Short‐term cyclosporin A treatment improves pregnancy outcomes in patients with unexplained pregnancy loss: A prospective, open‐label, observational study

Abstract

Background Various treatments to improve live birth rate in women suffering unexplained recurrent pregnancy loss (URPL) have proven ineffective. Cyclosporin A (CsA), an immunosuppressant widely used in organ transplantation, can induce maternal–foetal immune tolerance and improve trophoblast cell biological function. Whether CsA administration in the first trimester increases live birth rate in URPL women remains unknown. Methods A single‐centre, prospective, observational cohort study of URPL patients treated at Obstetrics and Gynecology Hospital of Fudan University was conducted between 2010 and 2016. Participants within 6 weeks of gestation were divided into two groups: CsA or dydrogesterone. To compare efficacy and safety of interventions, data describing maternal and foetal conditions throughout 180 days after labour were collected. Mathematical models were used to identify the miscarriage risk factors in the subsequent pregnancy. Findings 908 of 1931 women aged 18–40 with naturally conceived children and URPL history were recruited and received CsA (n = 660) or dydrogesterone (n = 248) treatment. The live birth rates in CsA and dydrogesterone groups were 88.31% and 89.36%, respectively (relative risk 0.99; 95% confidence interval 0.94–1.04; p = .72). Except for ectopic pregnancy only in dydrogesterone group (p = .005), there was no significant difference in outcomes of miscarriage, preterm birth, full‐term birth, stillbirth or continued pregnancy. There was no discernible difference between CsA and dydrogesterone groups regarding maternal complications, congenital foetal abnormalities and growth. Potential risk factors for miscarriage in URPL patients included maternal age, number of prior pregnancies and miscarriages, the levels of serum progesterone, regulatory T‐cell (Tregs, CD4+CD25+CD127−T), blocking antibody and anti‐idiotypic antibody. Interpretation In women with URPL, short‐term CsA therapy during the first trimester may increase the likelihood of live birth. The effectiveness of CsA is comparable to dydrogesterone without increasing risk of maternal complications or foetus congenital abnormalities. For women experienced URPL, CsA may be a potential therapeutic medicine.