The role of prostaglandins E1 and E2, dinoprostone, and misoprostol in cervical ripening and the induction of labor: a mechanistic approach

Arch Gynecol Obstet. 2017 Aug;296(2):167-179. doi: 10.1007/s00404-017-4418-5. Epub 2017 Jun 5.

Abstract

Purpose: Prostaglandins play a critical role in cervical ripening by increasing inflammatory mediators in the cervix and inducing cervical remodeling. Prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2) exert different effects on these processes and on myometrial contractility. These mechanistic differences may affect outcomes in women treated with dinoprostone, a formulation identical to endogenous PGE2, compared with misoprostol, a PGE1 analog. The objective of this review is to evaluate existing evidence regarding mechanistic differences between PGE1 and PGE2, and consider the clinical implications of these differences in patients requiring cervical ripening for labor induction.

Methods: We conducted a critical narrative review of peer-reviewed articles identified using PubMed and other online databases.

Results: While both dinoprostone and misoprostol are effective in cervical ripening and labor induction, they differ in their clinical and pharmacological profiles. PGE2 has been shown to stimulate interleukin-8, an inflammatory cytokine that promotes the influx of neutrophils and induces remodeling of the cervical extracellular matrix, and to induce functional progesterone withdrawal. Misoprostol has been shown to elicit a dose-dependent effect on myometrial contractility, which may affect rates of uterine tachysystole in clinical practice.

Conclusions: Differences in the mechanism of action between misoprostol and PGE2 may contribute to their variable effects in the cervix and myometrium, and should be considered to optimize outcomes.

Keywords: Cervical ripening; Dinoprostone; Labor induction; Mechanisms; Misoprostol; Prostaglandin.

MeSH terms

  • Adult
  • Alprostadil / administration & dosage
  • Alprostadil / pharmacology*
  • Cervical Ripening / drug effects*
  • Cervix Uteri / drug effects*
  • Cervix Uteri / physiology
  • Dinoprostone / administration & dosage
  • Dinoprostone / pharmacology*
  • Female
  • Humans
  • Interleukin-8
  • Labor, Induced*
  • Misoprostol / administration & dosage
  • Misoprostol / pharmacology*
  • Oxytocics / administration & dosage
  • Oxytocics / pharmacology*
  • Pregnancy
  • Pregnancy Outcome
  • Treatment Outcome
  • Uterine Contraction / drug effects
  • Uterine Contraction / physiology

Substances

  • CXCL8 protein, human
  • Interleukin-8
  • Oxytocics
  • Misoprostol
  • Alprostadil
  • Dinoprostone