Tacrolimus improved the pregnancy outcomes of patients with refractory recurrent spontaneous abortion and immune bias disorders: a randomized controlled trial.

OBJECTIVE

To investigate the effect of tacrolimus treatment on refractory recurrent spontaneous abortion (RSA) patients with elevated serum IL-33/ST2 levels.

METHODS

This study was a randomized controlled trial (RCT) of refractory RSA patients with elevated peripheral blood IL-33/ST2 levels or an elevated Th1/Th2 cell ratio. A total of 149 women were enrolled, each of whom had had at least 3 serial miscarriages and was confirmed to have elevated peripheral blood IL-33/ST2 levels or an elevated Th1/Th2 cell ratio. These women were randomly divided into two groups. The tacrolimus group (n = 75) received basic therapy with the addition of tacrolimus (Prograf). Tacrolimus was administered at a dose of 0.05 ~ 0.1 mg/kg/day from the end of the menstrual period to the beginning of the next menstrual period or to the 10th week of pregnancy. In contrast, basic therapy with the addition of placebo was given to the placebo group (n = 74). The main study outcome was the delivery of healthy newborns without deformities.

RESULTS

A total of 60 (80.00%) patients in the tacrolimus group and 47 (63.51%) patients in the placebo group delivered healthy newborns [P = 0.03, odds ratio = 2.30; 95% confidence interval (1.10 ~ 4.81)]. The peripheral blood IL-33/ST2 levels and Th1/Th2 cell ratio of the tacrolimus group were much lower than those of the placebo group (P < 0.05).

CONCLUSION

We validated our previous finding that serum IL-33 and sST2 concentrations are related to RSA. Immunosuppressive treatment with tacrolimus was demonstrated to be a promising method to treat refractory RSA with immune bias disorders.