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.

A clinical guide to rare male sexual disorders.

Conditions referred to as 'male sexual dysfunctions' usually include erectile dysfunction, ejaculatory disorders and male hypogonadism. However, some less common male sexual disorders exist, which are under-recognized and under-treated, leading to considerable morbidity, with adverse effects on individuals' sexual health and relationships. Such conditions include post-finasteride syndrome, restless genital syndrome, post-orgasmic illness syndrome, post-selective serotonin reuptake inhibitor (SSRI) sexual dysfunction, hard-flaccid syndrome, sleep-related painful erections and post-retinoid sexual dysfunction. Information about these disorders usually originates from case-control trials or small case series; thus, the published literature is scarce. As the aetiology of these diseases has not been fully elucidated, the optimal investigational work-up and therapy are not well defined, and the available options cannot, therefore, adequately address patients' sexual problems and implement appropriate treatment. Thus, larger-scale studies - including prospective trials and comprehensive case registries - are crucial to better understand the aetiology, prevalence and clinical characteristics of these conditions. Furthermore, collaborative efforts among researchers, health-care professionals and patient advocacy groups will be essential in order to develop evidence-based guidelines and novel therapeutic approaches that can effectively address these disorders. By advancing our understanding and refining treatment strategies, we can strive towards improving the quality of life and fostering healthier sexual relationships for individuals suffering from these rare sexual disorders.

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.

Surgical treatment of premature ejaculation: a narrative review.

Recurrence after drug cessation is the biggest drawback of medical premature ejaculation (PE) treatments. Although these treatments are demonstrated to be safe and effective, most of the PE patients are interested in a more permanent solution. Despite the fact that currently available guidelines do not recommend surgical treatment for PE, some surgical interventions have been commonly performed for many years, especially in the Asian countries. The main purpose of these surgical treatments is to decrease the sensitivity of the glans penis. However, they are associated with irreversible complications such as penile deformity, sensory loss and erectile dysfunction. The aim of this narrative review is to summarize the advantages and disadvantages of various surgical interventions introduced for the treatment of PE. PubMed, Scopus and Web of Science have been utilized to search articles about glans penis augmentation and penile dorsal nerve interventions. A total of 11 articles were included, three articles excluded because they were in non-English languages. Glans penis augmentation offered a less invasive treatment that avoids severe side effects but requires retreatment in time. Selective dorsal neurectomy provided a more invasive but curative treatment alternative. However, more clinical data are necessary before surgical treatment options can be recommended to patients with PE.

European Association of Urology Guidelines on Penile Size Abnormalities and Dysmorphophobia: Summary of the 2023 Guidelines.

CONTEXT: Recommendations regarding the management of penile size abnormalities and dysmorphophobia are important in guiding evidence-based clinical practice. OBJECTIVE: To present a summary of the 2023 European Association of Urology sexual and reproductive health evidence-based recommendations for the management of penile size abnormalities and dysmorphophobia. EVIDENCE ACQUISITION: A broad and comprehensive scoping exercise covering all areas of the guidelines was performed. Databases searched included Medline, EMBASE, and the Cochrane Libraries. A level of evidence and a strength of recommendation were assigned for each recommendation according to the evidence identified. The evidence cutoff date for the 2023 guidelines is June 1, 2022. EVIDENCE SYNTHESIS: Well-structured studies reporting high level of evidence, with standardized PROMS were deficient on penile size abnormalities and dysmorphohobia. A shared definition for short penis/micropenis was also lacking. Categorisation of penile abnormalities according to congenital, acquired, and dysmorphophobic aetiology is deemed compulsory. A detailed medical and psychosexual history and precise measurements of penile size are essential in the diagnostic pathway. Patients with normal penile size who are seeking penile augmentation should be referred for psychological evaluation for potential dysmorphophobic disorders. Penile length and girth enhancements can be achieved via a multitude of treatments, but a personalised management plan is crucial for satisfactory results. Endocrinological therapies, when indicated, are effective in the prepubertal setting only. Vacuum therapy has a limited evidence base in treatment protocols, although acceptable outcomes have been reported for penile traction therapy. Surgical techniques to enhance penile length and girth have limited evidence and should only be proposed after extensive patient counselling. CONCLUSIONS: Management of penile abnormalities and dysmorphophobia is a complex issue with considerable ethical concerns. The adoption of a structured diagnostic and therapeutic pathway is crucial, as recommended in the guidelines. PATIENT SUMMARY: Requests for medical/surgical treatments to increase penis size have increased dramatically worldwide. Several conservative and surgical treatments are available. However, few patients receive clear information on the benefits and possible harms of these treatments. These guidelines aim to provide a structured path to guide both physicians and patients in the selection of appropriate treatment(s) to increase penis size.

Recognition and practice patterns of sexual medicine experts towards postorgasmic illness syndrome.

Post-orgasmic illness syndrome (POIS) is a rare, but debilitating cluster of symptoms, occurring after ejaculation with unknown mechanism and uncertain treatment. To the best of our knowledge, this study, which is thought to be the first in the literature, is aimed to investigate the practice patterns of sexual medicine experts towards POIS. Worldwide sexual medicine experts were invited to participate anonymously in an online, open survey using SurveyMonkey between November 14, 2022, and January 15, 2023. In total 211 sexual medicine experts filled the survey. The majority of the participants were urologists (83.9%). Most participants stated that the available information about POIS was inadequate for both patients and physicians. 47.9% of the participants stated psychological disorder, 46.4% stated bio-psycho-social reasons for the responsibility for the pathophysiology of POIS. 56.4% of the participants stated that they would refer the patient for psychotherapy/sexual therapy to a sexologist, 41.7% would prefer antihistamine drugs to manage symptoms. Only 18% of participants reported symptom improvement in more than 30% of the patients. This survey study among sexual medicine experts from different parts of the world has developed representative estimates of knowledge, attitudes and practice patterns regarding POIS worldwide.

Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. MATERIALS AND METHODS: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. RESULTS: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. CONCLUSIONS: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

A novel on-demand therapy for lifelong premature ejaculation using a miniature transperineal electrical stimulator-the vPatch: an as-treated analysis.

BACKGROUND: While premature ejaculation (PE) is a common and disturbing sexual dysfunction in men, current available treatment modalities have limited efficacy and low treatment adherence. AIM: To assess the feasibility, safety, and efficacy of the vPatch, a miniaturized on-demand perineal transcutaneous electrical stimulation device for treating PE. METHODS: This prospective bicenter international first-in-human clinical study consisted of 2 arms, was sham controlled, and had a randomized double-blind design. In terms of statistical power calculation, 59 patients aged 21 to 56 years (mean ± SD, 39.8 ± 9.28) with lifelong PE were included. During the initial visit, intravaginal ejaculatory latency time (IELT) was measured over a 2-week run-in period. Eligibility was confirmed in visit 2, based on IELT values, medical and sexual history, and patients' individualized sensory and motor activation thresholds during perineal stimulation with the vPatch. Patients were randomized to the active (vPatch) and sham device groups in a 2:1 ratio, respectively. The vPatch device's safety profile was determined by comparing the incidence of treatment-emergent adverse events. During visit 3, IELTs, Clinical Global Impression of Change scores, and Premature Ejaculation Profile questionnaire outcomes were recorded. Primary end points assessed vPatch device efficacy as mean change in geometric mean IELT; each person was compared with himself, with and without the device, and the sham group was compared with the active group. OUTCOMES: Outcomes included changes in IELT and Premature Ejaculation Profile before and after treatment, last visit Clinical Global Impression of Change scores, and vPatch safety profile. RESULTS: Of 59 patients, 51 completed the study: 34 in the active group and 17 in the sham group. The baseline geometric mean IELT significantly increased from 67 to 123 seconds (P < .01) in the active group, as compared with an insignificant increase from 63 to 81 seconds (P = .17) in the sham group. The increase in mean IELT in the active group was significantly higher than in the sham group (56 vs 18 seconds, P = .01). IELT significantly increased by 3.1 times in the active vs sham group. The mean ratio of fold change (active:sham) was 1.4, significantly different from 1.0 (P = .02). No serious adverse events were reported. CLINICAL IMPLICATIONS: Therapeutic use of the vPatch during coitus may become an on-demand, noninvasive, and drug-free treatment for PE. STRENGTHS AND LIMITATIONS: To our knowledge, this is the first rigorous study investigating whether transcutaneous electrical stimulation during coitus could improve the symptoms of men with lifelong PE. The study is limited by the small number of patients, the exclusion of patients with acquired PE, the short-term follow up, and the use of a device based on a theoretic mechanism of action. CONCLUSION: We demonstrated the possibility to treat lifelong PE by prolonging coitus on demand, using electric stimulation of ejaculation muscles with the vPatch.Clinical trial registration: NCT03942367 (ClinicalTrials.gov).

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.

The effect of penis size on partner sexual satisfaction: a literature review.

Larger penis size has been associated with a sign of strength, masculinity, and social standing. Little study has examined the relationship between men's penis size and their partners' sexual satisfaction. The purpose of the present study was to detail and evaluate the effect of penis size on partner sexual satisfaction with a design of narrative literature review. A systematic search of MEDLINE/PubMed was conducted to discover relevant studies on this issue. Currently, available studies show incomplete results between the penis size and partners' sexual satisfaction and are limited by methodological drawbacks, including small sample's size. The link between penis size and the sexual satisfaction of the partner need to be supported by more robust scientific evidence.

Depictions of penises in historical paintings reflect changing perceptions of the ideal penis size.

OBJECTIVES: To investigate alterations in depicted penis size by evaluating nude male paintings from the 15th to 21st centuries. MATERIALS AND METHODS: Nude-male paintings were identified from various art history websites and analysed to determine changes in penis size over time. Two observers organised the paintings according to the century in which they were created and made the calculations. Penile length to ear length (PtEL) or penile length to nose length (PtNL) were calculated to standardise the measurements using professional image analysis software. PtEL was first attempted for all paintings; if PtEL could not be ascertained, then nose length was used instead of the ear, as the nose length is defined as equal to ear length according to the golden ratio. Thus, PtNL was ensured and both ratios were then referred to using a common term: penis depiction ratio (PDR). Further analysis was performed by dividing the paintings into three groups according to the historical development of art: Renaissance Period (1400-1599; 15th-16th centuries), Baroque-Rococo and Impressionism Period (1600-1899; 17th-19th centuries) and Contemporary Art Period (1900-2020; 20th and 21st centuries). RESULTS: Of 232 identified paintings, 72 (31.1%) were excluded because they depicted images of adolescents or an erect penis. The PDR was found to differ significantly between paintings created in different centuries (P < 0.001). Subgroup analysis revealed that paintings from the 21st century demonstrated significantly higher PDRs than paintings from previous centuries (P = 0.001). CONCLUSIONS: In paintings depicting nude males, the size of the penis has gradually increased throughout the past seven centuries, and especially after the 20th century. This observation illustrates the changing sociocultural inputs into male body image and emphasises the need for improved understanding of the sociocultural factors associated with the perception of penis size in 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.

Current and emerging treatment options for premature ejaculation.

Premature ejaculation (PE) is a prevalent male sexual dysfunction. Current standard treatment regimens include behavioural therapies, topical anaesthetics, dapoxetine and other selective serotonin reuptake inhibitors (SSRIs). Most of the pharmacotherapeutic options target neurotransmitters (such as serotonin and oxytocin) that have a role in the ejaculation mechanism. However, these treatments are mildly effective and only provide a temporary delay in the ejaculation latency time, and PE recurs when the treatment is stopped. Thus, a treatment for PE is urgently needed and research is ongoing to find the ideal PE therapy. The efficacy and safety of topical anaesthetics and SSRIs in delaying ejaculation have been confirmed in many well-designed controlled trials. Both preclinical and clinical studies on new-generation SSRIs are ongoing. Moreover, promising results came from clinical trials in which the efficacy of on-demand PE therapies targeting neurotransmitters other than serotonin, such as α1-adrenoceptor antagonists and oxytocin antagonists, was assessed. Surgical intervention and neuromodulation have been proposed as potential treatment options for PE; however, current PE guidelines do not recommend these treatments owing to safety concerns.

Conservative and medical treatments of non-sickle cell disease-related ischemic priapism: a systematic review by the EAU Sexual and Reproductive Health Panel.

Conservative and medical treatments are considered the first step in ischemic priapism (IP) management, although there is no clear evidence regarding their efficacy. We conducted a systematic review on behalf of the EAU Guidelines panel on Sexual and Reproductive health to analyse the available evidence on the efficacy and safety of conservative and medical treatment for non-sickle cell disease-related IP. Databases searched for relevant literature investigating efficacy and safety of conservative measures and medical treatment for IP included Medline, EMBASE, Cochrane Libraries and clinicaltrial.gov published up to September 2021. Overall, 41 retrospective, 3 prospective single-arm studies and 3 randomized controlled trials met the inclusion criteria. Intracavernous injection with sympathomimetic (ICIs) agents were the most frequently utilized treatment with efficacy ranging from 0 to 100% of cases. The combination of ICIs with corporeal aspiration with or without irrigation with saline was successful in 70 to 100% of cases. Oral treatment with ß2 receptor agonist (e.g., terbutaline) showed mild to moderate efficacy. Conservative methods including ice pack, exercise, cold enema and ejaculation depicted lower effectiveness in resolving priapism (1-55%). Longer time interval from the onset to the resolution of IP was associated with higher rate of erectile dysfunction at follow-up (30-70%), especially after 24 h.

A novel method for hemodynamic analysis of penile erection.

Measurement of blood flow velocity through the cavernosal arteries via penile color Doppler ultrasound (PDUS) is the most common objective method for the assessment of erectile function. However, in some clinical cases, this method needs to be augmented via the invasive intracavernosal pressure (ICP) measurement, which is arguably a more direct index for erectile function. The aim of this study is to develop a lumped parameter model (LPM) of the penile circulation mechanism integrated to a pulsatile, patient-specific, bi-ventricular circulation system to estimate ICP values non-invasively. PDUS data obtained from four random patients with erectile dysfunction are used to develop patient-specific LPMs. Cardiac output is estimated from the body surface area. Systemic pressure is obtained by a sphygmomanometer. Through the appropriate parameter set determined by optimization, patient-specific ICP values are predicted with only using PDUS data and validated by pre- and post-papaverine injection cavernosometry measurements. The developed model predicts the ICP with an average error value of 3 mmHg for both phases. Penile size change during erection is predicted with a ~15% error, according to the clinical size measurements. The developed mathematical model has the potential to be used as an effective non-invasive tool in erectile function evaluation, expanding the existing clinical decision parameters significantly.

Is there a line between ethics and market competition? Lights and shades of the withdrawal of collagenase treatment for Peyronie's disease.

Peyronie's disease treatments is changing again due the interruption of Xiapex® distrubution in Europe. There are many reasons that can be referred to this event. In this editorial we would like to shed light on the current cost items relating to treatment with collagenase clostridium histolyticum (CCH). The inaccessibility of the drug has seen both an increase in surgery for the treatments of both PD and Dupuytren's disease and an interruption of therapies in patients who had not completed their therapeutic cycle. Considering the aforementioned concerns, we would like to invite researchers dealing with PD to conduct studies with the available CCH products in collaboration with the drug companies in order to give again an efficacious treatment for PD.

European Association of Urology Guidelines Panel on Male Sexual and Reproductive Health: A Clinical Consultation Guide on the Indications for Performing Sperm DNA Fragmentation Testing in Men with Infertility and Testicular Sperm Extraction in Nonazoospermic Men.

Accumulating evidence has highlighted the contribution of oxidative stress and sperm DNA fragmentation (SDF) in the pathophysiology of male infertility. SDF has emerged as a novel biomarker of risk stratification for patients undergoing assisted reproductive technologies. Studies have also supported the use of testicular over ejaculated sperm at the time of intracytoplasmic sperm injection, as testicular sperm may have lower SDF than ejaculated samples. The European Association of Urology Working Panel on Male Sexual and Reproductive Health provides an evidence-based consultation guide on the indications for SDF testing in male infertility and also for testicular sperm extraction (TESE) in nonazoospermic men. We present the limitations and advantages of SDF testing and a framework to ensure that it is appropriately utilised in clinical practice. Furthermore, we critically appraise the current literature advocating the use of TESE in nonazoospermic men. PATIENT SUMMARY: This article reviews the evidence supporting the use of sperm DNA fragmentation testing in the assessment of male infertility and testicular sperm extraction in nonazoospermic men.

European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2021 Update on Male Infertility.

CONTEXT: The European Association of Urology (EAU) has updated its guidelines on sexual and reproductive health for 2021. OBJECTIVE: To present a summary of the 2021 version of the EAU guidelines on sexual and reproductive health, including advances and areas of controversy in male infertility. EVIDENCE ACQUISITION: The panel performed a comprehensive literature review of novel data up to January 2021. The guidelines were updated and a strength rating for each recommendation was included that was based either on a systematic review of the literature or consensus opinion from the expert panel, where applicable. EVIDENCE SYNTHESIS: The male partner in infertile couples should undergo a comprehensive urological assessment to identify and treat any modifiable risk factors causing fertility impairment. Infertile men are at a higher risk of harbouring and developing other diseases including malignancy and cardiovascular disease and should be screened for potential modifiable risk factors, such as hypogonadism. Sperm DNA fragmentation testing has emerged as a novel biomarker that can identify infertile men and provide information on the outcomes from assisted reproductive techniques. The role of hormone stimulation therapy in hypergonadotropic hypogonadal or eugonadal patients is controversial and is not recommended outside of clinical trials. Furthermore, there is insufficient evidence to support the widespread use of other empirical treatments and surgical interventions in clinical practice (such as antioxidants and surgical sperm retrieval in men without azoospermia). There is low-quality evidence to support the routine use of testicular fine-needle mapping as an alternative diagnostic and predictive tool before testicular sperm extraction (TESE) in men with nonobstructive azoospermia (NOA), and either conventional or microdissection TESE remains the surgical modality of choice for men with NOA. CONCLUSIONS: All infertile men should undergo a comprehensive urological assessment to identify and treat any modifiable risk factors. Increasing data indicate that infertile men are at higher risk of cardiovascular mortality and of developing cancers and should be screened and counselled accordingly. There is low-quality evidence supporting the use of empirical treatments and interventions currently used in clinical practice; the efficacy of these therapies needs to be validated in large-scale randomised controlled trials. PATIENT SUMMARY: Approximately 50% of infertility will be due to problems with the male partner. Therefore, all infertile men should be assessed by a specialist with the expertise to not only help optimise their fertility but also because they are at higher risk of developing cardiovascular disease and cancer long term and therefore require appropriate counselling and management. There are many treatments and interventions for male infertility that have not been validated in high-quality studies and caution should be applied to their use in routine clinical practice.