Endometrial receptivity under hormone replacement therapy in oocyte-donation recipient patients: transcriptomic approach

Purpose: Few studies have investigated the endometrial receptivity status of oocyte-donation (OD) recipient patients at the specific hormone replacement therapy (HRT)-cycle timing (5 to 6 days after progesterone administration) where embryos at blastocyst stage were mostly replaced. The aim of our study was to analyse, during the implantation window, (i) the global endometrial gene expression profile, and (ii) the endometrial receptivity exploration by the Win-Test^® in OD recipient patients under HRT compared to spontaneous cycle in patients awaiting for IVF.

Material and methods: This study included OD recipient patients without (n=7) or with (OD RIF, n=20) repeated implantation failures and 12 normal responder patients in spontaneous cycles used as control. Endometrial biopsies were performed during the peri-implantation phase. Samples were analysed using DNA microarrays and the endometrial gene expression profiles of HRT-treated OD recipient patients and of patients in spontaneous cycles were compared. Then, specific biomarkers of endometrial receptivity were assessed in the two groups of HRT-treated OD patients in comparison to control patients

Results: The global gene expression profile of peri-implantation endometrial samples from HRT-treated OD recipients and from patients in spontaneous cycles was different with  significant alterations in the oestrogen receptor signalling [GTF2H2B, POLR2B, POLR2E], VEGF family ligand-receptor interactions [VEGFR1, VEGFB] and integrin signalling [ITGAL, PAK7, ILK]. Using specific biomarkers of human endometrial receptivity, we found that endometrium was non-receptive (29 % and 43 % in OD and RIF OD patients, respectively) or partially receptive (71 and 43 % in OD and RIF OD patients, respectively), at Pg+5/+6, in majority of HRT-treated patients. In OD RIF patients, a delay of the implantation window was observed. However, by targeting personalized embryos transfer by identifying for each patient the HRT-cycle day where endometrium is receptive, with respect of the synchronization of embryo-endometrium dialogue, high pregnancy rate per frozen-thawed embryo replacement (50%) was obtained in OD RIF patients.