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Etiology spans Y-chromosome microdeletions, trauma, viral infections, radiation/toxin exposure, and idiopathic causes, yet many cases lack clear predictors. Clinical practice currently lacks validated prognostic markers and hormone-based tools. This review consolidates diagnostic and management standards and highlights research directions for future practical advances in fertility treatment.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/sertoli-cells-only-syndrome-current-clinical-approaches-and-ongoing-research-trends/415141/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/sertoli-cells-only-syndrome-current-clinical-approaches-and-ongoing-research-trends/415141.png","ImageObject",300,407,{"name":92,"@type":93},"Connor ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is Sertoli cells-only syndrome (SCOS) and why is it important in male infertility?","Question",{"text":112,"@type":113},"SCOS is a condition in which seminiferous tubules contain only Sertoli cells, causing a form of stem cell aplasia. It is a frequent cause of non-obstructive azoospermia and a major contributor to male-factor infertility.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What causes are associated with SCOS?",{"text":117,"@type":113},"SCOS can arise from multiple etiologies, including Y-chromosome microdeletions, trauma, viral infections, radiation or toxin exposure, and idiopathic causes. The review notes that many patients still have no clear etiological cause.",{"name":119,"@type":110,"acceptedAnswer":120},"What are the current limitations in clinical management, and what does the review aim to address?",{"text":121,"@type":113},"The review states that no reliable prognostic markers (hormonal or otherwise) are used in current clinical practice. 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Jannini,  \nUniversity of Rome Tor Vergata, Italy  \n*CORRESPONDENCE  \nElena Eugeni  \n [eugeni.elena@gmail.com](eugeni.elena@gmail.com)  \n†These authors share senior authorship ‡These authors share last authorship  \nRECEIVED 29 September 2025  \nACCEPTED 28 November 2025  \nPUBLISHED 19 December 2025  \nCITATION  \nEugeni E, Arato I, Mancuso F, Brancorsini S, Luca G and Kofler S (2025) Sertoli cells-only syndrome: current clinical approaches and ongoing research trends.  \nFront. Endocrinol. 16:1715642 .  \ndoi: 10.3389/fendo.2025.1715642  \nCOPYRIGHT  \n© 2025 Eugeni, Arato, Mancuso, Brancorsini, Luca and Kofler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nSertoli cells-only syndrome: current clinical approaches and ongoing research trends  \nElena Eugeni 1,2*, Iva Arato 2, Francesca Mancuso 2,  \nStefano Brancorsini 2,3, Giovanni Luca 2,3,4†‡ and Sieglinde Kofler1†‡  \n1 Department of Internal Medicine, Meran Hospital Südtiroler Sanitätsbetrieb (SABES), Merano, Italy, 2 Department of Medicine and Surgery, University of Perugia, Perugia, Italy, 3 International Biotechnological Center for Endocrine, Metabolic and Embryo-Reproductive Translational Research (CIRTEMER), Department of Medicine and Surgery, University of Perugia, Perugia, Italy, 4 Department of Medicine and Medical Specialties, Division of Endocrinology, Metabolic Diseases, Terni, Italy  \nSertoli Cells-Only Syndrome (SCOS), also known as Del Castillo syndrome or germ cell aplasia, is the most frequent cause of non-obstructive azoospermia, being found in 26-57% of patients affected by this condition. Although up to 10% of infertile males seeking medical attention are affected by SCOS and almost 80 years have already passed since this challenging syndrome was first described, therapeutic approaches to date are modest. The etiology of SCOS involves a large number of causes, including Y-chromosome microdeletions, trauma, viral infections, exposure to radiation or toxins, or idiopathic causes. The seminiferous tubule may be involved in its entirety or affected in a focal pattern only, with residual islands of spermatogenesis, which explains the variability in the success rate of sperm recovery in these patients. No prognostic markers, hormonal or of other nature, are currently employed in clinical practice. The purpose of this review is to organize the known information on SCOS and define current correct diagnostic and clinical practice, focusing in the second section on areas of research to look out for in terms of potential practical developments from the vast knowledge accumulated over recent decades.  \nKEYWORDS  \nSertoli cells-only syndrome, SCOS, NOA, ART, spermatogenesis, Sertoli cells  \n1 Introduction  \nInfertility, defined as the inability of a sexually active couple to conceive after a year of attempts, is a significant problem in our era (1, 2) . According to WHO data, this issue affects at least 15% of couples living in industrialized countries (2, 3) . Furthermore, about half of infertility cases are due to male partner pathologies, either alone in 20% of cases or in combination with the female partner problems in a further 30% of cases (1) . Alterations in the male partner’s semen can range in type and severity, but 10-15% of patients who consult fertility clinics are classified as azoospermic (4), meaning they have a total absence of sperm in their ejacu","cbCaiiQGTED0MJDW","https://ap.wps.com/l/cbCaiiQGTED0MJDW","pdf",2322771,15,"English","# Introduction\n# Diagnostic and clinical practice\n# Research directions and emerging therapies","[{\"question\":\"What is Sertoli cells-only syndrome (SCOS) and why is it important in male infertility?\",\"answer\":\"SCOS is a condition in which seminiferous tubules contain only Sertoli cells, causing a form of stem cell aplasia. It is a frequent cause of non-obstructive azoospermia and a major contributor to male-factor infertility.\"},{\"question\":\"What causes are associated with SCOS?\",\"answer\":\"SCOS can arise from multiple etiologies, including Y-chromosome microdeletions, trauma, viral infections, radiation or toxin exposure, and idiopathic causes. The review notes that many patients still have no clear etiological cause.\"},{\"question\":\"What are the current limitations in clinical management, and what does the review aim to address?\",\"answer\":\"The review states that no reliable prognostic markers (hormonal or otherwise) are used in current clinical practice. It aims to organize existing knowledge, define current correct diagnostic and clinical approaches, and outline research areas likely to drive practical developments.\"}]","Sertoli cells-only syndrome - current clinical approaches and ongoing research trends | PDF",1790600202,38]