Other tests that have limited use. Patients with ectopic pregnancy may have elevated serum markers of smooth muscle destruction such as creatinine phosphokinase (CPK), myoglobin, and smooth muscle heavy-chain myosin (SMHC). However, these tests are of limited value in diagnosing ectopic pregnancy.27 SMHC may be of use in evaluating pregnancies less than 5 weeks’ gestation when the TVUS is not diagnostic. Serum vascular endothelial growth factor is another marker elevated in women with ectopic pregnancy; levels greater than 200 pg/mL distinguish ectopic pregnancy from intrauterine pregnancy (sensitivity=60%, specificity=90%).28
Imaging
In normal pregnancies, a gestational sac is seen on TVUS between 4 and 5 weeks’ gestation;29 the yolk sac is visible at around 6 weeks; and an embryo can be detected between 6 and 7 weeks. A gestational sac greater than 10 mm in diameter without a yolk sac, or greater than 25 mm without an embryo, indicates an abnormal regnancy.9,29 Presence of an intrauterine pregnancy on ultrasound effectively rules out ectopic pregnancy because heterotopic pregnancy is rare (1 in 2600–30,000 pregnancies).30 Hormonal changes associated with pregnancy result in a uterine endometrial fluid collection (pseudo-sac) in 8% of ectopic pregnancies.31
Specific diagnostic finding for ectopic pregnancy. A gestational sac visible on ultrasound with a yolk sac or fetal pole outside the endometrial cavity (TABLE 2) is diagnostic of ectopic pregnancy. The initial ultrasound is indeterminate in 15% to 20% of women with clinical features suggesting ectopic pregnancy.14,15 Dart et al32 developed a subclassification system of indeterminate ultrasound including 5 categories that stratify the risk of ectopic pregnancy (TABLE 3).
Endometrial stripe thickness of dubious value. For patients with an empty uterus on TVUS and a β-hCG level below the discriminatory zone, endometrial stripe thickness may identify an abnormal pregnancy. In a retrospective study of 117 patients with β-hCG levels less than 1500 mIU/mL, stripe thickness <6 mm had a sensitivity of 100% in identifying ectopic pregnancy or miscarriage; at >13 mm, it had a specificity of 100%.33
Two recent studies, however, have called into question the value of stripe thickness in identifying ectopic pregnancy. One suggested it was of little value with β-hCG levels <1500 mIU/mL,34 and the other concluded its predictive value for ectopic pregnancy and the likelihood of obtaining chorionic villi on D&C is confined to β-hCG values at or below 1000 mIU/mL.35
Color-enhanced sonography. The addition of endovaginal color-flow imaging to sonography enables exclusion of ectopic pregnancy by establishing findings consistent with a nonviable intrauterine pregnancy: an intrauterine gestational sac, nonvisualization of an adnexal mass, and absent placental blood flow (sensitivity=95%, specificity=98%).12 Color-flow Doppler imaging shows enhanced blood flow to the affected tube. A cutoff value of 8% change in tubal blood flow has been used to diagnose ectopic pregnancy (sensitivity=85%, specificity=96%).36 In cases where the gestational sac is questionable or absent, color-flow Doppler may expedite diagnosis and possibly identify candidates for expectant or medical management.
When an MRI might help. Magnetic resonance imaging (MRI), in a small study of 37 patients, allowed recognition of tubal wall enhancements and fresh tubal hematoma, and was diagnostic in 21 patients.37 An MRI may be useful when precise and early diagnosis of ectopic pregnancy is imperative, such as pre-existing damage to the contralateral tube where preservation of tubal patency is paramount and when prior TVUS is inconclusive.37
TABLE 3
Detecting ectopic pregnancy with ultrasound and β-hCG levels
| SUBCLASS | β-hCG <1000 mIU/mL, % (95% CI) | β-hCG >1000 mIU/mL, % (95% CI) |
|---|---|---|
| Empty uterus | 17.9 (12.7–24.2) | 6.0 (2.2–12.8) |
| Nonspecific intrauterine fluid* | 12.2 (4.6–25.0) | 1.2 (0.1–5.9) |
| Echogenic intrauterine material | 10.5 (1.8–30.6) | 2.7 (0.5–8.4) |
| Abnormal intrauterine sac† | 0.0 (0.0–39.3) | 0.0 (0.0–3.1) |
| Normal intrauterine sac | 0.0 (0.0–34.8) | 0.0 (0.0–8.4) |
| * Anechoic intrauterine fluid collection >10 mm diameter with no echogenic border. | ||
| † Anechoic intrauterine fluid collection >10 mm diameter with no yolk sac or fetal pole or grossly irregular border. | ||
| Source: Dart et al 2002.32 | ||
A practical evaluation algorithm
Prediction models based on clinical presentation, which classify patients into high-, intermediate-, and low-risk groups, are useful for estimating the risk of ectopic pregnancy in first-trimester patients (FIGURE). Diagnostic pathways incorporating physical findings, quantitative β-hCG levels, and ultrasound results have been developed to manage possible ectopic pregnancy.38,39 A protocol created by Barnhart using β-hCG and TVUS was accurate and safe when applied to women presenting in emergency settings (sensitivity=100%, specificity=99.9%).30 If β-hCG levels were greater than 1500 mIU/mL, ultrasound was performed. Clinically stable patients with β-hCG levels below 1500 mIU/mL were followed with serial β-hCG levels.