Prostaglandin E1

Misoprostol—Cytotec—is a synthetic prostaglandin E1 (PGE1) that is approved as

a 100- or 200-μg tablet for peptic ulcer prevention. It has been used “off label” for
preinduction cervical ripening and may be administered orally or vaginally. The
tablets are stable at room temperature. Although widespread, the off-label use of
misoprostol has been controversial (Wagner, 2005; Weeks, 2005). Specifically, G.
D. Searle & Company notified physicians that misoprostol is not approved for
labor induction or abortion (Cullen, 2000). Still, the American College of
Obstetricians and Gynecologists (2016) reaffirmed its recommendation for use of
the drug because of proven safety and efficacy. It currently is the preferred
prostaglandin for cervical ripening at Parkland Hospital. In one review of 234
women administered misoprostol, no instances of asthma exacerbation were
associated with its use, and the risk of this was calculated to be <2 percent (Rooney
Thompson, 2015).
Vaginal Administration. Compared with intracervical or intravaginal PGE 2,
vaginally administered misoprostol tablets offer equivalent or superior efficacy for
cervical ripening or labor induction. A metaanalysis of 121 trials also confirmed
these findings (Hofmeyr, 2010). Compared with oxytocin or with intravaginal or
intracervical dinoprostone, vaginal misoprostol increased the vaginal delivery rate
within 24 hours. In this review, although the uterine tachysystole rate rose, this did
not affect cesarean delivery rates. Moreover, compared with dinoprostone,
misoprostol lowered the need for oxytocin induction, but it increased the frequency
of meconium-stained amnionic fluid. Higher doses of misoprostol are associated
with a decreased need for oxytocin but with more uterine tachysystole, with and
without fetal heart rate changes. The American College of Obstetricians and
Gynecologists (2016) recommends a 25-μg vaginal dose—a fourth of a 100-μg
tablet. The drug is evenly distributed among these quartered tablets.
Wing and colleagues (2013) described use of a vaginal polymer insert
containing 200 μg of PGE1. They compared its efficacy with 10-mg dinoprostone
inserts, and preliminary observations are favorable.
Oral Administration. PGE1 tablets are also effective when given orally. One
Cochrane metaanalysis of 76 trials reported that oral misoprostol compared with
placebo significantly raised the rate of vaginal birth within 24 hours, while
decreasing the need for oxytocin and lowering the cesarean delivery rate.
Comparisons of oral misoprostol and oxytocin and of oral misoprostol and
dinoprostone also found significantly reduced rates of cesarean delivery with
misoprostol. Similar efficacy was noted between oral misoprostol and vaginal
administration, although oral administration was associated with significantly
higher Apgar scores and less postpartum hemorrhage (Alfirevic, 2014).
Thorbiörnson and associates (2017) also reported lower rates of cesarean delivery
for oral misoprostol compared with vaginal dinoprostone.
METHODS OF INDUCTION AND AUGMENTATION
Labor induction has primarily been effected with the use of amniotomy,
prostaglandins, and oxytocin, alone or in combination. Because preinduction
cervical ripening frequently eventuates in labor, studies to determine induction
efficacy for some of these agents have produced sometimes confusing results. The
use of prostaglandins for labor augmentation has generally been considered
experimental due to their high rates of uterine tachysystole.
Prostaglandin E1
Both vaginal and oral misoprostol are used for either cervical ripening or labor
induction. For labor induction in women at or near term with either prematurely
ruptured membranes or a favorable cervix, 100 μg of oral or 25 μg of vaginal
misoprostol has similar efficacy compared with intravenous oxytocin. From these
studies, evidence supports that oral misoprostol may be superior (Alfirevic, 2014;
Hofmeyr, 2010; Lo, 2003). Misoprostol may be associated with a greater rate of
uterine tachysystole, particularly at higher doses. Also, induction with PGE 1 may
prove ineffective and require subsequent induction or augmentation with oxytocin.
Thus, although there are trade-offs regarding the risks, costs, and ease of
administration of each drug, either is suitable for labor induction. At Parkland
Hospital, we administer an initial oral 100-μg dose, which may be repeated after 6
hours for inadequate labor. Six hours after the second dose or in those with
tachysystole, an oxytocin infusion is begun, if needed, for hypotonic labor. Döbert
and colleagues (2017) have described preliminary use of a misoprostol vaginal
insert.
For labor augmentation, results of a randomized controlled trial showed oral
misoprostol, 75 μg given at 4-hour intervals for a maximum of two doses, to be
safe and effective (Bleich, 2011). The 75-μg dose was based on a previous
dosefinding
study (Villano, 2011). Although there was more uterine tachysystole
among women with labor augmented with misoprostol, the frequency of
nonreassuring fetal status or cesarean delivery did not differ between oxytocin and
misoprostol.
Oxytocin
In many instances, preinduction cervical ripening and labor induction are simply a
continuum. Thus, “ripening” can also stimulate labor. If not, induction or
augmentation may be continued with solutions of oxytocin given by infusion
pump. Its use in augmentation is a key component in the active management of
labor, described in Chapter 22 (p. 438). With oxytocin use, the American College
of Obstetricians and Gynecologists (2016) recommends fetal heart rate and uterine
contraction monitoring. Contractions can be monitored either by palpation or by
electronic means.