The 2025 World Health Organization (WHO) Guideline for the Prevention, Diagnosis, and Treatment of Infertility represents the first comprehensive global framework integrating male and female contributors to infertility within a unified public health strategy. This commentary examines the male-relevant components of the guideline from the perspective of reproductive biology and translational andrology. The WHO guideline mandates a parallel evaluation of both partners and structures male assessment around the medical history, a focused physical examination and semen analysis as a triage tool. While pragmatic and globally applicable, semen analysis remains a descriptive rather than a mechanistic test, underscoring the need for a deeper investigation into sperm chromatin integrity, epigenetics and molecular function. The guideline's conservative treatment recommendations - limited to clinical varicocele repair and antioxidant therapy - reflect Population, Intervention, Comparison, Outcome prioritization, the GRADE methodology and an emphasis on pregnancy and live-birth outcomes, as well as considerations of equity and feasibility across diverse health systems. By embedding male reproductive health within a global infertility approach, the guideline promotes structured evaluation, early specialist referral and reproductive equity, while highlighting critical gaps in mechanistic understanding that must inform future research and clinical innovation.
Reproductive biomedicine online. 2026 Feb 23 [Epub ahead of print]
Sandro C Esteves, Allan Pacey, Christopher J De Jonge
ANDROFERT, Andrology and Human Reproduction Clinic, Campinas, Brazil.; Department of Surgery (Division of Urology), University of Campinas (UNICAMP), Campinas, Brazil.; Faculty of Health, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.. Electronic address: ., School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Department of Urology, University of Minnesota Medical Center, University of Minnesota, Minneapolis, MN, USA.