O-040 The evolution of WHO Manual. Where are we now?
Authors: Esteves S 
Published: August 2021

Abstract text

Male factor infertility is associated with impaired overall health, decreased life expectancy, lower quality of life and may affect reproductive outcomes even under assisted reproductive technology (ART) settings. Male factors, alone or combined with female factors, contribute to at least 50% of reported infertility cases. Despite this, the male partner is often overlooked in the evaluation and treatment of infertility. A routine semen analysis is frequently the only test carried out to assess a man’s fertility potential.

The state-of-art on how the human semen should be assessed is provided by the World Health Organization (WHO), which periodically releases manuals that include specific protocols and reference standards. These manuals include detailed laboratory methods for semen examination, protocols for sperm preparation and cryopreservation, quality assurance and quality control, results’ interpretation, and reference ranges. Unlike the previous four versions, the latest 2010 WHO reference values relied on clinical chemistry principles to generate 95% intervals for sperm volume, count, motility, vitality, and morphology from recent fathers. The fifth centile was deemed suitable for representing semen characteristics at lower limits. The reference values ultimately obtained were markedly lower than those previously reported, raising concerns about its clinical utility and generalizability. Criticisms included the limited geographical area of patients analyzed, the methods used for semen evaluation, and the potential impact of the new reference range on patient referral, diagnosis, and treatment guidance. An updated new WHO manual (6th edition) is about to be released with much expectation.

Although semen analysis remains one of the cornerstones of the infertility evaluation, a male infertility workup primarily based on routine semen analysis does not provide men with an optimal fertility pathway for many reasons. First, reference intervals do not reliably distinguish fertile from subfertile subjects. Second, an individual patient’s results have limited prognostic value for both natural and assisted conception unless at extreme lower limits. Third, there is a wide variation in how laboratories perform a semen analysis. Lastly, routine semen analysis does not detect sperm DNA defects that might adversely impact embryo development, implantation, and offspring’s health.

Guidelines issued by professional societies recommend that a full andrological assessment be performed in all men with couple infertility. Well-trained reproductive urologists or clinical andrologists should perform the male evaluation, including a detailed history, physical examination, semen analysis, endocrine assessment, and other tests as needed. Therefore, the importance of WHO manuals remains critical. However, the goals of a comprehensive male infertility workup go beyond the laboratory assessment of human semen. It comprises i. Diagnosis, i.e., detection of any underlying relevant medical or lifestyle conditions potentially impairing the (reproductive) health of the male or his offspring; ii. Counselling, particularly regarding the impact of infertility, genetic factors, age, and lifestyle on pregnancy prospects, reproductive and overall health, and offspring’s well-being; and iii. Management Guidance, i.e., identifying optimal treatment options to improve the likelihood of achieving natural pregnancy or ART success. The prevention and management of male infertility are integral components of comprehensive sexual and reproductive health services needed to attain a sustainable development goal.