The level of evidence is dowgraded due to imprecision.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias «Additional comments for included studies ...»2. |
|---|---|---|---|---|---|
| «Coomarasamy A, Williams H, Truchanowicz E, ym. PRO...»1 | RCT (PROMISE) |
N= 836 women (18-39 y) with NUD RPL (≥3 first trimester losses, consecutive or non-consecutive)
UK (36 sites) and Netherlands (9 sites) |
I: vaginal progesteron 400 mg x2/day started after positive pregnancy test ≤ 6+0 –
12+0
C: placebo Intervention/placebo started from positive pregnancy test (not later than 6 weeks) and continued up to 12 weeks of pregnancy or loss whichever came first |
Live birth beyond 24 completed weeks (primary outcome) clinical pregnancy at 6-8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use |
Low |
| «Zhao Y, D'Souza R, Gao Y, ym. Progestogens in wome...»2 | SR/MA | 15 RCTs, N=6616 pregnancies Grouped according to number of previous pregnancy losses 0, 1, or ≥ 2 |
I: natural or synthetic progestogens (micronized, dydrogesterone, and 17- OHPC treatment
for up to 24 weeks of gestation C: placebo or no treatment |
Primary outcome: live birth
congenital anomalies, and severe adverse pregnancy events |
Low |
| RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis, NUD RPL= Unexplained Recurrent Pregnancy Loss | |||||
| Reference | Comments |
|---|---|
| «Coomarasamy A, Williams H, Truchanowicz E, ym. PRO...»1 | A multicenter, placebo-controlled, double-blinded RCT study) with a high follow-up rate to the primary outcome (98.8%). The intervention is well applicable to Finnish health care settings |
| «Zhao Y, D'Souza R, Gao Y, ym. Progestogens in wome...»2 | Most recent systematic review, well-conducted. No publication bias was detected. The meta-analysis was based on RCTs and risk of bias was evaluated using a modified version of the Cochrane risk-of-bias tool and the certainty of evidence using the GRADE approach. Eight studies were conducted in Asia, five in Europe and two in Oceania. The proportion of pregnancies lost to follow-up ranged from 0 to 19.3%. Intervention preparations, dosage and duration varied across studies. Duration varied from some days (until bleeding stopped) up to 24 weeks of gestation. |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| «Coomarasamy A, Williams H, Truchanowicz E, ym. PRO...»1 | (404/432) | up to 28 days after birth | 262/398 (65.8) |
271/428 (63.3) |
1.04 (95% CI 0.94–1.15) |
| «Zhao Y, D'Souza R, Gao Y, ym. Progestogens in wome...»2 | A) no prior miscarriage, no threatened miscarriage | Varied across studies | 963/1266 (76.1) |
966/1274 (75.8) |
Not reported |
| B) pregnancies with two or more prior miscarriage, without threatened miscarriage
N=1006 3 studies |
355/597 (70.0) |
323/499 (64.7) |
1.08 (95% CI 0.98–1.19) Absolute increase: 57 more/1000 +5.7% (95% CI 14 fewer −137 more) |
||
| Level of evidence: Moderate (due to imprecision) I=intervention; C=comparison; CI=confidence interval |
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