Ectopic pregnancy is the result of a flaw in human reproductive physiology that allows the conceptus to implant and mature outside the endometrial cavity (see the image below), which ultimately ends in the death of the fetus. Without timely diagnosis and treatment, ectopic pregnancy can become a life-threatening situation. 

Signs and symptoms

The classic clinical triad of ectopic pregnancy is as follows:

• Abdominal pain
• Amenorrhea
• Vaginal bleeding

Unfortunately, only about 50% of patients present with all 3 symptoms.

Patients may present with other symptoms common to early pregnancy (eg, nausea, breast fullness). The following symptoms have also been reported:

• Painful fetal movements (in the case of advanced abdominal pregnancy)
• Dizziness or weakness
• Fever
• Flulike symptoms
• Vomiting
• Syncope
• Cardiac arrest

The presence of the following signs suggests a surgical emergency:

• Abdominal rigidity
• Involuntary guarding
• Severe tenderness
• Evidence of hypovolemic shock (eg, orthostatic blood pressure changes, tachycardia)

Diagnosis

Serum β-HCG levels

In a normal pregnancy, the β-HCG level doubles every 48-72 hours until it reaches 10,000-20,000mIU/mL. In ectopic pregnancies, β-HCG levels usually increase less. Mean serum β-HCG levels are lower in ectopic pregnancies than in healthy pregnancies.

No single serum β-HCG level is diagnostic of an ectopic pregnancy. Serial serum β-HCG levels are necessary to differentiate between normal and abnormal pregnancies and to monitor resolution of ectopic pregnancy once therapy has been initiated.

The discriminatory zone of β-HCG (ie, the level above which an imaging scan should reliably visualize a gestational sac within the uterus in a normal intrauterine pregnancy) is as follows:

• 1500-1800 mIU/mL with transvaginal ultrasonography, but up to 2300 mIU/mL with multiple gestates ^[2]
• 6000-6500 mIU/mL with abdominal ultrasonography

Absence of an intrauterine pregnancy on a scan when the β-HCG level is above the discriminatory zone represents an ectopic pregnancy or a recent abortion.

Ultrasonography

Ultrasonography is probably the most important tool for diagnosing an extrauterine pregnancy.

Visualization of an intrauterine sac, with or without fetal cardiac activity, is often adequate to exclude ectopic pregnancy. ^[3]

Transvaginal ultrasonography, or endovaginal ultrasonography, can be used to visualize an intrauterine pregnancy by 24 days post ovulation or 38 days after the last menstrual period (about 1 week earlier than transabdominal ultrasonography). An empty uterus on endovaginal ultrasonographic images in patients with a serum β-HCG level greater than the discriminatory cut-off value is an ectopic pregnancy until proved otherwise.

Color-flow Doppler ultrasonography improves the diagnostic sensitivity and specificity of transvaginal ultrasonography, especially in cases in which a gestational sac is questionable or absent.

Laparoscopy

Laparoscopy remains the criterion standard for diagnosis; however, its routine use on all patients suspected of ectopic pregnancy may lead to unnecessary risks, morbidity, and costs. Moreover, laparoscopy can miss up to 4% of early ectopic pregnancies.

Laparoscopy is indicated for patients who are in pain or hemodynamically unstable.

Management

Therapeutic options in ectopic pregnancy are as follows:

• Expectant management
• Methotrexate
• Surgery

Expectant management

Candidates for successful expectant management should be asymptomatic and have no evidence of rupture or hemodynamic instability. Candidates should demonstrate objective evidence of resolution (eg, declining β-HCG levels).

Close follow-up and patient compliance are of paramount importance, as tubal rupture may occur despite low and declining serum levels of β-HCG.

Methotrexate

Methotrexate is the standard medical treatment for unruptured ectopic pregnancy. A single-dose IM injection is the more popular regimen. The ideal candidate should have the following:

• Hemodynamic stability
• No severe or persisting abdominal pain
• The ability to follow up multiple times
• Normal baseline liver and renal function test results

Absolute contraindications to methotrexate therapy include the following:

• Existence of an intrauterine pregnancy
• Immunodeficiency
• Moderate to severe anemia, leukopenia, or thrombocytopenia
• Sensitivity to methotrexate
• Active pulmonary or peptic ulcer disease
• Clinically important hepatic or renal dysfunction
• Breastfeeding
• Evidence of tubal rupture

Surgical treatment

Laparoscopy has become the recommended surgical approach in most cases. Laparotomy is usually reserved for patients who are hemodynamically unstable or for patients with cornual ectopic pregnancies; it also is a preferred method for surgeons inexperienced in laparoscopy and in patients in whom a laparoscopic approach is difficult.