Clinical overview
Ectopic pregnancy is the diagnosis that earns the most maternal mortality reviews and the most legal cases against gynaecologists, because the path to a poor outcome is almost always delayed recognition. The pathophysiology is at ectopic-pathophysiology; here we cover what to do at the bedside, the operational algorithm, the three modalities of treatment (expectant, medical, surgical), and the management of difficult sites (interstitial, cervical, scar, ovarian, abdominal, heterotopic).
The single-line summary every registrar should internalise: Any woman of reproductive age with abdominal pain, a positive pregnancy test, and no intrauterine pregnancy on transvaginal ultrasound has an ectopic until proven otherwise. This holds for IUD users, ART patients, postpartum women, sterilised women — anyone. Resist the urge to make a benign diagnosis early.
Core knowledge
Clinical presentations
The "classic triad" — amenorrhoea, pain, bleeding — is present in only ~50%. More commonly:
- A young woman in early pregnancy with one-sided pelvic pain and minimal bleeding.
- A woman on her "period" (which is actually decidual cast) with worsening unilateral pain.
- Shoulder-tip pain, syncope on standing, vague malaise — haemoperitoneum.
- IUD user with new pelvic pain — exclude ectopic.
- ART patient with abdominal pain regardless of intrauterine sac visualised — heterotopic.
Initial triage
- Unstable: shocked, tachycardic, peritonitic → resuscitate + theatre, do not delay for imaging.
- Stable but symptomatic: full workup with TVS + serum β-hCG → decide management.
- Asymptomatic with positive pregnancy test and uncertain location: pregnancy of unknown location (PUL) protocol.
Resuscitation in suspected rupture
- Two large-bore IV access.
- Crystalloid 1–2 L; permissive hypotension to systolic 80–90 mmHg until haemostasis.
- Group-specific or O-negative blood while cross-match runs.
- Activate massive transfusion protocol if hypotension persists.
- Inform theatre, consultant, anaesthetist, blood bank simultaneously.
- FBC, U&E, coagulation, lactate, group-and-cross-match (4 units), fibrinogen.
Definitive diagnosis
TVS diagnosis: an empty uterus, tubal ectopic, separate ovary, and free pelvic fluid.
Transvaginal ultrasound — the cornerstone:
- Look for an intrauterine pregnancy first.
- If not seen, scan adnexa systematically for: gestational sac with yolk sac or embryo at extrauterine site; "ring of fire" on Doppler (peritrophoblastic flow); haematosalpinx (tubal mass with mixed echogenicity); free fluid (anechoic = simple; echogenic = blood).
- Scan the CS niche specifically for scar ectopic.
- Note ovarian position relative to any adnexal mass.
Serum β-hCG quantitative. Use the dynamics:
- ≥3500 IU/L with no IUP on TVS → ectopic until proven otherwise.
- 1500–3500 IU/L with no IUP → high suspicion; close monitoring.
- <1500 with no IUP → PUL; repeat in 48 h.
β-hCG trajectory:
- Doubling time normal: 48–72 h up to ~10 weeks.
- Rise <53% in 48 h: abnormal (could be ectopic or failing IUP).
- Fall >50% in 48 h: resolving pregnancy.
- Plateau: typical of ectopic.
Decision tree
Positive β-hCG + abdominal pain
|
Unstable? — YES → resuscitate + theatre
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NO
|
TVS performed
|
IUP seen?
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YES — IUP confirmed (consider heterotopic in ART) — manage as appropriate
|
NO
|
Adnexal mass / free fluid?
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YES — ectopic confirmed (or highly suspicious) — proceed to management
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NO — PUL
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Serial β-hCG 0 + 48 h
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Rise >53% → likely early IUP — repeat TVS at β-hCG ≥1500
Rise <53% → likely ectopic — treat as ectopic
Fall >50% → resolving — continue surveillance
Assessment
History
- Confirm pregnancy, gestation, conception (spontaneous vs ART).
- Pain: onset, character, severity, radiation.
- Bleeding: amount, character.
- Shoulder-tip pain, dizziness, syncope.
- Risk factors: PID, prior ectopic, prior tubal surgery, IUD, smoking.
- Medication history (anticoagulants, methotrexate sensitivities — pre-existing liver/renal disease relevant for medical management).
Examination
- Vitals, capillary refill, peritonism.
- Pelvic exam (cervical motion tenderness, adnexal mass).
Investigations
As above plus: blood group + Rhesus status, HIV (always offered), syphilis, anti-D plan.
Management
Expectant management
Criteria:
- Stable, minimal symptoms.
- β-hCG <1000 IU/L and declining.
- No fetal cardiac activity.
- Adnexal mass <3 cm.
- Patient understands and can return for surveillance.
- Reliable follow-up available.
Protocol:
- Weekly β-hCG until <5 IU/L.
- Repeat TVS if any change in symptoms or β-hCG.
- Counsel about rupture warning signs and 24/7 access.
- Anti-D for Rh-negative.
Success: ~50–70% in well-selected cases.
Medical management — methotrexate
Eligibility (RCOG/NICE criteria):
- Haemodynamically stable.
- No significant pain.
- Unruptured (no significant free fluid).
- β-hCG ≤5000 IU/L (some units use ≤3500; lower threshold = higher success).
- No fetal cardiac activity.
- Adnexal mass ≤3.5 cm.
- No medical contraindications: normal LFTs, renal function, FBC; not breastfeeding; not pregnant with an IUP somewhere else (i.e., no heterotopic); no peptic ulcer disease; not on conflicting medications.
- Patient understands and consents to protocol with follow-up.
Protocol — single-dose regimen (most commonly used):
- Day 1: methotrexate 50 mg/m² IM (typically 75–90 mg total).
- Day 4: β-hCG (baseline trajectory).
- Day 7: β-hCG. Expected fall ≥15% from day 4 to day 7. If achieved → continue weekly β-hCG until <5. If not achieved → repeat dose (up to 3 doses, then surgical).
- Avoid: folate supplements (during treatment), NSAIDs, alcohol, intercourse, sun (photosensitivity), pregnancy attempt for 3 months.
- Side effects: stomatitis, nausea, transient abdominal pain (mimics rupture — distinguish carefully), transient hCG rise day 1–4, transaminitis.
Multi-dose regimen for higher β-hCG, larger lesions, interstitial ectopics: methotrexate alternating with folinic acid rescue (less common in routine practice).
Success rate: ~85–90% with single dose; up to 95% with up to 3 doses.
Surgical management
Indications:
- Ruptured or haemodynamically unstable.
- Severe pain.
- β-hCG > methotrexate criteria (typically >5000).
- Fetal cardiac activity.
- Large ectopic (>3.5 cm).
- Methotrexate contraindicated or failed.
- Patient preference for surgery.
- Heterotopic pregnancy (preserve IUP).
Choice of procedure:
Salpingectomy — removal of the affected tube:
- Preferred if contralateral tube is healthy.
- Lower rate of persistent trophoblast (~0%).
- Lower rate of repeat ectopic in same tube (obviously).
- Subsequent IUP rates similar to salpingostomy in most studies (ESEP trial).
Salpingostomy — incision over the ectopic, removal, preservation of the tube:
- Considered if contralateral tube is absent or diseased and the patient wants future fertility.
- Higher rate of persistent trophoblast (~5–8%) — requires post-op β-hCG follow-up.
- Repeat ectopic rate ~10% in preserved tube.
Approach:
- Laparoscopic in stable patients — quicker recovery, less adhesion formation, equivalent outcomes.
- Open (laparotomy) if haemodynamically unstable, surgeon inexperience with laparoscopy, dense adhesions.
- Pfannenstiel or midline incision depending on need for exposure.
Difficult sites
Interstitial (cornual) ectopic:
- High risk of catastrophic rupture (8–12 weeks).
- Options: methotrexate (multi-dose), laparoscopic cornual resection, hysteroscopic removal (specialist), laparotomy with cornuostomy or cornual resection ± wedge resection of uterine wall.
- Future pregnancies after cornual resection: risk of uterine rupture; counsel about elective CS.
Cervical ectopic:
- Methotrexate (often multi-dose) first-line; intra-sac KCl for fetal cardiac activity.
- Avoid blind curettage — catastrophic bleeding.
- If bleeding profuse: uterine artery embolisation, cervical cerclage (Shirodkar suture) to tamponade, Foley balloon, or hysterectomy as last resort.
Caesarean scar pregnancy (CSP):
- Treatment must be promptly given — risk of rupture or placenta percreta if continued.
- Options: intra-sac methotrexate + systemic methotrexate; uterine artery embolisation + curettage; laparoscopic or open scar resection.
- Avoid expectant management for typical CSP (high morbidity).
Ovarian ectopic:
- Often diagnosed at laparoscopy; salpingo-oophorectomy or ovarian cystectomy with reconstruction.
Abdominal pregnancy:
- Rare; high maternal mortality if missed.
- Surgical removal; leave placenta in situ if attached to bowel or major vessels (risk of catastrophic bleed if removed); methotrexate to involute residual trophoblast.
Heterotopic pregnancy:
- Surgical management of ectopic preserving IUP (laparoscopic salpingectomy is the typical approach).
- Methotrexate contraindicated (would harm IUP).
- Counsel on continued IUP outcomes.
Anti-D
All Rh-negative women with ectopic pregnancy must receive anti-D (250 IU IM if <20 weeks gestation, 1500 IU if more advanced). See rh-isoimmunisation.
Counselling
- Future fertility: ~65% will have a subsequent IUP within 18 months. Risk of repeat ectopic ~10–15%.
- Early ultrasound in next pregnancy at 6–7 weeks to confirm intrauterine location.
- Address grief — ectopic is a pregnancy loss; offer bereavement support.
- Contraception: usual reversible methods safe; IUD may be considered after careful counselling.
Red flags / pitfalls
- Wait-and-see in a shocked patient — go to theatre.
- Salpingostomy without warning patient about persistent trophoblast — needs weekly β-hCG.
- Methotrexate in heterotopic pregnancy — contraindicated.
- Curettage in cervical ectopic — can be fatal.
- Missing scar ectopic — TVS specifically.
- Inadequate anti-D.
- Not screening HIV / counselling sexual health.
- Failure to organise post-treatment surveillance β-hCG.
- Missing the second pregnancy (IUP + ectopic) in ART.
- Forgetting psychological impact — refer for support.
Evidence anchors
- RCOG Green-top Guideline No. 21 — Management of Tubal Pregnancy (2016).
- NICE NG126 — Ectopic Pregnancy and Miscarriage (2019).
- ACOG Practice Bulletin No. 193 — Tubal Ectopic Pregnancy.
- Mol F, et al. European Surgery in Ectopic Pregnancy (ESEP) study. Lancet 2014 — salpingotomy vs salpingectomy.
- ASRM Practice Committee — Medical Treatment of Ectopic Pregnancy.
- Society of Family Planning — Caesarean Scar Pregnancy guideline.
- South African National Department of Health Maternity Care Guidelines and STG/EML (latest).
- Saving Mothers Reports (NCCEMD, South Africa) — ectopic-related deaths and lessons.