SIGNS AND SYMPTOMS 
Classic triad of amenorrhea, vaginal bleeding, and abdominal pain are present in only 15% of women with ectopic pregnancies:
- Amenorrhea (75–95%)
- Abdominal pain (80–100%):
- Abnormal vaginal bleeding (50–80%)
- Symptoms of pregnancy (10–25%)
- Orthostatic hypotension, dizziness, and syncope (5–35%)
- Abdominal tenderness (55–95%)
- Adnexal tenderness (75–90%)
- Adnexal mass (35–50%)
- Cervical motion tenderness (43%)
History
- Last menstrual period (LMP):
- Majority of ectopics present 5–8 wk after LMP.
- Gestation and parity history
- Vaginal bleeding
- Location, nature, and severity of pain
- History of pelvic surgery, prior ectopic, IUD
- History of fertility treatments
Physical Exam
- Evaluate for signs of peritoneal irritation
- Pelvic exam:
- Note uterine size
- Adnexal size, mass
- Adnexal tenderness
- Presence of tissue in vaginal vault
- Cervical motion tenderness
- Cervical OS open or closed
ESSENTIAL WORKUP
- Pregnancy testing:
- Women of potential childbearing age with vaginal bleeding or abdominal pain must have urine or serum pregnancy test
- Include testing of patients with history of recent elective or spontaneous abortion, tubal ligations, or IUD use
- Quantitative β-human chorionic gonadotropin (β-hCG) in patients with positive qualitative test
- Vital signs unstable:
- 2 large-bore IVs
- Type and cross-match, hemoglobin (Hg)/hematocrit (Hct)
- Bedside ultrasound (US), if immediately available, simultaneous with resuscitation (transvaginal preferred)
- Consult obstetrics/gynecology (OB/GYN) and prepare for immediate surgical intervention
- Vital signs stable:
- Rapid Hg/Hct determination
- Type and Rh
- US (transvaginal preferred)
DIAGNOSIS TESTS & INTERPRETATION
Lab
- Urine pregnancy tests can detect β-hCG levels of 25–50 mIU/L
- Serum can detect β-hCG levels of 25 mIU/L
- Quantitative serum β-hCG; for diagnosis and follow-up:
- Doubles every 2 days in normal early pregnancy (early pregnancy < 10,000 β-hCG mIU/L, 8 days–7 wk)
- β-hCG increases less in ectopic pregnancy
- Correlation with vaginal US increases predictive value
Imaging
- Ultrasonographic evidence of IUP makes ectopic pregnancy less likely:
- Heterotopic pregnancies are possible
- Positive IUP is indicated by double-ringed gestational sac, yolk sac, or fetal pole, and heartbeat seen in uterus
- Transvaginal US; visualization of gestational sac at 5 wk, cardiac activity at 6.5 wk
- Transabdominal US; visualization of gestational sac at 5–6 wk, cardiac activity at 8 wk
- Complex adnexal mass and fluid in cul-de-sac seen in 22% of ectopics and has 94% positive predictive value when present
- Positive pregnancy test with no confirmed IUP and fluid in pelvis; high risk for bleeding ectopic pregnancy
Diagnostic Procedures/Surgery
- US in conjunction with quantitative β-hCG
- Patients with β-hCG levels > 6,500 mIU/L and no intrauterine gestational sac seen on US have 100% chance of having ectopic pregnancy
- Patients with β-hCG levels > 6,500 mIU/L with intrauterine gestational sacs present have 94% chance of having normal pregnancy
- Patients with β-hCG < 2,000 mIU/L are too early to have gestational sac seen by abdominal US and thus cannot be ruled out for ectopic pregnancy
- Patients with β-hCG > 2,000 and < 6,500 mIU/L should have IUP visualized on transvaginal US; suspect ectopic pregnancy if IUP is absent
- Discriminatory hCG value for transvaginal US is between 1,500 and 3,000 mIU/mL
- Culdocentesis to evaluate for intraperitoneal blood if US is unavailable
DIFFERENTIAL DIAGNOSIS
- Positive pregnancy test with vaginal bleeding:
- Positive pregnancy test with no evidence of IUP:
- Positive pregnancy test with evidence of IUP, abdominal pain, or adnexal tenderness:
[Outline]
PRE-HOSPITAL
Cautions: Female patients of childbearing age presenting in shock may have unrecognized ruptured ectopic pregnancy
INITIAL STABILIZATION/THERAPY
- Vital signs unstable:
- Airway management, resuscitate as needed
- Fluid therapy with 2 large-bore IVs, oxygen, and monitor
- Type specific, or O-negative blood if hypotensive after initial fluid bolus
- Consult gynecology and transport to OR immediately for surgery
- Vital signs stable:
- Evidence of ectopic pregnancy on US:
- Obstetric–gynecologic evaluation for surgery vs. outpatient methotrexate treatment
- For patients in whom future fertility is desired, methotrexate is the best option; otherwise surgery is the definitive treatment
- No evidence of ectopic pregnancy (pregnancy of unknown location [PUL]: Early IUP vs. early ectopic):
- Desired pregnancy: Serial β-hCG every 48 hr in stable, reliable patients and in conjunction with obstetrician
- Undesired pregnancy: Dilation and curettage to evacuate uterus and confirm presence of products of conception
ED TREATMENT/PROCEDURES
Methotrexate: Initiated only in conjunction with obstetric consultant and close follow-up:
- Reliable patients with unruptured ectopic pregnancies < 3.5 cm
- β-hCG levels < 6,000–15,000
- Contraindications:
- Breast-feeding
- Immunodeficiency
- Pre-existing blood dyscrasia
- Clinically significant anemia
- Known sensitivity to methotrexate
- Active pulmonary disease
- Peptic ulcer disease
- Hepatic dysfunction
- Renal dysfunction
- Alcoholism
- Alcoholic liver disease
- Ectopic mass > 3.5 cm (relative contraindication)
- Embryonic cardiac motion (relative contraindication)
- Most common dosing, single dose (50 mg/m2); serial β-hCG on days 2, 4, and 7
- If < 25% decline in β-hCG from day of 1st injection, 2nd dose is given
- Multidose treatment is associated with less treatment failure
- Common side effects:
- Worsening abdominal pain
- Nausea, vomiting, and diarrhea
- Worsening abdominal pain usually occurs 3–7 days after methotrexate initiation.
- These are usually tubal miscarriages
- Follow-up USs are essential to rule out ectopic rupture
- Most common complication, tubal rupture in 4%
- Factors associated with methotrexate treatment failure:
- Initial hCG > 5,000 mIU (5,000–9,999 mIU/mL—13% failure rate, > 15,000 mIU/mL failure rate as high as 32%)
- Moderate to large free peritoneal fluid on US
- Presence of fetal cardiac activity
- Pretreatment increase in serum hCG level of more than 50% over a 48 hr period
MEDICATION
- Methotrexate: 50 mg/m2 IM/IV × 1
- RhoGAM in Rh-negative women: 50 µg IM in women ≤12 wk pregnant; 300 µg IM in women > 12 wk pregnant
[Outline]
DISPOSITION
Admission Criteria
- Any patient with confirmed ectopic pregnancy who is hemodynamically unstable
- Unreliable patients with increased risk factors, no available US, β-hCG > 6,500 with no evidence of IUP should be admitted for observation and serial β-hCG tests
Discharge Criteria
- Decision for outpatient management should be made in conjunction with OB/GYN
- Hemodynamically stable and reliable patients with workup that cannot rule out ectopic pregnancy:
- Strict follow-up for serial β-hCG tests every 2 days
- Patients should be recorded in logbook with phone numbers to ensure follow-up
- Ectopic precautions: Patients should return to emergency room immediately for:
- Increasing abdominal pain
- Vaginal bleeding
- Syncope or dizziness
- Patients should not be left alone until diagnosis of ectopic pregnancy can be safely ruled out
- Family and friends should also be instructed on warning signs and symptoms of ruptured/bleeding ectopic pregnancies
Issues for Referral
Phone consultation (at a minimum) with OB/GYN is essential when discharging a possible ectopic pregnancy
FOLLOW-UP RECOMMENDATIONS
All patients with positive pregnancy tests and unconfirmed IUP must be followed by an OB/GYN
[Outline]
- Barnhart KT. Clinical practice. Ectopic pregnancy. N Engl J Med. 2009;361:379–387.
- Crochet JR, Bastian LA, Chireau MV. Does this woman have an ectopic pregnancy?: The rational clinical examination systematic review. JAMA. 2013;309:1722–1729.
- Huancahuari N. Emergencies in early pregnancy. Emerg Med Clin North Am. 2012;30:837–847.
- Marx JA, Hockberger RS, Walls RM, et al. Rosen's Emergency Medicine: Concepts and Clinical Practice. 7th ed. St. Louis, MO: Mosby; 2009.
- Stein JC, Wang R, Adler N, et al. Emergency physician ultrasonography for evaluating patients at risk for ectopic pregnancy: A meta-analysis. Ann Emerg Med. 2010;56:674–683.
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