Evaluating and managing ectopic pregnancy

In multiple-dose protocols, administer 1 mg/kg of methotrexate intramuscularly every other day with a minimum of 3 doses. A dosage of 0.1 mg/kg leucovorin also is given intramuscularly each day after a methotrexate injection. Once hCG levels have fallen 15%, patients are then monitored weekly. If hCG levels fail to fall appropriately, the protocol is restarted.

Salpingostomy is the procedure of choice, especially when the opposite tube is blocked or lost from a ruptured ectopic pregnancy.

Compared with multiple-dose protocols, single-dose methotrexate is less expensive, has fewer side effects, requires less intensive patient monitoring, has greater patient acceptance, and does not necessitate rescue with citrovorum. However, no randomized comparisons of success rates between multiple- and single-dose protocols are available. At our institution, the overall success rates were comparable between 100 patients treated with a multiple-dose protocol and 352 patients treated with single-dose methotrexate.^11,12 Those rates were 96% and 91.5%, respectively. Although they were slightly higher for the multiple-dose protocol, the difference was not statistically significant. However, in the single-dose group, treatment criteria were liberalized with respect to the size of the ectopic pregnancy. Only pregnancies less than 3 cm were treated with multiple-dose methotrexate, while 4 cm was the maximum size treated with the single-dose protocol.

Although the most commonly quoted predictors of success with methotrexate are hCG and progesterone levels, ectopic size, the presence of ectopic cardiac activity, and the presence of free peritoneal blood, there is no consensus on which are most reliable. Because of the small number of patients previously available for analysis, it has been difficult to determine the true effect of these parameters on success rates. In a recent review of 350 consecutive tubal pregnancies treated with single-dose methotrexate, logistic regression revealed hCG levels as the only significant predictor of failure.¹¹ Interestingly, ectopic size, hematoma volume, and free peritoneal blood confined to the pelvis were not significant risk factors for treatment failure. These data suggest that many previous relative contraindications for medical therapy may be invalid.

The success rates listed in Table 2 can be used to counsel patients considering single-dose methotrexate.

TABLE 1

Success rates for systemic methotrexate in series with at least 35 patients*

TABLE 2

Single-dose methotrexate success rates by hCG levels

Comparing treatments

Although multiple options are now available for the treatment of ectopic pregnancy, the best way to minimize morbidity and mortality while maximizing tubal patency and fertility remains uncertain. That is because most of the available data come from nonrandomized trials. The most comprehensive review of randomized trials was published in the Cochrane Library.¹³ The following is a comparison of the various practices.

Salpingostomy versus salpingectomy. No randomized prospective trials have compared fertility and/or recurrent ectopic pregnancy rates following salpingostomy versus salpingectomy. While a few small retrospective studies are available, the operations are lumped together and subsequent pregnancy outcomes are not specified. Presently, only 4 reports can be sufficiently analyzed.^14-17

Overall, the data show a slight increase in live birth rates in patients who undergo sal-pingostomy (Table 3). They also show a consistently higher number of recurrent ectopic pregnancies, although neither difference is statistically significant. Generally, salpingostomy is the procedure of choice, especially when the opposite tube is blocked or lost from a ruptured ectopic pregnancy.

There also is a greater risk of persistent trophoblastic tissue with salpingostomy, ranging from 3% to 20%.¹⁸ This outcome is rare with salpingectomy.

Laparoscopy versus laparotomy. Three prospective randomized trials involving 231 patients compared laparoscopy with laparotomy in hemodynamically stable patients.^19-21 In these trials, laparoscopic surgery proved to be superior to laparotomy with respect to blood loss, analgesic requirements, and duration of hospital stay (Table 4). It also resulted in cost savings of $1,200 to $1,500 (in 1992 dollars) per patient over laparotomy, primarily due to shorter hospital stays.

The rate of intrauterine pregnancy following laparoscopy and laparotomy was 61% and 53%, respectively, and the rate of recurrent ectopic pregnancy was 7% and 14%, respectively. In contrast, when salpingostomy was performed, laparoscopic surgery was less effective than laparotomy in preventing persistent trophoblastic disease.^13,22

Laparoscopic salpingostomy versus systemic methotrexate. In a multicenter study, 100 hemodynamically stable women with laparoscopically confirmed unruptured ectopic pregnancy and no evidence of intra-abdominal bleeding were allocated to receive systemic methotrexate or undergo laparoscopic salpingostomy.²³ Of the 51 patients treated medically, who were given methotrexate alternating with leucovorin in a multidose regimen, 86% were treated successfully, although 4% required a second course of methotrexate. The remaining 14% required surgery.