A Cochrane review [Abstract] 1 included 12 trials involving 2 359 women. There was reduced risk of miscarriage between progestogen and placebo or no treatment groups (RR 0.69, 95% CI 0.51 to 0.92; 11 trials, n=2359). In a subgroup analysis involving women with a history of three or more consecutive miscarriages, progestogen treatment was more efficacious. However, there was high heterogeneity in the subgroup of these women. There was a slight benefit for women receiving progestogen for live birth rate (RR 1.11, 95% CI 1.00 to 1.24; 7 trials, n=2086). No statistically significant differences were found between the route of administration of progestogen (oral, intramuscular, vaginal) versus placebo or no treatment.
Another meta-analysis 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 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.
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).
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