Differential Gene Expression during Placentation in Pregnancies Conceived with Different Fertility Treatments Compared to Spontaneous Pregnancies

Objective: To identify differences in the transcriptomic profiles during placentation from pregnancies conceived spontaneously to those with infertility, using non-in vitro fertilization (NIFT) or in vitro fertilization (IVF). Design: Cohort study. Setting: Academic Medical Center. Patient(s): Women undergoing chorionic villus sampling at gestational age 11–13 weeks (n=141), with pregnancies that were conceived spontaneously (n=74), with NIFT (n=33), or IVF (n=34) resulting in the delivery of viable offspring. Intervention(s): Collection of chorionic villus samples from women who conceived spontaneously, with NIFT or IVF for gene expression analysis using RNA sequencing. Main Outcome Measure(s): Baseline maternal, paternal and fetal demographics, maternal medical conditions, pregnancy complications and outcomes. Differential gene expression of first trimester placenta. Result(s): There were few differences in the transcriptome of first trimester placenta from NIFT, IVF, and spontaneous pregnancies. There was one protein-coding differentially expressed gene (DEG) between the spontaneous and infertility groups, CACNA1I, one protein-coding DEG between the spontaneous and IVF groups, CACNA1I, and five protein-coding DEGs between the NIFT and IVF groups, SLC18A2, CCL21, FXYD2, PAEP, and DNER. families were among the top upstream regulators that predicted transcript differences in spontaneous versus IVF pregnancies, but not spontaneous versus NIFT pregnancies. These results suggest that IVF pregnancies may have slightly altered regulation of cytokine signaling pathways in late first trimester, compared to other pregnancies, which may be altering normal placentation. By contrast, spontaneous versus NIFT pregnancies had more diverse top canonical pathways and upstream regulators, which may reflect different etiology of infertility between NIFT and IVF pregnancies.