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 The risk of malformation following assisted reproduction Bertelsmann H; de Carvalho Gomes H; Mund M; Bauer S; Matthias KDtsch Arztebl Int  2008[Jan]; 105 (1-2): 11-7INTRODUCTION: Intracytoplasmatic sperm injection (ICSI) is currently the most  frequently used human reproductive technology in Germany. ICSI was introduced as  routine, insurance-funded medical care in 2002 by the Federal Joint Committee. A  re-evaluation of published literature on malformation rates in children born of  ICSI pregnancies within a period of three years formed part of the committee's  decision. The analysis investigated whether ICSI increases the risk of  malformation in the offspring, compared to in vitro fertilization (IVF) and  natural conception. METHODS: Systematic literature review. RESULTS: 929 studies  were identified. Three meta-analyses, 15 studies investigating malformations, and  12 studies analyzing imprinting disorders were included. The risk of malformation  was not significantly different in nine studies comparing ICSI versus IVF. Two  meta-analyses and three of eight cohort studies and retrospective analysis showed  significantly more severe malformations after assisted reproduction than after  natural conception. The remaining five studies displayed no significant results.  Current evidence does not show a higher risk of major malformations in the  offspring resulting from the use of ICSI compared to IVF. However, there is  evidence that both techniques increase the risk for major malformations  considerably, compared to natural conception, and further research is needed. The  validity of the results is low since the studies were heterogeneous and the  cohorts used in the studies had limited comparability.ä
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