The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance-challenges and future research opportunities

Abstract

Background: Herein, we describe the consensus guideline methodology, summarize the evidence-based recommendations we provided to the World Health Organization (WHO) for their consideration in the development of global guidance and present a narrative review of the diagnosis of male infertility as related to the eight prioritized (problem or population (P), intervention (I), comparison (C) and outcome(s) (O) (PICO)) questions. Additionally, we discuss the challenges and research gaps identified during the synthesis of this evidence.

Objective and rationale: The aim of this paper is to present an evidence-based approach for the diagnosis of male infertility as related to the eight prioritized PICO questions.

Search methods: Collating the evidence to support providing recommendations involved a collaborative process as developed by WHO, namely: identification of priority questions and critical outcomes; retrieval of up-to-date evidence and existing guidelines; assessment and synthesis of the evidence; and the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation the quality of the supporting evidence was then graded and assessed for consideration during a WHO consensus.

Outcomes: Evidence was synthesized and recommendations were drafted to address the diagnosis of male infertility specifically encompassing the following: What is the prevalence of male infertility and what proportion of infertility is attributable to the male? Is it necessary for all infertile men to undergo a thorough evaluation? What is the clinical (ART/non ART) value of traditional semen parameters? What key male lifestyle factors impact on fertility (focusing on obesity, heat and tobacco smoking)? Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men? What are the evidence-based criteria for genetic screening of infertile men? How does a history of neoplasia and related treatments in the male impact on (his and his partner's) reproductive health and fertility options? And lastly, what is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility?

Wider implications: This evidence synthesis analysis has been conducted in a manner to be considered for global applicability for the diagnosis of male infertility.

Keywords: Y deletions; cancer; cystic fibrosis transmembrane conductance regulator; evidence-based guideline; genetics; male infertility; semen analysis; spermatozoa; varicocele.

Figure 1

Outline flowchart of WHO methodology for ESG Male Diagnosis. Flowchart outlining the WHO process for obtaining the evidence, and formulating and presenting recommendations for male infertility (Diagnosis). This includes stages and methods for synthesis of evidence according to WHO process. Dates in square bracket reflect specific meetings at WHO in Geneva. PICO: problem or population (P), intervention (I), comparison (C) and outcome(s) (O). WHO, World Health Organization; ESG, Evidence Synthesis Group.

Figure 2

Prevalence of male infertility. Prevalence of male infertility in surveys of general populations. Male infertility was generally defined as men reporting experience of infertility (generally >12 months in duration).

Figure 3

Flowchart summary of algorithm for diagnosis of male infertility. As detailed in section PICO 2 (Is it necessary for all infertile men to undergo a thorough evaluation?) the first line investigations should include Physical Examination, History and Semen Analysis. Abnormalities in these lead to further investigations. YCMD, Y chromosome microdeletion; CFTR, CF transmembrane conductance regulator.