Williams Manual of Pregnancy Complications, 23 ed.

CHAPTER 2. Ectopic Pregnancy

The fertilized ovum (blastocyst) normally implants in the endometrial lining of the uterine cavity. Implantation anywhere else is an ectopic pregnancy. Almost 2 in every 100 pregnancies in the United States are ectopic, and more than 95 percent of ectopic pregnancies involve the fallopian tube (see Figure 2-1).

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FIGURE 2-1 Sites of implantation of 1800 ectopic pregnancies from a 10-year population-based study. (Reproduced, with permission, from Cunningham FG, Leveno KJ, Bloom SL, et al (eds). Williams Obstetrics. 23rd ed. New York, NY: McGraw-Hill; 2010. Data from Callen PW (ed). Ultrasonography in Obstetrics and Gynecology. 4th ed. Philadelphia, PA: WB Saunders, 2000; p. 919. Bouyer J, Coste J, Shojaei T, et al: Risk factors for ectopic pregnancy: A comprehensive analysis based on a large case-control, population-based study in France. Am J Epidemiol 157:185, 2003.)

There has been a marked increase in both the absolute number and rate of ectopic pregnancies in the United States in the past two decades. Some likely causes are listed in Table 2-1. Ectopic pregnancy remains a leading cause of maternal mortality in the United States and is the most common cause of maternal mortality in the first trimester. The case-fatality rate, however, decreased significantly between 1980 and 1992. The dramatic decrease in deaths from ectopic pregnancies is probably due to improved diagnosis and management.

TABLE 2-1. Reasons for Increased Ectopic Pregnancy Rate in the United States

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TUBAL PREGNANCY

Fertilized ova may develop in any portion of the oviduct, giving rise to ampullary, isthmic, or interstitial (cornual) tubal pregnancies. The ampulla is the most frequent site of tubal ectopic pregnancies, with interstitial pregnancy accounting for only about 2 percent of all tubal gestations.

Signs and Symptoms

In contemporary practice, signs and symptoms of ectopic pregnancy are often subtle or even absent.

Pain

Symptoms are related to whether the ectopic pregnancy has ruptured. The most frequently experienced symptom is pelvic and abdominal pain. Gastrointestinal symptoms and dizziness or lightheadedness are also common, particularly after rupture. Pleuritic chest pain may occur from diaphragmatic irritation caused by the hemorrhage.

Abnormal Bleeding

A majority of women report amenorrhea with some degree of vaginal spotting or bleeding. The uterine bleeding that does occur with tubal pregnancy is often mistaken for true menstruation. It is usually scanty, dark brown, and may be intermittent or continuous. Profuse vaginal bleeding is uncommonly seen with tubal pregnancies.

Abdominal and Pelvic Tenderness

Exquisite tenderness on abdominal and vaginal examination, especially on motion of the cervix, is demonstrable in over three-fourths of women with ruptured tubal pregnancies. Such tenderness, however, may be absent prior to rupture.

Uterine Changes

Because of placental hormones, the uterus may grow during the first 3 months of a tubal pregnancy. Its consistency may also be similar to normal pregnancy. The uterus may be pushed to one side by an ectopic mass, or if the broad ligament is filled with blood, the uterus may be greatly displaced. Uterine decidual casts occur in 5 to 10 percent of women with an ectopic pregnancy. Their passage may be accompanied by cramps similar to those with a spontaneous abortion.

Blood Pressure and Pulse

Before rupture, vital signs are generally normal. Early responses to rupture may range from no change in vital signs to a slight rise in blood pressure, or a vasovagal response with bradycardia and hypotension. Blood pressure will fall and pulse rise only if bleeding continues and hypovolemia develops.

Pelvic Mass

On bimanual examination, a pelvic mass is palpable in 20 percent of women. It is almost always either posterior or lateral to the uterus. Such masses are often soft and elastic.

Culdocentesis

Culdocentesis is a technique for identifying hemoperitoneum commonly used in the past. The cervix is pulled toward the symphysis with a tenaculum, and a long 16- or 18-gauge needle is inserted through the posterior fornix into the cul-de-sac. Fluid-containing fragments of old clots, or bloody fluid that does not clot, are compatible with the diagnosis of hemoperitoneum resulting from an ectopic pregnancy.

Laboratory Tests

Hemoglobin, Hematocrit, and Leukocyte Count

After hemorrhage, depleted blood volume is restored toward normal by hemodilution over the course of a day or longer. Therefore, hemoglobin or hematocrit readings may at first show only a slight reduction. The degree of leukocytosis varies considerably in ruptured ectopic pregnancy. In about half of women leukocytosis up to 30,000/μL may be documented.

Human Chorionic Gonadotropin (β-hCG)

Current urine and serum tests using enzyme-linked immunosorbent assays (ELISA) are sensitive to 10 to 20 mIU/mL, and are positive in 99 percent of ectopic pregnancies. Because a single positive serum assay does not exclude an ectopic pregnancy, several different methods have been devised to use serial quantitative serum values to establish the diagnosis. These methods are commonly used in conjunction with sonography (see the later Section “Combined Serum β-hCG Plus Sonography”).

Serum Progesterone

A single progesterone measurement can often be used to establish a normally developing pregnancy. A value exceeding 25 ng/mL excludes ectopic pregnancy with 97.5 percent sensitivity. Values less than 5 ng/mL suggest that the fetusembryo is dead but do not indicate its location. Progesterone levels between 5 and 25 ng/mL are inconclusive.

Ultrasound Imaging

Transabdominal Sonography

Identification of pregnancy in the fallopian tube is difficult using abdominal sonography. Sonographic absence of a uterine pregnancy, a positive pregnancy test, fluid in the cul-de-sac, and an abnormal pelvic mass indicates an ectopic pregnancy. Unfortunately, ultrasound may suggest an intrauterine pregnancy in some cases of ectopic pregnancy while the appearance of a small intrauterine sac may actually be a blood clot or decidual cast. Conversely, demonstration of an adnexal or cul-de-sac mass by sonography is not necessarily helpful because corpus luteum cysts and matted bowel sometimes look like tubal pregnancies sonographically. Importantly, a uterine pregnancy is usually not recognized using abdominal ultrasound until 5 to 6 menstrual weeks.

Transvaginal Sonography (TVS)

Sonography with a vaginal transducer can detect a uterine pregnancy as early as 1 week after missed menses when the serum β-hCG level is greater than 1000 mIU/mL. An empty uterus with a serum β-hCG concentration of 1500 mIU/mL or higher is extremely accurate in identifying an ectopic pregnancy. Identification of a 1- to 3-mm or larger gestational sac, eccentrically placed in the uterus, and surrounded by a decidual–chorionic reaction implies intrauterine pregnancy. A fetal pole within the sac is diagnostic of an intrauterine pregnancy, especially when accompanied by fetal heart action. Without these criteria, the ultrasound may be nondiagnostic. In the event of a nondiagnostic study, most favor serial sonography along with serial β-hCG measurements.

Combined Serum β-hCG Plus Sonography

When a suspected ectopic pregnancy is diagnosed in a hemodynamically stable woman, subsequent management is based upon serum β-hCG values and ultrasound (see Figure 2-2).

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FIGURE 2-2 One suggested algorithm for evaluation of a woman with a suspected ectopic pregnancy. hCG, human chorionic gonadotropin; TVS, transvaginal sonography. (Modified from Gala RB: Ectopic pregnancy. In Shorge JO, Schaffer JI, Halvorson LM, et al (eds). Williams Gynecology. New York, NY: McGraw-Hill, 2008, pp. 160, 165, 170.)

Management

In the past, surgery was usually performed to remove a damaged, bleeding fallopian tube. Over the past two decades, earlier diagnosis and treatment have allowed definitive management of an unruptured ectopic pregnancy even before there are clinical symptoms. This early diagnosis has made many cases of ectopic pregnancy amenable to medical therapy.

Expectant Management

Some choose to observe very early tubal pregnancies that are associated with stable or falling serum β-hCG levels. As many as a third of women with ectopic pregnancy will present with declining β-hCG levels (Table 2-2). Eligibility criteria for expectant management are listed in Table 2-3. The potentially grave consequences of tubal rupture, coupled with the established safety of medical and surgical therapy, require that expectant therapy be undertaken only in appropriately selected and counseled women.

TABLE 2-2. Lower Normal Limits for Percentage Increase of Serum β-hCG during Early Uterine Pregnancy

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TABLE 2-3. Criteria for Expectant Management of Tubal Pregnancy

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Anti-D Immunoglobulin

If the woman is D-negative but not yet sensitized to D-antigen, then anti-D immunoglobulin should be administered.

Methotrexate

Medical treatment with methotrexate is the preferred management under certain clinical conditions. Active intra-abdominal hemorrhage is a contraindication to such chemotherapy. Success rates with appropriate patient selection are greater than 90 percent. Some women may require multiple courses.

Patient Selection. The size of the ectopic mass and the level of β-hCG are important. Success is greatest if the gestation is less than 6 weeks, the tubal mass is not more than 3.5 cm in diameter, the embryo is dead, and the β-hCG is less than 15,000 mIU/mL. According to the American College of Obstetricians and Gynecologists (Medical management of ectopic pregnancy, Practice Bulletin No. 94, June 2008), other contraindications include breastfeeding, immunodeficiency, alcoholism, liver or kidney disease, blood dyscrasias, active pulmonary disease, and peptic ulcer. Candidates for methotrexate therapy must be hemodynamically stable with a normal hemogram and normal liver and renal function. Other important considerations are listed in Table 2-4.

TABLE 2-4. Some Considerations in Selection of Women for Treatment of Ectopic Pregnancy with Methotrexate

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Dosing of Methotrexate. Methotrexate is an antineoplastic drug that acts as a folic acid antagonist and is highly effective against rapidly proliferating trophoblasts. The two general schemes used for methotrexate administration for ectopic pregnancy are shown in Table 2-5. Although single-dose therapy is easier to administer and monitor than variable-dose methotrexate therapy, single-dose therapy is associated with a higher incidence of persistent ectopic pregnancy. Single-dose therapy is preferred at Parkland Hospital.

TABLE 2-5. Methotrexate Therapy for Primary Treatment of Ectopic Pregnancy

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Toxicity may develop suddenly and be severe; however, most regimens result in minimal laboratory changes and symptoms. Any side effects generally resolve within 3 to 4 days. The most common side effects are liver dysfunction, stomatitis, and gastroenteritis. Isolated cases of life-threatening neutropenia and fever, transient drug-induced pneumonitis, and alopecia have been described.

After methotrexate therapy, β-hCG usually disappears from plasma in 28 days. Single-dose therapy should be monitored using repeat serum β-hCG determinations at 4- and 7-day intervals. With variable-dose methotrexate, serum concentrations are measured at 48-hour intervals until they fall more than 15 percent. After successful treatment, weekly serum β-hCG levels are measured until they are less than 5 mIU/mL. Outpatient surveillance is preferred, but if there is any question of safety, the woman is hospitalized. Failure is judged when there is no decline in β-hCG level, persistence of the ectopic mass, or any intraperitoneal bleeding. Five percent of methotrexate-treated women will experience subsequent tubal rupture.

Surgery

Laparoscopy is preferred over laparotomy unless the woman is unstable. Even though reproductive outcomes, including rates of uterine pregnancy and recurrent ectopic pregnancies, are similar, laparoscopy is more cost-effective and has a shorter recovery time.

Tubal surgery for ectopic pregnancy is considered conservative when there is tubal salvage. Examples include salpingostomy, salpingotomy, and fimbrial expression of the ectopic pregnancy. Radical surgeryis defined when salpingectomy is required.

Salpingostomy. This procedure is used to remove a small pregnancy that is usually less than 2 cm in length and located in the distal third of the fallopian tube (Figure 2-3). A linear incision, 10 to 15 mm in length or less, is made on the antimesenteric border immediately over the ectopic pregnancy. The products usually will extrude from the incision and can be carefully removed or flushed out. Small bleeding sites are controlled with needlepoint electrocautery or laser, and the incision is left unsutured to heal by secondary intention. This procedure is readily performed through a laparoscope.

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FIGURE 2-3 Linear salpingostomy for ectopic pregnancy. A. Linear incision for removal of a small tubal pregnancy is created on the antimesenteric border of the tube. B. Products of conception may be flushed from the tube using an irrigation probe. Alternatively, products may be removed with grasping forceps. Following evacuation of the tube, bleeding sites are treated with electrosurgical coagulation or laser, and the incision is not sutured. If the incision is closed, the procedure is termed a salpingotomy. (From Hoffman BL: Surgeries for benign gynecologic conditions. In Shorge JO, Schaffer JI, Halvorson LM, et al (eds). Williams Gynecology. New York: McGraw-Hill, 2008, p. 943.)

Salpingotomy. The procedure is the same as for salpingostomy except that the incision is closed with 7–0 vicryl or similar suture. There is no difference in prognosis with or without suturing.

Salpingectomy. Tubal resection can be performed through an operative laparoscope and may be used for both ruptured and unruptured ectopic pregnancies. When removing the fallopian tube, it is advisable to excise a wedge no more than the outer third of the interstitial portion of the tube. This cornual resection is done in an effort to minimize the rare recurrence of pregnancy in the tubal stump.


For further reading in Williams Obstetrics, 23rd ed.,

see Chapter 10, “Ectopic Pregnancy.”