A Phase 2 Randomized, Placebo-controlled Crossover Trial to Evaluate Safety and Efficacy of Platelet-rich Plasma Injections for Peyronie's Disease: Clinical Trial Update.

Intralesional injection of platelet-rich plasma for Peyronie's disease appears to be safe according to early observations from an ongoing clinical trial. Efficacy data remain elusive until completion of the trial.

Low-intensity extracorporeal shockwave therapy for diabetic men with erectile dysfunction: A systematic scoping review.

BACKGROUND: Erectile dysfunction (ED) is a very common complication in men with diabetes mellitus (DM). Low-intensity extracorporeal shockwave therapy (Li-ESWT) offers a promising nonsurgical treatment option for ED. A systematic scoping review investigating the outcomes of Li-ESWT in diabetic men with ED has not yet been performed. OBJECTIVES: To systematically review animal and clinical studies related to the use of Li-ESWT for treatment of DM-related ED. DATA SOURCES: PubMed, Embase, The Cochrane Library, Scopus, and Web of Science were searched, unrestricted by dates or study design. MATERIALS AND METHODS: We included qualitative studies, quantitative studies, primary research studies, meta-analyses, and research letters written in English. Full text reviewing was completed in all animal and human studies discussing Li-ESWT for the treatment of ED in subjects with DM. Data extracted included the journal citation, publication year, country of origin, study design, and a summary of the pertinent findings. RESULTS: Our search yielded nine clinical studies and 10 animal studies. The results of the clinical studies suggest that Li-ESWT is a safe and effective treatment in men with well-controlled DM and moderate or better ED. However, the benefit is less durable in diabetic men than nondiabetic men. The results of the animal studies suggest that Li-ESWT can significantly improve erectile function in diabetic rat models with ED. CONCLUSIONS: The examined studies present encouraging results for the use of Li-ESWT to treat diabetic men with ED. Future studies, particularly robust randomized controlled trials, are necessary to confirm these findings and provide long-term follow-up.

Strategies to Increase Testosterone in Men Seeking Fertility.

Prevalence of testosterone deficiency is increasing in the adolescent and young adult male population. As the average paternal age rises, there is a significant population of men with hypogonadism seeking testosterone therapy wishing to achieve or maintain fertility potential. Identification of potential lifestyle modifications that may improve the testosterone deficiency is one of the initial interventions of the holistic strategy in treatment. This is followed by drug therapy; however, traditional testosterone therapy acts as a contraceptive by suppressing the hypothalamus-pituitary-gonadal (HPG) axis and therefore cannot be used as a treatment strategy. A solution has been the off-label use of selective estrogen receptor modulators, human chorionic gonadotropin (hCG), and anastrozole inhibitors to treat hypogonadal symptoms while increasing intratesticular testosterone, a necessity for spermatogenesis. Recently, a novel therapy, Natesto intranasal testosterone gel, has been shown to increase serum testosterone levels while maintaining semen parameters. This is hypothesized to be because of its short-acting properties having lesser effect on the HPG axis, in contrast to the long-acting properties of traditional testosterone therapy. It is important to differentiate hypogonadal men between those seeking to achieve or maintain fertility status because the drug therapy of choice differs. This can be accomplished by determining the levels of 17-hydroxyprogesterone (17-OHP), because it is a biomarker for intratesticular testosterone. Those with low 17-OHP may wish to initiate treatment with alternative therapies, whereas those with high 17-OHP may trial short-acting testosterone therapies. As the urologist's armamentarium continues to increase, better strategies to increase testosterone levels in men seeking fertility can be achieved.

Effect of Radiofrequency Electromagnetic Radiation Emitted by Modern Cellphones on Sperm Motility and Viability: An In Vitro Study.

BACKGROUND: Cellphones emit radiofrequency electromagnetic radiation (RF-EMR) for transmission of data for social media communication, web browsing, and music/podcast streaming. Use of Bluetooth ear buds has probably prolonged the time during which cellphones reside in the trouser pockets of men. It has been postulated that RF-EMR increases oxidative stress and induces free radical formation. OBJECTIVE: To investigate the effect of wireless-spectrum (4G, 5G, and WiFi) RF-EMR emitted by modern smartphones on sperm motility and viability and explore whether these effects can be mitigated using a physical barrier or distance. DESIGN, SETTING, AND PARTICIPANTS: Semen samples were obtained from fertile normozoospermic men aged 25-35 yr. A current-generation smartphone in talk mode was used as the RF-EMR source. A WhatsApp voice call was made using either 4G, 5G, or WiFi wireless connectivity. We determined if exposure effects were mitigated by either a cellphone case or greater distance from the semen sample. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The semen samples were analyzed according to 2010 World Health Organization laboratory guidelines. Statistical analysis was performed using SPSS v.28. RESULTS AND LIMITATIONS: We observed decreases in sperm motility and viability with WiFi exposure but not with exposure to 4G or 5G RF-EMR. With large variability among smartphones, continued research on exposure effects is needed. CONCLUSIONS: Our exploratory study revealed that sperm motility and viability are negatively impacted by smartphones that use the WiFi spectrum for data transmission. PATIENT SUMMARY: We looked at the effect of cellphone use on sperm motility and viability. We found that cellphones using WiFi connectivity for data usage have harmful effects on semen quality in men.

Future of Male Infertility Evaluation and Treatment: Brief Review of Emerging Technology.

Over the past few decades, there have been significant advances in male infertility, particularly in the development of novel diagnostic tools. Unfortunately, there remains a substantial number of patients that remain infertile despite these improvements. In this review, we take heed of the emerging technologies that will shape the future of male infertility diagnosis, evaluation, and treatment. Improvement in computer-assisted semen analyses and portability allow males to obtain basic semen parameters from the comfort of their home. Additionally, breakthrough ultrasound technology allows for preoperative prediction of potential areas of spermatogenesis within the testes, high-resolution optics permits better visualization during microdissection testicular sperm extraction (mTESE), and artificial intelligence improves sperm selection and identification.

Utility of evaluating semen samples from adolescents with Klinefelter Syndrome for cryopreservation: A multi-institution evaluation.

INTRODUCTION: Klinefelter Syndrome (KS) is the most common genetic condition cause of non-obstructive azoospermia (NOA). KS also often results in decreased testicular growth and testosterone production. Because of this, exogenous testosterone therapy is commonly prescribed for KS patients to treat hypogonadism, but this may have additional impacts to future fertility potential. KS adolescent patients may be asked to provide multiple semen samples to identify potential sperm for early cryopreservation. OBJECTIVE: To develop a multi-institutional database to evaluate the prevalence of sperm in the ejaculate of adolescent KS patients. METHODS: A retrospective study was performed of all adolescent KS patients seen at two high-volume tertiary male infertility clinics between 2015 and 2020. Adolescence was defined as individuals aged 12-19 years, as per the World Health Organization. Demographic information data including weight, height, medical comorbidities, and concurrent medications were collected. Serum hormone levels including FSH, LH, and testosterone were collected, as well as any available semen analysis data. RESULTS: A total of 116 patients were identified and included in the database. A total of 100 (86.2%) had hormone data available and 48 (41.3%) had semen analysis data. Of the 48 patients with semen analyses, only 4 (8.3%) patients had rare sperm in the ejaculate while the remaining had azoospermia (91.7%). None of the specimens were suitable for cryopreservation. The average serum total testosterone level of adolescent KS patients was 181 ± 216 ng/dL. FSH levels were 14.3 ± 18.8 IU/L (normal 0.3-10.0 IU/L) and LH levels were 7.8 ± 12.4 IU/L (normal 1.2-7.8 IU/L). A total of 17 patients repeated a semen analysis, and in no instance did this result in sperm where there was none previously. CONCLUSION: The findings from a large multicenter retrospective cohort of adolescent KS patients suggest that a single semen analysis is sufficient for attempted cryopreservation purposes, and that multiple semen analyses is not needed.

COVID-19 Infection Is Associated With New Onset Erectile Dysfunction: Insights From a National Registry.

INTRODUCTION: The short- and long-term effects of coronavirus disease 2019 (COVID-19) on erectile function and penile vasculature remains poorly understood and is of particular importance as the virus has been found to be present within the penile tissue. AIM: We determined the association of COVID-19 infection and subsequent diagnoses of erectile dysfunction. METHODS: We assessed the risk of ED in men with COVID-19 in the United States (US) using the TriNetX Research Network, a federated electronic medical records network of over 42 healthcare organizations and 66 million patients from the US. We identified adult men (≥ 18 years) with a recorded COVID-19 infection (ICD-10-CM B34.2, U07.1, U07.2, J12.81, J12.82, B97.29) since January 1, 2020, and compared them to an equivalent number of adult men who did not have COVID-19 over the same timeframe. Men with prior history or diagnosis of ED before January 1, 2020 were excluded. We accounted for confounding variables through propensity score matching for age, race, body mass index (BMI), and history of the following comorbid medical conditions: diabetes mellitus (E11), hypertension (I10), ischemic heart disease (I20-25), or hyperlipidemia (E78). OUTCOMES: We assessed the association between COVID-19 and ED (N52) as a primary outcome through regression analysis with statistical significance assessed at P< .05. RESULTS: Prior to propensity score matching, men with COVID-19 were found to be older than men without COVID-19 (47.1 ± 21.4 vs 42.4 ± 24.3 years). Additionally, men with COVID-19 were noted to have increased prevalence of diabetes mellitus (DM) and hypertension (HTN) when compared to men without COVID-19 (13% DM and 27% HTN vs 7% DM and 22% HTN). After propensity score matching, we compared 230,517 men with COVID-19 to 232,645 men without COVID-19 and found that COVID-19 diagnosis was significantly associated with ED (odds ratio 1.20, 95% confidence interval 1.004-1.248, P= .04). CLINICAL IMPLICATIONS: Our findings indicate that clinicians should consider evaluating erectile dysfunction among men with recent COVID-19 diagnoses and counsel them regarding the risk of developing erectile dysfunction. STRENGTHS AND LIMITATIONS: Strengths include large sample size and adjustment for confounding variables. Limitations include reliance on a global federated dataset, retrospective study design, and lack of data regarding ED (mild vs moderate vs severe), COVID-19 infection severity, or history of prostate cancer and radiation. CONCLUSION: There is an increased chance of new onset erectile dysfunction post-COVID-19 infection.Chu KY, Nackeeran S, Horodyski L, et al. COVID-19 Infection Is Associated With New Onset Erectile Dysfunction: Insights From a National Registry. Sex Med 2022;10:100478.

Valorization of spent brewery yeast biosorbent with sonication-assisted adsorption for dye removal in wastewater treatment.

The effluent of textile industries containing synthetic dyes contributed to substantial pollution to water bodies. The biosorption process of Congo Red dye was successfully performed by integrating ultrasonication in the adsorption step with spent brewery yeast as a novel and renewable biosorbent. The adsorption process was hindered when ultrasonication was employed together with the biosorbent, indicating that desorption process had occurred. The adsorption process showed that 4 g/L of biosorbent was the optimum dosage for adsorption of 50 mg/L of Congo Red dye, and that the adsorption equilibrium fitted to the Langmuir model, with kinetics best fitted with pseudo-second order model. The maximum capacity of the adsorption was 52.6 mg/g, showing the potential of spent brewery yeast to aid in removing wastewater pollutants. Maximal Congo Red dye recovery (100%) was achieved in the sonication-assisted desorption studies using 0.01M NaOH as the eluting agent. The ultrasonication effects contributed to the efficient recovery of dye and good conversion of spent brewery yeast to biosorbent can be beneficial for treating pollution from textile wastewater.

Restorative Therapies for Erectile Dysfunction: Position Statement From the Sexual Medicine Society of North America (SMSNA).

INTRODUCTION: Current non-invasive treatments for erectile dysfunction (ED) include oral medications, intracavernosal injections, and vacuum-assisted devices. Though these therapies work well for many, a subset of patients have contraindications or are unsatisfied with these options. Restorative therapies for ED are a new frontier of treatments focused on regenerating diseased tissue and providing a potential "cure" for ED. AIM: The aim of this position statement is to examine existing clinical trial data for restorative therapies and identify elements that require further research before widespread adoption. METHODS: A literature review was performed to identify all clinical trials performed with regenerative therapy for ED. This includes treatments such as stem cell therapy (SCT), platelet rich plasma (PRP), and restorative related technologies like low-intensity shockwave therapy (LiSWT). MAIN OUTCOME MEASURES: Most clinical trials in restorative therapies were assessed for safety, feasibility, or efficacy. This included recording adverse events, changes in sexual function and erectile function questionnaires, and diagnostics measures. RESULTS: To date there is an absence of robust clinical data supporting the efficacy of restorative therapies regarding ED, though technologies such as LiSWT have established relative safety. CONCLUSIONS: Restorative therapies are a promising technology that represents a new frontier of treatment geared towards reversing disease pathology rather than just treating symptoms. However, current published clinical studies are limited. Future work needs to be adequately powered, multi-center, randomized, sham/placebo-controlled trials in well-characterized patient populations to ensure safety and demonstrate efficacy. Until these studies are done, restorative therapies should be reserved for clinical trials and not offered in routine clinical practice. Liu JL, Chu KY, Gabrielson AT, et al. Restorative Therapies for Erectile Dysfunction: Position Statement From the Sexual Medicine Society of North America (SMSNA). J Sex Med 2021;9:100343.

Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections on Testis.

PURPOSE: To evaluate the presence and analyze the pathological changes within the testes of patients who died or recovered from severe acute respiratory syndrome coronavirus 2 (COVID-19) complications. MATERIALS AND METHODS: Testis tissue was collected from autopsies of COVID-19 positive (n=6) and negative men (n=3). Formalin-fixed paraffin-embedded tissues were stained with hematoxylin and eosin (H&E) and subjected to immunofluorescence for angiotensin-converting enzyme 2 (ACE-2) expression. Fluorescent-labeled tissue slides were imaged on a quantitative pathology scope with various zoom levels allowing for qualitative and quantitative interpretation. Tissue from four COVID-19 positive autopsy cases and a live seroconverted patient was imaged with transmission electron microscopy (TEM). RESULTS: H&E histomorphology showed three of the six COVID-19 biopsies had normal spermatogenesis while the remaining three had impaired spermatogenesis. TEM showed the COVID-19 virus in testis tissue of one COVID-19 positive autopsy case and the live biopsy, H&E stain on the same autopsy case demonstrated interstitial macrophage and leukocyte infiltration. Immunofluorescent stained slides from six COVID-19 positive men demonstrated a direct association between increased quantitative ACE-2 levels and impairment of spermatogenesis. CONCLUSIONS: The novel COVID-19 has an affinity for ACE-2 receptors. Since ACE-2 receptor expression is high in the testes, we hypothesized that COVID-19 is prevalent in testes tissue of infected patients. This study suggests the male reproductive tract, specifically the testes, may be targets of COVID-19 infection. We found an inverse association between ACE-2 receptor levels and spermatogenesis, suggesting a possible mechanism of how COVID-19 can cause infertility.

Short-acting testosterone appears to have lesser effect on male reproductive potential compared to long-acting testosterone in mice.

OBJECTIVE: To compare the effect of exogenous short-acting and long-acting testosterone on male reproductive potential in mice. DESIGN: In vivo mouse model. SETTING: University-based basic science research laboratory. ANIMALS: A total of 30 wild-type C57BL/6 male and female mice were used for this experimentation. The male mice were used for control group and testosterone supplementation, while both male and female mice were used for the breeding portion of the study. INTERVENTIONS: Exogenous testosterone was administered either in short-acting formulation (Monday-Wednesday-Friday dosing schedule, testosterone propionate 0.2 mg/kg), or long-acting formulation (3-month dosing schedule - testosterone pellets 150 mg) to male mice. MAIN OUTCOME MEASURES: Time to pregnancy, Luteinizing hormone (LH) levels, and testicular weight. RESULTS: Mice treated with long-acting testosterone appear to have longer time to pregnancy when compared to wild-type (33 ± 11 vs 23 ± 2.6 days, p ≤ 0.05) and mice that received short-acting testosterone propionate (26 ± 5.9 days). Mice treated with long-acting testosterone had smaller testes weight when compared to control (0.08 ± 0.01 vs 0.11 ± 0.01g; p ≤ 0.01), while the short-acting testosterone treated mice had similar testis weight when compared to control (0.09 ± 0.02 vs 0.11 ± 0.01g; ns). The serum testosterone level was elevated in mice that received testosterone pellets (285.78 ng/dL) and testosterone propionate (122.16 ng/dL) versus control (68.4 ng/dL). In mice that received long-acting testosterone pellets, LH levels at 3 months were almost undetectable while those that received short-acting testosterone remained similar to control (0.017 ± 0.058 vs 0.348 ± 0.232 IU/L; p ≤ 0.01). Female reproductive potential parameters including litter size and pup weight were collected and observed to have no difference between groups. CONCLUSION: Through a mouse breeding study, mice that received short-acting testosterone were shown to have fertility potential similar to wild-type male mice. Long-acting exogenous testosterone appeared to impair male reproductive capacity and LH levels when compared to short-acting testosterone. Short-acting testosterone appeared to cause less LH suppression. Identifying strategies to increase testosterone while simultaneously preserving male fertility is important for treating young men with hypogonadism.

The pediatric patient and future fertility: optimizing long-term male reproductive health outcomes.

Globally, male factor infertility accounts for 20%-70% of couples struggling to conceive. Certain male pediatric developmental conditions, such as cryptorchidism, hypospadias, testicular and other childhood cancers, infections, and pediatric varicocele have been associated with future infertility. Early fertility preservation, especially in those with pending chemotherapy or genetic conditions such as Klinefelter syndrome, should be strongly considered in patients expected to experience testicular loss. Although optimal treatment timing may be unknown owing to a paucity of long-term prospective studies, early diagnosis and targeted treatment may optimize fertility potential in adulthood.

Artificial Intelligence in Reproductive Urology.

PURPOSE OF REVIEW: The promise of artificial intelligence (AI) in medicine has been widely theorized over the past couple of decades. It has only been with technological advances over the past few years that physicians and computer scientists have started discovering its true clinical potential. Reproductive urology is a sub-discipline that AI could be of great contribution, as current predictive models and subjectivity within the field have several limitations. We review the literature to summarize recent AI applications in reproductive urology. RECENT FINDINGS: Early AI applications in reproductive urology focused on predicting semen parameters based on questionnaires that identify potential environmental factors and/or lifestyle habits impacting male fertility. AI has shown success in predicting the patient subpopulation most likely to need a genetic workup for azoospermia. With recent advances in image processing, automated sperm detection is a reality. Semen analyses, once a laboratory-only diagnostic test, have moved into health consumer homes with the advent of AI. AI's prospects in medicine are considerable and there is strong potential for AI within reproductive urology. Research in identifying the factors that can affect reproductive success either naturally or with assisted reproduction is of paramount importance to move the field forward.

Consideration of gender differences in infertility evaluation.

PURPOSE OF REVIEW: We aim to provide a review of the literature to summarize the potential causes that lead to a disparity in infertility evaluation and the implications of male factor infertility. RECENT FINDINGS: Owing to current social constructs, women are more likely to seek medical attention and establish reproductive health evaluation at an earlier age. The male factor evaluation in infertility usually gets delayed and can contribute to a couple's inability to conceive. Furthermore, the cost of assisted reproductive technology is not inconsequential and identifying reversible causes of male infertility could lead to substantial cost-savings to the couple. Additionally, male infertility has been identified as a potential early surrogate for adverse health outcomes and an early identification could serve to counsel these patients on lifestyle modification. SUMMARY: Infertility is defined as the inability to conceive after 12 months of unprotected intercourse with 15% of couples reporting difficulties in conception. Traditionally, female factor evaluation has been the driver for the infertility workup. It is estimated that male factor is likely to play a role in 50% of infertile couples with sole contribution in 20% of cases. It is therefore crucial to ensure appropriate investigations of both partners to rule out potentially reversible causes of infertility to improve their chances of natural fecundity.

BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes.

BACKGROUND: Heart failure is a growing epidemic, and a typical aspect of heart failure pathophysiology is altered calcium transients. Normal cardiac calcium transients are initiated by Cav1.2 channels at cardiac T tubules. Bridging integrator 1 (BIN1) is a membrane scaffolding protein that causes Cav1.2 to traffic to T tubules in healthy hearts. The mechanisms of Cav1.2 trafficking in heart failure are not known. OBJECTIVE: To study BIN1 expression and its effect on Cav1.2 trafficking in failing hearts. METHODS: Intact myocardium and freshly isolated cardiomyocytes from nonfailing and end-stage failing human hearts were used to study BIN1 expression and Cav1.2 localization. To confirm Cav1.2 surface expression dependence on BIN1, patch-clamp recordings were performed of Cav1.2 current in cell lines with and without trafficking-competent BIN1. Also, in adult mouse cardiomyocytes, surface Cav1.2 and calcium transients were studied after small hairpin RNA-mediated knockdown of BIN1. For a functional readout in intact heart, calcium transients and cardiac contractility were analyzed in a zebrafish model with morpholino-mediated knockdown of BIN1. RESULTS: BIN1 expression is significantly decreased in failing cardiomyocytes at both mRNA (30% down) and protein (36% down) levels. Peripheral Cav1.2 is reduced to 42% by imaging, and a biochemical T-tubule fraction of Cav1.2 is reduced to 68%. The total calcium current is reduced to 41% in a cell line expressing a nontrafficking BIN1 mutant. In mouse cardiomyocytes, BIN1 knockdown decreases surface Cav1.2 and impairs calcium transients. In zebrafish hearts, BIN1 knockdown causes a 75% reduction in calcium transients and severe ventricular contractile dysfunction. CONCLUSIONS: The data indicate that BIN1 is significantly reduced in human heart failure, and this reduction impairs Cav1.2 trafficking, calcium transients, and contractility.

BIN1 localizes the L-type calcium channel to cardiac T-tubules.

The BAR domain protein superfamily is involved in membrane invagination and endocytosis, but its role in organizing membrane proteins has not been explored. In particular, the membrane scaffolding protein BIN1 functions to initiate T-tubule genesis in skeletal muscle cells. Constitutive knockdown of BIN1 in mice is perinatal lethal, which is associated with an induced dilated hypertrophic cardiomyopathy. However, the functional role of BIN1 in cardiomyocytes is not known. An important function of cardiac T-tubules is to allow L-type calcium channels (Cav1.2) to be in close proximity to sarcoplasmic reticulum-based ryanodine receptors to initiate the intracellular calcium transient. Efficient excitation-contraction (EC) coupling and normal cardiac contractility depend upon Cav1.2 localization to T-tubules. We hypothesized that BIN1 not only exists at cardiac T-tubules, but it also localizes Cav1.2 to these membrane structures. We report that BIN1 localizes to cardiac T-tubules and clusters there with Cav1.2. Studies involve freshly acquired human and mouse adult cardiomyocytes using complementary immunocytochemistry, electron microscopy with dual immunogold labeling, and co-immunoprecipitation. Furthermore, we use surface biotinylation and live cell confocal and total internal fluorescence microscopy imaging in cardiomyocytes and cell lines to explore delivery of Cav1.2 to BIN1 structures. We find visually and quantitatively that dynamic microtubules are tethered to membrane scaffolded by BIN1, allowing targeted delivery of Cav1.2 from the microtubules to the associated membrane. Since Cav1.2 delivery to BIN1 occurs in reductionist non-myocyte cell lines, we find that other myocyte-specific structures are not essential and there is an intrinsic relationship between microtubule-based Cav1.2 delivery and its BIN1 scaffold. In differentiated mouse cardiomyocytes, knockdown of BIN1 reduces surface Cav1.2 and delays development of the calcium transient, indicating that Cav1.2 targeting to BIN1 is functionally important to cardiac calcium signaling. We have identified that membrane-associated BIN1 not only induces membrane curvature but can direct specific antegrade delivery of microtubule-transported membrane proteins. Furthermore, this paradigm provides a microtubule and BIN1-dependent mechanism of Cav1.2 delivery to T-tubules. This novel Cav1.2 trafficking pathway should serve as an important regulatory aspect of EC coupling, affecting cardiac contractility in mammalian hearts.