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. Keywords: gamete biomarker; male fertility; sperm biomarker; sperm dysfunction INTRODUCTION Infertility is a significant global problem affecting approximately 80 million (1:7) couples worldwide. 1 In a landmark study by Mike Hull and colleagues, in which a representative British population was studied, sperm dysfunction (lacking 'normal' function) was identified as the single most common cause of infertility. 2 Subsequent studies have confirmed these observations 3 and highlighted dysfunctional cells in men with 'normal' semen parameters and conversely normal sperm function in oligozoospermic men. 4 What is remarkable is that, for this group, there is no drug a man can take or add to his spermatozoa in vitro to improve fertility. The only option is assisted reproductive technology (ART) which usually consists of a graduation of treatment depending on severity, i.e., intrauterine insemination for mild, in vitro fertilisation (IVF) for moderate and intracytoplasmic sperm injection (ICSI) for men with severe sperm dysfunction. 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. The purpose of this paper is to review the current state of the field and provide insights for further development. The initial focus is on the value of semen analysis as a clinical tool with the discussion progressing to examining sperm dysfunction in detail.

No abstract