What is the evidence of the uncertainty? We searched Medline, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, DARE (Database of Abstracts of Reviews of Effects), ISI proceedings, the International Standard Randomised Controlled Trial Number (ISRCTN) register, and the mRCT database for published and ongoing randomised trials. The search terms were “progesterone”, “progestagen”, “progestogen”, “progestin”, and “progestational [hormone or agent]”, which were combined with search terms for miscarriage. Four randomised trials were identified.2 3 4 5 The quality of the four trials was poor (modified Jadad quality scores ranged from 0/5 to 2/5 (table⇓). Participant numbers were small even when the trials were combined in meta-analysis, with only 132 women treated with progesterone. Although all four trials showed a trend towards benefit, with a 42-69% reduction in rate of miscarriage, the confidence intervals were wide and differences were not statistically significant for all but one of the four trials5). Meta-analysis showed a statistically significant reduction in miscarriages (figure⇓). We found no evidence of statistical heterogeneity in the results (heterogeneity, P=0.94). Data were not available for other clinically relevant outcomes such as live birth. Our review findings are consistent with the findings of a Cochrane review on this subject, published earlier and including three of the above four studies.6 View this table: In this window In a new window Characteristics of the randomised trials of progesterone in recurrent miscarriage View larger version: In this window In a new window Meta-analysis of trials of progesterone in recurrent miscarriage for the outcome of miscarriage Although the pooled analysis shows a statistically significant reduction in miscarriage rate, it is not surprising, given the poor quality of the trials (for example, none of them had evidence of allocation concealment), that most clinicians have called for a definitive placebo controlled randomised trial targeting live birth as the primary outcome.
Universita degli studi di Ferrara
Austral University (Argentina)
Fertinova Tampere, Finland (previously AVA Clinic)
Govt Zamindar Postgrduate Col Gujrat
Ahmadu Bello University