Chromosomal instability (CIN) is a common phenomenon in cleavage-stage embryogenesis that leads to a mixture of euploid and aneuploid cells within the same human embryo during in vitro fertilization (IVF). However, the rate of CIN in naturally conceived embryos is largely unknown, because it is impossible to study human embryos in vivo. Here, we developed and applied a novel haplarithmisis-based method to characterize allelic architecture of DNA samples derived from the placenta and cord blood of the same pregnancy. Specifically, we scrutinized genome-wide single nucleotide polymorphism profiles in DNA from the father, mother, placenta and neonate umbilical cord blood of 55 families (quartets), of which 26 and 29 quartets were from natural and IVF pregnancies, respectively. We demonstrate that CIN is not preserved at later stages of prenatal development, and that de novo genomic alterations occur at similar rates in IVF and naturally conceived neonates. The findings confirm that IVF treatment has no detrimental effect on the chromosomal constitution of fetal or placental lineages
