{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:40:16Z","timestamp":1791470416901,"version":"4.3.4"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T00:00:00Z","timestamp":1599523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>What is the relationship between sperm DNA fragmentation and oxidative stress (OS) with increasing male age?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>Sperm DNA fragmentation increases with age and is likely related to both defective spermatogenesis and increasing OS levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>Sperm quality declines with age. The presence of DNA damage in a high fraction of spermatozoa from a raw semen sample is associated with lower male fertility in natural conception and intrauterine insemination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>A retrospective cohort study of 16\u2009945 semen samples analysed at a single reference laboratory between January 2010 and December 2018.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>All males were undergoing an infertility evaluation. The cohort was divided into seven age categories: &amp;lt;30, 30\u201334, 35\u201339, 40\u201344, 45\u201349, 50 to &amp;lt;54 and \u226555 years. The mean age was 37.6 years (SD 6.8). Sperm DNA fragmentation index (DFI) and high DNA stainability (HDS) were calculated using flow cytometry. OS levels were measured using the oxidative stress adducts (OSA) test, by spectrophotometry. ANOVA with weighted polynomial contrast analysis was used to evaluate trends for DFI, OSA and HDS values across age categories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>Mean DFI significantly increased across all age groups (Ptrend\u2009&amp;lt;\u20090.001). OSA was lowest in patients &amp;lt;30 years old (mean 3.6, SD 1.0) and also increased as age increased (Ptrend\u2009&amp;lt;\u20090.001). There was a statistically significant difference between age groups for each of the three parameters (P\u2009&amp;lt;\u20090.001). There was a significant linear trend for DFI, OSA and HDS across the seven age categories (P\u2009&amp;lt;\u20090.001). Among patients with high DFI, there was a decreasing age-dependent trend in the patients observed with high OSA (P\u2009&amp;lt;\u20090.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>This is a retrospective study. All males included in the study were undergoing a work-up for infertility and may not be representative of a fertile population. Additional patient demographics and clinical data were not available.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>DNA and\/or oxidative damage in sperm may be just as important to understand as the chromosomal aberrations that are carried in the oocyte. Further studies are needed to evaluate the effect of advancing paternal age on the male genome and, ultimately, on the health of the offspring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>No funding was obtained for this study. V.D. is an employee of Reprosource\/Quest Diagnostics. D.S. reports he was a Scientific Advisor to Cooper Surgical.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>N\/A<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deaa159","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T15:10:57Z","timestamp":1591715457000},"page":"2188-2196","source":"Crossref","is-referenced-by-count":83,"title":["DNA fragmentation of sperm: a radical examination of the contribution of oxidative stress and age in 16\u2009945 semen samples"],"prefix":"10.1093","volume":"35","author":[{"given":"D A","family":"Vaughan","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA"},{"name":"Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Boston IVF, Waltham, MA 02445, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Tirado","sequence":"additional","affiliation":[{"name":"ReproSource Fertility Diagnostics, Marlborough, MA 01752, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Garcia","sequence":"additional","affiliation":[{"name":"Clinica EUGIN, Barcelona 08029, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Datta","sequence":"additional","affiliation":[{"name":"ReproSource Fertility Diagnostics, Marlborough, MA 01752, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Sakkas","sequence":"additional","affiliation":[{"name":"Boston IVF, Waltham, MA 02445, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,8]]},"reference":[{"key":"2020092514445669800_deaa159-B1","doi-asserted-by":"crossref","first-page":"935","DOI":"10.21037\/tau.2016.10.03","article-title":"Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios","volume":"5","author":"Agarwal","year":"2016","journal-title":"Transl Androl Urol"},{"key":"2020092514445669800_deaa159-B2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.4103\/aja.aja_5_19","article-title":"Multi-center evaluation of oxidation-reduction potential by the MiOXSYS in males with abnormal semen","volume":"21","author":"Agarwal","year":"2019","journal-title":"Asian J Androl"},{"key":"2020092514445669800_deaa159-B3","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.fertnstert.2006.02.088","article-title":"Oxidative stress in an assisted reproductive techniques setting","volume":"86","author":"Agarwal","year":"2006","journal-title":"Fertil Steril"},{"key":"2020092514445669800_deaa159-B4","doi-asserted-by":"crossref","first-page":"R189","DOI":"10.1530\/REP-19-0452","article-title":"Impact of oxidative stress on male and female germ cells: implications for fertility","volume":"159","author":"Aitken","year":"2020","journal-title":"Reproduction"},{"key":"2020092514445669800_deaa159-B5","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/molehr\/gat025","article-title":"The source and significance of DNA damage in human spermatozoa; a commentary on diagnostic strategies and straw man fallacies","volume":"19","author":"Aitken","year":"2013","journal-title":"Mol Hum Reprod"},{"key":"2020092514445669800_deaa159-B6","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1089\/ars.2010.3186","article-title":"Redox regulation of human sperm function: from the physiological control of sperm capacitation to the etiology of infertility and DNA damage in the germ line","volume":"14","author":"Aitken","year":"2011","journal-title":"Antioxid Redox Signal"},{"key":"2020092514445669800_deaa159-B7","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1002\/(SICI)1098-2795(199708)47:4<468::AID-MRD14>3.0.CO;2-S","article-title":"Reactive oxygen species generation by human spermatozoa is induced by exogenous NADPH and inhibited by the flavoprotein inhibitors diphenylene iodonium and quinacrine","volume":"47","author":"Aitken","year":"1997","journal-title":"Mol Reprod Dev"},{"key":"2020092514445669800_deaa159-B8","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.2164\/jandrol.112.016535","article-title":"Reactive oxygen species and sperm function\u2013in sickness and in health","volume":"33","author":"Aitken","year":"2012","journal-title":"J Androl"},{"key":"2020092514445669800_deaa159-B9","doi-asserted-by":"crossref","first-page":"S221","DOI":"10.1016\/S0098-2997(97)00040-X","article-title":"The protective role of ubiquinol-10 against formation of lipid hydroperoxides in human seminal fluid","volume":"18(Suppl","author":"Alleva","year":"1997","journal-title":"Mol Aspects Med"},{"key":"2020092514445669800_deaa159-B10","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1126\/science.1108190","article-title":"Epigenetic transgenerational actions of endocrine disruptors and male fertility","volume":"308","author":"Anway","year":"2005","journal-title":"Science"},{"key":"2020092514445669800_deaa159-B11","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1093\/humupd\/dmx021","article-title":"The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance-challenges and future research opportunities","volume":"23","author":"Barratt","year":"2017","journal-title":"Hum Reprod Update"},{"key":"2020092514445669800_deaa159-B12","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1093\/humrep\/del019","article-title":"The sperm chromatin structure assay as a diagnostic tool in the human fertility clinic","volume":"21","author":"Boe-Hansen","year":"2006","journal-title":"Hum Reprod"},{"key":"2020092514445669800_deaa159-B13","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41591-019-0711-0","article-title":"Autism risk in offspring can be assessed through quantification of male sperm mosaicism","volume":"26","author":"Breuss","year":"2020","journal-title":"Nat Med"},{"key":"2020092514445669800_deaa159-B14","doi-asserted-by":"crossref","first-page":"e13012","DOI":"10.1111\/and.13012","article-title":"Reactive oxygen species impact on sperm DNA and its role in male infertility","volume":"50","author":"Bui","year":"2018","journal-title":"Andrologia"},{"key":"2020092514445669800_deaa159-B15","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/aja.2010.73","article-title":"Sperm chromatin structure assay (SCSA): a tool in diagnosis and treatment of infertility","volume":"13","author":"Bungum","year":"2011","journal-title":"Asian J Androl"},{"key":"2020092514445669800_deaa159-B16","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1093\/humrep\/del326","article-title":"Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome","volume":"22","author":"Bungum","year":"2007","journal-title":"Hum Reprod"},{"key":"2020092514445669800_deaa159-B17","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/01485010290099390","article-title":"Sperm DNA fragmentation is increased in couples with unexplained recurrent pregnancy loss","volume":"49","author":"Carrell","year":"2003","journal-title":"Arch Androl"},{"key":"2020092514445669800_deaa159-B18","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.fertnstert.2007.04.055","article-title":"Do sperm DNA integrity tests predict pregnancy with in vitro fertilization?","volume":"89","author":"Collins","year":"2008","journal-title":"Fertil Steril"},{"key":"2020092514445669800_deaa159-B19","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1001\/jamapsychiatry.2013.4525","article-title":"Paternal age at childbearing and offspring psychiatric and academic morbidity","volume":"71","author":"D\u2019Onofrio","year":"2014","journal-title":"JAMA Psychiatry"},{"key":"2020092514445669800_deaa159-B20","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/S0015-0282(16)55992-5","article-title":"Human sperm hyperactivation in whole semen and its association with low superoxide scavenging capacity in seminal plasma","volume":"59","author":"de Lamirande","year":"1993","journal-title":"Fertil Steril"},{"key":"2020092514445669800_deaa159-B21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/13685538.2019.1600496","article-title":"Male age is associated with sperm DNA\/chromatin integrity","volume":"9","author":"Deenadayal Mettler","year":"2019","journal-title":"Aging Male"},{"key":"2020092514445669800_deaa159-B22","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/978-3-030-21664-1_7","article-title":"Oxidative damage to sperm DNA: attack and defense","volume":"1166","author":"Drevet","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"2020092514445669800_deaa159-B23","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1016\/j.fertnstert.2008.03.027","article-title":"Deoxyribonucleic acid repair and apoptosis in testicular germ cells of aging fertile men: the role of the poly(adenosine diphosphate-ribosyl)ation pathway","volume":"91","author":"El-Domyati","year":"2009","journal-title":"Fertil Steril"},{"key":"2020092514445669800_deaa159-B24","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/andr.12743","article-title":"Predictive value of oxidative stress testing in semen for sperm DNA fragmentation assessed by sperm chromatin dispersion test","volume":"8","author":"Elbardisi","year":"2019","journal-title":"Andrology"},{"key":"2020092514445669800_deaa159-B25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0891-5849(91)90192-6","article-title":"Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes","volume":"11","author":"Esterbauer","year":"1991","journal-title":"Free Radic Biol Med"},{"key":"2020092514445669800_deaa159-B26","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1126\/science.7444440","article-title":"Relation of mammalian sperm chromatin heterogeneity to fertility","volume":"210","author":"Evenson","year":"1980","journal-title":"Science"},{"key":"2020092514445669800_deaa159-B27","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0890-6238(91)90039-I","article-title":"Individuality of DNA denaturation patterns in human sperm as measured by the sperm chromatin structure assay","volume":"5","author":"Evenson","year":"1991","journal-title":"Reprod Toxicol"},{"key":"2020092514445669800_deaa159-B28","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1093\/humrep\/14.4.1039","article-title":"Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic","volume":"14","author":"Evenson","year":"1999","journal-title":"Hum Reprod"},{"key":"2020092514445669800_deaa159-B29","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1001\/jamapsychiatry.2013.1180","article-title":"Autism risk across generations: a population-based study of advancing grandpaternal and paternal age","volume":"70","author":"Frans","year":"2013","journal-title":"JAMA Psychiatry"},{"key":"2020092514445669800_deaa159-B30","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":"2020092514445669800_deaa159-B31","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1046\/j.1365-2605.1998.00106.x","article-title":"Evaluation of a spectrophotometric assay for the measurement of malondialdehyde and 4-hydroxyalkenals in human spermatozoa: relationships with semen quality and sperm function","volume":"21","author":"Gomez","year":"1998","journal-title":"Int J Androl"},{"key":"2020092514445669800_deaa159-B32","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/tera.1420450612","article-title":"Increased postimplantation loss and malformations among the F2 progeny of male rats chronically treated with cyclophosphamide","volume":"45","author":"Hales","year":"1992","journal-title":"Teratology"},{"key":"2020092514445669800_deaa159-B33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0140-6736(76)92981-0","article-title":"Estimates of maternal age-specific risks of Down-syndrome birth in women aged 34-41","volume":"2","author":"Hook","year":"1976","journal-title":"Lancet"},{"key":"2020092514445669800_deaa159-B34","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.fertnstert.2012.11.024","article-title":"Role of increased male age in IVF and egg donation: is sperm DNA fragmentation responsible?","volume":"99","author":"Humm","year":"2013","journal-title":"Fertil Steril"},{"key":"2020092514445669800_deaa159-B35","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1093\/humrep\/dex267","article-title":"The age of fathers in the USA is rising: an analysis of 168 867 480 births from 1972 to 2015","volume":"32","author":"Khandwala","year":"2017","journal-title":"Hum Reprod"},{"key":"2020092514445669800_deaa159-B36","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1080\/01485010390219728","article-title":"Antioxidant activity of seminal plasma in fertile and infertile men","volume":"49","author":"Koca","year":"2003","journal-title":"Arch Androl"},{"key":"2020092514445669800_deaa159-B37","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nature11396","article-title":"Rate of de novo mutations and the importance of father\u2019s age to disease risk","volume":"488","author":"Kong","year":"2012","journal-title":"Nature"},{"key":"2020092514445669800_deaa159-B38","first-page":"CD010461","article-title":"Advanced sperm selection techniques for assisted reproduction","volume":"7","author":"Lepine","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"2020092514445669800_deaa159-B39","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1080\/19396360801957739","article-title":"Sperm DNA tests as useful adjuncts to semen analysis","volume":"54","author":"Lewis","year":"2008","journal-title":"Syst Biol Reprod Med"},{"key":"2020092514445669800_deaa159-B40","doi-asserted-by":"crossref","first-page":"616","DOI":"10.4103\/1008-682X.153301","article-title":"The paternal genome and the health of the assisted reproductive technology child","volume":"17","author":"Lewis","year":"2015","journal-title":"Asian J Androl"},{"key":"2020092514445669800_deaa159-B41","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.fertnstert.2007.06.018","article-title":"Sperm chromatin structure assay parameters are not related to fertilization rates, embryo quality, and pregnancy rates in in vitro fertilization and intracytoplasmic sperm injection, but might be related to spontaneous abortion rates","volume":"90","author":"Lin","year":"2008","journal-title":"Fertil Steril"},{"key":"2020092514445669800_deaa159-B42","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S0140-6736(18)32989-1","article-title":"Physiological, hyaluronan-selected intracytoplasmic sperm injection for infertility treatment (HABSelect): a parallel, two-group, randomised trial","volume":"393","author":"Miller","year":"2019","journal-title":"Lancet"},{"key":"2020092514445669800_deaa159-B43","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1126\/science.aaf4945","article-title":"Transgenerational inheritance: Models and mechanisms of non-DNA sequence-based inheritance","volume":"354","author":"Miska","year":"2016","journal-title":"Science"},{"key":"2020092514445669800_deaa159-B44","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1365-2605.2009.01042.x","article-title":"The TUNEL assay consistently underestimates DNA damage in human spermatozoa and is influenced by DNA compaction and cell vitality: development of an improved methodology","volume":"34","author":"Mitchell","year":"2011","journal-title":"Int J Androl"},{"key":"2020092514445669800_deaa159-B45","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/humrep\/deh024","article-title":"Relationship between ROS production, apoptosis and DNA denaturation in spermatozoa from patients examined for infertility","volume":"19","author":"Moustafa","year":"2004","journal-title":"Hum Reprod"},{"key":"2020092514445669800_deaa159-B46","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":"2020092514445669800_deaa159-B47","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0301-2115(02)00194-X","article-title":"Detection of oxidative stress in seminal plasma and fractionated sperm from subfertile male patients","volume":"105","author":"Nakamura","year":"2002","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2020092514445669800_deaa159-B48","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1471-2393-13-29","article-title":"Characteristics of first-time fathers of advanced age: a Norwegian population-based study","volume":"13","author":"Nilsen","year":"2013","journal-title":"BMC Pregnancy Childbirth"},{"key":"2020092514445669800_deaa159-B49","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/humrep\/13.2.353","article-title":"Glutathione in spermatozoa and seminal plasma of infertile men","volume":"13","author":"Ochsendorf","year":"1998","journal-title":"Hum Reprod"},{"key":"2020092514445669800_deaa159-B50","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/humupd\/dmy005","article-title":"The effect of paternal factors on perinatal and paediatric outcomes: a systematic review and meta-analysis","volume":"24","author":"Oldereid","year":"2018","journal-title":"Hum Reprod Update"},{"key":"2020092514445669800_deaa159-B51","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/andr.12153","article-title":"Sperm chromatin structure assay in prediction of in vitro fertilization outcome","volume":"4","author":"Oleszczuk","year":"2016","journal-title":"Andrology"},{"key":"2020092514445669800_deaa159-B52","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0140-6736(92)92425-F","article-title":"Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte","volume":"340","author":"Palermo","year":"1992","journal-title":"Lancet"},{"key":"2020092514445669800_deaa159-B53","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1007\/s10815-019-01543-5","article-title":"A treatment approach for couples with disrupted sperm DNA integrity and recurrent ART failure","volume":"36","author":"Parrella","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"2020092514445669800_deaa159-B54","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s10815-007-9162-5","article-title":"The effects of age on DNA fragmentation, chromatin packaging and conventional semen parameters in spermatozoa of oligoasthenoteratozoospermic patients","volume":"24","author":"Plastira","year":"2007","journal-title":"J Assist Reprod Genet"},{"key":"2020092514445669800_deaa159-B55","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1016\/j.fertnstert.2014.12.103","article-title":"Diagnostic evaluation of the infertile male: a committee opinion","volume":"103","year":"2015","journal-title":"Fertil Steril"},{"key":"2020092514445669800_deaa159-B57","doi-asserted-by":"crossref","first-page":"e44679","DOI":"10.1371\/journal.pone.0044679","article-title":"Double stranded sperm DNA breaks, measured by Comet assay, are associated with unexplained recurrent miscarriage in couples without a female factor","volume":"7","author":"Ribas-Maynou","year":"2012","journal-title":"PLoS One"},{"key":"2020092514445669800_deaa159-B58","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/978-1-4419-9190-4_14","article-title":"Mechanisms of action of cyclophosphamide as a male-mediated developmental toxicant","volume":"518","author":"Robaire","year":"2003","journal-title":"Adv Exp Med Biol"},{"key":"2020092514445669800_deaa159-B59","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1093\/humrep\/des261","article-title":"The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis","volume":"27","author":"Robinson","year":"2012","journal-title":"Hum Reprod"},{"key":"2020092514445669800_deaa159-B60","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1007\/s10815-013-0091-1","article-title":"The impact of semen quality, occupational exposure to environmental factors and lifestyle on recurrent pregnancy loss","volume":"30","author":"Ruixue","year":"2013","journal-title":"J Assist Reprod Genet"},{"key":"2020092514445669800_deaa159-B61","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":"2020092514445669800_deaa159-B62","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/humupd\/dmi011","article-title":"Spermatozoal nuclear determinants of reproductive outcome: implications for ART","volume":"11","author":"Seli","year":"2005","journal-title":"Hum Reprod Update"},{"key":"2020092514445669800_deaa159-B63","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":"2020092514445669800_deaa159-B64","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3109\/01485018208987019","article-title":"Vitamin A and beta-carotene content of seminal fluid and sperm of normospermic and oligozoospermic men","volume":"8","author":"Singer","year":"1982","journal-title":"Arch Androl"},{"key":"2020092514445669800_deaa159-B65","author":"Tirado","year":"2010"},{"key":"2020092514445669800_deaa159-B66","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1093\/molehr\/gan062","article-title":"Use of comprehensive chromosomal screening for embryo assessment: microarrays and CGH","volume":"14","author":"Wells","year":"2008","journal-title":"Molecular Hum Reprod"},{"key":"2020092514445669800_deaa159-B56","first-page":"1","article-title":"Recent advances in medically assisted conception. Report of a WHO Scientific Group","volume":"820","year":"1992","journal-title":"World Health Organ Tech Rep Ser"},{"key":"2020092514445669800_deaa159-B67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12610-016-0046-3","article-title":"Predictive value of sperm deoxyribonucleic acid (DNA) fragmentation index in male infertility","volume":"27","author":"Wiweko","year":"2017","journal-title":"Basic Clin Androl"},{"key":"2020092514445669800_deaa159-B68","doi-asserted-by":"crossref","first-page":"9601","DOI":"10.1073\/pnas.0506468103","article-title":"Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm","volume":"103","author":"Wyrobek","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020092514445669800_deaa159-B69","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.fertnstert.2014.06.033","article-title":"Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization\/intracytoplasmic sperm injection: a systematic review and meta-analysis","volume":"102","author":"Zhao","year":"2014","journal-title":"Fertil Steril"},{"key":"2020092514445669800_deaa159-B70","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/S0015-0282(00)01796-9","article-title":"Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men","volume":"75","author":"Zini","year":"2001","journal-title":"Fertil Steril"},{"key":"2020092514445669800_deaa159-B71","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1093\/humrep\/den321","article-title":"Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis","volume":"23","author":"Zini","year":"2008","journal-title":"Hum Reprod"},{"key":"2020092514445669800_deaa159-B72","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/S0090-4295(00)00453-2","article-title":"Antioxidant activity in the semen of fertile and infertile men","volume":"55","author":"Zini","year":"2000","journal-title":"Urology"},{"key":"2020092514445669800_deaa159-B73","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1016\/j.fertnstert.2008.03.032","article-title":"Sperm head morphology is related to high deoxyribonucleic acid stainability assessed by sperm chromatin structure assay","volume":"91","author":"Zini","year":"2009","journal-title":"Fertil Steril"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/humrep\/article-pdf\/35\/10\/2188\/33793268\/deaa159.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/humrep\/article-pdf\/35\/10\/2188\/33793268\/deaa159.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T14:45:48Z","timestamp":1601045148000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/35\/10\/2188\/5903064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,8]]},"references-count":73,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,9,8]]},"published-print":{"date-parts":[[2020,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deaa159","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,10]]},"published":{"date-parts":[[2020,9,8]]}}}