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Evidence summaries

Progestogen for Preventing Miscarriage in Women with Recurrent Miscarriage

Progestogen may be effective for preventing miscarriage in early to mid pregnancy in women with recurrent miscarriages compared with placebo. Level of evidence: "C"

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).

    References

    • Haas DM, Hathaway TJ, Ramsey PS. Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology. Cochrane Database Syst Rev 2018;(10):CD003511. [PubMed]
    • 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):. [PubMed]
    • .Devall AJ, Papadopoulou A, Podesek M et al. Progestogens for preventing miscarriage: a network meta-analysis. Cochrane Database Syst Rev 2021;(4):CD013792. [PubMed]

Primary/Secondary Keywords