Summary of findings 7. Adverse drug events.

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: adverse drug events 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	1.07 [0.81, 1.39]	⊕⊕⊕⊝ MODERATEa	Unavailable	‐	52 per 1000 (vaginal micronized progesterone)	49 per 1000 (placebo)	3 more per 1000 (from 9 fewer to 19 more)
Dydrogesterone	2.00 [0.18, 21.88]	⊕⊝⊝⊝ VERY LOWb	Unavailable	‐	10 per 1000 (dydrogesterone)	5 per 1000 (placebo)	5 more per 1000 (from 4 fewer to 103 more)
17‐α‐hydroxyprogesterone	Unavailable	‐	Unavailable	‐	See comment*	See comment**	See comment***
Oral micronized progesteroneversus dydrogesterone	Not estimable	‐	Not estimable	‐	See comment*	See comment**	See comment***
Vaginal micronized progesterone versus dydrogesterone	Unavailable	‐	0.54 [0.05, 5.99]	⊕⊝⊝⊝ VERY LOWc	See comment*	See comment**	See comment***
Recurrent miscarriage
Vaginal micronized progesterone	1.46 [0.93, 2.29]	⊕⊕⊕⊝ MODERATEa	Unavailable	‐	101 per 1000 (vaginal micronized progesterone)	69 per 1000 (placebo)	32 more per 1000 (from 5 fewer to 90 more)
Dydrogesterone	Not estimable	‐	Unavailable	‐	See comment*	See comment**	See comment***
17‐α‐hydroxyprogesterone	Unavailable	‐	Unavailable	‐	See comment*	See comment**	See comment***
Oral micronized progesterone versus dydrogesterone	Not estimable	‐	Not estimable	‐	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 evidence High 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 serious 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).