The risk of malformation following assisted reproduction.

INTRODUCTION 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.