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Ectopic Pregnancy
Clinical Keys for this Chapter
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Ectopic pregnancy refers to those pregnancies that implant outside the uterine cavity. Although more than 95% of ectopic pregnancies implant in the fallopian tube, occasionally they may implant in other sites, such as the ovary, the uterine cervix, or, very rarely, in the abdominal cavity or a cesarean uterine scar. Following the use of assisted reproductive technologies (ARTs), the incidence of ectopic pregnancy has more than doubled to 2-3%, and the likelihood of implantation in more unusual sites has increased.
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The trophoblast of an early ectopic pregnancy that implants in the fallopian tube erodes through the tubal mucosal layer and into the tubal vessels. As the fetus grows, the blood from the eroded vessels dissects along the tubal wall, resulting in any of the following: (1) tubal rupture and intraperitoneal hemorrhage, (2) resorption of the pregnancy because of restricted blood supply, or (3) tubal abortion into the peritoneal cavity, where it may rarely result in an abdominal pregnancy.
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Clinical presentation of ectopic pregnancies may vary, but the classic triad of symptoms is (1) missed menses, (2) vaginal bleeding (usually spotting), and (3) lower abdominal pain. For individual women, there are three possible clinical presentations: (1) an acutely ruptured ectopic pregnancy, (2) a probable ectopic pregnancy with significant pelvic pain and vaginal spotting or bleeding, or (3) a possible ectopic pregnancy.
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Most often, the workup begins with testing to locate a “pregnancy of unknown location” (PUL). Other kinds of abnormal early pregnancies and other illnesses in early pregnancy may account for the signs and symptoms of ectopic pregnancy. The two most important diagnostic tests performed to diagnose an ectopic pregnancy are serial serum human chorionic gonadotropin (hCG) levels in maternal serum and sequential ultrasonic imaging.
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The key to proper management of ectopic pregnancy is early diagnosis. Treatment options depend on the clinical situation and, where possible, patient preferences. Surgery is necessary when rupture has occurred or is threatened or if the diagnosis remains uncertain. Medical therapy with methotrexate (MTX) is now widely used for probable and possible ectopic pregnancies. Irrespective of the type of treatment, most patients should be informed that they are at an increased risk of a future ectopic pregnancy.
An ectopic pregnancy is one that implants outside the endometrial cavity. The most common site for an ectopic pregnancy is in the fallopian tube, but a wide range of implantation sites is possible. Some treatments for infertility significantly increase the risk. They may also affect where the implantation occurs ( Table 24-1 ). Although early diagnosis has enabled more effective intervention and lowered maternal mortality caused by ectopic pregnancies, the disorder is still a leading cause of maternal death in the first trimester of pregnancy.
TABLE 24-1
Incidence and Sites of Ectopic Pregnancy
| Natural Conception | Assisted Reproductive Technologies | |
|---|---|---|
| Overall incidence | About 1% | 2-3% |
| Fallopian tube | >95% | <90% |
| Ovarian and abdominal | 1-2% | 5% |
| Cervical | 0.15% | 1.5% |
| Cesarean scar | 1 in 1800 | Unknown |
| Heterotopic * | 1 in 30,000 | 1 in 100 |
Etiology and Risk Factors
Ectopic pregnancies generally result from abnormalities in the structure or function of the fallopian tube. The role that the conceptus itself may play is not known, but it is clear that chromosomal abnormalities do not cause ectopic pregnancies.
The most common cause of tubal abnormality associated with ectopic pregnancy is internal inflammation (salpingitis). Other causes include external tubal scarring secondary to endometriosis, ruptured appendicitis, or previous surgery. Classically, gonococcal salpingitis causes significant symptoms of fever and pelvic pain and results in visible tubal damage. The fallopian tubes become distended with purulent material; the fimbriae can be clubbed; and the passage through the tube becomes tortuous with blind pouches (diverticuli) that physically block the progress of the fertilized egg into the endometrial cavity. Chlamydial salpingitis is usually associated with milder symptoms, and the tubal damage is more subtle. The heat shock protein released by Chlamydia trachomatis destroys the cilia lining the tubal mucosa, which are responsible for sweeping the conceptus through the tube.
Salpingitis isthmica nodosa is another inflammatory process that distorts the portion of the fallopian tube closest to the tubal ostia (opening into the uterine cavity). Thirty percent of all pregnancies that follow tubal ligation are ectopic. Other tubal surgeries (e.g., anastomosis, lysis of adhesions) also increase the risk of ectopic pregnancy. One of the greatest risk factors is a history of a previous ectopic pregnancy. Recurrence rates are about 30%. Uterine fibroids located near the ostia can distort or block tubal patency and increase the risk of ectopic pregnancy.
Tubal peristalsis is slowed by progestins, such as those that are released by the hormonal contraceptive intrauterine devices (IUDs), contraceptive implants, injections, and oral contraceptives. Although all of these methods of birth control significantly reduce the absolute risk of any pregnancy, when a failure (pregnancy) occurs during their use, the relative risk of an ectopic pregnancy is greatly increased. For example, it is estimated that 40-60% of pregnancies that occur during use of the levonorgestrel IUDs are ectopic (see Chapter 27 ).
The higher levels of progesterone induced by ovarian hyperstimulation during use of assisted reproductive technologies (ARTs) can also slow tubal motility. When multiple embryos are transferred during in vitro fertilization (IVF), the risk of ectopic pregnancy and the risk of heterotopic pregnancy (simultaneous intrauterine and ectopic) increase from 1 : 30,000 to 1 : 100 pregnancies. Other risk factors include a history of infertility and smoking.
Incidence and Classification
Now that many cases of ectopic pregnancy are managed medically in ambulatory settings, the incidence of ectopic pregnancy is not as well documented. The latest statistics from the mid-1990s indicated that 1-2% of all pregnancies in the United States were ectopic. Minority women have twice the risk of white women and a fourfold higher risk of ectopic pregnancy–related mortality. Recently, there have been counterbalancing shifts in the prevalence of risk factors for ectopic pregnancy (less pelvic infection but more advanced infertility treatment), so it is reasonable to assume that about 1 in 80 pregnancies in the United States will be located outside the uterine cavity.
The fallopian tubes are the site of over 95% of ectopic pregnancies. Those ectopic pregnancies are characterized by the portion of the salpinx in which the pregnancy implants: ampullary (75-80%), isthmic (12%), infundibular or fimbrial (6-10%), and interstitial or cornual (2-4%). Cornual ectopic pregnancies are particularly dangerous, because the pregnancy can continue to expand throughout the first trimester, and its rupture can lead to a sudden and rapid fatal exsanguination in less than 1 hour. Bilateral fallopian tube pregnancies occur in 1 in 200,000 pregnancies. Other sites for ectopic pregnancy include the cervix, the ovary (implantation below the ovarian cortex), the abdomen, and cesarean delivery scars. There has been a distinct increase in the numbers of cesarean scar pregnancies as cesarean delivery has become more common. Heterotopic pregnancies, in which pregnancies simultaneously implant in both the endometrium and in an extrauterine site, may occur as frequently as 1 in 100 IVF pregnancies.
Natural History
The trophoblasts of the conceptus implanted in the mucosa of the fallopian tube rapidly erode through that layer and invade into the underlying blood vessels. This induces local bleeding, some of which dissects into the tubal lumen and spills into the endometrial cavity (causing spotting), and some of it passes into the peritoneal cavity (causing a hemoperitoneum). Most of the blood generally is trapped between the serosal and mucosal layers and distends the tube with clot, which explains the common finding of cervical motion tenderness. If the bleeding is extensive enough, it can cause pressure necrosis of the overlying tubal serosa, resulting in acute rupture and causing a significant hemoperitoneum. Occasionally, the local blood supply to the pregnancy is so compromised that the pregnancy is resorbed (spontaneously resolved) or aborted into the peritoneal cavity, a process that may be asymptomatic.
Clinical Presentation
The clinical presentation of tubal ectopic pregnancies can vary from subtle lower abdominal discomfort and light uterine spotting to symptoms consistent with hypovolemic shock due to massive internal hemorrhage from tubal rupture. Ectopic pregnancies in other sites may have slightly different presentations, but the common finding of all ectopic pregnancies is that the symptoms occur in the setting of a positive pregnancy test. Clinical presentations should be evaluated in terms of three possibilities: (1) an acutely ruptured (or rupturing) ectopic pregnancy, (2) a probable ectopic pregnancy in a symptomatic woman, and (3) a possible ectopic pregnancy in a mildly symptomatic woman with a pregnancy of unknown location (PUL).
Acutely Ruptured Ectopic Pregnancy
Fortunately, only a small number of women with fallopian tube pregnancies present with symptoms indicative of massive internal hemorrhage from acute tubal rupture. This presentation is particularly likely to occur in women with poor access to care and occasionally in those whose medical therapy fails. Women may present with dizziness or loss of consciousness and sudden onset of severe pain. Some shoulder pain may be present because of irritation of the phrenic nerve by blood and clotting in the abdominal cavity.
During a physical examination, hemodynamic instability is indicated by tachycardia, diaphoresis, and hypotension. The abdomen may be distended, and both abdominal guarding and rebound tenderness may be present. There may be only minor bleeding from the cervix found by speculum examination, but noticeable cervical motion tenderness and a slightly enlarged, globular uterus may be detected by bimanual examination. A palpable adnexal mass may or may not be present.
An acute rupture of an ectopic pregnancy represents a surgical emergency. Large-bore intravenous lines must be established, and fluid resuscitation must be started immediately. Blood transfusion should follow as soon as possible, but surgery should not be delayed. In the hemodynamically unstable patient, laparotomy is usually required. Laparoscopy may be performed in less compromised patients. Generally, tubal damage after rupture is so extensive that salpingectomy is required.
Probable Ectopic Pregnancy
Hemodynamically stable women who have a positive pregnancy test and present with notable pelvic pain and vaginal spotting or bleeding should be classified as having a “probable ectopic pregnancy” after other disease processes that may present with similar symptoms in early pregnancy have been ruled out ( Box 24-1 ). Such patients generally have other clinical signs, such as tenderness of the abdomen with adnexal or cervical motion tenderness. On ultrasound, a variable amount of free fluid may be detected in the cul-de-sac. Only occasionally will the ectopic pregnancy be seen on ultrasound as a “double-ring” sign in the adnexa, but a corpus luteal cyst is often present. In such symptomatic women, even though they have stable vital signs, surgical exploration is generally recommended. Conservative surgical procedures that preserve the fallopian tube are generally performed in women desiring future fertility (see Management section below).
Box 24-1
Other Pain-Producing Problems that May Occur Early in Pregnancy
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