GnRH agonist treatment regulates IL-6 and IL-11 expression in endometrial stromal cells for patients with HRT regiment in frozen embryo transfer cycles

To evaluate the effect of gonadotropin-releasing hormone agonist (GnRHa) pretreatment time on clinical outcomes of patients who underwent endometrial preparation in HRT cycles and the molecular mechanism in frozen-thawed embryo transfer (FET) cycles, we retrospectively chose 1143 cycles and separated four groups. Endometrial tissues were collected from 44 patients who were cancelled on the day of embryo transfer (there were 10 patients refused to collect endometrium) and were tested for endometrial receptivity marker mRNA and miR-124-3p expression. Furthermore, endometrial stromal cells (ESCs) were transfected to investigate the molecular mechanism. The clinical pregnancy rate and live birth rate were significantly high in group B. The endometrial expression of the IL-6 and IL-11 mRNAs was significantly increased in groups with GnRHa pretreatment compared with group A without the GnRHa pretreatment. Similar results were obtained for the endometrial receptivity markers LIF and integrin αvβ3. The groups treated with GnRHa exhibited a progressive and significant time-dependent decrease in the IL-6 and IL-11 mRNA. In contrast, the levels of LIF and integrin αvβ3 expression remained unaltered among group B-D. In addition, transfection of ESCs with miR-124-3p mimics significantly reduced levels of the IL-6 and IL-11 mRNAs and proteins. The luciferase report assay demonstrated that IL-6 and IL-11 is a target gene of miR-124-3p. The results showed that ultra-long GnRHa administration can improve outcomes, especially after 3 cycles of GnRHa pretreatment, and endometrial receptivity through IL-6 and IL-11 expression levels of ESC regulated by the miR-124-3p for patients with HRT, who underwent FET cycles.