Dinoprostone (PGE2 ) is a naturally-occurring biomolecule. It is found in low concentrations in most
tissues of the body and functions as a local hormone (1-3). As with any local hormone, it is very rapidly
metabolized in the tissues of synthesis (the half-life estimated to be 2.5-5 minutes). The rate limiting
step for inactivation is regulated by the enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) (1,4).
Any PGE2 that escapes local inactivation is rapidly cleared to the extent of 95% on the first pass
through the pulmonary circulation (1,2).
In pregnancy, PGE2 is secreted continuously by the fetal membranes and placenta and plays an important
role in the final events leading to the initiation of labor (1,2). It is known that PGE2 stimulates the
production of PGFPGF2α which in turn sensitizes the myometrium to endogenous or exogenously
administered oxytocin. Although PGE2 is capable of initiating uterine contractions and may interact with
oxytocin to increase uterine contractility, the available evidence indicates that, in the concentrations
found during the early part of labor, PGE plays an important role in cervical ripening without affecting
uterine contractions (5-7). This distinction serves as the basis for considering cervical ripening and
induction of labor, usually by the use of oxytocin (8-10), as two separate processes.
PGE2 plays an important role in the complex set of biochemical and structural alterations involved in
cervical ripening. Cervical ripening involves a marked relaxation of the cervical smooth muscle fibers
of the uterine cervix which must be transformed from a rigid structure to a softened, yielding and
dilated configuration to allow passage of the fetus through the birth canal (11-13). This process
involves activation of the enzyme collagenase, which is responsible for digestion of some of the
structural collagen network of the cervix (1,14). This is associated with a concomitant increase in the
amount of hydrophilic glycosaminoglycan, hyaluronic acid and a decrease in dermatan sulfate (1).
Failure of the cervix to undergo these natural physiologic changes, usually assessed by the method
described by Bishop (15,16), prior to the onset of effective uterine contractions, results in an
unfavorable outcome for successful vaginal delivery and may result in fetal compromise. It is estimated
that in approximately 5% of pregnancies the cervix does not ripen normally (17). In an additional 10-11%
of pregnancies, labor must be induced for medical or obstetric reasons prior to the time of cervical
The delivery rate of PGE in vivo is about 0.3 mg/hour over a period of 12 hours. The controlled
release of PGE2 from the hydrogel insert is an attempt to provide sufficient quantities of PGE2 to the
local receptors to satisfy hormonal requirements. In the majority of patients, these local effects are
manifested by changes in the consistency, dilatation and effacement of the cervix as measured by the
Bishop score. Although some patients experience uterine hyperstimulation as a result of direct PGE2
or PGF2α mediated sensitization of the myometrium to oxytocin, systemic effects of PGE2 are rarely
encountered. The insert is fitted with a biocompatible retrieval system which facilitates removal at the
conclusion of therapy or in the event of an adverse reaction.
No correlation could be established between PGE2 release and plasma concentrations of PGEm . The
relative contributions of endogenously and exogenously released PGE2 to the plasma levels of the
metabolite PGEm could not be determined. Moreover, it is uncertain as to whether the measured
concentrations of PGEm reflect the natural progression of PGE2 concentrations in blood as birth
approaches or to what extent the measured concentrations following PGE administration represent an
increase over basal levels that might be measured in control patients.
Table 2 Efficacy of Cervidil in Double Blind Studies
|Time to Delivery
|Time to Onset of
|*Treatment success was defined as Bishop score increase at 12 hours of . 3, vaginal delivery within 12 hours or
Bishop score at 12 hours . 6. These studies were not designed with the power to show differences in cesarean
section rates between Cervidil and placebo groups and none were noted.
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