DCTs on research productivity among eligible Global Andrology Forum members. The questionnaire collected data on demographics, research output, collaboration patterns, DCT preferences, and institutional support. The productivity data of participants were extracted from Scopus and Google Scholar. The economic status of the participants' country was obtained from the World Bank. Two-group comparisons used the Mann-Whitney U test, while multi-group comparisons used the Kruskal-Wallis test with post hoc analyses when significant. Spearman's correlation analysis and a multivariable robust linear regression model were used to assess associations and evaluate the robustness of the findings, respectively. A total of 141 of 144 researchers completed the survey, representing 37 countries across diverse economic settings. Researchers from high-income countries demonstrated significantly higher productivity than those from middle-income countries. DCTs (WhatsApp and Zoom) were widely used for messaging and virtual meetings. Time spent on WhatsApp was positively correlated with research performance, including number of publications (ρ=0.224, p=0.008), total citations (ρ=0.259, p=0.002), most cited article (ρ=0.215, p=0.011), h-index (ρ=0.289, p=0.001), co-authorship (ρ=0.223, p=0.008), and international collaboration (ρ=0.274, p=0.001). Researchers who spent more than 4 hours per week on WhatsApp demonstrated significantly higher productivity indicators. DCTs and structured global research networks are essential for strengthening research capacity and promoting equitable participation across regions. While economic constraints may limit productivity, effective use of digital collaboration platforms can help narrow these gaps by expanding networking opportunities, enabling meaningful collaboration, and enhancing overall research output.
Phosphodiesterase type 5 inhibitors (PDE5i) are widely used to treat erectile dysfunction (ED). However, a subset of men does not respond to these agents or seek restoration of natural erections. Regenerative therapies (RT), including low-intensity shock wave therapy (LiSWT), platelet-rich plasma (PRP) therapy, and stem cell therapy (SCT), have emerged as potential alternative treatment options. This article reviews the available evidence and presents the Global Andrology Forum (GAF) graded statements and recommendations for the use of RT in ED. A GAF expert panel conducted a literature review of the PubMed and Scopus databases up to February 2025 to identify studies on RT for ED. Surveys and a modified Delphi consensus method were employed to develop position statements and clinical recommendations. These were graded according to the "GRADE" classification system as either "strong" or "weak." Recommendations receiving strong ratings from at least 80% of experts were classified as "strong," while others were classified as "weak." Seventeen statements and recommendations were accepted and graded by a panel of 36 GAF experts from 18 countries. Eleven were classified as "strong," and six as "weak." Current evidence indicates modest short-term benefits of LiSWT in young and middle-aged men with mild-to-moderate vasculogenic ED. The efficacy of PRP and SCT remains uncertain. The GAF statements and recommendations highlight the lack of standardized treatment protocols and insufficient evidence of long-term effectiveness and emphasize the need for further research and clinical trials. Meanwhile, patients and healthcare providers should remain cautious when applying RT for ED. Clinicians should avoid overclaiming the benefits of RT to patients and provide a realistic prognosis based on current evidence.
Male infertility significantly contributes to the global reproductive burden and serves as a critical indicator of overall male health. As clinical pathways have historically focused on female-factor evaluation and assisted reproductive technology (ART), there is an increasing need for etiology-directed and time-sensitive male management strategies. This Clinical Recommendation, developed by the Korean Society for Sexual Medicine and Andrology Guideline Committee, synthesizes recent evidence from major international guidelines with specific considerations for the Korean healthcare environment. Management should be couple-centered, integrating the female partner's reproductive timeline to avoid preventable delays in effective therapy. Core recommendations emphasize addressing modifiable risk factors as foundational care, while restricting empiric pharmacotherapy to phenotype-driven, time-limited trials. Disease-specific pathways for varicocele, endocrine disorders, and obstructive/non-obstructive azoospermia are delineated, emphasizing the individualized selection between microsurgical reconstruction and surgical sperm retrieval. In the ART interface, the selective use of intracytoplasmic sperm injection is recommended, prioritizing safety and the prevention of multiple pregnancies. Furthermore, structured follow-up should prioritize patient-important outcomes, such as live birth and treatment burden, over intermediate semen parameter changes. By harmonizing international evidence with local clinical constraints, including national insurance structures and referral patterns, these recommendations aim to facilitate consistent, safe, and patient-centered care for infertile men in Korea.
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Conventional semen analysis may overlook defects in sperm nuclear integrity, whereas molecular markers such as DNA Fragmentation Index (DFI) and protamine deficiency provide complementary information on sperm chromatin quality. The aim of this study was to investigate the associations between conventional semen parameters and two clinically relevant markers of sperm chromatin integrity: DFI and protamine deficiency assessed by chromomycin A3 (CMA3) staining. This was a cross-sectional analytical study conducted in a certified private andrology laboratory operating under standardised quality control protocols. A total of 150 men undergoing fertility evaluation between 2022 and 2024 were included. Semen analysis was performed according to the World Health Organization 2021 guidelines;[1] DFI was assessed using the Halosperm sperm chromatin dispersion test, and chromatin maturity was evaluated by CMA3 staining. Non-parametric statistical methods were applied to evaluate correlations between molecular markers (DFI and CMA3) and semen parameters. Elevated DFI and CMA3 were significantly and inversely correlated associated with total motility, progressive motility, vitality and normal morphology (P < 0.01), while DFI correlated positively with CMA3 positivity (ρ = 0.54, P < 0.001). Men with DFI >30% or CMA3 >40% showed significantly reduced semen quality parameters. DFI and CMA3 are strongly associated with key semen parameters and provide complementary information on sperm nuclear integrity with potential clinical relevance in male infertility.
Lower urinary tract symptoms (LUTS), particularly nocturia, may disrupt sleep and have been hypothesized to suppress the hypothalamic-pituitary-gonadal axis. Although anatomical endoscopic enucleation of the prostate (AEEP) has been associated with increased testosterone in men with low baseline levels, its effect in men with "biochemically normal" preoperative testosterone remains unclear. To evaluate postoperative total testosterone (TT) changes after AEEP and to identify a preoperative TT threshold that predicts clinically meaningful TT elevation. We conducted a single-center retrospective cohort study of men undergoing AEEP between 2018 and 2021. Of 560 cases, 304 met inclusion criteria. Morning TT was measured preoperatively and 6-12 months postoperatively. Clinically significant TT elevation was defined as a ≥20% increase from baseline. Receiver operating characteristic (ROC) analysis identified the optimal preoperative TT cut-off for predicting TT elevation, and multivariable logistic regression evaluated independent predictors. The mean age was 69.7 years, and 92 of 304 patients (30.3%) achieved postoperative TT elevation. ROC analysis demonstrated moderate discrimination (AUC 0.737; 95% CI 0.678-0.797), with a Youden-optimal TT cut-off of 4.525 ng/mL (sensitivity 72.8%, specificity 64.2%). On bootstrap internal validation, the optimism-corrected AUC was 0.738, and the optimal cut-off varied across resamples (95% range 3.13-5.07 ng/mL), indicating that the threshold is exploratory. Preoperative TT <4.5 ng/mL independently predicted TT elevation (adjusted OR 4.345; 95% CI 2.533-7.453; p < 0.001), as did TT <3.5 ng/mL (adjusted OR 3.682; 95% CI 2.158-6.283; p < 0.001). AEEP was associated with meaningful TT increases not only in hypogonadal men but also in those with conventionally normal baseline TT, particularly within the 3.5-4.5 ng/mL range. In this uncontrolled cohort, a preoperative TT threshold around 4.5 ng/mL identified men more likely to show postoperative TT elevation; this exploratory finding warrants prospective, controlled validation before the current "normal" TT range is reconsidered.
Although surgical techniques for later interruption have advanced since the legalisation of voluntary interruption of pregnancy (VIP), dilatation and curettage via aspiration (D&C) remains the conventional approach. Hysteroresectoscopy (HsR) presents a potential alternative. This study aims to evaluate the feasibility of using HsR to perform VIP in cases in the early first trimester. A case series involving patients treated for VIP in our department. Women seeking VIP between six and ten weeks of amenorrhoea. Hysteroscopic resection following cervical dilatation, performed as an outpatient procedure under general or spinal anaesthesia. Between January 2021 and January 2026, 15 patients underwent VIP via HsR at our institution. One suspected case of uterine perforation was reported, and one patient experienced retained products of conception, which were managed with hysteroscopy performed in consultation without anesthesia. Additionally, 46,6% of patients received simultaneous contraception implantation. This mini-series suggests that HsR is a feasible technique for first trimester VIP, ideally applicable to pregnancies of up to nine of amenorrhoea. Fertility gains are expected from the minimal endometrial damage permitted by the technique. The findings are limited by the small sample size, making it difficult to draw definitive conclusions regarding the safety or efficacy of hysteroscopy compared with medical management or D&C. Although hysteroscopy appears to be a safe and promising approach, larger prospective studies are needed to confirm these findings and better compare outcomes with those of D&C.
Puberty is a critical window for bone mass acquisition, determining lifelong fracture risk. Gonadotropin-releasing hormone agonist (GnRHa)-based pubertal suppression followed by gender-affirming hormone therapy (GAHT) is increasingly used in transgender and gender-diverse (TGD) adolescents, raising concerns about peak bone mass. To quantify changes in bone mineral density (BMD), bone mineral apparent density (BMAD), and z scores in TGD adolescents undergoing GnRHa with or without GAHT, and to identify predictors of skeletal outcomes. PubMed, Scopus, Web of Science, and Cochrane Library, from inception through September 2025. Longitudinal cohorts assessing BMD, BMAD, or z scores at the lumbar spine, total hip, or femoral neck in TGD adolescents treated with GnRHa with or without GAHT. Ten studies met the inclusion criteria. Data were extracted in duplicate; study quality was assessed using the Newcastle-Ottawa Scale. Random-effects models pooled mean changes across baseline (time 0 [T0]), after GnRHa (T1), and after GAHT (T2), stratified by skeletal site and sex assigned at birth. Metaregressions examined body mass index, age, Tanner stage, and treatment duration. Dual-energy x-ray absorptiometry-derived BMD, BMAD, and z scores. Ten cohorts comprising 751 adolescents (427 assigned female at birth [AFAB]; 324 assigned male at birth [AMAB]) were included. Lumbar spine z scores declined during GnRHa (AFAB: z-score change, -0.97 [95% CI, -1.09 to -0.85]; AMAB: z-score change, -0.73 [95% CI, -0.93 to -0.53]) despite stable BMD. z Scores used sex-assigned-at-birth normative references. After GAHT, BMD increased (AFAB: BMD mean difference, 0.09 g/cm2 [95% CI, 0.07-0.10 g/cm2]; AMAB: BMD mean difference, 0.13 g/cm2 [95% CI, 0.10-0.16 g/cm2]), with partial z-score recovery; values remained below baseline at T2 (AFAB: z-score change, -0.51 [95% CI, -0.69 to -0.34]; AMAB: z-score change, -0.52 [95% CI, -0.82 to -0.21]) but were not consistently statistically different across skeletal sites. Recovery at the total hip and femoral neck was smaller and more heterogeneous. Higher body mass index, shorter GnRHa duration, and longer GAHT exposure were associated with more favorable outcomes. This systematic review and meta-analysis found that pubertal suppression followed by GAHT was associated with transient z-score reductions and subsequent BMD increases. At T2, z scores remained numerically below baseline but were not consistently statistically different, suggesting an uncertain rather than demonstrated persistent deficit. Timely GAHT initiation is recommended.
Sex chromosome aneuploidies represent a heterogeneous group of chromosomal conditions, in which phenotypic complexity generally increases with the number of supernumerary sex chromosomes. While Turner syndrome and sex chromosome trisomies are relatively well characterized, less is known about congenital malformations in sex chromosome tetrasomies and pentasomies. This systematic review synthesizes published data on congenital malformations reported in individuals with sex chromosome tetrasomies and pentasomies, applying a standardized organ-system-based classification according to the International Classification of Diseases, Tenth Revision (ICD-10). A comprehensive literature search of PubMed and Embase identified 134 eligible publications comprising 369 individuals with at least one reported congenital malformation. Most studies were case reports (n = 105). The majority of individuals had karyotypes 48, XXYY (n = 147) and 49, XXXXY (n = 186), whereas 48, XXXX, 48, XXXY, 48, XYYY, 49, XXXXX, 49, XXXYY, 49, XXYYY, and 49, XYYYY were less frequently described. Across karyotypes, congenital malformations demonstrated a broad multisystem distribution. Musculoskeletal anomalies were most frequently reported, followed by genital and cardiac malformations. A stepwise increase in the mean number of reported malformations per individual was observed with increasing numbers of supernumerary X chromosomes (1.8 in 48, XXYY, 2.5 in 49, XXXXY, and 3.3 in 49, XXXXX), which may be compatible with, but does not establish a gene-dosage effect. Compared with population-based birth cohorts, the proportional distribution of malformations differed, suggesting redistribution across organ systems rather than a uniform increase in overall burden. Although prevalence cannot be inferred from this selected case-based evidence, this review provides the first structured synthesis of congenital malformations in these rare karyotypes and supports an organ-directed approach at clinical evaluation. Population-based studies with standardized phenotyping are needed to define absolute risks and the full phenotypic spectrum.
Lifelong premature ejaculation (LPE) is a prevalent male sexual dysfunction with unclear neurobiological mechanisms. Despite its high prevalence, the etiology of LPE remains debated, often attributed to psychological or biological factors. Recent neuroimaging studies have highlighted the role of central nervous system dysregulation in sexual behavior. This study investigates abnormal brain functions and altered network connectivity in LPE patients after visual sexual stimuli (VSS) using functional magnetic resonance imaging. Twenty-five LPE patients and 31 healthy controls (HCs) underwent resting-state and task-state functional magnetic resonance imaging (fMRI). Clinical data, including sexual history, self-reported intravaginal ejaculatory latency time, International Index of Erectile Function-5, the Chinese Index of Premature Ejaculation, anxiety/depression scores, and serum testosterone levels, were collected. Neuroimaging preprocessing and analysis focused on amplitude of low-frequency fluctuation, fractional ALFF, and regional homogeneity. Task-state fMRI compared brain activation patterns after VSS. Statistical analyses included voxel-based comparisons and network connectivity assessments using SPM12 and DPABI v3.0. LPE patients demonstrate distinct neurofunctional abnormalities after VSS, particularly hyperactivation in the precuneus. ‌Clinical Data‌: LPE patients exhibited significantly lower International Index of Erectile Function-5 scores and higher depression rates compared to HCs, with no differences in age, BMI, or testosterone levels. Brain Activation‌: During VSS, LPE patients showed relative signal decrease in the middle cingulate cortex and left precentral gyrus compared to HCs. Regional homogeneity analysis revealed hyperactivation in the precuneus and fusiform gyrus post-stimulus. Network Connectivity‌: Altered connectivity in premature ejaculation patients involved the fusiform gyrus (linked to posterior cingulate, hippocampus, parahippocampus, and supplementary motor areas) and the superior parietal lobule (connected to the angular gyrus). These findings suggest that aberrant central nervous system processing of sexual stimuli contributes to premature ejaculation pathophysiology, offering potential targets for neuromodulatory therapies. The study focuses on the different activation patterns of patients with LPE from the perspective of sexual arousal. The methodological aspects of research, such as the use of images or videos in sexual stimulation, remain controversial. The findings of our network analysis only demonstrated a limited number of altered functional connections, and no established network metrics were provided to substantiate the claim of extensive network disruption. These factors collectively represent important limitations of the present study. The hyperactivity in this brain region observed in patients could represent a unique response to VSS among those with LPE, ultimately leading to alterations in their ejaculatory behavior.‌‌‌.
Aromatase inhibitors (AIs) profoundly suppress estrogen synthesis and accelerate bone loss in postmenopausal women with early breast cancer (EBC). Although body mass index (BMI)-defined obesity has been considered protective for skeletal health, emerging evidence suggests a paradoxical association with fracture risk. To evaluate whether fat mass percentage (FM%) greater than 40.8%, measured by dual-energy x-ray absorptiometry (DXA), is associated with vertebral fracture (VF) progression in patients with EBC receiving AIs. This retrospective cohort study included consecutive postmenopausal women with EBC (stages I-III) recruited in a single referral center between September 2014 and June 2024. All patients received adjuvant endocrine therapy and underwent serial DXA assessments. Patients treated with tamoxifen or with major comorbidities affecting skeletal fragility were excluded. Body composition and bone fragility parameters evaluated by DXA at baseline and at 18, 24, and 30 months. Adiposity excess was defined as FM% greater than 40.8%, and VF progression was defined as new incident fractures and/or worsening by at least 1 Genant grade at a previously fractured vertebral level. Their association was evaluated using a joint model; time-dependent associations were evaluated using extended Cox regression. Secondary analyses explored associations with bone mineral density, trabecular bone score (TBS), appendicular lean mass index (ALMI), and traditional fracture risk factors. A total of 769 White women (median [range] age, 63 [30-87] years; median [range] BMI, 24.6 [15.6-46.1]) entered the study. During follow-up, 69 patients (9.0%) experienced VF progression. FM% greater than 40.8% was independently associated with increased VF progression (adjusted hazard ratio [HR], 2.00; 95% CI, 1.44-2.82; P < .001). Higher ALMI (HR, 0.38; 95% CI, 0.22-0.65; P < .001) and BMD (HR, 0.79; 95% CI, 0.66-0.94; P = .01) were associated with lower risk of VF progression. In this retrospective cohort study of patients with EBC receiving AIs, adiposity excess was identified as a novel fracture risk factor, whereas higher muscle mass was protective. These findings support incorporating body-composition assessment into fracture-risk evaluation and preventive strategies for patients undergoing AI therapy.
Infertility impacts 10%-15% of the population, with prominent male contributions. Routine semen analysis fails to fully evaluate male fertility. Sperm DNA fragmentation (SDF) links to poor reproductive outcomes. Although intracytoplasmic sperm injection (ICSI) is recommended for high SDF, its overuse in nonsevere male infertility is controversial. The divergent impacts of SDF on in vitro fertilization (IVF) and ICSI cumulative live birth rate (CLBR) remain unclear. To evaluate the effect of SDF on the CLBR in couples undergoing IVF and ICSI, and to explore the optimal choice of assisted reproductive fertilization methods under different levels of SDF in nonsevere male infertility. Sperm chromatin structure assay, propensity score matching (PS-matching), generalized additive model (GAM), and causal forest (CF) model analysis. After PS-matching: 398 cases in both IVF and ICSI groups (standardized difference <0.1). GAM: IVF group's CLBR decreased with DFI; ICSI group had no correlation. IVF's CLBR was higher when DFI < 14.3%, lower when DFI > 47.9%. CF model: DFI was a top predictor; SHAP analysis: DFI < 14.2% favored IVF, DFI > 14.2% favored ICSI. For nonsevere male infertility, IVF yields superior baseline CLBR at DFI < 14.3%. Rising DFI impairs IVF outcomes, whereas ICSI remains unaffected. Pretreatment DFI enables individualized IVF/ICSI selection.
Bone is a unique specialized connective tissue comprising inorganic and organic components which continuously undergoes remodeling through the activity of anabolic and catabolic pathways. Peptidases are enzymes cleaving peptide bonds in a broad range of substrates and hence involved in many pathophysiological mechanisms. We previously reported that lack of Dpp3 in the mouse model results in bone loss and here we aimed to establish whether it also affected bone matrix composition. We performed proteomic and lipidomics analysis of the flushed bone of 6-month-old wild type (WT) and Dpp3 knock-out (ko) male mice (4 mice/genotype); Western blot analysis of selected upregulated proteins and gene expression analysis of genes potentially involved in the identified pathways. We found that Dpp3 deficiency was associated with a proteomic signature in the bone matrix consistent with sustained oxidative stress and altered matrix turnover and pointing to a metabolic adaptation within the skeletal tissue. Accordingly, lack of Dpp3 resulted in a shift in lipid composition in the bone matrix, with enrichment of specific structural lipids and lack of others for energy production. Our work confirms the importance of DPP3 in the context of bone homeostasis and sheds some light on the matrix composition of DPP3-depleted bone. Owing to the foreseen translational implications of this evidence, further investigation is deserved to complete a comprehensive characterization.
Acephalic spermatozoa syndrome (ASS) is a rare cause of male infertility characterized by sperm tails lacking heads. Although zinc finger MYND-type containing 15 ( ZMYND15 ) mutations are linked to male infertility, their role in ASS is unknown. In this study, whole-exome sequencing identified novel homozygous truncating mutations, c.292C>T (p.Arg98Ter) and c.337G>T (p.Glu113Ter), in ZMYND15 from two infertile patients. These mutations caused protein truncation and impaired function, leading to extremely low sperm counts, poor motility, and numerous acephalic spermatozoa. Electron microscopy and sperm immunofluorescence revealed abnormal sperm neck structures, missing mitochondrial sheaths, failure of acrosome formation, and a lack of central microtubules. Experiments showed reduced mutant protein expression and high rates of degradation. Coimmunoprecipitation experiments indicated a direct interaction between ZMYND15 and Sad1 and UNC84 domain containing 5 (SUN5), crucial for forming the sperm head-tail connection. One patient achieved a live birth via intracytoplasmic sperm injection (ICSI), whereas the other had an early miscarriage. This study links ZMYND15 mutations directly to ASS, highlighting its role in spermatogenesis and offering insights for clinical diagnosis and treatment.
Selecting high-quality spermatozoa with optimal nuclear integrity is a crucial step in assisted reproductive technologies (ART). While density gradient centrifugation (DGC) is widely used, the associated centrifugation steps may induce cell stress, potentially damaging sperm DNA. Conversely, micro swim-up (MSU) is an innovative, centrifugation-free procedure using autonomous gamete migration in a polyvinylpyrrolidone medium. This study aimed to compare the sperm selection technique MSU with the conventional method DGC in terms of sperm chromatin integrity in 90 semen samples. Rapid progressive motility, sperm DNA fragmentation (sDF; SCD test), nuclear immaturity (aniline blue [AB] staining), and chromatin decondensation (chromomycin A3 [CMA3] staining) were evaluated before and after selection. Both procedures significantly improved motility and nuclear parameters compared to unselected samples. However, MSU outperformed DGC across all nuclear integrity markers. Specifically, sDF decreased from 18.50% (14.63-26.25) to 9.25% (6.00-16.00) with DGC and 1.00% (0.00-2.00) with MSU (p < 0.0001 MSU vs. DGC). Regarding nuclear immaturity, values improved from 21.00% (15.00-27.50) to 15.00% (8.00-18.00) with DGC and 5.00% (4.00-10.00) with MSU (p = 0.012 MSU vs. DGC). Similarly, chromatin decondensation decreased from 18.25% (10.88-23.63) to 13.50% (7.00-15.63) with DGC and 5.50% (2.75-10.00) with MSU (p = 0.0001 MSU vs DGC). MSU selects spermatozoa with significantly superior nuclear integrity compared to DGC, markedly reducing DNA fragmentation and improving chromatin maturation. Given the direct impact of these parameters on ART outcomes, MSU might represent a valuable alternative to traditional centrifugation-based methods in clinical settings.
The tumor immune microenvironment (TIME), composed of tumor cells, immune/stromal cells, cytokines, and other components, plays a central role in determining tumor immunogenicity and response to therapy. The balance between effector T/NK cells and immunosuppressive populations such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and M2-like tumor-associated macrophages (TAMs) determines whether tumors remain "cold" or become "hot". Triple-negative breast cancer (TNBC) remains challenging to treat because it lacks estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) targets and exhibits high heterogeneity. To address these limitations, tumor microenvironment (TME)-targeted nanocarriers have emerged as a promising strategy. By exploiting features such as hypoxia, acidity, redox imbalance, and abnormal vascular and mechanical cues, these systems enable prolonged circulation, active targeting, and stimulus-responsive release, thereby enhancing the efficacy of therapies such as immune checkpoint blockade. This review summarizes major nanoplatforms and therapeutic strategies, while highlighting translational barriers including TIME heterogeneity, enhanced permeability and retention (EPR) effect, and protein corona formation. Finally, this review explains why patient stratification should be incorporated into the future development of TNBC nano-immunotherapy and argues for simplified, reproducible nanocarrier designs to support clinically applicable precision treatment.
Gender-affirming hormone therapy (GAHT), particularly estrogen-based regimens, is associated with an increased risk of venous thromboembolic events (VTE), which may be exacerbated in individuals with hereditary thrombophilia. Despite this risk, the prevalence and clinical implications of hereditary thrombophilia in transgender individuals remain underexplored. We screened 114 transgender individuals (54 AMAB, 60 AFAB) at the University Hospital of Padua (Italy) for hereditary thrombophilia, including factor V Leiden (FVL), prothrombin G20210A (PT20210A), antithrombin (AT), protein C (PC), and protein S (PS) deficiencies, as well as antiphospholipid antibodies. Hereditary thrombophilia was identified in 9.6% of participants, including two cases of severe thrombophilia. No participants tested positive for antiphospholipid antibodies. Individuals with thrombophilia had a higher prevalence of personal and family history of VTE. Three thrombotic events were recorded prior to GAHT: one transgender woman (heterozygous FVL) with unprovoked lower limb VTE, one transgender man (PC deficiency) with neonatal cerebral ischemia, and one transgender man (heterozygous FVL) with subclavian VTE during chemotherapy. A multidisciplinary approach involving coagulation specialists and endocrinologists was implemented to optimize risk reduction strategies, including tailored GAHT regimens and anticoagulation when necessary. No VTE occurred during a 15-month follow up. These findings highlight the importance of thrombophilia screening to enable individualized care and enhance the safety of GAHT protocols.
Human spermatozoa are highly specialized cells whose function depends on tightly regulated metabolic and signaling networks. Following spermatogenesis and epididymal maturation, ejaculated spermatozoa must undergo capacitation in the female reproductive tract, a complex process characterized by extensive biochemical remodeling and high energy demand that enables hyperactivated motility and fertilizing competence. Human spermatozoa bioenergetics remains a prominent theme in the field of Andrology, whose advances are challenged by inter-species differences and difficulties in extrapolating data from in vitro and animal model studies to human physiology. In this comprehensive review, we discuss the current knowledge of the bioenergetic pathways governing capacitation and hyperactivation in human spermatozoa. While glycolysis remains a primary adenosine triphosphate (ATP) source, supported by sperm-specific glycolytic enzymes that provide a rapid and spatially localized ATP supply directly in the flagellum, accumulating evidence indicates that mitochondrial oxidative phosphorylation (OXPHOS) complements ATP production, assists in the regeneration of reducing equivalents to sustain a high glycolytic flux during capacitation and contributes to capacitation-activating signaling pathways. Besides these core bioenergetic pathways, the great metabolic flexibility of human spermatozoa is evidenced by the mobilization of endogenous energy substrates and engagement of additional metabolic pathways, such as fatty acid β-oxidation, pentose phosphate pathway, ketone body catabolism, and amino acids oxidation to meet the high energetic and redox demands required for capacitation and hyperactivation. Overall, these findings suggest that the metabolic potential of human spermatozoa is considerably broader than previously recognized. A comprehensive understanding of human spermatozoa bioenergetics will assist in the identification of novel biomarkers that may characterize previously male infertility cases identified as idiopathic, as well as identify therapeutic targets to improve medically assisted reproductive procedures.
Transverse testicular ectopia (TTE) is a rare anomaly often associated with persistent Müllerian duct syndrome and infertility. We report a 34-year-old man with primary infertility, a vacant right hemiscrotum, and a left scrotal mass. MRI showed both testes in the left hemiscrotum, with a heterogeneous right ectopic testicular tumor. Surgery confirmed TTE without gross Müllerian remnants; bilateral orchiectomy was performed because of malignancy and contralateral atrophy. Histopathology revealed seminoma. Genetic testing identified novel compound heterozygous AMHR2 variants. This case highlights the value of MRI, genetic evaluation, and early management to reduce infertility and malignant transformation risks in TTE patients worldwide.
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition that significantly impairs men's quality of life. Its pathogenesis remains incompletely understood, and there is a lack of specific diagnostic methods. As important signaling molecules in intercellular communication, microRNAs (miRNAs) in exosomes play a key role in the pathological progression of CP/CPPS. This review proposes that 'exosome miRNA-mediated interactions within the local urogenital microenvironment' constitute the core mechanism driving the chronicity and localization of CP/CPPS. We provide a comprehensive overview of the diagnostic and prognostic value of specific exosome miRNA expression profiles detected in the biofluids (such as prostatic fluid and urine) of CP/CPPS patients. Furthermore, we explore the dual role that exosomal miRNAs play in disease initiation and progression by regulating inflammation, oxidative stress, and immune responses. Finally, we discuss the potential of exosome-based miRNA delivery systems as novel targeted therapeutic strategies for CP/CPPS. In summary, exosomal miRNAs are of great significance for understanding the complex pathological networks underlying CP/CPPS. Future research should focus on the validation of specific biomarkers, the elucidation of intercellular communication networks, and the advancement of their clinical translation and application.