Microdissection testicular sperm extraction is the preferred method for sperm retrieval in men with non-obstructive azoospermia. However, the effects of sperm retrieval quantity and freezing on intracytoplasmic sperm injection outcomes remain incompletely understood. To evaluate the impact of sperm quantity and freezing status on fertilization and cumulative live birth rate following intracytoplasmic sperm injection using microdissection testicular sperm extraction spermatozoa in non-obstructive azoospermia patients. We retrospectively analyzed 1394 microdissection testicular sperm extraction-intracytoplasmic sperm injection cycles performed between 2017 and 2022 at a single tertiary center. Sperm retrieval yield was stratified into three groups: sufficient sperm count (>10 spermatozoa/100 fields), low sperm count (6-10/100), and extremely low sperm count (1-5/100). Fertilization rate (two pronuclei) and cumulative live birth rate were compared across sperm retrieval yield and freezing subgroups. Multivariable regression and interaction models assessed the independent and combined effects of sperm quantity and freezing status. Fertilization and cumulative live birth rate declined significantly with reduced sperm counts (two pronuclei: 53.6%→32.2%; cumulative live birth rate: 49.8%→21.8%; p<0.001). Frozen spermatozoa yielded comparable outcomes to fresh spermatozoa overall, but in the extremely low sperm count group, frozen spermatozoa were associated with a significantly lower cumulative live birth rate than fresh spermatozoa (12.3% vs. 29.3%; p=0.015). Interaction analysis confirmed this adverse effect (OR=0.39; 95% CI 0.16-0.95; p=0.038). No significant freezing effect was observed in the other groups. Sperm retrieval quantity is an important predictor of intracytoplasmic sperm injection success in men with non-obstructive azoospermia. Freezing generally does not affect outcomes, but may significantly reduce live birth rates when sperm availability is extremely limited. Prioritizing the use of fresh spermatozoa in such cases may improve clinical outcomes.

The most prevalent solid tumors in young men are testicular germ cell tumors (TGCTs), and embryonal carcinoma is the most common subtype among non-seminomatous germ cell tumors (NSGCTs). Despite the excellent cure rates of cisplatin-based chemotherapy, resistance develops in 15%-30% of patients with metastatic cancer, which results in a poor prognosis. The overexpression of the High Mobility Group A2 (HMGA2) protein has been linked to treatment resistance and cancer aggressiveness. It is well known that this protein promotes carcinogenesis. The purpose of this work was to investigate the functional role of HMGA2 in EC cell migration, survival, and proliferation, focusing on its role as a potential therapeutic target in cisplatin-resistant ECs. We employed human EC cell lines EP2102 and GCT27, as well as the cisplatin-resistant (CisR) versions of these cell lines that were produced by prolonged drug treatment. siRNA transfection was used to suppress HMGA2 expression. Growth curve and colony formation tests were used to measure cell proliferation. Apoptosis was assessed by Annexin V staining followed by flow cytometry, cell cycle distribution was analyzed by flow cytometry, and cell migration was detected by Boyden Chamber Assays. In both parental and resistant EC cell lines, HMGA2 knockdown markedly decreased proliferation. After HMGA2 knockdown, flow cytometric analysis revealed S phase arrest. Apoptosis was significantly elevated, especially in cells that were resistant to cisplatin. In addition, all HMGA2-depleted cell lines showed decreased migration. These impacts were true for both the GCT27 and EP2102 models. The data suggest that HMGA2 is necessary to preserve the EC cells' malignant characteristics. Its silencing interferes with several cancer-related functions, including motility, survival, and cell cycle progression. These results indicate HMGA2's participation in chemoresistance mechanisms and are consistent with its role in other solid cancers. Our results indicate a role of HMGA2 in the EC, because its inhibition reduces cell malignant characteristics, and may represent a viable therapeutic target to improve the prognosis of CisR TGCTs.

Erectile dysfunction (ED) and acute coronary events are closely linked, yet the trajectory of ED following percutaneous coronary intervention (PCI) remains incompletely understood. The residual SYNTAX score (RSS) quantifies incomplete revascularization and is an established prognostic tool in cardiology; however, its role in erectile function recovery after myocardial infarction (MI) is unclear. To evaluate whether RSS predicts recovery of erectile function after MI treated with PCI. In this prospective cohort study, 82 men aged 40-70 years who underwent PCI for MI were evaluated. ED was assessed using the International Index of Erectile Function-5 (IIEF-5) at baseline (after recovery from PCI, reflecting erectile functions before MI), and at 3 and 6 months. ED was defined as an IIEF-5 score ≤21. Patients were stratified according to RSS (<8 vs. ≥8). Anxiety (sexual-fear subscale) and depressive symptoms (BDI-II) were also assessed. ED was present in 57.3% of patients at baseline, increased to 68.7% at 3 months, and decreased to 37.3% at 6 months. At 6 months, mean IIEF-5 scores improved significantly in men with RSS <8 (from 17.9 to 21.2; p<0.001), but not in those with RSS ≥8 (from 17.2 to 16.3; p = 0.314). While severe ED remained largely unchanged over time, mild-to-moderate ED demonstrated the greatest improvement. Anxiety independently predicted ED at 3 months (OR 1.223, p = 0.049). At 6 months, RSS ≥8 independently predicted persistent ED (OR 3.22, p = 0.033), with moderate discriminatory accuracy (AUC 0.72). RSS ≥8 may identify men at increased risk for persistent ED after MI. The differential recovery patterns suggest that reversible functional impairment may predominate in milder forms of ED, whereas persistent severe ED may reflect more extensive systemic and penile vascular disease. Early recognition of anxiety and targeted sexual counseling may support erectile recovery following PCI.

Testicular germ cell cancer (TGCC) is the most frequent malignancy in young men of reproductive age. According to guidelines, semen cryopreservation should be performed prior to orchiectomy. Lack of time and local facilities as well as mental pressure are challenges in terms of fertility preservation before surgery. This study aims at comparing semen parameters before and after orchiectomy in TGCC patients. We prospectively recruited 25 patients with TGCC who performed semen cryopreservation at our Centre. Study participation included a pre-surgery cryopreservation (T0) and post-surgery visits within 8 weeks (T1) before any further gonadotoxic therapies. Testicular ultrasound, hormone values, and total sperm count (TSC), sperm concentration, sperm motility and vitality were included for analysis. The primary endpoint was the change in TSC (ΔTSC) from T0 to T1. p < 0.05 was considered statistically significant. Histopathology of the 25 patients revealed 16 seminomas and nine non-seminomas. Median age was 30 years (interquartile range [IQR]: 28-35; mean age ± standard deviation [SD] 30.96 ± 5.86). TSC was higher at T1 compared with T0 in seven patients, while 18 patients showed a lower TSC at T1. Median TSC for all patients was 52.8 Mill/ejac. (IQR: 26.8-88.8) before-and 26.5 Mill/ejac. (IQR: 4.4-82.6) after orchiectomy showing an overall decrease. Wilcoxon signed rank test however did not result in a statistically significant decrease in TSC (p = 0.083). There was a decline in sperm concentration (p = 0.004) and in motility (a+b) (p = 0.004). Because we found an overall decrease in sperm quality post-surgery, we suggest that semen cryopreservation in TGCC patients should always be performed before orchiectomy. However, in some patients higher TSC was observed after orchiectomy. Thus, an individualized additional potential for cryopreservation in selected patients post-surgery can be discussed. We consider our findings a starting point for a prospective multicenter study to validate the obligation for pre-surgical cryopreservation and to identify subgroups who might benefit from additional post-surgery cryopreservation.

The extracellular calcium concentration is important for sperm function, maturation, and survival, however, studies exploring the link between seminal calcium and reproductive function have reported inconsistent findings. To investigate the association between seminal calcium levels and semen quality in both healthy and infertile men. A total of 301 young men from the general Danish population who participated in a study of semen quality, and 228 infertile men who were supplemented with calcium (500mg) + cholecalciferol (300,000 IU bolus followed by 1400 IU daily), or placebo in a randomized controlled trial were included. Each man underwent a physical examination, routine semen analysis, analysis of calcium concentrations in the seminal fluid, and blood sampling for assessment of PTH, testosterone, estradiol, inhibin B, and AMH. In young men from the general population, sperm concentration was higher in those within the highest seminal calcium quartile (Q4: 9.0-19.2mmol/L) compared with the lowest (Q1: 1.3-4.7mmol/L; 53.0 million/mL vs. 31.0 million/mL, p = 0.010). Accordingly, infertile men in Q1 had the lowest sperm concentration (e.g., 6.6 vs. 22.5 million/mL in Q3), but also fewer progressively motile spermatozoa (p = 0.030). Supplementation with calcium and cholecalciferol did not affect seminal calcium concentration (p = 0.33), however, infertile men who experienced an increase in their seminal calcium concentrations > 30% at the end of intervention had a higher sperm concentration (p = 0.048) and total sperm count (p < 0.001) compared with baseline. There was a weak positive correlation between longitudinal changes of seminal calcium and serum estradiol (r = 0.17, p = 0.016). Lower seminal calcium concentration is associated with poorer semen quality but was not influenced by calcium supplementation. Future research should focus on uncovering possible regulators, for instance, estrogens. ClinicalTrials.gov no. NCT01304927 (registered February 28, 2011).

ABSTRACT Background Low parental education is associated with poorer offspring health, but its influence on male fecundity remains unclear. Objective To study the association between parental educational attainment at birth and biomarkers of male fecundity in young men and to explore whether this association is mediated by maternal smoking in pregnancy and overweight/obesity at 19 years of age. Materials and Methods A cohort study with 1058 sons born 1997–1999 from the Fetal Programming of Semen Quality (FEPOS). The exposure was the highest educational attainment among parents at their child's birth, obtained from administrative registers. Outcomes were measured at a clinical examination and included semen characteristics (semen volume, semen concentration, total sperm count, motility, morphology, DNA fragmentation index, and high DNA stainability), testicular volume, and reproductive hormone levels (estradiol, testosterone, Sex Hormone‐Binding Globulin, luteinizing hormone, and follicle‐stimulating hormone). Outcomes were analyzed using a multivariable negative binomial regression model adjusted for potential confounding factors and precision variables. Potential mediation by maternal smoking in pregnancy, as well as overweight or obesity at 19 years of age, was investigated in separate mediation analyses. Results Sons of parents with low educational attainment at birth had a tendency to have lower semen volume (relative percentage difference: −8% (95% confidence interval [CI]: −17%; 2%), lower semen concentration (−8% [95% CI: −20%; 6%]) and lower total sperm count (−12% [95% CI: −25%; 3%]) compared to sons of parents with high educational attainment. No major difference was observed for other biomarkers of male fecundity. Maternal smoking in pregnancy, but not overweight/obesity at 19 years of age, partly mediated the association. Conclusion Our findings suggest some association between parental educational attainment and biomarkers of male fecundity in young men. These findings were partly mediated by maternal smoking in pregnancy, but not by overweight or obesity in young adult sons.

Platelet-rich plasma (PRP) injection into penile plaques is an emerging, investigational approach for treating acquired penile curvature in men with stable-phase Peyronie's Disease (PD). We report preliminary findings from a two-center prospective pilot study. Thirty-eight men with stable PD underwent two PRP injections (≈8mL each), 4weeks apart. PRP was prepared using either double or single centrifugation (2-cycle vs. 1-cycle group). All patients initiated tadalafil 5mg daily and penile stretching with a vacuum device (5-15min/day) 1week after the first injection. Baseline and 3-month follow-up assessments included dynamic penile color doppler-duplex ultrasound (CDDU), International Index of Erectile Function (IIEF), and Peyronie's disease questionnaire (PDQ). Twenty-two patients (57.9%) received 2-cycle PRP; 16 (42.1%) received 1-cycle PRP. Baseline penile curvature was 45° (37-70) in the 2-cycle group and 60° (50-66) in the 1-cycle group, decreasing to 40° (30-50) and 50° (40-56), respectively (p=0.002 and p=0.008). Overall, median curvature decreased from 55° (45-70) to 45° (30-55), with a median reduction of 10° (0-15) (p<0.001). PDQ scores improved significantly in both groups (p≤0.006), while IIEF-EF and CDDU parameters remained unchanged. Plaque diameter showed a non-significant reduction. No treatment-emergent adverse events occurred. PRP injections appear safe and may modestly improve penile curvature and PDQ scores in men with stable-phase PD. However, the observed curvature reduction is insufficient to infer clinically meaningful long-term outcomes. Larger controlled studies are warranted.

Postprandial lipid testing is increasingly recognized as a marker of vascular health. However, its relationship with erectile dysfunction (ED) remains largely unexplored. Isolated postprandial dyslipidemia (IPD), in particular, may evade detection using conventional fasting-based assessments, despite potential atherogenic effects. To evaluate the association between IPD and erectile function, comparing the prevalence and severity of ED among men with IPD, combined dyslipidemia (CD), and those without dyslipidemia (WD). In this cross-sectional study, sexually active men aged ≥18 years underwent same-day fasting and postprandial lipid testing, as well as erectile function evaluation using the International Index of Erectile Function - Erectile Function domain (IIEF-EF) questionnaire. Dyslipidemia was defined according to the 2019 European Society of Cardiology/European Atherosclerosis Society criteria. Patients were categorized as WD (no dyslipidemia), IPD (postprandial abnormalities only), or CD (both fasting and postprandial abnormalities). Multivariable logistic regression was performed, adjusting for age, smoking status, BMI, and hypertension. The primary outcome was the prevalence of ED (IIEF-EF ≤25); secondary outcomes included ED severity and comparisons across lipid profile subgroups. Among 351 men, ED prevalence was higher in the IPD (55.1%) and CD (57.0%) groups compared to WD (32.8%; p < 0.001). Median (IQR) IIEF-EF scores were 26 (25-28) in the WD group, 22 (20-23) in the IPD group, and 21 (19-23) in the CD group. The differences between WD and both IPD and CD exceeded the minimal clinically important difference (4 points) and were statistically significant (p < 0.001). Adjusted analyses confirmed increased odds of ED in IPD (odds ratio [OR] = 2.36; 95% confidence interval [CI]: 1.41-3.96) and CD (OR = 2.58; 95% CI: 1.43-4.65) versus WD. ED severity was also greater in the IPD and CD groups. No differences emerged between IPD and CD in any outcome. Among IPD subtypes, elevated postprandial triglycerides were most common, but no single lipid abnormality was independently associated with ED severity. IPD is associated with both the prevalence and severity of ED, paralleling the impact of chronic dyslipidemia. Postprandial lipid testing may reveal hidden metabolic risks relevant to sexual health and should be considered in the evaluation of ED.

The Testicular Cancer Consortium (TECAC) was established in 2012 and is comprised of researchers from over 25 centers in Europe and North America. TECAC's overarching goal is to investigate the genetic susceptibility of testicular germ cell tumors (TGCT) to better understand their biology, impact prevention strategies, and inform treatment decisions. To provide an overview of TECAC genetic and phenotypic holdings. TECAC has composed by-laws describing the consortium structure and governance, codified the processes for manuscript development and data transfer, and developed guidance for the transfer of biological samples and access to data. TECAC has assembled a vast amount of genetic information on males with TGCT-including SNP-array data on over 13,500 cases, whole-exome sequencing data on over 4500 cases, and low-pass whole-genome sequence data on over 2700 cases. Genetic information on males without TGCT (controls) is derived from studies designed to assess risk factors for TGCT and from publicly available resources. When available, corresponding phenotypic information is collected and harmonized. Fifteen publications have resulted from genetic and phenotypic information curated by TECAC. The sharing of genetic and phenotypic data by TECAC centers to inform large studies of TGCT susceptibility has led to novel insights into the genetic architecture of this cancer, including the roles of genes involved in male germ cell development, sex determination, chromosomal segregation, and RNA transcription. These findings would not have been achievable by individual centers or smaller collaborative efforts. We invite investigators from any discipline who have access to collections of germline DNA, somatic cell DNA, or genomic information on males with TGCT to consider joining TECAC to further strengthen our efforts to reduce the global burden of TGCT.