What is the role of progesterone in early pregnancy?

From the Guidelines

Progesterone supplementation is recommended for women with a short cervix, particularly those with a transvaginal cervical length (CL) of ≤20 mm diagnosed before 24 weeks of gestation, to reduce the risk of preterm birth (PTB) and perinatal morbidity and mortality. This recommendation is based on the most recent and highest quality study available, which suggests that vaginal progesterone, either 90-mg gel or 200-mg suppository, is associated with a reduction in PTB and perinatal morbidity and mortality in women with a short cervix 1.

Key Points

• Vaginal progesterone is recommended for women with a singleton gestation and a short cervix (CL ≤20 mm) to reduce the risk of PTB and perinatal morbidity and mortality.
• The most studied formulations of vaginal progesterone are 90-mg (8%) progesterone gel and 200-mg micronized progesterone capsules.
• Treatment with vaginal progesterone should be considered at a CL of 21 to 25 mm based on shared decision-making.
• There is insufficient evidence to recommend the use of progestogens in women with multiple gestations, preterm labor, or preterm premature rupture of membranes.

Benefits and Risks

The benefits of progesterone supplementation in women with a short cervix include a reduction in PTB and perinatal morbidity and mortality. The risks associated with progesterone supplementation are minimal, and the treatment is generally well-tolerated. However, it is essential to note that the use of vaginal progesterone for the indication of a short cervix is currently off-label and requires patient counseling.

Clinical Implications

The recommendation to use vaginal progesterone in women with a short cervix has significant clinical implications. It highlights the importance of universal CL screening for asymptomatic individuals without a previous PTB and the need for early intervention to reduce the risk of PTB and perinatal morbidity and mortality. Clinicians should consider the use of vaginal progesterone in women with a short cervix, particularly those with a CL ≤20 mm, and engage in shared decision-making with patients to determine the best course of treatment.

From the Research

Progesterone in Early Pregnancy

• Progesterone is essential for the maintenance of pregnancy, and several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage 2, 3.
• The effects of first-trimester use of vaginal micronized progesterone have been evaluated in two large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages and the other targeting women with early pregnancy bleeding 2, 4.
• The results of these trials suggest that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages, with a significant benefit observed in women with a history of three or more previous miscarriages and current pregnancy bleeding 2, 4.
• A subgroup analysis of the PRISM trial found that women with a history of one or more miscarriage(s) and current pregnancy bleeding had a live birth rate of 75% with progesterone versus 70% with placebo, with a significant difference observed in the subgroup of women with three or more previous miscarriages 4.
• Other studies have also found that progesterone treatment is associated with an increased live birth rate in women with recurrent pregnancy loss, regardless of other treatments 5.
• The immunological effects of progesterone and dydrogesterone in pregnancy have been studied, and it is thought that these hormones may inhibit the activity of natural killer cells at the foeto-maternal interface and favor the production of pregnancy-protecting antibodies 6.

Benefits of Progesterone in Early Pregnancy

• Increased live birth rate in women with recurrent miscarriage or threatened miscarriage 2, 4, 5.
• Reduced risk of miscarriage in women with a history of recurrent pregnancy loss 3.
• Immunological benefits, including inhibition of natural killer cells and favoring the production of pregnancy-protecting antibodies 6.

Subgroups that May Benefit from Progesterone

• Women with a history of three or more previous miscarriages and current pregnancy bleeding 2, 4.
• Women with a history of one or more miscarriage(s) and current pregnancy bleeding 4.
• Women with recurrent pregnancy loss, regardless of other treatments 5.