title: Health outcomes of children born after IVF/ICSI: a review of current expert opinion and literature.
abstract: The Sixth Evian Annual Reproduction (EVAR) Workshop Group Meeting was held to evaluate the impact of IVF/intracytoplasmic sperm injection on the health of assisted-conception children. Epidemiologists, reproductive endocrinologists, embryologists and geneticists presented data from published literature and ongoing research on the incidence of genetic and epigenetic abnormalities and congenital malformations in assisted-conception versus naturally conceived children to reach a consensus on the reasons for potential differences in outcomes between these two groups. IVF-conceived children have lower birthweights and higher peripheral fat, blood pressure and fasting glucose concentrations than controls. Growth, development and cognitive function in assisted-conception children are similar to controls. The absolute risk of imprinting disorders after assisted reproduction is less than 1%. A direct link between assisted reproduction and health-related outcomes in assisted-conception children could not be established. Women undergoing assisted reproduction are often older, increasing the chances of obtaining abnormal gametes that may cause deviations in outcomes between assisted-conception and naturally conceived children. However, after taking into account these factors, it is not clear to what extent poorer outcomes are due to the assisted reproduction procedures themselves. Large-scale, multicentre, prospective epidemiological studies are needed to investigate this further and to confirm long-term health consequences in assisted-conception children. Assisted reproduction treatment is a general term used to describe methods of achieving pregnancy by artificial means and includes IVF and sperm implantation. The effect of assisted reproduction treatment on the health of children born using these artificial methods is not fully understood. In April 2011, fertility research experts met to give presentations based on research in this area and to look carefully at the evidence for the effects of assisted reproduction treatment on children's health. The purpose of this review was to reach an agreement on whether there are differences in the health of assisted-conception children with naturally conceived children. The researchers discovered no increased risk in birth defects in assisted-conception children compared with naturally conceived children. They found that IVF-conceived children have lower birth weights and higher fat under the skin, higher blood pressure and higher fasting glucose concentrations than naturally conceived children; however, growth, development and cognitive function are similar between groups. A very low risk of disorders of genetic control was observed in assisted-conception children. Overall, there did not appear to be a direct link between assisted reproduction treatment and children's health. The researchers concluded that the cause of some differences in the health of children conceived using assisted reproduction treatment may be due to the age of the woman receiving treatment. Large-scale, research studies are needed to study the long-term health of children conceived using assisted reproduction treatment.
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: b.c.fauser@umcutrecht.nl.
authors.forename: B C J M
authors.initials: BC
authors.lastname: Fauser
authors.affiliation: Center for Reproductive Medicine, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Devroey
authors.affiliation: Department of Obstetrics and Gynecology, University Clinic of Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Diedrich
authors.affiliation: Assisted Reproduction Unit, American Hospital of Istanbul, Guzelbahce Sokak No 20, Nisantasi, Istanbul 34365, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Balaban
authors.affiliation: Centre for Medical Genetics, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Bonduelle
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: H A
authors.initials: HA
authors.lastname: Delemarre-van de Waal
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Valencia University, and Instituto Universitario IVI/INCLIVA, Parc Científic Universitat de València C/Catedrático Agustín Escardino n(o) 9, Edificio 3, 46980 Paterna, Spain; Departamento de Biología Molecular and Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Estella
authors.affiliation: Global Development and Medical Unit, Merck Serono SA Geneva, Chemin des Mines 9, 1202 Geneva, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Ezcurra
authors.affiliation: Department of Genetics and Cell Biology, Research Institute GROW, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: J P M
authors.initials: JP
authors.lastname: Geraedts
authors.affiliation: Global Development and Medical Unit, Merck Serono SA Geneva, Chemin des Mines 9, 1202 Geneva, Switzerland.
authors.forename: C M
authors.initials: CM
authors.lastname: Howles
authors.affiliation: Woman and Child Health Research Unit, Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer 52621, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Lerner-Geva
authors.affiliation: Instituto Valenciano de Infertilidad (IVI) Zaragoza, C/María Zambrano, 31, 50018 Zaragoza, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Serna
authors.affiliation: University of Oxford, Nuffield Department of Obstetrics and Gynaecology, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: D
authors.initials: D
authors.lastname: Wells
mesh_terms: D002648:Child; D002657:Child Development / Q000502:physiology*; D000013:Congenital Abnormalities / Q000453:epidemiology*; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects / Q000706:statistics & numerical data*; D030342:Genetic Diseases, Inborn / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007246:Infertility / Q000628:therapy*; D009865:Oocytes / Q000166:cytology; D011247:Pregnancy; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects / Q000706:statistics & numerical data*
keywords: IVF; assisted reproduction; children outcome; imprinting disorders; infertility; intracytoplasmic sperm injection