Discussion
tubal ectopic pregnancy
TUBAL ECTOPIC PREGNANCY
To our knowledge, this is the largest prospective study assessing Days 1–4 serum hCG change as a predictor of single-dose methotrexate treatment success in tubal ectopic pregnancy. In our cohort, a fall in Days 1–4 serum hCG indicated an 85% (CI 76.8–90.6) likelihood of treatment success. Additionally, a <18% rise in Days 1–4 serum hCG signifies an 82% likelihood of treatment success, associated with high sensitivity and specificity. These findings support previous studies showing the predictive value of Days 1–4 hCG change (This study benefits from high-quality, carefully-phenotyped, prospectively collected data from a large multicentre clinical trial (GEM3) (Women with tubal ectopic pregnancy and hCG <1000 IU/l can be managed highly effectively with methotrexate or expectant management (We have presented Days 1–4 serum hCG change alongside serum hCG changes reliant on Day 7 data (Days 1–7 and Days 4–7), although we caution their direct comparison for two key reasons. Firstly, they represent different timepoints; Day 4 and Day 7 hCG are not contemporaneously available to inform clinical judgement or patient counselling. A compromise in predictive value may be worthwhile if the information could be available 3 days earlier. Secondly, the effect of intervention bias on Days 4–7 serum hCG change is important to consider. Current guidance from both the Royal College of Obstetricians and Gynaecologists (Any fall in Days 1–4 serum hCG signifies an 85% likelihood of treatment success for women with tubal ectopic pregnancy and hCG of ≥1000 and ≤5000 IU/l managed with single-dose methotrexate. Similarly, a modest (<18%) Days 1–4 serum hCG rise signifies an 82% likelihood of single-dose methotrexate treatment success with improved sensitivity. We therefore recommend that women are counselled at Day 4 in accordance with their Days 1–4 hCG change (see Implications for clinical practice.We recommend women with tubal ectopic pregnancy managed with methotrexate have a serum hCG sampled on Day 4 post-methotrexate administrationWe recommend women are counselled on Day 4 post-methotrexate administration in light of their Days 1–4 serum hCG changeWomen with a fall or modest (<18%) rise in Days 1–4 hCG can be provided with early reassurance that their treatment will likely be effectiveAny fall in Days 1–4 serum hCG signifies an 85% likelihood of treatment success for women with tubal ectopic pregnancy and hCG of ≥1000 and ≤5000 IU/l managed with single-dose methotrexateA modest (<18%) rise in Days 1–4 hCG signifies an 82% likelihood of single-dose methotrexate treatment success for women with tubal ectopic pregnancy and hCG of ≥1000 and ≤5000 IU/l managed with single-dose methotrexate