Investigating the regulation of male infertility

Infertility is defined as the inability to become pregnant following one year of practicing regular and unprotected sexual intercourse and is estimated to affect 72.4 million people globally. Within the U.K., infertility has been estimated to affect 14% of couples. In 50% of cases of infertility the cause will be attributable to poor sperm quality and the main treatment is assisted reproductive technologies (ART) such as in-vitro fertilisation (IVF). However, ART is resource limited and IVF has an estimated success rate of 29%. Thus, there is an urgent need to improve our understanding of the pathophysiological mechanisms that underpin male infertility to help develop more cost-effective therapies. Recent studies have highlighted the effects of oxidative stress (including seminal reactive oxygen species (ROS) and sperm DNA fragmentation (SDF)) in sperm dysfunction. Furthermore, there is limited data showing differences in seminal microbiome in infertile compared to fertile men. However, it is unclear from the literature how oxidative stress and the seminal microbiome correlate with semen analysis. This is pertinent given that semen analysis is the gold standard investigation for diagnosing male infertility. Non obstructive azoospermia (NOA) is the absence of sperm in the ejaculate due to impaired spermatogenesis. The only method for men with NOA to conceive biological children is through sperm retrieval surgery combined with ART. However, the success rate of testicular sperm extraction in men with NOA is only 50%. In half of all cases of NOA the cause is unknown but there is emerging data showing that genetic mutations may be contributory. This knowledge is helpful in both patient counselling and clinical management. For example, men with NOA who have either Azoospermia factor A or B gene deletions have a lower likelihood of testicular tissue containing sperm and should be counselled against sperm retrieval surgery. There is emerging data showing that in some cases of idiopathic NOA, a genetic mutation may be causal. Further genetic studies are needed to help improve our understanding of the aetiology of NOA and this may help identify future therapeutic targets for men with infertility. Spermatogenesis is stimulated by gonadotropins and intratesticular testosterone. Some clinicians have trialed hormone stimulation therapy to improve sperm retrieval rates in men with NOA. However, no study has critically evaluated the literature regarding the effects of hormone stimulation therapy in improving sperm retrieval rates and also the potential adverse events. This thesis includes the first study investigating how oxidative stress markers and seminal microbiome differ in different cohorts of male infertility and fertile controls. Furthermore, I performed the first meta-analysis investigating the effects of hormone stimulation therapy on surgical sperm retrieval rates in men with NOA. I have also investigated for novel genetic mutations in a cohort of infertile men with idiopathic NOA. Collectively, the results from this thesis will improve our understanding on the aetiological factors, pathophysiological mechanisms and management of male infertility.Open Acces

Surgical and minimally invasive treatment of ischaemic and non-ischaemic priapism : A systematic review by the EAU Sexual and Reproductive Health Guidelines panel

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What is the effectiveness of surgical and non-surgical therapies in the treatment of ischemic priapism in patients with sickle cell disease? A systematic review by the EAU Sexual and Reproductive Health Panel

The authors acknowledge the participants for their cooperation Conflict of Interest: None of the authors declare any interest. Formatting of funding sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Peer reviewedPostprin

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 extrac-tion in nonazoospermic men

Male Sexual and Reproductive Health—Does the Urologist Have a Role in Addressing Gender Inequality in Life Expectancy?

Despite considerable public health initiatives in the past century, there remains a significant gender inequality in life expectancy. The Global Burden of Diseases study has highlighted that the life expectancy for men is 70.5 years, compared with 75.6 years for women. This discrepancy in mortality appears to be related to a disproportionately higher number of preventable and premature male deaths. Whilst there has been an increased focus on men's health, as evidenced by the establishment of men's health charities and governmental legislation promoting equality, a recent World Health Organization report has highlighted that there is still a prevailing misconception that the higher rate of premature mortality amongst men is a natural phenomenon. We explore the association of male sexual and reproductive health–related diseases and the potential role of a urologist in addressing gender inequality in life expectancy. Patient summary: In this report, we discuss the causes for the gender gap in life expectancy and highlight that men continue to have a higher rate of premature death than women, which is associated with diseases of the male reproductive system. Furthermore, this not only appears to be related to a number of metabolic and lifestyle factors, but may also be the result of the increased risk of cancer in men with sexual and reproductive health–related diseases. Globally, the life expectancy for men is 5.1 yr less than that of women. We describe the association between diseases of the male reproductive system and cardiovascular disease and cancers, and highlight the important role of a urologist in reducing premature male death. © 2019 European Association of Urolog

Radiological features characterising indeterminate testes masses; A systematic review and meta-analysis.

ContextThe use of scrotal ultrasound (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.ObjectiveTo 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 acquisitionThis SR was conducted in accordance with Cochrane Collaboration guidance. Medline, Embase, Cochrane controlled trials and systematic reviews databases were searched from (1970 - March 26, 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 synthesis32 studies were identified, including 1692 masses of which 28 studies and 1550 masses reported SUS features, 4 studies and 142 masses reported MRI features. Meta-analysis of different SUS B mode values in post pubertal men demonstrated size of ≤0.5cm had a significant lower OR of malignancy compared to masses >0.5cm (p 1.5cm also demonstrated a significant lower OR of malignancy (p = 0.04). No significanct difference was observed between masses of 0.6-1.0cm and 1.1-1.5cm. SUS in post pubertal men also had a statistically significant lower odds of malignancy for heterogenous masses vs. homogenous masses (p = 0.04), hyperechogenic vs. hypoechogenic masses (p ConclusionsThis meta-analysis identifies radiological characteristics that have a lower odds of malignancy and may be of value in the management of the indeterminate testis mass

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. (c) 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved

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

The European Association of Urology (EAU) has updated its guidelines on sexual and reproductive health for 2021