BACKGROUND Prenatal screening and diagnosis of chromosomal abnormalities especially Down's syndrome in IVF pregnancies are complicated by higher maternal age, a high multiple pregnancy rate, a high risk of a vanishing twin and an increased risk of chromosomal abnormalities, particularly in pregnancies after ICSI. The aim of the present systematic review was to evaluate the findings of first trimester screening for chromosomal abnormalities in IVF/ICSI singleton and twin pregnancies. METHODS A systematic MESH-term search in MEDLINE using PubMed and the Cochrane Library was performed until May 2011, with no earlier date limit. RESULTS The electronic search retrieved 562 citations, 96 of which were evaluated in detail and 57 were then excluded for not meeting the selection criteria. A total of 61 articles were finally selected for review. Our analysis of the data shows that, for IVF/ICSI singletons, combined first trimester prenatal screening based on maternal age, nuchal translucency scan and biomarkers is appropriate. However, biomarkers seem to be altered, causing a higher false-positive rate, in IVF/ICSI singleton gestations. Correction factors have been developed and should be used when screening for Down's syndrome in singleton pregnancies. With regard to IVF/ICSI twin pregnancies, biomarker values seem to be dependent on chorionicity as well as gestational age. Whether the use of a correction factor for mode of conception in the risk calculations for Down's syndrome in twin pregnancies is valid has not been fully elucidated. In vanishing twin pregnancies with a second gestational sac with a dead fetus, first trimester screening should be based solely on the maternal age and the nuchal translucency scan as biomarkers are significantly altered in these cases. CONCLUSIONS First trimester prenatal screening after IVF/ICSI treatment requires specific precautions in both singleton and twin pregnancies.