Application of Minimally-Invasive Uterine Fluid Aspiration to Identify Candidate Biomarkers of Endometrial Receptivity through a Transcriptomic Approach.

摘要

The endometrium is receptive to the embryo during a restricted window in the mid-secretory phase. My objectives were to develop a minimally-invasive endometrial sampling method for gene expression profiling, and to identify genes differentially expressed in the receptive phase. Twenty-three normo-ovulatory women underwent uterine fluid aspiration during the pre-receptive (LH+2) and receptive (LH+7) phase of the same natural cycle. RNA was extracted, reverse transcribed, amplified and hybridized to whole-genome microarrays. Unsupervised hierarchical clustering revealed self-segregation of pre-receptive and receptive samples. Importantly, profiling by uterine fluid aspiration was representative of biopsy. An unpaired t-test with a false discovery rate of 0.05 and a ? threshold of 4-fold identified 245 unique transcripts as differentially expressed in the receptive phase. NanoString analysis validated 96% of these genes. This approach will now allow us to correlate expression of these candidate biomarkers to implantation outcomes, towards the development of clinical assays predictive for endometrial receptivity.