33
One study reported no incidences of heavy bleeding in women who received oral misoprostol and
34
women who received the same dose of sublingual misoprostol (600 micrograms). The evidence for
35
this outcome was of moderate quality.
36
Pain
37
One study did not find a statistically significant difference in the incidence of pain/cramps for women
38
who received oral misoprostol compared with women who received the same dose of sublingual
39
misoprostol (600 micrograms). The evidence for this outcome was of moderate quality.
40
One study did not find a statistically significant difference in the severity of pain for women who
41
received oral misoprostol compared with women who received the same dose of sublingual
42
misoprostol (600 micrograms). The evidence for this outcome was of high quality.
43
Satisfaction
44
One study did not find a statistically significant difference in the incidence of reported satisfaction for
45
women who received oral misoprostol compared with women who received the same dose of
46
sublingual misoprostol (600 micrograms). The evidence for this outcome was of moderate quality.
47
Evidence to recommendations
1
Relative value placed on the outcomes considered
2
The primary outcome measures for this question were the success rate of the treatment in terms of
3
live birth and the need for further interventions. The secondary outcomes were the various side
4
effects associated with treatment. Of these, the group felt that pain was less informative than the
5
others, as all women would be likely to experience a degree of pain as a natural consequence of the
6
miscarriage. It was also evident from the placebo trials that gastro-intestinal symptoms may
7
accompany miscarriage.
8
Consideration of clinical benefits and harms
9
When considering the appropriate dose and mode of administration, the group considered the main
10
priority to be the efficacy of the treatment. The evidence compared a number of different doses and
11
regimens. For women with missed miscarriage, a single dose of 800 micrograms (oral or vaginal) of
12
misoprostol was the most effective overall. For women with an incomplete miscarriage, the evidence
13
suggested that a single dose of 600 micrograms of misoprostol was effective, but the group
14
recognised that units might prefer to use 800 micrograms for alignment of protocols.
15
For women with missed miscarriage, the group noted that, used at the same dose, both vaginal and
16
oral routes of administration had similar effectiveness, and that both were more effective than sub-
17
lingual administration. The majority of side effects did not show a difference by route. There was
18
contradictory evidence regarding diarrhoea: one study showed more diarrhoea associated with a
19
vaginal route of administration than with an oral route, but two further studies showed no statistically
20
significant difference which matched the GDG’s clinical experience. The evidence suggested that
21
there were more side effects from sub-lingual administration than with vaginal administration. In
22
addition, the group recognised from their own clinical experience that there can often be difficulties
23
with sub-lingual administration as women are expected to hold up to 4 relatively large tablets under
24
their tongue for a long period of time.
25
For women with an incomplete miscarriage, one study found there was a significantly lower incidence
26
of diarrhoea with vaginal administration as compared with oral administration. A second study showed
27
no significant differences between oral and sub-lingual administration for all outcomes.
28
The group felt that an additional benefit of vaginal administration is that if women vomit after receiving
29
medication orally, this can interfere with the absorption of the drug and it can be difficult to determine
30
if the dose should be repeated.
31
Overall, the GDG agreed that vaginal misoprostol is the preferred treatment. However, they
32
recognised that it is important to take into account women’s preferences and thus agreed that the oral
33
route would be appropriate if vaginal administration was not acceptable to the woman.
34
Consideration of health benefits and resource uses
35
The group recognised that there was very little evidence which compared the efficacy of misoprostol
36
in combination with mifepristone compared with misoprostol alone for the treatment of miscarriage.
37
However, what evidence there was suggested that there was no difference in effectiveness. Given the
38
large cost of mifepristone compared with misoprostol‡‡‡, the group agreed that mifepristone should
39
not be used routinely in the management of miscarriage. It was recognised that mifepristone is
40
currently used in current UK practice for this indication and that it would be therefore helpful to
41
conduct further research. They agreed that a trial was needed to determine definitively whether the
42
addition of mifepristone improves the success rate of the medical management, the results of which
43
could then be used to evaluate whether it is a cost-effective treatment.
44
Quality of evidence
45
The evidence for this question was drawn from RCTs, however the quality was mixed and ranged
46
from high to very low. Generally, the group felt that the evidence was of sufficient quality to make
47
recommendations, although they recognised that it would have been helpful to have had further
48
evidence related to the efficacy of mifepristone and misoprostol in combination.
49
‡‡‡ A pack of three 200 mg mifepristone tablets costs approximately £50, whilst a pack of 60 200 microgram tablets costs approximately £10
Pain and bleeding in early pregnancy
158
Information giving and psychological support
1
The group stressed the importance of providing women with information about the treatment, what to
2
expect as the miscarriage progresses, the potential side effects of treatment, and also the next steps
3
if the treatment is ineffective. They felt that informing women about the likely length and extent of
4
bleeding was a particular consideration, as this could be particularly distressing or worrying.
5
Other considerations
6
The GDG discussed the fact that the majority of women receiving medical treatment would now be
7
receiving it as second line treatment, as a result of recommendations about first line expectant
8
management made in section 6.4 above. All of the studies evaluated medical management as first
9
line treatment. However, the group noted that the women participating in the studies were likely to
10
have presented at a variety of different points in the course of their miscarriage, depending on their
11
symptoms and ability to access health care. For example, women with no symptoms might have
12
sought care, and been diagnosed with a missed miscarriage, weeks after the miscarriage had actually
13
occurred, and therefore would be reasonably comparable to women presenting earlier who had then
14
been expectantly managed for a period of time. Despite this, the group did accept that the treatment
15
success rates reported in the trials might be higher than would be expected in women in whom
16
expectant management had already failed, and that this would be a consideration for women
17
choosing their preferred second line treatment. However, they also felt that the relative efficacy of
18
different routes of administration would be unlikely to vary according to whether the treatment was
19
first or second line, and therefore, that the results of the comparisons reported in the trials could
20
safely be extrapolated to women actively choosing medical management after a period of expectant
21
management.
22
The group recognised that there are a number of side-effects associated with miscarriage itself
23
andwith the drugs used in its management, and that clinicians should treat these side effects at the
24
same time as providing miscarriage management.
25
The group agreed that, for women with a missed miscarriage, if the treatment is ineffective (i.e.
26
bleeding has not started) after 24 hours, there should be clinical review. The group also recognised
27
the importance of having a follow-up process in place to ensure that there is no molar or ectopic
28
pregnancy. The group agreed that all women should be advised to check that a urine pregnancy test
29
is negative 3 weeks after receiving medical treatment to determine if it has been effective.
30
Whilst misoprostol is commonly used to treat miscarriage, it is not currently licensed for use for this
31
indication and so women’s consent should be obtained before it is used.
32
Recommendations
33
Number
Recommendation
58 Offer vaginal misoprostol for the medical treatment of missed or incomplete miscarriage. Oral administration is an acceptable alternative if this is the woman’s preference.§§§
59 For women with a missed miscarriage, use a single dose of 800 micrograms of misoprostol.****
60 If bleeding has not started 24 hours after treatment, there should be a clinical review to determine individualised care.
61 For women with an incomplete miscarriage, use a single dose of 600 micrograms of misoprostol. (800 micrograms can be used as an alternative to allow alignment of treatment protocols for missed and incomplete miscarriage.)††††
§§§ Although this use is common in UK clinical practice, at the time of publication (June 2012), misoprostol did not have UK marketing authorisation for this indication. Informed consent should be obtained and documented.
**** Although this use is common in UK clinical practice, at the time of publication (June 2012), misoprostol did not have UK marketing authorisation for this indication. Informed consent should be obtained and documented.
†††† Although this use is common in UK clinical practice, at the time of publication (June 2012), misoprostol did not have UK marketing authorisation for this indication. Informed consent should be obtained and documented.
62 Do not offer mifepristone as a treatment for missed or incomplete miscarriage. 63 Offer all women receiving medical management of miscarriage pain relief and anti-
emetics as required.
64 Inform women about what to expect throughout the process, including the length and extent of bleeding and the potential side effects of treatment including pain, diarrhoea and vomiting.
65 Advise women to take a urine pregnancy test 3 weeks after medical management unless they experience worsening symptoms, in which case advise them to return to the healthcare professional responsible for providing their medical management. 66 For women with a positive pregnancy test, a follow-up process should be in place
to ensure that there is no molar or ectopic pregnancy.
1
2
Number
Research recommendation
RR 7 Is the combination of mifepristone and misoprostol more effective than misoprostol alone in the medical management of miscarriage?
7.6
Setting for surgical management of miscarriage
3
Review question
4
What is the effectiveness of surgical management of miscarriage in an outpatient (office) setting
5
compared with any other setting for improving women’s clinical and psychological outcomes?
6
Introduction
7
Historically women diagnosed with a miscarriage who opted for surgical management would undergo
8
the procedure in a traditional theatre setting under a general anaesthetic. Recent advances in surgical
9
techniques and equipment have seen the introduction of surgical procedures being performed without
10
a general anaesthetic (but with some other form of anaesthesia/ analgesia/ sedation) in an outpatient
11
setting. This review sought to identify which settings are associated with better outcomes.
12
Description of included studies
13
Four studies were included in this review. Three studies were conducted in the USA (Blumenthal et
14
al., 1994; Dalton et al., 2006; Edwards et al., 2007) and one in South Africa (De Jonge et al., 1994).
15
One retrospective observational study (Edwards et al., 2007) assessed and compared the efficiency,
16
post procedure quality of life, and acceptability of manual vacuum aspiration (MVA) performed in an
17
outpatient setting with electric vacuum aspiration (EVA) performed in a hospital in-patient setting in
18
women experiencing a first-trimester miscarriage. EVA was performed under either general
19
anaesthesia, “monitored anaesthesia care” (MAC), or spinal anaesthesia. Analgesia for MVA was
20
provided with a paracervical block of lidocaine.
21
One randomised clinical trial (De Jonge et al., 1994) assessed evacuation under systemic analgesia
22
(fentanyl and midazolam) in a treatment room compared with evacuation under general anaesthesia
23
in an operating theatre.
24
One prospective observational study (Dalton et al., 2006) examined women’s satisfaction with an
25
office-based surgical procedure for early pregnancy failure and compared the resource use and cost
26
between office and operating room management. Anaesthesia for the MVA performed in an office
27
setting consisted of oral lorazepam, ibuprofen, and/or propoxyphene napsylate, with paracervical
28
block. EVA was performed under anaesthesia that included intravenous sedation, regional
29
anaesthesia, or general anaesthesia.