Genetic and epigenetic characteristics of ICSI children.

The outcome of pregnancy and the developmental wellbeing of children conceived from 12,866 consecutive intracytoplasmic sperm injection (ICSI) cycles was assessed. A total of 3277 couples delivered 5891 neonates. There was a higher than normal incidence of de-novo chromosomal abnormalities in a small sample of ICSI offspring. Controlling for maternal age showed that the incidence of low birth weight and gestational length were comparable with the naturally conceived counterpart. Rates of malformation in ICSI offspring ranged from 3.5 to 6.2%. At 3 years of age (n = 811), the proportion of children at risk for developmental delays was 10.4% in ICSI and 10.7% in IVF singletons. However, high order gestations were characterized by 19.4% of the children having compromised development. Epigenetic analysis of assisted reproductive technique conceptuses found minor imprinted gene expression imbalances. ICSI offspring presented with genetic defects that were inherited or arose de novo. Obstetric and neonatal outcomes of singleton pregnancies appeared to be dependent upon maternal age. ICSI and IVF appeared to exert a negative effect on the wellbeing of offspring mainly because of the association with multiple gestations. All assisted reproduction procedures should be monitored for the eventual effect of environmental aggressors on offspring epigenesis.