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Induction of Labour

 

The full guidance on induction of labour has been published in the International Journal of Gynecology and Obstetrics 2007;99(supp 2):S194-7, and is available as a read-only pfd file here.

 

Recommended Dosages:

25 mcg vaginally 4-hourly (max x6),

50 mcg orally 4-hourly (max x6), or

20 mcg of oral solution 2-hourly (max x12).    

Regimen
There are many possible misoprostol regimens for induction of labor. Each of the three below has been widely used. There is no evidence that any one regimen is better than the other.
 
1.     Vaginal Misoprostol.
Misoprostol tablet cut to 25 mcg size administered vaginally every 4 hours with a maximum of 6 doses [25mcg vaginal pessaries are currently only manufactured in Egypt and Brazil, but others may soon be available]
 
2.     Oral misoprostol solution
A single misoprostol tablet is dissolved in drinking water so that 1ml contains 1 mcg (e.g. 200mcg tablet in 200ml water, or a 100mcg tablet in 100mls water), and 20-25 mls of misoprostol solution (20-25mcg) are then given every 2 hours. If there is no response after 2 doses in nulliparous women then the dose can be doubled. The solution is stable for up to 24 hours at room temperature, but should then be discarded. [Misoprostol tablets can also be cut so as to obtain a 25mcg segment and then administered 2 hourly as above.]
 
3.     Oral misoprostol tablets
Misoprostol tablets cut to 50 mcg size and administered orally every 4 hours to a maximum of 6 doses.
 
These regimens can be used irrespective of the state of the membranes (ruptured or intact), parity, cervical state and gestation. Care is needed in women with favorable cervices and ruptured membranes as they often progress rapidly in labor once induced. The dose needed for induction of labor after intrauterine fetal death is lower.
 Course of Treatment
The woman should be admitted to hospital from the beginning of the labor induction process.
  1. Prior to starting the induction process, the woman should be carefully assessed for evidence of fetal compromise. This should include electronic fetal heart rate monitoring for 30 minutes if available.
  2. If electronic fetal heart rate monitoring is not available, the baby’s condition should be assessed by clinical assessment of growth and amniotic fluid volume, the mother’s report of fetal movements, and if necessary clinical fetal arousal tests.
4.     Once a misoprostol regimen has been started, the woman must be monitored closely. The fetal heart rate and uterine activity, as well as the mother's vital signs must be constantly monitored for 30 minutes after each dose of misoprostol has been administered, and every 30 minutes from the onset of uterine contractions. Where available, electronic fetal monitoring should be used from the time at which regular contractions of every 3 minutes or more commence.
  1. At the time of each planned misoprostol dose, the woman should be clinically reassessed. If there are 0-1 contractions every 10 minutes, then a further dose of misoprostol can be given. If there are 2 or more clinically adequate uterine contractions in 10 minutes, then clinical judgment should be used to assess the best way of continuing the induction to achieve optimal contractions (3 strong contractions in 10 minutes). An intravenous oxytocin infusion for labor induction should not be commenced less than 4 hours after the last dose of vaginal misoprostol or 2 hours after the last dose of oral misoprostol.
  2. If the cervix remains unfavorable after the course of misoprostol is completed, a senior member of staff should review the situation. The alternatives include switching to an alternative method, a repeat course of misoprostol, or a caesarean section.
  
Risks and Side Effects
 
Uterine hyperstimulation
 
Serious side effects may occur as a result of over-stimulation of the uterus. Although these are primarily seen with too high doses (or where the wrong route or dosage frequency has been used), they may also occur at recommended dosages. Serious maternal and fetal complications may result, principally uterine rupture (especially in women with previous uterine scars) and fetal hypoxia.
 
The majority of studies comparing labor induction with misoprostol and dinoprostone or oxytocin show a greater incidence of uterine hypercontractility with misoprostol. However, most of those studies were conducted using relatively high doses of vaginal or oral misoprostol. In studies using 25mg vaginal misoprostol 4-hourly, 50µg oral misoprostol 4-hourly or 20-40 mg oral misoprostol solution 2-hourly, hyperstimulation rates are similar to those in women induced with dinoprostone (4-12%).
 
Uterine rupture
 
There have been several reports of uterine rupture following misoprostol labor induction with and without previous caesarean section. One published trial of misoprostol for labor induction in women with prior caesarean section (using vaginal misoprostol 25 µg six hourly to a maximum of four doses) was terminated prematurely because of disruption of the uterine incision in two of the first 17 misoprostol-treated women. There is also evidence of an increased uterine rupture risk from observational studies: in a retrospective review, uterine rupture occurred in 5/89 (5.6%) of women with previous caesarean delivery who had labor induced with vaginal misoprostol, compared with 1/423 (0.2%) of those induced with dinoprostone. In contrast, other sources have found low rates of uterine rupture. In a retrospective review, no uterine ruptures were detected among 48 women with previous caesarean section whose labor was induced with misoprostol 50 mcg vaginally four hourly. In another study from the USA, there were 2 ruptures of 142 women (1.4%) with previous CS induced with misoprostol. In this study, various dosages of misoprostol were used and the study included women with more than one CS and classical uterine incisions. The uterine rupture rate with misoprostol was not statistically significantly different to that seen when oxytocin alone was used (5/430, 1.2%).
 
There is less evidence for oral misoprostol, but there was a rupture rate of 10% (4 of 41) in a study using oral misoprostol for induction. Whilst the lack of ruptures in the women in the Cochrane reviews' randomized trials who underwent induction with oral misoprostol is encouraging, it would take a trial of over 60,000 women to evaluate whether there was a significant increase in the 0.5% background scar rupture rate in women undergoing a trial of vaginal delivery.

An increase in uterine rupture rate also appears to occur with dinoprostone, albeit not to the same degree. In a large retrospective study of 8904 women undergoing induction following a previous CS the uterine rupture rate was 0.87% for those induced with prostaglandins compared to 0.3% for those induced without prostaglandins.
 

 

These recommendations are produced by an expert group on misoprostol brought together by WHO in Bellagio, Italy in Feb 2007. These recommendations do not reflect official WHO guidelines, but have been released early so as to provide guidance to clinicians worldwide. The excerpt above is taken from:

A Weeks, Z Alfirevic, A Faundes, GJ Hofmeyr, P Safar, D Wing. Misoprostol for induction of labour with a live fetus. International Journal of Gynecology and Obstetrics 2007;99(supp 2):S194-7.
Alternative Guidelines
Additional guidelines for induction of labour are available here.

Induction of Labour (live fetus> 24 wks)

 

Route

Dose

Time period

Max. Dose 

Levels of Evidence

Notes

Bellagio/FIGO

Vaginally

Orally

Oral solution (aq)

25µg

50µg

20µg

4-hrly

4-hrly

2-hrly

6 x

6 x

12 x

I A/B

Do not use if previous caesarean section

WHO

Oral

Vaginal

50µg

25µg

6-hrly

6-hrly

Doesn’t specify

I A

From 2010 draft

NICE

Vaginal

25 µg

6-hrly

Doesn’t specify

IA

It is not recommended by NICE to be used for IOL – only for IUFD.

RCOG

Vaginal

25 µg

6-hrly

Doesn’t specify

IA

Adopted NICE 2008

SOGC

-

-

-

-

Latest guidelines from 1996/2001

Guidelines from 2001 do not advocate using Misoprostol.

ACOG

-

-

-

-

-

Should be avoided in women with previous caesarean section – induce uterine rupture

Gynuity

-

-

-

-

-

No Guidelines

POPPHI

Vaginal

25µg

6-hrly

Doesn’t specify

I B

-

FLASOG p32

Vaginal

Oral

25µg

100µg

6-hrly

6-hrly

3 x day

I B

-