Progestogen treatment has not been associated with maternal or neonatal adverse events; however, long term safety data is lacking.
Level of evidence is downgraded due to imprecision.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis | |||||
| «Zhao Y, D'Souza R, Gao Y, ym. Progestogens in wome...»1 | 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: live birth
congenital anomalies, and severe adverse pregnancy events |
Low |
| «Coomarasamy A, Harb HM, Devall AJ, ym. Progesteron...»2 | RCT (PRISM) | N=4153 16-39 y With early pregnancy bleeding ≤ 12 weeks of pregnancy Progesteron 2079 Placebo 2074 UK 48 hospitals |
I: vaginal progesteron 400 mg x2/day started within 4 days of bleeding during first
12 weeks up to 16 weeks, confirmed intrauterine pregnancy
C: placebo |
Live birth ≥34 weeks
Cost effects |
Low |
| Reference | Comments |
|---|---|
| «Zhao Y, D'Souza R, Gao Y, ym. Progestogens in wome...»1 | Most recent systematic review (2024), well-conducted. Publication bias was assessed
via a funnel plot and not 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 0to 19.3%. Intervention preparations, dosage and duration varied across studies. Duration varied from some days (until bleeding stopped) up to 24 weeks of gestation. A Cochrane systematic review from 2021 was excluded because it included the same studies as Zhao et al (and fewer studies). |
| «Coomarasamy A, Harb HM, Devall AJ, ym. Progesteron...»2 | A multicenter, placebo-controlled, double-blinded RCT study, 48 hospitals in UK, subgroup
analysis according to the number of previous pregnancy losses, follow up rate 97.2%.
Also included in meta-analysis (Zhao et al), but the meta-analysis did not examine outcomes of pregnant women with a history of three or more miscarriages and therefore this study was included also separately. |
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) |
|---|---|---|---|---|---|
| «Zhao Y, D'Souza R, Gao Y, ym. Progestogens in wome...»1 | A) Threatened miscarriage with or without prior miscarriage
N=5610 12 studies |
Varied across studies | 2243/2825 (79.4) | 2134/2785 (76.6) | 1.04 (95% CI 0.99–1.10) Absolute increase: 31 more/1000 +3.1% (95% CI 8 fewer −78 more) |
| B) Threatened miscarriage with one or more prior miscarriages N=1973 3 studies |
756/995 (76.0) | 695/978 (71.1) | 1.06 (95% CI 0.97–1.16) Absolute increase: 44 more per 1000 +4.9% (95% CI 22 fewer −117 more) |
||
| «Coomarasamy A, Harb HM, Devall AJ, ym. Progesteron...»2 | I 2079/ C 2074 |
34 weeks of gestation | |||
| 0 previous pregnancy losses | 824/1111 (74.2) |
840/1127 (74.5) |
0.99, 95% CI 0.95–1.04 |
||
| 1–2 previous pregnancy losses | 591/777 (76.1) |
534/738 (72.4) |
1.05, 95% CI 1.00–1.12 |
||
| ≥3 previous pregnancy losses | 98/137 (71.5) |
85/148 (57.4) |
1.28, 95% CI 1.08–1.51 |
||
| Level of evidence: Moderate (due to imprecision) I=intervention; C=comparison; CI=confidence interval |
|||||
| 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) |
|---|---|---|---|---|---|
| «Zhao Y, D'Souza R, Gao Y, ym. Progestogens in wome...»1 | A) N=6015 7 studies |
Congenital anomalies 72/3029 (2.4) |
Congenital anomalies 65/2986 (2.2) |
RR 1.06, 95% CI 0.76–1.48. Absolute increase: 1 more per 1000, +0.2% (CI: 95% 5 fewer–11 more) |
|
| B) N=4684 2 studies |
Serious adverse pregnancy events 108/2423 (4.4) |
Serious adverse pregnancy events 100/2441 (4.1) |
RR 1.07, 95% CI 0.83–1.40. Absolute increase: 2 more per 1000, +0.3% (CI: 95% 5 fewer–11 more) |
||
| «Coomarasamy A, Harb HM, Devall AJ, ym. Progesteron...»2 | I 2079/ C 2074 |
28 days after labor | Multiple maternal and perinatal outcomes and adverse effects reported; no differences between groups. Numbers included in the meta-analysis above. | There was no evidence of a difference in the safety outcomes. | |
| Level of evidence: Moderate (due to imprecision) | |||||