Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in April 2013. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.


Off-label use of lower doses of vaginal misoprostol (after oral mifepristone) for the induction of labour in women with late intrauterine fetal death (IUFD) is supported by 2 small case series that provide limited evidence of similar effectiveness compared with higher doses. While there is some suggestion of improved tolerability with the lower dose regimen, in both case series, the analysis of serious adverse effects is limited by the small numbers in the studies.

Regulatory status: off-label


  • 2 case series comparing lower doses of vaginal misoprostol with higher doses

  • Limited evidence of similar effectiveness

  • More evidence is needed to confirm these findings


  • In 2 case series, the numbers of serious side effects were small and similar between the groups

Patient factors

  • Limited evidence of improved tolerability with lower dose regimens

  • Further evidence is required to confirm these findings


  • Approximately £10 for a pack of 60 misoprostol 200 microgram tablets

Key points

Misoprostol is a synthetic prostaglandin E1 analogue that softens the cervix and can stimulate uterine contractions. It is not currently licensed in the UK for the induction of labour in women with late intrauterine fetal death (IUFD); use for this indication is off-label.

Induction of labour (NICE clinical guideline 70) recommends that, if a woman who has had a late IUFD chooses to proceed with induction of labour, mifepristone should be used, followed by vaginal prostaglandin E2 or misoprostol.

An update to the Royal College of Obstetricians and Gynaecologists' (RCOG) guideline on the management of late IUFD and stillbirth noted that some hospitals in the UK were using larger doses of misoprostol than recommended, potentially leading to an increased risk of adverse effects.

This evidence summary describes the risks and benefits of vaginal misoprostol, when used after oral mifepristone, as in the NICE guidance on the induction of labour in late IUFD. It focusses particularly on the dose of vaginal misoprostol.

No randomised controlled trials were identified that met the inclusion criteria. Two case series were found that compared a low-dose misoprostol treatment regimen (administered vaginally following oral mifepristone as recommended by NICE) with a higher dose regimen (in 1 study administered orally and vaginally after mifepristone, and in 1 study administered vaginally without pre-treatment with mifepristone) for induction of labour after late IUFD, using a historical control group.

The results of the first case series (Fairley et al. 2005, n=47) suggest that oral mifepristone followed by low doses of vaginal misoprostol (mean total dose 167 micrograms) is similarly effective to oral mifepristone followed by a combination of vaginal and oral misoprostol (mean total dose 828 micrograms). However, the statistical significance of any differences between the groups was not reported.

The second case series (Vayrynen et al. 2007, n=130) suggests that oral mifepristone followed by a low dose of vaginal misoprostol (median total dose 100 micrograms) is similarly effective to a higher dose of vaginal misoprostol used on its own without mifepristone (median total dose 200 micrograms).

In both case series, the analysis of serious adverse effects is limited by the small numbers in the studies.

These 2 case series suggest that low dose vaginal misoprostol following mifepristone is effective at inducing labour in late IUFD. Further research is needed to evaluate the safety and efficacy of different dosages of vaginal misoprostol used for this indication.

About this evidence summary

'Evidence summaries: unlicensed or off-label medicines' summarise the published evidence for selected unlicensed or off-label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision-making and support the construction and updating of local formularies.

The summaries support decision-making on the use of an unlicensed or off-label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.

The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.