3.1 Baseline data
A total of 238 women with ectopic pregnancies were treated with MTX therapy. The maximum age of the patients was 44 years, and the minimum age was 15 years. After MTX treatment, all patients were divided into two groups according to the final treatment outcome: there were 166 patients in the successful treatment group and 72 patients who switched from MTX treatment to surgery in the failed treatment group (25 women underwent surgery before day 4 of MTX). Some patients were treated with antimicrobial drugs if necessary, such as if they presented with fever and an elevated white blood cell count (36 patients in the successful treatment group and 11 patients in the failed treatment group, with no statistically significant difference between the two groups). The follow-up duration was 1-6 months.
The overall success rate of MTX therapy was 69.75% (166/238), and 22 patients (13.25%) required a second dose of MTX to achieve complete resolution. There were 72 patients in whom treatment failed (30.25%, 72/238) (Fig 1). The baseline data for the successful and failed treatment groups are shown in Table 1. There were no statistically significant differences in the demographic profiles of the groups (Table 1).
3.2 Relationship between β-hCG changes and treatment outcomes
The mean β-hCG levels on day 0, day 4 and day 7 in the successful treatment group and failed treatment group are shown in Table 2. The rank-sum test showed statistically significant differences between the two groups (P<0.001). In total, 92.47% (135/146) of the patients in whom β-hCG levels were decreased on the 4th day were in the successful treatment group. In contrast, in the group of patients in whom the day-4 β-hCG levels had increased, only 56.27% (31/67) were successfully treated with MTX (P value = 0.000, chi-squared test).
The changes in β-hCG levels (hCG04) between the initial day and the 4th day were calculated as (HCG4-HCG0)/HCG0. The changes in β-hCG levels (hCG4-7) between the 4th day and the 7th day were calculated as (HCG7-HCG4)/HCG4. Negative numbers indicate that the β-hCG levels decreased, and positive numbers indicate that the levels increased (Table 2).
3.3 The initial β-hCG level and changes in the β-hCG levels between the initial day and day 4 and between day 4 and day 7 predict the outcome of treatment
The areas under the ROC curves (Figs 2, 3 and 4) for the initial β-hCG level, the change in the level from day 0 to 4 and the change in the level from day 4 to day 7 were 0.695 (95% CI: 0.624-0.767), 0.863 (95% CI: 0.805-0.920) and 0.767 (95% CI: 0.685-0.877), respectively. The diagnostic value of the change from day 0 to day 4 was higher than that of the other two. The best cutoff value for the initial β-hCG level was 3393.78 IU/L, which provided a sensitivity of 78.9% and a specificity of 62.5%. The positive predictive value was 67.78%, and the negative predictive value was 74.76%. The best cutoff value for the change in the β-hCG level from day 0 to day 4 was 0.082 (8.2%). This cutoff value provided a sensitivity of 88.6% and a specificity of 74.5%. The positive predictive value was 77.65%, and the negative predictive value was 86.73%. The best cutoff value for the change in the β-hCG level from day 4 to day 7 was -0.139 (-13.9%). This cutoff value provided a sensitivity of 85% and a specificity of 63.6%. The positive predictive value was 70.02%, and the negative predictive value was 80.92%. The various cutoff values for the initial β-hCG level, the change in the level from day 0 to day 4 and the change in the level from day 4 to day 7 are depicted in Tables 3, 4 and 5, respectively.
The chi-squared test was used to analyze the difference between the treatment success rate of the group with an initial β-hCG concentration greater than 4000 IU/L and that of the group with an initial β-hCG concentration less than 4000 IU/L (P=0.005<0.05), and the test indicated a significant difference. However, the success rate for the group with an initial β-hCG concentration greater than 4000 IU/L was still more than 50% (54.55%, Table 6).
3.4 Side effects
Of the 238 patients, 11 patients (4.62%) experienced nausea and vomiting after receiving the medication (similar to after receiving 10 mg of metoclopramide via intramuscular injection), which resolved without intervention, and 5 patients (2.10%) showed slight increases in transaminase levels, which normalized after hepatoprotective drug treatment (456 mg polyene phosphatidylcholine capsules 3 times/day with liver function evaluated every week until it returned to normal); however, the other patients had no obvious adverse reactions.