Cigarette smoking increases the likelihood of ectopic pregnancy 2.5 times,12 probably by affecting ciliary action within the fallopian tubes.
Salpingitis isthmic nodosa is anatomic thickening of the proximal portion of the fallopian tubes with multiple lumen diverticula. It increases the risk of ectopic pregnancy 1.5 times, compared with age- and race-matched controls.13
Don’t depend solely on risk factors. Many ectopic pregnancies present without them.
Symptoms. Many ectopic pregnancies never produce symptoms; rather, they resolve spontaneously or are timely diagnosed and treated medically. Risk factors should therefore be examined in any woman in early pregnancy and investigated further if ectopic pregnancy is likely.
When symptoms do occur, they usually involve 1 or all of the classic triad: amenorrhea, irregular bleeding, and lower abdominal pain. In addition, syncope, shock, and pain radiating to the patient’s shoulder can result from hemoperitoneum.
TABLE 1
High, moderate, and low levels of risk factors for ectopic pregnancy
| RISK FACTOR | ODDS RATIO* |
|---|---|
| High risk | |
| Tubal surgery | 21.0 |
| Tubal ligation | 9.3 |
| Previous ectopic pregnancy | 8.3 |
| In utero exposure to diethylstilbestrol | 5.6 |
| Use of intrauterine device | 4.2–45.0 |
| Documented tubal pathology | 3.8–21.0 |
| Assisted reproduction | 4.0 |
| Emergency contraception | High |
| Moderate risk | |
| Infertility | 2.5–21.0 |
| Previous genital infections | 2.5–3.7 |
| Multiple sexual partners | 2.1 |
| Salpingitis (isthmic) | 1.5 |
| Slight risk | |
| Previous pelvic, abdominal surgery | 0.9–3.8 |
| Cigarette smoking | 2.3–2.5 |
| Vaginal douching | 1.1–3.1 |
| Early age at first intercourse (<18 years) | 1.6 |
| Reprinted with permission from Elsevier (The Lancet, 1998, vol 351, 1115–1120). | |
| * Single values = common odds ratio from homogeneous studies; point estimates = range of values from heterogeneous studies | |
STEP 2Document the pregnancy and measure ß-hCG
Once you identify the high-risk patient, or a woman comes in complaining of pain and spotting or bleeding, run a pregnancy test to confirm that she is pregnant and, if it is positive, obtain a quantitative ß-hCG.
ß-hCG levels are normally measured using enzyme-linked immunosorbent assays (ELISA), which detect ß-hCG in urine and serum at levels as low as 20 mIU/mL and 10 mIU/mL, respectively.14 ß-hCG is produced by trophoblastic cells in normal pregnancy, and approximately doubles every 2 days when titers are below 10,000 mIU/mL15—although in some normal pregnancies, ß-hCG may increase as slowly as 53% or as rapidly as 230% over 2 days.16 Eighty-five percent of abnormal pregnancies—whether intrauterine or ectopic—have impaired ß-hCG production with prolonged doubling time. Thus, in failing pregnancies, ß-hCG levels will plateau or fail to rise normally.
A single ß-hCG level fails to predict the risk of rupture, since ectopic pregnancies can rupture at ß-hCG levels as low as 10 mIU/mL or far exceeding 10,000 mIU/mL, or at any level in between.
STEP 3Obtain an ultrasound scan
Transvaginal ultrasound reliably detects normal intrauterine gestations when ß-hCG passes somewhere between 1,000 mIU/mL and 2,000 mIU/mL (First International Reference Preparation), depending on the expertise of the ultrasonographer and the particular equipment used.8,17 This is known as the “discriminatory zone.” ß-hCG levels reach this zone as early as 1 week after missed menses.18
The discriminatory zone is not the lowest ß-hCG concentration at which an intrauterine pregnancy can be visualized via ultrasound. Rather, it is the value at which any intrauterine pregnancy will be apparent. At that value, the absence of an intrauterine pregnancy confirms—by negative conclusion—that the patient has a nonviable gestation.
When intrauterine pregnancy is visualized. The diagnosis is definitive and the woman’s symptoms can be explained as “threatened abortion.” No further investigation is necessary aside from routine prenatal care if the pregnancy continues.
When an extrauterine gestation is observed, such as a gestational sac with a detectable fetal heart rate, ectopic pregnancy can be diagnosed with 100% specificity but low sensitivity (15% to 20%). A complex adnexal mass without an intrauterine pregnancy improves sensitivity from 21% to 84% at the expense of lower specificity (93% to 99.5%).19
Even when an adnexal mass is visualized, cardiac activity is not usually present. If cardiac activity is apparent, proceed to surgery, since methotrexate usually will not resolve these gestations.
Be aware that some adnexal masses suspicious for ectopic pregnancy may turn out to be other entities, such as a corpus luteum, hydrosalpinx, ovarian neoplasm, or endometrioma. Unless a fetal heart rate is detected by ultrasound, the diagnosis is uncertain and curettage is needed to establish a definitive diagnosis.
No intrauterine pregnancy, no extrauterine mass. Despite the high resolution of transvaginal ultrasound, many patients with ectopic pregnancy have no apparent adnexal mass,20 particularly when diagnosis is early. In these cases, proceed to curettage (step 4).
Don’t interpret ultrasound findings in a vacuum
This is especially unwise when ß-hCG levels are low—even when the ultrasound report points to intrauterine pregnancy. At ß-hCG levels below 1,500 mIU/mL, the sensitivity of ultrasound in diagnosing intrauterine pregnancy drops from 98% to 33% and predictive value is substantially lower. Interpret ultrasound and ß-hCG levels together for greater accuracy.