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. 2021 Apr 19;2021(4):CD013792. doi: 10.1002/14651858.CD013792.pub2

Summary of findings 6. Congenital abnormalities.

Patient or population: women with threatened miscarriage or a history of recurrent miscarriage
Interventions: multiple progestogens (vaginal micronized progesterone, oral micronized progesterone, dydrogesterone and 17‐α‐hydroxyprogesterone)
Comparison: placebo and dydrogesterone
Outcome: congenital abnormalities
Settings: hospitals
Treatment Direct evidence Indirect evidence Anticipated absolute effects for direct estimate
RR (95% CI) Certainty RR (95% CI) Certainty Risk with intervention Risk with comparator Risk difference with intervention
Threatened miscarriage
Vaginal micronized progesterone 1.00 [0.68, 1.46] ⊕⊕⊕⊝
MODERATEa
Unavailable 34 per 1000 (vaginal micronized progesterone) 34 per 1000 (placebo) 0 fewer per 1000
(from 11 fewer to 16 more)
Dydrogesterone 0.71 [0.23, 2.21] ⊕⊝⊝⊝
VERY LOWb
Unavailable 24 per 1000 (dydrogesterone) 34 per 1000 (placebo) 10 fewer per 1000
(from 27 fewer to 42 more)
17‐α‐hydroxyprogesterone Unavailable aUnavailable See comment* See comment** See comment***
Oral micronized progesterone versus dydrogesterone Unavailable Unavailable See comment* See comment** See comment***
Vaginal micronized progesterone versus dydrogesterone Unavailable 1.41 [0.43, 4.65] ⊕⊝⊝⊝
VERY LOWc
See comment* See comment** See comment***
Recurrent miscarriage
Vaginal micronized progesterone 0.75 [0.31, 1.85] ⊕⊕⊝⊝
LOWd
Unavailable 30 per 1000 (vaginal micronized progesterone) 40 per 1000 (placebo) 10 fewer per 1000
(from 27 fewer to 34 more)
Dydrogesterone Unavailable Unavailable See comment* See comment** See comment***
17‐α‐hydroxyprogesterone Unavailable Unavailable See comment* See comment** See comment***
Oral micronized progesteroneversus dydrogesterone Unavailable Unavailable See comment* See comment** See comment***
*No included studies or there are no events in included studies to estimate the baseline risk.
**Absolute risk with intervention cannot be estimated in the absence of absolute risk with the comparator.
***Risk difference cannot be estimated in the absence of absolute risks with intervention and the comparator.
CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect..

a Direct evidence downgraded ‐1 due to imprecision (wide 95% CIs).

b Direct evidence downgraded ‐1 due to serious limitations in study design and ‐2 due to severe imprecision (wide 95% CIs and number of events less than 30).

c Indirect evidence downgraded ‐1 due to serious limitations in study design and ‐2 due to severe imprecision (wide 95% CIs and number of events less than 30).

d Direct evidence downgraded ‐2 due to severe imprecision (wide 95% CIs and number of events less than 30).