Proteomics of azoospermia: Towards the discovery of reliable markers for non‐invasive diagnosis

Azoospermia, as the most severe form of male infertility, no longer indicates sterility due to modern medical advancements. The current diagnostic procedure based on testicular biopsy has several drawbacks which urges the development of novel, non-invasive diagnostic procedures based on biomarkers. In the last two decades, there have been many proteomics studies investigating potential azoospermia biomarkers. In this review, we aimed to provide a critical evaluation of these studies.Published articles were gathered by systematic literature search using Pubmed, Science Direct, and Google Scholar databases until March 2022 and were further preselected to include only studies on human samples.A detailed review of these studies encompassed the proteomics platforms, sources of material, proposed candidate biomarkers, and their potential diagnostic specificity and sensitivity. In addition, emphasis was put on the top, most identified and validated biomarker candidates and their potential for discriminating azoospermia types and subtypes as well as predicting sperm retrieval success rate.Proteomics research of azoospermia has laid the groundwork for the development of a more streamlined biomarker testing. The future research should be focused on well-designed studies including samples from all types/subtypes as well as further testing of the most promising biomarkers identified so far.