What are the uses and risks of Gestanol (progesterone) in treating threatened abortion or miscarriage?

Gestanol (Progesterone) in Threatened Abortion

Vaginal progesterone (400 mg twice daily) should be offered to women with threatened abortion (early pregnancy bleeding) who have a history of one or more previous miscarriages, as this combination of risk factors is associated with a clinically meaningful 5% absolute increase in live birth rates. 1

Clinical Efficacy by Risk Profile

Women with Prior Miscarriage(s) AND Current Bleeding

• Live birth rate increases from 70% to 75% (5% absolute benefit, RR 1.09,95% CI 1.03-1.15) when treated with vaginal micronized progesterone 400 mg twice daily 1
• For women with ≥3 prior miscarriages plus current bleeding: live birth rate increases from 57% to 72% (15% absolute benefit, RR 1.28,95% CI 1.08-1.51) 1
• This represents the highest quality evidence from the PRISM trial (n=4,153 women, 48 hospitals), which fulfilled all 11 criteria for credible subgroup analysis 1

Women with Threatened Abortion and Luteal Phase Deficiency

• Vaginal progesterone (Crinone 8% daily for 5 days) significantly reduces:
  • Uterine contractions (P < 0.005) 2
  • Pain intensity 2
  • Miscarriage rate: 16% vs 32% in placebo group (P < 0.05) 2

Women with Threatened Abortion but NO Prior Miscarriages

• Evidence is insufficient to recommend routine progesterone in women with bleeding alone and no history of previous pregnancy loss 1
• The PRISM trial showed only a 3% difference with P=0.08 in the overall population 1

Dosing and Administration

Recommended regimen: Vaginal micronized progesterone 400 mg twice daily, starting immediately upon diagnosis of threatened abortion 1

• Continue until at least 12-16 weeks gestation based on standard practice for progesterone supplementation 2, 3
• Vaginal route is preferred over intramuscular for threatened abortion based on trial evidence 1

Safety Profile

Maternal Safety

• No short-term safety concerns identified in large randomized trials 1
• Progesterone treatment in early pregnancy does not increase risk of:
  • Preterm birth 4
  • Pregnancy complications 4
  • Low birth weight 4
• Generally classified as FDA Category B: animal studies show no fetal risk, though controlled human studies are limited 5

Important Contraindications

• Severe peanut allergies (anaphylaxis): Many micronized progesterone capsules contain peanut oil; use vaginal gel formulations instead 5
• Hormone receptor-positive breast cancer 5
• No association with gestational diabetes or glucose intolerance 5

Fetal Safety

• Progesterone is essential for pregnancy maintenance and acts as an "immunosteroid" promoting maternal-fetal tolerance 3
• No evidence of increased fetal malformations with progesterone use in early pregnancy 5
• Long-term follow-up shows no adverse obstetric or perinatal outcomes 4

Mechanism of Action in Threatened Abortion

Progesterone maintains pregnancy through multiple pathways:

• Immunomodulation: Induces progesterone-induced blocking factor (PIBF), promoting Th2-dominant cytokine production 3
• Uterine quiescence: Directly reduces uterine contractility 2
• NK cell regulation: Controls uterine homing of NK cells and upregulates HLA-G expression 3
• Cytokine balance: Induces Th2 cytokines, LIF, and M-CSF production at high concentrations 3

Clinical Decision Algorithm

Step 1: Woman presents with early pregnancy bleeding (threatened abortion)

Step 2: Assess miscarriage history

• If ≥1 prior miscarriage: Offer vaginal progesterone 400 mg twice daily (Grade 1A evidence) 1
• If ≥3 prior miscarriages: Strongly recommend progesterone (15% absolute benefit) 1
• If no prior miscarriages: Shared decision-making; evidence is weaker but progesterone is safe 1

Step 3: Screen for contraindications

• Severe peanut allergy → use gel formulation instead of capsules 5
• Hormone-sensitive breast cancer → avoid 5

Step 4: Initiate treatment immediately upon diagnosis, continue through first trimester 2, 1

Common Pitfalls to Avoid

• Do not use progesterone to reverse medical abortion: While one case series suggested this approach 6, there is insufficient evidence to recommend progesterone for reversing mifepristone-induced abortion
• Do not use in multiple gestations for preterm birth prevention: Progesterone has not shown benefit in twin pregnancies with short cervix 5
• Do not use misoprostol in third trimester if progesterone treatment fails, as it carries 13% uterine rupture risk in women with prior cesarean 5
• Do not confuse with 17-OHPC: The evidence for threatened abortion specifically supports vaginal progesterone, not intramuscular 17-alpha hydroxyprogesterone caproate 5