Objective: To investigate the effect and possible mechanism of downregulation of gonadotropin-releasing hormone agonist (GnRHa) on Th17/Treg (regulatory T cell) cells in peripheral blood of patients with unexplained repeated implantation failure (RIF).
Methods: Fifty-two patients who had RIF (≥ 3 consecutive transfers of ≥ 4 high-grade embryos in women under the age of 40 (excluding 40)) of frozen-thawed embryos were studied. Twenty-nine cases receiving simple hormone replacement therapy (HRT) were defined as transfer group, and the remaining 23 cases with HRT combined with GnRHa downregulation were defined as GnRHa downregulation group. In addition, 30 cases of the normal early pregnancy group were selected as control group.
Results: Before HRT, the number of Th17 and Treg cells in CD4+ lymphocytes was increased and decreased, respectively, with the ratio of Th17/Treg cells increased in HRT group compared with the control group (p < 0.05). On the day of progesterone conversion, compared with the HRT group, the percentage of Th17 and Treg cells was decreased and increased, respectively, with the ratio of Th17/Treg cells decreased significantly in GnRHa downregulation group (p < 0.05). The estrogen E2 levels of the GnRHa downregulation group were slightly higher than those of the HRT group, with no significant difference between the two groups (p > 0.05). Further, there was no significant difference in the levels of chorionic gonadotropin at the 14th day and the 21st day after transplantation between HRT group and GnRHa downregulation group (p > 0.05).
Conclusion: There were an increase and a decrease in the number of Th17 and Treg cells, respectively, with Th17/Treg cells imbalanced in unexplained RIF. GnRHa downregulation may play a direct immunomodulatory role in disrupting the imbalance and then improve the endometrial receptivity. These effects did not depend on the E2 levels in peripheral blood, nor affect early embryonic development.
Keywords: Gonadotropin-releasing hormone; Hormone replacement therapy (HRT); Repeated implantation failure (RIF); Th17; Th17/Treg; Treg.