Establishing a Human Chorionic Gonadotropin Cutoff to Guide Methotrexate Treatment of Ectopic Pregnancy: A Systematic Review

Abstract

Methotrexate is an established alternative to surgery for treating ectopic pregnancy. While lower levels of human chorionic gonadotropin (hCG) correlate with a decreased risk of treatment failure, there is as yet no agreement on an absolute hCG level that would be a relative contraindication to methotrexate therapy. The authors undertook a systematic MEDLINE search and encountered 5 observational studies, totaling 503 women, that purportedly documented increasing failure rates in conjunction with increasing hCG levels. All of these studies followed a single-dose methotrexate protocol. Failure rates increased with higher hCG levels, and a substantial, statistically significant increase in failures was evident when comparing patients whose initial hCG levels exceeded 5000 mIU/mL with those having lower baseline levels. The odds ratio (OR) was 5.45, with a 95% confidence interval (CI) of 3.04-9.78. Women whose initial serum hCG level ranged from 5000 to 9999 mIU/mL had a significantly higher failure rate than those whose initial serum concentrations were 2000-4999 mIU/mL (OR, 3.76; 95% CI, 1.16-12.33). Another way to express this is that, for every 10 treatments there will be 1 more failure if the serum hCG is 5000-9999 mIU/mL than if it is 2000-4999 mIU/mL. The difference in rates approximates 10%. There is little difference in failure rates between groups with cutoff values greater than 5000 mIU/mL because overall failure rates are increased for both groups. These findings dictate a cautious approach when planning single-dose methotrexate treatment for ectopic pregnancy when the initial serum hCG level exceeds 5000 mIU/mL. It is not clear whether the use of a 2-dose or multidose protocol would yield different results.