A Cochrane review «Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology»1 «Haas DM, Bofill Rodriguez M, Hathaway TJ, et al. Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology. Cochrane Database Syst Rev 2025;6(6):CD003511. »1 included 8 trials involving 1276 women with recurrent miscarriage of unclear etiology. There was little to no difference in the miscarriage rate for women given progestogen supplementation from the beginning of first trimester compared to placebo or no treatment (RR 0.91, 95% CI 0.76 to 1.07; I²=0%; 8 studies, n=1276; moderate-certainty evidence) and little to no difference in live birth rate compared to placebo (RR 1.04, 95% CI 0.96 to 1.12; 5 trials, n=1063; moderate-certainty evidence).
Another meta-analysis «Rasmark Roepke E, Hellgren M, Hjertberg R et al. Treatment efficacy for idiopathic recurrent pregnancy loss - a systematic review and meta-analyses. Acta Obstet Gynecol Scand 2018;(3):. »2 assessed the effects of different treatments on live birth rates and complications in women with unexplained recurrent pregnancy loss. 21 RCTs regarding acetylsalicylic acid, low-molecular-weight heparin, progesterone, intravenous immunoglobulin, or leukocyte immune therapy were included. Treatment with progesterone starting in the luteal phase seemed effective in increasing live birth rate (RR 1.18, 95% CI 1.09 to 1.27) but not when started after conception.
A network meta-analysis «.Devall AJ, Papadopoulou A, Podesek M et al. Progestogens for preventing miscarriage: a network meta-analysis. Cochrane Database Syst Rev 2021;(4):CD013792. »3 included 7 RCTs involving a total of 5 682 women. Vaginal micronized progesterone may increase the live birth rate for women with a history of one or more previous miscarriages and early pregnancy bleeding, with likely no difference in adverse events.
A retrospective cohort study «Bashiri A, Galperin G, Zeadna A, et al. Increased Live Birth Rate with Dydrogesterone among Patients with Recurrent Pregnancy Loss Regardless of Other Treatments. J Clin Med 2023;12(5): »4 included 866 patients. In a univariate analysis, no statistically significant differences were found between the dydrogesterone treatment group vs. the no treatment group in terms of live birth rates (80.6% vs. 84%; p-value = 0.209). In a multivariate logistic analysis adjusted for maternal age, the ratio of pregnancy losses to the number of pregnancies, other administered treatments, antiphospholipid syndrome, and body mass index, dydrogesterone treatment was associated with a higher rate of live births than the control group (adjusted OR 1.592; CI 95% 1.051 to 2.413; p-value = 0.028).
Comment: The quality of evidence is downgraded by limitations in study quality (e.g., inadequate or unclear allocation concealment and inadequate intention-to-treat adherence).