What role do hormones, specifically progesterone, play in maintaining pregnancy?

The Role of Progesterone in Maintaining Pregnancy

Progesterone is essential for pregnancy establishment and maintenance, playing multiple critical roles including modulation of maternal immune response, reduction of uterine contractility, and improvement of utero-placental circulation. 1

Mechanisms of Action

• Progesterone acts as a natural immunoregulator that prevents rejection of the allogeneic fetus by controlling the maternal immune response 2
• It suppresses inflammatory responses at the decidua level, which plays a major role in maternal defense strategy 1
• Progesterone reduces uterine contractility by counteracting prostaglandin stimulatory activity and oxytocin effects, maintaining uterine quiescence 1
• It promotes invasion of extravillous trophoblasts to the decidua by inhibiting apoptosis of these cells, improving utero-placental circulation 1

Sources of Progesterone During Pregnancy

• Two main sources provide progesterone during pregnancy: first the corpus luteum in early pregnancy, then the placenta takes over production later 2
• The corpus luteum is the primary source until approximately 7-9 weeks of gestation, after which the placenta becomes the dominant producer 3
• Progesterone levels must be maintained throughout pregnancy, with any deficiency potentially leading to complications 4

Clinical Evidence for Progesterone's Role

• Multiple studies have reported a significant positive relationship between progesterone deficiency and first-trimester miscarriage 4
• In threatened abortion, the use of progesterone leads to significantly improved outcomes when a viable fetus has been confirmed by ultrasound 2
• For recurrent pregnancy loss, some data indicate a significant benefit with progesterone supplementation compared to no treatment 2
• Vaginal progesterone (400 mg daily) has been shown to increase latency until delivery and reduce respiratory distress syndrome in women with singleton gestation after successful tocolysis for preterm labor 5

Progesterone in Preterm Birth Prevention

• For singleton pregnancies with prior spontaneous preterm birth, 17-alpha-hydroxy-progesterone caproate (17P) 250 mg IM weekly from 16-20 weeks until 36 weeks is recommended 5
• In singleton pregnancies without prior preterm birth but with short cervical length (≤20 mm) at ≤24 weeks, vaginal progesterone 90-mg gel or 200-mg suppository daily until 36 weeks is recommended 5
• In women with singleton gestation still pregnant after successful tocolysis for preterm labor, 17P 341 mg twice weekly was associated with significant reduction in preterm birth <37 weeks 5

Important Clinical Considerations

• The route of administration affects efficacy: progesterone can be administered orally, vaginally, or intramuscularly, with different bioavailability profiles 1
• Natural micronized progesterone is often preferred for hormone replacement therapy due to its favorable cardiovascular and thrombotic risk profile compared to synthetic progestogens 6
• Despite its widespread use, progesterone has not shown effectiveness in multiple gestations, active preterm labor, or preterm premature rupture of membranes 5
• Progesterone therapy has not been associated with any evidence of health-related harm to offspring development 4

Limitations and Caveats

• The evidence supporting progesterone use in threatened abortion and recurrent miscarriage is inconsistent across studies 7
• For women with preterm premature rupture of membranes (PPROM), there is insufficient evidence to recommend progesterone supplementation 5
• In multiple gestations (twins, triplets), progesterone supplementation has not shown effectiveness in preventing preterm birth 5
• When considering progesterone therapy, timing of initiation is critical - most protocols begin supplementation in early pregnancy for maximum effectiveness 2