Progesterone for Threatened Miscarriage
Progesterone supplementation is not routinely recommended for threatened miscarriage as there is insufficient high-quality evidence to support its use in this clinical scenario. 1
Evidence Assessment
The evidence regarding progesterone for threatened miscarriage presents a mixed picture:
The most recent Cochrane review (2018) suggests that progestogens probably reduce the risk of miscarriage compared to placebo or no treatment (RR 0.64,95% CI 0.47-0.87) 2. However, this finding must be interpreted with caution due to methodological limitations in the included studies.
When examining administration routes separately, oral progestogens showed a probable benefit (RR 0.57,95% CI 0.38-0.85), while vaginal progesterone showed no clear benefit (RR 0.75,95% CI 0.47-1.21) 2.
The PRISM trial (2020) found that vaginal micronized progesterone showed benefit primarily in women with both current pregnancy bleeding AND a history of previous miscarriage(s), with greater benefit observed in those with three or more previous miscarriages 3.
Clinical Management Algorithm
Initial Assessment:
- Confirm intrauterine pregnancy via ultrasound
- Assess viability (presence of fetal cardiac activity)
- Evaluate amount of bleeding
- Check for cervical dilation
Risk Stratification:
- Low risk: No previous miscarriages, minimal bleeding, closed cervix
- Moderate risk: 1-2 previous miscarriages with current bleeding
- High risk: ≥3 previous miscarriages with current bleeding
Management Recommendations:
- For low-risk patients: Supportive care only; progesterone not indicated
- For moderate-risk patients: Consider vaginal micronized progesterone 400mg twice daily if there is both previous miscarriage history AND current bleeding
- For high-risk patients: Offer vaginal micronized progesterone 400mg twice daily (strongest evidence of benefit in this subgroup)
Important Considerations
Serum progesterone levels may help with risk stratification. One study suggests that patients with levels ≥35 nmol/L have lower miscarriage rates (9.6%) compared to those with levels <35 nmol/L (70.8%) 4.
The Society for Maternal-Fetal Medicine (SMFM) guidelines do not specifically recommend progesterone for threatened miscarriage but do recommend progesterone for other indications such as prevention of recurrent preterm birth 1.
Progesterone supplementation appears safe with no evidence of increased congenital abnormalities, though the quality of evidence for this outcome is very low 2.
Clinical Caveats
Progesterone supplementation will not salvage a non-viable pregnancy or one with genetic abnormalities.
Patients should be counseled that approximately 25% of threatened miscarriages will progress to spontaneous miscarriage regardless of intervention 4.
If progesterone is used, vaginal administration may be preferred over oral routes for threatened miscarriage based on pharmacokinetics and local uterine effects, though the evidence is not definitive 3, 2.
For women already receiving progesterone for other indications (e.g., previous preterm birth), it is reasonable to continue this treatment if they develop threatened miscarriage 1.