Background: Ectopic pregnancy is a potentially life-threatening condition commonly managed with methotrexate in hemodynamically stable patients without absolute contraindications. Although methotrexate dosing is calculated using body surface area, the optimal weight-based strategy in obese patients remains uncertain. Historically, Northside Hospital Atlanta, Cherokee, and Forsyth utilized adjusted body weight for dosing due to concerns about toxicity. However, questions regarding potential underdosing and reduced efficacy prompted a transition to total body weight–based dosing on May 6, 2025. This study compares treatment success and adverse drug reactions between adjusted body weight and total body weight methotrexate dosing strategies in hemodynamically stable obese patients with tubal ectopic pregnancy.
Methods: This retrospective cohort study evaluated the safety and efficacy of single-dose intramuscular methotrexate dosed at 50 mg/m2 in obese patients diagnosed with tubal ectopic pregnancy before and after implementation of total body weight–based dosing. Obesity was defined as a total body weight greater than 130% of ideal body weight. The primary outcome was treatment success, defined as resolution of ectopic pregnancy without additional methotrexate doses or surgical intervention. Secondary outcomes included adverse drug reactions. Eligible patients were ≥18 years old and received methotrexate for tubal ectopic pregnancy. Patients with relative contraindications to methotrexate such as, β-hCG >5,000 mIU/mL, ectopic mass >4 cm, or fetal cardiac activity, were included. Data collected from electronic medical records included demographics, baseline labs, initial β-hCG levels, ultrasound findings, need for additional methotrexate dosing, surgical intervention, and documented adverse events. Comparative analyses were performed within and between adjusted and total body weight dosing groups.
Results: A total of 120 women were included in the study, with 60 patients in both the pre-implementation and post-implementation cohorts. In the pre-implementation cohort, 32 patients were obese and 28 were non-obese. Treatment resolution occurred in 81.3% (26/32) of obese patients and 64.3% (18/28) of non-obese patients. Among non-obese patients, 17.9% (5/28) had pre-methotrexate β-hCG levels >5,000 mIU/mL, 7.1% (2/28) had ectopic masses >4 cm, and 0% had cardiac embryonic activity. In contrast, 0% of obese patients had β-hCG levels >5,000 mIU/mL, and none had ectopic masses >4 cm or embryonic cardiac activity. The post-implementation cohort included 37 obese and 23 non-obese patients. Treatment resolution occurred in 59.5% (22/37) of obese patients and 56.5% (13/23) of non-obese patients. Among non-obese patients, 4.3% (1/23) had pre-methotrexate β-hCG levels >5,000 mIU/mL, 0% had an ectopic mass >4 cm, and 4.3% (1/23) had cardiac embryonic activity. Among obese patients, 13.5% (5/37) had pre-methotrexate β-hCG levels >5,000 mIU/mL, 5.4% (2/37) had ectopic masses >4 cm, and 0% had cardiac embryonic activity. After accounting for relative contraindications to methotrexate administration in obese and non-obese patients within each group, there was a lower difference in resolution rates within the pre-implementation arm (obese, 81.3% vs non-obese, 76.2%) vs the post-implementation arm (obese, 66.7% vs non-obese, 57.1%)
Conclusions: In this retrospective study, adjusted resolution rates for relative contraindications showed a greater difference in success rates, favoring obese patients, in the post-implementation group compared to the pre-implementation group. Although total body weight dosing was associated with a higher frequency of adverse events, no serious adverse events were observed. These findings confirm that relative contraindications to methotrexate reduce efficacy, and further prospective studies with larger sample sizes are needed to define the optimal methotrexate dosing strategy in obese patients. Considerations for future studies include utilizing a 2-dose methotrexate regimen for patients with an initial elevated hCG, evaluating differences in success rates across obese subgroups stratified by differences in BMI, and excluding patients with relative contraindications to methotrexate.
