Evolution of the World Health Organization semen analysis manual: where are we?

The WHO (World Health Organization) manuals provide state-of-the-art guidance on how a semen analysis should be carried out. The much anticipated sixth edition of the WHO semen analysis manual has been released 10 years after its previous version and includes essential updates, such as new reference standards for semen volume and microscopic sperm characteristics of recent fathers. A well-conducted semen analysis remains an essential foundation of the infertility evaluation process and affects patient referral, diagnosis and treatment. However, a male infertility work-up primarily based on routine semen analysis does not provide men with an optimal fertility pathway; the primary reasons for routine semen analysis inadequacy in this context include its low predictive value for natural and assisted conception success, its inability to detect sperm DNA and epigenetic deficiencies that might negatively affect embryo development, implantation and offspring well-being, and the substantial overlap between semen parameters of fertile and subfertile individuals. Ideally, a full andrological assessment should be carried out by reproductive urologists in all men dealing with couple infertility and should include a detailed history analysis, physical examination, semen analysis, endocrine assessment and other tests as needed. Only through a complete male infertility work-up will relevant underlying medical and infertility conditions be revealed and potentially treated or alleviated. The ultimate goals of a comprehensive andrological assessment are to positively influence overall male health, pregnancy prospects and offspring well-being.