Applied Evidence

Ectopic pregnancy: Zero in on these lab and imaging clues

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Quantitative β-hCG measurements and transvaginal ultrasound findings interpreted in light of a β-hCG “cutoff” can reliably guide clinical decisions.




Administer a urine pregnancy test for women of childbearing age who present with abdominal pain or vaginal bleeding. C

Initiate quantitative beta-human chorionic gonadotropin testing and order transvaginal ultrasound for women with abdominal pain or vaginal bleeding and a positive urine pregnancy test, but no confirmation of intrauterine pregnancy by abdominal ultrasound. B

Refer hemodynamically stable patients with ectopic pregnancy for laparoscopic salpingostomy. For selected patients, an alternative is medical treatment with methotrexate. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

CASE 1 Helen, who is 31 years old and G1P0, comes in to the office with a 10-day history of intermittent vaginal spotting without pelvic pain. A home pregnancy test 2 weeks earlier was positive, and this is a desired pregnancy. She has had no gynecologic disorders. It has been 6 weeks since her last menstrual period. Her vital signs are normal and her abdominal and pelvic exams are unremarkable. The cervical os is closed and there is a small amount of blood in the vaginal vault. Her family physician (FP) draws blood to measure the level of beta-human chorionic gonadotropin (β-hCG) and orders a transvaginal ultrasound (TVUS).

CASE 2 Mary is 28 years old and G2P1. She has experienced intermittent vaginal spotting and moderate pelvic discomfort for 3 days. She fears a return of pelvic inflammatory disease (PID). Her period is one week late and the office pregnancy test is positive. Her vital signs are normal. She has no cervical motion tenderness, but there is mild right adnexal tenderness to palpation. Her FP draws blood for a serum β-hCG level and orders a TVUS.

Assess physical and history findings for perspective

Abdominal or pelvic pain and vaginal bleeding in the first trimester are the most common presenting symptoms of ectopic pregnancies.1 Physical examination will often elicit lateral or bilateral abdominal or pelvic tenderness, peritoneal signs, and cervical motion tenderness. But such findings (or their absence) cannot confirm (or exclude) the diagnosis with a high level of reliability.2 A woman with a positive pregnancy test and pelvic pain or vaginal bleeding may instead have a normal pregnancy, spontaneous abortion (failing intrauterine pregnancy), or a disorder such as PID, acute appendicitis, tubo-ovarian abscess, or ovarian torsion.

In an early ectopic pregnancy, vital signs are usually normal. Even in cases of ruptured ectopic pregnancy, hypotension or tachycardia is present in <40% of cases.3

Factors conferring a relative risk ratio >2 for ectopic pregnancy are a previous ectopic pregnancy; documented tubal pathology or tubal instrumentation (eg, tubal sterilization or tubal corrective surgery); assisted reproductive technology such as in vitro fertilization; history of infertility; smoking; or a history of PID.4-11

Proceed with a laboratory and imaging strategy

When a woman who has tested positive for pregnancy presents with abdominal pain or vaginal bleeding and a normal intrauterine pregnancy (IUP) has not been confirmed by abdominal ultrasound, request a quantitative measurement of the β-hCG level and arrange for urgent TVUS.12,13 If pregnancy has been unsuspected in a patient with these symptoms, perform a urine test for pregnancy immediately and follow up with ultrasound.14

If TVUS reveals either IUP or ectopic pregnancy, management is relatively straightforward. However, an inconclusive TVUS result indicates a “pregnancy of unknown location” (PUL) and necessitates further testing and follow-up to achieve a final diagnosis.15

Monitor β-hCG levels
Valuable diagnostic measures include documenting the initial serum level of β-hCG, monitoring the subsequent rise-or-fall pattern in the level, and making use of the “discriminatory cutoff” value.

β-hCG, made by placental cells, can be detected in the mother’s blood approximately 11 days after conception, and in the urine 12 to 14 days after conception. The serum β-hCG level normally doubles every 48 to 72 hours until it reaches its peak in the first 8 to 11 weeks of pregnancy. The level then declines and plateaus.

”Discriminatory cutoff” is a widely accepted concept signifying the level of β-hCG at which a normal IUP can be visualized by ultrasonography with sensitivity approaching 100%.16 Generally an intrauterine sac can by visualized by abdominal ultrasound when the serum β-hCG level is >6500 mIU/mL.17 Visualization with TVUS (the preferred modality) has been demonstrated when the serum β-hCG level is as low as 1000 mIU/mL.17 However, the generally accepted cutoff range is 1500 to 2500 mIU/mL, based on several studies.13,18-20 The absence of an IUP in a pregnant woman with pain or bleeding and a β-hCG level above the cutoff implies an ectopic pregnancy18 or a failing IUP (spontaneous abortion).


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