Decreased spermatogonial numbers in boys with severe haematological diseases.

This study examines spermatogonial numbers in testicular samples from 43 prepubertal patients undergoing haematopoietic stem cell transplantation (HSCT). High-dose chemotherapy and/or radiation during HSCT can impact spermatogenesis requiring fertility preservation. Results show that 49% of patients have decreased and 19% severely depleted spermatogonial pool prior to HSCT. Patients with Fanconi anaemia exhibit significantly reduced spermatogonial numbers. Patients with immunodeficiency or aplastic anaemia generally present within the normal range, while results in patients with myelodysplastic syndrome or myeloproliferative neoplasm vary. The study emphasizes the importance of assessing spermatogonial numbers in patients with severe haematological diseases for informed fertility preservation decisions.

TRACK_9: Testosterone replacement assessment: Classical vs. functional hypogonadism­knowledge from a 9­year study

BACKGROUND AND OBJECTIVE: The longitudinal efficacy and clinical utility of Testosterone Therapy (TTh) in ameliorating functional hypogonadism (FH) remain contentious, with long-term data being scarce. To address this lacuna, a comprehensive long-term registry study, stratifying patients across a spectrum of hypogonadal etiologies, offers a robust investigative paradigm. MATERIALS AND METHODS: This 9-year registry, encompassing 650 patients (equivalent to 4,362 cumulative years of treatment), included 188 patients diagnosed with FH (mean age 42.3 ± 11.3 years) and 462 individuals with classical hypogonadism (CH). The cohort segregated into 266 men with primary hypogonadism (PH, mean age 34.0 ± 11.7 years) and 196 with secondary hypogonadism (SH, mean age 31.9 ± 12.0 years). Uniform treatment across the cohort involved intramuscular administration of testosterone undecanoate (1,000 mg). A comparative analysis was conducted focusing on anthropometric, metabolic, and safety parameters. RESULTS: Serum testosterone levels increased from 6.6 ± 2.4 to 19.3 ± 2.9 nmol/L (p < 0.001). TTh was linked with weight reduction and decreased waist circumference (WC) in both CH and FH cohorts (both p < 0.001). Cox regression and Kaplan-Meier analyses delineated disparities: men with FH demonstrated a higher propensity for losing > 10% body weight and > 5% WC compared to CH (hazard ratio [HR] 1.3 [1.1-1.4], p = 0.008 and HR 1.4 [1.3-1.5], p = 0.001). Increases in hematocrit > 50% were uniform across groups, albeit amelioration of anemia was more pronounced in FH versus CH (p = 0.002). Increments of prostate-specific antigen (PSA) levels were more likely to occur in FH (HR 1.3 [1.1-1.6], p = 0.003). FH patients exhibited pronounced improvements in metabolic parameters and in aging male symptom score (AMS) and IIEF-EF questionnaire scores. These effects were markedly modulated by age and initial weight. Subgroup analysis of age-matched obese patients revealed an accentuated impact of TTh in CH compared to FH. DISCUSSION AND CONCLUSION: The therapeutic outcomes of TTh across distinct hypogonadal populations demonstrate heterogeneous responses, significantly influenced by diagnostic categorization, age, and baseline risk factor profiles.

App-based Therapy of Erectile Dysfunction Using a Digital Health Application (EDDIG Study): A Randomized, Single-blind, Controlled Trial.

BACKGROUND AND OBJECTIVE: While international guidelines advocate for a multifaceted approach to treating erectile dysfunction (ED) involving physical activities, psychological support, and education, structured programs are infrequent. To address this gap, an app-based therapy was developed, offering a systematic approach. This randomized, single-blind controlled trial aimed to assess the effectiveness of an app-based therapeutic in improving ED. METHODS: A total of 241 patients (49.74, standard deviation 12.73 yr) with ED (International Index of Erectile Function [IIEF]-5 <22) were randomized to the 12-wk app-based therapy (treatment group [TG], n = 122) or a waiting list for the app with continuation of their current management protocol (control group [CG], n = 119). Patients on long-term medication for ED were included, but subsequent exclusion occurred for those starting new medication. Coprimary endpoints were improvements from baseline to 12 wk in erectile function (IIEF-5), disease-related quality of life (QOL-Med-15), and patient activation (Patient Activation Measure [PAM-13]). KEY FINDINGS AND LIMITATIONS: Erectile function (IIEF-5) improved by 4.5 points in the TG versus 0.2 points in the CG (p < 0.0001, 95% confidence interval [CI] 3.4-5.0) group. Quality of life (QOL-Med) improved by 20.5 points in the TG versus -0.0 points in the CG (p < 0.0001, 95% CI 19.2-26.0) group. Patient activation (PAM-13) improved by 11.2 points in the TG versus 0.6 points in the CG (p < 0.0001, 95% CI 9.1-13.6) group. Phosphodiesterase type 5 inhibitor intake had no influence on all observed treatment effects. CONCLUSIONS AND CLINICAL IMPLICATIONS: App-based therapy of patients with ED provided a significant, clinically meaningful improvement. Quality of life and patient activation were also enhanced significantly. This program has the potential to change clinical practice in the treatment of ED. PATIENT SUMMARY: A therapy app improved sexual function and overall well-being for men experiencing erectile dysfunction, leading to better quality of life.

Human fertilization in vivo and in vitro requires the CatSper channel to initiate sperm hyperactivation.

The infertility of many couples rests on an enigmatic dysfunction of the man's sperm. To gain insight into the underlying pathomechanisms, we assessed the function of the sperm-specific multisubunit CatSper-channel complex in the sperm of almost 2,300 men undergoing a fertility workup, using a simple motility-based test. We identified a group of men with normal semen parameters but defective CatSper function. These men or couples failed to conceive naturally and upon medically assisted reproduction via intrauterine insemination and in vitro fertilization. Intracytoplasmic sperm injection (ICSI) was, ultimately, required to conceive a child. We revealed that the defective CatSper function was caused by variations in CATSPER genes. Moreover, we unveiled that CatSper-deficient human sperm were unable to undergo hyperactive motility and, therefore, failed to penetrate the egg coat. Thus, our study provides the experimental evidence that sperm hyperactivation is required for human fertilization, explaining the infertility of CatSper-deficient men and the need of ICSI for medically assisted reproduction. Finally, our study also revealed that defective CatSper function and ensuing failure to hyperactivate represents the most common cause of unexplained male infertility known thus far and that this sperm channelopathy can readily be diagnosed, enabling future evidence-based treatment of affected couples.