{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T23:58:35Z","timestamp":1788393515604,"version":"build-2803163510"},"reference-count":70,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III, Ministry of Science and Innovation, Government of Spain","award":["PI21\/00564"],"award-info":[{"award-number":["PI21\/00564"]}]},{"name":"Instituto de Salud Carlos III, Ministry of Science and Innovation, Government of Spain","award":["2021SGR00122"],"award-info":[{"award-number":["2021SGR00122"]}]},{"name":"Instituto de Salud Carlos III, Ministry of Science and Innovation, Government of Spain","award":["UAB\/PIF2022"],"award-info":[{"award-number":["UAB\/PIF2022"]}]},{"name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca (AGAUR), Generalitat de Catalunya","award":["PI21\/00564"],"award-info":[{"award-number":["PI21\/00564"]}]},{"name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca (AGAUR), Generalitat de Catalunya","award":["2021SGR00122"],"award-info":[{"award-number":["2021SGR00122"]}]},{"name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca (AGAUR), Generalitat de Catalunya","award":["UAB\/PIF2022"],"award-info":[{"award-number":["UAB\/PIF2022"]}]},{"DOI":"10.13039\/501100011104","name":"UAB","doi-asserted-by":"publisher","award":["PI21\/00564"],"award-info":[{"award-number":["PI21\/00564"]}],"id":[{"id":"10.13039\/501100011104","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011104","name":"UAB","doi-asserted-by":"publisher","award":["2021SGR00122"],"award-info":[{"award-number":["2021SGR00122"]}],"id":[{"id":"10.13039\/501100011104","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011104","name":"UAB","doi-asserted-by":"publisher","award":["UAB\/PIF2022"],"award-info":[{"award-number":["UAB\/PIF2022"]}],"id":[{"id":"10.13039\/501100011104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Standard semen parameters remain the cornerstone of male infertility evaluation, though they often poorly reflect the likelihood of success in assisted reproductive technology (ART). This study evaluates sperm DNA fragmentation (SDF) as a diagnostic tool for male infertility and predictive biomarker for ART success. Semen samples were collected from 20 fertile donors and 40 infertile patients with abnormal semen parameters. A fraction of each sample was used for SDF assessment via TUNEL assay and flow cytometry, while the remaining portion was processed for conventional semen analysis and ART. Infertile patients exhibited higher SDF levels (32.77 \u00b1 13.61%) compared to donors (22.19 \u00b1 8.37%; p &lt; 0.01), a difference that remained statistically significant across all subgroups stratified by semen parameters. Additionally, significant correlations were obtained between the percentage of SDF and sperm count (r = \u22120.4036), motility (r = \u22120.6377), and morphology (r = \u22120.2783). Regarding ART outcomes, patients with low-quality embryos exhibited higher SDF levels compared to those with high-quality embryos (30.02 \u00b1 12.52% vs. 23.16 \u00b1 8.41%; p = 0.0036). Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) above 0.7 for the classification of male infertility as well as the assessment of embryo quality. Overall, our results support the utility of SDF as both a diagnostic biomarker for male infertility and a predictive indicator of embryo quality in ART, particularly in the presence of an oocyte-related female factor.<\/jats:p>","DOI":"10.3390\/ijms26136314","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"6314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Utility of Sperm DNA Fragmentation as a Diagnostic Tool for Male Infertility and Its Predictive Value for Assisted Reproductive Technology Outcomes"],"prefix":"10.3390","volume":"26","author":[{"given":"Coral","family":"Zurera-Egea","sequence":"first","affiliation":[{"name":"Genetics of Male Fertility Group, Unitat de Biologia Cel lular, Departament de Biologia Cel lular, de Fisiologia i d\u2019Immunologia, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e9s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00edlvia","family":"Mateo","sequence":"additional","affiliation":[{"name":"Dexeus Fertility, Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Universitari Dexeus, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Novo","sequence":"additional","affiliation":[{"name":"Fertilab, 08017 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Asensio","sequence":"additional","affiliation":[{"name":"Reproclinic, 08011 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0389-0638","authenticated-orcid":false,"given":"Montserrat","family":"Boada","sequence":"additional","affiliation":[{"name":"Dexeus Fertility, Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Universitari Dexeus, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Antich","sequence":"additional","affiliation":[{"name":"Fertilab, 08017 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Rovira","sequence":"additional","affiliation":[{"name":"Fertilab, 08017 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9677-1376","authenticated-orcid":false,"given":"Zaida","family":"Sarrate","sequence":"additional","affiliation":[{"name":"Genetics of Male Fertility Group, Unitat de Biologia Cel lular, Departament de Biologia Cel lular, de Fisiologia i d\u2019Immunologia, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e9s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0647-3856","authenticated-orcid":false,"given":"Joan","family":"Blanco","sequence":"additional","affiliation":[{"name":"Genetics of Male Fertility Group, Unitat de Biologia Cel lular, Departament de Biologia Cel lular, de Fisiologia i d\u2019Immunologia, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e9s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8914-2667","authenticated-orcid":false,"given":"Ester","family":"Anton","sequence":"additional","affiliation":[{"name":"Genetics of Male Fertility Group, Unitat de Biologia Cel lular, Departament de Biologia Cel lular, de Fisiologia i d\u2019Immunologia, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e9s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","unstructured":"(2025, January 29). Infertility, 2024. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/infertility."},{"key":"ref_2","first-page":"402","article-title":"Can we predict the IVF\/ICSI live birth rate?","volume":"23","author":"Metello","year":"2019","journal-title":"J. Bras. Reprod. Assist."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Agarwal, A., Mulgund, A., Hamada, A., and Chyatte, M.R. (2015). A unique view on male infertility around the globe. Reprod. Biol. Endocrinol., 13.","DOI":"10.1186\/s12958-015-0032-1"},{"key":"ref_4","unstructured":"Leslie, S.W., Soon-Sutton, T.L., and Khan, M.A. (2024). Male Infertility. StatPearls [Internet], StatPearls Publishing LLC."},{"key":"ref_5","unstructured":"Keel, B.A., and Webster, B. (1990). The semen analysis. CRC Handbook of the Laboratory Diagnosis and Treatment of Infertility, CRC Press."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.fertnstert.2021.11.034","article-title":"Extended semen examinations in the sixth edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen: Contributing to the understanding of the function of the male reproductive system","volume":"117","author":"Baldi","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1093\/biolre\/ioac105","article-title":"Advanced molecular approaches in male infertility diagnosis","volume":"107","author":"Botezatu","year":"2022","journal-title":"Biol. Reprod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1016\/j.urology.2010.04.036","article-title":"TUNEL as a test for sperm DNA damage in the evaluation of male infertility","volume":"76","author":"Sharma","year":"2010","journal-title":"Urology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1093\/humrep\/dei231","article-title":"Sperm DNA fragmentation: Threshold value in male fertility","volume":"20","author":"Sergerie","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.rbmo.2018.06.023","article-title":"Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management\u2013meta-analyses","volume":"37","author":"Santi","year":"2018","journal-title":"Reprod. Biomed. Online"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1007\/s10815-019-01476-z","article-title":"DNA fragmentation in concert with the simultaneous assessment of cell viability in a subfertile population: Establishing thresholds of normality both before and after density gradient centrifugation","volume":"36","author":"Punjabi","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1093\/humrep\/der461","article-title":"Alkaline and neutral Comet assay profiles of sperm DNA damage in clinical groups","volume":"27","author":"Abad","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.fertnstert.2015.06.005","article-title":"DNA fragmentation in brighter sperm predicts male fertility independently from age and semen parameters","volume":"104","author":"Muratori","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e221","DOI":"10.1111\/j.1365-2605.2009.00995.x","article-title":"Sperm chromatin structure assay as an independent predictor of fertility in vivo: A case-control study","volume":"33","author":"Giwercman","year":"2010","journal-title":"Int. J. Androl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.fertnstert.2004.08.042","article-title":"Sperm DNA fragmentation negatively correlates with velocity and fertilization rates but might not affect pregnancy rates","volume":"84","author":"Huang","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1093\/humrep\/deq103","article-title":"Clinical significance of sperm DNA damage in assisted reproduction outcome","volume":"25","author":"Simon","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s10815-021-02129-w","article-title":"Sperm selection during ICSI treatments reduces single- but not double-strand DNA break values compared to the semen sample","volume":"38","author":"Benet","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.fertnstert.2003.09.044","article-title":"Influence of deoxyribonucleic acid damage on fertilization and pregnancy","volume":"81","author":"Henkel","year":"2004","journal-title":"Fertil. Steril."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.fertnstert.2020.10.045","article-title":"Oocyte ability to repair sperm DNA fragmentation: The impact of maternal age on intracytoplasmic sperm injection outcomes","volume":"116","author":"Setti","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhu, C., Chen, F., Zhang, S., She, H., Ju, Y., Wen, X., Yang, C., Sun, Y., Dong, N., and Xue, T. (2022). Influence of sperm DNA fragmentation on the clinical outcome of in vitro fertilization-embryo transfer (IVF-ET). Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.945242"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sugihara, A., Punjabi, U., Roelant, E., and De Neubourg, D. (2022). Is There a Relationship between Sperm DNA Fragmentation and Intra-Uterine Insemination Outcome in Couples with Unexplained or Mild Male Infertility? Results from the ID-Trial. Life, 13.","DOI":"10.3390\/life13010011"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.fertnstert.2022.04.002","article-title":"Sperm deoxyribonucleic acid fragmentation (by terminal deoxynucleotidyl transferase biotin dUTP nick end labeling assay) does not impair reproductive success measured as cumulative live birth rates per donor metaphase II oocyte used","volume":"118","author":"Pacheco","year":"2022","journal-title":"Fertil Steril."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s10815-015-0635-7","article-title":"Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay using bench top flow cytometer for evaluation of sperm DNA fragmentation in fertility laboratories: Protocol, reference values, and quality control","volume":"33","author":"Sharma","year":"2016","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kadoch, E., Benguigui, J., Chow-Shi-Y\u00e9e, M., Tadevosyan, A., Bissonnette, F., Phillips, S., Zini, A., and Kadoch, I.J. (2024). The paternal clock: Uncovering the consequences of advanced paternal age on sperm DNA fragmentation. Reprod. Biol., 24.","DOI":"10.1016\/j.repbio.2024.100931"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ejogrb.2024.06.018","article-title":"A 2-step remote TUNEL approach for sperm DNA fragmentation assessment. Analysis in donors and patients","volume":"299","author":"Manjon","year":"2024","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ragosta, M.E., Traini, G., Tamburrino, L., Degl\u2019Innocenti, S., Fino, M.G., Dabizzi, S., Vignozzi, L., Baldi, E., and Marchiani, S. (2024). Sperm Chromatin Dispersion Test Detects Sperm DNA Fragmentation Mainly Associated with Unviable Spermatozoa and Underestimates the Values with Respect to TUNEL Assay. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084481"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"317","DOI":"10.4103\/jhrs.jhrs_140_23","article-title":"Explaining the Unexplained: Examining the Predictive Value of Semen Parameters, Sperm DNA Fragmentation and Metal Levels in Unexplained Infertility","volume":"16","author":"Ghuman","year":"2023","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ribas-Maynou, J., Garc\u00eda-Peir\u00f3, A., Fernandez-Encinas, A., Amengual, M.J., Prada, E., Cort\u00e9s, P., Navarro, J., and Benet, J. (2012). Double stranded sperm DNA breaks, measured by Comet assay, are associated with unexplained recurrent miscarriage in couples without a female factor. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044679"},{"key":"ref_29","unstructured":"WHO (2021). Laboratory Manual for the Examination and Processing of Human Semen, WHO. [6th ed.]."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Conti, D., Calamai, C., and Muratori, M. (2024). Sperm DNA Fragmentation in Male Infertility: Tests, Mechanisms, Meaning and Sperm Population to Be Tested. J. Clin. Med., 13.","DOI":"10.3390\/jcm13175309"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/j.2047-2927.2013.00111.x","article-title":"Comprehensive analysis of sperm DNA fragmentation by five different assays: TUNEL assay, SCSA, SCD test and alkaline and neutral Comet assay","volume":"1","author":"Abad","year":"2013","journal-title":"Andrology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e13308","DOI":"10.1111\/and.13308","article-title":"Investigating the relationship between BRCA1 and BRCA2 genes methylation profile and sperm DNA fragmentation in infertile men","volume":"51","author":"Kabartan","year":"2019","journal-title":"Andrologia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.fertnstert.2015.11.037","article-title":"Sperm DNA fragmentation and mitochondrial membrane potential combined are better for predicting natural conception than standard sperm parameters","volume":"105","author":"Golob","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yoshikawa-Terada, K., Takeuchi, H., Tachibana, R., Takayama, E., Kondo, E., and Ikeda, T. (2024). Age; sexual abstinence duration; sperm morphology, and motility are predictors of sperm DNA fragmentation. Reprod. Med. Biol., 23.","DOI":"10.1002\/rmb2.12585"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.fertnstert.2004.11.022","article-title":"Effect of reactive oxygen species produced by spermatozoa and leukocytes on sperm functions in non-leukocytospermic patients","volume":"83","author":"Henkel","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s10815-014-0194-3","article-title":"Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation","volume":"31","author":"Belloc","year":"2014","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4081\/aiua.2013.1.8","article-title":"The study of spermatic DNA fragmentation and sperm motility in infertile subjects","volume":"85","author":"Peluso","year":"2013","journal-title":"Arch. Ital. Urol. Androl."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.urology.2013.03.058","article-title":"Oxidative Stress Negatively Affects Human Sperm Mitochondrial Respiration","volume":"82","author":"Ferramosca","year":"2013","journal-title":"Urology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1530\/REP-16-0342","article-title":"Sperm of patients with severe asthenozoospermia show biochemical, molecular and genomic alterations","volume":"152","author":"Bonanno","year":"2016","journal-title":"Reproduction"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/j.1939-4640.1992.tb03328.x","article-title":"Reactive oxygen species and human spermatozoa. II. Depletion of adenosine triphosphate plays an important role in the inhibition of sperm motility","volume":"13","author":"Gagnon","year":"1992","journal-title":"J. Androl."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/S0891-5849(98)00275-5","article-title":"Characterization of reactive oxygen species induced effects on human spermatozoa movement and energy metabolism","volume":"26","author":"Armstrong","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/978-3-030-21664-1_5","article-title":"Sperm DNA Fragmentation: Mechanisms of Origin","volume":"1166","author":"Muratori","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1006\/excr.1999.4586","article-title":"Abnormal sperm parameters in humans are indicative of an abortive apoptotic mechanism linked to the Fas-mediated pathway","volume":"251","author":"Sakkas","year":"1999","journal-title":"Exp. Cell Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2119\/molmed.2014.00158","article-title":"Investigation on the origin of sperm DNA fragmentation: Role of apoptosis, immaturity and oxidative stress","volume":"21","author":"Muratori","year":"2015","journal-title":"Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/aja.2011.59","article-title":"Mechanisms and clinical correlates of sperm DNA damage","volume":"14","author":"Tamburrino","year":"2012","journal-title":"Asian J. Androl."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.fertnstert.2009.10.046","article-title":"Sperm DNA fragmentation: Mechanisms of origin, impact on reproductive outcome, and analysis","volume":"93","author":"Sakkas","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/humupd\/dml009","article-title":"Protamines and male infertility","volume":"12","author":"Oliva","year":"2006","journal-title":"Hum. Reprod. Update"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1095\/biolreprod.101.002667","article-title":"Combination of dithiothreitol and detergent treatment of spermatozoa causes paternal chromosomal damage","volume":"67","author":"Szczygiel","year":"2002","journal-title":"Biol. Reprod."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1016\/j.fertnstert.2014.02.006","article-title":"Sperm deoxyribonucleic acid damage in normozoospermic men is related to age and sperm progressive motility","volume":"101","author":"Belloc","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.fertnstert.2003.04.002","article-title":"Effects of age on DNA double-strand breaks and apoptosis in human sperm","volume":"80","author":"Singh","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1093\/humrep\/deaa159","article-title":"DNA fragmentation of sperm: A radical examination of the contribution of oxidative stress and age in 16\u2009945 semen samples","volume":"35","author":"Vaughan","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Baskaran, S., Agarwal, A., Selvam, M.K.P., Finelli, R., Robert, K.A., Iovine, C., Pushparaj, P.N., Samanta, L., Harlev, A., and Henkel, R. (2019). Tracking research trends and hotspots in sperm DNA fragmentation testing for the evaluation of male infertility: A scientometric analysis. Reprod. Biol. Endocrinol., 17.","DOI":"10.1186\/s12958-019-0550-3"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1111\/brv.12700","article-title":"Clinical implications of sperm DNA damage in IVF and ICSI: Updated systematic review and meta-analysis","volume":"96","author":"Yeste","year":"2021","journal-title":"Biol. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1111\/1471-0528.17796","article-title":"Quantifying the association of sperm DNA fragmentation with assisted reproductive technology outcomes: An umbrella review","volume":"131","author":"Maghraby","year":"2024","journal-title":"BJOG"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.fertnstert.2006.05.057","article-title":"Sperm deoxyribonucleic acid fragmentation as a prognostic indicator of assisted reproductive technology outcome","volume":"87","author":"Benchaib","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1093\/humrep\/deu040","article-title":"Comparative analysis of three sperm DNA damage assays and sperm nuclear protein content in couples undergoing assisted reproduction treatment","volume":"29","author":"Simon","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1093\/humrep\/del251","article-title":"Sperm DNA fragmentation: Paternal effect on early post-implantation embryo development in ART","volume":"21","author":"Borini","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.fertnstert.2007.02.022","article-title":"Adequate ovarian follicular status does not prevent the decrease in pregnancy rates associated with high sperm DNA fragmentation","volume":"89","author":"Frydman","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.rbmo.2011.07.010","article-title":"Impact of sperm DNA fragmentation on the outcome of IVF with own or donated oocytes","volume":"23","author":"Esbert","year":"2011","journal-title":"Reprod. Biomed. Online"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/mrd.1080380107","article-title":"Evidence for a Strong Paternal Effect on Human Preimplantation Embryo Development and Blastocyst Formation","volume":"38","author":"Janny","year":"1994","journal-title":"Mol. Reprod. Dev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4103\/aja.aja_19_17","article-title":"Sperm DNA damage has a negative effect on early embryonic development following in vitro fertilization","volume":"20","author":"Zheng","year":"2018","journal-title":"Asian J. Androl."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/humrep\/deh127","article-title":"Late; but not early, paternal effect on human embryo development is related to sperm DNA fragmentation","volume":"19","author":"Tesarik","year":"2004","journal-title":"Hum. Reprod."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.1093\/humrep\/17.12.3122","article-title":"Sperm DNA quality predicts intrauterine insemination outcome: A prospective cohort study","volume":"17","author":"Duran","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.fertnstert.2009.02.050","article-title":"DNA fragmentation of normal spermatozoa negatively impacts embryo quality and intracytoplasmic sperm injection outcome","volume":"94","author":"Franchi","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.fertnstert.2015.01.014","article-title":"Effect of sperm DNA fragmentation on the clinical outcomes for in vitro fertilization and intracytoplasmic sperm injection in women with different ovarian reserves","volume":"103","author":"Jin","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.fertnstert.2011.07.356","article-title":"Oxidative deoxyribonucleic acid damage in sperm has a negative impact on clinical pregnancy rate in intrauterine insemination but not intracytoplasmic sperm injection cycles","volume":"96","author":"Thomson","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1093\/humrep\/deg228","article-title":"Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique","volume":"18","author":"Benchaib","year":"2003","journal-title":"Hum. Reprod."},{"key":"ref_68","first-page":"42","article-title":"The Embryology Interest Group: Updating ASEBIR\u2019s morphological scoring system for early embryos, morulae and blastocysts","volume":"5","author":"Saiz","year":"2018","journal-title":"Med. Reprod. Embriol. Cl\u00edn."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/molehr\/gam046","article-title":"Characterization of M540 bodies in human semen: Evidence that they are apoptotic bodies","volume":"13","author":"Marchiani","year":"2007","journal-title":"Mol. Hum. Reprod."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4097\/kja.21209","article-title":"Receiver operating characteristic curve: Overview and practical use for clinicians","volume":"75","author":"Nahm","year":"2022","journal-title":"Korean J. 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