In vitro maturation of oocytes is not associated with altered deoxyribonucleic acid methylation patterns in children from in vitro fertilization or intracytoplasmic sperm injection

Objective To study the possible transmission, to the next generation, of epigenetic defects associated with in vitro maturation (IVM) of human oocytes. Design Case-control study using epigenetic data. Setting Two collaborating university departments. Patient(s) Eleven IVM newborns and 19 controls, conceived by conventional assisted reproduction. Intervention(s) Chorionic villus and cord-blood sampling. Main Outcome Measure(s) Using bisulfite pyrosequencing, we have measured average methylation levels of 6 imprinted (LIT1, MEG, MEST, NESPas, PEG3, and SNRPN), 5 tumor-suppressor (APC, ATM, BRCA1, RAD51C, and TP53), 2 pluripotency (NANOG and OCT4), and 2 metabolic (LEP and NR3C1) genes, as well as 2 repetitive elements (ALU and LINE1) in 2 tissues of IVM and control neonates. Using deep bisulfite sequencing, we have determined methylation patterns of many individual DNA molecules to detect rare RAD51C epimutations (allele methylation errors). Result(s) No statistically significant impact was found of IVM on chorionic villus and cord-blood DNA methylation at the studied developmentally important genes and interspersed repeats. The RAD51C epimutation rate was low (0.5% ± 0.1%) in all analyzed samples. Conclusion(s) IVM-induced epigenetic changes in offspring, if any, are relatively small in magnitude and/or infrequent.