Helena von Hertzen
Speeches:
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Cervical priming – where is the evidence?
Helena von Hertzen (WHO), Geneva
Cervical priming before surgical abortion is especially beneficial for women with cervical anomalies or previous surgery, young women and those with advanced pregnancy, as they have a higher risk of cervical injury or uterine perforation. WHO Scientific Group, therefore, recommended routine priming for durations of pregnancy over 9 completed weeks for nulliparous women, for women younger than 18 years old and for all women with durations of pregnancy over 12 completed weeks.
Recent research, however, suggests that all women (and doctors performing the procedure) benefit from routine priming, especially when misoprostol is used. The use of laminaria seems to be outdated, as in comparative studies more complications were seen after laminaria than after gemeprost. Further, gemeprost has been shown to be associated with more side-effects and complications when compared to oral (0.4 mg) or vaginal (0.2 mg) misoprostol, although cervical dilation, operation time or bleeding are similar. Only the use of mifepristone can compete with misoprostol in efficacy and low rate of side effects, but its high price and the long interval required between the treatment and procedure makes it less attractive.
The optimal dose of misoprostol is 0.4 mg: lower doses are less effective and higher doses do not give any advantage, they only cause more side effects. The appropriate interval between misoprostol administration and vacuum aspiration is 3 hours, because shorter intervals are not sufficient for full priming effect, even if the dose is increased. Oral, sublingual and vaginal routes of administration of misoprostol have been compared, sublingual administration may give somewhat better results compared to oral administration, but has more side effects, but when compared to vaginal administration there does not seem to be a difference in efficacy, but in some studies women have reported more side effects after sublingual administration.
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Cervical priming prior to surgical abortion
Helena von Hertzen (WHO)
WHO, Geneva
vonhertzenh@who.int
Cervical priming before surgical abortion is especially beneficial for young women and for those in the advanced stages of pregnancy, with cervical anomalies, as they have a higher risk of cervical injury or uterine perforation. When the use of laminaria was the main method to prepare the cervix, the WHO Scientific Group on Medical Methods for the Termination of Pregnancy recommended routine priming for durations of pregnancy of over 9 completed weeks for nulliparous women, for women younger than 18 years of age and for all women with durations of pregnancy of over 12 completed weeks.
This recommendation may need to be review, as recent research suggests that all women may benefit from routine priming of the cervix with misoprostol: a WHO study involving 4791 women demonstrated that routine priming of the cervix with two misoprostol tablets of 200 µg administered vaginally 3 hours prior to vacuum aspiration in pregnancies of up to 12 weeks, decreased the need for further dilatation of the cervix, shortened the time to complete the procedure and significantly decreased the rate of incomplete evacuations. The use of laminaria now seems outdated, as comparative studies report more complications after laminaria than after prostaglandins.
The optimal dose of misoprostol is 400 µg: lower doses are less effective and higher doses only produce more side effects. The appropriate interval between vaginal misoprostol and vacuum aspiration is 3 hours; shorter intervals are not sufficient for full priming effect, even if the dose is increased. The interval may be shortened to 2 hours when misoprostol is administered sublingually. Only the use of mifepristone can compete with misoprostol in efficacy and low rate of side effects, but its high price and the long interval required between the treatment and procedure render it less attractive.
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Cervical priming – the evidence
Helena von Hertzen, MD, WHO, Geneva,
Cervical priming before surgical abortion is especially beneficial for women with cervical
anomalies, for young women and for those with advanced pregnancy, as they have a
higher risk of cervical injury or uterine perforation. When the use of laminaria was the main
method to prepare the cervix, WHO Scientific Group recommended routine priming for
durations of pregnancy over 9 completed weeks for nulliparous women, for women
younger than 18 years old and for all women with durations of pregnancy over 12
completed weeks.
This recommendation may need to be reviewed as recent research suggests that all
women may benefit from routine priming of cervix with misoprostol: a WHO study including
4791 women demonstrated that routine priming of cervix with two misoprostol tablets of
0.2 mg administered vaginally 3 hours prior to vacuum aspiration in pregnancies of up to
12 weeks decreased the need for further dilatation of the cervix, shortened the time to
complete the procedure and significantly decreased the rate of incomplete evacuation. The
use of laminaria now seems to be outdated, as comparative studies report more
complications after laminaria than after prostaglandins.
The optimal dose of misoprostol is 0.4 mg: lower doses are less effective and higher doses
only cause more side effects. The appropriate interval between misoprostol administration
and vacuum aspiration is 3 hours, because shorter intervals are not sufficient for fullpriming effect, even if the dose is increased. Oral, sublingual and vaginal routes of
administration of misoprostol have been used. Only the use of mifepristone can compete
with misoprostol in efficacy and low rate of side effects, but its high price and the long
interval required between the treatment and procedure make it less attractive. -
Summary of current evidence
Helena von Hertzen, MD, WHO, Geneva
During the last ten years the use of misoprostol has escalated in the area of reproductive
health due to its many advantages compared to other prostaglandins, and a substantive
scientific evidence has accumulated suggesting that misoprostol is safe and effective for
various indications, provided the dosage is correct. However, with very few exceptions,
misoprostol has not been licensed for use in obstetrics and gynaecology and this has left
many doctors unsure of their position regarding the use of an off-label drug.
Depending on the indication the strength of scientific evidence varies: experts will agree
e.g. on the benefits of misoprostol compared to other available options for labour induction
and medical abortion. Consequently, misoprostol has been included in the complementary
list of WHO Essential Medicines Library: 25 microgram tablet for the induction of at-termlabour; and the termination of pregnancy of up to 9 weeks (200 microgram tablets) to be
used after mifepristone pretreatment.
More research results may be needed to assess whether evidence-based guidance can be
given regarding other indications. Clinicians agree that cervical priming prior to vacuum
aspiration, or other gynaecological procedures, has become easier thanks to misoprostol.
In addition to the sequential regimen with mifepristone, misoprostol may be used alone to
induce abortion in settings where mifepristone is not available, provided a somewhat lower
effectiveness is acceptable. Misoprostol may also be useful in the treatment of incomplete
abortion, intrauterine fetal death, or in the prevention, and perhaps also in the treatment, of
postpartum haemorrhage, but experts need to agree whether there is enough evidence to
recommend its routine use for these indications. -
Where is the evidence : results from clinical trials
Helena von Hertzen , MD, DDS,
Since 1990 Medical Officer, UNDP/UNFPA,WHO, World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland.
Managerial responsibility for the research initiated and carried out by the Research Group on Post-ovulatory Methods for Fertility Regulation, and for the research on breast-feeding with emphasis on its birth spacing effect.
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The absolute efficacy of emergency contraception (EC) can only be investigated in placebo controlled trials. As such trials have never been undertaken, we do not know with certainty how effective emergency contraceptive pills are. It is evident that the copper IUD is very effective when used for EC, as there were no pregnancies among nearly 2000 women who had a copper IUD inserted after unprotected intercourse.
Different hormonal EC regimens have been compared in large randomized controlled trials (RCT), which constitute a sound tool to estimate a difference between treatments if properly conducted. It should be noted, however, that comparison of pregnancy rates between trials is subject to bias as women's characteristics and eligibility criteria usually differ. The main outcome in efficacy trials of EC is the occurrence of pregnancy, which is a rare event even if no EC is used: it has been estimated that even without treatment only some 8% of women would become pregnant after one act of unprotected intercourse. Thus, the trial size has to be large enough to provide power for treatment comparisons. Such large RCTs have demonstrated that both levonorgestrel and mifepristone are more effective and better tolerated than the regimen of combined oral contraceptives.