Clinical Topic A-Z Clinical Speciality

Ectopic pregnancy

Ectopic pregnancy
D011271Pregnancy, Ectopic
PregnancyWomen's health
2013-07-01Last revised in July 2013

Ectopic pregnancy - Summary

An ectopic pregnancy develops outside the uterine cavity with most occurring in the fallopian tubes. Damaged fallopian tubes predispose a woman to ectopic pregnancy.

There are about 11,800 ectopic pregnancies in the UK each year, with an ectopic pregnancy occurring in about 11 in 1000 pregnancies.

Complications of ectopic pregnancy include:

Tubal rupture with intra-abdominal bleeding and hemodynamic instability, that may (rarely) cause maternal death.

Infertility.

Grief, anxiety, or depression.

Typically an ectopic pregnancy presents between 6 and 14 weeks gestation with features that include:

Amenorrhoea.

Abdominal or pelvic pain.

Vaginal bleeding.

Hemodynamic instability, abdominal tenderness, cervical motion tenderness, or pelvic tenderness.

If a woman is hemodynamically stable a urine pregnancy test should be arranged (if not already done) and if pregnancy is confirmed an abdominal examination undertaken.

Ectopic pregnancy should be strongly suspected if there is any abdominal pain and tenderness and immediate admission to early pregnancy assessment unit (EPAU) or out-of-hours gynaecology service arranged.

If there is NO abdominal pain and tenderness a limited pelvic examination should be carried out, without attempting to palpate for an adnexal mass which risks rupturing an ectopic pregnancy if present.

Strongly suspect ectopic pregnancy if there is any pelvic or cervical motion tenderness and arrange immediate admission to an early pregnancy assessment unit (EPAU) or out-of-hours gynaecology service.

If there is NO abdominal pain and tenderness, pelvic tenderness or cervical motion tenderness and they are more than 6 weeks pregnant (or of uncertain gestation) admission should be arranged to an early pregnancy assessment unit (EPAU) or out-of-hours gynaecology service, to determine the cause of symptoms. The urgency of the referral should depend on the clinical situation.

For women who are less than 6 weeks gestation who are bleeding but not in pain the National Institute for Health and Care Excellence (NICE) recommends:

Referring to an EPAU only if bleeding continues after 6 weeks of gestation, or they develop symptoms of an ectopic pregnancy.

If bleeding settles before 6 weeks of gestation, repeating a pregnancy test after 7-10 days to determine if they have had a miscarriage.

Arranging follow up to manage any changes in the clinical situation appropriately.

Possible secondary care treatments for ectopic pregnancy include surgical or medical management and rarely watchful waiting.

Following an ectopic pregnancy arrangements for routine antenatal care should be cancelled and the woman’s psychological well-being assessed and counselling offered if appropriate.

Have I got the right topic?

156months3060monthsFemale

This CKS topic is based on a guideline issued by the National Institute for Health and Care Excellence Ectopic pregnancy and miscarriage: Diagnosis and initial management in early pregnancy of ectopic pregnancy and miscarriage. This CKS topic provides a practical, evidence-based scheme for the assessment and management of a woman presenting with symptoms and signs of a possible ectopic pregnancy. Brief information is also provided about management following referral to secondary care.

There are separate CKS topics on Amenorrhoea, Miscarriage, and Pelvic inflammatory disease.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in July 2013

July 2013 — revised. A literature search was conducted in June 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. Changes have been made regarding the assessment of a woman presenting with symptoms and signs of an early pregnancy complication and the recommended urgency of referral to secondary care for assessment and management. These changes reflect the guidance published by the National Institute for Health and Care Excellence Ectopic pregnancy and miscarriage: Diagnosis and initial management in early pregnancy of ectopic pregnancy and miscarriage.

Previous changes

October 2009 to February 2010 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

Update

New evidence

Evidence-based guidelines

No new evidence-base guidelines since 1 June 2013.

HTAs (Health Technology Assessments)

No new HTAs since 1 June 2013.

Economic appraisals

No new economic appraisals relevant to England since 1 June 2013.

Systematic reviews and meta-analyses

No new systematic review or meta-analysis since 1 June 2013.

Primary evidence

No new randomized controlled trials published in the major journals since 1 June 2013.

New policies

No new national policies or guidelines since 1 June 2013.

New safety alerts

No new safety alerts since 1 June 2013.

Changes in product availability

No changes in product availability since 1 June 2013.

Goals and outcome measures

Goals

To recognize the condition at an early stage

To refer appropriately to secondary care or other specialist services

To provide appropriate advice

Background information

Definition

What is it?

An ectopic pregnancy is a pregnancy outside the uterine cavity [Seeber and Barnhart, 2008].

Most ectopic pregnancies are tubal (98%); most of the remainder occur either in the abdomen, the ovary, the cervix, or in a Caesarean section scar [Seeber and Barnhart, 2008; Barnhart, 2009].

A heterotopic pregnancy is the combination of both an intrauterine pregnancy and an extrauterine pregnancy [Seeber and Barnhart, 2008].

Causes

What causes it?

Ectopic pregnancy is often associated with risk factors that lead to tubal epithelial damage [Seeber and Barnhart, 2008].

Damage to the fallopian tube impairs its ability to transport gametes (the sperm or the egg) or embryos, and predisposes the woman to faulty implantation of the fertilized ovum.

Prevalence

How common is it?

There are about 11,800 ectopic pregnancies in the UK each year, with an ectopic pregnancy occurring in about 11 in 1000 pregnancies [CMACE, 2011]. Ectopic pregnancy is more common following assisted reproduction when the incidence is about 4% [Tay et al, 2000; Seeber and Barnhart, 2008].

A heterotopic pregnancy (when both an intrauterine and an ectopic pregnancy are present) occurs in about 1 in 4000 pregnancies. After in vitro fertilization, however, the incidence is about 1 in 100 pregnancies [Barnhart, 2009].

In northern Europe, the incidence of ectopic pregnancy increased from 11.2 to 18.8 per 1000 pregnancies between 1976 and 1993 [Tay et al, 2000]. The incidence increased six-fold in the US between 1970 and 1992, but has remained stable since [Barnhart, 2009]. This increase may in part be due to [Seeber and Barnhart, 2008]:

Earlier and more accurate diagnosis.

Increased incidence of sexually transmitted infections.

Earlier diagnosis of pelvic inflammatory disease, leading to tubal damage rather than complete blockage.

The use of assisted reproductive techniques, which are associated with a higher ectopic pregnancy rate.

Risk factors

What are the risk factors?

Factors strongly associated with risk of ectopic pregnancy include:

Previous ectopic pregnancy.

Damage to fallopian tubes from previous pelvic inflammatory disease.

Damage to fallopian tubes from tubal surgery:

Sterilization — although rare, if a pregnancy does occur there is a 15% risk that it will be ectopic.

Reversal of sterilization.

Tubal reconstruction and repair.

Current use of a copper intrauterine device or levonorgestrel-releasing intrauterine system (LNG-IUS). Although very effective in preventing pregnancy (including ectopic pregnancy), if a pregnancy does occur there is a high risk that it will be ectopic, especially if the woman has an LNG-IUS in situ.

Known tubal infertility.

Assisted reproduction techniques, especially in vitro fertilization.

Minor risk factors include:

Cigarette smoking.

Being older than 35 years of age.

Having multiple sexual partners.

[Mol et al, 1995; Xiong et al, 1995; Ankum et al, 1996; Bouyer et al, 2000; Seeber and Barnhart, 2008; Barnhart, 2009]

Complications

What are the complications?

Tubal rupture with intra-abdominal bleeding and shock. The time of rupture depends on the site of implantation and usually occurs after 6 weeks [Potdar and Konje, 2011]. There have been occasional case reports of ectopic pregnancies in the mid trimester and even later [Onuigbo, 1976; Klas and Gravett, 1990; Yoong et al, 2004].

Tubal infertility. About 40% of women who have had an ectopic pregnancy are unable to have a subsequent spontaneous intrauterine pregnancy [Barnhart, 2009].

Grief, anxiety, or depression are experienced by many women following pregnancy loss [Brier, 1999; Brier, 2004; Brier, 2008; National Collaborating Centre for Women's and Children's Health, 2012].

Prognosis

What is the prognosis?

If untreated

Spontaneous tubal abortion occurs in about 50% of ectopic pregnancies and the woman may have no symptoms. Some spontaneous tubal abortions may bleed, but the bleeding is self-limited [Seeber and Barnhart, 2008].

Risk of maternal death

Death due to an ectopic pregnancy is rare:

In the UK there were a total of 10 maternal deaths in the 3-year period 2006–2008 [CMACE, 2011].

The death rate for this period was 0.26 per 100,000 pregnancies that progressed to at least 24 weeks' gestation [CMACE, 2011].

Risk of recurrence

The risk of ectopic pregnancy occurring again is 8–14% [Seeber and Barnhart, 2008], but rises to 25% in women with two or more previous ectopic pregnancies [Barnhart, 2009].

When to suspect

When to suspect ectopic pregnancy

When to suspect an ectopic pregnancy

When should I suspect an ectopic pregnancy?

Suspect ectopic pregnancy in women who are pregnant, or with symptoms of pregnancy (amenorrhoea, missed period, breast tenderness), presenting with any of the following:

Common symptoms:

Abdominal or pelvic pain.

Vaginal bleeding with or without clots.

Less common symptoms:

Gastrointestinal symptoms.

Dizziness, fainting or syncope.

Shoulder tip pain.

Urinary symptoms.

Passage of tissue.

Rectal pressure or pain on defecation.

If any of these symptoms are present confirm pregnancy with a pregnancy test (if not already done) and examine the woman for signs of an ectopic pregnancy. For further information see primary care management of suspected ectopic pregnancy.

Basis for recommendation

Basis for recommendation

Non-specific presentation

The Guideline Development Group (GDG) from the National Institute for Health and Care Excellence (NICE) in the guideline Ectopic pregnancy and miscarriage recognized that women who have an ectopic pregnancy may present with a wide variety of non-specific symptoms and NICE recommends that health professionals should always consider the possibility of an ectopic pregnancy in women of reproductive age, and think about offering a pregnancy test even when symptoms are non-specific [National Collaborating Centre for Women's and Children's Health, 2012].

Symptoms suggesting ectopic pregnancy

These recommendations are based on moderate and low quality evidence from 29 studies (24 retrospective case series, four prospective observational studies, and one case control study) reviewed by the GDG of NICE [National Collaborating Centre for Women's and Children's Health, 2012]. In these studies:

Most women presented with:

Abdominal or pelvic pain (93%, 21 studies).

Amenorrhoea (73%, 11 studies).

Vaginal bleeding (64%, 25 studies).

Less common symptoms included:

In 20-30% of women, included breast tenderness (three studies, low quality), gastro-intestinal symptoms (10 studies), dizziness, fainting, or syncope (12 studies).

In 10-20% of women, included shoulder tip pain (seven studies), and urinary symptoms (three studies, low quality).

In less than 10% of women included passage of tissue (two studies), and rectal pressure or pain on defecation (three studies, low quality).

Differential diagnosis

What else might cause pain or bleeding in early pregnancy?

Pregnancy-related bleeding in the first and second trimesters may also occur with:

Threatened miscarriage which presents with vaginal bleeding in the first 24 weeks of pregnancy.

Bleeding is typically scanty, varying from a brownish discharge to bright red bleeding, and may recur over several days.

Midline cramping pain or lower backache, when it occurs, usually develops after the onset of bleeding.

Tenderness may be present on abdominal or pelvic examination. If present, ectopic pregnancy must be excluded.

The internal cervical os is closed.

It may be possible to hear a fetal heartbeat if the pregnancy is viable, but this may be difficult to hear with a Sonicaid before 12–14 weeks' gestation. However identifying a fetal heartbeat does not mean that the pregnancy will be viable. Rarely, a fetal heartbeat may be heard in an ectopic pregnancy; a heartbeat may also be present if there is an heterotopic pregnancy, which is a small but real risk after in vitro fertilization.

Inevitable miscarriage which presents with the same symptoms as threatened miscarriage but on examination the cervical os is found to be open or products of conception are found.

Completed miscarriage which presents with resolving symptoms and signs of a threatened miscarriage and a closed internal cervical os.

Molar pregnancy commonly presents with bleeding in early pregnancy. It is more likely if:

Bleeding is heavy and prolonged.

Symptoms of pregnancy are exaggerated.

The uterus is large for dates.

Vesicles are passed.

Non-pregnancy-related causes of bleeding in early pregnancy to consider include:

Cervicitis, cervical ectropion, or cervical polyps.

Vaginitis.

Cancer of the cervix, vagina, or vulva.

Trauma of the cervix, vagina, or vulva.

Haemorrhoids.

Urethral bleeding.

Pregnancy-related causes of abdominal pain in the first and second trimesters may also occur with:

Miscarriage.

Ruptured ovarian corpus luteal cyst.

Pregnancy-related degeneration of a fibroid.

Non-pregnancy-related causes of abdominal pain include:

Musculoskeletal pain.

Urinary tract infection.

Constipation.

Irritable bowel syndrome.

Pelvic inflammatory disease.

Appendicitis.

Renal colic.

Bowel obstruction.

Adhesions.

Ovarian cyst (due to torsion, rupture, or bleeding).

Torsion of a fibroid.

Pelvic vein thrombosis.

Basis for recommendation

Basis for recommendation

This information has been compiled from a number of textbooks [Porter et al, 2008; Clutterbuck, 2009; Latthe and Khan, 2009; Owen, 2009; Savage, 2009].

Management

Management

Scenario: Suspected ectopic pregnancy : covers the management of suspected ectopic pregnancy including a brief summary of management in secondary care.

Scenario: Review following an ectopic pregnancy : covers the management of women after an ectopic pregnancy, including psychological support and advice about contraception.

Scenario: Suspected ectopic pregnancy

Scenario: Suspected ectopic pregnancy

156months3060monthsFemale

Primary care management

How should I manage someone with suspected ectopic pregnancy?

For women with bleeding or any other symptoms of an early pregnancy complication:

Assess blood pressure and pulse.

For women who are not haemodynamically stable:

Arrange immediate ambulance transfer to hospital without undertaking a pelvic examination.

Resuscitate with intravenous fluids, if available.

For women who are haemodynamically stable arrange a urine pregnancy test (if not already done) and if pregnancy is confirmed:

Undertake an abdominal examination:

Strongly suspect ectopic pregnancy if there is any abdominal pain and tenderness and arrange immediate admission to early pregnancy assessment unit (EPAU) or out-of-hours gynaecology service .

If there is NO abdominal pain and tenderness, undertake a pelvic examination for pelvic or cervical motion tenderness without palpating for adnexal masses which risks rupturing an ectopic pregnancy if present.

Strongly suspect ectopic pregnancy if there is any pelvic or cervical motion tenderness and arrange immediate admission to an early pregnancy assessment unit (EPAU) or out-of-hours gynaecology service.

If there is NO abdominal pain and tenderness, pelvic tenderness or cervical motion tenderness and they are more than 6 weeks pregnant (or of uncertain gestation) ectopic pregnancy is still possible, although less likely.

Arrange admission to an early pregnancy assessment unit (EPAU) or out-of-hours gynaecology service, to determine the cause of symptoms, the urgency of which should depend on the clinical situation.

For women who are less than 6 weeks gestation who are bleeding but not in pain:

The National Institute for Health and Care Excellence (NICE) recommends:

Referring to an EPAU only if bleeding continues after 6 weeks of gestation, or they develop symptoms of an ectopic pregnancy.

If bleeding settles before 6 weeks of gestation, repeat a pregnancy test after 7-10 days to determine if they have had a miscarriage.

Arrange follow up to manage any changes in the clinical situation appropriately.

CKS recognises that the uncertainty caused by bleeding in early pregnancy can be very distressing and referral to an EPAU may be seen as a way of managing this uncertainty. However, before referring a woman who is less than 6 weeks pregnant with a suspected miscarriage consider the following:

The criteria recommended by the Royal College of Obstetricians and Gynaecologists for diagnosing miscarriage in early pregnancy were changed in 2011 in response to evidence that the previous criteria could lead to misdiagnosis. The changes mean that for most pregnancies of less than 6 weeks, miscarriage cannot be diagnosed with certainty.

NICE recommend that before referring a women to an EPAU she should be informed of the limitations of ultrasound in making a diagnosis. When a diagnosis cannot be made, investigations may need to be repeated after an interval of at least 7 days. In some cases further scans will be needed before a diagnosis can be made with any certainty.

For women with light bleeding in early pregnancy, the risk of miscarriage is not significantly different compared to women who are not bleeding.

Symptoms suggestive of an early pregnancy complication

Symptoms suggestive of an early pregnancy complication

Symptoms suggestive of an early pregnancy complication include:

Abdominal or pelvic pain.

Vaginal bleeding with or without clots.

Dizziness, fainting, or syncope.

Shoulder tip pain.

Passage of tissue.

Rectal pressure or pain on defecation.

[National Collaborating Centre for Women's and Children's Health, 2012]

Basis for recommendation

Basis for recommendation

Immediate admission to hospital for women who are haemodynamically unstable

The Guideline Development Group (GDG) of the National Institute for Health and Care Excellence (NICE) in the guideline Ectopic pregnancy and miscarriage recommends immediate admission to hospital for women who are haemodynamically unstable based on accepted good clinical practice [National Collaborating Centre for Women's and Children's Health, 2012].

Arranging a pregnancy test for women who are haemodynamically stable

This recommendation is based on the opinion of the NICE GDG who agreed that clinicians should consider doing a pregnancy test in women of reproductive age who present with non-specific symptoms. They advise continuing to assess the woman for an ectopic pregnancy or miscarriage only if the pregnancy test is positive [National Collaborating Centre for Women's and Children's Health, 2012].

All the CKS expert reviewers were of the opinion that if a urinary pregnancy test is negative, then an ectopic pregnancy is virtually ruled out. Several pointed out the rare possibility of a false-negative pregnancy test result and advised a repeat urine pregnancy test or serum human chorionic gonadotropin (hCG) measurement as a possibility. It was emphasized that the result needed to be considered with the clinical findings, and if discordant an urgent assessment should be arranged.

Advice not to examine for an adnexal mass

This recommendation is based on the expert opinion of the NICE GDG that palpation may increase the risk of an ectopic pregnancy rupturing [National Collaborating Centre for Women's and Children's Health, 2012].

Immediate referral for women who are haemodynamically stable with signs that are strongly suggestive of ectopic pregnancy

The NICE GDG in the guideline Ectopic pregnancy and miscarriage recommends immediate referral for women who are haemodynamically stable but with features that are strongly suggestive of ectopic pregnancy based on accepted good clinical practice [National Collaborating Centre for Women's and Children's Health, 2012].

Features that are strongly suggestive of ectopic pregnancy are based on moderate and low quality evidence from 29 studies (24 retrospective case series, four prospective observational studies, and one case control study) reviewed by the GDG of NICE that showed that [National Collaborating Centre for Women's and Children's Health, 2012]:

Most women with an ectopic pregnancy had at least one of the following:

Pelvic tenderness (91%, one study); adnexal tenderness (82%, seven studies); abdominal tenderness (78%, 11 studies).

Other important but less common signs:

In 40–75% of women included: cervical motion tenderness (eight studies); rebound tenderness or peritoneal signs (nine studies).

In 20–40% of women included abdominal distension (two studies, low quality); an enlarged uterus (six studies); an adnexal mass (nine studies); tachycardia or hypotension (five studies, low quality).

In less than 20% of women included a palpable pelvic mass (two studies); collapsed or in shock (eight studies), or orthostatic hypotension (three studies).

Referral of women who are more than 6 weeks pregnant, who have symptoms of an early pregnancy complication but no signs strongly suggestive of an ectopic pregnancy

These recommendations are based on moderate and low quality evidence from 29 studies (see above) that found that although most women with an ectopic pregnancy have abdominal pain and tenderness or pelvic or cervical motion tenderness, some women do not. Therefore, although the risk of ectopic pregnancy in these women is low, and miscarriage more likely, further investigations are required to establish the diagnosis with certainty [National Collaborating Centre for Women's and Children's Health, 2012].

Expectant management for women who are less than 6 weeks pregnant with bleeding but no pain

The recommendations for women who are less than 6 weeks pregnant are based on evidence reviewed by the GDG of NICE that demonstrates that [National Collaborating Centre for Women's and Children's Health, 2012]:

An ultrasound scan will not be able to give useful information about viability at a gestation of less than 6 weeks.

Many women have spotting in early pregnancy that resolves without needing intervention.

Checking a pregnancy test will determine if the pregnancy has miscarried.

Diagnosis in secondary care

How is a diagnosis made in secondary care?

If an ectopic pregnancy is suspected a trans-vaginal ultrasound scan (or abdominal ultrasound scan if a trans-vaginal ultrasound scan is unacceptable) is undertaken to determine if the pregnancy is:

An intrauterine pregnancy.

A definite or probable ectopic pregnancy.

A molar pregnancy.

A pregnancy of unknown location.

This is diagnosed if no pregnancy (intrauterine or ectopic) is visible on the trans-vaginal scan but the pregnancy test is positive. Serial serum human chorionic gonadotropin (hCG) levels, repeat trans-vaginal scans, and laparoscopy may be used to distinguish between miscarriage, intrauterine pregnancy, ectopic pregnancy and molar pregnancy.

Basis for recommendation

Basis for recommendation

The information about secondary care diagnosis has been taken from the guideline Ectopic pregnancy and miscarriage published by the National Institute for Health and Care Excellence [National Collaborating Centre for Women's and Children's Health, 2012].

Treatments in secondary care

What treatments are available in secondary care?

For women who are haemodynamically stable, the treatment options are surgical, medical, or (rarely) expectant management. The options offered to an individual woman will depend upon the serum human chorionic gonadotropin (hCG) level, the size of the adnexal mass, the amount of pain that the woman has, and the acceptability of the method of treatment to the woman. All women (except those who have had a salpingectomy) will be followed up according to local protocols to ensure that serum hCG levels decrease at an acceptable rate until non-pregnant levels are reached (this may take up to 6 weeks).

Surgical management: laparoscopic surgery may involve removing the fallopian tube with the pregnancy (hysterotomy) or an incision into the fallopian tube to remove the pregnancy (hysterostomy). After hysterostomy, serial serum hCG measurements are carried out to identify women who have persistent trophoblastic tissue in the fallopian tube.

Medical management: methotrexate is the most commonly used medical intervention. Some women may require repeat treatment with methotrexate or surgical intervention if the initial dose does not successfully terminate the pregnancy. It may be difficult to distinguish pain due to tubal rupture (which occurs in a few women after methotrexate treatment) from pain due to tubal abortion, and some women will need to be admitted for observation and further investigations.

Expectant management (watchful waiting): expectant management is an option for a few women including those who have a pregnancy of unknown location who have minimal or no symptoms who are clinically stable. Active intervention will be considered if symptoms of ectopic pregnancy occur or levels of serum hCG fail to decrease at an acceptable rate.

Rhesus-negative women who have had a surgical procedure to manage an ectopic pregnancy are given anti-D immunoglobulin. Anti-D rhesus prophylaxis is not required for women treated with methotrexate or other medical treatments alone or for women with a pregnancy of unknown location.

Basis for recommendation

Basis for recommendation

These recommendations are based on information in the Royal College of Obstetricians and Gynaecologists guideline The management of tubal pregnancy [RCOG, 2004], and the National Institute of Health and Clinical Excellence guideline Ectopic pregnancy and miscarriage [National Collaborating Centre for Women's and Children's Health, 2012].

Scenario: Review following an ectopic pregnancy

Scenario: Review following an ectopic pregnancy

156months3060monthsFemale

Follow up

What follow up should I offer following an ectopic pregnancy?

Ensure that arrangements for routine antenatal care are cancelled if they have been started.

Give the woman the opportunity to discuss any questions she has about the ectopic pregnancy, the risk of recurrence, and her future fertility. About 60% of women who have had an ectopic pregnancy are able to have a subsequent spontaneous intrauterine pregnancy.

Assess her psychological well-being and offer counselling if appropriate. Be aware that:

Grief, anxiety, and depression are common following pregnancy loss.

Grief following pregnancy loss is comparable in nature, intensity, and duration to grief reactions in people suffering other types of major loss.

Distress is commonly at its worst 4–6 weeks after pregnancy loss and may last 6–12 months.

Advise the woman that she should inform her GP as soon a possible about future pregnancies so that an ultrasound scan can be arranged at 6–7 weeks to establish the location and viability of the pregnancy.

Inform the woman about the availability of advice, information, and support for those who have had an ectopic pregnancy from the Ectopic Pregnancy Trust.

Patient information leaflets are available from:

The Miscarriage Association:

Ectopic Pregnancy (pdf)

Why me? (pdf)

The Royal College of Obstetricians and Gynaecologists:

Ectopic pregnancy (pdf)

Basis for recommendation

Basis for recommendation

Cancellation of routine antenatal care

This recommendation is pragmatic and based on accepted good clinical practice.

Assessing how the woman is coping with the pregnancy loss

Recommendations to assess for psychological distress following ectopic pregnancy are based on:

Expert opinion that the psychological effect of an ectopic pregnancy is often overlooked, as an ectopic pregnancy may not be viewed in the same way as other pregnancy loss [Tay et al, 2000].

Expert opinion that women who have had an ectopic pregnancy may have a similar grief reaction to women experiencing miscarriage, but also have the added stress of a potential reduction in fertility [Tay et al, 2000].

Extrapolated evidence on the prevalence and severity of psychological distress following miscarriage [Brier, 1999; Brier, 2004; Brier, 2008].

Future fertility

Figures regarding the future intrauterine pregnancy rate were obtained from a non-systematic review [Barnhart, 2009]. Limited evidence from a Cochrane systematic review (the trials were of poor methodological quality) suggests that the spontaneous intrauterine pregnancy rate is similar following salpingotomy or methotrexate therapy [Hajenius et al, 2007]. For further information on the management of infertility, see the CKS topic on Infertility.

Management in future pregnancies

All CKS expert reviewers recommended early assessment in future pregnancies.

Provision of easily accessible information

This recommendation is based on the expert opinion of the GDG of NICE who felt that it was important that women should be able to access information easily [National Collaborating Centre for Women's and Children's Health, 2012].

Contraceptive advice

What advice should I give about contraception?

Advise women that a history of ectopic pregnancy is not a contraindication to any form of hormonal contraception or intrauterine device.

Informed her that the risk of pregnancy with an intrauterine device or the levonorgestrel-releasing intrauterine system (LNG-IUS) is small. However, if she does conceive, the risk of ectopic pregnancy is high; particularly if she has an LNG-IUS in situ.

Reliable contraception should be used for at least 3 months following treatment with methotrexate for an ectopic pregnancy, as there is a possible teratogenic risk due to the prolonged effects of methotrexate.

Basis for recommendation

Basis for recommendation

No form of future contraception is contraindicated

These recommendations are based on expert opinion in the UK Medical Eligibility Criteria (UKMEC) for contraceptive use [FSRH, 2009], and a guideline from the Faculty of Sexual and Reproductive Healthcare [FSRH, 2007].

Risk of a further ectopic pregnancy if an intrauterine (IUD) device is used

This information is based on expert opinion in a text book [Guillebaud, 2003], and evidence from a meta-analysis [Xiong et al, 1995].

A copper IUD reduces the frequency of both extrauterine and intrauterine pregnancies but is more effective at preventing intrauterine compared with extrauterine pregnancies [Guillebaud, 2003].

Very few sperm are able to pass through the copper-containing uterine cavity to reach an egg and implant into a damaged tube, but the conceptus has even less chance of implanting in the uterus. Therefore, although the ratio of ectopic pregnancies to uterine pregnancies is increased in women with a copper IUD, the overall incidence of ectopic pregnancy is very low, and is estimated at 0.12 per 100 women-years [Guillebaud, 2003].

A meta-analysis of 16 case control studies carried out between 1977 and 1994 investigated the relationship between intrauterine device (IUD) use and ectopic pregnancy [Xiong et al, 1995].

After adjusting for confounding factors, women with an ectopic pregnancy were about six times more likely to have an IUD in situ than age-matched pregnant controls (OR 6.29, 95% CI 4.23–9.34). The authors concluded that a pregnancy with an IUD in situ is more often an ectopic pregnancy than a pregnancy without an IUD in situ.

Detailed information about the type of IUD was not available in most of the studies. Many of the studies used older types of non-medicated IUDs (such as the Dalkon Shield and the Lippes loop); only six studies looked at copper IUDs. As copper IUDs are more effective in preventing pregnancy, it is likely that the ectopic pregnancy rate associated with IUD use is now less than reported in this study.

Risk of a further ectopic pregnancy if the levonorgestrel-releasing intrauterine system (LNG-IUS) is used

The risk of an ectopic pregnancy seems to be particularly high if the woman has an LNG-IUS in situ. This information is based on evidence from a study that looked at outcomes in women using the LNG-IUS [Backman et al, 2004]. A questionnaire sent to 17,360 women using the LNG-IUS identified 132 pregnancies. Review of the hospital records concerning the pregnancies of 108 of these women found that 40 pregnancies had occurred with an LNG-IUS in situ. Fifteen pregnancies were intrauterine and 25 were ectopic. Therefore if a pregnancy does occur in a woman with an LNG-IUS in situ, it is very likely to be ectopic.

The manufacturer's summary of product characteristics states that the absolute rate of ectopic pregnancy for women with an LNG-IUS is estimated to be 0.1% per year [ABPI Medicines Compendium, 2013].

Teratogenic risk with methotrexate

Expert opinion in the guideline The management of tubal pregnancy published by the Royal College of Obstetricians and Gynaecologists [RCOG, 2004], and the British National Formulary [BNF 65, 2013] states that reliable contraception should be used for at least 3 months after treatment with methotrexate because of a possible teratogenic risk. The manufacturer's summary of product characteristics recommends that conception should be avoided for at least 6 months after methotrexate administration [ABPI Medicines Compendium, 2009].

Evidence

Evidence

Supporting evidence

Evidence for when to suspect ectopic pregnancy in primary care has been summarized within the Basis For Recommendations.

CKS does not summarize evidence for secondary care interventions and therefore, the evidence for the management of women with proven ectopic pregnancy has not been summarized here. However, this information is available in guideline issued by the National Institute for Health and Care Excellence Ectopic pregnancy and miscarriage: Diagnosis and initial management in early pregnancy of ectopic pregnancy and miscarriage [National Collaborating Centre for Women's and Children's Health, 2012].

Search strategy

Scope of search

A full literature search was not requested/required as this CKS topic is primarily based on the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: Diagnosis and initial management in early pregnancy of ectopic pregnancy and miscarriage [National Collaborating Centre for Women's and Children's Health, 2012].

Search dates

February 2012 - June 2013

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.

exp Pregnancy, Ectopic/, ectopic preg$.tw, tubal preg$.tw.

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSh subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

Royal College of Nursing

NICE Evidence

Health Protection Agency

World Health Organization

National Guidelines Clearinghouse

Guidelines International Network

TRIP database

GAIN

NHS Scotland National Patient Pathways

New Zealand Guidelines Group

Agency for Healthcare Research and Quality

Institute for Clinical Systems Improvement

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

British Columbia Medical Association

Canadian Medical Association

Alberta Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Singapore Ministry of Health

National Resource for Infection Control

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Driver and Vehicle Licensing Agency

NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Drug & Therapeutics Bulletin

TRIP database

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Patient experiences

Healthtalkonline

BMJ - Patient Journeys

Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

References

ABPI Medicines Compendium (2009) Summary of product characteristics for Methotrexate 100 mg/ml injection (Hospira UK Ltd). Electronic Medicines Compendium..Datapharm Communications Ltd.www.medicines.org.uk [Free Full-text]

ABPI Medicines Compendium (2013) Summary of product characteristics for Mirena. Electronic Medicines Compendium..Datapharm Communications Ltd.www.medicines.org.uk [Free Full-text]

Ankum, W.M., Mol, B.W., Van der Veen, F. and Bossuyt, P.M. (1996) Risk factors for ectopic pregnancy: a meta-analysis. Fertility and Sterility 65(6), 1093-1099. [Abstract]

Backman, T., Rauramo, I., Huhtala, S. and Koskenvuo, M. (2004) Pregnancy during the use of levonorgestrel intrauterine system. American Journal of Obstetrics and Gynecology 190(1), 50-54. [Abstract]

Barnhart, K.T. (2009) Clinical practice. Ectopic pregnancy. New England Journal of Medicine 361(4), 379-387.

BNF 65 (2013) British National Formulary. 65th edn. London: British Medical Association and Royal Pharmaceutical Society of Great Britain.

Bouyer, J., Rachou, E., Germain, E. et al. (2000) Risk factors for extrauterine pregnancy in women using an intrauterine device. Fertility & Sterility 74(5), 899-908. [Abstract]

Brier, N. (1999) Understanding and managing the emotional reactions to a miscarriage. Obstetrics & Gynaecology 93(1), 151-155. [Abstract]

Brier, N. (2004) Anxiety after miscarriage: A review of the empirical literature and implications for clinical practice. Birth 31(2), 138-142. [Abstract]

Brier, N. (2008) Grief following miscarriage: a comprehensive review of the literature. Journal of Women's Health 17(3), 451-464. [Abstract]

Clutterbuck, D. (2009) Female genital infections. In: Magowan, B.A., Owen, P. and Drife, J. (Eds.) Clinical obstetrics and gynaecology. 2nd edn. Edinburgh: Saunders Elsevier. 121-134.

CMACE (2011) Saving mothers' lives. Reviewing maternal deaths to make motherhood safer: 2006-2008. BJOG 118(S1), 1-203. [Abstract] [Free Full-text]

FSRH (2007) FSRH guidance (November 2007): intrauterine contraception. ..Faculty of Sexual & Reproductive Healthcare.www.fsrh.org [Free Full-text]

FSRH (2009) UK medical eligibility criteria for contraceptive use. ..Faculty of Sexual and Reproductive Healthcare.www.fsrh.org [Free Full-text]

Guillebaud, J. (2003) Contraception. In: Waller, D. and McPherson, A. (Eds.) Women's health. 5th edn. Oxford: Oxford University Press. 201-203.

Hajenius, P.J., Mol, F., Mol, B.W. et al. (2007) Interventions for tubal ectopic pregnancy (Cochrane Review). The Cochrane Library.Issue.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]

Klas, W.A. and Gravett, M.G. (1990) Midtrimester tubal pregnancy with markedly elevated maternal serum alpha-fetoprotein. A case report. Journal of Reproductive Medicine 35(9), 915-916. [Abstract]

Latthe, P. and Khan, K.S. (2009) Pelvic pain and ectopic pregnancy. In: Magowan, B.A., Owen, P. and Drife, J. (Eds.) Clinical obstetrics and gynaecology. 2nd edn. Edinburgh: Saunders Elsevier. 143-149.

Mol, B.W., Ankum, W.M., Bossuyt, P.M. and van, der, V (1995) Contraception and the risk of ectopic pregnancy: a meta-analysis. Contraception 52(6), 337-341. [Abstract]

National Collaborating Centre for Women's and Children's Health (2012) Ectopic pregnancy and miscarriage. Diagnosis and initial management in early pregnancy of ectopic pregnancy and miscarriage (full NICE guideline). Clinical guideline 154..National Institute for Health and Care Excellence.www.nice.org.uk [Free Full-text]

Onuigbo, W.I. (1976) Tubal pregnancy in Nigerian Igbos. International Journal of Fertility 21(3), 186-188. [Abstract]

Owen, P. (2009) Miscarriage. In: Magowan, B.A., Owen, P. and Drife, J. (Eds.) Clinical obstetrics and gynaecology. 2nd edn. Edinburgh: Saunders Elsevier. 97-102.

Porter, T.F., Branch, D.W. and Scott, J.R. (2008) Early pregnancy loss. In: Gibbs, R.S., Karlan, B.Y., Haney, A.F. and Nygaard, I. (Eds.) Danforth's Obstetrics and Gynecology. 10th edn. Philadelphia: Lippincott Williams & Wilkins. 60-70.

Potdar, N. and Konje, J.C. (2011) Ectopic pregnancy. In: Shaw, R.W., Luesley, D. and Monga, A. (Eds.) Gynaecology. 4th edn. Edinburgh: Churchill Livingstone. 363-381.

RCOG (2004) The management of tubal pregnancy. ..Royal College of Obstetrics and Gynaecologists.www.rcog.org.uk [Free Full-text]

Savage, P. (2009) Gestational trophoblastic disease. In: Magowan, B.A., Owen, P. and Drife, J. (Eds.) Clinical obstetrics and gynaecology. 2nd edn. Edinburgh: Saunders Elsevier. 212-216.

Seeber, B.E. and Barnhart, K.T. (2008) Ectopic pregnancy. In: Gibbs, R.S., Karlan, B.Y., Haney, A.F. and Nygaard, I.E. (Eds.) Danforth's obstetrics and gynecology. 10th edn. Philidelphia: Lippincott Williams & Wilkins. 71-87.

Tay, J.I., Moore, J. and Walker, J.J. (2000) Ectopic pregnancy. British Medical Journal 320(7239), 916-919. [Free Full-text]

Xiong, X., Buekens, P. and Wollast, E. (1995) IUD use and the risk of ectopic pregnancy: a meta-analysis of case-control studies. Contraception 52(1), 23-34. [Abstract]

Yoong, W., Shakya, R. and Hersson-Ringskog, J. (2004) Late presentation of tubal pregnancy: two cautionary tales. Journal of Obstetrics and Gynaecology 24(6), 706-707.