Originally published by 2 Minute Medicine^® (view original article). Reused on AccessMedicine with permission.

1. Active management (methotrexate or uterine evacuation followed by methotrexate if needed) more frequently resulted in pregnancy resolution among patients with persisting pregnancy of unknown location compared to expectant management.

2. Treatment with empirical methotrexate versus uterine evacuation (with methotrexate as required) demonstrated similar efficacy in pregnancy resolution among women with persisting pregnancy of unknown location.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Persisting pregnancy of unknown location occurs when there is neither an ongoing viable gestation nor a spontaneously resolving loss of pregnancy. Currently, there is no agreed-upon or consistent approach to managing these patients. The ACT or NOT randomized clinical trial assessed different management strategies to achieve pregnancy resolution in women with a persisting pregnancy of unknown location. The objectives were 1) to determine if active management is more effective than expectant management, and 2) whether treating with methotrexate empirically is as effective as uterine evacuation followed by methotrexate as needed. A greater proportion of women achieved pregnancy resolution with active management compared to expectant management. Furthermore, there was no significant difference in the proportion of women with successful pregnancy resolution between active management treatments (empirical methotrexate versus uterine evacuation). Vaginal bleeding was the most common adverse event for all three treatment groups. Overall, patients presenting with a persisting pregnancy of unknown location were more likely to achieve pregnancy resolution with active management compared to expectant management. Notably, many patients did not end up in the management group they were initially randomized to, which may have introduced bias into the study. Encouragingly, analysis based on as-treated (rather than as-randomized) resulted in similar findings.

Click to read the study in JAMA

Relevant Reading:Effectiveness of expectant management versus methotrexate in tubal ectopic pregnancy: a double-blind randomized trial

In-Depth [randomized controlled trial]:

This multicentre trial enrolled 255 patients (median [IQR] age: 31 years [27-36]) between July 25, 2014, and June 4, 2019; 253 patients were included in the final analysis. Participants were randomized into three groups: expectant management, empirical methotrexate, or uterine evacuation with methotrexate (if required). 99/255 (39%) patients declined the assigned management strategy they were randomized into and chose an alternative treatment group. The primary outcome was successful pregnancy resolution without requirement of a change from the original treatment plan. The percentage of patients with pregnancy resolution in those who underwent active management compared to expectant management was 51.5% versus 36.0% (difference: 15.4% [95% CI: 2.8-28.1]; relative risk [RR]: 1.43 [95%: 1.04-1.96]). Participants randomized to active management were less likely to undergo unscheduled surgery (RR: 0.47 [95% CI: 0.28-0.80]) or receive unscheduled methotrexate (RR: 0.33 [95% CI: 0.22-0.51]) compared to expectant management. The percentage of patients with pregnancy resolution in those who received methotrexate compared to uterine evacuation was 54.9% versus 48.3% (difference: 6.6% [1-sided 97.5% CI: -8.4-∞]).

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