title: Birth defects in children conceived by ICSI compared with children conceived by other IVF-methods; a meta-analysis.
abstract: BACKGROUND
  Intracytoplasmic sperm injection (ICSI) is a method of assisted reproductive technology that involves the selection of a single sperm cell and the manual injection of this cell into the egg. The lack of relevant experimental studies, the nature of the technology involving non-natural selection of the fertilizing sperm, and possible damage to the egg have caused concern that ICSI could increase the risk of birth defects. Data from available cohort studies comparing ICSI with standard in vitro fertilization (IVF) should be combined to evaluate the risks involved with ICSI.
  
  
  METHODS
  We reviewed more than 2500 titles and abstracts containing keywords related to ICSI and identified 22 scientific articles with data on birth defects among ICSI-births. A total of four peer-reviewed, non-overlapping prospective cohort studies provided reliable and comparable data on birth defects both for children conceived by ICSI and children conceived by standard IVF. These studies included a total of 5395 children born after ICSI.
  
  
  RESULTS
  The pooled estimate of the risk of a major birth defect was a 1.12-fold increase after ICSI when compared with standard IVF (risk ratio = 1.12, 95% confidence interval (CI): 0.97-1.28, P = 0.12). There was no marked heterogeneity of risk ratios between these studies (P = 0.10). We found no significantly increased risks after ICSI for any of the categories cardiovascular defects, musculoskeletal defects, hypospadias, neural tube defects, or oral clefts.
  
  
  CONCLUSIONS
  Our analysis does not indicate that the ICSI-procedure represents significant additional risks of major birth defects in addition to the risk involved in standard IVF. The data was limited, particularly on risks of specific categories of defects.
authors.affiliation: Department of Public Health and Primary Health Care, University of Bergen and The Medical Birth Registry of Norway, Norway. rolv.lie@smis.b.no
authors.forename: Rolv T
authors.initials: RT
authors.lastname: Lie
authors.forename: Anita
authors.initials: A
authors.lastname: Lyngstadaas
authors.forename: Karen Helene
authors.initials: KH
authors.lastname: Ørstavik
authors.forename: Leiv S
authors.initials: LS
authors.lastname: Bakketeig
authors.forename: Geir
authors.initials: G
authors.lastname: Jacobsen
authors.forename: Tom
authors.initials: T
authors.lastname: Tanbo
mesh_terms: D018376:Cardiovascular Abnormalities / Q000453:epidemiology / Q000209:etiology; D000013:Congenital Abnormalities / Q000453:epidemiology* / Q000209:etiology; D005307:Fertilization in Vitro / Q000009:adverse effects*; D006801:Humans; D007021:Hypospadias / Q000453:epidemiology / Q000209:etiology; D008297:Male; D009056:Mouth Abnormalities / Q000453:epidemiology / Q000209:etiology; D009139:Musculoskeletal Abnormalities / Q000453:epidemiology / Q000209:etiology; D009436:Neural Tube Defects / Q000453:epidemiology / Q000209:etiology; D012307:Risk Factors; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects