Prostaglandins for cervical ripening and induction of labour

The efficacy of prostaglandins for cervical ripening was shown in a seminal paper by Calder et al. [17]. Although highly effective in this regard, the cervical ripening effects of prostaglandins cannot easily be separated from their stimulatory effect on uterine contractions and it is largely this that causes the potential adverse effects of induction of labour with prostaglandins. Excessive uterine contractions are termed ‘hyperstimulation’ and can be associated with abnormalities of fetal heart rate (FHR). In some women, an abnormal FHR may require immediate delivery by caesarean section.

There are now extensive trial data on the use of prostaglandins for induction of labour. Demonstrated benefits of PGE₂ for cervical ripening compared with placebo or no treatment include a ‘probable’ reduced risk of vaginal delivery not being achieved within 24 hours, a ‘probable’ reduced risk of caesarean section and an increased risk of uterine hyperstimulation with FHR changes (4.8% vs. 1.0%; risk ratio, RR 3.16, 95% CI 1.67–5.98] [18].

When formulations of vaginal PGE₂ are compared, the latest Cochrane review suggests that ‘tablets, gels and pessaries appear to be as effective as each other, any differences between formulations are marginal but may be important’ [18].

In another Cochrane review, intracervical PGE₂ has been shown to be superior to placebo for cervical ripening, but inferior to vaginal prostaglandin in terms of the risk of not achieving vaginal delivery within 24 hours (RR 1.26, 95% CI 1.12–1.41) [14], leading the National Institute for Health and Care Excellence (NICE) to conclude that ‘intracervical PGE₂ should not be used for induction of labour’.

The effects of vaginal or oral PGE₁ (commonly administered as misoprostol) are similar to those of PGE₂ when placebo is used as the direct comparator of each; in other words PGE₁ also reduces the risk of vaginal delivery not occurring within 24 hours compared with placebo [19,20]. However, direct comparison between vaginal PGE₂ and vaginal misoprostol shows that labour induction with vaginal misoprostol is associated with a lower likelihood of vaginal birth not occuring within 24 hours (RR 0.77, 95% CI 0.66–0.89) and a trend to a greater risk of uterine hyperstimulation with FHR changes (RR 1.43, 95% CI 0.97–2.09) [21]. A systematic review of randomized comparisons demonstrated lower caesearean section rates with oral misoprostol compared with vaginal PGE₂ (RR 0.88, 95% CI 0.78–0.99) [20]. This same systematic review suggested that trials comparing vaginal misoprostol with oral misoprostol showed fewer babies with a low Apgar score and lower rates of postpartum haemorrhage in the oral group, but heterogeneous results for vaginal delivery within 24 hours and caesearan section rates [20]. In a sytematic review and network meta‐analysis comparing prostaglandins, the odds of failing to achieve a vaginal delivery were lowest with vaginal misoprostol and the odds of caesarean section were lowest with titrated oral misoprostol [22]. A newly marketed slow‐release formulation of misoprostol [23] now has licencing approval in the UK and some other European countries, but has not yet been comprehensively compared with other formulations of vaginal prostaglandin for labour induction.

Authorities in the UK and USA have come to different conclusions about the benefits of misoprostol over and above those of PGE₂. In the UK, NICE currently recommend that misoprostol not be used routinely except in the situation of intrauterine fetal death. In contrast, ACOG endorses the use of misoprostol for induction of labour in a woman with an unfavourable cervix (assuming there has been no previous uterine surgery) [4]. Cochrane suggests that if misoprostol is being used, that oral is ‘safer’ than vaginal, and a dose of 20–25 µg in solution is most appropriate [20].

Other methods of cervical ripening and induction of labour

Various alternative induction strategies have been investigated in order to avoid the stimulatory effects of prostaglandins on uterine contractions and hence avoid the adverse effects of prostaglandins in labour induction. Mechanical methods commonly involve extra‐amniotic saline solution infusion and laminaria, the hygroscopic dilator or extra‐amniotic Foley catheter placement or cervical ripening balloon. Enthusiasm for the Foley catheter as a cervical ripening/pre‐induction agent has increased following the publication of a large randomized trial demonstrating similar section rates to those observed with PGE₂, but with fewer maternal side effects [24]. A subsequent randomized trial compared the Foley catheter to oral misoprostol for labour induction, and again showed similar rates of adverse effects [25]. Importantly, a network meta‐analysis comparing the Foley catheter, misoprostol and dinoprostone for induction of labour showed the lowest rates of uterine hyperstimulation accompanied by FHR changes in association with Foley catheter use, although vaginal misoprostol was the most effective agent for achieving vaginal delivery within 24 hours [26].

Membrane sweeping is recommended on routine antenatal visits post‐term as an adjunct to labour induction as it reduces the risk of pregnancy prolongation beyond 41 weeks [27]. Of the pharmacological methods, nitric oxide donors [28] and intracervical hyaluronidase [29] both appear to ripen the cervix without inducing myometrial contractility, but there is insufficient evidence as yet to recommend their use in clinical practice. Mifepristone, a progesterone antagonist, has less stimulatory effects on myometrial contractions than prostaglandins but insufficient evidence about safety currently precludes use with a live baby [3,30].

Once the cervix is ripe, continuation of labour induction may involve forewater amniotomy (artificial rupture of the membranes) with or without augmentation of labour with oxytocin. Forewater amniotomy for induction of labour (without PGE₂ but sometimes with oxytocin) is commonly used as a primary method of induction in women with a ripe cervix, but is not routinely advised because of the increased requirement for oxytocin augmentation [31] if used alone, and because of lower acceptability compared with prostaglandin if used in combination with oxytocin [3]. It is probably for these reasons that use of artificial rupture of membranes with or without oxytocin is now much less commonly used as the primary method of induction of labour in the UK.

Amniotomy

A meta‐analysis of 14 trials in nearly 5000 women indicated that routine amniotomy had no effect on the duration of the first stage of labour, maternal satisfaction or Apgar scores at delivery, but that there was a trend to increased risk of caesarean section (RR 1.26, 95% CI 0.98–1.62) [32]. These facts support the authors’ conclusion that ‘we cannot recommend that amniotomy should be introduced routinely as part of standard labour management and care’.

There is a little more evidence in support of the use of amniotomy with oxytocin for augmentation of labour. As with prostaglandins, oxytocin has to be used carefully because the myometrial contractions it induces cause a reduction in blood flow to the uterus. This reduction in blood flow can lead to fetal distress, especially if the fetus is already compromised. A Cochrane systematic review and meta‐analysis showed that early amniotomy and oxytocin augmentation applied prior to any delay in labour being identified reduced the risk of caesarean section (RR 0.87, 95% CI 0.77–0.99) and shortened the duration of labour (average mean difference 1.28 hours, 95% CI –1.97 to –0.59) [33]. There were no differences in any neonatal outcomes or in maternal satisfaction rates.