Risk factors and prediction of ectopic pregnancy rupture following methotrexate treatment: A retrospective cohort study

Objective: Ectopic pregnancy (EP) rupture after methotrexate (MTX) treatment can have severe consequences. We examined clinical characteristics and beta-hCG trends that may predict EP rupture after MTX treatment. Study Design: In this 10-year retrospective study of 277 women with an EP, we compared clinical, sonographic and beta-hCG trends, before and after MTX treatment, between those who did and did not have an EP rupture after MTX treatment. Results: EP rupture was diagnosed in 41 women (15.1%) within 25 days of MTX treatment, and was correlated with higher parity and advanced pregnancy age: 2(0–5) vs. 1(0–6), P = 0.027 and 6.6(4.2–9.8) vs. 6.1(4–9.5), P = 0.045. EP rupture was also correlated with higher beta-hCG levels on days 0, 4 and 7 of MTX treatment: (2063 vs. 920 mIU/ml), (3221 vs. 921 mIU/ml) and (2368 vs. 703 mIU/ml), respectively, P < 0.001, for all. An increase of beta-hCG by>14% during days 0–4 showed a sensitivity of 71.4% CI 95% [55.4%-84.3%] and a specificity of 67.5% CI 95% [61.1%-73.6%] for predicting EP rupture after MTX treatment. Beta-hCG > 910 mIU/ml on day 0 showed a sensitivity of 80.9% CI 95% [66.7%-90.8%] and a specificity of 70.4% CI 95% [64.1%-76.3%] for predicting EP rupture after MTX treatment. A beta-hCG increase by>14% during days 0–4, and a beta-hCG value > 910 mUI/mL on day 0 were associated with increased risks of EP rupture after MTX treatment; the odds ratios were 6.4 and 10.5, respectively. Odds ratios were 8.06 [CI 95% (3.70–17.56)], P < 0.001 for every percent rise in beta-hCG during days 0–4; 1.37 [CI 95% (1.06–1.86)], P = 0.046 for every week change in gestational age; and 1.001 [CI 95% (1.000–1.001)], P < 0.001 for every unit rise in beta-hCG at day 0. Conclusion: Beta-hCG > 910 mIU/ml at day 0, a rise in beta-hCG by>14% during days 0–4, and more advanced gestational age were associated with EP rupture after MTX treatment.