Low-dose interleukin-2 for recurrent early pregnancy loss: a proof-of-concept study

Regulatory T cells (Tregs) are essential for maternal-fetal tolerance, and their deficiency is implicated in unexplained recurrent early pregnancy loss (uREPL). Low-dose interleukin-2 (IL-2 _LD ) selectively activates Tregs. In the FACIL-2 open-label trial (NCT03970954), 15 women with ≥5 uREPLs received a 5-day IL-2 _LD treatment, starting 10 days after menses onset. Nine additional patients received similar treatment under compassionate use. IL-2 _LD significantly expanded Tregs at 8 days post-treatment initiation (p<0.001; primary endpoint met). Of eight pregnancies in FACIL-2, four progressed beyond 14 weeks, yielding three live births. Remarkably, compared to pregnancy losses, these successful pregnancies were associated with a significantly greater Treg expansion (p= 0.008). In the compassionate group, two of five pregnancies resulted in live births. Thus, a short-course IL-2 _LD expanded Tregs and achieved an almost 50% viable pregnancy rate in this high-risk population. These results support further investigation of IL-2 _LD for uREPL, with regimens extending through early pregnancy.