{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:07:38Z","timestamp":1789031258288,"version":"build-2803163510"},"reference-count":91,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>In non-obstructive azoospermia (NOA), microdissection testicular sperm extraction can provide sperm for intracytoplasmic sperm injection, but retrieval fails in approximately half of procedures. Genomic, transcriptomic, noncoding RNA, proteomic, metabolomic, and microbiome studies have reported molecular associations and prediction estimates. This critical narrative review examines the requirements for an assay\u2013model system to support preoperative retrieval counseling. A focused PubMed\/MEDLINE search updated on 31 August 2026 and targeted reference checking identified representative human reports and methodological guidance. Selected reports mainly illustrate discovery, development, and same-source evaluation. Common limitations include small cohorts, local assay optimization, heterogeneous outcomes, incomplete calibration, and uncertain transportability. Established karyotyping and Y-chromosome testing must be distinguished from discovery-scale genomics, which currently supports etiologic and qualified genotype-specific counseling rather than a universal calibrated retrieval model. A routine-variable multicenter model reported an external-cohort area under the receiver-operating-characteristic curve (AUC) of 0.8301, although cohort provenance, calibration, and clinical utility require independent confirmation. An author-developed seven-gate framework integrates clinical-question definition, assay specification, model development, internal validation, external evaluation, incremental value, and prospective impact. Future omics studies should test incremental value beyond a prespecified routine-variable model in the same patients and assess calibration, threshold consequences, net benefit, assay failure, cost, and patient outcomes.<\/jats:p>","DOI":"10.3390\/genes17091088","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:07:41Z","timestamp":1789027661000},"page":"1088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Omics-Based Sperm-Retrieval Prediction in Non-Obstructive Azoospermia: A Critical Narrative Review and Validation Framework"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4651-312X","authenticated-orcid":false,"given":"Aris","family":"Kaltsas","sequence":"first","affiliation":[{"name":"Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2141-4937","authenticated-orcid":false,"given":"Maria-Anna","family":"Kyrgiafini","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleftheria","family":"Markou","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chrisofos","sequence":"additional","affiliation":[{"name":"Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.eururo.2025.02.026","article-title":"European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2025 update on male infertility","volume":"87","author":"Minhas","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1093\/humupd\/dmz028","article-title":"Sperm recovery and ICSI outcomes in men with non-obstructive azoospermia: A systematic review and meta-analysis","volume":"25","author":"Corona","year":"2019","journal-title":"Hum. Reprod. Update"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"30","DOI":"10.4103\/aja.aja_5_17","article-title":"Predictive value of FSH, testicular volume, and histopathological findings for the sperm retrieval rate of microdissection TESE in nonobstructive azoospermia: A meta-analysis","volume":"20","author":"Li","year":"2018","journal-title":"Asian J. Androl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.euros.2024.05.001","article-title":"Role of follicle-stimulating hormone, inhibin B, and anti-M\u00fcllerian hormone in predicting sperm retrieval from men with non-obstructive azoospermia undergoing microdissection testicular sperm extraction: A systematic review and meta-analysis","volume":"65","author":"Pozzi","year":"2024","journal-title":"Eur. Urol. Open Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kaltsas, A., Stavros, S., Kratiras, Z., Zikopoulos, A., Machairiotis, N., Potiris, A., Dimitriadis, F., Sofikitis, N., Chrisofos, M., and Zachariou, A. (2024). Predictors of successful testicular sperm extraction: A new era for men with non-obstructive azoospermia. Biomedicines, 12.","DOI":"10.3390\/biomedicines12122679"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/andr.13514","article-title":"EAA\/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: State of the art 2023","volume":"12","author":"Krausz","year":"2024","journal-title":"Andrology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kaltsas, A., Markou, E., Zachariou, A., Dimitriadis, F., Symeonidis, E.N., Zikopoulos, A., Mamoulakis, C., Tien, D.M.B., Takenaka, A., and Sofikitis, N. (2023). Evaluating the predictive value of diagnostic testicular biopsy for sperm retrieval outcomes in men with non-obstructive azoospermia. J. Pers. Med., 13.","DOI":"10.3390\/jpm13091362"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fontana, L., Sirchia, S.M., Pesenti, C., Colpi, G.M., and Miozzo, M.R. (2024). Non-invasive biomarkers for sperm retrieval in non-obstructive patients: A comprehensive review. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1349000"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kaltsas, A., Gasparos, F., Koumenis, A., Stavropoulos, M., and Chrisofos, M. (2026). Seminal-plasma molecular biomarkers as a liquid biopsy of testicular function: Toward AI-ready sperm-retrieval prediction in non-obstructive azoospermia. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27135965"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.5534\/wjmh.250367","article-title":"Artificial intelligence in non-obstructive azoospermia: State of the art in sperm retrieval","volume":"44","author":"Kandil","year":"2026","journal-title":"World J. Men\u2019s Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"hoae070","DOI":"10.1093\/hropen\/hoae070","article-title":"AI predictive models and advancements in microdissection testicular sperm extraction for non-obstructive azoospermia: A systematic scoping review","volume":"2025","author":"Jamalirad","year":"2025","journal-title":"Hum. Reprod. Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41073-019-0064-8","article-title":"SANRA\u2014A scale for the quality assessment of narrative review articles","volume":"4","author":"Baethge","year":"2019","journal-title":"Res. Integr. Peer Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/andr.13448","article-title":"Predictors of successful salvage microdissection testicular sperm extraction after failed initial TESE in patients with non-obstructive azoospermia: A systematic review and meta-analysis","volume":"12","author":"Zhang","year":"2024","journal-title":"Andrology"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Moons, K.G.M., de Groot, J.A.H., Bouwmeester, W., Vergouwe, Y., Mallett, S., Altman, D.G., Reitsma, J.B., and Collins, G.S. (2014). Critical appraisal and data extraction for systematic reviews of prediction modelling studies: The CHARMS checklist. PLoS Med., 11.","DOI":"10.1371\/journal.pmed.1001744"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"55","DOI":"10.7326\/M14-0697","article-title":"Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): The TRIPOD statement","volume":"162","author":"Collins","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e078378","DOI":"10.1136\/bmj-2023-078378","article-title":"TRIPOD+AI statement: Updated guidance for reporting clinical prediction models that use regression or machine-learning methods","volume":"385","author":"Collins","year":"2024","journal-title":"BMJ"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"51","DOI":"10.7326\/M18-1376","article-title":"PROBAST: A tool to assess the risk of bias and applicability of prediction model studies","volume":"170","author":"Wolff","year":"2019","journal-title":"Ann. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e082505","DOI":"10.1136\/bmj-2024-082505","article-title":"PROBAST+AI: An updated quality, risk of bias, and applicability assessment tool for prediction models using regression or artificial intelligence methods","volume":"388","author":"Moons","year":"2025","journal-title":"BMJ"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e073538","DOI":"10.1136\/bmj-2022-073538","article-title":"Transparent reporting of multivariable prediction models for individual prognosis or diagnosis: Checklist for systematic reviews and meta-analyses (TRIPOD-SRMA)","volume":"381","author":"Snell","year":"2023","journal-title":"BMJ"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s12958-025-01497-7","article-title":"Genetic and epigenetic insights into non-obstructive azoospermia: Mechanisms, biomarkers, and clinical perspectives","volume":"23","author":"Wang","year":"2025","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s10815-025-03409-5","article-title":"Genetic insights into non-obstructive azoospermia: Implications for diagnosis and TESE outcomes","volume":"42","author":"Sharifi","year":"2025","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5683","DOI":"10.1038\/s41467-020-19414-4","article-title":"Single-cell analysis of developing and azoospermia human testicles reveals central role of Sertoli cells","volume":"11","author":"Zhao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1093\/humrep\/dey072","article-title":"Exosomal microRNAs in seminal plasma are markers of the origin of azoospermia and can predict the presence of sperm in testicular tissue","volume":"33","author":"Mata","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1093\/humrep\/deaa184","article-title":"A panel of extracellular-vesicle long non-coding RNAs in seminal plasma for predicting testicular spermatozoa in non-obstructive azoospermia patients","volume":"35","author":"Xie","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1093\/humrep\/deab196","article-title":"Potential of testis-derived circular RNAs in seminal plasma to predict the outcome of microdissection testicular sperm extraction in patients with idiopathic non-obstructive azoospermia","volume":"36","author":"Ji","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"392","DOI":"10.21037\/atm-21-5100","article-title":"Circulating microRNAs in seminal plasma as predictors of sperm retrieval in microdissection testicular sperm extraction","volume":"10","author":"Zhang","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1007\/s10815-021-02101-8","article-title":"Outcome prediction of microdissection testicular sperm extraction based on extracellular-vesicle piRNAs","volume":"38","author":"Chen","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1111\/andr.13173","article-title":"Multi-stage screening of cell-free seminal mRNAs to diagnose completion of meiosis and predict testicular sperm retrieval in men with non-obstructive azoospermia","volume":"10","author":"Dai","year":"2022","journal-title":"Andrology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s12958-022-00978-3","article-title":"Seminal-plasma extracellular vesicles tRF-Val-AAC-010 can serve as a predictive factor of successful microdissection testicular sperm extraction in patients with non-obstructive azoospermia","volume":"20","author":"Han","year":"2022","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kyrgiafini, M.-A., Kaltsas, A., Chatziparasidou, A., and Mamuris, Z. (2025). The small RNA landscape in azoospermia: Implications for male infertility and sperm retrieval\u2014A preliminary study. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083537"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.fertnstert.2021.11.010","article-title":"Circulatory exosomal tRF-Glu-CTC-005 and tRF-Gly-GCC-002 serve as predictive factors of successful microdissection testicular sperm extraction in patients with nonobstructive azoospermia","volume":"117","author":"Zhang","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"23119","DOI":"10.1038\/s41598-026-49620-x","article-title":"Hsa-circ_0081481\u2013miR-3960\u2013FBXO24 regulatory axis in non-obstructive azoospermia identifies potential biomarkers of spermatogenic failure","volume":"16","author":"Babakhanzadeh","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_33","first-page":"193","article-title":"A novel hsa_circ_0070963\/miR-223-3p\/CCDC96\u2013CCDC112 regulatory axis as a non-invasive biomarker for predicting sperm retrieval outcomes in non-obstructive azoospermia: A case-control study","volume":"24","author":"Babakhanzadeh","year":"2026","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"23039","DOI":"10.1038\/s41598-026-47513-7","article-title":"Uncovering hidden spermatogenesis: INPP1 and GTSF1 as non-invasive predictors of sperm retrieval in non-obstructive azoospermia","volume":"16","author":"Babakhanzadeh","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Babakhanzadeh, E., Khodadadian, A., Nazari, M., Mozhdeh, M., Vahidi Mehrgardi, S., Jafari, M.H., Dehghani, M., Ghafouri-Fard, S., and Ghasemi, N. (2026). Circular RNA-Mediated ceRNA networks predict sperm retrieval outcomes in non-obstructive azoospermia. J. Assist. Reprod. Genet., Online ahead of print.","DOI":"10.1007\/s10815-026-04013-x"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1111\/andr.13617","article-title":"A detection model of testis-derived circular RNAs in serum for predicting testicular sperm retrieval rate in non-obstructive azoospermia patients","volume":"12","author":"Lv","year":"2024","journal-title":"Andrology"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Shi, S., Wang, T., Wang, L., and Wang, M. (2023). Nomogram based on a circular RNA biomarker for predicting the likelihood of successful sperm retrieval via microdissection testicular sperm extraction in patients with idiopathic non-obstructive azoospermia. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1109807"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Korbakis, D., Schiza, C., Brinc, D., Soosaipillai, A., Karakosta, T.D., L\u00e9gar\u00e9, C., Sullivan, R., Mullen, B., Jarvi, K., and Diamandis, E.P. (2017). Preclinical evaluation of a TEX101 protein ELISA test for the differential diagnosis of male infertility. BMC Med., 15.","DOI":"10.1186\/s12916-017-0817-5"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/j.2047-2927.2012.00059.x","article-title":"Comparative proteomic analysis coupled with conventional protein assay as a strategy to identify predictors of successful testicular sperm extraction in patients with non-obstructive azoospermia","volume":"1","author":"Freour","year":"2013","journal-title":"Andrology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Fietz, D., Sgaier, R., O\u2019Donnell, L., Stanton, P.G., Dagley, L.F., Webb, A.I., Schuppe, H.-C., Diemer, T., and Pilatz, A. (2024). Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1327800"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e3931","DOI":"10.1002\/bmc.3931","article-title":"Untargeted metabolomic profiling of seminal plasma in non-obstructive azoospermia men: A non-invasive detection of spermatogenesis","volume":"31","author":"Gilany","year":"2017","journal-title":"Biomed. Chromatogr."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Cheng, J., Tang, Y., Zhao, Q., Weng, J., Fang, Z., Qi, Y., Jiang, H., and Zhang, Z. (2026). Seminal plasma metabolomic profiling reveals key metabolic signatures linked to spermatogenic potential in non-obstructive azoospermia with cryptorchidism. Metabolites, 16.","DOI":"10.3390\/metabo16020147"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.xfss.2026.05.001","article-title":"Testicular sperm extraction prediction for patients with nonobstructive azoospermia by Raman spectroscopy","volume":"7","author":"Aleksandrov","year":"2026","journal-title":"F&S Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Yao, G., Pan, X., Chen, F., Yang, L., Zhou, L., Peng, M., and Yang, X. (2026). Gut Bacteroidales and AMH\/INH-B ratio predict sperm retrieval: Mechanistic insights via SCFA-mediated regulation of blood-testis barrier and steroidogenesis. Front. Cell. Infect. Microbiol., 16.","DOI":"10.3389\/fcimb.2026.1777930"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Huang, I.-S., Bregente, C.J.B., Lin, T.-P., Huang, E.Y.-H., Kao, C.-Y., and Huang, W.J. (2026). Gut microbiota signatures associated with spermatogenic capacity and sperm retrieval outcomes in non-obstructive azoospermia. J. Assist. Reprod. Genet., Online ahead of print.","DOI":"10.1007\/s10815-026-04002-0"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.ajhg.2022.01.011","article-title":"Whole-exome sequencing improves the diagnosis and care of men with non-obstructive azoospermia","volume":"109","author":"Kherraf","year":"2022","journal-title":"Am. J. Hum. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"hoaf049","DOI":"10.1093\/hropen\/hoaf049","article-title":"Genetic determinants of testicular sperm extraction outcomes: Insights from a large multicentre study of men with non-obstructive azoospermia","volume":"2025","author":"Arafa","year":"2025","journal-title":"Hum. Reprod. Open"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/cncy.20147","article-title":"Biospecimen reporting for improved study quality (BRISQ)","volume":"119","author":"Moore","year":"2011","journal-title":"Cancer Cytopathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nbt1329","article-title":"The minimum information about a proteomics experiment (MIAPE)","volume":"25","author":"Taylor","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","article-title":"Proposed minimum reporting standards for chemical analysis: Chemical Analysis Working Group, Metabolomics Standards Initiative","volume":"3","author":"Sumner","year":"2007","journal-title":"Metabolomics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6562","DOI":"10.1073\/pnas.102102699","article-title":"Selection bias in gene extraction on the basis of microarray gene-expression data","volume":"99","author":"Ambroise","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"m441","DOI":"10.1136\/bmj.m441","article-title":"Calculating the sample size required for developing a clinical prediction model","volume":"368","author":"Riley","year":"2020","journal-title":"BMJ"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e2200302","DOI":"10.1002\/bimj.202200302","article-title":"Stability of clinical prediction models developed using statistical or machine learning methods","volume":"65","author":"Riley","year":"2023","journal-title":"Biom. J."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Van Calster, B., McLernon, D.J., van Smeden, M., Wynants, L., and Steyerberg, E.W. (2019). Calibration: The Achilles heel of predictive analytics. BMC Med., 17.","DOI":"10.1186\/s12916-019-1466-7"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4230","DOI":"10.1002\/sim.9025","article-title":"Minimum sample size for external validation of a clinical prediction model with a binary outcome","volume":"40","author":"Riley","year":"2021","journal-title":"Stat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e074819","DOI":"10.1136\/bmj-2023-074819","article-title":"Evaluation of clinical prediction models (part 1): From development to external validation","volume":"384","author":"Collins","year":"2024","journal-title":"BMJ"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e074820","DOI":"10.1136\/bmj-2023-074820","article-title":"Evaluation of clinical prediction models (part 2): How to undertake an external validation study","volume":"384","author":"Riley","year":"2024","journal-title":"BMJ"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1373\/clinchem.2012.182550","article-title":"Quantifying the added value of a diagnostic test or marker","volume":"58","author":"Moons","year":"2012","journal-title":"Clin. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1016\/j.spinee.2021.02.024","article-title":"Decision curve analysis to evaluate the clinical benefit of prediction models","volume":"21","author":"Vickers","year":"2021","journal-title":"Spine J."},{"key":"ref_62","first-page":"64","article-title":"Patient and practitioner expectations for treatment of non-obstructive azoospermia","volume":"17","author":"Wong","year":"2023","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1093\/humrep\/dew147","article-title":"Prediction model for obtaining spermatozoa with testicular sperm extraction in men with non-obstructive azoospermia","volume":"31","author":"Cissen","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1093\/humrep\/dey366","article-title":"A risk prediction model of sperm retrieval failure with fine-needle aspiration in males with non-obstructive azoospermia","volume":"34","author":"Ma","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e44047","DOI":"10.2196\/44047","article-title":"A machine-learning approach for the prediction of testicular sperm extraction in non-obstructive azoospermia: Algorithm development and validation study","volume":"25","author":"Bachelot","year":"2023","journal-title":"J. Med. Internet Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/s43032-023-01362-1","article-title":"A prediction model of sperm retrieval in males with idiopathic non-obstructive azoospermia for microdissection testicular sperm extraction","volume":"31","author":"Zheng","year":"2024","journal-title":"Reprod. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1111\/andr.70111","article-title":"Development of a nomogram for sperm retrieval at microTESE for idiopathic non-obstructive azoospermia in a multi-center cohort study","volume":"14","author":"Russo","year":"2026","journal-title":"Andrology"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Jiang, X., Li, D., Zheng, Y., Li, Y., Bai, H., Zhao, G., Zhang, Y., and Ma, Y. (2024). Does the FNA sperm retrieval failure prediction model work well for current NOA individuals undertaking risk screening before the operation? Model validation, high-risk population identification and potential alternative sperm retrieval exploration. BMC Med. Inform. Decis. Mak., 24.","DOI":"10.1186\/s12911-024-02816-5"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12958-025-01433-9","article-title":"Development of a predictive model and nomogram in sperm retrieval rate based on testicular pathological morphometric parameters in non-obstructive azoospermia patients: A multi-center study","volume":"24","author":"Wang","year":"2026","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"G\u00fcl, M., \u015eahin, A., \u00d6zer, C., Altan, M., G\u00fcdelci, T., Sahin, K.C., G\u00fcltekin, M.H., \u0130bis, M.A., Duran, M.B., and Sivasl\u0131o\u011flu, B. (2026). Machine Learning-Based Prediction of Sperm Retrieval Outcomes in Patients With Klinefelter Syndrome: A Multicenter Study With External Validation. Andrology, Epub ahead of print.","DOI":"10.1111\/andr.70297"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.urology.2024.10.038","article-title":"A nomogram predicting testicular sperm extraction success in men with non-obstructive azoospermia: A multi-center study","volume":"196","author":"Ceyhan","year":"2025","journal-title":"Urology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/andr.70114","article-title":"Machine learning-based personalized prediction of sperm retrieval in patients with non-obstructive azoospermia prior to microdissection testicular sperm extraction: A multi-center cohort study","volume":"14","author":"Xi","year":"2026","journal-title":"Andrology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e070904","DOI":"10.1136\/bmj-2022-070904","article-title":"Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI","volume":"377","author":"Vasey","year":"2022","journal-title":"BMJ"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Abdallah, H.Y., Hosny, N., Ahmed, N., and Ismail, E.A. (2026). Seminal long non-coding RNAs as prognostic non-invasive bi-omarkers in non-obstructive azoospermia. BMC Med. Genom., 19.","DOI":"10.1186\/s12920-025-02207-3"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/andr.13461","article-title":"Seminal extracellular vesicle sncRNA sequencing reveals altered miRNA\/isomiR profiles as sperm retrieval biomarkers for azoospermia","volume":"12","author":"Larriba","year":"2024","journal-title":"Andrology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1080\/14647273.2022.2104136","article-title":"Evaluation of PGK2 and ACR proteins in seminal plasma: Suggestion of potential new biomarkers for prediction of sperm retrieval in non-obstructive azoospermia patients","volume":"26","author":"Kabodmehri","year":"2023","journal-title":"Hum. Fertil."},{"key":"ref_77","first-page":"246","article-title":"Seminal Plasma ExLncRNA Pairs: Updating Perspectives in the Search for Testicular Spermatozoa Retrieval Biomarkers in Nonobstructive Azoospermia Patients with mTESE by WGCNA","volume":"20","author":"Cao","year":"2023","journal-title":"Urol. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"32","DOI":"10.18565\/urology.2022.4.32-37","article-title":"Prognostic ability of seminal plasma lipidomic analysis in predicting the success of mi-croTESE in men with azoospermia","volume":"4","author":"Gamidov","year":"2022","journal-title":"Urologiia"},{"key":"ref_79","first-page":"S31","article-title":"Can PCNA and LIM15 gene expression levels predict sperm retrieval success in men with non-obstructive azoospermia?","volume":"20","author":"Ibis","year":"2022","journal-title":"Rev. Int. Androl."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Willems, M., Devriendt, C., Olsen, C., Caljon, B., Janssen, T., Gies, I., Vloeberghs, V., Tournaye, H., Van Saen, D., and Goossens, E. (2023). Micro RNA in Semen\/Urine from Non-Obstructive Azoospermia Patients as Biomarkers to Predict the Presence of Testicular Spermatozoa and Spermatogonia. Life, 13.","DOI":"10.3390\/life13030616"},{"key":"ref_81","first-page":"108","article-title":"Evalu-ation of the Utility of Seminal Plasma Resistin and Leptin in Predicting Successful Surgical Sperm Retrieval in Men with Non-Obstructive Azoospermia","volume":"24","author":"Amer","year":"2023","journal-title":"J. Reprod. Infertil."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e13483","DOI":"10.1111\/and.13483","article-title":"Could analysis of testis-specific genes, as bi-omarkers in seminal plasma, predict presence of focal spermatogenesis in non-obstructive azoospermia?","volume":"52","author":"Hashemi","year":"2020","journal-title":"Andrologia"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1093\/humrep\/deu261","article-title":"ESX1 mRNA expression in seminal fluid is an indicator of residual spermatogenesis in non-obstructive azoospermic men","volume":"29","author":"Pansa","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1111\/andr.12874","article-title":"Over-expression of hsa_circ_0000116 in patients with non-obstructive azoospermia and its predictive value in testicular sperm retrieval","volume":"8","author":"Lv","year":"2020","journal-title":"Andrology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1071\/RD17423","article-title":"MicroRNA profile comparison of testicular tissues derived from successful and unsuccessful microdissection testicular sperm extraction retrieval in non-obstructive azoospermia patients","volume":"31","author":"Fang","year":"2019","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s10815-018-1134-4","article-title":"Testicular piRNA profile comparison between successful and unsuccessful micro-TESE retrieval in NOA patients","volume":"35","author":"Cao","year":"2018","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1111\/andr.12528","article-title":"Among seven testis-specific molecular markers, SPEM1 appears to have a significant clinical value for prediction of sperm retrieval in azoospermic men","volume":"6","author":"Hashemi","year":"2018","journal-title":"Andrology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"711","DOI":"10.2164\/jandrol.110.012278","article-title":"Expression of VASA mRNA in testis as a significant predictor of sperm recovery by microdissection testicular sperm extraction in patient with nonobstructive azoospermia","volume":"33","author":"Ando","year":"2012","journal-title":"J. Androl."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.fertnstert.2011.05.055","article-title":"Heat shock factor Y chromosome (HSFY) mRNA level predicts the presence of retrievable testicular sperm in men with nonobstructive azoospermia","volume":"96","author":"Stahl","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1016\/j.fertnstert.2011.03.020","article-title":"CDY1 and BOULE transcripts as-sessed in the same biopsy as predictive markers for successful testicular sperm retrieval","volume":"95","author":"Kleiman","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_91","first-page":"109","article-title":"Metabolic Fingerprinting of Seminal Plasma from Non-obstructive Azoo-spermia Patients: Positive Versus Negative Sperm Retrieval","volume":"19","author":"Gilany","year":"2018","journal-title":"J. Reprod. 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