The WHO 2025 Guideline for the Prevention, Diagnosis and Treatment of Infertility: A Comprehensive Review with Focus on Male Reproductive Health
WHO's first unified infertility guideline backs varicocele repair conditionally but won't endorse antioxidants—evidence too heterogeneous
Journal: International braz j urol | Published: 2026 | Type: Review | PMID:41770990Authors: Esteves SC (ANDROFERT, Clínica de Andrologia e Reprodução Humana, Campinas, Brazil)
Funding/COI: Not listed; no conflicts declared
Summary
The WHO issued its first comprehensive infertility guideline in 2025—historically overdue—establishing a single global framework covering prevention, diagnosis, and treatment for both male and female infertility. This review by a single Brazilian andrologist summarizes the guideline's male-focused content, developed using GRADE methodology and structured consensus by a multidisciplinary panel. The headline calls: conditional support for varicocele repair, no recommendation for antioxidant supplementation.
Claims
This is the first WHO guideline to address both male and female infertility within a unified public-health framework
Varicocele repair: conditional recommendation supported—evidence deemed sufficient to justify it
Antioxidant supplementation: no recommendation issued—evidence characterized as "too heterogeneous and indirect"
Guideline endorses standardized semen analysis per WHO laboratory manual methods as the diagnostic baseline
Recommends structured history, physical exam, and timely urologist referral when semen abnormalities persist
Explicitly excludes advanced sperm function testing, endocrine management, and genetic evaluation as outside the guideline's public-health scope
Identifies persistent evidence gaps in: molecular diagnostics, targeted treatments, oxidative stress, and psychosocial dimensions of male infertility
Study Quality
This is a narrative review of a guideline, not a clinical study—so traditional quality metrics (sample size, control group, blinding) don't apply. What does apply: how faithfully it represents the guideline and whether it adds analytical value. The review describes the WHO development process accurately: PICO-structured questions, systematic evidence synthesis, GRADE-rated certainty levels, formal GDG voting, external expert review, and WHO internal committee approval. That's a credible methodological chain.
The GRADE framework is the appropriate tool here—it forces explicit reasoning about evidence certainty, and the antioxidant/varicocele distinction is a direct output of that reasoning. However, this is a single-author review summarizing a guideline the author appears to endorse. It reads as explanatory rather than critical; gaps in the guideline are noted but not probed.
Red Flags
Single author, no co-authors to catch gaps or provide alternative interpretation
No funding listed for the review itself—the WHO guideline had institutional backing, but this secondary review's production is unexplained
Advocacy tone: the conclusion frames the guideline as establishing a "global foundation" and emphasizes potential benefits without examining what the GDG got wrong or where consensus was weak
GDG composition not examined: the review doesn't assess whether the development panel adequately represented low-resource settings that the guideline is explicitly meant to serve
The exclusion of advanced diagnostics (genetic evaluation, endocrine workup) is framed as a scoping decision—but for clinicians in settings where specialty care exists, this leaves the guideline thin precisely where diagnosis gets difficult
Strengths
GRADE methodology is the appropriate gold standard for guideline development; its application here is documented, not assumed
Clear delineation of scope limits—the guideline explicitly declines to replace specialty andrology practice guidelines
The antioxidant finding is clinically meaningful: widely sold, widely used, and this guideline declines to endorse them based on evidence heterogeneity
Equity framing (feasibility across resource settings) is structurally baked in, not rhetorical
Verdict
If you work in male reproductive medicine, the WHO guideline itself is the document to read—this review is a useful orientation but adds limited independent analysis. The meaningful news is in two calls: varicocele repair gets a conditional nod, antioxidants get none. That antioxidant finding matters because the supplements are aggressively marketed and this is now a WHO-level "insufficient evidence" ruling. The review earns its place as a summary of a landmark document, but don't mistake it for a critical appraisal.