Grand Rounds

Can Oral Micronized Progesterone Prevent Preterm Labor?

BACKGROUND AND PURPOSE:

Interventions proven to reduce incidence of preterm delivery and/or neonatal complications related to prematurity include
- Single embryo transfers resulting in fewer multiple births
- Limiting elective delivery in the late preterm and early term
- Specialty preterm birth prevention clinics
- Reducing maternal exposure to smoke/smoking via legislation and education
- Cervical cerclage
- Progesterone supplementation
Oral progesterone was the first and least studied route
Micronization increases the bioavailability of oral progesterone
Ashoush et al. (Acta Obstet Gynecol Scand., 2017) assessed the role and optimal dosage of micronized progesterone

Prospective, double-blind, randomized control trial
Patients were randomized into either
- Progesterone group
  - 100 mg oral micronized progesterone, six-hourly, starting at 14-18 weeks until 37 weeks or delivery
- Placebo: Identical oral capsules
Protocol
- Progesterone levels were checked at 20 and 28 weeks
- Transvaginal ultrasound was done at 20 weeks for cervical length assessment
- Emergency/rescue cervical cerclage was done for those with a cervical length <15 mm
- Follow-up scans were continued till 28 weeks (twice monthly) for those with a cervical length of 20–25 mm and weekly for shorter cervical lengths
Primary outcome
- Rate of spontaneous preterm delivery
Secondary outcomes
- Gestational age at birth
- NICU admission

212 patients with previous spontaneous preterm delivery were randomized
Comparing progesterone group to placebo group
- Women delivered at a later gestational age
  - 35.4 weeks vs 33.9 weeks, p = 0.01
- Tocolysis-to-delivery intervals were longer
  - 87 days vs 36 days, p < 0.001
- Spontaneous preterm delivery was reduced
  - Relative risk (RR) of 0.7 (95% CI 0.54-0.92; p = 0.01)
- Neonatal mortality rates were lower
  - 7.3% vs 25.2%, p < 0.001
- NICU admissions were shorter
  - 15.4 days vs 19.5 days, p = 0.008
Number needed-to-treat (NTT) to prevent one case of spontaneous preterm delivery was 5 (95% CI 3-20)
The two groups had similar rates of operative delivery and postpartum complications
Adverse events related to progesterone
- Mild maternal dizziness (29.1% vs. 9.8%, p = 0.002)
- Somnolence (41.6% vs. 19.7%, p = 0.002)
- Vaginal dryness (20.8% vs. 8.7%, p = 0.03)

Oral micronized progesterone is effective in preventing spontaneous preterm delivery
There may be advantage to oral administration due to affordability, and high safety profile
The authors state that further research on the oral route is warranted

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