C.**Intravaginal gel (Prostin),**

• It is a translucent triacetin-based thixotropic gel formulation that contains either 1 mg or 2 mg of dinoprostone, as the active ingredient in each unit dose of 3 grams (2.5 mL).


The advantage of the controlled-release vaginal insert (Cervidil) over the intracervical one is that it easier to administrate than intracervical (Prepidil) preparations, and it allows easier removal in the case of onset of active labor, rupture of membranes, or with the development of uterine tachsystole. It also requires only a 30 minute delay before the initiation of oxytocin upon its removal compared with an interval of 6 hours for the latter [32, 42].

In conclusion, as other methods, the use of PGE2 has its own advantages and limitations.

#### **Advantages:**


#### **Limitations:**


**Prostaglandin E1 (Misoprostol):** It is another form of synthetic prostaglandine1 analogue that has uterotonic properties, by contracting smooth muscle fibers in the myometrium and facilitation of cervical opening by relaxing of the cervix [45]. It is considered as a safe and effective off-label use for induction of labor or cervical ripening by ACOG [46]. It is available as 100 μg and 200 μg tablets that could be divided to provide 25 or 50 μg doses.

Due to higher dosing (50 μg every 6 hours), it may be associated with uterine tachsystole and fetal heart rate decelerations; ACOG recommends using 25 μg dosing every 3–6 hours with vaginally applied misoprostol and suggests that the higher doses should be used only in select circumstances [47]. If necessary, oxytocin may be initiated 4 hours after the final misoprostol dose in using 25 μg.

A meta-analysis that compared 25 μg with 50 μg dosing reported that 50 μg dosing resulted in a higher rate of vaginal delivery within 24 hours with higher rates of uterine tachsystole meconium passage and higher frequency of fetal acidosis with an umbilical arterial pH of less than 7.16 but without compromising the neonatal outcomes [48].

Advantages of misoprostol are that it is inexpensive, stable at room temperature, and can be administered orally or placed vaginally with few systemic side effects. However, compared with vaginal misoprostol, administration of misoprostol by the buccal or sublingual route increases uterine tachsystole [31].

**Mode of administration:** Misoprostol can be administered orally or placed vaginally with few systemic side effects, with studies reporting that misoprostol tablets placed vaginally are either superior to or equivalent in efficacy compared with intracervical PGE2 gel [49]. Although no difference in clinical outcomes are apparent when comparing intravaginal or intracervical PGE2 preparations, for ease of administration and patient satisfaction, vaginal administration is recommended [48, 50, 51].

**NOTE:** PG formulations of any kind should be avoided in women with a prior uterine scar, such as a prior cesarean delivery or myomectomy, because their use has been associated with an increased risk of uterine rupture.

#### *6.1.2 Oxytocin*

Oxytocin is the most potent uterotonic and common pharmacologic agent used to induce labor. It stimulates the smooth muscles of the uterus in similar fashion with the natural hormone that secretes from the posterior lobe of the pituitary gland in a pulsatile fashion. It also causes contraction of the myoepithelial cells surrounding the mammary alveoli leading to milk ejection during lactation [31, 52].

It has been used either alone or with other drugs and methods. Its administration produces periodic uterine contractions first demonstrable at approximately 20 weeks' gestation, with increasing responsiveness with advancing gestational age primarily due to the upregulation of oxytocin receptor MRNA levels and strong increase in the density of myometrial oxytocin receptors, reaching a peak during early labor [31, 53]. **Once spontaneous labor begins, the uterine sensitivity to oxytocin increases rapidly.** This physiologic mechanism makes oxytocin less effective as a cervical ripening agent [31].

Although oxytocin is an effective means of labor induction, in women with a favorable cervix, as noted earlier, it is less effective as a cervical ripening agent and commonly used in combination with other cervical ripening methods. It could also be used alone given the cervix is favorable [54].

**Oxytocin protocols and mode of administration:** Oxytocin is most often given intravenously and cannot be given orally because the polypeptide could be degraded to small, inactive forms by gastrointestinal enzymes. Its plasma half-life is short, estimated at 3–6 minutes, and steady-state concentrations are reached within 30–40 minutes of initiation or dose change.

It is generally diluted by placing 10 units in 1000 mL of an isotonic solution, such as normal saline, yielding an oxytocin concentration of 10 mU/mL. And given by infusion pump to allow continuous, precise control of the dose is administered [31, 32]. The dosage can be divided into high-dose and low-dose protocols depending on the initial dose and the amount and rate of sequential increase in dose [47, 52].

However, despite the frequent use of oxytocin in clinical practice, and suggestion of several experts for the implementation of a standardized protocol in oxytocin administration [47, 55]. There is little consensus regarding which protocol is most appropriate. And oxytocin protocols in induction of labor remain one of the challenges in the field of obstetrics. Protocols differ as to the initial dose, incremental time period, and steady-state dose [47].
