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.

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.

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.

Evaluating the Impact of Benign Prostatic Hyperplasia Surgical Treatments on Sexual Health.

Benign prostatic hyperplasia (BPH), a prevalent condition in older men, is often managed through various surgical interventions. This narrative review aims to explore the impact of these surgical treatments on sexual function, a critical aspect of patient quality of life often overlooked in BPH management. The methodology encompassed a thorough review of contemporary surgical techniques for BPH, including prostate resection, enucleation, vaporization, and minimally invasive therapies such as UroLift, Rezum, and Aquablation. Additionally, the focus was on patient-centered outcomes, with a special emphasis on sexual health following surgery. Findings reveal that, while surgical interventions effectively alleviate BPH symptoms, they often have significant repercussions in sexual function, including erectile and ejaculatory dysfunction. However, emerging techniques demonstrate potential in preserving sexual function, underscoring the need for patient-centric treatment approaches. The study highlights the complex interplay between BPH surgery and sexual health, with minimally invasive treatments showing promise in balancing symptom relief and sexual function preservation. In conclusion, the study advocates for an integrated, interdisciplinary approach to BPH treatment, emphasizing the importance of considering sexual health in therapeutic decision-making. This narrative review suggests a paradigm shift towards minimally invasive techniques could optimize patient outcomes, marrying symptom relief with quality-of-life considerations. The need for further research in this domain is evident, particularly in understanding long-term sexual health outcomes following different surgical interventions for BPH.

Supervised Pelvic Floor Muscle Training Improves Sexual Function and Diminishes Sexual Distress in Women with Relapsing-Remitting Multiple Sclerosis: A Randomised Controlled Study.

This study investigates the impact of pelvic floor muscle training (PFMT) on sexual function and distress in women with multiple sclerosis (MS), a prevalent chronic nervous system disorder associated with sexual dysfunction. This study's primary aim was to assess the effectiveness of PFMT at improving sexual function and alleviating sexual distress in this population. In a randomised controlled trial, 82 women with MS were divided into two groups: Group A (41 women) underwent 12 weeks of PFMT, while Group B (41 women) served as a control group with no intervention. Both groups were assessed at the beginning and end of this study using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R). Statistical analysis, including Chi-square tests, was employed to compare the outcomes between the two groups, with a p-value of less than 0.05 considered significant. The results revealed no significant differences in baseline sexual function and distress between the groups. However, at the conclusion of the 12-week period, Group A exhibited statistically significant improvements in nearly all domains of FSFI and FSDS-R compared to Group B, except in the pain domain. This study concludes that PFMT can effectively enhance sexual function and reduce sexual distress in women suffering from MS. These findings underscore the potential of PFMT as a therapeutic intervention in managing sexual dysfunction associated with MS.

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.

From Diagnosis to Treatment: Comprehensive Care by Reproductive Urologists in Assisted Reproductive Technology.

Infertility is a global health concern, with male factors playing an especially large role. Unfortunately, however, the contributions made by reproductive urologists in managing male infertility under assisted reproductive technology (ART) often go undervalued. This narrative review highlights the important role played by reproductive urologists in diagnosing and treating male infertility as well as any barriers they face when providing services. This manuscript presents a comprehensive review of reproductive urologists' role in managing male infertility, outlining their expertise in diagnosing and managing male infertility as well as reversible causes and performing surgical techniques such as sperm retrieval. This manuscript investigates the barriers limiting urologist involvement such as limited availability, awareness among healthcare professionals, and financial constraints. This study highlights a decrease in male fertility due to lifestyle factors like sedentary behavior, obesity, and substance abuse. It stresses the significance of conducting an evaluation process involving both male and female partners to identify any underlying factors contributing to infertility and to identify patients who do not require any interventions beyond ART. We conclude that engaging urologists more effectively in infertility management is key to optimizing fertility outcomes among couples undergoing assisted reproductive technology treatments and requires greater education among healthcare providers regarding the role urologists and lifestyle factors that could have an effect on male fertility.

Microbial Dysbiosis and Male Infertility: Understanding the Impact and Exploring Therapeutic Interventions.

The human microbiota in the genital tract is pivotal for maintaining fertility, but its disruption can lead to male infertility. This study examines the relationship between microbial dysbiosis and male infertility, underscoring the promise of precision medicine in this field. Through a comprehensive review, this research indicates microbial signatures associated with male infertility, such as altered bacterial diversity, the dominance of pathogenic species, and imbalances in the genital microbiome. Key mechanisms linking microbial dysbiosis to infertility include inflammation, oxidative stress, and sperm structural deterioration. Emerging strategies like targeted antimicrobial therapies, probiotics, prebiotics, and fecal microbiota transplantation have shown potential in adjusting the genital microbiota to enhance male fertility. Notably, the application of precision medicine, which customizes treatments based on individual microbial profiles and specific causes of infertility, emerges as a promising approach to enhance treatment outcomes. Ultimately, microbial dysbiosis is intricately linked to male infertility, and embracing personalized treatment strategies rooted in precision medicine principles could be the way forward in addressing infertility associated with microbial factors.

Evaluating the Predictive Value of Diagnostic Testicular Biopsy for Sperm Retrieval Outcomes in Men with Non-Obstructive Azoospermia.

BACKGROUND: Non-obstructive azoospermia (NOA) presents a challenge in male infertility management. This study aimed to assess the efficacy of diagnostic testicular biopsy (DTB) in predicting sperm retrieval success via therapeutic testicular biopsy (TTB) and to understand the role of systemic inflammation in microdissection testicular sperm extraction (mTESE) outcomes. METHODS: A retrospective analysis was conducted on 50 NOA males who underwent mTESE at the University of Ioannina's Department of Urology from January 2017 to December 2019. All participants underwent thorough medical evaluations, including semen analyses and endocrinological assessments. RESULTS: DTB did not detect spermatozoa in half of the patients who later showed positive sperm findings in TTB. Preoperative variables, such as age, plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), prolactin (PRL), estradiol (E2), and inflammation biomarkers (neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-eosinophil ratio (MER)), were not consistently predictive of sperm retrieval success. Notably, TTB-negative patients had elevated NLR and PLR values, suggesting a possible link between systemic inflammation and reduced sperm retrieval during mTESE. CONCLUSIONS: The findings question the necessity of an initial DTB, which might provide misleading results. A negative DTB should not deter further TTB or intracytoplasmic sperm injection (ICSI) attempts. The study emphasizes the need for further research to refine diagnostic approaches and deepen the understanding of factors influencing sperm retrieval in NOA patients, ultimately enhancing their prospects of biological parenthood.

COVID-19 and Male Infertility: Is There a Role for Antioxidants?

Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), jeopardizes male fertility because of the vulnerability of the male reproductive system, especially the testes. This study evaluates the effects of the virus on testicular function and examines the potential role of antioxidants in mitigating the damage caused by oxidative stress (OS). A comprehensive PubMed search examined exocrine and endocrine testicular function alteration, the interplay between OS and COVID-19-induced defects, and the potential benefit of antioxidants. Although the virus is rarely directly detectable in sperm and testicular tissue, semen quality and hormonal balance are affected in patients, with some changes persisting throughout a spermatogenesis cycle. Testicular pathology in deceased patients shows defects in spermatogenesis, vascular changes, and inflammation. Acute primary hypogonadism is observed mainly in severely infected cases. Elevated OS and sperm DNA fragmentation markers suggest redox imbalance as a possible mechanism behind the fertility changes. COVID-19 vaccines appear to be safe for male fertility, but the efficacy of antioxidants to improve sperm quality after infection remains unproven due to limited research. Given the limited and inconclusive evidence, careful evaluation of men recovering from COVID-19 seeking fertility improvement is strongly recommended.

The Silent Threat to Women's Fertility: Uncovering the Devastating Effects of Oxidative Stress.

Oxidative stress (OS), which arises through an imbalance between the formation of reactive oxygen species (ROS) and antioxidant defenses, plays a key role in the pathophysiology of female infertility, with the latter constituting just one of a number of diseases linked to OS as a potential cause. The aim of the present article is to review the literature regarding the association between OS and female infertility. Among the reproductive diseases considered are endometriosis and polycystic ovary syndrome (PCOS), while environmental pollutants, lifestyle variables, and underlying medical conditions possibly resulting in OS are additionally examined. Current evidence points to OS likely contributing to the pathophysiology of the above reproductive disorders, with the amount of damage done by OS being influenced by such variables as duration and severity of exposure and the individual's age and genetic predisposition. Also discussed are the processes via which OS may affect female fertility, these including DNA damage and mitochondrial dysfunction. Finally, the last section of the manuscript contains an evaluation of treatment options, including antioxidants and lifestyle modification, capable of minimizing OS in infertile women. The prime message underlined by this review is the importance of considering OS in the diagnosis and treatment of female infertility. Further studies are, nevertheless required to identify the best treatment regimen and its ideal duration.

Antioxidant Supplementation on Male Fertility-A Systematic Review.

Our aim was to review the current literature regarding the effect of antioxidant supplementation (AS) on male fertility parameters, as AS is commonly used to treat male infertility due to the availability and affordability of antioxidants in many parts of the world. MATERIALS AND METHODS: PubMed, Medline, and Cochrane electronic bibliographies were searched using the modified Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate studies on the benefit of antioxidant therapy on infertile men. Results were analyzed regarding the following aspects: (a) ingredient and dose; (b) potential mechanism of action and rationale for use; and (c) effect on various reported outcomes. RESULTS: Thus, 29 studies found a substantial positive effect of AS on outcomes of assisted reproductive therapy (ART), WHO semen parameters, and live-birth rate. Carnitines, Vitamin E and C, N-acetyl cysteine, coenzyme Q10, selenium, zinc, folic acid, and lycopene were beneficial ingredients. Nevertheless, some studies did not show a substantial change in one or more factors. CONCLUSION: AS seems to have a positive effect on male fertility. Environmental factors may play an increasing role in fertility. Further studies are needed to determine the optimal AS combination and the influence of environmental factors.

Controversy and Consensus on the Management of Elevated Sperm DNA Fragmentation in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. MATERIALS AND METHODS: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. RESULTS: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. CONCLUSIONS: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.

Telemedicine in Urology: Where Have We Been and Where Are We Heading?

Context: Humanity is facing significant challenges, and in 2019, a new coronavirus caused an unprecedented global disease outbreak. The coronavirus disease 2019 (COVID-19) pandemic vastly impacted health care delivery, generating devastating economic, social, and public health disruption. Although previously underutilized, it was not until recently that telemedicine emerged and amassed tremendous popularity. Objective: To examine and assess telemedicine's past, present, and future roles in urology. Evidence acquisition: We queried relevant literature investigating the role of telemedicine in urology using the electronic PubMed database and mainly focused on English-language studies of any design. Evidence synthesis: Growing attention has been paid to the widespread adoption of novel telehealth technologies for managing various diseases. Meanwhile, solid evidence supports the meaningful use of telemedicine for most urological diagnoses. Existing literature delineates telemedicine as a viable, safe, and convenient alternative to in-person clinical visits. Conclusions: The present article overviews the evolution of telemedicine in urology, and discusses its application in outpatient and physician's office settings. In addition, it highlights the technical, legal, ethical, and financial aspects of telemedicine while providing valuable insights and practical considerations for the future of telehealth in urology. Patient summary: Urologists must adopt telemedicine carefully in daily practice, always adhering to predefined regulatory frameworks.

Impact of Advanced Paternal Age on Fertility and Risks of Genetic Disorders in Offspring.

The average age of fathers at first pregnancy has risen significantly over the last decade owing to various variables, including a longer life expectancy, more access to contraception, later marriage, and other factors. As has been proven in several studies, women over 35 years of age have an increased risk of infertility, pregnancy problems, spontaneous abortion, congenital malformations, and postnatal issues. There are varying opinions on whether a father's age affects the quality of his sperm or his ability to father a child. First, there is no single accepted definition of old age in a father. Second, much research has reported contradictory findings in the literature, particularly concerning the most frequently examined criteria. Increasing evidence suggests that the father's age contributes to his offspring's higher vulnerability to inheritable diseases. Our comprehensive literature evaluation shows a direct correlation between paternal age and decreased sperm quality and testicular function. Genetic abnormalities, such as DNA mutations and chromosomal aneuploidies, and epigenetic modifications, such as the silencing of essential genes, have all been linked to the father's advancing years. Paternal age has been shown to affect reproductive and fertility outcomes, such as the success rate of in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and premature birth rate. Several diseases, including autism, schizophrenia, bipolar disorders, and paediatric leukaemia, have been linked to the father's advanced years. Therefore, informing infertile couples of the alarming correlations between older fathers and a rise in their offspring's diseases is crucial, so that they can be effectively guided through their reproductive years.

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.

Impact of Varicocele Repair on Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis.

PURPOSE: Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls. MATERIALS AND METHODS: A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies). RESULTS: A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; p<0.001; I²=97.6%), total sperm count (SMD 1.894; 95% CI 0.566 to 3.222; p<0.05; I²=97.8%), progressive sperm motility (SMD 3.301; 95% CI 2.164 to 4.437; p<0.01; I²=98.5%), total sperm motility (SMD 0.887; 95% CI 0.036 to 1.738; p=0.04; I²=97.3%) and normal sperm morphology (SMD 1.673; 95% CI 0.876 to 2.470; p<0.05; I²=98.5%). All the outcomes showed a high inter-study heterogeneity, but the sensitivity analysis showed that no study was sensitive enough to change these results. Publication bias was present only in the analysis of the sperm concentration and progressive motility. No significant difference was found for the semen volume (SMD 0.313; 95% CI -0.242 to 0.868; I²=89.7%). CONCLUSIONS: This study provides a high level of evidence in favor of a positive effect of VR to improve conventional semen parameters in infertile men with clinical varicocele. To the best of our knowledge, this is the first SRMA to compare changes in conventional semen parameters after VR with changes in parameters of a control group over the same period. This is in contrast to other SRMAs which have compared semen parameters before and after VR, without reference to a control group. Our findings strengthen the available evidence and have a potential to upgrade professional societies' practice recommendations favoring VR to improve conventional semen parameters in infertile men.

Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations.

PURPOSE: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. MATERIALS AND METHODS: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. RESULTS: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. CONCLUSIONS: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

Synchronous bilateral testicular cancer with discordant histopathology occurring in a 20-year-old patient: A case report and review of the literature.

INTRODUCTION: Bilateral testicular tumors are very rare, accounting for 1%-5% of all testicular germ-cell tumors (TGCTs). The vast majority of primary bilateral TGCTs are metachronous, with synchronous tumors comprising approximately 0.5%-1% of all cases. Those occurring synchronously share mostly the same histological pattern, predominantly seminoma, with synchronous bilateral TGCTs (SBTGCTs) with discordant subtypes being extremely rare. CASE PRESENTATION: We present the case of a 20-year-old male complaining of a palpable painless right testicular mass incidentally noticed during sexual intercourse. Ultrasonography (US) and magnetic resonance imaging (MRI) of the scrotum demonstrated bilateral testicular lesions, while staging with contrast-enhanced computed tomography (CT) exhibited normal findings. Right radical orchiectomy and left testis-sparing surgery (TSS) with concomitant onco-testicular sperm extraction (onco-TESE) were initially performed. Histology of the right testis revealed a mixed germ-cell tumor, consisting of seminoma and embryonal carcinoma, while that from the left testis disclosed embryonal carcinoma and intratubular germ-cell neoplasia unclassified (IGCNU) infiltrating the surgical margins. Hence, left orchiectomy was subsequently scheduled with histology unveiling IGCNU in the greatest part of the remaining testicular parenchyma. Following adjuvant chemotherapy, with bleomycin, etoposide, and cisplatin (BEP), the patient received testosterone replacement therapy and remained free of recurrence at an 18-month follow-up. CONCLUSION: This case highlights both the rarity of a bilateral testicular tumor's synchronous appearance and its extremely infrequent discordant histopathology. A comprehensive review of the major series of SBTGCTs with discordant histology cited in the literature is additionally presented.