Ectopic Pregnancy: Diagnosis and Management in the ER
Definition: A conceptus is implanted outside of the uterine cavity.
Pathophysiology: Fertilization occurs in the ampulla of the fallopian tube. The zygote then passes through the remainder of the fallopian tube to implant into the endometrium of the uterus. Ectopic pregnancy (EP) occurs when the zygote implants elsewhere. Most EPs occur in the fallopian tube. The zygote can also implant in the abdominal cavity, and on the cervix and ovary. Abdominal EPs most commonly occur due to early rupture or abortion of a tubal pregnancy with subsequent reimplantation in the peritoneal cavity.
Ectopic pregnancies do not usually have normal placentas. This may be why there is a higher incidence of blighted ovums with EPs. When the vascular supply to the placenta is disrupted, tubal abortion occurs. This results in bleeding into the fallopian tube and hematoma formation. The fallopian tube can intermittently become distended with leakage of the blood from the fimbriated end of the tube into the peritoneal cavity. The aborted EP and hematoma can partially or completely extrude out of the end of the fallopian tube or through a rupture site in the tube wall. Usually, tubal rupture is spontaneous. However, some precipitating factors can include trauma associated with coitus and bimanual examination.
Epidemiology: The incidence of EP in 1992 was 19.7 per 1000 or almost 2%. This increased from 4.5 per 1000 reported in 1970. One caveat to this statistic is that the number of reported pregnancies could be under-reported due to illegal terminations and unknown spontaneous abortions, resulting in a falsely-high incidence rate of EPs. Some reasons that could be attributed to the increase include an increased incidence of sexually transmitted tubal infections, unsuccessful tubal sterilizations, assisted reproductive techniques, previous pelvic surgery, and more sensitive and earlier diagnostic techniques.
The case-fatality rate per 10,000 EPs decreased from 35.5 in 1970 and 8.8 in 1980 to 3.8 in 1989. This decrease is observed in both white and non-white women. However, non-white women have a 3.4 times greater risk of death with EP. Teenagers have the highest mortality rate. EPs remain the leading cause of death in the first trimester of pregnancy and the second leading cause of maternal mortality overall.
Major Risk Factors: Major risk factors of EP include pelvic inflammatory disease, history of tubal surgery, use of an intrauterine device, in-utero exposure to diethylstilbestrol, assisted reproduction techniques, and previous ectopic pregnancy. Although these risk factors are often absent, they can be useful if present to raise clinical suspicion of EP.
History: The classic triad of EP symptoms are abdominal pain, vaginal bleeding or spotting, and a history of amenorrhea. However, these symptoms have a low positive predictive value as they are more commonly seen in threatened or spontaneous abortion and may also occur due to other causes in non-pregnant women. Other presentations include sudden abdominal pain with hypovolemic shock and asymptomatic patients with an incidental finding on ultrasound examination. Patients can also present with the typical symptoms of early pregnancy. EP should be considered in all women of childbearing age who present with abdominal or pelvic complaints or with unexplained signs or symptoms of hypovolemia.
The most common symptom of EP is abdominal pain and is reported in 90% of all EPs. The pain is due to tubal distention or rupture. The classic presentation of such pain is lateralized, sudden, and severe. The patient can also have shoulder pain secondary to diaphragmatic irritation of a ruptured EP. EPs should be suspected with lateral or bilateral abdominal discomfort or tenderness.
The menstrual history of the patient is often abnormal with 70% of patients reporting amenorrhea 4 to 12 weeks after their last menstrual period. Vaginal bleeding is reported in 50 to 80 percent of patients but 15 percent will have a normal menses. Although scant bleeding is more common with EP, it cannot be excluded with a history of heavy bleeding.
Physical Examination: The physical examination in a patient can be highly variable. A patient with a ruptured EP can present with the symptoms of shock: peritoneal signs, and adnexal mass, tenderness, bradycardia, and fever. An unruptured EP may have an adnexal mass or fullness, tenderness, cervical motion tenderness, blood in the vaginal vault, a blue-hued cervix, or may be a normal pelvic exam.
Differential: There are many possible diagnoses for the symptoms of EP that can be attributed to pregnancy or can be caused by pathology outside of the uterus. (See Table 1).
Testing: A broad differential can be easily narrowed with pregnancy testing. A bedside urine β-HCG can quickly establish whether the patient is pregnant. If EP is still suspected, a quantitative serum β-HCG can be done to detect low levels that may have been diluted in the urine and can also be useful as a baseline level when serial measurements are later needed. No single measurement can distinguish normal pregnancy from pathologic since there is considerable overlap of measurements. Therefore, serial measurements can be used to make a diagnosis of EP more or less likely.
Ultrasound is a very useful tool in the diagnosis of EP. First, it can determine whether the pregnancy is intrauterine. It can also be used in the management of EP in terms of therapeutic options. Medical management of EP is often reserved for EPs without cardiac activity or less than a certain size. If the pregnancy is intrauterine, the ultrasound can be used to determine fetal age and viability. Although the incidence of heterotopic pregnancy, which is the presence of both an intrauterine and ectopic pregnancy, is only 1 in 3000 pregnancies in the general population, the incidence is increased with in-vitro fertilization and should be considered in the assisted reproduction patient. Both transvaginal and transabdominal ultrasound are recommended. When EP is suspected, sonography should be performed even in patients with low β-HCG levels.
Invasive diagnostic techniques include culdocentesis, laparoscopy and dilation and curettage. Culdocentesis may be considered when ultrasonography is not available. A positive test consists of aspiration of non-clotting blood indicating rupture. Laparoscopy is mainly useful when EP is suspected but the ultrasound is nondiagnostic. Dilation and curettage provides a sampling of the chorionic villi for a definitive diagnosis of intrauterine pregnancy. However, all of these exams carry with them the complications involved with invasive procedures and can also be non-diagnostic or false positive.
Treatment: Traditionally, EPs have been treated surgically by laparotomy and salpingectomy. Laparoscopic salpingostomy is now the preferred surgical method in patients who wish to preserve fertility. Specific indications for this procedure include hemodynamic stability, ectopic size less than 5 cm, unruptured or minimally ruptured fallopian tube, appropriate tubal ******** of the conceptus and patient desire to preserve reproductive potential. Laparoscopic salpingectomy can be done in patients in which fertility is not an issue. Laparotomy is reserved for cases that are too difficult for laparoscopic surgery and hemodynamically unstable patients, or when laparoscopic surgery is not an option. Weeklyβ-HCG measurements are then done to assess for persistent EP. It may then be treated with repeat surgery, methotrexate, or expectant management.
Medical management of ectopic pregnancy is becoming more common. Although other pharmaceutical agents have been used to treat EP, methotrexated is the only drug currently recommended. As a common drug used for chemotherapy and rheumatoid arthritis, it is also effective in EP by inhibiting cell division. Systemic intramuscular administration is most commonly used with a success rate of 91.5 percent. Side effects include abdominal pain, flatulence and stomatitis. The pain is secondary to methotrexate-induced tubal abortion or to distention due to hematoma formation. It is usually self-limited lasting up to 12 hours 3 to 7 days after treatment and may respond to NSAIDs.
Patients with suspected EP should also be typed and screened. This can be useful if unstable patients require blood transfusions and is also used to determine Rh status to treat women with anti-D immunoglobulin to prevent alloimmunization.
Disposition: If a patient is unstable, resuscitation, urgent consultation and operative intervention should be done immediately. All pregnant patients with a suspected EP should ideally receive immediate sonography. However, in the event that it is not possible, stable patients at low risk for EP can be discharged with outpatient follow-up and serial quantitative serum β-HCG measurements. Stable patients who are pregnant with an empty uterus on ultrasound should receive consultation in the ED. Patients with low β-HCG levels and indeterminate ultrasound findings can be seen by a consultant or discharged with expected return in two days for a re-examination and repeat serum β-HCG levels .