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

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.

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.

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.

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?

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

Human reproduction update. 2017 Jul 19 [Epub ahead of print]

Christopher L R Barratt, Lars Björndahl, Christopher J De Jonge, Dolores J Lamb, Francisco Osorio Martini, Robert McLachlan, Robert D Oates, Sheryl van der Poel, Bianca St John, Mark Sigman, Rebecca Sokol, Herman Tournaye

Department of Reproductive and Developmental Biology, Medical School, Ninewells Hospital, University of Dundee, Dundee, DD1 9SY, Scotland., Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden., University of Minnesota, Minneapolis, MN, USA., Baylor College of Medicine, Houston, TX, USA., Clinica Alemana de Santiago, Santiago, Chile., Hudson Institute of Medical Research, Clayton, Australia., Boston University School of Medicine and Boston Medical Center, Boston, MA, USA., Department of Reproductive Health and Research, Human Reproduction Programme, (HRP, The UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction), WHO, Geneva, Switzerland., Warren Alpert Medical School of Brown University, RI, USA., Department of Obstetrics and Gynaecology and Medicine, Keck School of Medicine, University of Southern California, CA, USA., Centre for Reproductive Medicine, Vrije Universiteit Brussel, Brussels, Belgium.