Does progesterone supplementation prevent spontaneous abortion (miscarriage)?

From the Guidelines

Progesterone supplementation is not proven to prevent miscarriage in the general population, but it may be beneficial in specific situations, such as in women with a short cervix, as evidenced by a reduction in preterm birth (PTB) risk 1.

Key Points to Consider

• The use of vaginal progesterone in women with a short cervix has been shown to reduce the risk of PTB 1.
• The American College of Obstetricians and Gynecologists recommends vaginal progesterone as a management option for pregnant individuals with a short cervix 1.
• The most studied formulations of vaginal progesterone are 90-mg (8%) progesterone gel and 200-mg micronized progesterone capsules 1.

Important Considerations

• The FDA did not approve vaginal progesterone for the indication of prevention of PTB in the setting of a short cervix, in part due to lack of benefit in US patients and specific subgroups such as Black patients or those with obesity 1.
• Despite this, the potential benefits and lack of harm support the use of vaginal progesterone in certain cases, particularly in women with a short cervix 1.

Recommendations

• Asymptomatic individuals with a singleton gestation and a transvaginal CL of ≤20 mm diagnosed before 24 weeks of gestation should be prescribed vaginal progesterone to reduce the risk of PTB 1.
• Treatment with vaginal progesterone may be considered at a CL of 21 to 25 mm based on shared decision-making 1.

From the Research

Progesterone Supplementation and Miscarriage Prevention

• The use of progesterone supplementation to prevent miscarriage has been studied in several trials, with varying results 2, 3, 4, 5, 6.
• A critical evaluation of randomized evidence found that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage, but the trials were small and had methodologic weaknesses 2.
• Two large, high-quality, multicenter placebo-controlled trials, the PROMISE and PRISM trials, found a 3% greater live birth rate with progesterone, but with substantial statistical uncertainty 2.
• A network meta-analysis found that progestogens probably make little or no difference to live birth rate for women with threatened or recurrent miscarriage, but vaginal micronized progesterone may increase the live birth rate for women with a history of one or more previous miscarriages and early pregnancy bleeding 3.
• A review of progestogen treatment for recurrent miscarriage found that supplementation with progestogen therapy may reduce the rate of miscarriage in subsequent pregnancies, but the evidence is moderate-quality and further research is needed 5.
• The PRISM RCT found that progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified in women with a history of previous miscarriages and early pregnancy bleeding 6.

Subgroup Analysis

• The PRISM trial found a significant subgroup effect in women with a history of one or more previous miscarriages and early pregnancy bleeding, with a live birth rate of 75% in the progesterone group vs. 70% in the placebo group 6.
• The PROMISE trial found a significant subgroup effect in women with a history of three or more previous miscarriages and early pregnancy bleeding, with a live birth rate of 72% in the progesterone group vs. 57% in the placebo group 2.

Safety and Adverse Events

• The trials found no significant differences in the rate of adverse events between the progesterone and placebo groups 2, 3, 6.
• The PRISM trial found that progesterone therapy was more costly than placebo, with a mean cost difference of £83 between the two arms 6.