{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:49:23Z","timestamp":1782103763162,"version":"3.54.5"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The sperm DNA fragmentation index (DFI) provides important reference for evaluating male fertility and assisted reproductive outcomes, and its degree of damage is influenced by multiple factors. Our study aims to develop a machine learning-based predictive model for identifying high sperm DFI in infertile men using clinical and semen parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively collected data on infertile male patients from two centers in Shanghai, China from March 2023 to March 2024. We used data from one center as the training cohort to construct the model and data from another center for external validation. The semen data of the included subjects is combined with clinical features as training features for machine learning. We have developed and validated the effectiveness of six models: Decision Tree (DT), Random Forest (RF), eXtreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), Logistic Regression (LR), and Naive Bayes Classifier (NB). We comprehensively evaluated the performance of machine learning models with different features using ROC curves, accuracy, and other relevant indicators. The SHapley Additive exPlanations (SHAP) diagram was used to illustrate the importance of variables in the model, Lasso regression is used to screen for core features. Finally, a convenient and practical DFI quality early prediction platform was constructed based on core features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      1037 patients from one center were included in the development cohort, while 290 patients from another center were included in the external validation queue. The RF model performed the best in predicting the quality of DFI in infertile male patients, with a 10\u2212fold cross\u2212validation AUC of 0.979 (0.972\u22120.986) in the development cohort, and an AUC of 0.945 (95% CI: 0.916\u22120.975) in the external validation cohort. Finally, the core factors obtained through screening were included in the model, including progressive motility sperm rate, sperm concentration, sperm viability, daily exercise time, smoking status, alcohol consumption, stress level, and insomnia symptoms were incorporated to generate a publicly accessible online platform (\n                      <jats:ext-link>https:\/\/4sjajo-0-0.shinyapps.io\/dfi-prediction-v4\/<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>The RF model using semen parameters and lifestyle factors shows good discrimination for predicting DFI abnormality in infertile men. However, the model exhibits notable miscalibration in external validation (calibration slope 2.196, intercept -0.196), indicating systematic overestimation of risk and insufficient dispersion of predictions. Therefore, in its current form, the model and its associated online calculator should be considered investigational. Prospective validation and recalibration in independent populations are required before any clinical application. Its impact on patient\u2212important reproductive outcomes (e.g., live birth) remains unknown.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1838500","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:34:11Z","timestamp":1782102851000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and validation of a machine learning model for sperm DNA fragmentation rate in infertile men: a multicenter retrospective study"],"prefix":"10.3389","volume":"17","author":[{"given":"Ke","family":"Wang","sequence":"first","affiliation":[{"name":"Center of Reproductive Medicine, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxia","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanxuan","family":"Ge","sequence":"additional","affiliation":[{"name":"Taian Central Hospital, The Affiliated Taian City Central Hospital of Qingdao University","place":["Taian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Bai","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]},{"name":"School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningxin","family":"Qin","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Huang","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, Xinhua Hospital Affiliated Shanghai Jiao Tong University, School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Zhang","sequence":"additional","affiliation":[{"name":"Information Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dem046","article-title":"International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care","volume":"22","author":"Boivin","year":"2007","journal-title":"Hum Reprod"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32708-2","article-title":"A Lancet Commission on 70 years of women's reproductive, maternal, newborn, child, and adolescent health in China","volume":"397","author":"Qiao","year":"2021","journal-title":"Lancet"},{"key":"B3","article-title":"WHO laboratory manual for the examination and processing of human semen (fifth edition) [M]","year":"2010"},{"key":"B4","unstructured":"WHO laboratory manual for the examination and processing of human semen (sixth edition) [EB\/OL]\n          \n          \n          \n          2021"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.56434\/j.arch.esp.urol.20267903.44","article-title":"Sperm DNA Fragmentation Testing in the Era of Assisted Reproduction: Clinical Utility, Thresholds, and Management Strategies","volume":"79","author":"Zhao","year":"2026","journal-title":"Arch Esp Urol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9020134","article-title":"Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility","volume":"9","author":"Nowicka-Bauer","year":"2020","journal-title":"Antioxid (Basel)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.fertnstert.2023.05.157","article-title":"Artificial intelligence for sperm selection-a systematic review","volume":"120","author":"Cherouveim","year":"2023","journal-title":"Fertil Steril"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.24703","article-title":"Sperm-cell DNA fragmentation prediction using label-free quantitative phase imaging and deep learning","volume":"103","author":"Noy","year":"2023","journal-title":"Cytometry A"},{"key":"B9","doi-asserted-by":"publisher","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":"B10","doi-asserted-by":"publisher","DOI":"10.13263\/j.cnki.nja.2022.09.013","article-title":"Chinese expert consensus on male fertility assessment","volume":"28","year":"2022","journal-title":"Chin J Andrology"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2147\/JMDH.S440778","article-title":"The Impact of Using Donor Sperm After ICSI Failure in Severe Oligozoospermia on Male Mental Health and Erectile Function","volume":"17","author":"Yin","year":"2024","journal-title":"J Multidiscip Healthc"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2147\/JMDH.S494319","article-title":"Effect of Donor Sperm on Quality of Life in Patients with Severe Oligoasthenosperm After ICSI Failure","volume":"18","author":"Wang","year":"2025","journal-title":"J Multidiscip Healthc"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.508","article-title":"Sperm Chromatin Structure Assay (SCSA\u00ae) for Fertility Assessment","volume":"2","author":"Evenson","year":"2022","journal-title":"Curr Protoc"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoy004","article-title":"ESHRE guideline: recurrent pregnancy loss","volume":"2018","author":"Bender Atik","year":"2018","journal-title":"Hum Reprod Open"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.21037\/tau.2019.06.22","article-title":"The effect of sperm DNA fragmentation index on assisted reproductive technology outcomes and its relationship with semen parameters and lifestyle","volume":"8","author":"Yang","year":"2019","journal-title":"Transl Androl Urol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"15","DOI":"10.5603\/FHC.a2019.0002","article-title":"The impact of sedentary work on sperm nuclear DNA integrity","volume":"57","author":"Gill","year":"2019","journal-title":"Folia Histochem Cytobiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.18502\/ijrm.v19i10.9825","article-title":"Impacts of garlic extract on testicular oxidative stress and sperm characteristics in type 1 and 2 diabetic rats: An experimental study","volume":"19","author":"Lotfi","year":"2021","journal-title":"Int J Reprod BioMed"},{"key":"B18","doi-asserted-by":"publisher","first-page":"25","DOI":"10.4103\/aja202329","article-title":"Decreased AKAP4\/PKA signaling pathway in high DFI sperm affects sperm capacitation","volume":"26","author":"Zhang","year":"2024","journal-title":"Asian J Androl"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12111937","article-title":"Effect of Micronutrients and L-Carnitine as Antioxidant on Sperm Parameters, Genome Integrity, and ICSI Outcomes: Randomized, Double-Blind, and Placebo-Controlled Clinical Trial","volume":"12","author":"Lahimer","year":"2023","journal-title":"Antioxid (Basel)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/jpm13030518","article-title":"How Well Do Semen Analysis Parameters Correlate with Sperm DNA Fragmentation? A Retrospective Study from 2567 Semen Samples Analyzed by the Halosperm Test","volume":"13","author":"Chua","year":"2023","journal-title":"J Pers Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.5534\/wjmh.180028","article-title":"Superoxide Anion Production by the Spermatozoa of Men with Varicocele: Relationship with Varicocele Grade and Semen Parameters","volume":"36","author":"Alkan","year":"2018","journal-title":"World J Mens Health"},{"key":"B22","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1093\/biolre\/ioad050","article-title":"Aerobic exercises regulate the epididymal anion homeostasis of high-fat diet-induced obese rats through TRPA1-mediated Cl- and HCO3- secretion","volume":"109","author":"Gao","year":"2023","journal-title":"Biol Reprod"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2012.04419.x","article-title":"Sleep timing may modulate the effect of sleep loss on testosterone","volume":"77","author":"Schmid","year":"2012","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsycho.2012.09.011","article-title":"Sleep deprivation lowers reactive aggression and testosterone in men","volume":"92","author":"Cote","year":"2013","journal-title":"Biol Psychol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.01.098","article-title":"Association of state and trait anxiety to semen quality of in vitro fertilization patients: a controlled study","volume":"99","author":"Vellani","year":"2013","journal-title":"Fertil Steril"},{"key":"B26","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s12880-025-01701-5","article-title":"Deep learning approaches for classification tasks in medical X-ray, MRI, and ultrasound images: a scoping review","volume":"25","author":"La\u00e7i","year":"2025","journal-title":"BMC Med Imaging"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/andr.13436","article-title":"Novel sperm chromatin dispersion test with artificial intelligence-aided halo evaluation: A comparison study with existing modalities","volume":"11","author":"Kuroda","year":"2023","journal-title":"Andrology"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201900712","article-title":"Prediction of DNA Integrity from Morphological Parameters Using a Single-Sperm DNA Fragmentation Index Assay","volume":"6","author":"Wang","year":"2019","journal-title":"Adv Sci (Weinh)"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1838500\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:34:25Z","timestamp":1782102865000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1838500\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":28,"alternative-id":["10.3389\/fendo.2026.1838500"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1838500","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]},"article-number":"1838500"}}