How does prostaglandin E2 (PGE2) help in the induction of labor?

How Prostaglandin E2 (PGE2) Helps in Labor Induction

PGE2 induces labor through two distinct mechanisms: it directly stimulates myometrial contractions similar to natural labor, and it causes local cervical ripening by degrading collagen through collagenase secretion, resulting in cervical softening, effacement, and dilation. 1

Dual Mechanism of Action

Myometrial Stimulation

• PGE2 stimulates the gravid uterus to contract in a manner similar to term labor contractions, though whether this results from direct myometrial effects remains incompletely understood 1
• This oxytocic effect works synergistically with the cervical changes to facilitate labor progression 1

Cervical Ripening (Primary Mechanism)

• PGE2 initiates local cervical changes independent of myometrial activity, causing softening, effacement, and dilation through collagen degradation 1
• The biochemical changes induced by PGE2 mirror those occurring during spontaneous cervical ripening as pregnancy progresses to term 1
• Collagenase secretion in response to PGE2 breaks down cervical collagen, which is the key mechanism reducing cervical resistance 1

Clinical Effectiveness

Superior Outcomes Compared to Traditional Methods

• In women with unfavorable cervices (Bishop score ≤4), PGE2 results in lower failed induction rates and higher rates of delivery within reasonable intervals compared to amniotomy and/or oxytocin alone 2
• PGE2 gel significantly enhances cervical effacement and dilation, reduces initial induction failures, shortens the induction-delivery interval, reduces oxytocin requirements, and lowers cesarean section rates for failure to progress 3
• A single intracervical dose of 0.5 mg PGE2 resulted in 46% of women going into spontaneous labor within 12 hours versus only 11% with placebo 4

Quantifiable Benefits

• Women receiving PGE2 achieve a 40% higher Bishop score improvement compared to placebo 5
• The overall successful induction rate reaches 85% with PGE2 versus 72% with placebo 4
• Mean time from gel administration to delivery is significantly shorter (19.8 hours with PGE2 versus 24.1 hours with placebo) 4

Pharmacokinetics Supporting Clinical Use

• PGE2 is rapidly absorbed when administered endocervically, with peak metabolite levels (DHK-PGE2) occurring at 0.5-0.75 hours 1
• Mean peak concentrations in gel-treated subjects reach 433 pg/mL versus 137 pg/mL in untreated controls, with clinical responders showing even higher levels at 484 pg/mL 1
• PGE2 undergoes complete metabolism primarily in the lungs, with further metabolism in liver and kidney, and renal elimination of metabolites 1

Practical Administration Considerations

Route Selection

• Vaginal administration has superseded virtually all other routes except endocervical, though endocervical results vary depending on spillage from the canal 2
• The vaginal route offers easier administration technique and lower risk of inadvertent extra-amniotic instillation 6

Monitoring Requirements

• Continuous fetal heart rate and uterine activity monitoring is mandatory from 30 minutes to 2 hours after PGE2 gel administration 7
• When using PGE2 vaginal inserts, monitoring must continue from placement until at least 15 minutes after removal 7

Safety Profile

Low Complication Rates

• Uterine hyperstimulation or pathologic fetal heart rate patterns before oxytocin administration occur in less than 1% of cases 3
• These complications are typically dose-related, self-contained, and reversible with beta-adrenergic tocolytic therapy 3
• Maternal systemic effects at doses used for cervical ripening are negligible 3

Common Pitfall to Avoid

• Higher doses (3-4 mg) are effective but associated with uterine hypertonus and fetal heart rate changes, whereas lower doses (0.5-2 mg) provide effective ripening without these adverse effects 5
• More than three gel applications rarely increase efficacy and should be avoided 6