Jake Schutzman, MS4
The Article: Richardson, A. , Gallos, I. , Dobson, S. , Campbell, B. K., Coomarasamy, A. and Raine‐Fenning, N. (2016), Accuracy of first‐trimester ultrasound in diagnosis of tubal ectopic pregnancy in the absence of an obvious extrauterine embryo: systematic review and meta‐analysis. Ultrasound Obstet Gynecol, 47: 28-37. doi:10.1002/uog.14844
The Idea: Despite advances in management and detection of ectopic pregnancies over the past few decades, these pregnancies are still associated with significant maternal morbidity and mortality. Early diagnosis is essential to reducing mortality, though this can be difficult at times. Although high-resolution transvaginal ultrasound (TVS) can aid in early detection of ectopic pregnancies, direct visualization of a living embryo located outside of the uterus is only present in a minority of patients. In the absence of an obvious ectopic on TVS, a number of different signs have been identified for detection of ectopic pregnancies, including an empty uterus (i.e. one that does not contain a gestational sac, pseudosac or retained products of conception), a pseudosac, free fluid, and an adnexal mass.
The Study: This study was a systematic review and meta-analysis aimed at assessing the accuracy of the above-mentioned signs in the diagnosis of tubal ectopic pregnancies in the absence of an obvious extrauterine living embryo.
· Databases Searched:
o MEDLINE (1951 to March 2013)
o EMBASE (1980 to March 2013)
o The Cochrane Library (2013)
· Inclusion Criteria:
o Primary study evaluating use of 1st trimester ultrasound in diagnosis of ectopic pregnancy
· Exclusion Criteria:
o Case report or case study with sample size < 10 cases
o Commentary, Narrative review, or Letter
· Data Collected:
o Study characteristics (first author, year of publication, population, age group, inclusion and exclusion criteria)
o Study methodology (study design, study period, recruitment method)
o Details of the intervention (ultrasound approach i.e. transabdominal or transvaginal, frequency/resolution of ultrasound machine, operator; ultrasonographic feature under evaluation, i.e. pseudosac, empty uterus, free fluid, adnexal mass)
o Outcome investigated
o Quality and accuracy of the results
Results: The initial search identified 19 959 potential papers. After review of titles & abstracts, and then further application of inclusion and exclusion criteria, 31 studies, including 5858 women, were incorporated into the review.
Diagnostic accuracy of the follow individual and combinations of signs were analyzed:
· Empty uterus [13, 2499, 81.1 (42.1-96.2), 79.5 (62.8-87.1), 3.95 (2.70-5.77), 0.24 (0.06-0.94), 29.6 (7.2-77.7), 62 (60-65), 9 (8-11)]
· Pseudosac [8, 1838, 5.5 (3.3–9.0), 94.2 (75.9–98.8), 0.96 (0.26–3.48), 1 (0.93–1.08), 31.6 (7.2–68.8), 12 (8–16), 35 (34–35)]
· Adnexal mass [21, 2787, 63.5 (48.5–76.3), 91.4 (83.6–95.7), 7.39 (3.63–15.05), 0.4 (0.27–0.59), 39.4 (24.2–88.0), 83 (80–85), 21 (19–22)]
· Free fluid [19, 3232, 47.2 (33.2–61.7), 92.3 (85.6–96.0), 6.12 (3.08–12.18), 0.57 (0.43–0.76), 30.7 (5.19–77.7), 73 (70–76), 20 (19–21)]
· Pseudosac + Adnexal mass [7, 1023, 45 (34–56), 96 (93–98), 12 (5.9–24.1), 0.57 (0.46–0.71), 54.3 (33.2–77.7), 93 (90–96), 40 (38–42)]
· Pseudosac + Free fluid [1, 265, 2.9 (1.1–6.2), 100 (93.4–100), ∞ , 0.97 (0.95–0.99), 77.7 , 100 , 22.8]
· Adnexal mass + Free fluid [1, 265, 3.9 (1.7–7.5), 96.6 (88.3–99.5), 1.15 (0.25–5.25), 0.99 (0.94–1.05), 77.7 , 80 , 22.3]
· Pseudosac + Adnexal mass + Free fluid [1, 265, 5.8 (3.1–10.0), 100 (93.9–100), ∞ , 0.94 (0.91–0.97), 77.7 , 100 , 23.3]
Sign [# studies, # women, sensitivity (95% CI) (%), specificity (95% CI) (%), LR+ (95% CI), LR- (95% CI), Pre-test probability, Post-test probability if positive, Post-test probability if negative]
In additional, a subgroup analysis of eight studies found to have a low risk of bias and low applicability concerned using the quality assessment of diagnostic accuracy studies (QUADAS‐2) tool was performed and the estimated summary sensitivities and specificities as well as positive and negative likelihood ratios of an empty uterus, adnexal mass, and free fluid were calculated as follows:
· Empty uterus [5, 1341, 75.8 (31.4–95.5), 71 (52.6–84.4), 2.61 (1.49–4.58), 0.34 (0.09–1.35)]
· Pseudosac [4, 444, 67.3 (42.6–85.1), 94.9 (74.3–99.2), 13.3 (1.73–102.0), 0.34 (0.16–0.74)]
· Adnexal mass [4, 805, 52.3 (35.9–68.2), 93.5 (74.4–98.6), 8.09 (1.87–35.10), 0.51 (0.36–0.72)]
Sign [# studies, # women, sensitivity (95% CI) (%), specificity (95% CI) (%), LR+ (95% CI), LR- (95% CI)]
The Takeaway: Overall, in the absence of an obvious extrauterine pregnancy the ultrasound findings of an empty uterus, pseudosac, adnexal mass, and free fluid both individually and combined have poor sensitivity but relatively good specificity for identifying a tubal ectopic pregnancy; subgroup analysis among only high quality studies produced similar findings. This suggests that these signs may be helpful for “ruling in” but not “ruling out” an ectopic pregnancy. The main limitations of this study included significant heterogeneity among included studies on prevalence of ectopic pregnancies, definitions of ultrasound signs, and ultrasound approach (i.e. transabdominal vs transvaginal, frequency / resolution of machines); there was also a wide variability in the reported accuracy, which may be due to the aforementioned heterogeneity. Individual institutions can improve the clinical usefulness of this research through the collection of data on the prevalence ectopic pregnancies in their patient population in various contexts. This research may underestimate the current accuracy and useful of these signs given recent advances in ultrasound technology as well as more consistent use of the higher quality transvaginal approach (when required in addition to transabdominal) currently compared to the its use during the time of some of the included studies. Subgroup analysis on high- vs low-risk patients was not possible due to limited availability of this data in the primary data (most studies only included intermediate-risk patients). Further research including data may in this area could likely prove helpful.