DNA methylation in newborns conceived by assisted reproductive technology

Assisted reproductive technology (ART) may affect fetal development through epigenetic mechanisms as the timing of ART procedures coincides with the extensive epigenetic remodeling occurring between fertilization and embryo implantation. However, it is unknown to what extent ART procedures alter the fetal epigenome. Underlying parental characteristics and subfertility may also play a role. Here we identify differences in cord blood DNA methylation, measured using the Illumina EPIC platform, between 962 ART conceived and 983 naturally conceived singleton newborns. We show that ART conceived newborns display widespread differences in DNA methylation, and overall less methylation across the genome. There were 607 genome-wide differentially methylated CpGs. We find differences in 176 known genes, including genes related to growth, neurodevelopment, and other health outcomes that have been associated with ART. Both fresh and frozen embryo transfer show DNA methylation differences. Associations persist after controlling for parents' DNA methylation, and are not explained by parental subfertility. Timing of assisted reproduction technology (ART) procedures coincides with extensive epigenetic remodeling early after conception. Here the authors identify 176 DNA methylation differences in cord blood of newborns conceived with ART. including genes related to growth, neurodevelopment, and cancer.

Automated summary

Assisted reproductive technology (ART) may affect fetal development through epigenetic mechanisms, leading to widespread differences in DNA methylation and variations in genes related to growth, neurodevelopment, and other health outcomes.