Open Access Open Badges Research article

Using a decline in serum hCG between days 0–4 to predict ectopic pregnancy treatment success after single-dose methotrexate: a retrospective cohort study

Monika Skubisz12*, Philip Dutton3, William Colin Duncan3, Andrew W Horne3 and Stephen Tong1

Author Affiliations

1 Translational Obstetrics Group, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria 3084, Australia

2 The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Victoria 3168, Australia

3 MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, EH16 4TJ, United Kingdom

For all author emails, please log on.

BMC Pregnancy and Childbirth 2013, 13:30  doi:10.1186/1471-2393-13-30

Published: 1 February 2013



The current measure of treatment efficacy of single-dose methotrexate for ectopic pregnancy, is a fall in serum hCG of ≥15% between days 4–7 of treatment, which has a positive predictive value of 93% for treatment success. Two small studies have proposed a fall in serum hCG between days 0–4 after treatment confers similar, earlier prognostic information, with positive predictive values of 100% and 88% for treatment success. We sought to validate this in a large, independent cohort because of the potentially significant clinical implications.


We conducted a retrospective study of women (n=206) treated with single-dose methotrexate for ectopic pregnancy (pre-treatment serum hCG levels ≤3000 IU/L) at Scottish hospitals between 2006–2011. Women were divided into two cohorts based on whether their serum hCG levels rose or fell between days 0–4 after methotrexate. Treatment outcomes of women in each cohort were compared, and the test performance characteristics calculated. This methodology was repeated for the current measure (≥15% fall in serum hCG between days 4–7 of treatment) and an alternate early measure (<20% fall in serum hCG between days 0–4 of treatment), and all three measures were compared for their ability to predict medical treatment success.


In our cohort, the positive predictive value of the current clinical measure was 89% (95% CI 84-94%) (121/136). A falling serum hCG between days 0–4 predicted treatment success in 85% (95% CI 79-92%) of cases (94/110) and a <20% fall in serum hCG between days 0–4 predicted treatment success in 94% (95% CI 88-100%) of cases (59/63). There was no significant difference in the ability of these tests to predict medical treatment success.


We have verified that a decline in serum hCG between days 0–4 after methotrexate treatment for ectopic pregnancies, with pre-treatment serum hCG levels ≤3000 IU/L, provides an early indication of likelihood of treatment success, and performs just as well as the existing measure, which only provides prognostic information on day 7.

Ectopic pregnancy; Human chorionic gonadotrophin; Medical management; Methotrexate; Positive predictive value; Treatment success