Efficacy of tacrolimus treatment in two-dose single-group controlled trial for patients with refractory infertility

In this clinical trial, we aimed to confirm that immunosuppressant tacrolimus could be an effective and safe treatment option for patients with unexplained refractory infertility. Trial participants were women aged between 18 and 40 with refractory infertility who did not have underlying factors despite appropriate infertility evaluation and did have a Th1-dominant cytokine pattern defined as a Th1/Th2 cell ratio ≥ 10.3 in peripheral blood. Patients were randomly assigned (2:1 ratio) to receive immunosuppressive therapy with tacrolimus at a daily dose of 2 (low dose) or 4 (high dose) mg. Tacrolimus was orally administered for 16 days, starting 2 days before embryo transfer. The primary efficacy outcome was the presence of clinical pregnancy 3 weeks after embryo transfer. The clinical pregnancy proportion in the low- and high-dose groups was tested against the assumed proportion of 5% in the untreated group using a one-sided exact binomial test with a significance level of 0.0125. In the full analysis set, the proportion of clinical pregnancy at 3 weeks after embryo transfer was 66.7% (95% CI, 38.4-88.2) and 55.6% (95% CI, 21.2-86.3) in the low- and high-dose groups, respectively (p < 0.0001 for both). Immunosuppressive therapy with tacrolimus is a viable treatment option for patients with infertility who exhibit a Th1-dominant cytokine pattern without underlying factors.