| Study characteristics |
| Methods |
2‐arm placebo‐controlled randomised trial |
| Participants |
836 women were randomised in a hospital setting in the UK from June 2010 to October 2013. The population comprised women aged 18‐39 years with a history of 3 or more unexplained miscarriages and conceived naturally within 1 year of being approached about the trial. Exclusion criteria comprised women that were unable to conceive naturally within 1 year after recruitment; had the antiphospholipid syndrome or other recognized thrombophilic conditions; had uterine cavity abnormalities (as assessed with the use of ultrasonography, hysterosonography, hysterosalpingogram, or hysteroscopy), an abnormal parental karyotype, or other identifiable cause of recurrent miscarriage such as diabetes, thyroid disease, or systemic lupus erythematosus (tests were initiated only if clinically indicated); were currently receiving heparin therapy; or had contraindications to progesterone use. |
| Interventions |
Twice daily vaginal suppositories containing 400 mg of micronized progesterone versus placebo. |
| Outcomes |
The study recorded the following outcomes relevant for this review: live birth, miscarriage (< 24 weeks), preterm birth (< 37 weeks), stillbirth, ectopic pregnancy, congenital abnormalities and adverse drug events. |
| Notes |
Contact with study authors for additional information: no. Additional data from authors: no. Funded by the United Kingdom NIHR Health Technology Assessment program (project number HTA 08/38/01). The authors declare no relevant conflicts of interest. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Computer generated in 1:1 ratio with the use of minimisation. |
| Allocation concealment (selection bias) |
Low risk |
Assignment through secure Internet facility. |
| Blinding of participants and personnel (performance bias)
All outcomes |
Low risk |
Study participants and caregivers were blinded to treatment allocations. |
| Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
Assessors were blinded to treatment allocations. |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Attrition bias was < 10% and balanced across study arms. |
| Selective reporting (reporting bias) |
Low risk |
The study report matches the study protocol (ISRCTN92644181) that was registered prospectively. |
| Other bias |
Low risk |
Funded by the United Kingdom NIHR Health Technology Assessment program (project number HTA 08/38/01). |
