Tacrolimus improved reproductive outcomes of women with recurrent pregnancy loss (PRL) showing elevated T helper 1 (Th1) /Th2 cell ratios

Abstract Purpose: Elevated T helper 1 (Th1)/Th2 cell ratio has been associated with recurrent pregnancy losses (PRL). In this study, the clinical efficacy of tacrolimus, a calcineurin inhibitor, was investigated in women with consecutive four or more recurrent pregnancy losses (RPL) and elevated Th1/Th2 (CD4+IFN-γ+/ CD4+IL-4+) cell ratio. The live-birth rate (LBR) was prospectively investigated in women with RPL who received tacrolimus treatment. Methods: A total of 100 pregnant women with PRL with elevated Th1/Th2 cell ratios (≥10.3) were recruited from November 2013 to December 2019. Seventy-one women received tacrolimus between 1 mg and 4 mg daily (treatment group) and 29 women did not receive tacrolimus (control group). Results: In the treatment group, the LBR was 70.4% (50/71), which was significantly higher than that of the control group (48.2%, p<0.05). According to the tacrolimus doses, the treatment group was divided into three subgroups. The LBRs of women with tacrolimus 1mg, 2mg, and ≥3mg daily were 52.2%, 72.3%, and 93.3%, respectively. In women with tacrolimus ≥3mg daily, the LBR was significantly higher than women with tacrolimus 1mg daily (P<0.05). Conclusion: In conclusion, the LBR of RPL women with increased Th1/Th2 cell ratios was significantly improved with tacrolimus treatment.