This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials
1. Sonographic demonstration of any non-cystic adnexal mass is both sensitive and specific for in the diagnosis of ectopic pregnancy (EP) by transvaginal ultrasonography (TVUS).
2. Visualization of a non-cystic adnexal mass is comparably specific to direct imaging of a living extrauterine pregnancy or gestational sac, but significantly more sensitive for EP.
Original Date of Publication: April 1994
Study Rundown: EP is life threatening obstetric emergency in which gestation occurs outside the uterus, often presenting as an acute onset of pelvic pain with vaginal bleeding. The majority of EPs occur within the fallopian tube, but the embryo may also implant within the cervix, ovaries, or abdomen, and may require emergent laparoscopic removal in any of these locations. Accurate diagnosis includes both the measurement of serum human chorionic gonadotropin levels to confirm pregnancy and ultrasonographic visualization of ectopic products of conception, as confirmed by the works of Shalev et al., Condous et al., and Gracia and Barnhart. Once multiple studies confirmed the appropriateness of TVUS as the first-line study in the diagnosis of EP, the question arose regarding what must specifically be visualized at the threshold of positivity to most sensitively and specifically diagnose EP. The referenced study reviewed and meta-analyzed the contemporary literature to determine which of four criteria, in descending order of stringency, was most appropriate to use as the broad threshold for TVUS positivity in the diagnosis of EP. The four criteria reviewed were, at the most stringent, (1) direct visualization of a living extrauterine pregnancy, followed by (2) an extrauterine gestational sac with yolk sac or embryo, (3) an empty tubal ring, or extrauterine fluid collection with a surrounding hyperechoic ring, or (4) any adnexal mass other than a simple cyst, allowing inclusion of visualized hematoma in addition to any products of conception. The authors found that while the more stringent criteria were most specific (99-100%), they were highly insensitive (20-65%), and bore only moderate negative predictive values (78-89%). The least stringent criterion traded a minimally decreased specificity (98.9%) for a significant improvement in sensitivity (84%) and negative predictive value (95%). By these criteria, TVUS interpretation in the diagnosis of EP was simplified, thereby reducing failures to diagnose a potentially fatal condition while improving early recognition of EP and increasing opportunities for medical management with methotrexate over laparoscopic intervention. Notably, this study did not evaluate the effect on visualization of free fluid within the peritoneum, which may occur following rupture of an EP, but nonetheless established the most sensitive and specific criterion by which to interpret TVUS in the diagnosis of EP.
In-Depth [systematic review and meta-analysis]: This systematic review and meta-analysis pooled data from studies published between 1986 and 1993 examining the use of TVUS in the diagnostic workup of patients with suspected EP. A total of 2216 patients (1651 with EP, and 565 without) spanning 10 studies were included in which all enrolled patients were assessed by TVUS in the workup for EP with subsequent surgical confirmation of all cases. Sensitivity, specificity, positive and negative predictive values were calculated using Bayes’ theorem for each of four different positivity criteria used as the diagnostic threshold in TVUS assessment. Given that EPs may be visualized as anything ranging from an intact extrauterine pregnancy to an adnexal hematoma or other complex adnexal mass, the four tested criteria sought to encompass a stepwise progression in sonographic specificity as follows: the most stringent criterion required visualization of an extrauterine embryo with a heartbeat (20.1% sensitivity, 100% specificity, NPV 78.5%); followed by an extrauterine gestational sac with yolk sac or embryo (36.6% sensitivity, 100% specificity, NPV 82.2%); an adnexal mass with a central anechoic region or hyperechoic rim, known as an “empty tubal ring” (64.6% sensitivity, 99.5% specificity, NPV 89.1%); or the least stringent criterion, any adnexal mass other than a simple cyst or intraovarian lesion (84.4% sensitivity, 98.9% specificity, NPV 94.8%). As the threshold for positivity became less stringent, the sensitivity dramatically increased, yet with minimal decrease in overall specificity, finding that TVUS performed best using the most lax threshold when EP is suspected. This study established the simplest and most effective interpretation strategy for TVUS in the diagnosis of EP for both presurgical and medical management, and created an interpretative baseline for comparison to alternative diagnostic techniques.
Brown DL, Doubilet PM. Transvaginal sonography for diagnosing ectopic pregnancy: positivity criteria and performance characteristics. JUM. 1994 Apr 1;13(4):259–66.
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