Edited By: Luan Lawson, MD
Brody School of Medicine at East Carolina University
Greenville, North Carolina
- Describe the mortality and morbidity associated with ectopic pregnancies.
- Explain difficulties associated with making an accurate diagnosis.
- Demonstrate understanding of different treatment modalities for ectopic pregnancy.
- Understand diagnostic and treatment algorithms to make appropriate dispositions for patients suspected of having an ectopic pregnancy.
Ectopic pregnancy is a "can't miss diagnosis" for all clinicians. Ectopic pregnancy is defined as any pregnancy implanted outside the uterus, with approximately 97% occurring in the fallopian tube. It is a life threatening condition complicating 1 in 80 pregnancies presenting to emergency departments. The incidence of ectopic pregnancies has risen over the past several decades, but improved modalities of diagnosis and management have decreased the case fatality rate from 69% in 1876, to 0.35% in 1970, to 0.05% in 1986. Despite the improved diagnostic modalities, ectopic pregnancy is still frequently misdiagnosed on initial presentation with up to 40-50% of patients correctly diagnosed on repeat visits. Overall, it accounts for about 9% of all pregnancy-related maternal deaths, and is one of the leading causes of maternal death in the first trimester. Early diagnosis and treatment is essential in reducing maternal mortality and preserving future fertility.
Patients at greatest risk for developing an ectopic pregnancy are those with anatomic abnormalities impairing the ability of a fertilized egg to implant in the uterus. Tubal factors including history of salpingitis, tubal surgery, and previous ectopic pregnancy are the most important risk factors for ectopic pregnancy. It is important to recognize that many ectopic pregnancies occur in women without any recognized risk factors, so maintaining a high index of suspicion is paramount to making an accurate diagnosis.
Risk Factors for Ectopic Pregnancy
- Pelvic Inflammatory Disease
- Previous ectopic pregnancy
- Tubal surgery including BTL
- Previous pelvic or abdominal surgery
- Tubal Pathology
- In utero diethylstilbestrol (DES) exposure
- Intrauterine device use
- Infertility and infertility treatments
Classic Presentation - Frequently Atypical
Symptoms of an ectopic pregnancy develop as the fetus grows by distorting surrounding tissue or rupturing causing peritoneal irritation. The classic triad of abdominal pain, delayed menses, and vaginal bleeding is neither sensitive nor specific for ectopic pregnancy. Symptoms and physical findings are highly variable among patients, making the diagnosis extremely challenging. Abdominal pain is the most common symptom and is reported in as many as 98.6% of patients, but its severity and quality is highly variable. Amenorrhea is present in almost 75% of women with ectopic pregnancies, and irregular vaginal bleeding occurs in 56.4%, but may be minimal even in the critically ill patient. Tenderness on pelvic exam is the most common physical exam finding, but few patients will have a palpable pelvic mass. The diagnosis of ectopic pregnancy should be considered in female patients presenting to the ED with syncope or unexplained hypotension. The majority of patients with an ectopic pregnancy have normal vital signs until they have experienced significant blood loss. Paradoxic bradycardia can occur in ectopic pregnancy, thus vital signs should not be reassuring and all patients with ectopic pregnancy should be considered potentially unstable.
Initial Actions and Primary Survey
Initial evaluation of all ED patients should focus on the ABC's. A pregnancy test should be obtained on all female patients of childbearing age (consider ages 10-60) who present to the ED with complaint of abdominal pain, amenorrhea, or vaginal bleeding. The newer generations of urine pregnancy tests are excellent screening tools for pregnancy and can detect β-hCG levels in the range of 25-50 mIU/mL. Any patient suspected of having an ectopic pregnancy should be immediately placed on a monitor with rapid assessment of vital signs. Concurrently, 2 large bore IVs should be obtained and CBC, type and screen, and quantitative β-hCG should be ordered. Narcotic analgesia should be administered to control the patient's pain. If the patient is ill appearing, has severe pain, or any abnormal vital signs, they should receive an immediate bolus of normal saline. Transfusion of O negative blood should be strongly considered in the setting of hypotension. In unstable patients suspected of having a ruptured ectopic pregnancy, a FAST (Focused Abdominal Sonogram in Trauma) exam can be performed to rapidly detect hemoperitoneum.
In one study, only 10% of physicians were able to identify the presence of less than 400cc of free intraperitoneal fluid, suggesting that a positive FAST typically indicates a large amount of acute blood loss. The combination of positive FAST and positive pregnancy test should prompt an immediate call to OB-GYN to take the patient to the OR for a presumptive diagnosis of ruptured ectopic pregnancy. Bedside pelvic ultrasonography by emergency medicine physicians has led to improved time to diagnosis and should be performed whenever feasible.
All women of childbearing age presenting to the ED with abdominal or pelvic pain should have a urine pregnancy test performed immediately on arrival. If you have a strong suspicion of pregnancy and the patient provides a dilute urine, a serum pregnancy test should be considered. Hemodynamically unstable patients with a positive pregnancy test in the first trimester should be assumed to have an ectopic pregnancy until proven otherwise and should be immediately taken to the OR by OB/GYN for definitive diagnosis and treatment.
Stable patients in the first trimester of pregnancy with abdominal pain and vaginal bleeding can be further evaluated in the ED. A transvaginal ultrasound should be obtained to evaluate for the presence or absence of an IUP. If an IUP is visualized, a concurrent ectopic pregnancy (heterotopic pregnancy) is statistically unlikely unless the patient has received fertility treatments. This occurs spontaneously at a rate of only 1 in 10,000 pregnancies, but the incidence is much higher for women using infertility drugs or assisted reproductive technologies . Finding an IUP in these subsets of patients does not exclude an ectopic because a heterotopic pregnancy is no longer statistically improbable.
The earliest sign of an IUP by transvaginal ultrasound is the double decidual sac sign (click on Figure to the left), occurring at around 4.5-5 weeks after the last menstrual period (LMP). A yolk sac (click the Figure just below the one to the left) is typically identified at 5-6 weeks and the presence of a yolk sac has 100% predictive value for an intrauterine pregnancy. An ectopic pregnancy cannot be excluded until the patient has a yolk sac demonstrated within the gestational sac. A fetal pole and embryonic cardiac activity are usually seen by 6-7 weeks.
The β-hCG is a glycoprotein hormone produced by trophoblasts that doubles approximately every 48-72 hours in the first trimester. The discriminatory zone of β-hCG is the level at which an IUP should be visible by transvaginal ultrasonography, typically 1500-2000 mIU/mL. ACEP's clinical policy on patients presenting to the ED in early pregnancy states that a transvaginal ultrasound should be performed on all patients in whom the diagnosis of ectopic pregnancy is considered despite the β-hCG level, as both IUP's and ruptured ectopics have been diagnosed at very low levels. An ectopic pregnancy is highly likely in patients with a β-hCG level greater than 1500 with the absence of intrauterine pregnancy on transvaginal ultrasound. A serum β-hCG level alone cannot be used to predict the presence of an ectopic or an IUP.
Most patients do not have definitive evidence of an ectopic pregnancy on ultrasound. The likelihood of finding a live extrauterine embryo with positive heart motion using ultrasound is only 8-26%. Ultrasound signs of an ectopic include an empty uterus, extraovarian mass, tubal ring sign (click Figure to the left), and pelvic free fluid.
For stable patients without significant pain, diagnosing an ectopic pregnancy in the absence of an IUP or secondary findings suggestive of an ectopic is accomplished in the outpatient setting by OB/GYN using serial ultrasonography in conjunction with serial serum quantitative β-hCG levels. Patients with a rise in serum β-hCG level slower than expected are highly suspicious for ectopic pregnancy. The doubling rate of β-hCG in ectopics is not consistent and cannot be used as the sole diagnostic marker.
Although rarely used since the advent of ultrasound, culdocentesis is a simple, bedside procedure that can be performed when ultrasonography is not rapidly available on a potentially unstable patient to detect the presence of intraperitoneal blood. A needle is advanced through the posterior vaginal wall into the peritoneal space. Greater than 2ml of nonclotting blood is suggestive of hemoperitoneum and ruptured ectopic pregnancy.
Any patient strongly suspected of having an ectopic pregnancy needs to be medically or surgically managed in conjunction with OB-GYN. Patients with signs of clinical instability or rupture should be managed surgically on an emergent basis. The cornerstones of ED management for these patients include fluid and blood resuscitation, pain management, and OB-GYN consultation. Additionally, 50 �g of anti-D immunoglobulin (RhoGAM) should be administered to any Rh-negative woman in all cases of suspected ectopic pregnancy or vaginal bleeding to prevent alloimmunization of the mother.
Methotrexate is the most successful method to medically manage a patient with ectopic pregnancy and may preserve fertility better than surgical interventions. Methotrexate should only be given in conjunction with OB/GYN consultation. . It works by interfering with syntheses of DNA and cell replication of fetal cells, resulting in involution of the pregnancy. Treatment failure with single dose methotrexate occurs in up to 36% of patients necessitating administration of a second dose of methotrexate if β-hCG values are not decreasing as expected. Contraindications for receiving methotrexate include hemodynamic instability, inability to return for follow-up, breastfeeding, immunodeficiency, renal, liver or pulmonary disease, peptic ulcer disease, and blood dyscrasias. Patients receiving methotrexate often experience abdominal pain 3-7 days after administration which is thought to be secondary to tubal abortion or expanding hematoma within the fallopian tube. Patients presenting with worsening pain need to be evaluated for tubal rupture, and the need for immediate rescue laparoscopy. Unstable patients, those with contraindications to methotrexate therapy, and patients failing medical management should undergo laparoscopy.
All patients suspected of having an ectopic pregnancy are managed in conjunction with OB-GYN. Clinically unstable patients should be managed surgically on an emergent basis. Patients with significant pain without signs of rupture should be admitted for close observation and serial reassessments. Clinically stable patients with an ectopic pregnancy may be managed medically with methotrexate if they have an excellent follow up plan. For those hemodynamically stable patients with inconclusive ultrasound findings where the diagnosis is in doubt, they may be managed as an outpatient with serial ultrasound examinations and β-hCG levels. These patients must have follow-up scheduled with OB/GYN in 48-72 hours. All patients discharged from the ED who have the potential to have an ectopic pregnancy must receive and understand the "ectopic precautions" and be instructed to return to the ED immediately if they develop worsening pain, vaginal bleeding, dizziness, syncope, or weakness.
Pearls and Pitfalls
- The presentation of ectopic pregnancy can be highly variable, so maintaining a high index of suspicion is paramount to making the diagnosis.
- The discriminatory zone is the level of β-hCG at which an IUP should typically be identified, and ranges from 1500-2000 mIU/mL for transvaginal ultrasonography.
- Serum β-hCG values should not be used to determine which patients should have transvaginal ultrasound.
- An ectopic pregnancy can be 'ruled out' in the presence of an IUP in a patient not undergoing infertility treatment.
- Ruptured ectopic pregnancies can be present at very low β-hCG levels.
- Ectopic pregnancy is managed surgically in cases of clinical instability, contraindications to medical therapy, or failure of medical therapy.
- Rh status should be checked on all pregnant patients with vaginal bleeding.
- Any patient discharged from the ED with a potential ectopic pregnancy should understand "ectopic precautions" and have the means to return immediately to the ED.
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