title: In vitro fertilization is associated with an increase in major birth defects.
abstract: OBJECTIVE
  To determine the risk of major birth defects in cohorts of children conceived through IVF or through IUI as compared with naturally conceived children.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  Children conceived by IVF or IUI at the University of Iowa from 1989 through 2002, compared with a matched cohort of naturally conceived children.
  
  
  METHODS
  None.
  
  
  METHODS
  Outcome data were obtained from Iowa state birth and fetal death certificates and from the Iowa Birth Defects Registry.
  
  
  RESULTS
  Ninety of 1,462 IVF-conceived children (6.2%) and 17 of 343 IUI-conceived children (5.0%) had a major birth defect, compared with 369 of 8,422 naturally conceived children (4.4%). The adjusted odds ratio of a major birth defect in all IVF-conceived children was 1.30 (95% confidence interval [CI] 1.00-1.67) and 1.11 (95% CI 0.67-1.84) for IUI-conceived children. The birth defect rate was increased after IVF when the analysis was limited to term singletons. Cardiovascular and musculoskeletal defects and known birth defect syndromes were increased after IVF. Among IVF-conceived children, there was no difference in birth defect rates after intracytoplasmic sperm injection (ICSI) or after transfer of cryopreserved embryos.
  
  
  CONCLUSIONS
  Infants conceived through IVF have a slightly higher rate of major birth defects. More birth defects are noted among children born to infertile couples treated with IUI, although this difference is not statistically significant. Larger studies of infants conceived by infertile couples after all types of infertility treatment are needed to definitively determine whether the increased risk of birth defects is secondary to problems inherent in the infertile couple and/or factors associated with some aspect of the treatment.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Christine K
authors.initials: CK
authors.lastname: Olson
authors.forename: Kim M
authors.initials: KM
authors.lastname: Keppler-Noreuil
authors.forename: Paul A
authors.initials: PA
authors.lastname: Romitti
authors.forename: William T
authors.initials: WT
authors.lastname: Budelier
authors.forename: Ginny
authors.initials: G
authors.lastname: Ryan
authors.forename: Amy E T
authors.initials: AE
authors.lastname: Sparks
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Van Voorhis
mesh_terms: D000015:Abnormalities, Multiple / Q000453:epidemiology* / Q000209:etiology*; D000328:Adult; D000704:Analysis of Variance; D015331:Cohort Studies; D016001:Confidence Intervals; D000013:Congenital Abnormalities / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects* / Q000706:statistics & numerical data*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007315:Insemination, Artificial / Q000009:adverse effects / Q000706:statistics & numerical data; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011247:Pregnancy; D012042:Registries / Q000706:statistics & numerical data; D012189:Retrospective Studies