{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T06:09:18Z","timestamp":1788588558195,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>The term infertility is defined as the lack of conception within 1 year of unprotected intercourse. It affects more than 80 million individuals worldwide. It is estimated that 10-15% of couples of reproductive age are challenged by reproductive issues. Assisted reproduction techniques (ART) are responsible for more than 4% of live births. Our aim is to review the research on neurodevelopmental outcomes of newborns born after the implementation of assisted reproduction methods compared to those conceived naturally. We conducted a comprehensive search of the PubMed, Crossref and Google Scholar electronic databases for related articles up to June 2022 using the PRISMA guidelines. Our research revealed a large number of long term follow-up studies between 2 and 18 years of age, with comparable developmental outcomes. Many studies compared the effects of different infertility treatments against natural conception. The review of the literature revealed that ART is safe, as the majority of studies showed no effect on the neurodevelopmental outcomes of the offspring. In most cases when such an effect was observed, it could be attributed to confounding factors such as subfertility, multiple pregnancies and gestational age at delivery. Finally, the increase in the prevalence of neurodevelopmental disorders after ART, as described in studies with statistically significant results, is predominantly marginal, and given the low incidence of neurodevelopmental disorders in the general population, its clinical significance is debatable.<\/jats:p>","DOI":"10.3390\/children9101511","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T01:52:21Z","timestamp":1665193941000},"page":"1511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Neurodevelopmental Outcomes of Pregnancies Resulting from Assisted Reproduction: A Review of the Literature"],"prefix":"10.3390","volume":"9","author":[{"given":"Paraskevas","family":"Perros","sequence":"first","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cAlexandra\u201d General Hospital, National and Kapodistrian University of Athens, 11526 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9570-3969","authenticated-orcid":false,"given":"Alexandros","family":"Psarris","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cAlexandra\u201d General Hospital, National and Kapodistrian University of Athens, 11526 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Antsaklis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cAlexandra\u201d General Hospital, National and Kapodistrian University of Athens, 11526 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-7796","authenticated-orcid":false,"given":"Marianna","family":"Theodora","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cAlexandra\u201d General Hospital, National and Kapodistrian University of Athens, 11526 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Syndos","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cAlexandra\u201d General Hospital, National and Kapodistrian University of Athens, 11526 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7229-9983","authenticated-orcid":false,"given":"Antonios","family":"Koutras","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cAlexandra\u201d General Hospital, National and Kapodistrian University of Athens, 11526 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ntounis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cAlexandra\u201d General Hospital, National and Kapodistrian University of Athens, 11526 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0216-3420","authenticated-orcid":false,"given":"Zaharias","family":"Fasoulakis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cAlexandra\u201d General Hospital, National and Kapodistrian University of Athens, 11526 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Rodolakis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cAlexandra\u201d General Hospital, National and Kapodistrian University of Athens, 11526 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Daskalakis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cAlexandra\u201d General Hospital, National and Kapodistrian University of Athens, 11526 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ajog.2017.03.012","article-title":"Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: With an emphasis on US population-based studies","volume":"217","author":"Luke","year":"2017","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1093\/humrep\/deq377","article-title":"The Groningen ART cohort study: The effects of ovarian hyperstimulation and the IVF laboratory procedures on neurological condition at 2 years","volume":"26","author":"Schendelaar","year":"2011","journal-title":"Hum. Reprod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/1471-0528.14257","article-title":"Obstetric and neonatal complications in pregnancies conceived after oocyte donation: A systematic review and meta-analysis","volume":"124","author":"Storgaard","year":"2017","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1161\/CIRCULATIONAHA.111.071183","article-title":"Systemic and Pulmonary Vascular Dysfunction in Children Conceived by Assisted Reproductive Technologies","volume":"125","author":"Scherrer","year":"2012","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.jacc.2018.06.060","article-title":"Association of Assisted Reproductive Technologies with Arterial Hypertension During Adolescence","volume":"72","author":"Meister","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_6","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."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1055\/s-0032-1307420","article-title":"Long-term outcomes in children born after assisted conception","volume":"30","author":"Eisenberg","year":"2012","journal-title":"Semin. Reprod. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.fertnstert.2012.05.049","article-title":"Adverse obstetric and perinatal outcomes of singleton pregnancies may be related to maternal factors associated with infertility rather than the type of assisted reproductive technology procedure used","volume":"98","author":"Hayashi","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_9","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":"Tiitinen","year":"2016","journal-title":"Hum. 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Reprod."},{"key":"ref_12","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":"ref_13","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1016\/j.fertnstert.2015.03.018","article-title":"Pregnancy-related complications and adverse pregnancy outcomes in multiple pregnancies resulting from assisted reproductive technology: A meta-analysis of cohort studies","volume":"103","author":"Qin","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., Altman, D., Antes, G., and the PRISMA Group (2009). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med., 6.","DOI":"10.2427\/5768"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"F205","DOI":"10.1136\/archdischild-2012-302040","article-title":"Neurodevelopmental outcomes of extremely premature infants conceived after assisted conception: A population based cohort study","volume":"98","author":"Bajuk","year":"2013","journal-title":"Arch. Dis. Child.-Fetal Neonatal Ed."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1111\/j.1471-0528.2005.00663.x","article-title":"Two-year neurodevelopmental outcome in children conceived by intracytoplasmic sperm injection: Prospective cohort study","volume":"112","author":"Agarwal","year":"2005","journal-title":"BJOG Int. J. Obstet. 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Pediatr."},{"key":"ref_28","first-page":"79","article-title":"Neurodevelopmental Status of Infants Conceived Assisted Reproductive Techniques in Royan Institute","volume":"5","author":"Kermani","year":"2011","journal-title":"J. Fam. Reprod. Health"},{"key":"ref_29","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":"ref_30","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1093\/humrep\/des430","article-title":"Autism spectrum disorders in IVF children: A national case-control study in Finland","volume":"28","author":"Lehti","year":"2013","journal-title":"Hum. 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