Grace LP, et al. - This study aimed to research the impact of mifepristone on endometrial receptivity targeting the expression of genes that composed the signature of endometrial receptivity in the endometrial receptivity analysis (ERA) test. These outcomes exhibit at the molecular level the progesterone inhibition action of the mifepristone, demonstrating proliferative profiles in 6 out of 7 secretory treated endometrium. Differences at gene expression level between proliferative reference signature and T samples proposes that the antagonist impact at the glucocorticoid receptor of mifepristone might contribute to it.

Methods

• In this study, they investigated the transcriptomic signature of endometrial biopsies obtained in natural cycle amid the window of implantation from 7 women treated with mifepristone (T) and 11 women with proven fertility and without treatment (C).
• Gene expression data from T samples were compared to proliferative reference transcriptomic signature (P).
• Endometrial biopsies were obtained at LH+7 in the natural cycle.
• For mifepristone treatment, it was administered 200 mg starting at LH+2.
• RNA was extracted by Quick-RNA microprep (Zymo Research) as per the manufacturer’s protocol.
• All the samples were DNAse treated, and cDNA was obtained by retrotranscription and examined by customized assay on IonTorrent Next Generation Sequencing, for 236 ERA genes in an Ion S5 system.
• The samples were classified utilizing the ERA computational predictor.
• EdgeR package was utilized to perform the differential expression investigation among the three groups of samples (C, T and P).

Results

• Endometrial samples from T and C groups were examined in the same batch, and results compared.
• Six out of 7 samples from T group showed expression profile of proliferative phase demonstrating no impact of progesterone, and the remaining one had the expression profile of early pre-receptive.
• All the endometrium from the C group had a profile clinically similar for LH+7: 63% Receptive (including early and late receptive) and 37% Pre-receptive.
• There were found 133 genes differentially expressed (FDR<0.05) between these two groups (T and C), allegedly due to different endometrial stages.
• When comparing endometrial samples taken in proliferative stage versus proliferative samples because of mifepristone treatment, there were 95 genes differentially expressed.