Sperm DNA fragmentation and infertility: a narrative review.

PURPOSE: The purpose of this narrative review is to provide a practical understanding of sperm DNA fragmentation (SDF) in the management of male infertility. METHODS: A search for systematic reviews and meta-analyses (SRMA) on SDF between April 1st, 2018 and April 1st, 2023 was performed using PubMed and articles were selected as per their relevance to the topic. Guidelines from major societies were also reviewed. Three clinical cases are reported and discussed. RESULTS: The search initially identified 80 articles. We selected 13 SRMAs based on their relevance to the topic. Of the 13 SRMAs, 7 evaluated the effect of SDF on assisted reproductive technology (ART) outcomes and recurrent pregnancy loss, 3 studied the effect of varicocele repair on SDF, and 3 evaluated the role of SDF involving lifestyle and environmental health factors including body mass index and male factor treatment strategies. CONCLUSION: Evidence suggests that increased SDF has a negative impact on natural pregnancy and ART outcomes. SDF testing may be particularly important in the infertility evaluation of men with varicoceles, idiopathic or unexplained infertility, recurrent pregnancy loss, or previous ART failure. Further studies are needed on SDF testing and the implications it can have on male factor infertility and pregnancy outcomes as well as its implementation in the setting of ART.

Predictive value of seminal oxidation-reduction potential analysis for reproductive outcomes of ICSI.

RESEARCH QUESTION: Is seminal oxidation-reduction potential (ORP) clinically relevant to reproductive outcome? DESIGN: Prospective observational study including a total of 144 couples who had an intracytoplasmic sperm injection (ICSI) cycle between June 2018 and December 2020. The study included patients undergoing fresh ICSI cycles with autologous gametes. Cycles that had day 3 embryo transfers and cryopreservation cycles were excluded. There was no restriction on patients with severe male infertility; couples with unexplained infertility and unexplained male infertility were included, those with azoospermia were excluded. Semen analysis, seminal ORP as determined by means of the MiOXSYS system, sperm DNA fragmentation (SDF) and reproductive outcomes (fertilization, blastocyst development, clinical pregnancy and live birth) were determined. RESULTS: Seminal ORP was significantly negatively correlated with fertilization rate (r = -0.267; P = 0.0012), blastocyst development rate (r = -0.432; P < 0.0001), implantation/clinical pregnancy (r = -0.305; P = 0.0003) and live birth (r = -0.366; P < 0.0001). Receiver operating characteristic curve analysis showed significant predictive power for ORP for fertilization (≥80%; area under the curve [AUC] 0.652; P = 0.0012), blastocyst development rate (≥60%; AUC 0.794; P < 0.0001), implantation/clinical pregnancy (AUC 0.680; P = 0.0002) and live birth (AUC 0.728; P < 0.0001). Comparable results were obtained for SDF (fertilization: AUC 0.678; blastocyst development: AUC 0.777; implantation/clinical pregnancy: AUC 0.665; live birth: AUC 0.723). Normal sperm morphology showed the lowest predictive power for all reproductive outcome parameters. With male age as confounding factor, ORP (cut-off value of 0.51 mV/106 sperm/ml) has significant (P < 0.04667) effects on odds ratios for all reproductive outcome parameters. Multivariate logistic regression to investigate potential seminal and female confounding factors revealed that seminal ORP significantly (P < 0.0039; P < 0.0130) affects reproductive outcome. CONCLUSION: Seminal ORP is relevant for good fertilization, blastocyst development, implantation, clinical pregnancy and live birth.

The impact of COVID-19 on urology office visits and adoption of telemedicine services.

PURPOSE OF REVIEW: The purpose of this review article is to discuss the impact of Coronavirus Disease 2019 (COVID-19) on the evolution of telemedicine use for urology office visits. RECENT FINDINGS: The COVID-19 pandemic has caused a dramatic change in the delivery of healthcare. Fraught with numerous barriers previously, the need for healthcare delivery during a time of social distancing and increased healthcare requirements drove the adoption of telemedicine forward. This 'trial period' over the last year has allowed us to appreciate the potential utility of telehealth-associated services in practice and consider its role even after the pandemic. Multiple studies equating its utility to in-person visits whereas simultaneously providing added convenience and cost-related savings have been published in the urologic literature. Permanent regulatory changes will need to be implemented to allow us the flexibility to use telehealth in the future. SUMMARY: It is clear that telemedicine is an effective strategy for delivery of healthcare under the right circumstances. Although it initially started to fill a need out of necessity, it can help us effectively deliver healthcare as long as the regulations surrounding telemedicine allow us to continue to use it. This period has been challenging for healthcare delivery and led to policy changes that served as a catalyst to help us better understand this previously underutilized resource.

COVID-19 Infection in Men on Testosterone Replacement Therapy.

BACKGROUND: Men who contract coronavirus disease 2019 (COVID-19) appear to have worse clinical outcomes compared with women which raises the possibility of androgen-dependent effects. AIM: We sought to determine if testosterone replacement therapy (TRT) is associated with worse clinical outcomes. METHODS: Through a retrospective chart review, we identified 32 men diagnosed with COVID-19 and on TRT. They were propensity score matched to 63 men diagnosed with COVID-19 and not on TRT. Data regarding comorbidities and endpoints such as hospital admission, intensive care unit admission, ventilator utilization, thromboembolic events, and death were extracted. Chi-square and Kruskal-Wallis tests examined differences in categorical and continuous variables, respectively. Logistic regression analysis tested the relationship between TRT status and the study endpoints. RESULTS: There were no statistically significant differences between the 2 groups, and TRT was not a predictor of any of the endpoints on multivariate analysis. CONCLUSION: These results suggest that TRT is not associated with a worse clinical outcome in men diagnosed with COVID-19. Rambhatla A, Bronkema CJ, Corsi N, et al. COVID-19 Infection in Men on Testosterone Replacement Therapy. J Sex Med 2021;18:215-218.

The State of Men's Health Services in the Veterans Health Administration.

PURPOSE OF REVIEW: For many diseases that place a large burden on our health care system, men often have worse health outcomes than women. As the largest single provider of health care to men in the USA, the Veterans Health Administration (VA) has the potential to serve as leader in the delivery of improved men's health care to address these disparities. RECENT FINDINGS: The VA system has made recent strides in improving benefits for aspects of men's health that are traditionally poorly covered, such as treatment for male factor infertility. Despite this, review of Quality Enhancement Research Initiatives (QUERIs) within the VA system reveals few efforts to integrate disparate areas of care into a holistic men's health program. Policies to unify currently disparate aspects of men's health care will ensure that the VA remains a progressive model for other health care systems in the USA.

Nonobstructive azoospermia: an etiologic review.

ABSTRACT: Azoospermia is the complete absence of spermatozoa in the ejaculate in two or more semen analyses after centrifugation. Nonobstructive azoospermia (NOA) represents the most severe form of male factor infertility accounting for 10%-15% of cases and stems from an impairment to spermatogenesis. Understanding of the hypothalamic-pituitary-testicular axis has allowed NOA to be subcategorized by anatomic and/or pathophysiologic level. The etiologies of NOA, and therefore, the differential diagnoses when considering NOA as a cause of male factor infertility, can be subcategorized and condensed into several distinct classifications. Etiologies of NOA include primary hypogonadism, secondary hypogonadism, defects in androgen synthesis and/or response, defective spermatogenesis and sperm maturation, or a mixed picture thereof. This review includes up-to-date clinical, diagnostic, cellular, and histologic features pertaining to the multitude of NOA etiologies. This in turn will provide a framework by which physicians practicing infertility can augment their clinical decision-making, patient counseling, thereby improving upon the management of men with NOA.

Andrology laboratory technique for analysis of semen in men with azoospermia.

ABSTRACT: Discovery of spermatozoa during the 17th century led to developing technologies for semen analysis in the early 1900s, and then, standard techniques were implemented during the 20th century. Semen analysis has a pivotal role in the male infertility evaluation, and azoospermia is an important finding. Azoospermia is identified in 15% of infertile men. However, the accurate laboratory assessment of azoospermia poses certain technical challenges. Laboratories currently perform semen assessment with great variability; thus, a standard method should be used. Planning suitable management and determining the cause of infertility require a precise evaluation of azoospermia. This review aims to address the definition of azoospermia and highlight laboratory methods in the assessments of azoospermia. Basic methods such as centrifugation, repeat pellet analysis, and staining and advanced methods such as genetic testing and biomarkers have been discussed. These methods have helped in standardizing the protocol for accurate azoospermia assessments with less variability.

Differentiation between nonobstructive azoospermia and obstructive azoospermia: then and now.

Male infertility has seen an increase in prevalence with cases of azoospermia estimated to affect 10%-15% of infertile men. Confirmation of azoospermia subsequently necessitates an early causal differentiation between obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). Although less common when compared to NOA, OA can represent upward 20%-40% of cases of azoospermia. While there are a multitude of etiologies responsible for causing NOA and OA, correctly distinguishing between the two types of azoospermia has profound implications in managing the infertile male. This review represents an amalgamation of the current guidelines and literature which will supply the reproductive physician with a diagnostic armamentarium to properly distinguish between NOA and OA, therefore providing the best possible care to the infertile couple.

Impact of Varicocele on Testicular Oxidative Stress and Sperm Parameters in Experimental Animals: A Systematic Review and Meta-Analysis.

PURPOSE: Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele. MATERIALS AND METHODS: A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×106), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist. RESULTS: Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p<0.01), sperm vitality (SMD: -16.41 [-26.30, -6.52]; p<0.01), total sperm motility (SMD: -17.67 [-24.90, -10.44]; p<0.01), and a significant increase of SDF (SMD: 7.41 [1.23, 13.59]; p=0.02), in rats with varicocele vs. controls. The quality of the included studies was ranked as high. CONCLUSIONS: This SRMA indicates a significant increase in levels of testicular MDA and SDF and a reduction of sperm quality in experimental animals with varicocele. These findings support the potential role of testicular OS in the development of varicocele-induced testicular damage.

Changes in Testosterone Levels Following Surgical Sperm Retrieval in Men with Non-Obstructive Azoospermia: Systematic Review and Meta-Analysis.

PURPOSE: Surgical sperm retrieval (SSR) is used to extract spermatozoa for use with intracytoplasmic sperm injection in men with obstructive and non-obstructive azoospermia (NOA). The procedure may lead to segmental devascularization, postoperative fibrosis, and atrophy with a subsequent decrease in testosterone. The aim of the study is to investigate the impact of SSR on serum levels of total testosterone (TT), follicle-stimulating hormone (FSH), luteinizing hormone (LH) testicular volume, and sexual function in infertile azoospermic men. MATERIALS AND METHODS: In this systematic review and meta-analysis (SRMA), we searched articles in "PubMed" and "Scopus" exploring the impact of SSR on TT, FSH, LH, and testicular volume. The full-text articles were screened to assess eligibility before data extraction, quality assessment, and meta-analysis. RESULTS: Seventeen studies meeting the inclusion criteria were finally analyzed and included 1,685 infertile, azoospermic men. Patients underwent SSR and were followed in the postoperative period (one week to 32 months). The analysis showed a significant reduction in TT (mean difference [MD] 3.81 nmol/L, 95% confidence interval [CI] 0.55:7.06; p=0.02) compared to pre-SSR values. We also observed insignificant differences in serum FSH (MD 5.08 IU/L, 95% CI -5.6:15.8; p=0.35), LH (MD -2.96 IU/L, 95% CI -6.31:0.39; p=0.08), and no change in testicular volume (MD 0.07 mL, 95% CI -1.92:2.07; p=0.94) after SSR. Sexual dysfunction was associated with hypogonadism, depression, and anxiety, especially in men with unsuccessful SSR and Klinefelter syndrome. CONCLUSIONS: The results of this SRMA indicate a significant reduction in TT after SSR. Sexual dysfunction after testicular sperm extraction and the potential negative impact of future SSR repeat should be considered during preoperative counseling.

Effects of Varicocele Repair on Sperm DNA Fragmentation and Seminal Malondialdehyde Levels in Infertile Men with Clinical Varicocele: A Systematic Review and Meta-Analysis.

PURPOSE: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA). MATERIALS AND METHODS: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD). RESULTS: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I²=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogeneity (I²=93.7%). CONCLUSIONS: Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.

Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study of Before-After Data.

PURPOSE: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. MATERIALS AND METHODS: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). RESULTS: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864. CONCLUSIONS: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele.

Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Regenerative Therapy in Erectile Dysfunction: A Survey on Current Global Practice Trends and GAF Expert Recommendations.

PURPOSE: This study aimed to examine current global practices in regenerative therapy (RT) for erectile dysfunction (ED) and to establish expert recommendations for its use, addressing the current lack of solid evidence and standardized guidelines. MATERIALS AND METHODS: A 39-question survey was developed by senior Global Andrology Forum (GAF) experts to comprehensively cover clinical aspects of RT. This was distributed globally via a secure online Google Form to ED specialists through the GAF website, international professional societies, and social media, the responses were analyzed and presented for frequencies as percentages. Consensus on expert recommendations for RT use was achieved using the Delphi method. RESULTS: Out of 479 respondents from 62 countries, a third reported using RT for ED. The most popular treatment was low-intensity shock wave therapy (54.6%), followed by platelet-rich plasma (24.5%) and their combination (14.7%), with stem cell therapy being the least used (3.7%). The primary indication for RT was the refractory or adverse effects of PDE5 inhibitors, with the best effectiveness reported in middle-aged and mild-to-moderate ED patients. Respondents were confident about its overall safety, with a significant number expressing interest in RT's future use, despite pending guidelines support. CONCLUSIONS: This inaugural global survey reveals a growing use of RT in ED treatment, showcasing its diverse clinical applications and potential for future widespread adoption. However, the lack of comprehensive evidence and clear guidelines requires further research to standardize RT practices in ED treatment.

Temporal decline of sperm concentration: role of endocrine disruptors.

INTRODUCTION: Male infertility is a widespread disease with an etiology that is not always clear. A number of studies have reported a decrease in sperm production in the last forty years. Although the reasons are still undefined, the change in environmental conditions and the higher exposure to endocrine-disrupting chemicals (EDCs), namely bisphenol A, phthalates, polychlorinated biphenyls, polybrominated diphenyl esters, dichlorodiphenyl-dichloroethylene, pesticides, and herbicides, organophosphates, and heavy metals, starting from prenatal life may represent a possible factor justifying the temporal decline in sperm count. AIM: The aim of this study is to provide a comprehensive description of the effects of the exposure to EDCs on testicular development, spermatogenesis, the prevalence of malformations of the male genital tract (cryptorchidism, testicular dysgenesis, and hypospadias), testicular tumor, and the mechanisms of testicular EDC-mediated damage. NARRATIVE REVIEW: Animal studies confirm the deleterious impact of EDCs on the male reproductive apparatus. EDCs can compromise male fertility by binding to hormone receptors, dysregulating the expression of receptors, disrupting steroidogenesis and hormonal metabolism, and altering the epigenetic mechanisms. In humans, exposure to EDCs has been associated with poor semen quality, increased sperm DNA fragmentation, increased gonadotropin levels, a slightly increased risk of structural abnormalities of the genital apparatus, such as cryptorchidism and hypospadias, and development of testicular tumor. Finally, maternal exposure to EDCs seems to predispose to the risk of developing testicular tumors. CONCLUSION: EDCs negatively impact the testicular function, as suggested by evidence in both experimental animals and humans. A prenatal and postnatal increase to EDC exposure compared to the past may likely represent one of the factors leading to the temporal decline in sperm counts.