Surveillance Review Proposal

Surveillance report 2016 Ectopic
pregnancy and miscarriage

National Institute for Health and Care
Excellence
Surveillance programme
Surveillance proposal consultation document
Ectopic pregnancy and miscarriage: diagnosis and
initial management NICE guideline CG154 4-year
surveillance review
Background information
Guideline issue date: December 2012
2-year surveillance review: no update
3-year surveillance review: no update
Surveillance proposal for consultation

We will not update the guideline at this time.
We also propose to remove the following NICE research recommendations

from the NICE version of the guideline and the NICE research
recommendations database:
RR 02: How does the timing and frequency of ultrasound examination

affect diagnosis and outcomes of early pregnancy complications, including
womens experience and cost effectiveness?
RR 03: Are progesterone or progestogens effective in treating threatened
miscarriage?
Surveillance proposal consultation document August 2016

Ectopic pregnancy and miscarriage. (2012) NICE guideline CG154
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RR 04: In women with confirmed miscarriage, does the type of
management strategy (expectant, medical and surgical) impact on women's
experience, including psychological and emotional outcomes?
RR 05: In women with ectopic pregnancy, does the type of intervention
(laparoscopy or medical management) impact on women's experience,
including psychological and emotional outcomes?
Reason for the proposal
New evidence
We found 23 new studies in a search for randomised controlled trials and
systematic reviews published between 8 July 2014 and 2 May 2016. We also
considered 2 additional studies identified by members of the guideline
committee who originally worked on this guideline.
Evidence identified in previous surveillance 2 years after publication of the

guideline was also considered. This included 8 studies identified by search.
From all sources, 33 studies were considered to be relevant to the guideline.
This included new evidence on support and information giving, diagnosis of

viable intrauterine pregnancy and of ectopic pregnancy, management of
miscarriage and management of ectopic pregnancy which supports current
recommendations. We also identified evidence on medical management of
miscarriage in outpatient settings, diagnostic accuracy of serum biomarkers,
expectant management for ectopic pregnancy and laparotomy compared with
laparoscopic techniques for managing non-tubal ectopic pregnancy. We
asked topic experts whether this new evidence would affect current
recommendations on ectopic pregnancy and miscarriage. Generally, the topic
experts thought that an update was not needed.
We did not find any new evidence on early pregnancy assessment services,
symptoms and signs of ectopic pregnancy and initial assessment or anti-D
rhesus prophylaxis.

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None of the new evidence considered in surveillance of this guideline was
thought to have an effect on current recommendations.
No equalities issues were identified during the surveillance process.
Research recommendations
At 4-year and 8-year surveillance reviews of guidelines published after 2011,
we assess progress made against prioritised research recommendations. See
the research recommendations section for further information.
For this surveillance review we assessed 5 prioritised research

recommendations, and proposed that 4 should be removed from the NICE
NICE version of guideline and NICE database
Overall decision
After considering all the new evidence and views of topic experts, we decided
not to update this guideline.
We also propose to remove 4 prioritised research recommendations from the

NICE version of the guideline and the NICE research recommendations
database.
Further information
See appendix A: summary of new evidence from surveillance below for further
information.
For details of the process and update decisions that are available, see
ensuring that published guidelines are current and accurate in Developing
NICE guidelines: the manual.

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Appendix A: summary of new evidence from
surveillance
Support and information giving
154 01 What interventions are the most effective for improving womens
psychological and/or emotional health following pain, bleeding or
pregnancy loss, in the first trimester of pregnancy?
Recommendations derived from this question

1.1.1 Treat all women with early pregnancy complications with dignity and respect. Be aware that
women will react to complications or the loss of a pregnancy in different ways. Provide all
women with information and support in a sensitive manner, taking into account their individual
circumstances and emotional response*.
1.1.2 Healthcare professionals providing care for women with early pregnancy complications in any
setting should be aware that early pregnancy complications can cause significant distress for
some women and their partners. Healthcare professionals providing care for these women
should be given training in how to communicate sensitively and breaking bad news. Non-
clinical staff such as receptionists working in settings where early pregnancy care is provided
should also be given training on how to communicate sensitively with women who experience
early pregnancy complications.
1.1.3 Throughout a woman's care, give her and (with agreement) her partner specific evidence-
based information in a variety of formats. This should include (as appropriate):
When and how to seek help if existing symptoms worsen or new symptoms develop,
including a 24-hour contact telephone number.
What to expect during the time she is waiting for an ultrasound scan.
What to expect during the course of her care (including expectant management), such as
the potential length and extent of pain and/or bleeding, and possible side effects. This
information should be tailored to the care she receives.
Information about post-operative care (for women undergoing surgery).
What to expect during the recovery period for example, when it is possible to resume
sexual activity and/or try to conceive again, and what to do if she becomes pregnant
again. This information should be tailored to the care she receives.
Information about the likely impact of her treatment on future fertility.
Where to access support and counselling services, including leaflets, web addresses and
helpline numbers for support organisations.
Ensure that sufficient time is available to discuss these issues with women during the course of their
care and arrange an additional appointment if more time is needed.
1.1.4 After an early pregnancy loss, offer the woman the option of a follow-up appointment with a
healthcare professional of her choice.
* For further guidance about providing information, see Patient experience in adult NHS services (NICE clinical
guidance 138).
Surveillance decision
This review question should not be updated.

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Mobile phone messages bleeding (p<0.001), pain (p=0.042) and side
effects (p=0.027) they experienced.
2-year Evidence Update and 3-year
surveillance review summary Topic expert feedback
No relevant evidence was identified No topic expert feedback was relevant to this
evidence.
4-year surveillance summary
1
An RCT of 469 women were randomised to Impact statement
into two groups: one group receive standard of The study is unlikely to change guideline
care (SOC) only whilst the other group received recommendations as the evidence base in this
SOC and a messaging intervention. The study area is still emerging with only one study
showed that anxiety decreased more identified in this area.
(p=0.013), and less emotional stress was
experienced (p=0.015), in the intervention
New evidence is unlikely to change guideline
compared to the SOC group. Participants in the
recommendations.
intervention group were also more likely to
report that they felt very well prepared for the
Test to predict viability the test (cases) than those who have not
(controls, p=0.04).
No relevant evidence was identified. No topic expert feedback was relevant to this
evidence.
2
An RCT of 138 women with a single Impact statement
intrauterine gestational sac of <20mm mean The study is unlikely to change
diameter, with no visible embryo on their first recommendations as the evidence base is
ultrasound scan were randomised to have a currently relatively small. Only one study has
test to calculate the probability of viability been identified where a test is used to predict
(cases) or not (controls). After seven days, the probability of viability.
anxiety levels (measured using the Hospital
Anxiety and Depression Score) were
significantly lower in women who have received
recommendations.
Supportive counselling 4.5 in counselling and control groups; P = 0.04)

and 3 months (median score 1 versus 2.5 in
counselling and control groups; P = 0.03).
surveillance review summary
No relevant evidence was identified. Topic expert feedback
No topic expert feedback was relevant to this
3 evidence.
An RCT of 188 women were randomised to
receive supportive counselling from a nurse or Impact statement
routine care. Although there was no difference The study identified is consistent with the
in proportion of women suffering psychological recommendations.
distress at 3 months (p=0.19), subgroup of
women with high baseline scores, the median
score in the counselling group was significantly
recommendations.
lower than the control group who only received
routine care at 6 weeks (median score 3 versus

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Early pregnancy assessment services
154 02 What is the clinical and cost effectiveness of early pregnancy assessment
unites (EPAUs) compared with other models of service provision in
improving womens clinical and psychological outcomes?

1.2.1 Regional services should be organised so that an early pregnancy assessment service is
available 7 days a week for women with early pregnancy complications, where scanning can
be carried out and decisions about management made.
1.2.2 An early pregnancy assessment service should:
be a dedicated service provided by healthcare professionals competent to diagnose and
care for women with pain and/or bleeding in early pregnancy and
offer ultrasound and assessment of serum human chorionic gonadotrophin (hCG) levels
and
be staffed by healthcare professionals with training in sensitive communication and
breaking bad news.
1.2.3 Early pregnancy assessment services should accept self-referrals from women who have had
recurrent miscarriage* or a previous ectopic or molar pregnancy. All other women with pain
and/or bleeding should be assessed by a healthcare professional (such as a GP, accident
and emergency [A&E] doctor, midwife or nurse) before referral to an early pregnancy
assessment service.
1.2.4 Ensure that a system is in place to enable women referred to their local early pregnancy
assessment service to attend within 24 hours if the clinical situation warrants this. If the
service is not available, and the clinical symptoms warrant further assessment, refer women
to the nearest accessible facility that offers specialist clinical assessment and ultrasound
scanning (such as a gynaecology ward or A&E service with access to specialist gynaecology
support).
*Although additional care for women with recurrent miscarriage is not included in the scope of the guideline, the
Guideline Development Group recognised that it is common clinical practice to allow these women to self-refer to an
early pregnancy assessment service and wished this to remain the case.
No new information was identified at any surveillance review.
154 03 What is the appropriate model for service organisation and delivery of
EPAUs?

The full version of the guideline addressed evidence for this question in conjunction with the evidence
for question 154-02 above to make recommendations 1.2.1 to 1.2.4.

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Symptoms and signs of ectopic pregnancy and initial

assessment
154 04 What are the signs and symptoms associated with ectopic pregnancy?

1.3.1 Refer women who are haemodynamically unstable, or in whom there is significant concern
about the degree of pain or bleeding, directly to A&E.
1.3.2 Be aware that atypical presentation for ectopic pregnancy is common.
1.3.3 Be aware that ectopic pregnancy can present with a variety of symptoms. Even if a symptom
is less common, it may still be significant. Symptoms of ectopic pregnancy include:
common symptoms:
abdominal or pelvic pain
amenorrhoea or missed period
vaginal bleeding with or without clots
other reported symptoms:
breast tenderness
gastrointestinal symptoms
dizziness, fainting or syncope
shoulder tip pain
urinary symptoms
passage of tissue
rectal pressure or pain on defecation.
1.3.4 Be aware that ectopic pregnancy can present with a variety of signs on examination by a
healthcare professional. Signs of ectopic pregnancy include:
more common signs:
pelvic tendernesssy
adnexal tenderness
abdominal tenderness
other reported signs:
cervical motion tenderness
rebound tenderness or peritoneal signs
pallor
abdominal distension
enlarged uterus
tachycardia (more than 100 beats per minute) or hypotension (less than
100/60 mmHg)
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shock or collapse
orthostatic hypotension.
1.3.5 During clinical assessment of women of reproductive age, be aware that:
they may be pregnant, and think about offering a pregnancy test even when symptoms
are non-specific and
the symptoms and signs of ectopic pregnancy can resemble the common symptoms and
signs of other conditions for example, gastrointestinal conditions or urinary tract
infection.
1.3.6 All healthcare professionals involved in the care of women of reproductive age should have
access to pregnancy tests.
1.3.7 Refer immediately to an early pregnancy assessment service (or out-of-hours gynaecology
service if the early pregnancy assessment service is not available) for further assessment
women with a positive pregnancy test and the following on examination:
pain and abdominal tenderness or
pelvic tenderness or
cervical motion tenderness.
1.3.8 Exclude the possibility of ectopic pregnancy, even in the absence of risk factors (such as
previous ectopic pregnancy), because about a third of women with an ectopic pregnancy will
have no known risk factors.
1.3.9 Refer to an early pregnancy assessment service (or out-of-hours gynaecology service if the
early pregnancy assessment service is not available) women with bleeding or other
symptoms and signs of early pregnancy complications who have:
pain or
a pregnancy of 6 weeks gestation or more or
a pregnancy of uncertain gestation.
The urgency of this referral depends on the clinical situation.
1.3.10 Use expectant management for women with a pregnancy of less than 6 weeks gestation who
are bleeding but not in pain. Advise these women:
to repeat a urine pregnancy test after 710 days and to return if it is positive
a negative pregnancy test means that the pregnancy has miscarried
to return if their symptoms continue or worsen.
1.3.11 Refer women who return with worsening symptoms and signs that could suggest an ectopic
pregnancy to an early pregnancy assessment service (or out-of-hours gynaecology service if
the early pregnancy assessment service is not available) for further assessment. The
decision about whether she should be seen immediately or within 24 hours will depend on the
clinical situation.
1.3.12 If a woman is referred to an early pregnancy assessment service (or out-of-hours
gynaecology service if the early pregnancy assessment service is not available), explain the
reasons for the referral and what she can expect when she arrives there.

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Diagnosis of viable intrauterine pregnancy and of ectopic
pregnancy
154 05 What is the diagnostic value of ultrasound for determining a viable

intrauterine pregnancy?

1.4.1 Offer women who attend an early pregnancy assessment service (or out-of-hours
gynaecology service if the early pregnancy assessment service is not available) a
transvaginal ultrasound scan to identify the location of the pregnancy and whether there is a
fetal pole and heartbeat.
1.4.2 Consider a transabdominal ultrasound scan for women with an enlarged uterus or other
pelvic pathology, such as fibroids or an ovarian cyst.
1.4.3 If a transvaginal ultrasound scan is unacceptable to the woman, offer a transabdominal
ultrasound scan and explain the limitations of this method of scanning.
1.4.4 Inform women that the diagnosis of miscarriage using 1 ultrasound scan cannot be
guaranteed to be 100% accurate and there is a small chance that the diagnosis may be
incorrect, particularly at very early gestational ages.
1.4.5 When performing an ultrasound scan to determine the viability of an intrauterine pregnancy,
first look to identify a fetal heartbeat. If there is no visible heartbeat but there is a visible fetal
pole, measure the crownrump length. Only measure the mean gestational sac diameter if
the fetal pole is not visible.
1.4.6 If the crownrump length is less than 7.0 mm with a transvaginal ultrasound scan and there is
no visible heartbeat, perform a second scan a minimum of 7 days after the first before making
a diagnosis. Further scans may be needed before a diagnosis can be made.
1.4.7 If the crownrump length is 7.0 mm or more with a transvaginal ultrasound scan and there is
no visible heartbeat:
seek a second opinion on the viability of the pregnancy and/or
perform a second scan a minimum of 7 days after the first before making a diagnosis.
1.4.8 If there is no visible heartbeat when the crownrump length is measured using a
transabdominal ultrasound scan:
record the size of the crownrump length and
1.4.9 If the mean gestational sac diameter is less than 25.0 mm with a transvaginal ultrasound
scan and there is no visible fetal pole, perform a second scan a minimum of 7 days after the
first before making a diagnosis. Further scans may be needed before a diagnosis can be
made.
1.4.10 If the mean gestational sac diameter is 25.0 mm or more using a transvaginal ultrasound
scan and there is no visible fetal pole:
seek a second opinion on the viability of the pregnancy and/or
1.4.11 If there is no visible fetal pole and the mean gestational sac diameter is measured using a
transabdominal ultrasound scan:
record the size of the mean gestational sac diameter and
1.4.12 Do not use gestational age from the last menstrual period alone to determine whether a fetal
heartbeat should be visible.
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1.4.13 Inform women that the date of their last menstrual period may not give an accurate
representation of gestational age because of variability in the menstrual cycle.
1.4.14 Inform women what to expect while waiting for a repeat scan and that waiting for a repeat
scan has no detrimental effects on the outcome of the pregnancy.
1.4.15 Give women a 24-hour contact telephone number so that they can speak to someone with
experience of caring for women with early pregnancy complications who understands their
needs and can advise on appropriate care*.
1.4.16 When diagnosing complete miscarriage on an ultrasound scan, in the absence of a previous
scan confirming an intrauterine pregnancy, always be aware of the possibility of ectopic
pregnancy. Advise these women to return for further review if their symptoms persist.
1.4.17 All ultrasound scans should be performed and reviewed by someone with training in, and
experience of, diagnosing ectopic pregnancies.
*See also recommendation 1.1.3 for details of further information that should be provided.
Tools for predicting viability specificity and sensitivity for the pseudosac
was 5.5% (95%CI, 3.3-9.0%) and 94.2%
2-year Evidence Update and 3-year (95%CI, 75.9-98.8%), the adnexal mass was
surveillance review summary 63.5% (95%CI, 48.5-76.3%) and 91.4%
4,5
A prospective observational cohort study (95%CI, 83.6-95.7%) and free fluid was 47.2%
developed and evaluated a simple scoring (95%CI, 33.2-61.7%) and 92.3% (95%CI, 85.6-
system to predict viable intrauterine pregnancy 96.0%). The authors conclude that visualisation
beyond the first trimester. A simple scoring of an empty uterus, adnexal mass, free fluid or
system combining demographic and symptom a pseudosac has poor sensitivity for the
variables (maternal age and amount of diagnosis of a tubal pregnancy when an
bleeding) with initial ultrasound variables (mean obvious extrauterine embryo is absent, but it
gestation-sac diameter, mean yolk-sac has good specificity.
diameter, and presence of a fetal heart beat) Topic expert feedback
appeared able to predict pregnancy viability
Topic experts have identified a prospective
beyond the first trimester. The panel of experts 7
multicentre observational trial which
who reviewed this study at the 2 year
established cut off values for embryo crown-
surveillance review agreed that the value of the
rump length and mean gestational sac
study was limited as psychological morbidity
diameter to diagnose miscarriage with high
was not considered as an outcome. The panel
levels of certainty. The following indicated a
also recognised that, as the study was
miscarriage at initial scan: mean gestational
conducted in a single centre and involved 1500
sac diameter > 25 mm with an empty sac
patients, further research would be beneficial in
(specificity: 100%, 95% confidence interval
validating the findings before considering for
99.0% to 100%), embryo with crown-rump
inclusion in the guideline.
length > 7 mm without visible embryo heart
4-year surveillance summary activity (specificity: 100%, 96.7% to 100%),
6
A systematic review of 5858 women aimed to mean gestational sac diameter > 18 mm for
determine the accuracy of ultrasound in the gestational sacs without an embryo presenting
diagnosis of tubal ectopic pregnancy in the after 70 days' gestation (specificity: 100%,
absence of an obvious extrauterine embryo. It 99.6% to 100%), embryo with crown-rump
indicated that an empty uterus on ultrasound length > 3 mm without visible heart activity
was found to predict an ectopic pregnancy with presenting after 70 days' gestation (specificity:
a sensitivity of 81.1% (95%CI, 42.1-96.2%) and 100%, 95.8% to 100%).
specificity of 79.5% (95%CI, 68.9-87.1%). The
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than 25mm, then a repeat scan is required after
A topic expert also expressed concern that 7 days to confirm diagnosis. The multicentre
theres a danger for misdiagnosing observational trial presents strong evidence to
miscarriages as some services are unable to suggest that a second scan may not be
implement a second opinion or offer the woman required due to the high specificity. The studies
a rescan. identified are currently in line with current
recommendations.
Impact statement
Current recommendations state that if crown-
rump length measurement is less than 7.00mm New evidence is unlikely to change guideline
recommendations.
and the gestational sac measurement is less
154 06 What is the accuracy of transvaginal ultrasound compared with

transabdominal ultrasound for diagnosing ectopic pregnancy?

154 07 What is the diagnostic accuracy of two or more hCG measurements for
determining an ectopic pregnancy in women with pain and bleeding and
pregnancy of unknown location?

1.4.18 Be aware that women with a pregnancy of unknown location could have an ectopic
pregnancy until the location is determined.
1.4.19 Do not use serum hCG measurements to determine the location of the pregnancy.
1.4.20 In a woman with a pregnancy of unknown location, place more importance on clinical
symptoms than on serum hCG results, and review the woman's condition if any of her
symptoms change, regardless of previous results and assessments.
1.4.21 Use serum hCG measurements only for assessing trophoblastic proliferation to help to
determine subsequent management.
1.4.22 Take 2 serum hCG measurements as near as possible to 48 hours apart (but no earlier) to
determine subsequent management of a pregnancy of unknown location. Take further
measurements only after review by a senior healthcare professional.
1.4.23 Regardless of serum hCG levels, give women with a pregnancy of unknown location written
information about what to do if they experience any new or worsening symptoms, including
details about how to access emergency care 24 hours a day. Advise women to return if there
are new symptoms or if existing symptoms worsen.
1.4.24 For a woman with an increase in serum hCG concentration greater than 63% after 48 hours:

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Inform her that she is likely to have a developing intrauterine pregnancy (although the
possibility of an ectopic pregnancy cannot be excluded).
Offer her a transvaginal ultrasound scan to determine the location of the pregnancy
between 7 and 14 days later. Consider an earlier scan for women with a serum hCG level
greater than or equal to 1500 IU/litre.
If a viable intrauterine pregnancy is confirmed, offer her routine antenatal care*
If a viable intrauterine pregnancy is not confirmed, refer her for immediate clinical
review by a senior gynaecologist.
1.4.25 For a woman with a decrease in serum hCG concentration greater than 50% after 48 hours:
inform her that the pregnancy is unlikely to continue but that this is not confirmed and
provide her with oral and written information about where she can access support and
**
counselling services and
ask her to take a urine pregnancy test 14 days after the second serum hCG test, and
explain that:
if the test is negative, no further action is necessary
if the test is positive, she should return to the early pregnancy assessment service for
clinical review within 24 hours.
1.4.26 For a woman with a change in serum hCG concentration between a 50% decline and 63%
rise inclusive, refer her for clinical review in the early pregnancy assessment service within 24
hours.
1.4.27 For women with a pregnancy of unknown location, when using serial serum hCG
measurements, do not use serum progesterone measurements as an adjunct to diagnose
either viable intrauterine pregnancy or ectopic pregnancy.
* See Antenatal care (NICE clinical guideline 62).

** See also recommendation 1.1.3 for details of further information that should be provided.
Diagnosis Topic expert feedback

evidence.
5
A systematic review of 23 cohort studies Impact statement
(n=9078) to determine the diagnostic accuracy The evidence suggests that in women with a
of the various serum hCG strategies in women pregnancy of unknown location, the ratio of
with pregnancy of unknown location. The study serum hCG levels appears to be effective in
found that serum hCG ratios and logistic diagnosing ectopic pregnancy. This is
regression models had a better performance as consistent with the current recommendation of
compared with an absolute single serum hCG calculating the percentage change in 2 serum
level. hCG measurements taken as near as possible
to 48 hours apart.
No relevant evidence was identified.
recommendations.

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154 08 What is the diagnostic accuracy of two or more hCG measurements plus
progesterone for determining an ectopic pregnancy in women with pain and
bleeding and pregnancy of unknown location?

154 09 What is the diagnostic accuracy of two or more hCG measurements for
determining a viable intrauterine pregnancy in women with pain and
bleeding and pregnancy of unknown location?
154 10 What is the diagnostic accuracy of two or more hCG measurements plus
progesterone for determining a viable intrauterine pregnancy in women
with pain and bleeding and pregnancy of unknown location?


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Management of miscarriage
154 11 What is the effectiveness of progesterone in improving outcomes in women

with threatened miscarriage?

1.5.1 Advise a woman with vaginal bleeding and a confirmed intrauterine pregnancy with a fetal
heartbeat that:
if her bleeding gets worse, or persists beyond 14 days, she should return for further
assessment
if the bleeding stops, she should start or continue routine antenatal care.
154 12 How effective is expectant management of miscarriage compared with

active treatment for improving womens clinical and psychological
outcomes?

1.5.2 Use expectant management for 714 days as the first-line management strategy for women
with a confirmed diagnosis of miscarriage. Explore management options other than expectant
management if:
the woman is at increased risk of haemorrhage (for example, she is in the late first
trimester) or
she has previous adverse and/or traumatic experience associated with pregnancy (for
example, stillbirth, miscarriage or antepartum haemorrhage) or
she is at increased risk from the effects of haemorrhage (for example, if she has
coagulopathies or is unable to have a blood transfusion) or
there is evidence of infection.
1.5.3 Offer medical management to women with a confirmed diagnosis of miscarriage if expectant
management is not acceptable to the woman.
1.5.4 Explain what expectant management involves and that most women will need no further
treatment. Also provide women with oral and written information about further treatment
options.
1.5.5 Give all women undergoing expectant management of miscarriage oral and written
information about what to expect throughout the process, advice on pain relief and where and
when to get help in an emergency*.
1.5.6 If the resolution of bleeding and pain indicate that the miscarriage has completed during 714
days of expectant management, advise the woman to take a urine pregnancy test after 3
weeks, and to return for individualised care if it is positive.
1.5.7 Offer a repeat scan if after the period of expectant management the bleeding and pain:
have not started (suggesting that the process of miscarriage has not begun) or
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are persisting and/or increasing (suggesting incomplete miscarriage).
Discuss all treatment options (continued expectant management, medical management, and surgical
management) with the woman to allow her to make an informed choice.
1.5.8 Review the condition of a woman who opts for continued expectant management of
miscarriage at a minimum of 14 days after the first follow-up appointment.
* See also recommendation 1.1.3 for details of further information that should be provided.
Fertility outcomes pregnancy rates were comparable in expectant

management, systemic methotrexate and
surgery.
No relevant evidence was identified. Impact statement
Expectant management is recommended as a
first-line treatment in the guideline, with medical
and surgical also available to the woman if
Topic expert feedback clinically relevant. The study suggests no
Topic experts have identified a retrospective difference in fertility outcomes between the two
8
analysis study of women diagnosed with tubal methods and is therefore unlikely to affect
ectopic pregnancy (n=151). Spontaneous recommendations.
intrauterine pregnancy rates were 62.9 % in
expectantly managed women, 58.4 % in
women with systemic methotrexate and 68.7 %
recommendations.
in women with surgery (p > 0.05). The authors
conclude that spontaneous intrauterine
Preterm labour Topic expert feedback

evidence.
The study is consistent with guideline
9 recommendations that do not offer dilation and
A systematic review and meta-analysis of
curettage for the management of miscarriage.
cohorts and case-control studies of 1 853 017
women showed that dilation and curettage
(D&C) increased the risk of preterm labour New evidence is unlikely to change guideline
compared to women who have no history of recommendations.
D&C (the odds ratio for preterm birth <37
weeks was 1.29, 95% CI 1.17; 1.42).
Success rates 4-year surveillance summary

10
An RCT (n=217) has shown the expectant
management of women with first trimester
miscarriage is safe and effective as an
alternative to surgery. However, the total

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success rate at 4 weeks was lower for single intramuscular dose). Successful
expectant than for surgical management (81.4 treatment with negative titers of beta-hCG
vs 95.7 %; P = 0.0029). The study also found a occurred in 9 cases (90.0%) of the
longer duration of bleeding and pain in women methotrexate group and in 12 (92.3%) of the
expectantly managed than those surgically placebo group (p > 0.999), indicating no
managed (mean 11 vs 7 days; P < 0.0001 and difference between expectant and medical
mean 8.1 vs 5.5 days; P < 0.0001). management.
11
An RCT of 360 women with early pregnancy Topic expert feedback
loss were randomised into expectant No topic expert feedback was relevant to this
management or surgical evacuation and found evidence.
that there was no difference in the success
Impact statement
rates between the groups. The rates of
Success rates of expectant management are
unplanned admissions (18.1%) and unplanned
comparable to surgical management of ectopic
surgical evacuations (17.5%) in the expectant
pregnancies. Expectant management is
group were significantly higher than the rates
associated with an increased risk of unplanned
(7.4% and 8% respectively) in the surgical
admissions and longer durations of bleeding.
group.
The evidence is consistent with current
12
Another RCT of 23 women with ectopic recommendations.
pregnancy were randomised into expectant
management (saline solution administered in a
single intramuscular dose) and management recommendations.
2
with methotrexate (50 mg/m administered as a
Safety needed transfusion (RR 6.45; 95% CI 1.21 to

34.42).
surveillance review summary 4-year surveillance summary
14
A systematic review of 7 RCTs (n=1521) No relevant evidence was identified.
compared the safety profile of expectant
Topic expert feedback
management and surgical management of
miscarriage. The expectant group was more
evidence.
likely to have an incomplete miscarriage by two
weeks (RR 3.98; 95% CI 2.94 to 5.38) or by six Impact statement
to eight weeks (RR 2.56; 95% CI 1.15 to 5.69). Expectant management is associated with
The need for unplanned surgical treatment was more risks than surgical management but the
greater for the expectant-care group (RR 7.35; evidence base does not indicate superiority for
95% CI 5.04 to 10.72). The mean percentage either treatment. The study is in line with
needing surgical management in the expectant- current recommendations which offer the
care group was 28%, while 4% of the surgical- choice of both to the woman.
treatment group needed additional surgery.
The expectant-care group had more days of
bleeding (MD 1.59; 95% CI 0.74 to 2.45).
recommendations.
Further, more of the expectant-care group
Methotrexate protocols 4-year surveillance summary

31
An RCT of 76 women with an ectopic
pregnancy were randomised to receive either a
surveillance review summary 2
single dose of 50 mg/m of methotrexate given
at day 0 or a double dose at day 0 and 4.
Success rates were not different between the
two groups (p=0.29), nor were the operation
16 of 34
rates and additional methotrexate doses. Topic expert feedback
Duration of hospitalisation was significantly No topic expert feedback was relevant to this
lower in double dose compared to the single evidence.
dose (11.55 d vs. 14.76 d, P < 0.001).
Impact statement
32
Another RCT of 92 women with a tubal The studies are unlikely to affect
ectopic pregnancy were randomised to receive recommendations as the results of the two
a single-dose or two-dose protocol of systemic methotrexate protocols were similar.
methotrexate. The success rates between the
single-dose and two-dose groups did not show
a significant difference (82.6 versus 87.0%; recommendations.
relative risk 0.95; 95% confidence interval 0.80-
1.13).
154 13 How effective is surgical management of miscarriage compared with

medical management for improving womens clinical and psychological
outcomes?

Cost effectiveness medical management is cost effective and

more efficacious.
surveillance review summary 4-year surveillance summary
15
A cost-analysis of a multi-centre RCT (n=652) No relevant evidence was identified.
indicated that cost-effectiveness largely
depends on circumstances. For instance,
inpatient electric aspiration was more effective
evidence.
than medical treatment (incremental
efficacy=0.134) and cost $745 more, giving an Impact statement
ICER of $5580. Outpatient manual aspiration The study identified is unlikely to affect the
was also more effective than medical treatment guideline as both surgical and medical
(incremental efficacy=0.112) but cost $202 less management of miscarriage is offered to the
than medical treatment, therefore manual women in current recommendations.
aspiration was cost saving versus medical
treatment. Surgery is cost effective and more
efficacious when performed in an outpatient recommendations.
setting. For incomplete or inevitable abortion,

17 of 34
154 14 What is the most appropriate dose of misoprostol and mifepristone to
provide for managing miscarriage?

1.5.9 Do not offer mifepristone as a treatment for missed or incomplete miscarriage.
1.5.10 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*.
1.5.11 For women with a missed miscarriage, use a single dose of 800 micrograms of misoprostol*.
1.5.12 Advise the woman that if bleeding has not started 24 hours after treatment, she should
contact her healthcare professional to determine ongoing individualised care.
1.5.13 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 both missed and incomplete miscarriage*.)
1.5.14 Offer all women receiving medical management of miscarriage pain relief and anti-emetics as
needed.
1.5.15 Inform women undergoing medical management of miscarriage 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.
1.5.16 Advise women to take a urine pregnancy test 3 weeks after medical management of
miscarriage unless they experience worsening symptoms, in which case advise them to
return to the healthcare professional responsible for providing their medical management.
1.5.17 Advise women with a positive urine pregnancy test after 3 weeks to return for a review by a
healthcare professional to ensure that there is no molar or ectopic pregnancy.
*Although this use is common in UK clinical practice, at the time of publication (December 2012), misoprostol did not
have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance,
taking full responsibility for the decision. Informed consent should be obtained and documented. See the General
Medical Council's Good practice in prescribing medicines guidance for doctors for further information.
Etonogestrel implants and mifepristone between the groups (P=0.28). Insertion of

etonogestrel implants with mifepristone did not
increase medical abortion failure risk and there
is no evidence that it decreased repeat
pregnancy rates.
16 Topic expert feedback
An RCT of 476 women were randomised to
receive etonogestrel implants either with
evidence.
mifepristone (Quickstart group) or after the
abortion (Afterstart group) to evaluate medical Impact statement
abortion efficacy and repeat pregnancy. The The study identified is unlikely to affect
study found 3.9% of the Quickstart group and guideline recommendations. A do not offer
3.8% of the Afterstart group required surgery to recommendation is in place for mifepristone as
complete the abortion, a difference of 0.08% there is no evidence to suggest clinical
(90% confidence interval -3.1% to 3.3%). At 6 superiority over misoprostol but there is a large
months follow up, 0.5% of Quickstart group and difference in cost. It has also been noted that
1.4% of Afterstart group became pregnant, Etonogestrel implants are not licensed for this
although pregnancy rates did not differ indication in the UK.
18 of 34
recommendations.
Letrozole as effective as misoprostol alone in complete

abortion rate.
evidence.
17
An RCT of 214 were randomised to either Impact statement
receive letrozole 10 mg daily for 3 days The study identified is consistent with current
followed by 800 micrograms of vaginal guideline recommendations.
misoprostol, while the placebo group received
It has also been noted that Letrozole implants
placebo for 3 days followed by the same
are not licensed for this indication in the UK.
dosage of misoprostol. Complete abortion rate
in the letrozole group was not significantly
higher than that of the placebo group (84.1% New evidence is unlikely to change guideline
compared 78.5%). The authors conclude that recommendations.
the combination of letrozole and misoprostol is
Oral vs vaginal misoprostol Impact statement

In the evidence used to produce the guideline,
both routes of administration were shown to be
equally effective. The committees decision was
based on additional benefit of vaginal
4-year surveillance summary administration is that if women vomit after
18
A double-blind RCT of 184 women receiving medication orally, this can interfere
investigated whether oral or vaginal misoprostol with the absorption of the drug and it can be
was superior for cervical dilation prior to difficult to determine if the dose should be
surgical abortion. Misoprostol and placebo was repeated. Current guideline recommendations
self-administered 1 h or 3 h prior to surgery and offer both routes of administration and the
all women received 2 tablets of 200 mcg womens preference is also taken into account.
misoprostol and 2 identical looking placebo The study is consistent with the
tablets. The vaginal route of administration was recommendations.
shown to be more effective with longer priming
time. (P = 0.034, 95% confidence interval (CI) -
2.202, -0.086).
recommendations.
evidence.
Mifepristone failure (EPF). The success rates of sequential

treatment with mifepristone and misoprostol in
case of EPF varied between 52% and 95% with
the authors concluding that the evidence is
insufficient to draw any conclusions of
4-year surveillance summary mifepristones added value.
19
A systematic review of 16 studies looked at
the added value of mifepristone to misoprostol
alone for the treatment of early pregnancy
19 of 34
Topic expert feedback there is no evidence to suggest clinical
No topic expert feedback was relevant to this superiority over misoprostol but there is a large
evidence. difference in cost.
Impact statement
The study identified is unlikely to affect New evidence is unlikely to change guideline
guideline recommendations. A do not offer recommendations.
recommendation is in place for mifepristone as
Dose of misoprostol Impact statement

The evidence used to produce the guideline
suggests 800mg misoprostol for missed
20 miscarriage and 600mg for incomplete
An RCT of 310 women compared the safety
miscarriage as these were shown to be most
and effectiveness of 400 vs 800 micrograms
effective for complete evacuation. The
doses of intravaginal misoprostol. The rate of
guideline committee suggested a range of 600-
induced complete miscarriage was equivalent
800g for alignment of protocols. The present
using both ultrasound criteria (observed risk
study is small in size, but does suggest that a
difference (ORD) -4.6%, 95% CI -12.8 to 3.7%;
lower dose of 400g is more beneficial to
P = 0.313) and clinical criteria (ORD -5.6%,
reduce rates of fever and rigors. However, the
95% CI -14.8 to 3.6%; P = 0.273). Following
adverse-effects were patient reported and the
the 400g dose, the reported rate of
questionnaires had a low compliance rate of
fever/rigors was lower (ORD -15.6%, 95% CI -
completion. The panel of experts who reviewed
28.1 to -3.0%; P = 0.015).
this study at the 2 year surveillance review felt
4-year surveillance summary that there was insufficient evidence at this
No relevant evidence was identified. stage to justify updating this question.
No relevant evidence was identified. New evidence is unlikely to change guideline
recommendations.
154 15 What is the effectiveness of surgical management of miscarriage in an

outpatient (office) setting compared with any other setting for improving
womens clinical and psychological outcomes?

1.5.18 Where clinically appropriate, offer women undergoing a miscarriage a choice of:
manual vacuum aspiration under local anaesthetic in an outpatient or clinic setting or
surgical management in a theatre under general anaesthetic.
1.5.19 Provide oral and written information to all women undergoing surgical management of
miscarriage about the treatment options available and what to expect during and after the
procedure*.

20 of 34
Complications necessary in < 0.5% of cases in most studies.

Anaesthesia-related complications occurred in
< 0.2% of procedures in six office-based
studies and < 0.5% of procedures performed in
surgical centres or hospital-based clinics. The
4-year surveillance summary prevalence of major complications was similar
21
A systemic review of 36 studies compared the across clinic context.
prevalence of complications that required
additional interventions for abortions performed
A topic expert has noted that some services do
in office-based clinics and surgical centre or
not offer manual vacuum aspiration under local
hospital clinic settings. Haemorrhage not
anaesthetic for the surgical management of
requiring transfusion occurred in 0-4.7% of
miscarriage due to service constraints.
office-based procedures and 0-4.1% of
hospital-based procedures. Haemorrhage not Impact statement
requiring transfusion occurred in 0-4.7% of The risk of complications across different
office-based procedures and 0-4.1% of settings is comparable. The evidence identified
hospital-based procedures. Major is consistent with current recommendations.
complications requiring intervention, including
haemorrhage requiring transfusion and uterine
perforation needing repair, occurred in < 0.1%
recommendations.
of procedures, and hospitalisation was
Management of ectopic pregnancy
154 16 How effective is surgical management of tubal ectopic pregnancy

compared with medical management for improving womens clinical and
psychological outcomes?

1.6.1 Inform women who have had an ectopic pregnancy that they can self-refer to an early
pregnancy assessment service in future pregnancies if they have any early concerns.
1.6.2 Give all women with an ectopic pregnancy oral and written information about:
how they can contact a healthcare professional for post-operative advice if needed, and
who this will be and
where and when to get help in an emergency*.
1.6.3 Offer systemic methotrexate** as a first-line treatment to women who are able to return for
follow-up and who have all of the following:
no significant pain
an unruptured ectopic pregnancy with an adnexal mass smaller than 35 mm with no
visible heartbeat
a serum hCG level less than 1500 IU/litre
no intrauterine pregnancy (as confirmed on an ultrasound scan).

21 of 34
1.6.4 Offer surgery as a first-line treatment to women who are unable to return for follow-up after
methotrexate treatment or who have any of the following:
an ectopic pregnancy and significant pain
an ectopic pregnancy with an adnexal mass of 35 mm or larger
an ectopic pregnancy with a fetal heartbeat visible on an ultrasound scan
an ectopic pregnancy and a serum hCG level of 5000 IU/litre or more.
1.6.5 Offer the choice of either methotrexate** or surgical management to women with an ectopic
pregnancy who have a serum hCG level of at least 1500 IU/litre and less than 5000 IU/litre,
who are able to return for follow-up and who meet all of the following criteria:
no significant pain
an unruptured ectopic pregnancy with an adnexal mass smaller than 35 mm with no
visible heartbeat
no intrauterine pregnancy (as confirmed on an ultrasound scan).
Advise women who choose methotrexate that their chance of needing further intervention is increased
and they may need to be urgently admitted if their condition deteriorates.
1.6.6 or women with ectopic pregnancy who have had methotrexate, take 2 serum hCG
measurements in the first week (days 4 and 7) after treatment and then 1 serum hCG
measurement per week until a negative result is obtained. If hCG levels plateau or rise,
reassess the woman's condition for further treatment.
**Although this use is common in UK clinical practice, at the time of publication (December 2012), methotrexate did
not have UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance,
taking full responsibility for the decision. Informed consent should be obtained and documented. See the General
Medical Council's Good practice in prescribing medicines guidance for doctors for further information.
154 17 What is the effectiveness of laparotomy compared with laparoscopic

techniques for managing tubal ectopic pregnancy?

1.6.7 When surgical treatment is indicated for women with an ectopic pregnancy, it should be
performed laparoscopically whenever possible, taking into account the condition of the
woman and the complexity of the surgical procedure.
1.6.8 Surgeons providing care to women with ectopic pregnancy should be competent to perform
laparoscopic surgery.
1.6.9 Commissioners and managers should ensure that equipment for laparoscopic surgery is
available.

22 of 34
Fertility outcomes SLL group than in the control group (6.3% vs
16.2%; p = 0.021).
evidence.
23
An RCT of 216 women after laparoscopic Impact statement
salpingostomy for tubal pregnancy were The study is unlikely to affect the guideline
randomised into 2 groups: one group received recommendations as the evidence base for
second-look laparoscopy whilst second group second-look laparoscopy is relatively small.
did not. At 3-year follow-up, the intrauterine
pregnancy rate was higher in the SLL group
compared with the control group (63.1% vs
recommendations.
48.6%; p = 0.032), and the incidence of
recurrent ectopic pregnancy was lower in the
154 18 What is the effectiveness of salpingectomy compared with salpingotomy in

improving outcomes in women with tubal ectopic pregnancy?

1.6.10 Offer a salpingectomy to women undergoing surgery for an ectopic pregnancy unless they
have other risk factors for infertility.
1.6.11 Consider salpingotomy as an alternative to salpingectomy for women with risk factors for
infertility such as contralateral tube damage.
1.6.12 Inform women having a salpingotomy that up to 1 in 5 women may need further treatment.
This treatment may include methotrexate and/or a salpingectomy.
1.6.13 For women who have had a salpingotomy, take 1 serum hCG measurement at 7 days after
surgery, then 1 serum hCG measurement per week until a negative result is obtained.
1.6.14 Advise women who have had a salpingectomy that they should take a urine pregnancy test
after 3 weeks. Advise women to return for further assessment if the test is positive.
Fertility outcomes the salpingotomy group and 5% of women in

the salpingectomy group (RR 1.6, CI 0.8-3.3).
25
surveillance review summary A multicentre RCT (n=406) at 17 centres
24
An open-label, multicentre RCT of 446 examined whether management of ectopic
women with a tubal pregnancy showed that the pregnancy with methotrexate, salpingotomy or
cumulative ongoing pregnancy rate was 60.7% salpingectomy affected ongoing fertility. In arm
after salpingotomy and 56.2% after 1, fertility did not differ significantly after the 2
salpingectomy (fecundity rate ratio 1.06, 95% interventions: the 2-year rate of intrauterine
CI 0.81-1.38; log-rank p=0.678). Persistent pregnancy was 67% after methotrexate alone
trophoblast occurred more frequently in the and 71% after salpingotomy plus methotrexate
salpingotomy group than in the salpingectomy (HR=0.85, 95% CI 0.59 to 1.22, p=0.37).
group (7% vs 1; RR 15.0, 2.0-113.4). Repeat Similarly in arm 2, fertility did not differ
ectopic pregnancy occurred in 8% of women in significantly after the 2 interventions: the 2-year

23 of 34
rate of intrauterine pregnancy was 70% after Salpingotomy also increased the risk of REP
salpingotomy plus methotrexate and 64% after rate (RR = 2.27, 95% CI = 1.12-4.58, P = 0.02).
salpingectomy (hazard ratio=1.06, 95% CI 0.69 The persistent ectopic pregnancy (PEP)
to 1.63, p=0.78). occurred more frequently in the salpingotomy
group than the salpingectomy group (RR =
26 11.61, 95% CI = 3.17-42.46, P = 0.0002).
A surveillance review considered 2 RCTs and
8 cohort studies (n=1229) and found that Topic expert feedback
fertility prospects are not improved via Topic experts identified the open-label,
24
salpingotomy compared with salpingectomy in multicentre RCT noted in the 2 year
women with a tubal pregnancy. The meta- surveillance summary.
analysis of the RCT subgroup indicated that
Impact statement
there was no statistically significant difference
Studies outlined confirm that salpingotomy
in intrauterine pregnancy (IUP) rates (RR =
does not improve fertility prospects in women
1.04, 95% CI = 0.89-1.21, P = 0.61) nor the
with a healthy contralateral tube. This is in line
repeat ectopic pregnancy (REP) rate (RR =
with guideline recommendations which offer
1.30, 95% CI = 0.72-2.38, P = 0.39) between
salpingectomy to women who do not have
the salpingotomy and salpingectomy group. In
contralateral tube damage.
contrast, the cohort study subgroup analysis
revealed that the intrauterine pregnancy (IUP)
rate was higher in the salpingotomy group New evidence is unlikely to change guideline
compared with the salpingectomy group (RR = recommendations.
1.24, 95% CI = 1.08-1.42, P = 0.002).
Cost effectiveness Topic expert feedback

evidence.
The study identified is consistent with the
27 guideline recommendations which offer
An RCT of 446 women with a tubal
salpingectomy to women undergoing surgery
pregnancy were randomised into a
for ectopic pregnancy unless they have risk
salpingotomy or a salpingectomy group. Mean
factors for infertility.
direct medical costs per woman in the
salpingotomy group and in the salpingectomy
group were 3319 versus 2958, respectively, New evidence is unlikely to change guideline
with a mean difference of 361 (95% confidence recommendations.
interval 217 to 515). Salpingotomy resulted in
additional treatments for persistent trophoblast
and interventions for repeat ectopic pregnancy.
Anti-D rhesus prophylaxis
154 19 Should anti-D rhesus prophylaxis be given to women with a threatened

miscarriage, miscarriage or ectopic pregnancy in the first trimester?

1.7.1 Offer anti-D rhesus prophylaxis at a dose of 250 IU (50 micrograms) to all rhesus negative
women who have a surgical procedure to manage an ectopic pregnancy or a miscarriage.
24 of 34
1.7.2 Do not offer anti-D rhesus prophylaxis to women who:
receive solely medical management for an ectopic pregnancy or miscarriage or
have a threatened miscarriage or
have a complete miscarriage or
have a pregnancy of unknown location.
1.7.3 Do not use a Kleihauer test for quantifying fetomaternal haemorrhage.
154 20 What is the appropriate dose of anti-D that should be administered to

women with a threatened miscarriage, miscarriage or ectopic pregnancy in
the first trimester?

NQ 01 What is the effectiveness of medical management of miscarriage in an

outpatient setting compared with any other setting for improving womens
clinical and psychological outcomes.
This question was not addressed by the guideline.
New evidence has subsequently been identified and considered for possible addition to the guideline as
a new question.
This question should not be added.
Intravaginal misoprostol 4-year surveillance summary

28
An RCT of 154 women with first trimester
incomplete miscarriage were randomised into
inpatient or outpatient setting and received
misoprostol 800 micrograms eight hourly to a
maximum of three doses. Outpatient
administration of misoprostol was as effective

25 of 34
as inpatient treatment with success rate of 89.2 Impact statement
and 85.7 % (p = 0.520). The side effects were The study indicates that inpatient and
not significantly different between the two outpatient use of misoprostol lead to similar
groups. outcomes. This study is unlikely to change
guideline recommendations.
No topic expert feedback was relevant to this New evidence is unlikely to impact on the
evidence. guideline.
NQ 02 What is diagnostic accuracy of serum biomarkers for determining a

viable intrauterine pregnancy in women with threatened miscarriage or an
ectopic pregnancy?
a new question.
Serum biomarkers negative test is likely to identify those who are

likely to continue with the pregnancy.
29
A systematic review and meta-analysis of 26 No topic expert feedback was relevant to this
cohort studies (n=9436) examined the accuracy evidence.
of progesterone to diagnose a viable ectopic or
Impact statement
intrauterine pregnancy. A progesterone test
The study identified is unlikely to change
(cut-off values from 3.2 to 6 ng/mL) predicted a
guideline recommendations. At the last
non-viable pregnancy with pooled sensitivity of
surveillance review (2015), the panel of experts
74.6% (95% confidence interval 50.6% to
felt that a single progesterone measurement
89.4%), specificity of 98.4% (90.9% to 99.7%),
cannot be considered in isolation without
positive likelihood ratio of 45 (7.1 to 289), and
regard to full clinical assessment of the patient
negative likelihood ratio of 0.26 (0.12 to 0.57).
and ultrasound scan is the main test used for
4-year surveillance summary determining viability. The guideline currently
A systematic review and diagnostic meta- recommends serial hCG testing which requires
30
analysis of 19 studies investigated 2 patient visits 48 hours apart, so a
biochemical markers to determine outcomes for progesterone measurement (or another serum
women with threatened miscarriage at 5-32 biomarker) might be useful in reducing
weeks of 1263 women. The study found that appointments (reducing two visits to one). But
CA 125 (n=648) showed a sensitivity of 90% there is no difference in the cost of tests per se,
(95% confidence interval (CI) 83-94%), and the panel agreed that a follow-up scan
specificity of 88% (95% CI 79-93%), positive would still be necessary to check the location of
likelihood ratio of 7.86 (95% CI 4.23-14.60) and the pregnancy.
negative likelihood ratio of 0.10 (95% CI 0.06-
0.20). The inverse of negative likelihood ratio
New evidence is unlikely to impact on the
was 9.31 (95% CI 5-17.1) indicating that a
guideline.

26 of 34
NQ 03 How effective is expectant management compared to medical
management for ectopic pregnancy?
a new question.
Quality of life Topic expert feedback

evidence.
The study identified is unlikely to change
13 guideline recommendations. The study showed
An RCT of 62 women with ectopic pregnancy
there was no difference in the health related
or pregnancy of an unknown location were
quality of life between expectant management
randomised to receive expectant management
and methotrexate. The study identified was
or systemic methotrexate. Using standardised
small in sample size, therefore it is unlikely to
questionnaires, there was no difference in the
impact the guideline at this time.
health related quality of life in women receiving
expectant management or methotrexate.
guideline.
NQ 04 What is the effectiveness of laparotomy compared with laparoscopic

techniques for managing non-tubal ectopic pregnancy?
a new question.

27 of 34
Success rates suspicion index for arteriovenous malformation.
Systemic methotrexate and D&C are not
recommended as first-line approaches for
CSEP, as these procedures are associated
with high complication and hysterectomy rates.
22 Topic expert feedback
A systemic review identified the success rates
A topic expert has noted that molar
for best first-line approach treatments for
(hydatidiform mole) pregnancy was excluded
caesarean section ectopic pregnancy (CSEP)
but may need a small mention in the guideline
as follows: systemic methotrexate 8.7%, uterine
recommendations regarding information and
artery embolisation 18.3%, hysteroscopy
referral.
39.1%, dilation and curettage 61.6%, and
hysterotomy 92.1%. The ability to achieve a Impact statement
subsequent term pregnancy is related to The management of non-tubal ectopic
successful systemic methotrexate treatment (p pregnancies was not considered in the original
= 0.001) or hysterotomy (p = 0.009). Future guideline. The new evidence identified
term pregnancy was significantly more frequent suggests that non-tubal ectopic pregnancies
in the hysterotomy group (p = 0.001).The could be considered by the guideline, however
authors conclude that hysteroscopy and the evidence was limited and therefore it is
laparoscopic hysterotomy are safe and efficient unlikely to impact the guideline at this time.
surgical procedures that can be adopted as
primary treatment modalities for CSEP. Uterine
artery embolisation should be reserved for
guideline.
cases with significant bleeding and/or a high

28 of 34
Research recommendations
Prioritised research recommendations

At 4-year and 8-year surveillance reviews of guidelines published after 2011, we assess
progress made against prioritised research recommendations. We may then propose to
remove research recommendations from the NICE version of the guideline and the NICE
database for research recommendations. The research recommendations will remain in the
full versions of the guideline. See NICEs research recommendations process and methods
guide 2015 for more information.
These research recommendations were deemed priority areas for research by the Guideline Committee;
therefore, at this 4-year surveillance review time point a decision will be taken on whether to retain the
research recommendations or stand them down.
We applied the following approach:
New evidence relevant to the research recommendation was found and an update of the related
review question is planned.
The research recommendation will be removed from the NICE version of the guideline and the
NICE research recommendations database. If needed, a new research recommendation may be
made as part of the update process.
New evidence relevant to the research recommendation was found but an update of the related
review question is not planned because the new evidence is insufficient to trigger an update.
The research recommendation will be retained because there is evidence of research activity in
this area.
New evidence relevant to the research recommendation was found but an update of the related
review question is not planned because evidence supports current recommendations.
The research recommendation will be removed from the NICE version of the guideline and the
NICE research recommendations database because further research is unlikely to impact on the
guideline.
Ongoing research relevant to the research recommendation was found.
The research recommendation will be retained and evidence from the ongoing research will be
considered when results are published.
No new evidence relevant to the research recommendation was found and no ongoing studies were
identified.
The research recommendation will be removed from the NICE version of guideline and the NICE
research recommendations database because there is no evidence of research activity in this
area.
The research recommendation would be answered by a study design that was not included in the
search (usually systematic reviews or randomised controlled trials).
The research recommendation will be retained in the NICE version of the guideline and the NICE
research recommendations database.
The new research recommendation was made during a recent update of the guideline.
The research recommendation will be retained in the NICE version of the guideline and the NICE
research recommendations database.

29 of 34
RR 01 A national evaluation of early pregnancy assessment unit service
provision should be carried out to identify factors affecting outcomes. Factors
should include whether care is provided in a dedicated unit, staffing
configuration and opening hours of dedicated services. Outcomes should
include both process (service) outcomes and pregnancy-related outcomes.
Data collected should be used to analyse the cost effectiveness of early
pregnancy assessment units compared with other models of care.
No new evidence was found but it is not expected that this research recommendation would
be answered by systematic reviews or RCTs. Therefore it is proposed to keep this research
recommendation.
RR 02 How does the timing and frequency of ultrasound examination affect

diagnosis and outcomes of early pregnancy complications, including womens
experience and cost effectiveness?
The research recommendation will be removed from the NICE version of guideline and the
NICE research recommendations database because there is no evidence of research activity
in this area.
RR 03 Are progesterone or progestogens effective in treating threatened

miscarriage?
in this area.
RR 04 In women with confirmed miscarriage, does the type of management

strategy (expectant, medical and surgical) impact on women's experience,
in this area.
RR 05 In women with ectopic pregnancy, does the type of intervention

(laparoscopy or medical management) impact on women's experience,

30 of 34
in this area.
Other research recommendations

The following research recommendations were not deemed as priority areas for research by
the guideline committee. No decisions will be taken the status of these research
recommendations.
RR 01 What interventions improve emotional and psychological outcomes for

women following ectopic pregnancy?
RR 02 Research should be undertaken to design and validate a decision tool

for evaluating signs, symptoms and risk factors for correctly identifying ectopic
pregnancy.
RR 03 Is the combination of mifepristone and misoprostol more effective than

misoprostol alone in the medical management of miscarriage?
New evidence was found but an update is not planned because the evidence is consistent
with current guideline recommendations.
RR 04 Does the administration of anti-D rhesus prophylaxis following pain and

bleeding in early pregnancy improve outcomes? Outcomes should include
rhesus sensitisation in the woman attributable to the early pregnancy event and
morbidity related to rhesus disease in subsequent unborn and newborn babies.

31 of 34
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2. Davison AZ, Appiah A, Sana Y et al. (2014) The psychological effects and patient acceptability of
a test to predict viability in early pregnancy: a prospective randomised study. European Journal
of Obstetrics, Gynecology, & Reproductive Biology 178:95-99.
3. Kong GW, Chung TK, and Lok IH. (2014) The impact of supportive counselling on women's
psychological wellbeing after miscarriage--a randomised controlled trial. BJOG: An International
Journal of Obstetrics & Gynaecology 121:1253-1262.
4. Bottomley C, Van Belle V, Kirk E et al. (2013) Accurate prediction of pregnancy viability by means
of a simple scoring system. Hum Reprod 28:68-76.
5. van Mello NM, Mol F, Opmeer BC et al. (2012) Diagnostic value of serum hCG on the outcome of
pregnancy of unknown location: a systematic review and meta-analysis. Hum Reprod Update
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Surveillance Review Proposal

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Surveillance Review Proposal

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Surveillance report 2016 Ectopic

pregnancy and miscarriage

2-year surveillance review: no update

3-year surveillance review: no update

Surveillance proposal for consultation

We also propose to remove the following NICE research recommendations

RR 02: How does the timing and frequency of ultrasound examination

Surveillance proposal consultation document August 2016

Reason for the proposal

Evidence identified in previous surveillance 2 years after publication of the

From all sources, 33 studies were considered to be relevant to the guideline.

This included new evidence on support and information giving, diagnosis of

Surveillance proposal consultation document August 2016

No equalities issues were identified during the surveillance process.

For this surveillance review we assessed 5 prioritised research

We also propose to remove 4 prioritised research recommendations from the

Surveillance proposal consultation document August 2016

Support and information giving

Recommendations derived from this question

Surveillance proposal consultation document August 2016

Supportive counselling 4.5 in counselling and control groups; P = 0.04)

Surveillance proposal consultation document August 2016

Recommendations derived from this question

Recommendations derived from this question

Surveillance proposal consultation document August 2016

Symptoms and signs of ectopic pregnancy and initial

Recommendations derived from this question

Surveillance proposal consultation document August 2016

154 05 What is the diagnostic value of ultrasound for determining a viable

Recommendations derived from this question

154 06 What is the accuracy of transvaginal ultrasound compared with

Recommendations derived from this question

Recommendations derived from this question

Surveillance proposal consultation document August 2016

* See Antenatal care (NICE clinical guideline 62).

Diagnosis Topic expert feedback

Surveillance proposal consultation document August 2016

Recommendations derived from this question

Recommendations derived from this question

Surveillance proposal consultation document August 2016

154 11 What is the effectiveness of progesterone in improving outcomes in women

Recommendations derived from this question

154 12 How effective is expectant management of miscarriage compared with

Recommendations derived from this question

Fertility outcomes pregnancy rates were comparable in expectant

Preterm labour Topic expert feedback

Success rates 4-year surveillance summary

Surveillance proposal consultation document August 2016

Safety needed transfusion (RR 6.45; 95% CI 1.21 to

Methotrexate protocols 4-year surveillance summary

154 13 How effective is surgical management of miscarriage compared with

Recommendations derived from this question

Cost effectiveness medical management is cost effective and

Surveillance proposal consultation document August 2016

Recommendations derived from this question

Etonogestrel implants and mifepristone between the groups (P=0.28). Insertion of

Letrozole as effective as misoprostol alone in complete

Oral vs vaginal misoprostol Impact statement

Mifepristone failure (EPF). The success rates of sequential

Dose of misoprostol Impact statement

154 15 What is the effectiveness of surgical management of miscarriage in an

Recommendations derived from this question

Surveillance proposal consultation document August 2016