{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T23:37:57Z","timestamp":1784677077150,"version":"3.55.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Hjalmar Svensson Research Foundation and Nordforsk","award":["71450"],"award-info":[{"award-number":["71450"]}]},{"DOI":"10.13039\/501100005754","name":"Sahlgrenska University Hospital","doi-asserted-by":"publisher","award":["ALFGBG-70 940"],"award-info":[{"award-number":["ALFGBG-70 940"]}],"id":[{"id":"10.13039\/501100005754","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>Do children conceived after ICSI have similar school performance as children born after IVF?<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>Children born after ICSI have similar school performance compared to children born after IVF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>Studies concerning the cognitive skills of children born after ICSI have shown diverging results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>This nationwide, register-based cohort study included all singleton children born after ICSI (n\u2009=\u20096953), IVF (n\u2009=\u200911\u2009713) or spontaneous conception (SC) (n\u2009=\u20092\u2009022\u2009995), in Sweden between 1985 and 2006.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>Singleton children born after ICSI were identified in national IVF registers, cross-linked with the Medical Birth Register (MBR), the National Patient Register (NPR) and the Swedish Cause of Death Register (CDR) for characteristics and medical outcomes. Data on school performance, parental education and other parental characteristics were obtained through cross-linking to the National School Registry and to Statistics Sweden. The main control group, which consisted of children born after IVF, was identified in the national IVF registries while the second control group, consisting of children born after SC, was identified from the MBR. Simple and multivariable linear regression was used for analysis of continuous variables, and logistic regression was used for the analysis of binary outcomes. Adjustments were made for sex, year of birth, maternal smoking during pregnancy, parental age, parity, parental region of birth, parental level of education and frozen embryo transfer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>In the adjusted analyses, there was no significant difference between ICSI and IVF children for total score (adjusted odds ratios (AORs) 1.03; 95% CI \u22120.22 to 2.28; P\u2009=\u20090.11), specific subjects, qualifying for secondary school (AOR 1.02; 95% CI 0.82\u20131.26; P\u2009=\u20090.87) or poor school performance (AOR 0.92; 95% CI 0.75\u22121.14; P\u2009=\u20090.47). In the third grade, children born after ICSI had a significantly lower chance of passing all of the subtests in Mathematics (AOR 0.89; 0.83\u20130.96; P\u2009=\u20090.002) and Swedish (AOR 0.92; 0.85\u20130.99; P\u2009=\u20090.02) compared to children born after SC. When cross-linking children with missing data on school performances (2.1% for ICSI, 2.0% for IVF and 2.3% for SC) with the Cerebral Palsy Follow-up Register (CPUP) for cerebral palsy, 2.7% of ICSI children, 5.7% of IVF children and 1.7% of SC children without registered education were found. When cross-linking children with missing data on school performances with the NPR for mental retardation, 29.9% of ICSI children, 32.6% of IVF children and 35.0% of SC children with missing data were registered under such a diagnosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                  <jats:p>The main limitation was that test scores were missing in a small percentage in both ICSI and IVF children. Although we were able to cross-link this subpopulation with the CPUP and the NPR, these diagnoses only partly explained the missing scores. Other limitations were unmeasured and unknown possible confounders, such as information about infertility diagnoses and indication for ICSI, were not available.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                  <jats:p>These findings are important to most countries where IVF and ICSI are used since there may be differences in choice of procedure. In recent years, there has been an increasing trend towards using ICSI not only for treatment of male infertility but also when the sperm quality is normal. Our results indicate that the school performance of children born after ICSI is reassuring.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>Financial support was received through Sahlgrenska University Hospital (ALFGBG \u2013 70 940), Hjalmar Svensson Research Foundation and Nordforsk, project number 71 450. None of the authors declare any conflict of interest.<\/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\/dez281","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T07:12:00Z","timestamp":1575529920000},"page":"340-354","source":"Crossref","is-referenced-by-count":16,"title":["School performance in children born after ICSI"],"prefix":"10.1093","volume":"35","author":[{"given":"Emma","family":"Norrman","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital\/\u00d6stra, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Petzold","sequence":"first","affiliation":[{"name":"School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Bergh","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Reproductive Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla-Britt","family":"Wennerholm","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital\/\u00d6stra, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"2020022823094702600_ref1","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"},{"key":"2020022823094702600_ref2","first-page":"0","article-title":"ICMART World Report 2014 ESHRE 2018, Barcelona, Abstract","author":"Adamson","year":"2018"},{"key":"2020022823094702600_ref3","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1097\/EDE.0000000000000171","article-title":"School performance after preterm birth","volume":"26","author":"Ahlsson","year":"2015","journal-title":"Epidemiol"},{"key":"2020022823094702600_ref4","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.fertnstert.2013.05.034","article-title":"Assisted reproduction and child neurodevelopmental outcomes: a systematic review","volume":"100","author":"Bay","year":"2013","journal-title":"Fertil Steril"},{"key":"2020022823094702600_ref5","doi-asserted-by":"crossref","first-page":"f3978","DOI":"10.1136\/bmj.f3978","article-title":"Fertility treatment and risk of childhood and adolescent mental disorders: register based cohort study","volume":"347","author":"Bay","year":"2013","journal-title":"BMJ"},{"key":"2020022823094702600_ref6","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1001\/jama.288.6.728","article-title":"Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis","volume":"288","author":"Bhutta","year":"2002","journal-title":"JAMA"},{"key":"2020022823094702600_ref7","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/humrep\/deh592","article-title":"A multi-centre cohort study of the physical health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception","volume":"20","author":"Bonduelle","year":"2005","journal-title":"Hum Reprod"},{"key":"2020022823094702600_ref8","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/andr.12526","article-title":"Long-term follow-up of intra-cytoplasmic sperm injection-conceived offspring compared with in vitro fertilization-conceived offspring: a systematic review of health outcomes beyond the neonatal period","volume":"6","author":"Catford","year":"2018","journal-title":"Andrology"},{"key":"2020022823094702600_ref9","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1177\/140349489001800209","article-title":"A quality study of a medical birth register","volume":"18","author":"Cnattingius","year":"1990","journal-title":"Scand J Soc Med"},{"key":"2020022823094702600_ref10","first-page":"169","article-title":"The smoking addiction of pregnant women and the consequences on their offspring\u2019s intellectual development","volume":"15","author":"Frydman","year":"1996","journal-title":"J Environ Pathol Toxicol Oncol"},{"key":"2020022823094702600_ref11","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1093\/jpepsy\/jsn120","article-title":"Cognitive development of singletons conceived by intracytoplasmic sperm injection or in vitro fertilization at age 5 and 10 years","volume":"34","author":"Goldbeck","year":"2009","journal-title":"J Pediatr Psychol"},{"key":"2020022823094702600_ref12","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1136\/bmj.37957.560278.EE","article-title":"Perinatal outcome of singletons and twins after assisted conception; a systematic review of controlled studies","volume":"328","author":"Helmerhorst","year":"2004","journal-title":"BMJ"},{"key":"2020022823094702600_ref13","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/01.AOG.0000114989.84822.51","article-title":"Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis","volume":"103","author":"Jackson","year":"2004","journal-title":"Obstet Gynecol"},{"key":"2020022823094702600_ref14","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1093\/humrep\/deu338","article-title":"Association of assisted reproductive technology (ART) treatment and parental infertility diagnosis with autism in ART-conceived children","volume":"30","author":"Kissin","year":"2015","journal-title":"Hum Reprod"},{"key":"2020022823094702600_ref15","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1542\/peds.2006-0735","article-title":"Health of children born as a result of in vitro fertilization","volume":"118","author":"Klemetti","year":"2006","journal-title":"Pediatrics"},{"key":"2020022823094702600_ref16","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.fertnstert.2007.06.090","article-title":"Cognitive development of singletons born after intracytoplasmic sperm injection compared with in vitro fertilization and natural conception","volume":"90","author":"Knoester","year":"2008","journal-title":"Fertil Steril"},{"key":"2020022823094702600_ref17","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1097\/01.ede.0000231561.49208.be","article-title":"Maternal smoking during pregnancy and school performance at age 15","volume":"17","author":"Lambe","year":"2006","journal-title":"Epidemiology"},{"key":"2020022823094702600_ref18","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s10654-009-9350-y","article-title":"The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research","volume":"24","author":"Ludvigsson","year":"2009","journal-title":"Eur J Epidemiol"},{"key":"2020022823094702600_ref19","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1186\/1471-2458-11-450","article-title":"External review and validation of the Swedish national inpatient register","volume":"11","author":"Ludvigsson","year":"2011","journal-title":"BMC Public Health"},{"key":"2020022823094702600_ref20","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1093\/humrep\/deg408","article-title":"Children conceived using ICSI do not have an increased risk of delayed mental development at 5 years of age","volume":"18","author":"Leslie","year":"2003","journal-title":"Hum Reprod"},{"key":"2020022823094702600_ref21","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1093\/humrep\/deq218","article-title":"Achievement test performance in children conceived by IVF","volume":"25","author":"Mains","year":"2010","journal-title":"Hum Reprod"},{"key":"2020022823094702600_ref22","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ejogrb.2009.05.035","article-title":"Preterm birth and low birth weight among in vitro fertilization singletons: a systematic review and meta-analysis","volume":"146","author":"McDonald","year":"2009","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2020022823094702600_ref23","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1365-3016.2004.00622.x","article-title":"A dose-response relationship between maternal smoking during late pregnancy and adult intelligence in male off-spring","volume":"19","author":"Mortensen","year":"2005","journal-title":"Paediatr Perinat Epidemiol"},{"key":"2020022823094702600_ref24","first-page":"244","article-title":"Intelligence and achievement: just how correlated are they?","volume":"21","author":"Naglieri","year":"2003","journal-title":"JPA"},{"key":"2020022823094702600_ref25","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1093\/humrep\/dey273","article-title":"School performance in singletons born after assisted reproductive technology","volume":"33","author":"Norrman","year":"2018","journal-title":"Hum Reprod"},{"key":"2020022823094702600_ref26","doi-asserted-by":"crossref","first-page":"17:18","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":"2020022823094702600_ref27","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/humupd\/dms018","article-title":"Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF\/ICSI: a systematic review and meta-analysis","volume":"18","author":"Pandey","year":"2012","journal-title":"Hum Reprod Update"},{"key":"2020022823094702600_ref28","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1093\/humrep\/dei142","article-title":"Consequences of vanishing twins in IVF\/ICSI pregnancies","volume":"20","author":"Pinborg","year":"2005","journal-title":"Hum Reprod"},{"key":"2020022823094702600_ref29","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1093\/humupd\/dms044","article-title":"Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis","volume":"19","author":"Pinborg","year":"2013","journal-title":"Hum Reprod Update"},{"key":"2020022823094702600_ref30","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/j.fertnstert.2003.06.004","article-title":"A prospective longitudinal study of the physical, psychomotor, and intellectual development of singleton children up to 5 years who were conceived by intracytoplasmic sperm injection compared with children conceived spontaneously and by in vitro fertilization","volume":"80","author":"Place","year":"2003","journal-title":"Fertil Steril"},{"key":"2020022823094702600_ref31","doi-asserted-by":"crossref","first-page":"e283","DOI":"10.1542\/peds.2004-1445","article-title":"International collaborative study of intracytoplasmic sperm injection-conceived, in vitro fertilization-conceived, and naturally conceived 5-year-old child outcomes: cognitive and motor assessments","volume":"115","author":"Ponjaert-Kristoffersen","year":"2005","journal-title":"Pediatrics"},{"key":"2020022823094702600_ref32","doi-asserted-by":"crossref","first-page":"S151","DOI":"10.1016\/j.fertnstert.2004.05.037","article-title":"Does intracytoplasmic sperm injection (ICSI) carry inherent genetic risks?","volume":"82","author":"Practice Committee of the American Society for Reproductive Medicine","year":"2004","journal-title":"Fertil Steril"},{"key":"2020022823094702600_ref33","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/humrep\/dev273","article-title":"Mental health and developmental outcomes for children born after ART: a comparative prospective study on child gender and treatment type","volume":"31","author":"Punamaki","year":"2015","journal-title":"Hum Reprod"},{"key":"2020022823094702600_ref34","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1093\/humrep\/dex085","article-title":"The impact of specific fertility treatments on cognitive development in childhood and adolescence: a systematic review","volume":"32","author":"Rumbold","year":"2017","journal-title":"Hum Reprod"},{"key":"2020022823094702600_ref35","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1001\/jama.2013.7222","article-title":"Autism and mental retardation among offspring born after in vitro fertilization","volume":"310","author":"Sandin","year":"2013","journal-title":"JAMA"},{"key":"2020022823094702600_ref36","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1093\/humrep\/der241","article-title":"Factors affecting obstetric outcome of singletons born after IVF","volume":"26","author":"Sazonova","year":"2011","journal-title":"Hum Reprod"},{"key":"2020022823094702600_ref37","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1001\/jamapsychiatry.2015.2917","article-title":"Associations of parental depression with child school performance at age 16 years in Sweden","volume":"73","author":"Shen","year":"2016","journal-title":"JAMA Psychiat"},{"key":"2020022823094702600_ref38","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1037\/0033-2909.130.6.989","article-title":"Birth weight and cognitive ability in childhood: a systematic review","volume":"130","author":"Shenkin","year":"2004","journal-title":"Psychol Bull"},{"key":"2020022823094702600_ref39","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1093\/humrep\/dew334","article-title":"Academic performance in adolescents born after ART-a nationwide registry-based cohort study","volume":"32","author":"Spangmose","year":"2017","journal-title":"Hum Reprod"},{"key":"2020022823094702600_ref40","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0140-6736(02)07674-2","article-title":"Neurological sequelae in children born after in-vitro fertilisation: a population-based study","volume":"359","author":"Stromberg","year":"2002","journal-title":"Lancet"},{"key":"2020022823094702600_ref41","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0024771","article-title":"Implications of advancing paternal age: does it affect offspring school performance?","volume":"6","author":"Svensson","year":"2011","journal-title":"PLoS One"},{"key":"2020022823094702600_ref42","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1007\/s00431-008-0677-2","article-title":"School functioning in 8- to 18-year-old children born after in vitro fertilization","volume":"167","author":"Wagenaar","year":"2008","journal-title":"Eur J Pediatr"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/humrep\/article-pdf\/35\/2\/340\/32711047\/dez281.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/humrep\/article-pdf\/35\/2\/340\/32711047\/dez281.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T23:10:10Z","timestamp":1582931410000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/35\/2\/340\/5709764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,20]]},"references-count":42,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,1,20]]},"published-print":{"date-parts":[[2020,2,29]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/dez281","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,2]]},"published":{"date-parts":[[2020,1,20]]}}}