Abnormal methylation patterns at the IGF2/H19 imprinting control region in phenotypically normal babies conceived by assisted reproductive technologies

Objective: To evaluate epigenetic risks linked to assisted reproductive technologies (ART) by determining the methylation status of the IGF2/H19 imprinting control region (ICR) in offspring born after ART.

Study design: A combined bisulfite restriction analysis (COBRA) and sequencing technique were used to determine the methylation status of the IGF2/H19 ICR in 61 phenotypically normal newborns conceived by ART. Thirty naturally conceived newborns were studied as controls.

Results: There was no significant difference in methylation between ART newborns and naturally conceived newborns (46.7 ± 8.2% vs. 48.5 ± 8.7%, p>0.05). Abnormal demethylation patterns of the IGF2/H19 ICR were found in three dizygotic twins conceived by intracytoplasmic sperm injection (ICSI), but all three were phenotypically normal, and their sibling twins exhibited normal methylation patterns.

Conclusion: We hypothesize that the aberrant methylation patterns probably resulted from imprinting errors of paternal gametes or from in vitro embryo culture. Further investigation to determine whether gene expression can be regulated by other mechanisms in addition to DNA methylation would be beneficial.