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.

Does Testicular Sperm Improve Intracytoplasmic Sperm Injection Outcomes for Nonazoospermic Infertile Men with Elevated Sperm DNA Fragmentation? A Systematic Review and Meta-analysis.

CONTEXT: For nonazoospermic infertile men with elevated sperm DNA fragmentation (SDF), it is unclear whether the use of testicular sperm for intracytoplasmic sperm injection (ICSI) may offer advantages over ejaculated sperm. OBJECTIVE: To determine whether ICSI outcomes (fertilisation rate, pregnancy rate, miscarriage rate, and live birth rate) are better with testicular sperm than with ejaculated sperm for men with elevated SDF. EVIDENCE ACQUISITION: We searched the Cochrane Central, EMBASE, MEDLINE, Web of Science, and Scopus databases (1946-2023) in February 2023 for relevant human comparative studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. EVIDENCE SYNTHESIS: Out of 2032 records, nine studies (more than 536 participants, mean age range 33-40.5 yr for males and 30.1-37.9 yr for females) were included in the systematic review and meta-analysis. Pooled estimates demonstrated that the pregnancy rate was significantly higher with testicular than with ejaculated sperm according to a sperm chromatin structure assay (SCSA)/sperm chromatin integrity test (SCIT) (odds ratio [OR] 2.51; p = 0.001) and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assays (OR 3.65; p = 0.005). The live birth rate was significantly higher according to SCSA/SCIT (OR 2.59; p = 0.005). There were no significant differences in the fertilisation rate or miscarriage rate. CONCLUSIONS: Although significant improvements in pregnancy and live birth rates were observed with testicular sperm, the strength of findings is limited by availability and quality of evidence, both of which undermine recommendations for clinical practice. Standardised randomised controlled trials are needed to definitively determine whether the use of testicular sperm improves ISCI outcomes for men with high SDF. Until such evidence exists, ICSI after testicular sperm extraction or aspiration should not be routinely performed. PATIENT SUMMARY: Our review showed that for infertile men with a high level of DNA damage in their sperm, use of sperm extracted from the testicles may give better results than ejaculated sperm for a particular IVF (in vitro fertilisation) technique. However, there is a lack of high-quality data.

Strategies in Infertile Azoospermic Patients with Negative Microdissection Testicular Sperm Extraction Surgery.

Non-obstructive azoospermia is reported to affect 1 in 100 men, and despite advances in surgical practice, the succesful sperm retrieval rate for microdissection testicular sperm extraction surgery (mTESE) is only 46%. This article reviews the potential causes for mTESE failure and provides a management strategy to guide the clinicians on how to treat this challenging cohort of patients.

The use of hormone stimulation in male infertility.

Infertility affects 15% of couples worldwide and in approximately 50% of cases the cause is secondary to an abnormality of the sperm. However, treatment options for male infertility are limited and empirical use of hormone stimulation has been utilised. We review the contemporary data regarding the application of hormone stimulation to treat male infertility. There is strong evidence supporting the use of hormone stimulation in hypogonadotropic hypogonadism but there is inadequate evidence for all other indications.

The management of erectile dysfunction in men with diabetes mellitus unresponsive to phosphodiesterase type 5 inhibitors.

INTRODUCTION: Erectile dysfunction is associated with diabetes mellitus with an estimated prevalence of 52.5% in the diabetic population. The first-line therapy for erectile dysfunction is phosphodiesterase type 5 inhibitors, but data suggest that diabetic men may be less responsive than non-diabetic men. Thus, other treatments, including intracavernosal injections, intraurethral prostaglandin, vacuum erection devices and penile prosthetic surgery, should be considered in management of diabetic men with erectile dysfunction refractory to phosphodiesterase type 5 inhibitors. Furthermore, combination therapy of phosphodiesterase type 5 inhibitors and other oral treatments such as arginine or l-carnitine may have synergistic effects resulting in better outcomes. In addition, there are novel therapies such as low-intensity shockwave therapy and stem-cell therapy, which may also be effective in targeted treatment modalities. Furthermore, studies suggest that erectile dysfunction can be improved by targeting concurrent comorbidities or metabolic diseases such as depression, hypertension, hypogonadism, and dyslipidaemia. We present an evidence-based narrative review focusing on the management of erectile dysfunction in diabetic men who have not responded to phosphodiesterase type 5 inhibitors. CONCLUSIONS: Both clinicians and patients should be aware of the different management options in diabetic patients who have not responded to phosphodiesterase type 5 inhibitors.

Radiological features characterising indeterminate testes masses: a systematic review and meta-analysis.

CONTEXT: The use of scrotal ultrasonography (SUS) has increased the detection rate of indeterminate testicular masses. Defining radiological characteristics that identify malignancy may reduce the number of men undergoing unnecessary radical orchidectomy. OBJECTIVE: To define which SUS or scrotal magnetic resonance imaging (MRI) characteristics can predict benign or malignant disease in pre- or post-pubertal males with indeterminate testicular masses. EVIDENCE ACQUISITION: This systematic review was conducted in accordance with Cochrane Collaboration guidance. Medline, Embase, Cochrane controlled trials and systematic reviews databases were searched from (1970 to 26 March 2021). Benign and malignant masses were classified using the reported reference test: i.e., histopathology, or 12 months progression-free radiological surveillance. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). EVIDENCE SYNTHESIS: A total of 32 studies were identified, including 1692 masses of which 28 studies and 1550 masses reported SUS features, four studies and 142 masses reported MRI features. Meta-analysis of different SUS (B-mode) values in post-pubertal men demonstrated that a size of ≤0.5 cm had a significantly lower odds ratio (OR) of malignancy compared to masses of >0.5 cm (P < 0.001). Comparison of masses of 0.6-1.0 cm and masses of >1.5 cm also demonstrated a significantly lower OR of malignancy (P = 0.04). There was no significant difference between masses of 0.6-1.0 and 1.1-1.5 cm. SUS in post-pubertal men also had a statistically significantly lower OR of malignancy for heterogenous masses vs homogenous masses (P = 0.04), hyperechogenic vs hypoechogenic masses (P < 0.01), normal vs increased enhancement (P < 0.01), and peripheral vs central vascularity (P < 0.01), respectively. There were limited data on pre-pubertal SUS, pre-pubertal MRI and post-pubertal MRI. CONCLUSIONS: This meta-analysis identifies radiological characteristics that have a lower OR of malignancy and may be of value in the management of the indeterminate testis mass.

Investigating the therapeutic options for diabetes-associated male infertility as illustrated in animal experimental models.

Diabetes is a rising global health concern and an increasingly common cause of male infertility. Although the definitive pathophysiological mechanisms underpinning the association between diabetes and infertility is unclear, there are several animal studies showing diabetes to be a detrimental factor on reproductive health through apoptosis, oxidative stress and impairment of steroidogenesis. Furthermore, as reflected in animal models, antidiabetic strategies and relevant treatments are beneficial in the management of infertile men with diabetes as the recovery of euglycemic status affects positively the spermatogenesis. However, the available data are still evolving and specific conclusion in human populations are not possible yet. In this review, we are discussing the current literature concerning the association of diabetes and male infertility, focusing on the therapeutic approach as illustrated in animals' models.

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.

Novel androgen therapies including selective androgen receptor modulators.

Male hypogonadism is associated with reduced quality of life and the development of co-morbidities including obesity, diabetes mellitus, and dyslipidaemia. The mainstay of treatment for male hypogonadism is testosterone replacement therapy (TRT). However, TRT has recognised side effects including impaired spermatogenesis and there are concerns regarding its use in men with concurrent cardiovascular disease. Thus, there has been an impetus to develop novel androgen therapies for treating male hypogonadism to mitigate the side effects of TRT. This review will discuss the benefits and adverse effects of TRT, and novel therapies including nasal testosterone, aromatase inhibitors, selective oestrogen receptor modulators, and selective androgen receptor modulators.

Understanding and managing the suppression of spermatogenesis caused by testosterone replacement therapy (TRT) and anabolic-androgenic steroids (AAS).

Use of testosterone replacement therapy (TRT) and anabolic-androgenic steroids (AAS) has increased over the last 20 years, coinciding with an increase in men presenting with infertility and hypogonadism. Both agents have a detrimental effect on spermatogenesis and pose a clinical challenge in the setting of hypogonadism and infertility. Adding to this challenge is the paucity of data describing recovery of spermatogenesis on stopping such agents. The unwanted systemic side effects of these agents have driven the development of novel agents such as selective androgen receptor modulators (SARMs). Data showing natural recovery of spermatogenesis following cessation of TRT are limited to observational studies. Largely, these have shown spontaneous recovery of spermatogenesis after cessation. Contemporary literature suggests the time frame for this recovery is highly variable and dependent on several factors including baseline testicular function, duration of drug use and age at cessation. In some men, drug cessation alone may not achieve spontaneous recovery, necessitating hormonal stimulation with selective oestrogen receptor modulators (SERMs)/gonadotropin therapy or even the need for assisted reproductive techniques. However, there are limited prospective randomized data on the role of hormonal stimulation in this clinical setting. The use of hormonal stimulation with agents such as gonadotropins, SERMs, aromatase inhibitors and assisted reproductive techniques should form part of the counselling process in this cohort of hypogonadal infertile men. Moreover, counselling men regarding the detrimental effects of TRT/AAS on fertility is very important, as is the need for robust randomized studies assessing the long-term effects of novel agents such as SARMs and the true efficacy of gonadotropins in promoting recovery of spermatogenesis.

Does hormonal therapy improve sperm retrieval rates in men with non-obstructive azoospermia: a systematic review and meta-analysis.

BACKGROUND: The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates. OBJECTIVE AND RATIONALE: The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men. SEARCH METHODS: A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated. OUTCOMES: A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias. WIDER IMPLICATIONS: This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings.

Safety of androgen therapy in men with prostate cancer.

Prostate cancer is one of the most frequently diagnosed malignancies in men worldwide and the life expectancy for men with prostate cancer is improving due to advancements in diagnostics and treatment. Male hypogonadism is associated with obesity, diabetes, and other comorbidities and also has been linked with increasing age; the primary therapy modality for this condition is testosterone replacement therapy (TRT). There are concerns that testosterone therapy may cause prostate cancer disease progression. However, contemporary evidence suggests that testosterone replacement therapy may be safe in specific groups of patients with prostate cancer. This chapter will summarise the contemporary literature regarding TRT use in hypogonadal men with prostate cancer, including limitations and future research goals.

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.

Are sex disparities in COVID-19 a predictable outcome of failing men's health provision?

The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has taken a catastrophic toll on society, health-care systems and the economy. Notably, COVID-19 has been shown to be associated with a higher mortality rate in men than in women. This disparity is likely to be a consequence of a failure to invest in men's health, as it has also been established that men have a lower life expectancy and poorer outcomes from non-communicable diseases than women. A variety of biological, social and economic factors have contributed to the sex disparities in mortality from COVID-19. A streamlined men's health programme - with the urologist as the gatekeeper of men's health - is needed to help prevent future tragedies of this nature.

The relationship between genitourinary microorganisms and oxidative stress, sperm DNA fragmentation and semen parameters in infertile men.

An imbalance in the genitourinary microbiome is emerging as a contributing factor to male infertility. The purpose of this study was to determine whether there is an association between genitourinary microorganisms and seminal oxidative stress, sperm DNA fragmentation and semen parameters. It included 770 men attending for diagnostic testing for subfertility. Genitourinary microorganisms were identified in 43.0% men; 20.1% had microorganisms in semen; 18.7% in urine; and 5.8% had microorganisms in urine and semen. Enterococcus faecalis was the most prevalent organism in semen (22.0% samples; 61.5% organisms) with Ureaplasma spp. (16.9% samples; 53.3% organisms) and Gardnerella vaginalis (11.4% samples; 37.4% organisms) most prevalent in urine. Semen parameters were unaffected by microorganisms (p > 0.05). Seminal ROS were significantly higher in men with microorganisms compared to those without (p < 0.001), particularly when present in both urine and semen (p < 0.01). Microorganisms were associated with significantly higher DNA fragmentation, irrespective of whether they were in semen or urine (p < 0.001). An imbalance in the genitourinary microbiome is associated with DNA damage and oxidative stress which may have considerable consequences for achieving an ongoing pregnancy. This highlights the need for incorporating genitourinary microorganism screening for all men as part of diagnostic evaluation prior to undergoing treatment for infertility.

Penile implant surgery-managing complications.

Penile prosthesis surgery represents the end-stage treatment for erectile dysfunction. It is conventionally used only in cases of erectile dysfunction refractory to pharmacological treatments or vacuum constriction devices. Contemporary literature suggests that penile prothesis surgery is associated with a high satisfaction rate and a low complication profile. However, it must be appreciated that the complications of surgery can have devastating consequences on a patient's quality of life and satisfaction and include infection, prosthesis malfunction, penile corporal perforation and penile length loss. Several factors - such as appropriate patient selection, methodical preoperative assessment and patient optimization, specific intraoperative protocols and postoperative recommendations - can reduce the risk of surgical complications. This narrative review discusses the diagnosis and management of both intraoperative and postoperative complications of penile prosthesis surgery.

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.

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

CONTEXT: The present summary of the European Association of Urology (EAU) guidelines is based on the latest guidelines on male sexual health published in March 2021, with a last comprehensive update in January 2021. OBJECTIVE: To present a summary of the 2021 version of the EAU guidelines on sexual and reproductive health. EVIDENCE ACQUISITION: A literature review was performed up to January 2021. The guidelines were updated, and a strength rating for each recommendation was included based on either a systematic review of the evidence or a consensus opinion from the expert panel. EVIDENCE SYNTHESIS: Late-onset hypogonadism is a clinical condition in the ageing male combining low levels of circulating testosterone and specific symptoms associated with impaired hormone production and/or action. A comprehensive diagnostic and therapeutic work-up, along with screening recommendations and contraindications, is provided. Erectile dysfunction (ED) is the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance. Along with a detailed basic and advanced diagnostic approach, a novel decision-making algorithm for treating ED in order to better tailor therapy to individual patients is provided. The EAU guidelines have adopted the definition of premature ejaculation (PE), which has been developed by the International Society for Sexual Medicine. After the subtype of PE has been defined, patient's expectations should be discussed thoroughly and pharmacotherapy must be considered as the first-line treatment for patients with lifelong PE, whereas treating the underlying cause must be the initial goal for patients with acquired PE. Haemospermia is defined as the appearance of blood in the ejaculate. Several reasons of haemospermia have been acknowledged; the primary goal over the management work-up is to exclude malignant conditions and treat any other underlying cause. CONCLUSIONS: The 2021 guidelines on sexual and reproductive health summarise the most recent findings, and advise in terms of diagnosis and treatment of male hypogonadism and sexual dysfunction for their use in clinical practice. These guidelines reflect the multidisciplinary nature of their management. PATIENT SUMMARY: Updated European Association of Urology guidelines on sexual and reproductive health are presented, addressing the diagnosis and treatment of the most prevalent conditions in men. Patients must be fully informed of all relevant diagnostic and therapeutic options and, together with their treating physicians, decide on optimal personalised management strategies.

Non-obstructive azoospermia: current and future perspectives.

Infertility affects 1 in 6 couples, and male factor infertility has been implicated as a cause in 50% of cases. Azoospermia is defined as the absence of spermatozoa in the ejaculate and is considered the most extreme form of male factor infertility. Historically, these men were considered sterile but, with the advent of testicular sperm extraction and assisted reproductive technologies, men with azoospermia are able to biologically father their own children. Non-obstructive azoospermia (NOA) occurs when there is an impairment to spermatogenesis. This review describes the contemporary management of NOA and discusses the role of hormone stimulation therapy, surgical and embryological factors, and novel technologies such as proteomics, genomics, and artificial intelligence systems in the diagnosis and treatment of men with NOA. Moreover, we highlight that men with NOA represent a vulnerable population with an increased risk of developing cancer and cardiovascular comorbodities.

The semen microbiome and its impact on sperm function and male fertility: A systematic review and meta-analysis.

BACKGROUND: Male factor is attributable in up to 50% of cases of infertility. In vitro studies demonstrate that bacteria can negatively impact sperm function. The use of next-generation sequencing techniques has provided a better understanding of the human microbiome, and dysbiosis has been reported to impact health. Evidence regarding the impact of the semen microbiome on sperm function and fertility remains conflicting. MATERIALS AND METHODS: A systematic search was conducted in accordance with the Preferred Reporting Items for Reviews and Meta-analysis (PRISMA) statement. The databases MEDLINE, OVID and PubMed were searched to identify English language studies related to the identification of bacteria in the semen of infertile and fertile men, between 1992 and 2019. Fifty-five observational studies were included, with 51 299 subjects. We included studies identifying bacteria using next-generation sequencing, culture or polymerase chain reaction. RESULTS: The semen microbiome was rich and diverse in both fertile and infertile men. Three NGS studies reported clustering of the seminal microbiome with a predominant species. Lactobacillus and Prevotella were dominant in respective clusters. Lactobacillus was associated with improvements in semen parameters. Prevotella appeared to exert a negative effect on sperm quality. Bacteriospermia negatively impacted sperm concentration and progressive motility, and DNA fragmentation index (DFI; MD: 3.518, 95% CI: 0.907 to 6.129, P = .008). There was an increased prevalence of ureaplasma urealyticum in infertile men (OR: 2.25, 95% CI: 1.47-3.46). Ureaplasma urealyticum negatively impacted concentration and morphology. There was no difference in the prevalence of chlamydia trachomatis between fertile and infertile men and no significant impact on semen parameters. Enterococcus faecalis negatively impacted total motility, and Mycoplasma hominis negatively impacted concentration, PM and morphology. DISCUSSION AND CONCLUSIONS: Ureaplasma urealyticum, Enterococcus faecalis, Mycoplasma hominis and Prevotella negatively impact semen parameters, whereas Lactobacillus appears to protect sperm quality. These findings may facilitate the development of novel therapies (eg probiotics), although the evidence regarding the impact of the seminal microbiome on fertility is inconclusive and further studies are needed to investigate this association.