Clinical Review

Evaluating and managing ectopic pregnancy

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While the incidence of ectopic pregnancy has increased dramatically over the past several decades, maternal mortality rates have steadily declined. Earlier detection and refinements in treatment account for most of this decline. Here, the authors outline current therapeutic options.



Key points
  • Ectopic pregnancy is the leading cause of maternal death in the first trimester.
  • More sensitive and specific radioimmunoassays for progesterone and hCG have made early diagnosis feasible.
  • Persistent trophoblastic tissue is not uncommon after salpingostomy, but rare after salpingectomy.
  • Studies have shown that laparoscopy is superior to laparotomy with respect to blood loss, analgesic requirements, and duration of hospital stay.

Ectopic pregnancy is the leading cause of maternal death in the first trimester.1 Fortunately, despite an almost 5-fold increase in the incidence of ectopic pregnancy in the United States since 1970, deaths have declined approximately 10-fold. The lower maternal mortality rates can be attributed to earlier diagnosis of the unruptured ectopic pregnancy, along with nonsurgical therapy and other alternatives to the traditional salpingectomy. On the other hand, the rising ectopic pregnancy rate is thought by many to be the result of an increased incidence of tubal disease due to gonorrhea and chlamydia infections, and tubal surgery.

The development of more sensitive and specific radioimmunoassays for progesterone and human chorionic gonadotropin (hCG), along with the widespread availability of laparoscopy and high-resolution transvaginal sonography, have made early diagnosis feasible. Diagnostic algorithms have been developed to simplify the management of suspected ectopic pregnancy. Initially, these algorithms relied on quantitative hCG titers and transabdominal ultrasound followed by diagnostic laparoscopy to confirm an ectopic pregnancy. But as the sensitivity and specificity of the diagnostic tests increased, the need for laparoscopy to confirm the diagnosis decreased. In a randomized clinical trial, Stovall and colleagues developed an algorithm that proved 100% accurate without the use of laparoscopy.2 This algorithm was an extension of one then in use at the University of Tennessee, Memphis.

Past treatment options

Prior to the development of surgical treatments, presumed ectopic pregnancies had a mortality rate of 67%.3 In 1884, Tait examined a series of 5 patients treated with salpingectomy and reported a mortality rate of 5%.4 Soon after, laparotomy with salpingectomy became the standard treatment for tubal pregnancy.

Approximately 80% of all patients receiving the single-dose protocol require only 1 treatment of methotrexate.

In 1887, the first case report of a tubal pregnancy removed by opening the tube, extracting the trophoblas-tic tissue, and suturing the tubal incision was published by Martin in the German literature.5 However, salpingectomy remained the treatment of choice for almost a century following this report. In fact, it was not until 1953 that a similar procedure was reported in the English literature by Strome.6

In the early 1970s, laparoscopy replaced exploratory laparotomy as the definitive tool for the diagnosis of ectopic pregnancy. Initially, the laparoscope was used only to diagnose a patient with an ectopic pregnancy before committing to a laparotomy, but in 1973, Shapiro and Adler reported the first laparoscopic salpingectomy for the treatment of ectopic pregnancy.7 In the 1980s, Bruhat and associates published their experience with laparoscopic salpingostomies.8,9 Despite these advances, salpingectomy remains the most commonly performed procedure for ectopic pregnancy in the United States.

Researchers have found that hCG levels are the only significant predictor of methotrexate failure.

Nonsurgical treatment

The most recent development in the treatment of ectopic pregnancy is medical management. In a review of all studies involving more than 35 patients treated with systemic methotrexate, the nonsurgical alternative was successful in 810 of 915 women (88.5%) (Table 1).

Systemic methotrexate is administered in 1 of 2 ways: as a single-dose protocol or a multiple-dose protocol in which an injection is given every other day for at least 3 doses. The latter usually alternates with citrovorum rescue factor (leucovorin). Approximately 80% of all patients receiving the single-dose protocol require only 1 treatment of methotrexate. If subsequent doses of the agent are needed, they are administered on a weekly basis.

In the single-dose protocol, methotrexate is given intramuscularly (IM) (50 mg/m2) based on actual body weight. The initial treatment day is considered day 1. Titers of hCG are repeated on days 4 and 7. (Levels of hCG frequently continue to rise until day 4.) If the hCG titer declines less than 15% between days 4 and 7, a second dose of methotrexate is given and the protocol restarted at a new day 1. If the hCG titer declines 15% or more between days 4 and 7, hCG titers are followed weekly until they reach less than 15 mIU/mL. If the hCG level declines less than 15% in any week, another dose of methotrexate is given, and the protocol is restarted. The mean time of resolution in successfully treated women is approximately 35 days, but resolution in individual patients may take as long as 109 days.10

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