What is an ectopic pregnancy and where does it implant?
An ectopic pregnancy is one that implants outside the endometrial cavity. It affects roughly 1–2% of pregnancies in the United States and accounts for about 2.7% of pregnancy-related deaths, mostly from rupture and haemorrhage. About 97% occur in the fallopian tube, usually because the tube is damaged and delays the embryo's passage.
| Site | Frequency / key point |
|---|---|
| Ampulla of the tube | Most common — about 70% of tubal ectopics |
| Isthmus, fimbria | Other tubal sites |
| Interstitial (cornual) | Up to 4% of ectopics; the intramural part of the tube |
| Ovarian | Under 3% |
| Cervical | Under 1%; often follows dilatation and curettage |
| Caesarean scar | Under 1%, rising with caesarean rates |
| Abdominal | 0.9–1.4%; mortality about 10% because of late diagnosis and major bleeding |
What are the risk factors for ectopic pregnancy?
- Previous ectopic pregnancy — the strongest: recurrence about 10% after one and over 25% after two or more.
- Tubal damage — pelvic inflammatory disease (gonorrhoea, chlamydia), previous pelvic or tubal surgery including sterilisation, endometriosis.
- Infertility and assisted reproduction (IVF).
- Conception with an IUD or progestogen-only contraception in place.
- Smoking, and in-utero diethylstilbestrol exposure.
How does ectopic pregnancy present, and what does ultrasound show?
The usual picture is lower abdominal pain and vaginal bleeding in early pregnancy, especially when an intrauterine pregnancy has not yet been confirmed. Rupture adds signs of haemoperitoneum — more generalised pain, shoulder-tip pain, dizziness and fainting. Free fluid or blood in the pouch of Douglas with a positive hCG is about 70% specific for ectopic pregnancy.
Transvaginal ultrasound (TVS) is the first investigation. NICE lists the signs by strength:
| Strength | Finding |
|---|---|
| Diagnostic | Adnexal mass moving separately from the ovary ('sliding sign') containing a gestational sac with a yolk sac, or a fetal pole (with or without heartbeat) |
| High probability | Adnexal mass moving separately from the ovary with an empty sac ('tubal ring' or 'bagel sign'), or a complex inhomogeneous adnexal mass |
| Possible | Empty uterus, or a fluid collection in the uterine cavity (pseudosac); free fluid |
What is the stepwise approach to suspected ectopic pregnancy?
- Pregnancy test in every woman of reproductive age with abdominal pain or bleeding — ectopic mimics miscarriage, ovarian cyst rupture and appendicitis.
- Assess haemodynamic status. An unstable woman with a suspected rupture goes for urgent surgery; imaging and hCG must not delay it.
- Transvaginal ultrasound to locate the pregnancy and look for a fetal pole and heartbeat (transabdominal if the uterus is large or there is ovarian pathology).
- Serum hCG — interpreted with the scan, never alone, and repeated at 48 hours if the location is unknown.
- Choose management — expectant, methotrexate or surgery — by pain, mass size, heartbeat, hCG level and the woman's ability to return for follow-up.
What is the β-hCG discriminatory zone and how is a pregnancy of unknown location managed?
The discriminatory zone is the β-hCG level above which an intrauterine pregnancy should be visible on TVS. Historically it was set at 1,000–2,000 mIU/mL; ACOG now suggests a cut-off of up to 3,500 mIU/mL, because it varies with equipment, operator and multiple pregnancy. In a viable early pregnancy with hCG below 1,500, a rise of at least 49% over 48 hours is seen in 99%; a slower rise or a fall raises concern for miscarriage or ectopic.
A pregnancy of unknown location (PUL) is a positive test with no pregnancy seen inside or outside the uterus on TVS. NICE says to treat it as a possible ectopic until proven otherwise, to give clinical symptoms more weight than hCG, and not to use hCG to determine location — only to judge trophoblast activity.
| Change over 48 h | Interpretation | Action |
|---|---|---|
| Rise >63% | Likely developing intrauterine pregnancy (ectopic not excluded) | TVS in 7–14 days; earlier if hCG ≥1,500 IU/L |
| Fall >50% | Pregnancy unlikely to continue | Urine pregnancy test after 14 days |
| Rise <63% or fall <50% | Suboptimal — ectopic possible | Clinical review in the early pregnancy unit within 24 hours |
Who can have expectant or methotrexate treatment?
| Option | Criteria |
|---|---|
| Expectant — offer | Clinically stable and pain-free, tubal mass <35 mm, no heartbeat, hCG ≤1,000 IU/L, able to return |
| Expectant — consider | As above with hCG >1,000 and <1,500 IU/L |
| Methotrexate — offer | No significant pain, unruptured mass <35 mm, no heartbeat, hCG <1,500 IU/L, no intrauterine pregnancy, able to return for follow-up |
| Methotrexate or surgery — choice | Same, with hCG 1,500 to <5,000 IU/L (higher chance of needing further treatment) |
| Surgery first-line | Significant pain, mass ≥35 mm, visible fetal heartbeat, hCG ≥5,000 IU/L, or unable to return |
Methotrexate is a folate antagonist that kills the rapidly dividing trophoblast; medical treatment succeeds in about 70–95%, less often as starting hCG rises. In the common single-dose protocol, methotrexate 50 mg/m² is given intramuscularly on day 0 and hCG is checked on days 4 and 7; a fall of at least 15% between days 4 and 7 is an adequate response, after which hCG is followed weekly to negative. Two-dose regimens are more effective when hCG or the mass is larger; multidose regimens have more adverse effects. See anticancer drugs for methotrexate pharmacology.
| Absolute | Relative |
|---|---|
| Haemodynamic instability; ruptured ectopic | Fetal cardiac activity |
| Anaemia, leucopenia, thrombocytopenia; immunodeficiency | hCG >5,000 mIU/mL or adnexal mass >4 cm |
| Renal or hepatic dysfunction; active pulmonary or peptic ulcer disease | Refusal of blood transfusion |
| Breastfeeding; unreliable follow-up | — |
When is surgery needed, and is salpingectomy or salpingotomy better?
A ruptured ectopic with haemodynamic instability needs urgent surgery. Otherwise surgery is chosen by the criteria above, and NICE recommends it be done laparoscopically whenever possible.
| Salpingectomy | Salpingotomy (salpingostomy) | |
|---|---|---|
| What | Removal of part or all of the affected tube | Ectopic removed through a tubal incision; tube preserved |
| When | Default — offer unless there are other risk factors for infertility | Consider if there are infertility risk factors, e.g. contralateral tube damage |
| Persistent trophoblast | Rare | Up to 1 in 5 need further treatment (methotrexate or salpingectomy) |
| Follow-up | Urine pregnancy test after 3 weeks | Serum hCG at 7 days, then weekly until negative |
What is a heterotopic pregnancy and why do unusual sites matter?
A heterotopic pregnancy is an intrauterine pregnancy and an ectopic pregnancy at the same time. It is rare after natural conception but has become more frequent with assisted reproduction: after ART, about 11% of ectopic pregnancies are heterotopic, and 82% of ART ectopics are tubal. Seeing an intrauterine sac therefore does not exclude an ectopic in an IVF patient — the method of conception must be asked.
- Heterotopic: NICE's methotrexate criteria require no intrauterine pregnancy on scan, so medical treatment is not the standard route.
- Interstitial/cornual: up to 4% of ectopics, in the part of the tube that runs through the uterine wall.
- Cervical: under 1%, often after dilatation and curettage.
- Caesarean scar: under 1%; becoming more common as caesarean rates rise.
- Abdominal: highest mortality (about 10%) because of late diagnosis and torrential bleeding.
Do Rh-negative women need anti-D after an ectopic pregnancy?
NICE changed this advice in 2026. Anti-D immunoglobulin is not offered for ectopic pregnancy, miscarriage or threatened miscarriage up to and including 11+6 weeks. For RhD-negative women at 12+0 to 12+6 weeks having medical or surgical management of an ectopic pregnancy or miscarriage, offer anti-D at at least 250 IU (50 micrograms). Gestation should be taken from the ultrasound if it differs from the menstrual dates, and a Kleihauer test is not used to quantify bleeding.
Profuse bleeding from ruptured ectopics is a cause of early-pregnancy haemorrhage; for bleeding later in pregnancy see antepartum haemorrhage and postpartum haemorrhage.