Cyclosporine A to Treat Unexplained Recurrent Spontaneous Abortions: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial

BACKGROUND: The World Health Organization (WHO) has defined Unexplained Recurrent Spontaneous Abortion (URSA) as three and more consecutive miscarriages before the 20th week of gestation. To date, empiric therapy for patients with unexplained recurrent pregnancy loss (URPL) is not precise. Studies have shown that URSAs are associated with Th1/Th2 and Th17/Treg immune imbalances at the maternal-fetal interface. The immunosuppressant cyclosporine A (CsA) is widely used in patients with organ transplantation or autoimmune diseases, and it has a good safety profile in pregnant women. However, high-quality evidence for CsA treatment of URSAs is lacking. Our purpose with this study is to evaluate the efficacy and safety of CsA for improving pregnancy outcomes in patients with URSAs and to explore the role of CsA in regulating the immune balance. METHODS/DESIGN: We expect to officially initiate our study at the Taizhou People's Hospital in March 2022. We defined the live birth rate as the primary outcome, and the secondary outcomes include the rates of successful pregnancy, miscarriage, pregnancy complications, and adverse pregnancy outcomes, and newborn birth weights. Patients who meet URSA eligibility criteria will be randomized in a 1:1 ratio into either a study group receiving CsA 2 weeks after fertilization or a control group receiving placebo at 2 weeks after fertilization (the women in both groups will receive the relevant treatment for 6 months). In addition, we will collect peripheral blood samples of the participants before and after the treatments, and we will isolate mononuclear cells and measure cytokine levels (IFN-γ, TNF-α, IL-2, IL-10, IL-6, IL-4) and Th1/Th2, Th17/Treg ratios. DISCUSSION: This is the first randomized controlled trial to evaluate the clinical and immunomodulatory effects of CsA on the pregnancy outcomes of women with URSA and our results will provide evidence to evaluate the use of CsA as a treatment for women with URSAs.