Clinical outcomes according to the endometrial HCG infusion time in thawed blastocyst transfer cycles and gene expression profiling of infused endometrium

To investigate the optimal time of endometrial hCG infusion before frozen thawed blastocyst tranfer in unexplained or refractory repeated implantation failure. Retrospective study. Exp1: comparison of optimal infusion time of hCG in endometrium. Compared infusion time; group 1) the day of thawed embryo transfer (TET) and group 2) 2-3 days before TET. Exp2: comparison of endometrial gene expression between non-hCG infusion and hCG infusion. Total 54 unexplained or refractory repeated implantation failure patients were included from November 1, 2014 to April 10, 2015. Infusion time of 42 patients were the day of thawed embryo transfer (TET) cycles and 12 patients were 2-3 days before TET. They received intrauterine administration of 500IU of urinary hCG. Two blastocysts were transferred. Comparison of endometrial gene expression and histological evaluation between non-hCG infusion and hCG infusion, 2-3 days before transfer (P+5 vs. P+5) in same patient (n=1) were accomplished. Endometrial samples were obtained after endometrial infusion of hCG. The profiling of transcriptome and histologic evaluation (H&E staining) were accomplished for evaluation of the endometrial dating and receptive status. The clinical pregnancy rates (CPR) were no significanty different between two groups (group1; 40.5% (17/42) and group2 58.3% (7/12), but implantation rates were significantly higher in group2 (group1; 14.3% (12/84)) and group2; 33.3% (8/24)) (P<0.05). There is a different transcriptomic signature and histological feature between hCG non-infused and infused endometrium obtained on the same day of menstrual cycles. The 4329 genes (2070 up-regulated and 2259 down-regulated) exhibited altered expression patterns between non-hCG infused and hCG infused endometriums (P+5 vs. P+5 phase). This study shows higher IR in intrauterine hCG infusion at 2-3 before ET than the day of thawed embryo transfer in TET cycles in unexplained or refractory RIF. In comparison of endometrial gene expression profiling and histological evaluation of endometrium obtained after direct infusion of hCG at the time of ET provide many different patterns when compared to non-infusion.