Definition

Ectopic pregnancy is implantation of a pregnancy outside the uterine cavity; the great majority are tubal. NICE NG126 covers tubal ectopic pregnancy specifically. A pregnancy of unknown location is a positive pregnancy test with no pregnancy seen inside or outside the uterus on transvaginal ultrasound. It remains potentially ectopic until the site is identified.

Epidemiology

Around 1 in 90 UK pregnancies is ectopic, roughly 11,000 a year. Risk rises with previous ectopic pregnancy, tubal damage or surgery, pelvic inflammatory disease, assisted conception, pregnancy with an intrauterine device in place, smoking and increasing age. About a third of affected women have no known risk factor, and ectopic pregnancy is the most frequent cause of maternal death in early pregnancy in the UK and Ireland.

Pathophysiology

A fertilised ovum implants outside the uterine cavity, usually in a fallopian tube. The tube has no decidua, so trophoblast invades the muscular wall and its vessels directly. Bleeding tracks into the tubal lumen and the peritoneal cavity, and progressive distension ends in rupture with haemoperitoneum and shock. Impaired tubal transport after infection, surgery or inflammation explains many cases, but most women have no identifiable risk factor. That is why the diagnosis is made by scanning, not by risk assessment.

First principles

The tube cannot expand, so the pregnancy destroys it

Trophoblast invades the tubal wall and its blood supply. The tube has no decidua and cannot enlarge, so bleeding tracks into the lumen and the peritoneum. Rupture is not the end of a long illness; it can be the first event, and symptoms typically begin between the fourth and twelfth week. About 95% of ectopic pregnancies are tubal and about 3% interstitial; cervical, caesarean-scar, ovarian and abdominal sites are each under 1%.^1,2,3,4

A reassuring number does not make a stable patient

Symptoms and haemodynamic state decide urgency, not serum human chorionic gonadotrophin (hCG). NICE is explicit that hCG must not be used to locate a pregnancy; it measures trophoblastic proliferation only. A pregnancy of unknown location (PUL) remains potentially ectopic until the site is seen, and rupture has been reported with low, falling and even negative levels.^1,5,6,4

Five variables choose the treatment

Pain, adnexal mass size, a visible heartbeat, serum hCG in international units per litre (IU/L) and the ability to return for follow-up decide between expectant management, methotrexate and surgery. Each threshold is a proxy for rupture risk and for how much trophoblast has to be cleared. Methotrexate is only for a definitive diagnosis with a viable intrauterine pregnancy excluded, and NG126 records this use as off label.^7,6,4

Anti-D prophylaxis changed on 17 June 2026

NICE no longer offers anti-D immunoglobulin for ectopic pregnancy up to and including 11+6 weeks, including for surgical management. From 12+0 to 12+6 weeks, offer at least 250 IU (50 micrograms) by deep intramuscular injection to RhD-negative (rhesus D negative) people having medical or surgical management. Where ultrasound dating and the last menstrual period differ, the ultrasound decides.^8,9

Presentation

Abdominal or pelvic pain, a missed period and vaginal bleeding is the classic triad, but NICE warns that atypical presentation is common. Shoulder-tip pain, syncope, peritonism or shock suggests haemoperitoneum and needs emergency assessment.^1,3

Cardinal features

Abdominal or pelvic pain in early pregnancy, usually one-sided
Amenorrhoea or a missed period
Vaginal bleeding, with or without clots
Less common but still significant: breast tenderness, gastrointestinal symptoms, urinary symptoms or passage of tissue
Rectal pressure or pain on defecation
Dizziness, fainting or syncope, and shoulder-tip pain from diaphragmatic irritation
Pelvic, adnexal or abdominal tenderness on examination, with or without cervical motion tenderness
A positive pregnancy test with no intrauterine pregnancy seen on transvaginal ultrasound
About a third of women with an ectopic pregnancy have no known risk factor, so a clean risk history does not exclude it

Red flags

Tachycardia above 100 beats per minute or blood pressure below 100/60 mmHg
Shock, collapse or orthostatic hypotension
Sudden severe or worsening abdominal or pelvic pain
Rebound tenderness, peritoneal signs or abdominal distension
Pallor accompanying pain or bleeding
Shoulder-tip pain with pain or bleeding
Significant concern about the degree of pain or bleeding: refer directly to A&E, not to routine early-pregnancy follow-up

Investigations

Urine pregnancy test in anyone who could be pregnant

NICE expects every healthcare professional caring for women of reproductive age to have access to pregnancy tests, and to consider one even when symptoms are non-specific. Ectopic pregnancy mimics gastrointestinal illness and urinary tract infection.

Expected finding: Positive. Refer immediately to an early pregnancy assessment service (EPAS) if there is pain with abdominal tenderness, pelvic tenderness or cervical motion tenderness.

¹

Transvaginal ultrasound

This is the test that locates the pregnancy. Look for an intrauterine sac, an adnexal mass moving separately from the ovary, a fetal pole or heartbeat, and free fluid. Offer a transabdominal scan, explaining its limitations, if transvaginal scanning is unacceptable.

Expected finding: An intrauterine pregnancy, a visualised tubal ectopic, or a pregnancy of unknown location. Free fluid suggests bleeding but is interpreted with the clinical picture, never alone.

^5,6

Serial serum hCG when the pregnancy location is unknown

Take two serum human chorionic gonadotrophin (hCG) measurements as near as possible to 48 hours apart, and no earlier. Further measurements need senior review. Do not use serum progesterone as an adjunct, and never use hCG to locate the pregnancy.

Expected finding: A rise above 63% suggests a developing intrauterine pregnancy but does not exclude ectopic pregnancy. A fall greater than 50% suggests a failing pregnancy. Anything between the two needs review within 24 hours.

^5,6

Bloods and preparation for haemorrhage

With significant pain, bleeding or suspected rupture, send FBC, group and save or crossmatch and whatever anaesthesia needs, while escalating care. Check RhD status, because it decides anti-D eligibility at 12+0 to 12+6 weeks. Do not delay surgery or transfer for serial hCG.

Expected finding: A falling haemoglobin suggests continuing intraperitoneal bleeding. Crossmatched blood and senior gynaecology and anaesthetic support may be needed.

^1,7,8

Baseline bloods before methotrexate

Before methotrexate, check FBC, U&E and LFT, plus serum hCG on the day of treatment. The BNF requires a full blood count and renal and liver function tests before methotrexate is started. Active lung, liver or kidney disease and marrow impairment rule it out.

Expected finding: Normal blood count, renal and liver function. Abnormal results, or active hepatic, renal or pulmonary disease, mean surgery instead.

^10,4

Management

Step	Detail	Source
Resuscitate and operate when unstable or rupture is suspected	Refer anyone haemodynamically unstable, or where there is significant concern about the degree of pain or bleeding, directly to A&E. ABCDE (airway, breathing, circulation, disability, exposure), two large-bore cannulae, FBC and crossmatch, and call senior gynaecology and anaesthetics. Proceed to urgent surgical control of bleeding: laparoscopy where condition and complexity allow, laparotomy for severe haemorrhage.^1,7,6	NICE NG126, symptoms and signs of ectopic pregnancy and initial assessment, and management of tubal ectopic pregnancy
Triage by gestation, pain and risk factors	Refer to an early pregnancy assessment service (EPAS) anyone with bleeding plus pain, a pregnancy of 6 weeks or more, or uncertain gestation. Under 6 weeks, bleeding, pain free and no risk factors: expectant management, repeat a urine pregnancy test after 7 to 10 days, return if positive. A negative test means the pregnancy has miscarried.¹	NICE NG126, symptoms and signs of ectopic pregnancy and initial assessment
Locate the pregnancy with transvaginal ultrasound	Transvaginal ultrasound is the test that locates the pregnancy. If no intrauterine pregnancy is seen this is a pregnancy of unknown location, and it stays potentially ectopic until the site is identified. Place more weight on symptoms than on hCG, and give written 24-hour emergency advice whatever the hCG level.^5,6	NICE NG126, diagnosis of viable intrauterine pregnancy and of tubal ectopic pregnancy
Act on the 48-hour hCG pattern	Rise above 63%: likely intrauterine pregnancy, scan in 7 to 14 days, earlier if hCG is 1,500 IU/L or above. Fall above 50%: likely failing, urine pregnancy test 14 days after the second hCG, return within 24 hours if positive. Anything in between: clinical review in the EPAS within 24 hours.^5,6	NICE NG126, diagnosis of viable intrauterine pregnancy and of tubal ectopic pregnancy
Offer expectant management within the NICE criteria	Offer it when the person is stable and pain free, the tubal ectopic is under 35 mm with no heartbeat, hCG is 1,000 IU/L or less, and they can return. Consider it on the same terms when hCG is above 1,000 but below 1,500 IU/L. Advise that resolution time and future fertility look the same as with methotrexate.^7,6	NICE NG126, management of tubal ectopic pregnancy
Monitor expectant management on days 2, 4 and 7	Repeat hCG on days 2, 4 and 7 after the original test. A fall of 15% or more from the previous value at each point means weekly measurements until a negative result, below 20 IU/L. A smaller fall, a plateau or a rise means reviewing the clinical condition and seeking senior advice.^7,6	NICE NG126, management of tubal ectopic pregnancy
Offer methotrexate only for a definitive, stable, unruptured ectopic	Criteria: no significant pain, unruptured tubal ectopic with an adnexal mass under 35 mm and no heartbeat, hCG below 1,500 IU/L, no intrauterine pregnancy on scan, and able to return. Give it on a first visit only when the diagnosis is definitive and a viable intrauterine pregnancy is excluded. Offer surgery if methotrexate is unacceptable.^7,6	NICE NG126, management of tubal ectopic pregnancy
Give methotrexate 50 mg/m2 intramuscularly and monitor it	Single-dose methotrexate 50 mg/m2 by deep intramuscular injection, typically 70 to 100 mg by body surface area and capped at 100 mg. NG126 gives no dose and records the use as off label, so the number comes from your unit's protocol. Check hCG on days 4 and 7, then weekly until negative; plateau or rise means reassessment.^4,7,6	Royal Cornwall Hospitals NHS Trust ectopic pregnancy guideline V4.0, February 2026, for the dose; NICE NG126 for the monitoring schedule
Counsel on methotrexate safety and contraception	Avoid alcohol, NSAIDs and aspirin, folic acid or vitamin supplements containing it, sexual intercourse and sun exposure. Warn that crampy abdominal pain is common. Return urgently for severe pain, dizziness, shoulder-tip pain, heavy bleeding, breathlessness, mouth ulcers, bruising or fever. Use effective contraception and avoid conception for at least 3 months.^4,3,10	Royal Cornwall Hospitals NHS Trust ectopic pregnancy guideline V4.0, February 2026, NHS ectopic pregnancy information and the BNF methotrexate monograph
Use surgery when the thresholds make it first-line	Offer surgery first-line for inability to return for follow-up, significant pain, an adnexal mass 35 mm or larger, a visible fetal heartbeat, or hCG 5,000 IU/L or more. Between 1,500 and under 5,000 IU/L with all other criteria met, offer a choice of methotrexate or surgery, warning that methotrexate more often needs further intervention.^7,6	NICE NG126, management of tubal ectopic pregnancy
Choose salpingectomy or salpingotomy, then follow the hCG	Operate laparoscopically whenever possible. Offer salpingectomy unless there are other infertility risk factors; consider salpingotomy when the other tube is damaged. Warn that up to 1 in 5 salpingotomies need further treatment. After salpingotomy check hCG at 7 days then weekly until negative; after salpingectomy a urine pregnancy test at 3 weeks.^7,6	NICE NG126, management of tubal ectopic pregnancy
Apply the June 2026 anti-D rule	Do not offer anti-D immunoglobulin for ectopic pregnancy up to and including 11+6 weeks, including surgical management. At 12+0 to 12+6 weeks, offer at least 250 IU (50 micrograms) by deep intramuscular injection to RhD-negative people having medical or surgical management. Use ultrasound dating over the last menstrual period. Do not use a Kleihauer test to quantify feto-maternal haemorrhage.^8,9	NICE NG126 anti-D immunoglobulin prophylaxis, updated 17 June 2026, and the BNF anti-D immunoglobulins monograph
Discuss the blood-product decision and arrange follow-up	Anti-D is a protein obtained from blood plasma that contains no blood cells, so discuss it and let the person choose. 250 IU is a minimum and a larger stocked dose is acceptable. Give written information on treatment, emergency symptoms and how to get help, and offer self-referral to the EPAS in a future pregnancy.^8,7,6	NICE NG126 anti-D immunoglobulin prophylaxis and management of tubal ectopic pregnancy
Recognise that non-tubal sites sit outside NG126	Interstitial, cervical, caesarean-scar, ovarian and abdominal ectopic pregnancies are specialist-managed under RCOG Green-top Guideline No. 21, not NG126. Heterotopic pregnancy, a coexisting intrauterine and ectopic pregnancy, is rare but is why the adnexa are checked even when an intrauterine pregnancy has been seen.^2,4	RCOG Green-top Guideline No. 21, November 2016, and Royal Cornwall Hospitals NHS Trust ectopic pregnancy guideline V4.0

Illustrations

Tubal implantation and rupture mechanismDiagram showing trophoblastic invasion of the tubal wall, progressive distension of mesosalpinx vessels and the point of rupture causing intraperitoneal haemorrhage.PassFinals · original

Ectopic pregnancy at laparoscopyLaparoscopic view of a tubal ectopic pregnancy distending the fallopian tube.Mikael Häggström, Wikimedia Commons · CC-BY-SA-3.0

Anatomical sites of ectopic implantationDiagram of the fallopian tube and pelvis marking ampullary, isthmic, fimbrial, interstitial and non-tubal implantation sites.PassFinals · original

Differentials

Miscarriage

Bleeding and pain with an intrauterine pregnancy or pregnancy loss confirmed on ultrasound. Until the location is confirmed, ectopic pregnancy stays in the differential.

Ruptured or haemorrhagic ovarian cyst

Adnexal pain with an ovarian finding on scan. An adnexal mass that moves with the ovary is not an ectopic; the pregnancy still has to be located.

Pelvic inflammatory disease

Pelvic pain with fever, discharge and cervical motion tenderness, usually with a negative pregnancy test.

Appendicitis

Right iliac fossa pain with gastrointestinal symptoms. Pregnancy does not exclude appendicitis, and appendicitis does not exclude a concurrent ectopic.

Urinary tract infection or renal colic

Urinary symptoms, loin-to-groin pain or haematuria. NICE specifically warns that ectopic pregnancy can be mistaken for a urinary tract infection.

Complications

Tubal rupture with life-threatening intraperitoneal haemorrhage and shock
Need for emergency laparoscopy or laparotomy
Persistent trophoblast after methotrexate or salpingotomy, needing further treatment
Recurrent ectopic pregnancy and reduced fertility
Methotrexate adverse effects: crampy abdominal pain, stomatitis, marrow suppression, hepatotoxicity, pneumonitis
Psychological distress and pregnancy-loss grief

Prognosis

Most stable ectopic pregnancies resolve with expectant, medical or surgical management, but follow-up is not optional: rupture can occur during observation and after methotrexate. Around 1 in 10 women treated with methotrexate still need surgery. Future fertility is usually preserved, although the recurrence risk is around 10%, so an early scan should be arranged in the next pregnancy.

Guidelines

Ectopic pregnancy and miscarriage: diagnosis and initial management (NG126) (NICE, 2019)
NG126 anti-D immunoglobulin prophylaxis update (NICE, 2026)
Diagnosis and Management of Ectopic Pregnancy (Green-top Guideline No. 21) (Royal College of Obstetricians and Gynaecologists, 2016)