Effect of hysteroscopic-guided endometrial local injury on pregnancy outcomes of frozen embryo transfer cycle and preliminary exploration of the mechanism
Objective:To explore the effects of hysteroscopic-guided endometrial local injury(HS-ELI)on endometrial receptivity and pregnancy outcomes during the implantation window of frozen embryo transfer(FET)cycle,and the molecular mechanism of HS-ELI affecting endometrial receptivity.Methods:A total of 270 patients with a history of at least two IVF-ET embryo transplant failure who underwent FET in Reproductive Medicine Center in Shijiazhuang 4th hospital from December 2020 to August 2022 were recruited.They were divided into the study group(135 cases)and the control group(135 cases)according to whether HS-ELI was performed in the same cycle,and the pregnancy outcomes of the two groups were statistically analyzed.Other ten patients were recruited,all of whom planned to undergo FET but gave up transplantation due to personal reasons.According to whether HS-ELI was performed in the same cycle,they were divided into the study group(5 cases)and the control group(5 cases).The uterine cavity washing fluid was obtained in the mid-luteal phase(7-9 days after the LH peak).Fluid samples were subjected to Olink proteomics detection and the bioinformatics analysis.Results:The biochemical pregnancy rate of HS-ELI group was 62.22％,the embryo implantation rate was 42.60％,and the clinical pregnancy rate was 59.30％,which were all higher than those of the control group(49.63％,31.63％,42.96％,P＜0.05).The results of the omics analysis showed that there were three differential proteins with significantly up-regulated expression in the study group compared with the control group,including monocyte chemoattractant protein 4(MCP-4/CCL13),thymic stromal lymphopoietin(TSLP),and macrophage chemotactic protein 2(MCP-2/CCL8)(P＜0.05).These three differentially expressed proteins were enriched in four signaling pathways,namely cytokine-cytokine receptor interaction signaling pathway,chemokine signaling pathway,NF-kappa B signaling pathway,and JAK-STAT signaling pathway,which were mainly related to inflammatory and immune responses induced by external stimulation.Conclusions:HS-ELI performed during the same FET cycles could significantly increase the biochemical pregnancy rate,embryo implantation rate and clinical pregnancy rate.The mechanism involves in induction of endometrial inflammatory response,promotion of the secretion of TSLP and chemokines ect.,resulting in improving endometrial receptivity as well as enhancing the proliferation and invasion capabilities of trophoblast cells for improving pregnancy outcomes.
Endometrial receptivityHysteroscopic-guided endometrial local injuryUterine washing fluidIVF-ET
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