Assessment of the intracavernosal injection platelet-rich plasma in addition to daily oral tadalafil intake in diabetic patients with erectile dysfunction non-responding to on-demand oral PDE5 inhibitors.

This study aimed to evaluate the effectiveness of ICI of platelet-rich plasma (PRP) in addition to daily oral tadalafil intake in diabetic erectile dysfunction (ED) patients non-responding to PDE5 inhibitors. Overall, 48 patients complaining of ED non-responding to on-demand PDE5 inhibitors were allocated into 2 equal groups, diabetics and non-diabetics that were given a daily dose of 5 mg tadalafil plus vardenafil 20 mg on demand during the study besides being subjected to 3 doses of ICI of PRP, 4 weeks apart. Responses to on-demand PDE5 inhibitors, International index of erectile function-5 (IIEF-5) score, erection hardness scores (EHS) and pharmaco-dynamic duplex studies were assessed. After PRP injections, 33% and 50% of cases were satisfied with on-demand PDE5 inhibitors, respectively, whereas 41% and 66% of them showed improved EHS response. Compared with baseline scores, the mean IIEF-5 scores were significantly improved after PRP therapy in the diabetic ED group (12.1 vs. 8.04, p = 0.003) as well as in the non-diabetic ED group (14.8 vs. 10.2, p = 0.001) linked to pharmaco-penile duplex readings. Both good and fair diabetic control exhibited significant responses to ICI therapy of PRP compared with bad controlled cases. The significant improvement included; the IIEF-5 score increase (86.7%, 126% vs. 16.1%), improved EHS as well as penile duplex readings. Baseline HbA1C demonstrated a significant negative correlation with IIEF-5 score before (p = 0.019) and after PRP therapy (p = 0.002) respectively. It could be concluded that ICI of PRP could be an effective therapy for treating ED patients non-responding to on-demand oral PDE5 treatment.

Assessment of seminal cystatin C levels in infertile men with varicocele: A preliminary study.

Varicocele has been raised as a contributor to male infertility supported by the improvement of sperm parameters after varicocelectomy. Cystatin C (Cys C) has been linked to several cellular changes that are common in male infertility cases associated with varicocele such as apoptosis and autophagy. This preliminary study aimed to assess the seminal levels of Cys C in infertile oligoasthenoteratozoospermic (OAT) men associated with varicocele that have been shown to have spermatic vein vasodilation and active death pathway. Overall, 60 men were investigated being divided into two equivalent groups-infertile OAT men with varicocele who underwent varicocelectomy and healthy fertile men as a control group. These men were subjected to history taking, clinical examination, semen analysis and assessment of seminal Cys C pre and 6 months post-varicocelectomy. The results showed a significant increase of seminal Cys C in infertile OAT men with varicocele than the fertile control (55.57 ± 25.6 ng/ml versus 10.78 ± 1.88 ng/ml, p = .001). Seminal Cys C was a significantly decreased post-operative than its pre-operative level (34.69 ± 14.02 versus 55.57 ± 25.6 ng/ml, p = .01). These results show a potential role of Cys C in varicocele-induced infertility.

Seminal SIRT1-oxidative stress relationship in infertile oligoasthenoteratozoospermic men with varicocele after its surgical repair.

This work assessed seminal SIRT1-oxidative stress (OS) relationship in infertile oligoasthenoteratozoospermic (OAT) men after varicocele repair. Overall, thirty OAT men with varicocele were investigated. Inclusion criteria were infertile males (males who were unable to initiate a pregnancy within 1 year of regular unprotected intercourse), confirmed OAT and normal female factor. These cases were subjected to history taking, clinical checkup and semen analysis. In their semen, seminal SIRT1, malondialdehyde (MDA) and glutathione peroxidase (GPx) levels were assessed. These men were subjected to varicocele surgical repair and were followed up for 3 months. Post-operatively, the mean seminal SIRT1, GPx levels showed significant increases and the mean MDA level showed significant decrease compared to the pre-operative levels linked to improved sperm parameters. The mean seminal SIRT1, GPx, MDA levels showed more significant improvement in grade III varicocele cases compared to grade II cases after surgical repair. Seminal SIRT1 levels showed significant positive correlations with sperm concentration, sperm motility, sperm normal morphology, seminal GPx levels and a significant negative correlation with seminal MDA levels. It could be concluded that seminal SIRT1 is significantly decreased in infertile OAT men with varicocele after its surgical repair linked to improved sperm parameters as well as seminal OS.

Assessment of seminal YKL-40 in infertile men with varicocele.

Several studies attempted to explain the negative impact of varicocele on spermatogenesis and fertilisation processes. YKL-40 is a novel glycoprotein biomarker that had been associated with several diseases. This quasi-interventional study aimed to assess the seminal levels of YKL-40 in infertile men with varicocele before and after varicocelectomy. Overall, 50 men were included in this study divided into 20 healthy fertile men and 30 infertile oligoasthenoteratozoospermic (OAT) men with varicocele that underwent varicocelectomy. All participants were subjected to history taking, clinical examination and scrotal Doppler. Also, semen analysis and seminal YKL-40 assessment were carried out in the start and 6 months after varicocele surgical repair. The results showed a significant increase in the mean seminal YKL-40 level in infertile OAT men with varicocele compared with the healthy fertile men. Six months post-varicocelectomy, the mean seminal KYL-40 level exhibited significant decreases correlated with improved sperm parameters. Overall, seminal levels of YKL-40 showed significant negative correlations with sperm concentration, total sperm motility and sperm normal morphology. It could be concluded that seminal YKL-40 is elevated in infertile OAT men with varicocele where varicocelectomy induces decreased seminal YKL-40 levels correlated with improved semen parameters.

Oral dapoxetine versus topical lidocaine as on-demand treatment for lifelong premature ejaculation: A randomised controlled trial.

This trial aimed to assess the efficacy of on-demand oral dapoxetine versus topical lidocaine treatments for lifelong PE. Cases with lifelong PE were randomised to start treatment by oral dapoxetine 60 mg or topical lidocaine 10% spray. The intravaginal ejaculatory latency time (ILET), validated Arabic Index for PE (AIPE), Sexual Health Inventory for Men (SHIM) and frequency of intercourse/week were recorded at the baseline and after 12 weeks treatment period of the first medication before two weeks washout period and then crossing over to the other one for another 12 weeks. Results showed that both medications significantly increased both IELT and AIPE scores compared with the baseline being significantly better with topical lidocaine (63.44 s, 179.4 s versus 21.87 s, p < .05). Significant decrease of SHIM score was recorded with lidocaine but not with dapoxetine. Global Efficacy Question for the patient's assessment of the effectiveness of drugs showed that lidocaine was described as being effective by 43 cases and ineffective by 12 cases, oral dapoxetine was described as being effective by 16 cases and ineffective by 39 cases. From these accumulated data, it is concluded that topical lidocaine is more effective on-demand therapy for lifelong PE compared with oral dapoxetine.

Spontaneous Penile Tumescence by Sparing Cavernous Tissue in the Course of Malleable Penile Prosthesis Implantation.

INTRODUCTION: Spontaneous penile tumescence after penile prosthesis implantation has been sporadically reported in the literature. AIM: To preserve residual erectile function of patients' spontaneous penile tumescence by sparing cavernous tissue in the course of malleable penile prosthesis implantation. METHODS: Overall, 92 patients were randomized into 2 equal arms; patients undergoing conventional malleable penile prosthesis implantation, and patients undergoing the cavernous tissue-sparing technique. 1 month after surgery, these patients underwent penile duplex examination to assess the maximal cavernous tissue thickness around the implant cylinders. Additionally, they were asked about the occurrence of any spontaneous or arousal-induced penile tumescence. MAIN OUTCOME MEASURES: Postoperative changes were compared with the preoperative ones. RESULTS: The mean maximal cavernous tissue thickness was shown to be significantly higher in the cavernous tissue-sparing group compared with the conventional surgery group (5.2 ± 0.8 mm vs 2.2 ± 1.04 mm, P < .01). In the cavernous tissue-sparing group, 41 of 46 patients (89.13%) reported having a significantly higher incidence of residual penile tumescence vs 7 of 46 patients (15.2%) in the conventional surgery group (P < .001). The postoperative penile girth was significantly higher in the cavernous tissue-sparing group than in the conventional surgery group (11.16 ± 1.1 cm vs 10.11 ± 1.15 cm, P < .001). CLINICAL IMPLICATIONS: This study provides a step-by-step approach to maintaining post-implantation penile tumescence and preserving penile girth in a reproducible manner. STRENGTHS & LIMITATIONS: This is the first study to demonstrate the benefits of implanting a penile prosthesis while the penis is in a pharmacologically induced tumescent state. It is also the first to make use of ultrasound imaging in assessing postoperative corporal tissue. The main limitations are the short postoperative follow-up period and the non-blinding of measurements. CONCLUSION: It could be concluded that the cavernous tissue-sparing technique is a reproducible technique that has the added value of preserving residual erectile function in the form of retained postoperative penile tumescence and preserved penile girth. Zaazaa A, Mostafa T. Spontaneous Penile Tumescence by Sparing Cavernous Tissue in the Course of Malleable Penile Prosthesis Implantation. J Sex Med 2019;16:474-478.

Assessment of seminal granulysin in infertile men with varicocele.

Varicocele has a common association with male infertility, but its exact role is still debated. Apoptosis has been suggested as one of the mechanisms of varicocele-associated infertility. Granulysin is a molecule that plays a role in apoptosis with no previous study about its role in male infertility. This case-controlled study aimed to assess seminal plasma granulysin level in infertile patients with varicocele. This study involved 90 men that were allocated into fertile normozoospermic men (n = 20), infertile men without varicocele (n = 30) and infertile men with varicocele (n = 40). These men were subjected to history taking, clinical examination, semen analysis and estimation of seminal granulysin. In general, seminal granulysin level was significantly elevated in infertile men compared with fertile men. Infertile men with varicocele showed significantly higher seminal granulysin compared with infertile men without varicocele, in bilateral varicocele cases and in grade III varicocele. Seminal granulysin level was negatively correlated with sperm concentration, sperm motility, sperm normal forms percentage and testicular volumes. It is concluded that increased seminal granulysin has a negative impact on spermatogenesis in infertile men in general and in infertile men associated with varicocele in particular.

Does being overweight affect seminal variables in fertile men?

The effect of being overweight on seminal variables was assesed in 165 fertile men. Participants were divided into three groups: fertile men with normal body mass index (BMI) (18.5-24.9 kg/m2), fertile overweight men (BMI 25-29.9 kg/m2) and fertile obese men (BMI >30 kg/m2). Medical history was taken, a clinical examination conducted. Semen analysis was undertaken and BMI measured. Seminal reactive oxygen species (ROS) was estimated by chemiluminescent assay, sperm vitality by the hypo-osmotic swelling test and sperm DNA fragmentation by propidium iodide staining with flowcytometry. Fertile obese men had significantly lower sperm concentration, progressive sperm motility and sperm normal morphology, with significantly higher seminal ROS and sperm DNA fragmentation compared with fertile normal-weight men and overweight men (all P < 0.05). BMI was negatively correlated with sperm concentration (r = -0.091; P = 0.014), progressive sperm motility (r = -0.697; P = 0.001), normal sperm morphology (r = -0.510; P = 0.001), sperm vitality (r = -0.586; P = 0.001), but positively correlated with sperm DNA fragmentation percentage (r = 0.799; P = 0.001) and seminal ROS (r = 0.673; P = 0.001). Increased BMI was found to affect semen parameters negatively even in fertile men.

A review of testicular histopathology in nonobstructive azoospermia.

One major challenge in male factor infertility is nonobstructive azoospermia (NOA), which is characterized by spermatozoa-deficient semen without physical duct blockage. This review offers a thorough overview of the histopathology of the testes in NOA cases, clarifying its complex etiology and emphasizing the possible value of histopathology inspection for both diagnosis and treatment. Variable histopathological findings have been linked to NOA, such as tubular hyalinization, Sertoli cell-only syndrome, hypospermatogenesis, and germ cell arrest. Understanding the pathophysiology and forecasting the effectiveness of treatment are further enhanced by both morphometric and ultrastructural analyses. The potential significance of testicular biopsy in forecasting reproductive outcomes is assessed, especially concerning assisted reproductive technologies like intracytoplasmic sperm injection (ICSI). Besides, testicular microlithiasis, serum hormone profiles, and testicular size are investigated concerning NOA histopathology. It is concluded that understanding the histopathological patterns in NOA is crucial for its accurate diagnosis and appropriate management. Further research is still warranted to improve understanding of the complex pathophysiology underlying NOA.

Male Infertility: New Developments, Current Challenges, and Future Directions.

There have been many significant scientific advances in the diagnostics and treatment modalities in the field of male infertility in recent decades. Examples of these include assisted reproductive technologies, sperm selection techniques for intracytoplasmic sperm injection, surgical procedures for sperm retrieval, and novel tests of sperm function. However, there is certainly a need for new developments in this field. In this review, we discuss advances in the management of male infertility, such as seminal oxidative stress testing, sperm DNA fragmentation testing, genetic and epigenetic tests, genetic manipulations, artificial intelligence, personalized medicine, and telemedicine. The role of the reproductive urologist will continue to expand in future years to address different topzics related to diverse questions and controversies of pathophysiology, diagnosis, and therapy of male infertility, training researchers and physicians in medical and scientific research in reproductive urology/andrology, and further development of andrology as an independent specialty.

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.

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.

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.

Androgen receptor expression relationship with semen variables in infertile men with varicocele.

PURPOSE: Androgen receptor, a member of the nuclear receptor superfamily, has important roles in male reproductive function. It is required for sexual differentiation, pubertal development, spermatogenesis regulation, meiosis completion and spermatocyte transition to haploid round spermatids. We assessed the association of androgen receptor expression and semen variables in infertile men with varicocele. MATERIALS AND METHODS: A total of 299 men were grouped into healthy, fertile controls, infertile men without varicocele and men with infertility associated with varicocele. A history was obtained, clinical examination and semen analysis were done and reproductive hormones were estimated. Androgen receptor expression and the acrosome reaction were determined in recovered spermatozoa. RESULTS: Androgen receptor expression was significantly decreased in infertile men with varicocele more than in infertile men without varicocele compared to fertile controls. Androgen receptor correlated positively with sperm count, motility, normal forms, velocity, linear velocity, acrosome reaction and α-glucosidase. It correlated negatively with serum follicle-stimulating hormone and estradiol. Multiple stepwise regression analysis of androgen receptor expression revealed that the sperm acrosome reaction and linearity index were the most affected independent variables. CONCLUSIONS: Androgen receptor expression was significantly decreased in infertile men with varicocele more than in infertile men without varicocele compared to fertile men. Androgen receptor expression correlated positively with sperm count, motility, normal forms, velocity, linear velocity and acrosome reaction.

Substance abuse and male sexual dysfunction: what lies beneath?

INTRODUCTION: Substance abuse has become a worldwide health problem, leading to numerous consequences such as social problems among family members, abnormal behavior, adverse health effects, and psychological problems as well as economic consequences. OBJECTIVES: We sought to assess the relationship between substance abuse and male sexual health. METHODS: A search was carried out in the following databases: PubMed, MeSH (Medical Subject Headings), Science Direct, Scopus, Cochrane Library, EMBASE, CINAHL, Academic Search Complete, and the Egyptian Knowledge Bank. The following keywords were used to assess the outcomes for relevant associations: illicit drugs, addiction, substance abuse, sexual health, erectile dysfunction, ejaculatory disorders, impotence, orgasm disorders, and sexual performance. RESULTS: The initial literature search identified a total of 148 articles in all searched databases. After removal of duplicate studies and application of inclusion/exclusion criteria, 75 reported studies were retained for review, including 38 case-control studies and 37 cross-sectional studies. These articles were classified into the following categories according to the type of abused substance addressed: cannabis/marihuana, 16 articles; opioids, 13 articles; heroin, 11 articles; cocaine, 5 articles; tramadol, 6 articles; ketamine, 2 articles; ecstasy, 4 articles; amphetamine, 2 articles; khat, 7 articles; androgen anabolic steroids, 2 articles; and polydrugs, 7 articles. Most of these recruited articles demonstrated a negative impact of the addressed substance on male sexual health, with variable levels. CONCLUSION: Substance abuse has negative impacts on male sexual health that should be addressed. More studies conducted with proper methodological and statistical approaches, including logistic regression analysis, are needed to predict the effects of specific substances, considering the rapidly growing effects of non-substance-use disorders on male sexual health.

Genetic variants in varicocele-related male infertility: a systematic review and future directions.

Genetic association studies (GAS) may have the capability to probe the genetic susceptibility alleles in many disorders. This systemic review aimed to assess whether an association exists between gene(s)/allelic variant(s), and varicocele-related male infertility (VRMI). This review included 19 GAS that investigated 26 genes in 1,826 men with varicocele compared to 2,070 healthy men, and 263 infertile men without varicocele. These studies focussed on candidate genes and relevant variants, with glutathione S-transferase gene being the most frequently studied (n = 5) followed by the nitric oxide synthase 3 (NOS3) gene (n = 3) and the phosphoprotein tyrosine phosphatase 1 gene (n = 2). In one study the genes for NAD(P)H quinone oxidoreductase 1, sperm protamine, human 8-oxoguanine DNA glycosylase 1, methylenetetrahydrofolate reductase, polymerase gamma, heat shock protein 90, mitochondrial DNA, superoxide dismutase 2, transition nuclear protein 1, and transition nuclear protein 2, were assessed. There is no clear indication that any of these polymorphisms are sturdily associated with VRMI. However, three studies established that the polymorphic genotype (GT + TT) for rs1799983 polymorphism of the NOS3 gene is more frequent in varicocele patients. Further endeavours such as standardising reporting, exploring complementary designs, and the use of GWAS technology are justified to help replicate these early findings.

Oral phosphodiesterase type 5 inhibitors and male reproductive potential: an overview.

BACKGROUND: Phosphodiesterase type 5 inhibitors (PDE5Is), due to their efficacy and tolerable profile for more than 2 decades,are considered a good addition to the available treatments in patients with erectile dysfunction (ED). AIM: We sought to assess the possible influence of oral PDE5Is on male human reproduction. METHODS: A literature review was performed in several databases, including the PubMed/Medline database, Scopus, Cochrane Library, EMBASE, Academic Search Complete, and Egyptian Knowledge Bank databases. The keywords/search terms were "PDE5Is," "sildenafil," "vardenafil," "tadalafil," or "avanafil," combining and crossing them with "male infertility," "semen," "reproductive hormones," or "sperm." RESULTS: Overall, 101 articles were selected. After removal of duplicates and animal studies, 75 articles were finally subjected to review covering the different items related to male human reproduction, including effects of PDE5Is on different parameters of semen or reproductive hormones, as uses of PDE5Is in cases related to distinctive male factor infertility, such as ED, temporary ED, or ejaculatory failure alongside assisted reproduction (AR) procedures, and ejaculatory dysfunction in spinal cord lesions. We found 26 articles that addressed the direct effects of PDE5Is on semen and reproductive hormonal profiles, 16 in vivo studies and 10 in vitro studies. Oral PDE5Is have in general a stimulatory effect on sperm motility, while other semen parameters and reproductive hormonal profiles showed varied outcomes. Such effects are more pronounced with a long-term daily regimen than with an on-demand regimen. However, it seems that the best-controlled studies suggested no change in the sperm quality of male reproductive potential. CONCLUSION: Oral PDE5Is have in general stimulatory effects on sperm motility, while other semen parameters and hormone profiles showed varied results. In addition, oral PDE5Is have played a useful role in conditions related to distinctive male factor infertility, such as ED, temporary ED, ejaculatory failure alongside AR, and ejaculatory dysfunction in spinal cord lesions.

The Renaissance of Male Infertility Management in the Golden Age of Andrology.

Infertility affects nearly 186 million people worldwide and the male partner is the cause in about half of the cases. Meta-regression data indicate an unexplained decline in sperm concentration and total sperm count over the last four decades, with an increasing prevalence of male infertility. This suggests an urgent need to implement further basic and clinical research in Andrology. Andrology developed as a branch of urology, gynecology, endocrinology, and, dermatology. The first scientific journal devoted to andrological sciences was founded in 1969. Since then, despite great advancements, andrology has encountered several obstacles in its growth. In fact, for cultural reasons, the male partner has often been neglected in the diagnostic and therapeutic workup of the infertile couple. Furthermore, the development of assisted reproductive techniques (ART) has driven a strong impression that this biotechnology can overcome all forms of infertility, with a common belief that having a spermatozoon from a male partner (a sort of sperm donor) is all that is needed to achieve pregnancy. However, clinical practice has shown that the quality of the male gamete is important for a successful ART outcome. Furthermore, the safety of ART has been questioned because of the high prevalence of comorbidities in the offspring of ART conceptions compared to spontaneous conceptions. These issues have paved the way for more research and a greater understanding of the mechanisms of spermatogenesis and male infertility. Consequently, numerous discoveries have been made in the field of andrology, ranging from genetics to several "omics" technologies, oxidative stress and sperm DNA fragmentation, the sixth edition of the WHO manual, artificial intelligence, management of azoospermia, fertility in cancers survivors, artificial testis, 3D printing, gene engineering, stem cells therapy for spermatogenesis, and reconstructive microsurgery and seminal microbiome. Nevertheless, as many cases of male infertility remain idiopathic, further studies are required to improve the clinical management of infertile males. A multidisciplinary strategy involving both clinicians and scientists in basic, translational, and clinical research is the core principle that will allow andrology to overcome its limits and reach further goals. This state-of-the-art article aims to present a historical review of andrology, and, particularly, male infertility, from its "Middle Ages" to its "Renaissance", a golden age of andrology.