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Pregnancy Women's health

Ectopic pregnancy

Last revised in June 2026

An ectopic pregnancy develops outside the uterine cavity with most occurring in the fallopian tubes.

Ectopic pregnancy: Summary

  • An ectopic pregnancy is a fertilised ovum implanting and maturing outside the uterine cavity.
  • Most ectopic pregnancies (97%) implant in the fallopian tube. The others are non-tubal and may implant in the ovary, abdomen, cervix, caesarean section scar, interstitial part of the fallopian tube, or the cornua of a unicornuate or bicornuate uterus.
  • There are about 12,000 ectopic pregnancies in the UK each year, with an ectopic pregnancy occurring in about 11 in 1000 pregnancies.
  • Risk factors include tubal damage, maternal age over 35 years, and smoking. However, there are no identifiable risk factors in about a third of cases.
  • Complications include:
    • Tubal rupture (which may lead to maternal death, if treatment is delayed).
    • Recurrent ectopic pregnancy.
    • Adverse effects of treatment. 
    • Grief, anxiety, or depression.
  • The clinical features of an ectopic pregnancy may be atypical and can resemble those of other more common conditions, such as urinary tract infections and gastrointestinal conditions.
    • Common symptoms include abdominal or pelvic pain, amenorrhoea or missed period, and vaginal bleeding. Less common symptoms include gastrointestinal symptoms, dizziness, shoulder tip pain, and urinary symptoms.
    • Common signs include pelvic, adnexal, and abdominal tenderness. Less common signs include cervical motion tenderness, pallor, abdominal distension, shock, and hypotension.
  • If a woman presents with symptoms of an ectopic pregnancy:
    • Pregnancy should be confirmed (if not already done).
    • The woman should be examined for signs of an ectopic pregnancy.
  • Immediate hospital admission should be arranged if there are signs of haemodynamic instability or significant concerns about the degree of pain or bleeding.
  • Immediate referral to an early pregnancy assessment service or out-of-hours gynaecology service should be arranged for women with a positive pregnancy test, and the following on examination:
    • Abdominal pain and tenderness.
    • Pelvic tenderness.
    • Cervical motion tenderness.
  • Referral to an early pregnancy assessment service (with urgency depending on clinical judgement) should be arranged for women if they have bleeding or have other symptoms and signs of early pregnancy complications if they also have any of the following: 
    • Pain.
    • A pregnancy of 6 weeks' gestation or more.
    • A pregnancy of uncertain gestation.
  • Expectant management should be used for women with a pregnancy of less than 6 weeks' gestation who are bleeding but not in pain, and who have no risk factors, such as a previous ectopic pregnancy. Advise these women: 
    • To return if bleeding continues or pain develops.
    • To repeat a urine pregnancy test after 7 to 10 days and to return if it is positive.
    • That a negative pregnancy test means that the pregnancy has miscarried.
  • Transvaginal ultrasound is the diagnostic tool of choice for ectopic pregnancy.
  • Secondary care treatments options include expectant management (watchful waiting), medical management (commonly with methotrexate), or surgery.
  • After treatment for an ectopic pregnancy, the woman should be followed up in primary care and offered appropriate support, information, and advice.

Have I got the right topic?

From age 16 years onwards (Female).

This CKS topic is largely based on the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: diagnosis and initial management [NICE, 2021], the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Diagnosis and management of ectopic pregnancy [Elson, 2016], and the British Medical Journal (BMJ) Best Practice guide Ectopic pregnancy [BMJ Best Practice, 2023].

This CKS topic covers the assessment and initial management of a woman presenting with symptoms and signs of a possible ectopic pregnancy.

This CKS topic does not cover in great detail the management of the woman following referral to secondary care or other specialist services but makes recommendations on how the women should be followed up in primary care after treatment for an ectopic pregnancy.

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 healthcare.

How up-to-date is this topic?

Changes

June 2026 — minor update. The section on Follow up after an ectopic pregnancy has been updated in line with NICE's Ectopic pregnancy and miscarriage: diagnosis and initial management.

Previous changes

February 2023 — reviewed. A literature search was conducted in January 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. There have been some minor structural changes to this topic, but no changes to recommendations.

December 2022 — minor update. Information on secondary care management of threatened miscarriage has been removed from this topic and added to the CKS topic on Miscarriage. 

November 2021 — minor update. Added information to provide detail on use of a secondary care advice that vaginal micronised progesterone 400 mg twice daily should be offered to women with an intrauterine pregnancy confirmed by a scan, if they have vaginal bleeding and have previously had a miscarriage. 

May 2018 — minor update. The section on Managing suspected ectopic pregnancy has been clarified, and information on anti-D immunoglobulin for rhesus-negative women who have had surgical removal of an ectopic pregnancy has been included in the section on Follow up after an ectopic pregnancy.

April 2018 — reviewed. A literature search was conducted in February 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of the topic. No changes to clinical recommendations have been made.

July 2013 — revised. A literature search was conducted in June 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of the topic. Based on recommendations in 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, changes have been made regarding the following:

  • Assessment of a woman presenting with symptoms and signs of an early pregnancy complication.
  • The recommended urgency of referral to secondary care or other specialist services for assessment and management.

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-based guidelines since 1 January 2023.

HTAs (Health Technology Assessments)

No new HTAs since 1 January 2023.

Economic appraisals

No new economic appraisals relevant to England since 1 January 2023.

Systematic reviews and meta-analyses

No new systematic review or meta-analysis since 1 January 2023.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 January 2023.

New policies

No new national policies or guidelines since 1 January 2023.

New safety alerts

No new safety alerts since 1 January 2023.

Changes in product availability

No changes in product availability since 1 January 2023.

Goals and outcome measures

Goals

To support primary healthcare professionals to:

  • Promptly recognize the symptoms and signs of a possible ectopic pregnancy.
  • Refer the woman appropriately to secondary care or other specialist services.
  • Follow up the woman after treatment for an ectopic pregnancy.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

Ectopic pregnancy and miscarriage

  • Women, trans men and non-binary people referred to early pregnancy assessment services are seen by the service at least within 24 hours of referral.
  • Women, trans men and non-binary people who are referred with suspected ectopic pregnancy or miscarriage are offered a transvaginal ultrasound scan to identify the location and viability of the pregnancy.
  • Women, trans men and non-binary people with a suspected miscarriage who have had an initial transvaginal ultrasound scan are offered a second assessment to confirm the diagnosis.
  • Women, trans men and non-binary people who are rhesus D (RhD) negative with an ectopic pregnancy or miscarriage up to and including 11+6 weeks of pregnancy are not prescribed anti-D immunoglobulin prophylaxis.

[NICE, 2026]

Background information

What is it?

  • An ectopic pregnancy is a fertilised ovum implanting and maturing outside the uterine cavity [BMJ Best Practice, 2023].
    • Most ectopic pregnancies (97%) occur in the fallopian tube and may implant in the ampulla (73.3%), isthmus (12.5%), or fimbria (11.6%), interstitium and cornua (2.6%).
    • The others are non-tubal and may implant in the [Elson, 2016; BMJ Best Practice, 2023]:
      • Ovary (3.2%).
      • Abdomen (1.3%).
      • Cervix (less than 1%).
      • Caesarean section scar (less than 1%). 
      • Interstitial part of the fallopian tube (within the uterus at the junction of the uterus and the proximal part of the fallopian tube, 1–6.3%). 
      • Cornua (or horn) of a unicornuate or bicornuate uterus (the rarest form with a reported incidence of 1 in 76,000 pregnancies).
  • A heterotopic pregnancy is the coexistence of both an intrauterine pregnancy and an ectopic pregnancy [Elson, 2016; BMJ Best Practice, 2023].

What are the causes and risk factors?

  • Ectopic pregnancy is often associated with risk factors that lead to tubal epithelial damage.
  • About a third of women diagnosed with an ectopic pregnancy have no identifiable risk factor [NICE, 2021]. However, the following factors are associated with an increased risk of ectopic pregnancy [Elson, 2016; ACOG, 2018; Kumar, 2022; BMJ Best Practice, 2023].
    • Previous ectopic pregnancy — the risk of recurrence of ectopic pregnancy is about 18.5%. The risk is 10% if the woman has had one previously, and 25% with two or more previous ectopic pregnancies.
    • History of pelvic inflammatory disease.
    • Previous pelvic surgery (including sterilization [rare], tubal reconstruction surgery, caesarean section).
      • In one long-term multicentre prospective cohort study, the cumulative rate of ectopic pregnancy after tubal sterilisation surgery was 7.3 ectopic pregnancies per 1000 procedures [BMJ Best Practice, 2023].
    • Black ethnicity — black women are at increased risk compared to white women. 
    • History of infertility.
    • Assisted reproduction techniques, especially in vitro fertilization.
    • Cigarette smoking.
    • Salpingitis.
    • Maternal age over 35 years — the rate of ectopic pregnancy is 4.1% in women aged 35 years or over compared to 1.8% in the general population.
    • Maternal in-utero exposure to diethylstilbesterol — prenatal exposure alters fallopian tube development [Seeber and Barnhart, 2008].  
    • Having multiple sexual partners.
    • Intrauterine contraception (IUC) — the overall risk of ectopic pregnancy when using IUC is reduced compared to using no contraception. However, if pregnancy does occur with IUC in situ, the risk of an ectopic pregnancy is increased and in some studies, half of pregnancies that occurred were ectopic [CoSRH, 2019]. 
    • Sterilization — pregnancies following female sterilization are rare, but when they do occur, there is an increased risk of ectopic pregnancy. The incidence of ectopic pregnancy after female sterilization varies depending on the method used to occlude the fallopian tubes [CoSRH, 2014].

How common is it?

  • In the UK, the incidence is approximately 11 in 1000 pregnancies [NICE, 2021], with an estimated 12,000 ectopic pregnancies diagnosed each year [HSIB, 2020].
  • The incidence of ectopic pregnancy reported in women attending early pregnancy units is 2–3% [Elson, 2016].
  • The reported rates of ectopic pregnancy after assisted reproduction vary from 0.8–8.6% [Kirk, 2014; Panelli, 2015; Perkins, 2015; Santos-Ribeiro, 2016], although the incidence has decreased over time due to factors such as extended embryo culture and fewer embryos being transferred [Perkins, 2015; Santos-Ribeiro, 2016].
  • The incidence of heterotopic pregnancy is rising, and is around 1% in women undergoing in vitro fertilization, but is low in the general population (ranging from 1 in 4,000 to 1 in 30,000) [Panelli, 2015; BMJ Best Practice, 2023]. 
  • There have been case reports of ectopic pregnancies occurring in women who have had a hysterectomy (both total and supracervical), but this is extremely rare [BMJ Best Practice, 2023].

What is the prognosis?

  • Prompt diagnosis and management of an ectopic pregnancy are critically important to reduce the risk of complications [Crochet, 2013; NICE, 2021].
    • If undiagnosed and untreated, spontaneous tubal abortion occurs in about 50% of ectopic pregnancies, and the woman may have no symptoms. Bleeding may occur in some cases, but this is usually self-limiting [Seeber and Barnhart, 2008]. 
    • If the ectopic pregnancy persists and remains undiagnosed and untreated, the tube may rupture, causing intra-abdominal bleeding, haemodynamic instability, and maternal death [Crochet, 2013; NICE, 2021; BMJ Best Practice, 2023]. 
  • Following treatment for an ectopic pregnancy:
    • The rate of recurrence is about 18.5% [Elson, 2016].
    • About 64–76% of women are able to have a subsequent spontaneous intrauterine pregnancy [de Bennetot, 2012; Fernandez, 2013].
    • In women with no history of subfertility or tubal pathology, there is no difference in the rate of fertility, the risk of future tubal ectopic pregnancy, or tubal patency rates between the different treatment methods [Elson, 2016].
    • In women with a previous history of subfertility, some treatment methods are associated with a lower rate of subsequent intrauterine pregnancy [Elson, 2016]. 

What are the complications?

  • Complications of ectopic pregnancy include:
    • Maternal death — ectopic pregnancy is the leading cause of maternal death in early pregnancy [Elson, 2016; MBRRACE-UK, 2022].
      • If the ectopic pregnancy persists and remains undiagnosed and untreated, the tube may rupture, causing intra-abdominal bleeding, haemodynamic instability, and maternal death [NICE, 2021]. Spontaneous tubal abortion occurs in about 50% of cases [Seeber and Barnhart, 2008]. 
      • In the UK, about 0.2 per 1000 estimated ectopic pregnancies result in maternal death, two-thirds of which are associated with substandard care.  Women who do not seek medical help readily (such as women who are recent migrants, asylum seekers, refugees, or women who have difficulty reading or speaking English) are particularly vulnerable [NICE, 2021]. 
      • Vulnerable and young women remain disproportionately represented amongst those who have died from ectopic pregnancy [MBRRACE-UK, 2022].
      • Non-tubal ectopic pregnancies (particularly interstitial and cornual ectopic pregnancies) are associated with significantly higher mortality and morbidity than tubal ectopic pregnancies because they are often difficult to diagnose and tend to present late with sudden rupture  [Jurkovic, 2011]. 
    • Recurrent ectopic pregnancy — the rate of recurrence of ectopic pregnancy is about 18.5%. Studies have shown no statistical difference in the rate of recurrence between the different treatment methods for ectopic pregnancy [Elson, 2016].
    • Adverse effects of treatment
      • Surgery – possible damage to surrounding organs after surgical intervention [BMJ Best Practice, 2023].  
      • Medication – adverse effects of methotrexate (for example, hepatotoxicity, nephrotoxicity, myelosuppression, pulmonary toxicity) [BMJ Best Practice, 2023].
    • Psychological effects — grief, anxiety, and depression are experienced by many women after pregnancy loss [Elson, 2016; NICE, 2021]. 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 [Brier, 1999; Tay et al, 2000; Brier, 2004; Brier, 2008]. 

Diagnosis of ectopic pregnancy

When should I suspect an ectopic pregnancy?

Be aware that ectopic pregnancy can present with a wide variety of symptoms and signs which may be atypical and can resemble those of other more common conditions (such as urinary tract infections and gastrointestinal conditions). 

  • Suspect ectopic pregnancy in a woman of child-bearing potential who presents with any of the following:
    • Common symptoms: 
      • Abdominal or pelvic pain.
      • Amenorrhoea or missed period.
      • Vaginal bleeding (with or without clots).
    • Less common symptoms: 
      • Breast tenderness.
      • Gastrointestinal symptoms (such as diarrhoea and/or vomiting). 
      • Dizziness, fainting, or syncope.
      • Shoulder tip pain.
      • Urinary symptoms.
      • Passage of tissue.
      • Rectal pressure or pain on defecation.
  • Be aware that:
    • Symptoms generally appear 6–8 weeks after the last normal menstrual period (or much later for a non-tubal ectopic pregnancy). 
    • Clinical presentation can be highly variable and ranges from no symptoms to cardiovascular collapse.  
  • Common signs of ectopic pregnancy include:
    • Abdominal tenderness.
    • Pelvic tenderness.
    • Adnexal tenderness. 
  • Other signs include:
    • 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).
    • Shock or collapse.
    • Orthostatic hypotension. 
  • Be alert for symptoms and signs of tubal rupture and intra-abdominal bleeding. For example:
    • Vomiting and diarrhoea may be the presenting symptoms of abdominal bleeding. 
    • Shoulder pain may be caused by irritation of the diaphragm due to leakage of blood from the implantation site. 
    • Pallor, tachycardia, hypotension, and shock or collapse may indicate tubal rupture and severe bleeding. 

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: diagnosis and initial management [NICE, 2021], the British Medical Journal (BMJ) Best Practice guide Ectopic pregnancy [BMJ Best Practice, 2023], the Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK (MBRRACE-UK) report Saving lives, improving mother's care. Lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2018-20 [MBRRACE-UK, 2022], expert opinion in a chapter on Early pregnancy care in the medical textbook Clinical Obstetrics and Gynaecology [Kumar, 2022], expert opinion in a narrative review Diagnosis and management of ectopic pregnancy [Jurkovic, 2011], and a systematic review [Crochet, 2013].

Signs of an ectopic pregnancy

  • The NICE guideline development group [NICE, 2021] felt that it was not appropriate to include ‘adnexal mass’ or ‘palpable pelvic mass’ in the list of signs and symptoms. In their clinical experience, they noted that palpation can increase the risk of an ectopic pregnancy rupturing, and they also felt that, while palpation to detect an internal mass might once have been used in the diagnosis of ectopic pregnancy, the development of new diagnostic modalities (such as transvaginal ultrasound and biochemical tests) has meant that it is no longer appropriate.

How should I assess a woman with suspected ectopic pregnancy?

  • If immediate hospital transfer is not indicated confirm pregnancy with a urine pregnancy test (if not already done). 
  • Take a medical history, and ask about: 
    • Signs and symptoms. 
    • Sexual activity and use of contraception.
    • Date of the last menstrual period and when symptoms started. 
      • Symptoms generally appear 6 to 8 weeks after the last normal menstrual period, but they can occur earlier, or much later in cases of non-tubal ectopic pregnancy.
    • Date of the positive pregnancy test (if one has been done). 
    • Risk factors for ectopic pregnancy.
      • Exclude the possibility of ectopic pregnancy, even in the absence of risk factors, as in about a third of cases there are no identifiable risk factors. 
  • Perform an abdominal examination.
  • Perform a gentle pelvic examination if there is no abdominal pain and tenderness.
    • Do not palpate for an adnexal or pelvic mass as this may increase the risk of rupture of an ectopic pregnancy if present. 

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: diagnosis and initial management [NICE, 2021], the British Medical Journal (BMJ) Best Practice guide Ectopic pregnancy [BMJ Best Practice, 2023], the American College of Obstetricians and Gynecologists (ACOG) guideline Tubal ectopic pregnancy [ACOG, 2018], a chapter on Early pregnancy care in the medical textbook Clinical Obstetrics and Gynaecology [Kumar, 2022], and what CKS considers good medical practice. 

Arranging a pregnancy test 

  • NICE recommends that during clinical assessment of women of reproductive age, clinicians should be aware that [NICE, 2021]:
    • They may be pregnant and should think about offering a pregnancy test even when symptoms are non-specific, as 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.
  • ACOG recommends that every sexually active, reproductive-aged woman who presents with abdominal pain or vaginal bleeding should be screened for pregnancy, regardless of whether she is currently using contraception [ACOG, 2018].
  • Previous expert reviewers of this CKS topic were of the opinion that if a urinary pregnancy test is negative, 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.
  • The BMJ Best Practice guide advises that there have been numerous case reports of ectopic pregnancies following both total and supracervical hysterectomies and that although this condition is extremely rare, clinicians should be aware of the possibility of its occurrence [BMJ Best Practice, 2023].
    • Provided that at least one ovary has been retained, a pregnancy test should be performed for a woman of reproductive age who has previously had a hysterectomy and presents with abdominal pain of unknown origin.

Performing an abdominal examination

  • The recommendation to perform an abdominal examination first to assess for abdominal pain and tenderness is pragmatic, based on what CKS considers to be good medical practice, and is extrapolated from the NICE guideline which recommends referral to an early pregnancy assessment service for further assessment of women with a positive pregnancy test if they have pain and abdominal tenderness, or pelvic tenderness, or cervical motion tenderness [NICE, 2021].
    • Pelvic examination is uncomfortable, and in the presence of abdominal pain and tenderness in women with suspected ectopic pregnancy it is unnecessary as NICE recommends that urgent referral should be arranged regardless of whether or not pelvic tenderness or cervical motion tenderness are present. 

Performing a pelvic examination 

  • CKS recommends performing a gentle pelvic examination without palpating for an adnexal or pelvic mass based on expert opinion in the NICE guideline development group [NICE, 2021] and what CKS considers good medical practice.
    • The NICE guideline development group noted that in their experience palpation to detect an internal mass can increase the risk of an ectopic pregnancy rupturing, and while it might once have been used in the diagnosis of ectopic pregnancy, the development of new diagnostic modalities (such as transvaginal ultrasound and biochemical tests) has meant that it is no longer appropriate.
      • However, a systematic review found that while some experts are concerned about a small risk of ectopic pregnancy rupture from palpation, the risk is not supported with evidence from case series [Crochet, 2013].
    • An Irish guideline advises that speculum and bimanual examination are uncomfortable, have limited diagnostic value in women with ectopic pregnancy, and as transvaginal ultrasound scanning is widely available it should be the initial investigation of choice [IOG, 2017].

What else might cause pain or bleeding in early pregnancy?

  • Pregnancy-related conditions that can cause bleeding in the first and second trimesters include:
    • Miscarriage — see the CKS topic on Miscarriage for more information.
    • Molar pregnancy — a rare condition of a slow-growing cystic tumour which develops from trophoblastic cells after fertilization. A molar pregnancy can spread to nearby tissues, which is known as an 'invasive mole', or become a malignant choriocarcinoma. This is more likely if bleeding is heavy and prolonged, symptoms of pregnancy are exaggerated, the uterus is large for dates, and vesicles or cysts are passed. 
  • Pregnancy-related conditions that can cause abdominal pain in the first and second trimesters include:
    • Miscarriage — see the CKS topic on Miscarriage for more information.
    • Ruptured ovarian corpus luteal cyst. 
    • Pregnancy-related degeneration of a fibroid. 
  • Non-pregnancy-related conditions that can cause bleeding in early pregnancy include:
    • Urethral bleeding.
    • Haemorrhoids. See the CKS topic on Haemorrhoids for more information.
    • Trauma of the cervix, vagina, or vulva. 
    • Cancer of the cervix, vagina, or vulva. See the CKS topic on Cervical cancer and HPV for more information.
    • Vaginitis.
    • Cervicitis, cervical ectropion, or cervical polyps. 
  • Non-pregnancy-related conditions that can cause abdominal pain in early pregnancy include: 

Basis for recommendation

This information is taken from the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: diagnosis and initial management [NICE, 2021], the British Medical Journal (BMJ) Best Practice guide Ectopic pregnancy [BMJ Best Practice, 2023], chapters on Pelvic pain and endometriosis [Potdar, 2022], Heavy menstrual bleeding, dysmenorrhoea and pre-menstrual syndrome [Sassarini, 2022], Gestational trophoblastic disease [Tidy, 2022] and Sexually transmitted infections [Clutterbuck, 2022] in the medical textbook Clinical obstetrics and gynaecology, and expert opinion in a narrative review Ectopic pregnancy: diagnosis and management [Hendriks, 2020].

Management

Scenario: Suspected ectopic pregnancy

From age 16 years onwards (Female).

How should I manage a woman with suspected ectopic pregnancy?

  • Refer women who are haemodynamic unstable (including pallor, tachycardia, hypotension, shock, and collapse), or in whom there is significant concern about the degree of bleeding or pain directly to Accident and Emergency. 
  • Refer women 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 (with urgency depending on clinical judgement) if they have a positive pregnancy test and any of the following are present on examination: 
    • Pain and abdominal tenderness.
    • Pelvic tenderness.
    • Cervical motion tenderness. 
  • Refer women to an early pregnancy assessment service (with urgency depending on clinical judgement) if they have bleeding or have other symptoms and signs of early pregnancy complications if they also have any of the following: 
    • Pain.
    • A pregnancy of 6 weeks' gestation or more.
    • A pregnancy of uncertain gestation.
  • Use expectant management for women with a pregnancy of less than 6 weeks' gestation who are bleeding but not in pain, and who have no risk factors, such as a previous ectopic pregnancy. Advise these women: 
    • To return if bleeding continues or pain develops.
    • To repeat a urine pregnancy test after 7 to 10 days and to return if it is positive.
    • That a negative pregnancy test means that the pregnancy has miscarried.
  • 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 (with urgency depending on clinical judgement). 
  • For all women referred to an early pregnancy assessment service (or out-of-hours gynaecology service):
    • Explain the reasons for the referral and what she can expect on arrival.  
    • Arrange follow up and offer appropriate support, information, and advice.
  • Provide all women, and (with her consent) 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 postoperative 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.
  • Offer the woman the option of a follow-up appointment with a healthcare professional of her choice. 

Diagnosis and treatment in secondary care

Diagnosis
  • Transvaginal ultrasound is the diagnostic tool of choice for a suspected ectopic pregnancy. It is used to identify the location of the pregnancy and whether there is a fetal pole and heartbeat. 
    • A transabdominal ultrasound may be used in some cases (for example in women with an enlarged uterus or other pelvic pathology such as fibroids or an ovarian cyst or if a transvaginal scan is unacceptable), but imaging is of poorer quality. 
    • Magnetic resonance imaging (MRI) may be used as a second-line investigation tool in certain cases, for example, if the diagnosis of a caesarean scar ectopic pregnancy is equivocal and there is local expertise in MRI diagnosis. 
  • In women with pregnancy of unknown location (PUL, defined as a positive pregnancy test but no visible evidence of the location of the pregnancy on an ultrasound scan), measurements of serum human chorionic gonadotrophin (hCG) may be used to determine subsequent management. However, clinical symptoms are of more significance than hCG levels. 
  • Repeat transvaginal scans, serial hCG levels, and laparoscopy may be used to confirm the diagnosis. 
Treatment
  • After an ectopic pregnancy has been confirmed, treatment options include expectant management (watchful waiting), medical management, and surgery. 
    • The choice of treatment will depend on factors such as the haemodynamic stability of the woman, the site of implantation of the ectopic pregnancy, the risk of tubal rupture, serum hCG level, the level of pain the woman has, and the acceptability of the method of treatment to the woman. 
  • Expectant management is an option for a few women who are clinically stable and pain free. Active intervention will be considered if symptoms of ectopic pregnancy occur or if levels of serum hCG fail to decrease at an acceptable rate.
  • Medical management involves the use of drug treatment, most commonly parenteral methotrexate. It is offered first line 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.
    • Serum hCG level less than 1500 IU/L.
    • No intrauterine pregnancy (as confirmed on an ultrasound scan).
  • Surgery, by means of salpingectomy or salpingotomy, is performed laparoscopically or by open surgery. It is offered first line to women who are unable to return for follow up after methotrexate treatment or who have an ectopic pregnancy and any of the following: 
    • Significant pain.
    • Adnexal mass of 35 mm or larger.
    • Fetal heartbeat visible on an ultrasound scan.
    • Serum hCG level of 5000 IU/L or more.
  • A choice of either methotrexate or surgical management is offered to women with an ectopic pregnancy who have a serum hCG level of at least 1500 IU/L and less than 5000 IU/L, are able to return for follow up, and 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).
  • 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. 
  • Anti-D immunoglobulin is offered to all rhesus-negative women who have had surgical removal of an ectopic pregnancy. 

[Elson, 2016; ACOG, 2018; NICE, 2021; BMJ Best Practice, 2023]

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: diagnosis and initial management [NICE, 2021], the American College of Obstetricians and Gynecologists (ACOG) guideline Tubal ectopic pregnancy [ACOG, 2018], and what CKS considers good medical practice. 

Scenario: Follow up after an ectopic pregnancy

From age 16 years onwards (Female).

How should I follow up a woman after treatment for an ectopic pregnancy?

  • Ensure that arrangements for routine antenatal care are cancelled (if they have begun).
  • Give the woman the opportunity to discuss any questions she has about the ectopic pregnancy, including the risk of recurrence and the effect on future fertility. See the section on Prognosis for information. 
  • Assess the woman's psychological wellbeing and offer counselling if appropriate.
    • Advise the woman on how to access support via patient support groups, such as the Ectopic Pregnancy Trust, or local bereavement counselling services. 
    • Be aware that:
      • Pregnancy loss, irrespective of gestation or location of pregnancy is a bereavement, and while the emotional trauma experienced is variable, the potential adverse impact should not be underestimated.  
      • The psychological impact of early pregnancy loss may seriously affect a significant proportion of women, their partners and families.
      • Women experience high levels of post-traumatic stress, anxiety, and depression after early pregnancy loss. Distress declines over time but can remain at clinically significant levels at 9 months. 
  • Advise women treated with methotrexate to wait at least 3 months before trying to conceive again. 
    • Women who have been treated with methotrexate should be advised that effective contraception is recommended during and for at least 3 months after treatment in view of the teratogenic effects of methotrexate.
  • Give appropriate contraception advice, including that:
    • Any method of contraception can be safely used after ectopic pregnancy.   
      • A history of ectopic pregnancy is not a contraindication to any form of hormonal or intrauterine contraception. See the CKS topic on Contraception - assessment for more information.
    • Additional contraceptive precautions (e.g. barrier methods/abstinence) are required if hormonal contraception is started 5 days or more after surgical treatment or administration of methotrexate for ectopic pregnancy. Additional contraceptive precaution is not required if contraception is initiated immediately or within 5 days of treatment of ectopic pregnancy.
    • The absolute risk of ectopic pregnancy when contraception is used is extremely small and that the risk of pregnancy is lowest with long-acting reversible contraception. 
    • That intrauterine contraception (IUC) is one of the most effective methods of contraception and so the absolute risk of any pregnancy including ectopic pregnancy is extremely low. 
    • If pregnancy occurs with IUC in situ, or after tubal occlusion, there is an increased risk of ectopic pregnancy and therefore the location of the pregnancy should be confirmed by ultrasound as soon as possible. 
  • Ensure that all rhesus-negative women who have had an ectopic pregnancy at 12+0 weeks or beyond and have undergone surgical or medical management have received anti-D immunoglobulin at a dose of at least 250 IU (50 micrograms).
    • Anti-D immunoglobulin is not required for ectopic pregnancy up to and including 11+6 weeks' gestation.
    • Anti-D immunoglobulin should not be given to women who have a pregnancy of unknown location.
  • Provide additional information on ectopic pregnancy and ectopic pregnancy support groups. For example: 
  • Advise the woman that she should inform her GP as soon as possible about any future pregnancy so that an ultrasound scan can be arranged at 6–7 weeks to establish the location and viability of the pregnancy. 
  • 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. 

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: diagnosis and initial management [NICE, 2021], the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Diagnosis and management of ectopic pregnancy [Elson, 2016], the American College of Obstetricians and Gynecologists (ACOG) guideline Tubal ectopic pregnancy [ACOG, 2018], a chapter on Early pregnancy care [Kumar, 2022] in the medical textbook Clinical Obstetrics and Gynaecology, the College of Sexual and Reproductive Healthcare (CoSRH) guideline Contraception after pregnancy [CoSRH, 2020], a prospective cohort study [Farren, 2020], the manufacturer's Summary of Product Characteristics for methotrexate [ABPI, 2023], and what CKS considers good medical practice. 

Assessing the woman's psychological wellbeing 
  • The recommendation to assess the woman's wellbeing is based on what CKS considers good medical practice, and:
    • The NICE guideline which advises that the emotional impact of ectopic pregnancy can be significant, and in some circumstances lead to post-traumatic stress disorder [NICE, 2021]. 
    • Expert opinion in a narrative review that the psychological effect of ectopic pregnancy is often overlooked, as it may not be viewed in the same way as other pregnancy loss, and 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].
    • Expert opinion in another narrative review that some women are severely emotionally traumatised and may require dedicated one-to-one counselling and long-term psychological support [Jurkovic, 2011]. 
    • Extrapolated evidence on the prevalence and severity of psychological distress following miscarriage [Brier, 1999; Brier, 2004; Brier, 2008].
Managing future pregnancies
  • The recommendation that women should inform their GP as soon as possible about any future pregnancy so that an ultrasound scan can be arranged at 6–7 weeks to establish the location and viability of the pregnancy is based on the expert opinion of the previous expert reviewers of this CKS topic.
  • ACOG recommends that women who become pregnant and have known significant risk factors (for example, previous ectopic pregnancy) should be evaluated for possible ectopic pregnancy even in the absence of symptoms [ACOG, 2018].
  • NICE recommends that women who have had an ectopic pregnancy should be informed that they can self-refer to an early pregnancy assessment service in future pregnancies if they have any early concerns [NICE, 2021].
Contraception advice after methotrexate treatment
  • The CoSRH recommends that women who have been treated with methotrexate should be advised that effective contraception is recommended during and for at least 3 months after treatment in view of the teratogenic effects of this medication [CoSRH, 2020].
  • The RCOG guideline also recommends that women treated with methotrexate should wait at least 3 months before trying to conceive again [Elson, 2016].
  • However, the manufacturer of methotrexate advises that reliable contraception should be used for at least 6 months after treatment with methotrexate for an ectopic pregnancy, as there is a possible teratogenic risk due to the prolonged effects of methotrexate [ABPI, 2023]. 

Supporting evidence

This CKS topic is largely based on the National Institute for Health and Care Excellence (NICE) guideline Ectopic pregnancy and miscarriage: diagnosis and initial management [NICE, 2021], the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Diagnosis and management of ectopic pregnancy [Elson, 2016], and the British Medical Journal (BMJ) Best Practice guide Ectopic pregnancy [BMJ Best Practice, 2023]. The rationale for individual recommendations is discussed in the relevant basis for recommendation sections of this topic.

How this topic was developed

This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website.

Search strategy

A full literature search was not requested/required as this CKS topic is primarily based on the National Institute for Health and Clinical Excellence (NICE) guideline Ectopic pregnancy and miscarriage: Diagnosis and initial management in early pregnancy of ectopic pregnancy and miscarriage (2012).

Search dates

April 2018 - January 2023

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

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

Sources of guidelines

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

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

Sources of national policy

Patient experiences

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.

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

  • Clinical accuracy.
  • Consistency with other providers of clinical knowledge for primary care.
  • Accuracy of implementation of national guidance (in particular NICE guidelines).
  • Usability.

Principles of the consultation process

  • The process is inclusive and any individual may participate.
  • To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
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  • Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
  • External reviewers are not paid for commenting on the draft topics.
  • Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
  • All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
  • All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

  • Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
  • Stakeholders identified from the following groups are invited to review draft topics:
    • Experts in the topic area.
    • Professional organizations and societies (for example, Royal Colleges).
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Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

  • Topic selection
  • Scoping of topic
  • Selection of clinical scenarios
  • First draft internal review
  • Second draft internal review
  • External review
  • Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

  • Animal studies
  • Original research is not written in English

Possible exclusions for reviewed literature:

  • Sample size too small or study underpowered
  • Bias evident or promotional literature
  • Population not relevant
  • Intervention/treatment not relevant
  • Outcomes not relevant
  • Outcomes have no clear evidence of clinical effectiveness
  • Setting not relevant
  • Not relevant to UK
  • Incorrect study type
  • Review article
  • Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

  • Feasibility
    • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
  • Organizational and Financial Impact Analysis
  • Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
    • Eligible population
    • Current interventions
    • Likely uptake of new intervention or recommendation
    • Cost of the current or new intervention mix
    • Impact on other costs
    • Condition-related costs
    • In-direct costs and service impacts
    • Time dependencies
  • Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

  • Personal financial interests
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  • Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.

References

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  • ACOG (2018) ACOG Practice Bulletin No. 191: Tubal ectopic pregnancy. Obstetrics and Gynecology 131(2), e65-e77. [Free Full-text]
  • BMJ Best Practice (2023) Ectopic pregnancy. BMJ Publishing Group. https://bestpractice.bmj.com
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  • Brier, N. (2004) Anxiety after miscarriage: A review of the empirical literature and implications for clinical practice. Birth 31(2), 138-142. [Abstract]
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  • Santos-Ribeiro, S., Tournaye, H. and Polyzos, N.P. (2016) Trends in ectopic pregnancy rates following assisted reproductive technologies in the UK: a 12-year nationwide analysis including 160 000 pregnancies. Human Reproduction 31(2), 393-402. [Abstract] [Free Full-text]
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  • 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.
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