DNA methylation differences at birth after conception through assisted reproductive technologies

Summary The possible health consequences of assisted reproductive technology (ART) are a topic of intense study. Epigenetic mechanisms, such as changes in DNA methylation (DNAm), come forward from animal studies as a potential mechanism linking ART and health. Here we report on an epigenome-wide association study (EWAS) of DNAm in cord blood of 87 infants conceived with in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI) and 70 who were not. We found no difference in global methylation levels, but identified nineteen CpG dinucleotides (CpGs) associated with ART (effect estimates: 0.5-4.9%). There was no difference between IVF and ICSI and the CpGs map to genes related to brain function/development or the plethora of conditions linked to subfertility. Functional annotation did not point to likely functional consequences. Concluding, ART is associated with DNA methylation differences in cord blood, but these differences are limited in number, effect size and with unknown functional consequences.