Gene Expression Profiling of Peripheral Blood during In Vitro Fertilisation Treatment Reveals Predictive Markers of Pregnancy
C Allen, CM Martin, JJ O'Leary. Rotunda Hospital, Dublin, Ireland; Coombe Women's Hospital, Dublin, Ireland
Background: Infertility is an increasing global disease but the molecular pathways surrounding human conception remain poorly understood. There are no reliable predictors of success for invasive fertility treatments. Here we examine the functional transcriptome in IVF induced pregnancy and non-pregnant controls, to elucidate predictive biomarkers which identify implantation events, maintenance of pregnancy, and pregnancy outcome.
Design: Gene expression patterns in RNA extracted from peripheral blood at time points during IVF cycles from 5 women who achieved clinical pregnancies, 3 women who had implantation failure, and 3 subfertile women who conceived spontaneously were evaluated. Total RNA was extracted from whole blood collected in Tempus RNA collection Tubes using the ABI PRISM 6100 Nucleic Acid PrepStation. Gene expression analysis was performed using AB Human Genome Survey Microarrays. Data analysis was performed using R statistical package, molecular function and biological process analysis was performed using Panther.
Results: 128 genes were differentially expressed in early pregnancy compared with a non-pregnant state (p < 0.05). Associated molecular pathways include angiogenesis, endothelin signaling, inflammation, oxidative stress, VEGF, and pyruvate metabolism. 200 genes were differentially expressed at a pre-treatment time-point in women who became pregnant compared to those who did not (p<0.05). Associated molecular pathways include angiogenesis, blood coagulation, endogenous cannabiniod, inflammation, and Wnt signaling pathway. Transcripts associated with cysteine biosynthesis were differentially expressed in the early post-conceptual period in the pregnant women compared to those with implantation failure. 237 genes were differentially expressed in first trimester IVF conceptions compared with spontaneous conceptions in subfertile women (p<0.05). Associated molecular pathways include Heterotrimeric G protein signaling.
Conclusions: This is the first report of gene expression profiles in peripheral blood during in vitro fertilization. The transcriptome signature for early human pregnancy is influenced by the trimera of mother, fetus, and placenta. Gene expression profiles prior to IVF are predictive of outcome, and could aid clinical decision-making for future patients. Significant differences in gene expression between assisted and natural conceptions is of concern and highlights the need to optimize IVF protocols.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 239, Wednesday Afternoon