Effects of treatment with hydroxychloroquine on the modulation of Th17/Treg ratio and pregnancy outcomes in women with recurrent implantation failure: clinical trial

羟氯喹治疗对复发性着床失败女性 Th17/Treg 比例调节及妊娠结局的影响:临床试验

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作者:Sonia Sadeghpour, Morteza Ghasemnejad Berenji, Hamid Nazarian, Tohid Ghasemnejad, Mohammad Hadi Nematollahi, Sina Abroon, Shahrokh Paktinat, Heidar Heidari Khoei, Hojjat Ghasemnejad Berenji, Marefat Ghaffari Novin

Aim

The imbalance of Th17/Treg cells has been recently suggested as a new risk factors for recurrent implantation failure (RIF). Furthermore Th17/Treg cells are involved in immune regulation in peripheral blood and endometrial tissue of patients with RIF. In this research, we investigated the effects of Hydroxychloroquine (HCQ) on the level and function of Th17 and Treg cells in women with RIF. It may be possible to improve pregnancy outcomes by modulating high cytokine levels.

Conclusion

Our results demonstrated that the administration of HCQ in RIF women with immune cell disorders during pregnancy could affect the Th17/Treg ratio and enhance Treg and diminish Th17 responses which may be associated with successful pregnancy outcomes. However, significant difference in pregnancy outcomes was not observed in the present study.

Methods

Women with RIF received oral HCQ (n = 60) on day 4 of the menstrual cycle and continued until day 20 of the menstrual cycle and 2 days before embryo transfer and continued until the day of the pregnancy test, for a total of 16 days in another cycle. The serum levels of IL-17 and IL-10, the expression of transcription factors related to Th17 and Treg cells and the immune-reactivity of IL-17, IL-21 as Th17 related cytokines and IL-10, TGF- β as Treg related cytokines in endometrial tissues were evaluated by ELISA, real-time PCR, and fluorescent immunohistochemistry respectively.

Results

Treatment with HCQ down-regulated Th17 related cytokines and function and up-regulated Treg related cytokines and function significantly (p < .001). RORγt, the Th17 transcription factor, expression was down-regulated and FOXP-3, the T-reg transcription factor, expression was up-regulated. The biochemical pregnancy rate was not significantly different in RIF patients before and after treatment.

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