Anne S., a 32-year-old marketing analyst, arrives at your emergency department (ED) complaining of 2 hours of pelvic pain. Her temperature is 37.2°C, respiratory rate 14 breaths/minute, pulse 95 beats/min and blood pressure 110/70 mm Hg with no postural change. She’s otherwise healthy and sexually active with one partner, her common-law spouse. She isn’t using birth control and her last normal menstrual period was about 5 ½ weeks ago. She’s had vaginal spotting for the last 2 days, but her periods are somewhat irregular, occurring every 4-6 weeks and lasting 4-5 days. She’s never been pregnant before. A urine pregnancy test is ordered according to department protocol, and is positive.
On examination, her abdomen is soft and non-tender, and the cervix is closed, with some blood at the cervical os. You don’t feel any adnexal masses or adnexal tenderness. She’s uncomfortable during the bimanual exam with definite cervical motion tenderness.
If she has no risk factors, it’s not an ectopic pregnancy
Ectopic pregnancy remains the most common life-threatening emergency in the first trimester, despite advances in both early diagnosis and treatment. The frequency has been steadily increasing, from an estimated 4.5 per 1,000 pregnancies in 1970 to 19.7 in 1992.1,2 In the ED, the prevalence is much higher than in the general population, affecting 6-16% of women who present with pain, bleeding or both in the first few months of gestation; i.e. up to 1 out of 6 patients.3
Risk factors are well-documented and consist mainly of conditions that affect the fallopian tubes — pelvic inflammatory disease, tubal scarring, prior tubal surgery, infertility and smoking.Family doctors can use risk factors to identify asymptomatic expectant mothers who might benefit from screening imaging, but this doesn’t help in the ED. More than half of the women diagnosed with ectopic pregnancy have no identifiable risk factors.4,5
A simple physical exam will rule it out
Though most clinicians are well aware that hypotension and tachycardia in the setting of early pregnancy represents a ruptured ectopic pregnancy until proven otherwise, an unruptured one can be very difficult to identify on physical examination. The classic findings of unilateral adnexal mass and tenderness can often be identified in patients without ectopic pregnancy (but with a large corpus luteum cyst, for example) and conversely, many women with the condition won’t demonstrate any of these signs. Ectopic pregnancy is associated with cervical motion tenderness,4 but again, this can be seen in other conditions such as cervicitis.
Serum beta-hCG levels are sufficient
Confirmation of pregnancy is clearly the first step in assessing the possibility of an extrauterine gestation. Urine β-human chorionic gonadotropin (β-hCG) tests can detect levels of 20-50 IU/L, while serum testing can identify as little as 5 IU/L. In most cases, a negative urine value is adequate to rule out pregnancy. If there’s still a high suspicion, the serum test will provide a definitive answer. Once established, however, serum β-hCG levels won’t help you in confirming the pregnancy location. Although it’s true that patients with low β-hCG (< 1,000 IU/L) have a higher risk of ectopic pregnancy relative to people with higher levels, there’s no cut-off that serves as an absolute criterium.5,6 Furthermore, extremely low or declining levels (< 100 IU/L) don’t guarantee a benign clinical course, as rupture has been reported in patients with serum β-hCG below even this minimal level.7
Ultrasound imaging — no myths here!
Targeted bedside ultrasound (EDTU) is now an established part of the ED physician’s skill set for a variety of conditions. Evidence is mounting that ultrasound (US) imaging of early pregnancy has improved in resolution, familiarity and ease of use. EDTU by trained emergency physicians in the assessment of first trimester bleeding or pain shortens ED length of stay and time to definitive treatment, and reduces overall costs as compared to traditional US.8,9 Where possible, these patients should all undergo EDTU during their initial assessment.
Transvaginal US is better than transabdominal US at visualizing intrauterine gestations, particularly in the first 2 weeks after an expected menstrual period (4-6 weeks’ gestation). If a definite intrauterine gestational sac or yolk sac and fetal pole with or without a heartbeat can be demonstrated, then for most individuals, an ectopic pregnancy has been ruled out. The exception to this rule is women who are undergoing fertility treatments (particularly ovulation induction), as they’re at higher risk of heterotopic pregnancy — dizygotic twins with one intrauterine and the other extrauterine.
If the EDTU doesn’t identify a definitive intrauterine pregnancy, or the patient is receiving fertility treatments, then you should order a formal US (technologist performed and radiologist interpreted). When a FAST exam — focused assessment with sonography for trauma — demonstrates pelvic and intra-abdominal free fluid, call for an urgent gynecologic consultation and begin aggressive fluid resuscitation — it could be a ruptured ectopic pregnancy. Individuals with significant pain and an empty uterus on EDTU who have no visible intra-abdominal free fluid should have a second EDTU performed after a brief period in the Trendelenburg position (supine, with feet higher than the head). Often an initially negative scan for free fluid will become positive following this intervention.
US plus serum beta-hCG
To better clarify the situation in the stable patient with a nondiagnostic bedside or formal US, it may be helpful to order a serum β-hCG. The discriminatory threshold — a term used to define the level of hormone at which a normally developing intrauterine pregnancy can be visualized on US — varies from institution to institution and is operator-dependent, with more experienced technicians having lower thresholds. Generally it’s 1,000-1,500 IU/L for a formal transvaginal ultrasound. So if you had a case where the US showed no definitive evidence of either intrauterine or ectopic pregnancy but the serum β-hCG was above the centre’s threshold, you could assume a high likelihood of ectopic pregnancy. Repeated imaging in 48 hours may be necessary to confirm a rising level with an empty uterus.
In the last decade, medical therapy with intramuscular methotrexate has become commonplace in selected lower-risk individuals. Although there are a variety of protocols, the patient must be hemodynamically stable with serum β-hCG levels generally < 5,000 IU/L and no evidence of ectopic fetal cardiac activity or tubal rupture.3 Remember that your patient will remain at risk for rupture after the drug’s administration until the serum β-hCG levels are undetectable.
Surgical treatment of ectopic pregnancy is reserved for those who can’t have or haven’t responded to pharmacologic therapy. It has evolved from open incision removal of the fallopian tube and its ovary — salpingo-oophorectomy — to laparoscopic removal of the gestational sac only, sparing the tube (salpingostomy).
Back to the case
Anne S. underwent a bedside EDTU, where no evidence of intrauterine gestation or intra-abdominal free fluid was found. She was sent for a formal US, which confirmed the absence of intrauterine gestation and showed a complex adnexal mass separate from the ovary. A serum β-hCG was ordered and indicated a level of 1,800 IU/L, well above your centre’s discriminatory threshold. She was diagnosed with an ectopic pregnancy, referred to a gynecologist and treated successfully with methotrexate.
Heather Murray, MD, FRCPC, is an emergency physician and an assistant professor in the Department of Emergency Medicine and the Department of Community Health and Epidemiology at Queen’s University in Kingston, ON.
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