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To understand differences between asymptomatic colonized and infected states of indwelling medical devices, we sought to determine penile prosthesis biofilm composition, microbe-metabolite interaction networks, and association with clinical factors. Patients scheduled for penile prosthesis removal/revision were included. Samples from swabbed devices and controls underwent next-generation sequencing, metabolomics, and culture-based assessments. Biofilm formation from device isolates was reconstituted in a continuous-flow stir tank bioreactor. 93% of 27 analyzed devices harbored demonstrable biofilm. Seven genera including Faecalibaculum and Jeotgalicoccus were more abundant in infected than uninfected device biofilms (p < 0.001). Smokers and those with diabetes mellitus or cardiac disease had lower total normalized microbial counts than those without the conditions (p < 0.001). We identified microbe-metabolite interaction networks enriched in devices explanted for infection and pain. Biofilm formation was recapitulated on medical device materials including silicone, PTFE, polyurethane, and titanium in vitro to facilitate further mechanistic studies. Nearly all penile prosthesis devices harbor biofilms. Staphylococcus and Escherichia, the most common causative organisms of prosthesis infection, had similar abundance irrespective of infection status. A series of other uncommon genera and metabolites were differentially abundant, suggesting a complex microbe-metabolite pattern–rather than a single organism–is responsible for the transition from asymptomatic to infected or painful states. [ABSTRACT FROM AUTHOR]

To describe the first known case of recurrent acute priapism after penile prosthesis implantation. A 60-year-old gentleman with a history of recurrent ischemic priapism without hemoglobinopathy presented with refractory erectile dysfunction and underwent uncomplicated penile prosthesis placement. His course was complicated by early acute ischemic priapism confirmed via ultrasound. Due to his pain, attempts to relieve the priapism using ultrasound-guided phenylephrine injections were attempted but were unsuccessful. He subsequently underwent exploration with confirmation of distal ischemic priapism followed by brisk bright red blood from the proximal corpora upon device externalization. A perineal exploration was performed and the bilateral cavernosal arteries were suture ligated with immediate relief. The device was reimplanted and the patient recovered uneventfully. We report the first known case of ischemic priapism following inflatable penile prosthesis implantation. The details of this case challenge the dogma that priapism is a binary event and instead supports an imbalance between unopposed cavernosal artery inflow possibly due to vascular calcifications and compromised venous outflow due to the presence of the device. Prosthetic urologists should be aware of this rare phenomenon and consider all available approaches on an individualized case-by-case basis. [ABSTRACT FROM AUTHOR]

Clomiphene citrate is a commonly prescribed empiric medical therapy for male infertility, but outcomes data and response rates remain incompletely understood. We retrospectively reviewed our single‐institutional experience of infertile men prescribed clomiphene. Clomiphene treatment in the final cohort of 140 men was associated with a modest increase in median sperm concentration from 2.2 to 2.5 million/ml (p < 0.001). A total of 46/140 (33%) of men upgraded according to World Health Organization concentration categories. Clomiphene treatment in 26/113 (23%) of previously ineligible men became eligible for intrauterine insemination. Using both univariate and multivariable regression, pre‐treatment follicle‐stimulating hormone was inversely associated with change in semen concentration with clomiphene treatment. On binary logistic regression, follicle‐stimulating hormone level was inversely related to World Health Organization concentration category upgrade (p = 0.01). Unfortunately, 17/140 (12%) of men paradoxically worsened on clomiphene, but no predictors for this could be identified. In summary, clomiphene citrate confers a clinically relevant but modest benefit in a subset (1/3rd) of infertile men, particularly those with lower pre‐treatment follicle‐stimulating hormone levels. Men with elevated follicle‐stimulating hormone over 15 IU/ml are less likely to benefit from treatment and should be counselled on other relevant treatment alternatives. [ABSTRACT FROM AUTHOR]

Little is known about the role of the genitourinary and gastrointestinal microbiota in the pathogenesis of male infertility. To compare the taxonomic and functional profiles of the gut, semen, and urine microbiomes of infertile and fertile men. We prospectively enrolled 25 men with primary idiopathic infertility and 12 healthy men with proven paternity, and we collected rectal swabs, semen samples, midstream urine specimens, and experimental controls. We performed comprehensive semen analysis, 16S rRNA sequencing for quantitative high-resolution taxonomy, and shotgun metagenomics with a median of 140 million reads per sample for functional metabolic pathway profiling. We identified a diverse semen microbiome with modest similarity to the urinary microbiome. Infertile men harbored increased seminal α-diversity and distinct β-diversity, increased seminal Aerococcus, and decreased rectal Anaerococcus. Prevotella abundance was inversely associated with sperm concentration, and Pseudomonas was directly associated with total motile sperm count. Vasectomy appeared to alter the seminal microbiome, suggesting a testicular or epididymal contribution. Anaerobes were highly over-represented in the semen of infertile men with a varicocele, but oxidative stress and leukocytospermia were associated with only subtle differences. Metagenomics data identified significant alterations in the S-adenosyl-L-methionine cycle, which may play a multifaceted role in the pathogenesis of infertility via DNA methylation, oxidative stress, and/or polyamine synthesis. This pilot study represents the first comprehensive investigation into the microbiome in male infertility. These findings provide the foundation for future investigations to explore causality and identify novel microbiome-based diagnostics and therapeutics for men with this complex and emotionally devastating disease. We explored the resident populations of bacteria living in the gut, semen, and urine of infertile and fertile men. We found several important bacterial and metabolic pathway differences with the potential to aid in diagnosing and treating male infertility in the future. We explored the resident populations of bacteria living in the gut, semen, and urine of infertile and fertile men. We found several important bacterial and metabolic pathway differences with the potential to aid in diagnosing and treating male infertility in the future. [ABSTRACT FROM AUTHOR]

Polycythemia (erythrocytosis) is a known side effect of testosterone (T) replacement therapy (TRT) and appears to correlate with maximum T levels. There is also a well-established association between obstructive sleep apnea (OSA) and the development of polycythemia, which confers additional long-term cardiovascular morbidity. Synergy between TRT and OSA in the development of polycythemia remains poorly understood. The objective of this study was to retrospectively assess the relationship of OSA and secondary polycythemia in hypogonadal men receiving TRT. We performed a retrospective chart review of all men treated by a single provider from 2015 to 2019 for the diagnosis of hypogonadism. Patients who developed a hematocrit of 52% or greater were classified as having polycythemia. OSA was identified via clinical documentation or use of nocturnal continuous positive airway pressure. Demographics, laboratory values, treatment details, and comorbidities were recorded. Data were reported as mean ± SD for parametric variables and median [interquartile range] for non-parametric values. The primary outcome of this study was the association between OSA and polycythemia in hypogonadal men on TRT. 474 men were included in this study. 62/474 (13.1%) men met the criteria for the diagnosis of polycythemia with a median hematocrit of 53.6 [interquartile range 52.6, 55.5]. Univariate analysis demonstrated a strong positive association between polycythemia and the concomitant diagnosis of OSA in hypogonadal men (P =.002). Even after correcting for age, body mass index (BMI), and peak T levels in the multivariate analysis (P =.01), this relationship remained significant with an odds ratio of 2.09 [95% CI 1.17, 3.76]. 37 men on TRT with polycythemia and OSA were included in the final cohort with a mean age of 59.2 ± 11.4 years, mean BMI of 32.4 ± 6.0, and median time from TRT initiation to polycythemia diagnosis of 3 years. All patients diagnosed with OSA were prescribed continuous positive airway pressure with poor compliance noted in 52.8% of men. 37.8% were managed via phlebotomy and 59.5% were managed via dose de-escalation of TRT. In hypogonadal men on TRT with polycythemia, BMI was the only risk factor strongly associated with OSA (P =.013). In hypogonadal men (particularly those with elevated BMI) on TRT who develop secondary polycythemia, a diagnosis of OSA should be strongly considered. This is a single provider retrospective study and further studies are needed to assess generalizability. In this retrospective single-center cohort, the development of polycythemia in hypogonadal men on TRT was associated with an increased prevalence of OSA. Lundy SD, Parekh NV, Shoskes DA. Obstructive Sleep Apnea Is Associated With Polycythemia in Hypogonadal Men on Testosterone Replacement Therapy. J Sex Med 2020;17:1297–1303. [ABSTRACT FROM AUTHOR]

The article provides an overview of studies on male sexual health and reproductive medicine. Topics discussed include a study by R. Lee and colleagues which examined the power of artificial intelligence to detect human sperm in semen and mTESE samples using bright-field microscopy for nonobstructive azoospermic (NOA) patients and the need for a structured educational curriculum in residency for male infertility according to K. Asanad and colleagues.

Abstract: The transplantation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is a promising strategy to treat myocardial infarction and reverse heart failure, but to date the contractile benefit in most studies remains modest. We have previously shown that the nucleotide 2-deoxyadenosine triphosphate (dATP) can substitute for ATP as the energy substrate for cardiac myosin, and increasing cellular dATP content by globally overexpressing ribonucleotide reductase (R1R2) can dramatically enhance cardiac contractility. Because dATP is a small molecule, we hypothesized that it would diffuse readily between cells via gap junctions and enhance the contractility of neighboring coupled wild type cells. To test this hypothesis, we performed studies with the goals of (1) validating gap junction-mediated dATP transfer in vitro and (2) investigating the use of R1R2-overexpressing hPSC-CMs in vivo as a novel strategy to increase cardiac function. We first performed intracellular dye transfer studies using dATP conjugated to fluorescein and demonstrated rapid gap junction-mediated transfer between cardiomyocytes. We then cocultured wild type cardiomyocytes with either cardiomyocytes or fibroblasts overexpressing R1R2 and saw more than a twofold increase in the extent and rate of contraction of wild type cardiomyocytes. Finally, we transplanted hPSC-CMs overexpressing R1R2 into healthy uninjured rat hearts and noted an increase in fractional shortening from 41±4% to 53±5% just five days after cell transplantation. These findings demonstrate that dATP is an inotropic factor that spreads between cells via gap junctions. Our data suggest that transplantation of dATP-producing hPSC-CMs could significantly increase the effectiveness of cardiac cell therapy. [Copyright &y& Elsevier]

Despite preclinical studies demonstrating the functional benefit of transplanting human pluripotent stem cellderived cardiomyocytes (PSC-CMs) into damaged myocardium, the ability of these immature cells to adopt a more adult-like cardiomyocyte (CM) phenotype remains uncertain. To address this issue, we tested the hypothesis that prolonged in vitro culture of human embryonic stem cell (hESC)- and human induced pluripotent stem cell (hiPSC)-derived CMs would result in the maturation of their structural and contractile properties to a more adult-like phenotype. Compared to their early-stage counterparts (PSC-CMs after 20-40 days of in vitro differentiation and culture), late-stage hESC-CMs and hiPSC-CMs (80-120 days) showed dramatic differences in morphology, including increased cell size and anisotropy, greater myofibril density and alignment, sarcomeres visible by bright-field microscopy, and a 10-fold increase in the fraction of multinucleated CMs. Ultrastructural analysis confirmed improvements in the myofibrillar density, alignment, and morphology. We measured the contractile performance of late-stage hESC-CMs and hiPSC-CMs and noted a doubling in shortening magnitude with slowed contraction kinetics compared to the early-stage cells. We then examined changes in the calciumhandling properties of these matured CMs and found an increase in calcium release and reuptake rates with no change in the maximum amplitude. Finally, we performed electrophysiological assessments in hESC-CMs and found that late-stage myocytes have hyperpolarized maximum diastolic potentials, increased action potential amplitudes, and faster upstroke velocities. To correlate these functional changes with gene expression, we performed qPCR and found a robust induction of the key cardiac structural markers, including β-myosin heavy chain and connexin-43, in late-stage hESC-CMs and hiPSC-CMs. These findings suggest that PSC-CMs are capable of slowly maturing to more closely resemble the phenotype of adult CMs and may eventually possess the potential to regenerate the lost myocardium with robust de novo force-producing tissue. [ABSTRACT FROM AUTHOR]

To assess the incidence of discordant testicular pathology in men undergoing bilateral microdissection testicular sperm extraction (mTESE) and association with sperm retrieval rate. We performed a retrospective single-institutional review of all patients undergoing mTESE from 2007 to 2021 and aggregated clinical history, physical exam, semen analysis, and operative findings. Specimens with discordant pathology were re-reviewed by an experienced genitourinary.ßpathologist and categorized in a standardized fashion. Data were analyzed using SPSS. One hundred fourteen non-obstructive azoospermia.ßmen undergoing 132 mTESEs were identified within the study period. Eighty-five percent (112/132) of cases had pathology specimens available, and within this specific cohort the success rate was 41.9% (47/112). A total of 206 pathological reports resulted including 52.4% Sertoli cell only, 4.9% Leydig cell hyperplasia, 8.7% fibrosis, 16.5% maturation arrest, and 17.5% hypospermatogenesis. Twelve percent of testicles had more than 1 pathologic diagnosis. Sixty-six men had synchronous bilateral testicular pathology, and 11/66 (16.6%) had at least partially discordant pathology on initial review. Focused re-review by a genitourinary pathologist confirmed exclusively discordant pathology in 7/66 (10.6%) cases, with a sperm retrieval rate of 57% (4/7). The sperm retrieval rate.ßin men with discordant pathology was not significantly different from those with concordant pathology. Over 1 in 10 men undergoing mTESE may have discordant pathology between testicles, though this may not affect sperm retrieval rate.ßat the time of procedure. Clinicians should consider submitting bilateral testicular specimens for pathology to (1) clarify their outcomes data, and (2) assist with clinical decision-making and surgical planning if a repeat mTESE is indicated. [ABSTRACT FROM AUTHOR]

Findings from several high profile meta-analyses have raised concerns about an ongoing global decline in sperm concentration and male fertility. However, these studies exhibit considerable heterogeneity in key variables including study population, methodology, fertility status, and geographic region. To perform a systematic review and meta-analysis exploring temporal trends in sperm concentration among fertile men and men unselected for fertility status in the United States. A literature search performed in Scopus and PubMed databases for studies published between 1970 and 2023. Additional studies were included from citations of prior global meta-analyses and reviews evaluating temporal trends in sperm count. Studies were included if they presented original data on sperm concentration in US men without known infertility from 1970 to 2023. Aggregate data were assessed across all study populations, with additional subgroup analyses stratified by fertility status and US region. Weighted generalized linear models were generated to evaluate the association between mean sperm concentration and sample collection year. A total of 874 articles were screened, with 58 meeting the inclusion criteria. These represented 75 unique study populations totaling 11,787 men in the United States. Across all study populations, no change in sperm concentration was observed between 1970 and 2018 in unadjusted models (β = 0.14 million/mL per year). When adjusting for US region, no statistically significant decline in sperm concentration was seen. When adjusting for both region and fertility status, a modest annual decline was observed to meet statistical significance (β = –0.35 million/mL per year). Of the 49 study populations reporting adequate data to determine mean total sperm count, there was a significant increase in total sperm count of 2.9 million per year between 1970 and 2018. Subgroup analysis found no statistically significant change in mean sperm concentration among any US census region or fertility status cohort. In contrast to prior global studies, this analysis suggests no clinically significant decline in sperm concentration among confirmed fertile men and the general male US population without known infertility. Although these findings provide some reassurance against a widespread rapid decline, further studies are necessary to better understand this important topic. [ABSTRACT FROM AUTHOR]

Background: Approximately 8%–12% of couples worldwide face infertility, with infertility of individuals assigned male at birth (AMAB) contributing to at least 50% of cases. Conventional semen analysis commonly used to detect sperm abnormalities is insufficient, as 30% of AMAB patients experiencing infertility show normal results in this test. From a genetic perspective, the assessment of sperm DNA fragmentation (SDF) is important as a parameter of sperm quality. Methods: In this narrative study, we review and discuss pathophysiological causes, DNA repair mechanisms, and management of high SDF. We then summarize literature exploring the association between SDF and reproductive outcomes. Main Findings: Recent systematic reviews and meta‐analyses have revealed a significant association between high SDF in AMAB individuals and adverse reproductive outcomes including embryo development, natural conception, intrauterine insemination, and in vitro fertilization. However, the association with live birth rates and pregnancy rates following intracytoplasmic injection remains inconclusive. The disparities among quantitative assays, inconsistent reference range values, absent high‐quality prospective clinical trials, and clinical heterogeneity in AMAB patients with elevated SDF represent the main limitations affecting SDF testing. Conclusion: The evaluation and management of SDF plays an important role in a subset of AMAB infertility, but widespread integration into clinical guidelines will require future high‐quality clinical trials and assay standardization. [ABSTRACT FROM AUTHOR]

Postoperative incisional hernia is a relatively common complication following abdominal surgery. Herniation of the kidney is a less common entity and typically occurs as a congenital or acquired diaphragmatic defect, and rare case reports have demonstrated partial flank or lumbar herniation of the kidney. Herein we present a unique case of a postoperative incisional hernia containing the entire right kidney. [ABSTRACT FROM AUTHOR]

Testicular replantation represents a unique circumstance. There are very few reports documenting their experience with testicle replantation and to the best of the authors' knowledge, this is the first case that has been reported in the peer-reviewed literature following a wrong site surgery. Therefore, we detail our technique and outcome when faced with such a rare event. In addition we review the literature, in order to compare and report the experience of others. This case highlights the value of applied microsurgical knowledge and the importance of cross-disciplinary efforts to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction Materials and Methods Results Conclusions Microsurgical testicular sperm extraction (microTESE) is crucial for treating non‐obstructive azoospermia (NOA), offering both ‘fresh’ and ‘frozen’ options. This study evaluates the impact of fresh versus frozen microTESE on the progression to intra‐cytoplasmic sperm injection (ICSI) cycles, focusing on sperm motility.We conducted a retrospective analysis of microTESE procedures at a major medical centre from 2007 to 2021, excluding cases of obstructive azoospermia and cryptozoospermia. Patients were divided into two groups: fresh microTESE (Group FR) and frozen microTESE (Group FZ). Sperm motility was assessed, and ICSI outcomes were compared between groups.Out of 128 microTESE procedures on 113 NOA patients, 31 were fresh and 97 were frozen. Sperm was found in 67.7% of fresh cases and 45.3% of frozen cases. In fresh cases, 85.7% had motile sperm for ICSI, whereas in frozen cases, 81.8% had motile sperm initially, but only 52.7% retained motility post‐thaw.Our findings indicate a significant drop in motile sperm availability for ICSI in frozen microTESE cases compared to fresh ones. This suggests a potential advantage of fresh microTESE for certain couples, despite the logistical challenges, highlighting the need for careful patient selection and counselling. [ABSTRACT FROM AUTHOR]

Objective Materials and methods Results Conclusions Elevated sperm DNA fragmentation has potential implications for semen quality and fertility. The commonly used sperm chromatin dispersion test offers an indirect estimation but has limitations in terms of bias and variability. This study aimed to assess the reliability of the sperm chromatin dispersion assay for predicting assisted reproductive technology outcomes.This systematic review included studies published until December 2023 that adhered to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. PubMed/MEDLINE, Scopus, and Google Scholar databases were searched. Various assisted reproductive technology outcomes in patients with high (≥ 30%) versus low (< 30%) sperm DNA fragmentation were compared using a sperm chromatin dispersion assay and including a sub‐analysis of intracytoplasmic sperm injection versus in vitro fertilization. A comprehensive meta‐analysis software facilitated quantitative analysis with statistical comparisons between cases and controls. Interstudy heterogeneity was assessed, and sensitivity and publication bias tests were performed.Of the 199 abstracts assessed, 64 full‐text articles were screened, and 44 articles were qualitatively synthesized. Fourteen articles representing 5346 participants were quantitatively analyzed. Using the sperm chromatin dispersion assay, elevated sperm DNA fragmentation was associated with lower fertilization and embryo cleavage rates. Notably, high sperm DNA fragmentation levels did not affect the clinical pregnancy, implantation, miscarriage, or live birth outcomes. Sub‐analysis revealed lower fertilization, embryo cleavage, clinical pregnancy, live birth rates, and higher miscarriage rates in the intracytoplasmic sperm injection subgroup only.The sperm chromatin dispersion assay did not show significant differences in pregnancy or live birth rates between the high‐ and low‐sperm DNA fragmentation groups. Noteworthy, high sperm DNA fragmentation was associated with worse assisted reproductive technology outcomes in the intracytoplasmic sperm injection group. Given the current quality of the evidence, affected by the experimental design and the absence of correction for female factors of infertility, clinicians should be wary of the assay's limited predictive power for pregnancy and live birth outcomes. [ABSTRACT FROM AUTHOR]

To characterize the surgical management, perioperative, and cancer-specific outcomes, and the influence of aggressive histologic variants (AHV) on operative management among patients with renal cell carcinoma (RCC) and inferior vena cava (IVC) thrombus. RCC with rhabdoid and/or sarcomatoid differentiation, which we defined as AHV, portends a worse prognosis. AHV can be associated with a desmoplastic reaction which may complicate resection. We reviewed patients undergoing radical nephrectomy and IVC thrombectomy between 1990 and 2020. Comparative statistics were employed as appropriate. Survival analysis was performed according to the Kaplan-Meier method, and intergroup analysis performed with log-rank statistics. Multivariable cox proportional hazards regression was used to assess the effect of AHV, age, thrombus level, vena cavectomy, metastases, and medical comorbidities on recurrence and overall survival (OS). Ninety-four of 403 (23.3%) patients had AHV, including 43 (46%) rhabdoid, 39 (41%) sarcomatoid, and 12 (13%) with both. AHV were more likely to present with advanced disease; however, increased perioperative complications or decreased OS were not observed. Median (IQR) survival was 16.7 (4.8-47) months without AHV and 12.6 (4-29) months with AHV (P =.157). Sarcomatoid differentiation was independently associated with worse OS (HR = 2.016, CI 1.38-2.95, P <.001), whereas rhabdoid alone or with sarcomatoid demonstrated similar OS (P = 0.063). RCC and IVC thrombus with AHV are more likely to present with metastatic disease, and sarcomatoid differentiation is associated with a worse OS. Resection of tumors with and without AHV have similar perioperative complications, suggesting that surgery can be safely accomplished in patients with RCC and IVC thrombus with AHV. [ABSTRACT FROM AUTHOR]

Simple Summary: Male-factor infertility is a condition affecting nearly half of all infertile couples, and the most common correctable cause is a cluster of dilated veins above the testicle called a varicocele. How a varicocele forms and how exactly it impairs sperm production remains a mystery. In this review article, we explore the historical studies describing various theories for this condition. We also review the modern literature that uses large data sets, termed "-omics" analyses, to better understand the genes, RNA, proteins, and bacteria that may play a role. Using this information, future non-surgical treatments for varicoceles may be on the horizon for the millions of men with this condition. Male-factor infertility is implicated in over half of the millions of cases of infertility worldwide, and varicoceles are the most common correctable cause of male-factor infertility. The pathophysiologic mechanism for varicoceles is complex and next-generation technologies offer promising insights into the molecular underpinnings of this condition. In this narrative review, we highlight historical and contemporary paradigms associated with varicoceles, with an emphasis on the biological underpinnings of this disease. Specifically, we review the literature describing the underlying causes of varicoceles, discuss the molecular and cellular mechanisms causing pathological changes in some (but not all) men, and highlight key articles regarding the next-generation analyses (e.g., transcriptome, epigenome, proteome, and microbiome) being applied to better understand the condition and its treatment. These data demonstrate an ongoing evolution of the knowledge of varicoceles and the potential for improved personalized care in the future for men with this condition. [ABSTRACT FROM AUTHOR]

Background: Culture-based studies have shown that penile prostheses harbor biofilms in the presence and absence of infection, but these findings have not been adequately validated using contemporary microbiome analytic techniques. Aim: The study sought to characterize microbial biofilms of indwelling penile prosthesis devices according to patient factors, device components, manufacturer, and infection status. Methods: Upon penile prostheses surgical explantation, device biofilms were extracted, sonicated, and characterized using shotgun metagenomics and culture-based approaches. Device components were also analyzed using scanning electron microscopy. Outcomes: Outcomes included the presence or absence of biofilms, alpha and beta diversity, specific microbes identified and the presence of biofilm, and antibiotic resistance genes on each prosthesis component. Results: The average age of participants from whom devices were explanted was 61 ± 11 years, and 9 (45%) of 20 had a diagnosis of diabetes mellitus. Seventeen devices were noninfected, and 3 were associated with clinical infection. Mean device indwelling time prior to explant was 5.1 ± 5.1 years. All analyzed components from 20 devices had detectable microbial biofilms, both in the presence and absence of infection. Scanning electron microscopy corroborated the presence of biofilms across device components. Significant differences between viruses, prokaryotes, and metabolic pathways were identified between individual patients, device manufacturers, and infection status. Mobiluncus curtisii was enriched in manufacturer A device biofilms relative to manufacturer B device biofilms. Bordetella bronchialis, Methylomicrobium alcaliphilum, Pseudoxanthomonas suwonensis, and Porphyrobacter sp. were enriched in manufacturer B devices relative to manufacturer A devices. The most abundant bacterial phyla were the Proteobacteria, Actinobacteria, and Firmicutes. Glycogenesis, the process of glycogen synthesis, was among the predominant metabolic pathways detected across device components. Beta diversity of bacteria, viruses, protozoa, and pathways did not differ among device components. Clinical Implications: All components of all penile prostheses removed from infected and noninfected patients have biofilms. The significance of biofilms on noninfected devices remains unknown and merits further investigation. Strengths and Limitations: Strengths include the multipronged approach to characterize biofilms and being the first study to include all components of penile prostheses in tandem. Limitations include the relatively few number of infected devices in the series, a relatively small subset of devices included in shotgun metagenomics analysis, and the lack of anaerobic and other expanded conditions for culture. Conclusion: Penile prosthesis biofilms are apparent in the presence and absence of infection, and the composition of biofilms was driven primarily by device manufacturer, individual variability, and infection, while being less impacted by device component. [ABSTRACT FROM AUTHOR]

Think about 6 loved ones of reproductive age in your life. Now imagine that 1 of these 6 individuals is suffering from infertility. Perhaps they feel alone and isolated, unable to discuss their heartbreak with their closest friends, family, and support network. Suffering in silence. In this editorial, we discuss the infertility journey through the lens of the patients, the providers, and the scientists who struggle with infertility each and every day. Our goal is to open a dialogue surrounding infertility, with an emphasis on dismantling the longstanding societal barriers to acknowledging male infertility as a disease. Through education, communication, compassion, and advocacy, together we can all begin to break the deafening silence of male infertility. [ABSTRACT FROM AUTHOR]

Background: Sperm chromatin dispersion test is a common and inexpensive technique to assess sperm DNA fragmentation, but its subjectivity in assessing a small number of spermatozoa is a disadvantage. Objectives: To study the efficacy of a new sperm chromatin dispersion test kit (R10) combined with an artificial intelligence‐aided halo‐evaluation platform (X12) and compare the results to those of existing sperm DNA fragmentation testing methods. Materials and methods: Semen samples from normozoospermic donors (n = 10) and infertile men with abnormal semen parameters (n = 10) were enrolled. DNA fragmentation indices were examined by multiple assays, including R10, Halosperm G2 (G2), sperm chromatin structure assay, and terminal deoxynucleotidyl transferase deoxynucleotidyl transferase nick end labeling. In R10 assay, the DNA fragmentation indices were obtained both manually (manual R10) and by X12 (AI‐R10). The obtained DNA fragmentation indices were analyzed by agreement analyses. Results: The DNA fragmentation indices obtained by manual R10 and those obtained by AI‐R10 showed a strong significant correlation (r = 0.97, p < 0.001) and agreement. The number of spermatozoa evaluated by AI‐R10 was 2078 (680–5831). The DNA fragmentation indices obtained by manual R10 and AI‐R10 both correlated with those of G2 (r = 0.90, p < 0.001; r = 0.88, p < 0.001). Between the AI‐R10 and G2 results, Passing–Bablok regression showed no systematic or proportional difference, and Bland–Altman plots revealed overall agreement and a mean bias of 6.3% with an SD of 6.9% (95% limit of agreement: −7.2% to 19.9%). AI‐R10 and sperm chromatin structure assays showed systematic differences with a mean bias of −1.9%, while AI‐R10 and terminal deoxynucleotidyl transferase deoxynucleotidyl transferase nick end labeling revealed proportional differences with a mean bias of −10.7%. Conclusions: The novel sperm chromatin dispersion kit and artificial intelligence‐aided platform demonstrated significant correlation and agreement with existing sperm chromatin dispersion methods by assessing greater number of spermatozoa. This technique has the potential to provide a rapid and accurate assessment of sperm DNA fragmentation without technical expertise or flow cytometry. [ABSTRACT FROM AUTHOR]

To identify patient factors associated with a clinically significant improvement in semen parameters among infertile men treated with the aromatase inhibitor anastrozole. Multi-institutional retrospective cohort study. Two Tertiary Academic Medical Centers. A total of 90 infertile men treated at 2 tertiary academic medical centers who met inclusion criteria and obtained pretreatment and posttreatment semen analyses. Prescription of anastrozole (median 3 mg/wk). Upgrade in the World Health Organization sperm concentration category (WHO-SCC). Univariate logistic regression, multivariable logistic regression, and partitioning analyses were performed to identify statistically significant patient factors capable of predicting treatment response. With anastrozole treatment, 46% (n = 41/90) of men responded favorably with a WHO-SCC upgrade, and 12% (n = 11/90) experienced a downgrade. Responders exhibited lower pretreatment levels of luteinizing hormone (LH, 4.7 vs. 8.3 IU/L) and follicle-stimulating hormone (4.7 vs. 6.7 IU/mL), higher pretreatment levels of testosterone (T, 356 vs. 265 ng/dL), and similar baseline level of estradiol (E 2 , 73% vs. 70% with detectible level). Baseline semen parameters differed, with anastrozole responders demonstrating higher baseline semen concentration (3.6 vs. 0.3 M/mL) and higher total motile sperm counts (3.7 vs. 0.1 M). Anastrozole therapy converted 29% (n = 26/90) of the cohort to normozoospermia and enabled intrauterine insemination access in 31% (n = 20/64) of previously ineligible patients. Interestingly, neither body mass index nor the baseline E 2 level or E 2 -T ratio was associated with WHO-SCC upgrade. Multivariable logistic regression revealed the T-LH ratio (odds ratio: 1.02, 95% confidence interval: 1.00–1.03) and baseline nonazoospermia (odds ratio: 9.4, 95% confidence interval: 1.1–78.9) to be statistically significant predictors of WHO-SCC upgrade (area under receiver operating characteristic curve: 0.77). The final user-friendly partitioning model consisting of the T-LH ratio ≥100 and baseline non-azoospermia was 98% sensitive and 33% specific for WHO-SCC upgrades (area under the curve: 0.77). Anastrozole therapy decreases serum E 2 levels, increases serum gonadotropins, and clinically improves semen parameters in half of men with idiopathic infertility. Nonazoospermic infertile men with T-LH ratios ≥100 are likely to benefit from anastrozole treatment irrespective of baseline E 2 level or E 2 -T ratio. Men with azoospermia rarely respond to anastrozole and should be counseled on alternative treatments. [ABSTRACT FROM AUTHOR]

BACKGROUND. Generally, clinical assessment of gonadal testosterone (T) in human physiology is determined using concentrations measured in peripheral blood. Prostatic T exposure is similarly thought to be determined from peripheral T exposure. Despite the fact that androgens drive prostate cancer, peripheral T has had no role in the clinical evaluation or treatment of men with localized prostate cancer. METHODS. To assess the role of local androgen delivery in prostate cancer, we obtained blood from the (periprostatic) prostatic dorsal venous complex in 266 men undergoing radical prostatectomy from July 2014 to August 2021 and compared dorsal T (DT) levels with those in circulating peripheral blood (PT) and prostatic tissue. Comprehensive targeted steroid analysis and unbiased metabolomics analyses were performed. The association between the DT/PT ratio and progression-free survival after prostatectomy was assessed. RESULTS. Surprisingly, in some men, DT levels were enriched several-fold compared with PT levels. For example, 20% of men had local T concentrations that were at least 2-fold higher than peripheral T concentrations. Isocaproic acid, a byproduct of androgen biosynthesis, and 17-OH-progesterone, a marker of intratesticular T, were also enriched in the dorsal vein of these men, consistent with testicular shunting. Men with enriched DT had higher rates of prostate cancer recurrence. DT/PT concentration ratios predicted worse outcomes even when accounting for known clinical predictors. CONCLUSIONS. These data suggest that a large proportion of men have a previously unappreciated exposure to an undiluted and highly concentrated T supply. Elevated periprostatic T exposure was associated with worse clinical outcomes after radical prostatectomy. FUNDING. National Cancer Institute (NCI), NIH grants R01CA172382, R01CA236780, R01CA261995, R01CA249279, and R50CA251961; US Army Medical Research and Development Command grants W81XWH2010137 and W81XWH-22-1-0082. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis summarize the difference in the methylation of the H19 gene in patients with abnormal versus normal conventional sperm parameters. It also evaluates the effects of age and sperm concentration on H19 methylation in spermatozoa using meta-regression analysis. It was performed according to the MOOSE guidelines for meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The quality of the evidence reported in the studies included was assessed using the Cambridge Quality Checklists. A total of 11 articles met our inclusion criteria. Quantitative analysis showed that H19 methylation levels were significantly lower in the group of infertile patients than in fertile controls. The reduction in methylation was much more pronounced in patients with oligozoospermia (alone or associated with other sperm parameter abnormalities) and in those with recurrent pregnancy loss. Meta-regression analysis showed the results to be independent of both patient age and sperm concentration. Therefore, the H19 methylation pattern should be evaluated among couples accessing assisted reproductive techniques (ART), in order to gain prognostic information on ART outcome and offspring health. [ABSTRACT FROM AUTHOR]

To better understand the internet advertising material published on clinician websites for the 30,000 men who undergo evaluation for vasectomy reversal (VR), which is a technically demanding procedure requiring microsurgical expertise. Internet search trends for "vasectomy" and "vasectomy reversal" from 2004 to 2022 were assessed using Google Trends. Search engines were then queried on a state-by-state basis for physicians performing VR and the available information aggregated and analyzed using standard statistical approaches. VR search volume consistently represented roughly one-tenth of the search volume for vasectomy. One hundred and ninety reversal clinics were identified in 44 of 50 states with the highest number identified in the southeast region and an overall median price of $6500. Ninety percent of physicians were male and completed residencies in urology. Other specialties included obstetrics and gynecology, general surgery, family medicine and orthopedic surgery. Forty-two percent of urologists had completed infertility fellowships. Sixty percent of physicians utilized a microscope, and 4.7% of physicians explicitly stated they did not perform vasoepididymostomy even when indicated. Fifty two percent of clinics reported VR success rates as high as 100%, and 34% of clinics reported pregnancy outcomes. Twenty-five percent of clinics reported out-of-pocket VR pricing and 26% discussed possible complications. VR is a technically demanding cash-pay procedure being performed by physicians with a wide array of backgrounds and outcomes. Urologists should strive to lead by example and report their training, personal experiences, and expected outcomes to enable optimal medical decision making for each patient. [ABSTRACT FROM AUTHOR]

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause. [ABSTRACT FROM AUTHOR]

Key points The contractile properties of human fetal skeletal muscle are unknown., Reductionist approaches such as isolated myofibril and isolated contractile protein biomechanical assays allow study of activation and relaxation properties of skeletal muscle from different sources., We have tested the contractile properties of human fetal skeletal myofibrils and myosin in comparison with myosin and myofibrils from human adult skeletal muscle and rabbit psoas muscle., Human fetal skeletal myofibrils have much slower kinetics of activation and relaxation compared to myofibrils from adult human or rabbit psoas skeletal muscle., Investigations using altered substrate and product conditions for both the in vitro motility assay and myofibril mechanics/kinetics indicate that fetal muscle acto-myosin crossbridges cycle more slowly than, but with similar rate-limiting steps to, the adult myosin isoforms., Abstract Little is known about the contraction and relaxation properties of fetal skeletal muscle, and measurements thus far have been made with non-human mammalian muscle. Data on human fetal skeletal muscle contraction are lacking, and there are no published reports on the kinetics of either fetal or adult human skeletal muscle myofibrils. Understanding the contractile properties of human fetal muscle would be valuable in understanding muscle development and a variety of muscle diseases that are associated with mutations in fetal muscle sarcomere proteins. Therefore, we characterised the contractile properties of developing human fetal skeletal muscle and compared them to adult human skeletal muscle and rabbit psoas muscle. Electron micrographs showed human fetal muscle sarcomeres are not fully formed but myofibril formation is visible. Isolated myofibril mechanical measurements revealed much lower specific force, and slower rates of isometric force development, slow phase relaxation, and fast phase relaxation in human fetal when compared to human adult skeletal muscle. The duration of slow phase relaxation was also significantly longer compared to both adult groups, but was similarly affected by elevated ADP. F-actin sliding on human fetal skeletal myosin coated surfaces in in vitro motility (IVM) assays was much slower compared with adult rabbit skeletal myosin, though the Km(app) (apparent (fitted) Michaelis-Menten constant) of F-actin speed with ATP titration suggests a greater affinity of human fetal myosin for nucleotide binding. Replacing ATP with 2 deoxy-ATP (dATP) increased F-actin speed for both groups by a similar amount. Titrations of ADP into IVM assays produced a similar inhibitory affect for both groups, suggesting ADP binding may be similar, at least under low load. Together, our results suggest slower but similar mechanisms of myosin chemomechanical transduction for human fetal muscle that may also be limited by immature myofilament structure. [ABSTRACT FROM AUTHOR]