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IMPORTANCE: Advances in the treatment of childhood cancer have significantly improved survival rates, with more than 80% of survivors reaching adulthood. However, gonadotoxic cancer treatments endanger future fertility and prepubertal males have no option to preserve fertility by sperm cryopreservation. Also, boys with cryptorchidism are at risk of compromised fertility in adulthood.OBJECTIVE: This scoping review focuses on male fertility restoration, particularly relevant for prepubertal male cancer survivors and boys with cryptorchidism. The aim was to investigate current evidence for fertility restoration strategies, explore barriers to clinical implementation, and outline potential steps to overcome these barriers.EVIDENCE REVIEW: The review was conducted following the PRISMA-ScR criteria and previously published guidelines and examines studies using human testis tissue of prepubertal boys or healthy male adults. A literature search in PubMed was conducted and 72 relevant studies were identified, including in vivo and in vitro approaches.FINDINGS: In vivo strategies, such as testis tissue engraftment and spermatogonial stem cell (SSC) transplantation, hold promise for promoting cell survival and differentiation. Yet complete spermatogenesis has not been achieved. In vitro approaches focus on the generation of male germ cells from direct germ cell maturation in various culture systems, alongside human induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs). These approaches mark significant advancements in understanding and promoting spermatogenesis but achieving fully functional spermatozoa in vitro remains a challenge. Barriers to clinical implementation include the risk of reintroducing malignant cells and introduction of epigenetic changes.CONCLUSION: Male fertility restoration is an area in rapid development. Based on the reviewed studies the most promising and advanced strategy for restoring male fertility using

Objectives Men with erectile dysfunction (ED) are at elevated risk of heart disease. However, data on the prevalence of abnormal cardiac structure and function in ED is scarce. We utilized echocardiography to assess cardiac characteristics in men with ED. Methods In this prospective cohort study of men with ED referred to a tertiary urology clinic, all participants underwent transthoracic echocardiography following a predefined protocol and electrocardiogram. Erectile function was graded according to the International Index of Erectile Function - Erectile Function (IIEF-EF) questionnaire. Participants with neurological disease, a medical history of pelvic surgery or trauma were excluded. Left ventricular (LV) structure was evaluated by ventricular mass index (LVMi). LV diastolic function was evaluated according to early diastolic mitral annular velocity (e'), ratio of early transmitral filling velocity to (E/e’) and left atrial volume index (LAVi). LV systolic function was evaluated by LV ejection fraction (LVEF), and global longitudinal strain (GLS). Results We included 100 patients with a median age of 61 yr (IQR 13) and median IIEF-EF was 15 (IQR 14). Comorbidities included hypertension (43%), dyslipidemia (41%), diabetes mellitus (29%), ischemic heart disease (12%), arrhythmia (12%), and heart failure (3%). Regarding cardiac structure, 25 patients had LV hypertrophy. Signs of LV diastolic dysfunction were a common observation; 21 patients had an E/e' ratio > 9, while 30 patients had reduced septal and/or lateral e' velocities with only 1 patient having left atrial dilation (LAVi > 34 ml/m2). Regarding LV systolic dysfunction, 83 patients had reduced GLS (< 16%) with 14 suffering reduced LVEF < 52%. 4 patients were referred for further evaluation, due to previously undiagnosed left bundle branch block, mitral valve regurgitation, aortic valve regurgitation, and incident heart failure, respectively. Conclusions, Objectives Men with erectile dysfunction (ED) are at elevated risk of heart disease. However, data on the prevalence of abnormal cardiac structure and function in ED is scarce. We utilized echocardiography to assess cardiac characteristics in men with ED. Methods In this prospective cohort study of men with ED referred to a tertiary urology clinic, all participants underwent transthoracic echocardiography following a predefined protocol and electrocardiogram. Erectile function was graded according to the International Index of Erectile Function - Erectile Function (IIEF-EF) questionnaire. Participants with neurological disease, a medical history of pelvic surgery or trauma were excluded. Left ventricular (LV) structure was evaluated by ventricular mass index (LVMi). LV diastolic function was evaluated according to early diastolic mitral annular velocity (e'), ratio of early transmitral filling velocity to (E/e’) and left atrial volume index (LAVi). LV systolic function was evaluated by LV ejection fraction (LVEF), and global longitudinal strain (GLS). Results We included 100 patients with a median age of 61 yr (IQR 13) and median IIEF-EF was 15 (IQR 14). Comorbidities included hypertension (43%), dyslipidemia (41%), diabetes mellitus (29%), ischemic heart disease (12%), arrhythmia (12%), and heart failure (3%). Regarding cardiac structure, 25 patients had LV hypertrophy. Signs of LV diastolic dysfunction were a common observation; 21 patients had an E/e' ratio > 9, while 30 patients had reduced septal and/or lateral e' velocities with only 1 patient having left atrial dilation (LAVi > 34 ml/m2). Regarding LV systolic dysfunction, 83 patients had reduced GLS (< 16%) with 14 suffering reduced LVEF < 52%. 4 patients were referred for further evaluation, due to previously undiagnosed left bundle branch block, mitral valve regurgitation, aortic valve regurgitation, and incident heart failure, respectively. Conclusions

Introduction The purpose of this study was to investigate the association between baseline androgen concentrations and outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line enzalutamide or abiraterone acetate plus prednisone (AAP). Materials and Methods We previously randomized men with mCRPC to enzalutamide or AAP to compare side-effects and measured androgen concentrations. In this post-hoc analysis, patients were grouped in quartiles (Q) based on their serum androgen values. Kaplan-Meier and Cox regression were used to analyze progression-free and overall survival for baseline androgen groups, treatment subgroups and their interaction. The trial was registered at clinicaltrialsregister.eu (2017-000099-27). Results Eighty-four patients received enzalutamide and 85 AAP. Overall, higher (Q4) compared with lower (Q1) baseline serum testosterone was associated with longer progression-free survival (24.8 vs. 10.7 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.33; 0.84) and overall survival (52.8 vs. 31.5 months, HR 0.49, 95% CI 0.28; 0.85). The risk reduction in death seemed to be treatment dependent (treatment subgroup interaction P = .04). For men in the AAP subgroup, the Q4 compared with Q1 group had a significant lower risk of death (HR 0.30, 95% CI 0.13; 0.73), while no difference was found for enzalutamide (HR 0.77, 95% CI 0.35; 1.69). Similar results were found for the other androgens. Conclusion Pre-treatment serum testosterone levels may be a clinically useful biomarker for predicting mCRPC treatment responses and guiding treatment selection., Introduction: The purpose of this study was to investigate the association between baseline androgen concentrations and outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line enzalutamide or abiraterone acetate plus prednisone (AAP). Materials and Methods: We previously randomized men with mCRPC to enzalutamide or AAP to compare side-effects and measured androgen concentrations. In this post-hoc analysis, patients were grouped in quartiles (Q) based on their serum androgen values. Kaplan-Meier and Cox regression were used to analyze progression-free and overall survival for baseline androgen groups, treatment subgroups and their interaction. The trial was registered at clinicaltrialsregister.eu (2017-000099-27). Results: Eighty-four patients received enzalutamide and 85 AAP. Overall, higher (Q4) compared with lower (Q1) baseline serum testosterone was associated with longer progression-free survival (24.8 vs. 10.7 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.33; 0.84) and overall survival (52.8 vs. 31.5 months, HR 0.49, 95% CI 0.28; 0.85). The risk reduction in death seemed to be treatment dependent (treatment subgroup interaction P =. 04). For men in the AAP subgroup, the Q4 compared with Q1 group had a significant lower risk of death (HR 0.30, 95% CI 0.13; 0.73), while no difference was found for enzalutamide (HR 0.77, 95% CI 0.35; 1.69). Similar results were found for the other androgens. Conclusion: Pre-treatment serum testosterone levels may be a clinically useful biomarker for predicting mCRPC treatment responses and guiding treatment selection.

Masterson et al. [1] have presented the third randomized controlled trial (RCT) on platelet-rich-plasma (PRP) and erectile dysfunction (ED). Men with vasculogenic ED were assigned to intracavernosal PRP injections (n = 28) or placebo (n = 33). No significant differences were noted between the arms: 58.3%, 41.7%, and 60% of the PRP group, and 53.6%, 52%, and 41.7% of the placebo group met the minimal clinically important difference (MCID) for the International Index of Erectile Function-Erectile Function (IIEF-EF) scale at 1, 3, and 6 mo, respectively. The findings are in contrast to two previous RCTs and the inconsistencies necessitate a closer examination of the studies.

OBJECTIVE: To explore how the use of the ProPep® Nerve Monitoring System (ProPep Surgical, Austin, TX, USA) for intraoperative specific sparing of the pudendal nerve fibres influences postoperative functional outcomes after unilateral nerve-sparing (UNS) or non-nerve-sparing (NNS) robot-assisted radical prostatectomy (RARP).PATIENTS AND METHODS: We randomised 100 men undergoing UNS or NNS RARP to ProPep nerve monitoring during RARP (intervention) or standard of care RARP (control). Functional outcomes were assessed at 3, 6, and 12 months using the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), the International Prostate Symptom Score, the Danish Prostate Symptom Score, the International Index of Erectile Function, the Erection Hardness Scale, and 24-h pad tests. The primary outcome was the difference in ICIQ-SF score between the groups at 12 months. Secondary outcomes included differences in the remaining outcome measures and continence rates at all time points. Continence was defined as the use of no pads and the answer 'Never' to the question: 'How often do you experience urinary incontinence?' or a urine loss of <8 g on the 24-h pad test.RESULTS: A total of 82 patients were included in the per-protocol analysis at 12 months with 41 in each group. At 12 months the mean ICIQ-SF scores were 5.37 (95% confidence interval [CI] 3.71-7.03) and 5.66 (95% CI 4.05-7.27) for the intervention and control groups, respectively (P = 0.8). There were no statistically significant differences in any of the remaining outcomes. However, the continence rate was higher in the intervention group at 6 months (63% vs 44%, P = 0.09).CONCLUSIONS: Intraoperative nerve monitoring did not result in better functional outcomes following UNS or NNS RARP. Larger studies are needed to explore if ProPep can reduce the time to continence after RARP.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for children with life-threatening hematological diseases, but the procedure comprises a high risk of infertility. We have previously shown that two-thirds of male survivors had azoospermia median 18 years after pediatric HSCT [1]. However, some patients with azoospermia may produce sperm that do not reach the ejaculate, giving hope for biological paternity. Microdissection testicular sperm extraction (mTESE) is a surgical procedure for men with non-obstructive azoospermia [2]. During mTESE, the testicular tissue is systematically examined using an operating microscope to identify dilated seminiferous tubules that may contain active sperm production. Biopsies from such areas are examined for the presence of mature spermatozoa that, if found, are cryopreserved for assisted reproduction. mTESE is not routinely offered to men with azoospermia after HSCT, and the literature is, to our knowledge, limited to 15 case reports worldwide [3,4,5]. Here we present a case series of five male survivors of pediatric allogeneic HSCT who, due to their wish of biological paternity, underwent mTESE for the purpose of future assisted reproduction.

Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent or incomplete spermatogenesis resulting in the lack of spermatozoa in the ejaculate (non-obstructive azoospermia, NOA). Currently, testicular tissue from pre-pubertal boys extracted before treatment with gonadotoxic cancer therapy can be cryopreserved with good survival of spermatogonial stem cells. However, strategies for fertility restoration, after successful cancer treatment, are still experimental and no clinical methods have yet been developed. Similarly, no clinically available treatments can help men with NOA to become biological fathers after failed attempts of testicular surgical sperm retrieval. We present a case of a 31-year-old man with NOA who had three pieces of testis tissue (each ∼2 × 4 × 2 mm3) extracted and cryopreserved in relation to performing microdissection testicular sperm extraction (mTESE). Approximately 2 years after mTESE, the thawed tissue pieces were engrafted in surgically created pockets bilaterally under the scrotal skin. Follow-up was performed after 2, 4, and 6 months with assessment of reproductive hormones and ultrasound of the scrotum. After 6 months, all engrafted tissue was extracted and microscopically analyzed for the presence of spermatozoa. Furthermore, parts of the extracted tissue were analyzed histologically and by immunohistochemical analysis. Active blood flow in the engrafted tissue was demonstrated by doppler ultrasound after 6 months. No spermatozoa were found in the extracted tissue. Histological and immunohistochemical analysis demonstrated graft survival with intact clear tubules and normal cell organization. Sertoli cells and spermatocytes with normal morphology were located near the basement membrane. MAGE-A and VASA positive spermatogonia/spermatocytes were detected together with SOX9 positive Sertoli cells. Spermatocytes and/or Sertoli cells, Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent or incomplete spermatogenesis resulting in the lack of spermatozoa in the ejaculate (non-obstructive azoospermia, NOA). Currently, testicular tissue from pre-pubertal boys extracted before treatment with gonadotoxic cancer therapy can be cryopreserved with good survival of spermatogonial stem cells. However, strategies for fertility restoration, after successful cancer treatment, are still experimental and no clinical methods have yet been developed. Similarly, no clinically available treatments can help men with NOA to become biological fathers after failed attempts of testicular surgical sperm retrieval. We present a case of a 31-year-old man with NOA who had three pieces of testis tissue (each ∼2 × 4 × 2 mm3) extracted and cryopreserved in relation to performing microdissection testicular sperm extraction (mTESE). Approximately 2 years after mTESE, the thawed tissue pieces were engrafted in surgically created pockets bilaterally under the scrotal skin. Follow-up was performed after 2, 4, and 6 months with assessment of reproductive hormones and ultrasound of the scrotum. After 6 months, all engrafted tissue was extracted and microscopically analyzed for the presence of spermatozoa. Furthermore, parts of the extracted tissue were analyzed histologically and by immunohistochemical analysis. Active blood flow in the engrafted tissue was demonstrated by doppler ultrasound after 6 months. No spermatozoa were found in the extracted tissue. Histological and immunohistochemical analysis demonstrated graft survival with intact clear tubules and normal cell organization. Sertoli cells and spermatocytes with normal morphology were located near the basement membrane. MAGE-A and VASA positive spermatogonia/spermatocytes were detected together with SOX9 positive Sertoli cells. Spermatocytes and/or Sertoli ce

Background Low-dose-rate brachytherapy (LDR-B) is an established treatment for localized prostate cancer. However, while erectile function is relatively well documented, other changes in sexual function are sparsely investigated. Aim The study sought to investigate orgasmic dysfunction, urinary incontinence during sexual activity (UIS), changes in penile morphology, and sensory disturbances in the penis following LDR-B. Methods A cross-sectional questionnaire-based study in patients who underwent LDR-B at our center from 2010 to 2020. The questionnaire included the International Index of Erectile Function–Erectile Function Domain (IIEF-EF) and questions on orgasm, UIS, changes in penile morphology, and penile sensory disturbances. Outcomes Outcomes were prevalence rates of altered perception of orgasm, orgasm associated pain, anejaculation, UIS, alterations in penile morphology, penile sensory disturbances, and predictors of these side effects. Results Overall, 178 patients responded to the questionnaire. The median age was 70 years (range, 51-83 years), and the median time since LDR-B was 93 months (range, 21-141 months). Overall, 142 (80%) were sexually active and 126 (70.8%) had erectile dysfunction (ED). Of the sexually active patients, 8 (5.6%) reported anejaculation and 7 (4.9%) reported anorgasmia. Another 67 (46.9%) had decreased orgasmic intensity, while 69 (49.3%) reported an increased time to orgasm. Twenty-six (18.3%) patients had experienced orgasm-associated pain with a median visual analog pain score of 2. Considering overlap, 44 (31.0%) patients had an unchanged orgasmic function. Six (3.3%) patients had experienced UIS at least a few times. Penile length loss was reported by 45 (25.2%) patients. Seventeen (9.6%) patients reported an altered curvature of their penis and 9 (5%) had experience painful erection. Thirty-three (18.5%) patients had experienced decreased penile sensitivity. On, BACKGROUND: Low-dose-rate brachytherapy (LDR-B) is an established treatment for localized prostate cancer. However, while erectile function is relatively well documented, other changes in sexual function are sparsely investigated.AIM: The study sought to investigate orgasmic dysfunction, urinary incontinence during sexual activity (UIS), changes in penile morphology, and sensory disturbances in the penis following LDR-B.METHODS: A cross-sectional questionnaire-based study in patients who underwent LDR-B at our center from 2010 to 2020. The questionnaire included the International Index of Erectile Function-Erectile Function Domain (IIEF-EF) and questions on orgasm, UIS, changes in penile morphology, and penile sensory disturbances.OUTCOMES: Outcomes were prevalence rates of altered perception of orgasm, orgasm associated pain, anejaculation, UIS, alterations in penile morphology, penile sensory disturbances, and predictors of these side effects.RESULTS: Overall, 178 patients responded to the questionnaire. The median age was 70 years (range, 51-83 years), and the median time since LDR-B was 93 months (range, 21-141 months).Overall, 142 (80%) were sexually active and 126 (70.8%) had erectile dysfunction (ED). Of the sexually active patients, 8 (5.6%) reported anejaculation and 7 (4.9%) reported anorgasmia. Another 67 (46.9%) had decreased orgasmic intensity, while 69 (49.3%) reported an increased time to orgasm. Twenty-six (18.3%) patients had experienced orgasm-associated pain with a median visual analog pain score of 2. Considering overlap, 44 (31.0%) patients had an unchanged orgasmic function. Six (3.3%) patients had experienced UIS at least a few times. Penile length loss was reported by 45 (25.2%) patients. Seventeen (9.6%) patients reported an altered curvature of their penis and 9 (5%) had experience painful erection. Thirty-three (18.5%) patients had experienced decreased penile sensitivity. On multivariate analyses, ED was the

Background: Serum insulin-like factor 3 (INSL3) is a Leydig cell biomarker, but little is known about the circulating concentration of INSL3 during hypothalamus-pituitary-testicular suppression.Aim: To study the concomitant changes in serum concentrations of INSL3, testosterone and LH during experimental and therapeutic testicular suppression.Methods: We included serum samples from three different cohorts comprising subjects before and after testicular suppression; 1) 6 healthy young men who were treated with androgens (Sustanon®, Aspen Pharma, Dublin, Ireland), 2) 10 transgender girls (male sex assigned at birth) who were treated with three-monthly GnRH agonist injections (Leuprorelinacetat, Abacus Medicine, Copenhagen, Denmark) and 3) 55 patients with prostate cancer who were randomized to surgical castration (bilateral subcapsular orchiectomy) or treatment with GnRH agonist (Triptorelin, Ipsen Pharma, Kista, Sweden). Serum INSL3 and testosterone concentrations were quantified in stored serum samples using validated liquid chromatography-tandem mass spectrometry methodologies, and LH was measured by an ultrasensitive immunoassay.Results: The circulating concentrations of INSL3, testosterone and LH decreased during experimental testicular suppression in healthy young men by Sustanon injections and subsequently returned to baseline levels after release of suppression. All 3 hormones decreased during therapeutic hormonal hypothalamus-pituitary-testicular suppression in transgender girls and in patients with prostate cancer.Conclusion: INSL3 resembles testosterone as a sensitive marker of testicular suppression and reflects Leydig cell function, also during exposure to exogenous testosterone. Serum INSL3 measurements may complement testosterone as a Leydig cell marker in male reproductive disorders, during therapeutic testicular suppression as well as in surveillance of illicit use of androgens.

Context: Erectile dysfunction (ED) is associated with an increased risk of cardiovascular morbidity and mortality. Objective: To systematically review and analyze the cardiac structure and function in men with ED assessed with echocardiography. Evidence acquisition: We performed a systematic review and meta-analysis according to the guideline of the Preferred Reporting Items for Systematic Reviews and Meta-analyses. We searched PubMed and the Cochrane Library on June 2, 2022, and included studies evaluating cardiac structure and function using echocardiography in men with ED compared with controls without ED. The Newcastle-Ottawa Quality Assessment Scale was used for assessing the quality of studies. We analyzed the mean differences in left ventricular ejection fraction (LVEF), the ratio of early transmitral filling velocity to early diastolic mitral annular velocity (E/e′), ratio of the early to late diastolic transmitral flow velocity (E/A), isovolumic relaxation time (IVRT), and left ventricular mass index (LVMi) in a random-effect model computed using means and standard deviations. The review was preregistered with PROSPERO (CRD42022337183). We received no funding. Evidence synthesis: We included ten studies with 763 men diagnosed with ED (mean age: 55.6 yr) and 358 control men (mean age: 54.4 yr). E/e′ was significantly worse in men with ED than in controls (mean absolute difference = 1.17, 95% confidence interval or CI [0.68, 1.65], p < 0.005). No significant differences were observed in LVEF, E/A, IVRT, or LVMi (–0.06, 95% CI [–1.06, 0.95], p = 0.91; –0.06, 95% CI [–0.24, 0.13], p = 0.55; 11.76, 95% CI [–0.88, 24.39], p = 0.07; and 4.37, 95% CI [–2.91, 11.65], respectively). The studies exhibited heterogeneity regarding study populations, reported echocardiography data, and variations in adjustments for confounding factors. Conclusions: Left ventricle diastolic dysfunction, as assessed by E/e′, was more frequent in men with ED than in matched controls w

Introduction: Enzalutamide and abiraterone acetate plus prednisone (AAP) have similar efficacy in metastatic castration-resistant prostate cancer (mCRPC). Herein, we compare fatigue, health-related quality-of-life (HRQoL) and metabolic changes in men with mCRPC treated with enzalutamide and AAP. Materials and methods: In this single-centre, open-labelled, phase IV trial, patients with metastatic prostate cancer progressing on androgen deprivation therapy were randomly assigned to enzalutamide (160 mg daily) or AAP (1000 mg abiraterone acetate and 10 mg prednisone daily) as first-line mCRPC treatment. The primary outcome was the difference in changed fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire). The secondary outcomes were differences in changed HRQoL (Functional Assessment of Cancer Therapy-Prostate questionnaire), body composition, weight, glucose homeostasis, lipid profile and blood pressure. All outcomes were assessed at baseline and at 12-week follow-up. Trial registration: clinicaltrialsregister.eu (2017-000099-27). Results: 170 patients were randomised (1:1) to enzalutamide or AAP. The primary outcome was positive with a clinically meaningful difference in fatigue, favouring AAP (3.4 points, 95% CI 1.2; 5.6, P = 0.003). The group difference in changed HRQoL did not reach clinical significance. The most important metabolic finding was a higher increase in glycated haemoglobin (HbA1c) for AAP than enzalutamide (3.4 mmol/mol, 95% CI 2.1; 4.8, P = 0.001). Eight patients developed type 2 diabetes (T2D) in the AAP group and none in the enzalutamide group. No treatment-related serious adverse event was observed. Conclusions: AAP resulted in less fatigue than enzalutamide in a randomised setting. This was at the expense of a higher HbA1c increase and incidence of T2D.