Methylome-wide analysis of IVF neonates that underwent embryo culture in different media revealed no significant differences

Abstract

A growing number of children born are conceived through in vitro fertilisation (IVF), which has been linked to an increased risk of adverse perinatal outcomes, as well as altered growth profiles and cardiometabolic differences in the resultant individuals. Some of these outcomes have also been shown to be influenced by the use of different IVF culture media and this effect is hypothesised to be mediated epigenetically, e.g. through the methylome. As such, we profiled the umbilical cord blood methylome of IVF neonates that underwent preimplantation embryo development in two different IVF culture media (G5 or HTF), using the Infinium Human Methylation EPIC BeadChip. We found no significant methylation differences between the two groups in terms of: (i) systematic differences at CpG sites or regions, (ii) imprinted sites/genes or birth weight-associated sites, (iii) stochastic differences presenting as DNA methylation outliers or differentially variable sites, and (iv) epigenetic gestational age acceleration. ; We thank the IVF couples who have agreed for their children to participate in this study. We thank all the employees of the IVF clinics and obstetrics departments involved in recruiting participants and collecting samples for this study. We thank E. Pishva for his consultation regarding data analysis and for the critical reading of the manuscript. This study was funded by March of Dimes (6-FY13-153). It was further supported by the stichting fertility foundation, EVA (Erfelijkheid Voortplanting & Aanleg) speciality programme (grant no. KP111513) of Maastricht University Medical Centre (MUMC+), and the Horizon 2020 innovation (ERIN) (grant no. EU952516) of the European Commission. We thank the FLEHS Supervisory Board for the provision of data. The FLEHS studies are commissioned, financed, and steered by the Flemish Government (Department of Economy, Science and Innovations, Agency for Care and Health and Department of Environment). The FLEHS dataset has been generated by the Flemish Center of Expertise on ...