{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:07:34Z","timestamp":1740136054073,"version":"3.37.3"},"reference-count":50,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,17]]},"abstract":"Abstract<\/jats:title>\n \n Context<\/jats:title>\n Assisted reproductive technologies (ART) and non\u2013in vitro fertilization fertility treatments (NIFT) are treatments for infertility. These technologies may have long-term health effects in children such as increased hypertension, glucose intolerance, and hypertriglyceridemia. Few studies have compared children born following ART and NIFT to those conceived spontaneously by subfertile couples.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n This work aimed to describe metabolic differences in children conceived by ART and NIFT compared to children conceived spontaneously by infertile couples.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Children conceived by parent(s) receiving infertility care at the University of California, San Francisco, between 2000 and 2017 were invited to participate in the Developmental Epidemiological Study of Children born through Reproductive Technology (DESCRT). Serum metabolomic analyses were conducted using samples from 143 enrolled children (age range 4-12 years, 43% female) conceived using NIFT or ART (with fresh or frozen embryos with and without intracytoplasmic sperm injection [ICSI]) and children conceived spontaneously by subfertile couples. Principal component analysis and multivariable regression were used to compare the distribution of metabolites between groups.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n There was no separation in metabolites based on treatment or sex. NIFT-conceived children showed no differences compared to spontaneously conceived controls. Only spontaneously conceived children had different metabolomics profiles from children conceived from fresh ART, frozen ART, and all ICSI. Pantoate and propionylglycine levels were elevated in fresh ART compared to the spontaneous group (P &lt; .001). Propionylglycine levels were elevated in the ICSI (both fresh and frozen) vs the spontaneous group (P &lt; .001). Finally, 5-oxoproline levels were decreased in frozen ART compared to the spontaneous group (P &lt; .001).<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n NIFT-conceived children did not show any metabolic differences compared with spontaneously conceived children. The metabolic differences between ART-conceived children and children conceived spontaneously were small but unlikely to be clinically significant but should be examined in future studies.<\/jats:p>\n <\/jats:sec>","DOI":"10.1210\/clinem\/dgac589","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T20:18:01Z","timestamp":1665433081000},"page":"315-322","source":"Crossref","is-referenced-by-count":1,"title":["Metabolomic Profile of Children Conceived With Medically Assisted Technologies"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2146-5451","authenticated-orcid":false,"given":"Alisha T","family":"Tolani","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California , San Francisco, California 94158 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelle I","family":"Cedars","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California , San Francisco, California 94158 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia B","family":"Zablotska","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California , San Francisco, California 94158 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6528-6009","authenticated-orcid":false,"given":"Paolo F","family":"Rinaudo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California , San Francisco, California 94158 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"issue":"12","key":"2023052322372412700_dgac589-B1","doi-asserted-by":"crossref","first-page":"e1001356","DOI":"10.1371\/journal.pmed.1001356","article-title":"National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys","volume":"9","author":"Mascarenhas","year":"2012","journal-title":"PLoS Med"},{"issue":"6","key":"2023052322372412700_dgac589-B2","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1093\/humrep\/dem046","article-title":"International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care","volume":"22","author":"Boivin","year":"2007","journal-title":"Hum Reprod"},{"author":"Rutstein","key":"2023052322372412700_dgac589-B3"},{"issue":"11","key":"2023052322372412700_dgac589-B4","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1093\/aje\/kwp281","article-title":"Estimation of the contribution of non\u2013assisted reproductive technology ovulation stimulation fertility treatments to US singleton and multiple births","volume":"170","author":"Schieve","year":"2009","journal-title":"Am J Epidemiol"},{"author":"Centers for Disease Control and Prevention","key":"2023052322372412700_dgac589-B5"},{"issue":"6","key":"2023052322372412700_dgac589-B6","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1093\/humrep\/deab008","article-title":"Effect of parental and ART treatment characteristics on perinatal outcomes","volume":"36","author":"Pontesilli","year":"2021","journal-title":"Hum Reprod"},{"issue":"3","key":"2023052322372412700_dgac589-B7","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.fertnstert.2016.12.007","article-title":"Cardiovascular and metabolic profiles of offspring conceived by assisted reproductive technologies: a systematic review and meta-analysis","volume":"107","author":"Guo","year":"2017","journal-title":"Fertil Steril"},{"issue":"25","key":"2023052322372412700_dgac589-B8","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1093\/eurheartj\/ehv145","article-title":"Cardiovascular dysfunction in children conceived by assisted reproductive technologies","volume":"36","author":"Scherrer","year":"2015","journal-title":"Eur Heart J"},{"key":"2023052322372412700_dgac589-B9","doi-asserted-by":"crossref","first-page":"8170518","DOI":"10.1155\/2018\/8170518","article-title":"Metabolic syndrome and its components in young adults conceived by ICSI","volume":"2018","author":"Belva","year":"2018","journal-title":"Int J Endocrinol"},{"issue":"5","key":"2023052322372412700_dgac589-B10","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1016\/j.fertnstert.2007.09.005","article-title":"Growth and development of children born after in vitro fertilization","volume":"90","author":"Ceelen","year":"2008","journal-title":"Fertil Steril"},{"issue":"4","key":"2023052322372412700_dgac589-B11","doi-asserted-by":"crossref","first-page":"e94001","DOI":"10.1371\/journal.pone.0094001","article-title":"Plasma metabolomic profiling suggests early indications for predisposition to latent insulin resistance in children conceived by ICSI","volume":"9","author":"Gkourogianni","year":"2014","journal-title":"PLoS One"},{"issue":"10","key":"2023052322372412700_dgac589-B12","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1007\/s00125-020-05241-1","article-title":"Increased risk of metabolic dysfunction in children conceived by assisted reproductive technology","volume":"63","author":"Cui","year":"2020","journal-title":"Diabetologia"},{"issue":"5","key":"2023052322372412700_dgac589-B13","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1016\/j.fertnstert.2009.09.049","article-title":"Absence of insulin resistance and low-grade inflammation despite early metabolic syndrome manifestations in children born after in vitro fertilization","volume":"94","author":"Sakka","year":"2010","journal-title":"Fertil Steril"},{"issue":"7","key":"2023052322372412700_dgac589-B14","doi-asserted-by":"crossref","first-page":"e0132638","DOI":"10.1371\/journal.pone.0132638","article-title":"Superovulation induced changes of lipid metabolism in ovaries and embryos and its probable mechanism","volume":"10","author":"Wang","year":"2015","journal-title":"PLoS One"},{"issue":"3","key":"2023052322372412700_dgac589-B15","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.rbmo.2014.11.006","article-title":"Subfertility and assisted reproduction techniques are associated with poorer cardiometabolic profiles in childhood","volume":"30","author":"Pontesilli","year":"2015","journal-title":"Reprod Biomed Online"},{"issue":"5","key":"2023052322372412700_dgac589-B16","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1002\/ijc.28110","article-title":"Increased risk for cancer among offspring of women with fertility problems: cancer in offspring of women with fertility problems","volume":"133","author":"Hargreave","year":"2013","journal-title":"Int J Cancer"},{"issue":"9","key":"2023052322372412700_dgac589-B17","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1681\/ASN.2005020160","article-title":"Developmental antecedents of cardiovascular disease: a historical perspective","volume":"16","author":"Barker","year":"2005","journal-title":"J Am Soc Nephrol"},{"issue":"4","key":"2023052322372412700_dgac589-B18","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nrm3314","article-title":"Innovation: metabolomics: the apogee of the omics trilogy","volume":"13","author":"Patti","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"5","key":"2023052322372412700_dgac589-B19","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1210\/en.2013-2081","article-title":"Use of a mouse in vitro fertilization model to understand the developmental origins of health and disease hypothesis","volume":"155","author":"Feuer","year":"2014","journal-title":"Endocrinology"},{"issue":"5","key":"2023052322372412700_dgac589-B20","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1210\/en.2016-1475","article-title":"Assisted reproductive technologies predispose to insulin resistance and obesity in male mice challenged with a high-fat diet","volume":"158","author":"Cerny","year":"2017","journal-title":"Endocrinology"},{"issue":"11","key":"2023052322372412700_dgac589-B21","doi-asserted-by":"crossref","first-page":"4554","DOI":"10.1210\/en.2014-1465","article-title":"Sexually dimorphic effect of in vitro fertilization (IVF) on adult mouse fat and liver metabolomes","volume":"155","author":"Feuer","year":"2014","journal-title":"Endocrinology"},{"issue":"4","key":"2023052322372412700_dgac589-B22","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1210\/jc.2018-01118","article-title":"Differences in first-trimester maternal metabolomic profiles in pregnancies conceived from fertility treatments","volume":"104","author":"Sun","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2023052322372412700_dgac589-B23","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1214\/aos\/1074290335","article-title":"The positive false discovery rate: a Bayesian interpretation and the q-value","volume":"31","author":"Storey","year":"2003","journal-title":"Ann Stat"},{"issue":"16","key":"2023052322372412700_dgac589-B24","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1073\/pnas.1530509100","article-title":"Statistical significance for genomewide studies","volume":"100","author":"Storey","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2065","key":"2023052322372412700_dgac589-B25","first-page":"20150202","article-title":"Principal component analysis: a review and recent developments","volume":"374","author":"Jolliffe","year":"2016","journal-title":"Philos Trans R Soc Math Phys Eng Sci"},{"issue":"6","key":"2023052322372412700_dgac589-B26","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.fertnstert.2018.06.039","article-title":"International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2011","volume":"110","author":"Adamson","year":"2018","journal-title":"Fertil Steril"},{"issue":"7","key":"2023052322372412700_dgac589-B27","doi-asserted-by":"crossref","first-page":"e1001033","DOI":"10.1371\/journal.pgen.1001033","article-title":"Inter- and intra-individual variation in allele-specific DNA methylation and gene expression in children conceived using assisted reproductive technology","volume":"6","author":"Turan","year":"2010","journal-title":"PLoS Genet"},{"issue":"7","key":"2023052322372412700_dgac589-B28","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1093\/humrep\/des151","article-title":"Methylation levels at imprinting control regions are not altered with ovulation induction or in vitro fertilization in a birth cohort","volume":"27","author":"Rancourt","year":"2012","journal-title":"Hum Reprod"},{"issue":"2","key":"2023052322372412700_dgac589-B29","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1093\/humrep\/dex366","article-title":"The epigenetic control of transposable elements and imprinted genes in newborns is affected by the mode of conception: ART versus spontaneous conception without underlying infertility","volume":"33","author":"Choux","year":"2018","journal-title":"Hum Reprod"},{"issue":"5","key":"2023052322372412700_dgac589-B30","doi-asserted-by":"crossref","first-page":"e96994","DOI":"10.1371\/journal.pone.0096994","article-title":"Transition of LINE-1 DNA methylation status and altered expression in first and third trimester placentas","volume":"9","author":"He","year":"2014","journal-title":"PLoS One"},{"key":"2023052322372412700_dgac589-B31","doi-asserted-by":"crossref","first-page":"696840","DOI":"10.3389\/fgene.2021.696840","article-title":"Whole-genome methylation analysis revealed ART-specific DNA methylation pattern of neuro- and immune-system pathways in Chinese human neonates","volume":"12","author":"Liu","year":"2021","journal-title":"Front Genet"},{"issue":"20","key":"2023052322372412700_dgac589-B32","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1093\/hmg\/ddp319","article-title":"DNA methylation and gene expression differences in children conceived in vitro or in vivo","volume":"18","author":"Katari","year":"2009","journal-title":"Hum Mol Genet"},{"issue":"12","key":"2023052322372412700_dgac589-B33","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1093\/humrep\/deg486","article-title":"Epigenetic risks related to assisted reproductive technologies: epigenetics, imprinting, ART and icebergs?","volume":"18","author":"Maher","year":"2003","journal-title":"Hum Reprod"},{"issue":"7","key":"2023052322372412700_dgac589-B34","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1093\/humrep\/deq117","article-title":"Obstetric outcomes after transfer of vitrified blastocysts","volume":"25","author":"Wikland","year":"2010","journal-title":"Hum Reprod"},{"issue":"2","key":"2023052322372412700_dgac589-B35","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1073\/pnas.71.2.293","article-title":"Formation of 5-oxoproline from glutathione in erythrocytes by the \u03b3-glutamyltranspeptidase-cyclotransferase pathway","volume":"71","author":"Palekar","year":"1974","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"2023052322372412700_dgac589-B36","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1016\/j.bbagen.2012.09.008","article-title":"Glutathione synthesis","volume":"1830","author":"Lu","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"2023052322372412700_dgac589-B37","first-page":"43","volume-title":"Profiles of Drug Substances, Excipients and Related Methodology","author":"Alanazi","year":"2015"},{"issue":"1","key":"2023052322372412700_dgac589-B38","doi-asserted-by":"crossref","first-page":"51","DOI":"10.32604\/biocell.2007.31.051","article-title":"Preimplantation embryotoxicity after mouse embryo exposition to reactive oxygen species","volume":"31","author":"Cebral","year":"2007","journal-title":"Biocell"},{"issue":"5","key":"2023052322372412700_dgac589-B39","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/S1472-6483(10)60312-4","article-title":"Contribution of culture media to oxidative stress and its effect on human oocytes","volume":"17","author":"Mart\u00edn-Romero","year":"2008","journal-title":"Reprod Biomed Online"},{"issue":"1","key":"2023052322372412700_dgac589-B40","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0891-5849(93)90126-F","article-title":"Increased generation of reactive oxygen species in embryos cultured in vitro","volume":"15","author":"Goto","year":"1993","journal-title":"Free Radic Biol Med"},{"issue":"4","key":"2023052322372412700_dgac589-B41","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1080\/19396368.2020.1754961","article-title":"The effect of low and ultra-low oxygen tensions on mammalian embryo culture and development in experimental and clinical IVF","volume":"66","author":"Belli","year":"2020","journal-title":"Syst Biol Reprod Med"},{"issue":"6","key":"2023052322372412700_dgac589-B42","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1095\/biolreprod.104.033589","article-title":"Mitochondrial dysfunction in mouse oocytes results in preimplantation embryo arrest in vitro","volume":"71","author":"Thouas","year":"2004","journal-title":"Biol Reprod"},{"issue":"12","key":"2023052322372412700_dgac589-B43","first-page":"2892","article-title":"Dynamic comparisons of high-resolution expression profiles highlighting mitochondria-related genes between in vivo and in vitro fertilized early mouse embryos","volume":"30","author":"Ren","year":"2015","journal-title":"Hum Reprod"},{"issue":"2","key":"2023052322372412700_dgac589-B44","doi-asserted-by":"crossref","DOI":"10.1128\/ecosalplus.3.6.3.4","article-title":"Biosynthesis of pantothenic acid and coenzyme A","volume":"2","author":"Leonardi","year":"2007","journal-title":"EcoSal Plus"},{"issue":"5","key":"2023052322372412700_dgac589-B45","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.jacl.2015.07.003","article-title":"Efficacy and tolerability of coenzyme A vs pantethine for the treatment of patients with hyperlipidemia: a randomized, double-blind, multicenter study","volume":"9","author":"Chen","year":"2015","journal-title":"J Clin Lipidol"},{"issue":"8","key":"2023052322372412700_dgac589-B46","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.nutres.2011.08.001","article-title":"Pantethine, a derivative of vitamin B5 used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low- to moderate-cardiovascular risk north American subjects: a triple-blinded placebo and diet-controlled investigation","volume":"31","author":"Rumberger","year":"2011","journal-title":"Nutr Res"},{"issue":"4","key":"2023052322372412700_dgac589-B47","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.nutres.2004.12.009","article-title":"Treatment of hyperlipoproteinemia with pantethine: a review and analysis of efficacy and tolerability","volume":"25","author":"McRae","year":"2005","journal-title":"Nutr Res"},{"key":"2023052322372412700_dgac589-B48","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1007\/3-540-27660-2_38","volume-title":"Magnetic Resonance of Myelination and Myelin Disorders","author":"van der Knaap","year":"2005"},{"key":"2023052322372412700_dgac589-B49","first-page":"1423","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Fenton","year":"1995","edition":"7th ed."},{"issue":"6","key":"2023052322372412700_dgac589-B50","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/BF01799166","article-title":"Plasma total odd-chain fatty acids in the monitoring of disorders of propionate, methylmalonate and biotin metabolism","volume":"19","author":"Coker","year":"1996","journal-title":"J Inherit Metab Dis"}],"container-title":["The Journal of Clinical Endocrinology & Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgac589\/46700921\/dgac589.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/2\/315\/50424936\/dgac589.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/2\/315\/50424936\/dgac589.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T22:38:19Z","timestamp":1684881499000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/108\/2\/315\/6754907"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,10]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,10,10]]},"published-print":{"date-parts":[[2023,1,17]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgac589","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"type":"print","value":"0021-972X"},{"type":"electronic","value":"1945-7197"}],"subject":[],"published-other":{"date-parts":[[2023,2,1]]},"published":{"date-parts":[[2022,10,10]]}}}