Frequency, morbidity and equity - the case for increased research on male fertility.

Currently, most men with infertility cannot be given an aetiology, which reflects a lack of knowledge around gamete production and how it is affected by genetics and the environment. A failure to recognize the burden of male infertility and its potential as a biomarker for systemic illness exists. The absence of such knowledge results in patients generally being treated as a uniform group, for whom the strategy is to bypass the causality using medically assisted reproduction (MAR) techniques. In doing so, opportunities to prevent co-morbidity are missed and the burden of MAR is shifted to the woman. To advance understanding of men's reproductive health, longitudinal and multi-national centres for data and sample collection are essential. Such programmes must enable an integrated view of the consequences of genetics, epigenetics and environmental factors on fertility and offspring health. Definition and possible amelioration of the consequences of MAR for conceived children are needed. Inherent in this statement is the necessity to promote fertility restoration and/or use the least invasive MAR strategy available. To achieve this aim, protocols must be rigorously tested and the move towards personalized medicine encouraged. Equally, education of the public, governments and clinicians on the frequency and consequences of infertility is needed. Health options, including male contraceptives, must be expanded, and the opportunities encompassed in such investment understood. The pressing questions related to male reproductive health, spanning the spectrum of andrology are identified in the Expert Recommendation.

WHO 2021 and 2030 reference values for semen assessment: three challenges for andrology in the journey ahead.

Whilst formulating the World Health Organization reference values for semen assessment for 2021, three key challenges were identified, namely the quality of semen assessments, the transparency and reporting of data and, lastly, the paucity of studies with primary data. There is an urgent need to address these issues and we present suggested solutions that will have a real-world influence on the next iteration of the reference values for semen assessments and andrology in general.

Methods for the assessment of sperm capacitation and acrosome reaction excluding the sperm penetration assay.

Assessing the ability of human spermatozoa to acquire fertilizing potential (capacitation) by stimulating exocytosis of the contents of the acrosome (acrosome reaction) is thought to have diagnostic potential (De Jonge, Reprod Med Rev 3:159-178, 1994). Calcium-mobilizing agents, such as calcium ionophores (A23187) and progesterone, stimulate the acrosome reaction in vitro (Brucker and Lipford, Hum Reprod Update 1:51-62, 1995). Acrosomal status is easily detected using Pisum sativum Agglutinin labeled with fluorescein isothiocyanate (Cross and Meizel, Biol Reprod 41:635-641, 1989). Herein we describe a procedure for assessing capacitation and the acrosome reaction of human spermatozoa in vitro.

Diagnostic tools in male infertility-the question of sperm dysfunction.

Sperm dysfunction is the single most common cause of infertility, yet what is remarkable is that, there is no drug a man can take or add to his spermatozoa in vitro to improve fertility. One reason for the lack of progress in this area is that our understanding of the cellular and molecular workings of the mature spermatazoon is limited. However, over the last few years there has been considerable progress in our knowledge base and in addressing new methods to diagnose sperm dysfunction. We review the current state of the field and provide insights for further development. We conclude that: (i) there is little to be gained from more studies identifying/categorizing various populations of men using a basic semen assessment, where an effort is required in making sure the analysis is performed in an appropriate high quality way; (ii) technological development is likely to bring the reality of sperm function testing closer to implementation into the clinical pathways. In doing this, these assays must be robust, cheap (or more appropriately termed cost effective), easy to use and clinically useful; and (iii) clinical necessity, e.g., the need to identify the highest quality spermatozoon for injection is driving basic research forward. This is an exciting time to be an andrologist and, likely, a fruitful one.

Clinical relevance of sperm DNA assessment: an update.

For sperm DNA assessments to be widespread effective clinical tools, key objectives need to be urgently achieved. These include robust standardized methods, systems for training staff and ongoing quality control; and rigorous examination of the clinical outcomes. We discuss the significance of these objectives and conclude that, if achieved, the clinical utility of DNA damage assessment will be fully realized.