A 2026 narrative review maps the landscape of non-invasive biomarkers for azoospermia diagnosis, covering small RNAs, proteomics, genetic markers, and imaging
Journal: Biomolecules | Published: 2026-06-15 | Type: Review | PMID: 42352343 Authors: Zou Jiazhen, Gao Huihui, Gu Qingdan, Zhang Peng, Cao Heran (Southern University of Science and Technology Yantian Hospital; Tongji Medical College Huazhong University; NHC Key Laboratory of Male Reproduction and Genetics, Guangdong) Funding/COI: Hubei Clinical Research Center for Reproductive Medicine; Wuhan Municipal Health Commission. COI not reported.
Azoospermia — complete absence of sperm in ejaculate — is the most severe form of male infertility and affects roughly 1% of all men. The core clinical problem the authors address is distinguishing obstructive azoospermia (OA, blocked ducts, intact testicular function) from non-obstructive azoospermia (NOA, testicular failure) without resorting to biopsy. This review catalogs candidate biomarkers across four categories — small non-coding RNAs, proteomic profiles, genetic/genetic polymorphism markers, and imaging features — and argues the field is converging toward integrated, multi-marker panels that could make non-invasive diagnosis viable.
This is a narrative review, not a systematic review or meta-analysis. No PRISMA methodology is described, no search strategy is reported, no inclusion/exclusion criteria are stated, and there is no quantitative synthesis of diagnostic accuracy (sensitivity, specificity, AUC). That means the reader has no way to assess whether the authors systematically captured the evidence or cherry-picked supportive papers. For a field as heterogeneous as azoospermia biomarkers — where small, single-center studies dominate — narrative reviews carry a high risk of presenting the most favorable candidates without contextualizing the replication failures.
The five authors are spread across Chinese institutions; the review likely reflects the Chinese literature's representation in this space, which is substantial but may not capture contradictory findings published in other languages or negative results that typically go unpublished.
This review is a literature map, not a clinical verdict. It tells you the biomarker field for azoospermia is active and organized around four categories; it does not tell you which markers are close to clinical use or how well any of them actually perform. The absence of diagnostic accuracy numbers is the central deficiency — a review that cannot report an AUC for its top candidates is not yet actionable science. Read it to orient yourself to the space and generate a reading list; do not read it as evidence that non-invasive azoospermia diagnosis is near. The systematic review this field actually needs would pre-register a search strategy, pool diagnostic accuracy data, and apply QUADAS-2 quality assessment. That paper has not been written yet.