OR15-6 Epigenetic Differences in First Trimester Pregnancies Conceived with Infertility

Abstract

Pregnancies conceived with infertility are at increased risk of adverse outcomes. It is unclear if these outcomes are due to the underlying infertility or the fertility treatments, which includes in vitro fertilization (IVF) and non-IVF (NIFT) treatments. Adverse outcomes, such as low birth weight and preeclampsia, are likely due to implantation and placentation defects early in pregnancy. Previously, we identified hormonal differences in maternal plasma early in gestation that may influence placentation. The underlying treatment including the hormonal influence may impact the epigenome during placentation. Therefore, we investigated DNA methylation in the late first trimester of ongoing pregnancies conceived with and without infertility with respect to the fertility treatments utilized. Tissue was obtained via chorionic villus sampling. DNA methylation for 112 subjects was performed using the Illumina Infinium MethylationEPIC BeadChip array for 866,836 human sites. Two analyses were performed to assess the effect of infertility on the human epigenome: spontaneous pregnancies versus all pregnancies with infertility (including IVF and NIFT pregnancies), and spontaneous pregnancies versus IVF pregnancies only. After normalization, regression analysis for each comparison was performed to identify differentially methylated positions. Three sites were significantly differentially methylated in both patient comparisons, overlapping with gene regions for melanotranferrin (MFI2), apoptotic chromatin condensation inducer 1 (ACIN1), and ankyrin repeat domain 17 (ANKRD17). These genes are involved in iron-binding, alternative splicing, apoptotic chromatin condensation, DNA replication, and innate immune pathways. Since these three differentially methylated genes are seen in the infertility as well as the IVF cohort, the methylation differences may arise from the infertility itself rather than the specific fertility treatments. In contrast, additional DNA methylated differences only found in the spontaneous versus IVF comparison may be due to the underlying treatment, including in vitro embryo development as well as the high hormonal state found in IVF pregnancies. Additional studies investigating the cause as well as the impact of these differentially methylated genes in placentation and pregnancy outcomes are needed.