{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T18:25:32Z","timestamp":1792693532966,"version":"4.5.0"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"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. Reprod. Health"],"abstract":"<jats:p>Worldwide, infertility is a rising problem. A couple's lifestyle, age and environmental exposures can interfere with reproductive health. The scientific field tries to understand the various processes how male and female factors may affect fertility, but translation to the clinic is limited. I here emphasize potential reasons for failure in optimal treatment planning and especially why current prediction modelling falls short. First, Assisted Reproductive Technology (ART) has become a mainstream solution for couples experiencing infertility, while potential causes of infertility remain unexplored or undetermined. For instance, the role of men is generally left out of preconceptional testing and care. Second, regularly used statistical or computational methods to estimate pregnancy outcomes miss important biological and environmental factors, including features from the male side (e.g., age, smoking, obesity status, alcohol use and occupation), as well as genetic and epigenetic characteristics. I suggest using an integrated approach of biostatistics and machine learning methods to improve diagnostics and prediction modelling in the fertility clinic. The novelty of this concept includes the use of empirically collected information on the sperm epigenome combined with readily available data from medical records from both partners and lifestyle factors. As the reproductive field needs well-designed models at different levels, derivatives are needed. The objectives of patients, clinicians, and embryologists differ slightly, and mathematical models need to be adapted accordingly. A multidisciplinary approach where patients are seen by both, clinicians and biomedically skilled counsellors, could help provide evidence-based assistance to improve pregnancy success. Next, when it concerns factors that may change the ability to produce optimal embryos in ART, the embryologist would benefit from a personalized prediction model, including medical history of the patient as well as genetic and epigenetic data from easily accessible germ cells, such as sperm.<\/jats:p>","DOI":"10.3389\/frph.2025.1506312","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T07:17:44Z","timestamp":1740640664000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Introducing artificial intelligence and sperm epigenetics in the fertility clinic: a novel foundation for diagnostics and prediction modelling"],"prefix":"10.3389","volume":"7","author":[{"given":"Adelheid","family":"Soubry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"B1","article-title":"Infertility Facts","year":"2021"},{"key":"B2","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s12958-015-0032-1","article-title":"A unique view on male infertility around the globe","volume":"13","author":"Agarwal","year":"2015","journal-title":"Reprod Biol Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.2147\/IJGM.S241099","article-title":"Some of the factors involved in male infertility: a prospective review","volume":"13","author":"Babakhanzadeh","year":"2020","journal-title":"Int J Gen Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/S0140-6736(78)92957-4","article-title":"Birth after the reimplantation of a human embryo","volume":"312","author":"Steptoe","year":"1978","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.fertnstert.2023.04.022","article-title":"Long-term outcomes for children conceived by assisted reproductive technology","volume":"120","author":"Pinborg","year":"2023","journal-title":"Fertil Steril"},{"key":"B6","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1093\/humupd\/dmad028","article-title":"Declining global fertility rates and the implications for family planning and family building: an IFFS consensus document based on a narrative review of the literature","volume":"30","author":"Fauser","year":"2024","journal-title":"Hum Reprod Update"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3127","DOI":"10.1093\/humrep\/dep340","article-title":"When and why do subfertile couples discontinue their fertility care? A longitudinal cohort study in a secondary care subfertility population","volume":"24","author":"Brandes","year":"2009","journal-title":"Hum Reprod"},{"key":"B8","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1111\/j.1471-0528.1999.tb08217.x","article-title":"Cumulative probability of clinical pregnancy and live birth after a multiple cycle IVF package: a more realistic assessment of overall and age-specific success rates?","volume":"106","author":"Engmann","year":"1999","journal-title":"Br J Obstet Gynaecol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1080\/09513590500453916","article-title":"Cumulative live birth rate following in vitro fertilization: study of 5,310 cycles","volume":"22","author":"Elizur","year":"2006","journal-title":"Gynecol Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1016\/j.rbmo.2010.02.013","article-title":"Cumulative live-birth delivery after IVF\/ICSI since the progressive introduction of single-embryo transfer","volume":"20","author":"De Neubourg","year":"2010","journal-title":"Reprod Biomed Online"},{"key":"B11","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1093\/humrep\/dev270","article-title":"How do cumulative live birth rates and cumulative multiple live birth rates over complete courses of assisted reproductive technology treatment per woman compare among registries?","volume":"31","author":"De Neubourg","year":"2016","journal-title":"Hum Reprod"},{"key":"B12","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.rbmo.2016.08.010","article-title":"Seven out of 10 couples treated by IVF achieve parenthood following either treatment, natural conception or adoption","volume":"33","author":"Troude","year":"2016","journal-title":"Reprod Biomed Online"},{"key":"B13","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.rbmo.2014.01.002","article-title":"Cumulative success rates following mild IVF in unselected infertile patients: a 3-year, single-centre cohort study","volume":"28","author":"Bodri","year":"2014","journal-title":"Reprod Biomed Online"},{"key":"B14","doi-asserted-by":"publisher","first-page":"102349","DOI":"10.1016\/j.bpobgyn.2023.102349","article-title":"Evaluation of costs associated with fertility treatment leading to a live birth after one fresh transfer: a global perspective","volume":"89","author":"Matorras","year":"2023","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1016\/j.fertnstert.2009.04.029","article-title":"The economic impact of assisted reproductive technology: a review of selected developed countries","volume":"91","author":"Chambers","year":"2009","journal-title":"Fertil Steril"},{"key":"B16","doi-asserted-by":"publisher","first-page":"586.e1","DOI":"10.1016\/j.ajog.2013.10.005","article-title":"Healthcare expenses associated with multiple vs singleton pregnancies in the United States","volume":"209","author":"Lemos","year":"2013","journal-title":"Am J Obstet Gynecol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.fertnstert.2015.10.032","article-title":"Costs of achieving live birth from assisted reproductive technology: a comparison of sequential single and double embryo transfer approaches","volume":"105","author":"Crawford","year":"2016","journal-title":"Fertil Steril"},{"key":"B18","doi-asserted-by":"publisher","first-page":"S303","DOI":"10.21037\/tau.2018.05.03","article-title":"Gaps in male infertility health services research","volume":"7","author":"Leung","year":"2018","journal-title":"Transl Androl Urol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"314","DOI":"10.4103\/UA.UA_48_20","article-title":"Cost burden of male infertility investigations and treatments: a survey study","volume":"12","author":"Al-Kandari","year":"2020","journal-title":"Urol Ann"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e75061","DOI":"10.7554\/eLife.75061","article-title":"The need for more research into reproductive health and disease","volume":"11","author":"Mercuri","year":"2022","journal-title":"Elife"},{"key":"B21","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.rbmo.2021.09.023","article-title":"Male fertility as a marker for health","volume":"44","author":"Chen","year":"2021","journal-title":"Reprod Biomed Online"},{"key":"B22","doi-asserted-by":"publisher","first-page":"13564","DOI":"10.3390\/ijms241713564","article-title":"Long-term effects of ART on the health of the offspring","volume":"24","author":"Ahmadi","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1038\/s41390-021-01435-4","article-title":"A multifactorial model for the etiology of neuropsychiatric disorders: the role of advanced paternal age","volume":"91","author":"Vervoort","year":"2022","journal-title":"Pediatr Res"},{"key":"B24","volume-title":"Koninklijk Besluit Houdende Invoering van een Forfaitaire Tegemoetkoming Voor de Behandeling van Vruchtbaarheidsstoornissen bij Vrouwen","year":"2008"},{"key":"B25","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/2049-3258-73-S1-P46","article-title":"Predicting pregnancy rate and live birth rate in the IVF clinic by analyzing patient profiles","volume":"73","author":"Wang","year":"2015","journal-title":"Arch Public Health"},{"key":"B26","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1186\/s12967-019-2062-5","article-title":"Personalized prediction of live birth prior to the first in vitro fertilization treatment: a machine learning method","volume":"17","author":"Qiu","year":"2019","journal-title":"J Transl Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"20925","DOI":"10.1038\/s41598-020-76928-z","article-title":"Machine learning predicts live-birth occurrence before in vitro fertilization treatment","volume":"10","author":"Goyal","year":"2020","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","first-page":"i5735","DOI":"10.1136\/bmj.i5735","article-title":"Predicting the chances of a live birth after one or more complete cycles of in vitro fertilisation: population based study of linked cycle data from 113 873 women","volume":"355","author":"McLernon","year":"2016","journal-title":"Br Med J"},{"key":"B29","doi-asserted-by":"publisher","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":"B30","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1016\/j.fertnstert.2005.11.040","article-title":"Fathers over 40 and increased failure to conceive: the lessons of in vitro fertilization in France","volume":"85","author":"de La Rochebrochard","year":"2006","journal-title":"Fertil Steril"},{"key":"B31","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1093\/humrep\/deaa256","article-title":"Male age interferes with embryo growth in IVF treatment","volume":"36","author":"Van Opstal","year":"2021","journal-title":"Hum Reprod"},{"key":"B32","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.fertnstert.2013.03.021","article-title":"Aging sperm negatively impacts in vivo and in vitro reproduction: a longitudinal murine study","volume":"100","author":"Katz-Jaffe","year":"2013","journal-title":"Fertil Steril"},{"key":"B33","article-title":"Assisted Reproductive Technology National Summary Report, Belgium","year":"2015"},{"key":"B34","article-title":"ART Success Rates","year":"2019"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e13874","DOI":"10.1111\/and.13874","article-title":"Sperm DNA fragmentation testing: summary evidence and clinical practice recommendations","volume":"53","author":"Esteves","year":"2021","journal-title":"Andrologia"},{"key":"B36","volume-title":"WHO Laboratory Manual for the Examination and Processing of Human Semen","year":"2021"},{"key":"B37","article-title":"2022 (January 18, 2022)","year":""},{"key":"B38","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.fertnstert.2019.12.004","article-title":"Consistency and objectivity of automated embryo assessments using deep neural networks","volume":"113","author":"Bormann","year":"2020","journal-title":"Fertil Steril"},{"key":"B39","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12884-021-04373-5","article-title":"Using deep learning to predict the outcome of live birth from more than 10,000 embryo data","volume":"22","author":"Huang","year":"2022","journal-title":"BMC Pregnancy Childbirth"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1007\/s10815-019-01498-7","article-title":"An artificial neural network for the prediction of assisted reproduction outcome","volume":"36","author":"Vogiatzi","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"B41","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1016\/j.fertnstert.2021.11.022","article-title":"Characterization of an artificial intelligence model for ranking static images of blastocyst stage embryos","volume":"117","author":"Loewke","year":"2022","journal-title":"Fertil Steril"},{"key":"B42","doi-asserted-by":"publisher","first-page":"717288","DOI":"10.3389\/fendo.2021.717288","article-title":"Development and validation of a clinical pregnancy failure prediction model for poor ovarian responders during IVF\/ICSI","volume":"12","author":"Li","year":"2021","journal-title":"Front Endocrinol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1080\/19396368.2018.1504347","article-title":"Making IVF more effective through the evolution of prediction models: is prognosis the missing piece of the puzzle?","volume":"64","author":"Simopoulou","year":"2018","journal-title":"Syst Biol Reprod Med"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e037289","DOI":"10.1136\/bmjopen-2020-037289","article-title":"Predicting the chance on live birth per cycle at each step of the IVF journey: external validation and update of the van Loendersloot multivariable prognostic model","volume":"10","author":"Devroe","year":"2020","journal-title":"BMJ Open"},{"key":"B45","article-title":"Fertility patients' awareness on the effect of lifestyle and maternal age on pregnancy and miscarriage rates (thesis in public health)","author":"van Asseldonk","year":"2013"},{"key":"B46","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1093\/humupd\/dms050","article-title":"BMI In relation to sperm count: an updated systematic review and collaborative meta-analysis","volume":"19","author":"Sermondade","year":"2013","journal-title":"Hum Reprod Update"},{"key":"B47","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.rbmo.2015.07.012","article-title":"Paternal obesity negatively affects male fertility and assisted reproduction outcomes: a systematic review and meta-analysis","volume":"31","author":"Campbell","year":"2015","journal-title":"Reprod Biomed Online"},{"key":"B48","doi-asserted-by":"publisher","first-page":"311","DOI":"10.3390\/healthcare9030311","article-title":"Obesity in Saudi Arabia in 2020: prevalence, distribution, and its current association with Various health conditions","volume":"9","author":"Althumiri","year":"2021","journal-title":"Healthcare"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1016\/j.fertnstert.2013.01.142","article-title":"Obesity and poor reproductive outcome: female and male body weight matter","volume":"99","author":"Bellver","year":"2013","journal-title":"Fertil Steril"},{"key":"B50","doi-asserted-by":"publisher","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":"B51","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1016\/S0015-0282(03)00339-X","article-title":"Male smokers have a decreased success rate for in vitro fertilization and intracytoplasmic sperm injection","volume":"79","author":"Zitzmann","year":"2003","journal-title":"Fertil Steril"},{"key":"B52","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.eururo.2016.04.010","article-title":"Cigarette smoking and semen quality: a new meta-analysis examining the effect of the 2010 world health organization laboratory methods for the examination of human semen","volume":"70","author":"Sharma","year":"2016","journal-title":"Eur Urol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1111\/andr.12416","article-title":"Cigarette smoking significantly alters sperm DNA methylation patterns","volume":"5","author":"Jenkins","year":"2017","journal-title":"Andrology"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1038\/ejhg.2014.31","article-title":"Prepubertal start of father\u2019s Smoking and increased body fat in his sons: further characterisation of paternal transgenerational responses","volume":"22","author":"Northstone","year":"2014","journal-title":"Eur J Hum Genet"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1093\/ije\/dyy031","article-title":"A three-generation study on the association of tobacco smoking with asthma","volume":"47","author":"Accordini","year":"2018","journal-title":"Int J Epidemiol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"6967","DOI":"10.7314\/APJCP.2015.16.16.6967","article-title":"Tobacco use increases oxidative DNA damage in sperm\u2014possible etiology of childhood cancer","volume":"16","author":"Kumar","year":"2015","journal-title":"Asian Pac J Cancer Prev"},{"key":"B57","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.fertnstert.2013.05.043","article-title":"In women, the reproductive harm of toxins such as tobacco smoke is reversible in 6 months: basis for the \u201colive tree\u201d hypothesis","volume":"100","author":"de Ziegler","year":"2013","journal-title":"Fertil Steril"},{"key":"B58","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s40738-017-0032-2","article-title":"Discrete survival model analysis of a couple\u2019s smoking pattern and outcomes of assisted reproduction","volume":"3","author":"Vanegas","year":"2017","journal-title":"Fertil Res Pract"},{"key":"B59","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.envres.2015.04.009","article-title":"Exposure to select phthalates and phenols through use of personal care products among Californian adults and their children","volume":"140","author":"Philippat","year":"2015","journal-title":"Environ Res"},{"key":"B60","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1002\/tox.20259","article-title":"Effect of di(n-butyl) phthalate on testicular oxidative damage and antioxidant enzymes in hyperthyroid rats","volume":"22","author":"Lee","year":"2007","journal-title":"Environ Toxicol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1021\/acs.estlett.6b00475","article-title":"Temporal trends in exposure to organophosphate flame retardants in the United States","volume":"4","author":"Hoffman","year":"2017","journal-title":"Environ Sci Technol Lett"},{"key":"B62","doi-asserted-by":"publisher","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":"B63","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1016\/j.fertnstert.2014.01.022","article-title":"Urinary bisphenol A, phthalates, and couple fecundity: the longitudinal investigation of fertility and the environment (LIFE) study","volume":"101","author":"Buck Louis","year":"2014","journal-title":"Fertil Steril"},{"key":"B64","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/nrendo.2016.186","article-title":"Early-life exposure to EDCs: role in childhood obesity and neurodevelopment","volume":"13","author":"Braun","year":"2017","journal-title":"Nat Rev Endocrinol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.cotox.2017.09.003","article-title":"Environmental toxicant exposures and type 2 diabetes Mellitus: two interrelated public health problems on the rise","volume":"7","author":"Bonini","year":"2018","journal-title":"Curr Opin Toxicol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/j.reprotox.2012.09.005","article-title":"Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers","volume":"34","author":"Guerrero-Bosagna","year":"2012","journal-title":"Reprod Toxicol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.reprotox.2010.10.012","article-title":"Epigenetic transgenerational actions of endocrine disruptors","volume":"31","author":"Skinner","year":"2011","journal-title":"Reprod Toxicol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"e249640","DOI":"10.1001\/jamanetworkopen.2024.9640","article-title":"Prediction models and clinical outcomes-A call for papers","volume":"7","author":"Fihn","year":"2024","journal-title":"JAMA Netw Open"},{"key":"B69","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4161\/epi.4.1.7311","article-title":"Perturbation of genomic imprinting in oligozoospermia","volume":"4","author":"Filipponi","year":"2009","journal-title":"Epigenetics"},{"key":"B70","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1080\/19396368.2016.1274791","article-title":"Sperm epigenetics in the study of male fertility, offspring health, and potential clinical applications","volume":"63","author":"Jenkins","year":"2017","journal-title":"Syst Biol Reprod Med"},{"key":"B71","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/aja.2010.101","article-title":"Mouse models in male fertility research","volume":"13","author":"Jamsai","year":"2011","journal-title":"Asian J Androl"},{"key":"B72","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1095\/biolreprod.106.059030","article-title":"Transcriptome analysis of bull semen with extreme nonreturn rate: use of suppression-subtractive hybridization to identify functional markers for fertility","volume":"78","author":"Lalancette","year":"2008","journal-title":"Biol Reprod"},{"key":"B73","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s13148-022-01275-x","article-title":"Predicting male fertility from the sperm methylome: application to 120 bulls with hundreds of artificial insemination records","volume":"14","author":"Costes","year":"2022","journal-title":"Clin Epigenetics"},{"key":"B74","doi-asserted-by":"publisher","first-page":"e12913","DOI":"10.1111\/and.12913","article-title":"Aberrations in sperm DNA methylation patterns of males suffering from reduced fecundity","volume":"50","author":"Laqqan","year":"2018","journal-title":"Andrologia"},{"key":"B75","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.fertnstert.2015.09.013","article-title":"Decreased fecundity and sperm DNA methylation patterns","volume":"105","author":"Jenkins","year":"2016","journal-title":"Fertil Steril"},{"key":"B76","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.1007\/s10815-021-02157-6","article-title":"Sperm DNA integrity status is associated with DNA methylation signatures of imprinted genes and non-imprinted genes","volume":"38","author":"Song","year":"2021","journal-title":"J Assist Reprod Genet"},{"key":"B77","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.fertnstert.2009.02.051","article-title":"Methylation defects of imprinted genes in human testicular spermatozoa","volume":"94","author":"Marques","year":"2010","journal-title":"Fertil Steril"},{"key":"B78","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1111\/j.1365-2605.2009.01000.x","article-title":"Idiopathic male infertility is strongly associated with aberrant methylation of MEST and IGF2\/H19 ICR1","volume":"33","author":"Poplinski","year":"2010","journal-title":"Int J Androl"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1016\/j.fertnstert.2015.08.019","article-title":"Aberrant sperm DNA methylation predicts male fertility status and embryo quality","volume":"104","author":"Aston","year":"2015","journal-title":"Fertil Steril"},{"key":"B80","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13148-020-00854-0","article-title":"The sperm epigenome does not display recurrent epimutations in patients with severely impaired spermatogenesis","volume":"12","author":"Leit\u00e3o","year":"2020","journal-title":"Clin Epigenetics"},{"key":"B81","first-page":"122","article-title":"Economic benefit of an epigenetic male infertility assessment","author":"Brogaard","year":"2024"},{"key":"B82","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.xfss.2023.09.001","article-title":"Epigenetic determinants of reproductive potential augment the predictive ability of the semen analysis","volume":"4","author":"Miller","year":"2023","journal-title":"F S Sci"},{"key":"B83","doi-asserted-by":"publisher","first-page":"3216","DOI":"10.1038\/s41598-020-80857-2","article-title":"Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment","volume":"11","author":"Oluwayiose","year":"2021","journal-title":"Sci Rep"},{"key":"B84","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1186\/s12864-018-5153-4","article-title":"Paternal germ line aging: DNA methylation age prediction from human sperm","volume":"19","author":"Jenkins","year":"2018","journal-title":"BMC Genomics"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.18632\/aging.204546","article-title":"Age-related methylation changes in the human sperm epigenome","volume":"15","author":"Bernhardt","year":"2023","journal-title":"Aging (Albany NY)"},{"key":"B86","doi-asserted-by":"publisher","first-page":"e13178","DOI":"10.1111\/acel.13178","article-title":"The inherited methylome landscape is directly altered with paternal aging and associated with offspring neurodevelopmental disorders","volume":"19","author":"Denomme","year":"2020","journal-title":"Aging Cell"},{"key":"B87","doi-asserted-by":"publisher","first-page":"e13242","DOI":"10.1111\/acel.13242","article-title":"A germ cell-specific ageing pattern in otherwise healthy men","volume":"19","author":"Laurentino","year":"2020","journal-title":"Aging Cell"},{"key":"B88","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.fsigen.2015.05.014","article-title":"Epigenetic age signatures in the forensically relevant body fluid of semen: a preliminary study","volume":"19","author":"Lee","year":"2015","journal-title":"Forensic Sci Int Genet"},{"key":"B89","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13148-020-00997-0","article-title":"Male obesity impacts DNA methylation reprogramming in sperm","volume":"13","author":"Keyhan","year":"2021","journal-title":"Clin Epigenetics"},{"key":"B90","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.cmet.2015.11.004","article-title":"Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans","volume":"23","author":"Donkin","year":"2016","journal-title":"Cell Metab"},{"key":"B91","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13148-016-0217-2","article-title":"Obesity-related DNA methylation at imprinted genes in human sperm: results from the TIEGER study","volume":"8","author":"Soubry","year":"2016","journal-title":"Clin Epigenetics"},{"key":"B92","doi-asserted-by":"publisher","first-page":"dvab009","DOI":"10.1093\/eep\/dvab009","article-title":"Refraining from use diminishes cannabis-associated epigenetic changes in human sperm","volume":"7","author":"Schrott","year":"2021","journal-title":"Environ Epigenet"},{"key":"B93","doi-asserted-by":"publisher","first-page":"e0170085","DOI":"10.1371\/journal.pone.0170085","article-title":"Differential DNA methylation regions in adult human sperm following adolescent chemotherapy: potential for epigenetic inheritance","volume":"12","author":"Shnorhavorian","year":"2017","journal-title":"PLoS One"},{"key":"B94","doi-asserted-by":"publisher","first-page":"dvx003","DOI":"10.1093\/eep\/dvx003","article-title":"Human exposure to flame-retardants is associated with aberrant DNA methylation at imprinted genes in sperm","volume":"3","author":"Soubry","year":"2017","journal-title":"Environ Epigenet"},{"key":"B95","doi-asserted-by":"publisher","first-page":"dvy007","DOI":"10.1093\/eep\/dvy007","article-title":"POHad: why we should study future fathers","volume":"4","author":"Soubry","year":"2018","journal-title":"Environ Epigenet"},{"key":"B96","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1080\/15592294.2017.1329068","article-title":"Machine learning for epigenetics and future medical applications","volume":"12","author":"Holder","year":"2017","journal-title":"Epigenetics"},{"key":"B97","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13148-020-00842-4","article-title":"Machine learning and clinical epigenetics: a review of challenges for diagnosis and classification","volume":"12","author":"Rauschert","year":"2020","journal-title":"Clin Epigenetics"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1038\/s42003-023-05459-w","article-title":"Pan-cancer landscape of epigenetic factor expression predicts tumor outcome","volume":"6","author":"Cheng","year":"2023","journal-title":"Commun Biol"},{"key":"B99","doi-asserted-by":"publisher","first-page":"5761","DOI":"10.1016\/j.csbj.2022.10.016","article-title":"Multi-task deep autoencoder to predict Alzheimer\u2019s disease progression using temporal DNA methylation data in peripheral blood","volume":"20","author":"Chen","year":"2022","journal-title":"Comput Struct Biotechnol J"},{"key":"B100","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/S2213-8587(16)30040-7","article-title":"Novel concepts in the aetiology of male reproductive impairment","volume":"5","author":"Tournaye","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/s41746-019-0193-y","article-title":"Integrating machine learning and multiscale modeling-perspectives, challenges, and opportunities in the biological, biomedical, and behavioral sciences","volume":"2","author":"Alber","year":"2019","journal-title":"NPJ Digit Med"},{"key":"B102","doi-asserted-by":"publisher","first-page":"101077","DOI":"10.1016\/j.newideapsych.2024.101077","article-title":"Combining theoretical modelling and machine learning approaches: the case of teamwork effects on individual effort expenditure","volume":"73","author":"Eisbach","year":"2024","journal-title":"New Ideas Psychol"},{"key":"B103","first-page":"1","volume-title":"National Men\u2019s Health Strategy 2020\u20132030","year":"2019"}],"container-title":["Frontiers in Reproductive Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frph.2025.1506312\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T07:17:49Z","timestamp":1740640669000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frph.2025.1506312\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,27]]},"references-count":103,"alternative-id":["10.3389\/frph.2025.1506312"],"URL":"https:\/\/doi.org\/10.3389\/frph.2025.1506312","relation":{},"ISSN":["2673-3153"],"issn-type":[{"value":"2673-3153","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,27]]},"article-number":"1506312"}}