Ectopic pregnancy is a cause of significant morbidity and mortality. Although many EPs are diagnosed with ultrasound, up to 50% are diagnosed by following serial hCG values. In line with a previous report (15
), this study confirms that there is no single hCG pattern to predict EP and many may mimic that of an IUP or SAB. Validating these results in a diverse set of patients, as presented in this report, is important as prediction models may lose test characteristics when applied externally, or may need to be amended to maintain accuracy (18
). Importantly, the use of a more representative population highlights the value of our conclusions, as EP epidemiologic indices vary among different races and ethnicities (3
Our analysis primarily focused on the first two hCG values, as this reflects common clinical practice. We found that the median slope for EP patients with increasing hCG values was a 32% increase in 2 days, which is slower than the 124% median increase for a viable IUP (13
). In addition, the median slope for those with falling hCG levels was a 15% decline in 2 days, which is less than the mean 70%–75% decrease for complete SAB (14
). However, extensive overlap exists. Our results confirm that the pattern of hCG increase or decrease in EP may also be consistent with that of a viable IUP or SAB (15
), and that this mimic occurred in 27% of the total EP cases. Stratified by initial increase or decrease of the slope, 30% of women who had initially increasing hCG curves met the criteria of growing IUP (13
) and 23% of those with an initially decreasing slope were consistent with the established cutoffs for spontaneous miscarriage (14
). There was no difference in these distributions based on race or ethnicity.
In contrast to hCG curves describing a viable IUP or SAB, 16% of the EP curves in our population experienced a change in the direction of the slope of the hCG curve, or an inflection point. These findings indicate that an inflection point is highly predictive of EP. Although a change in direction of serial hCG values is classically associated with an EP, perhaps counterintuitively, in practice the presence of inflection point(s) in hCG curves made the diagnosis more challenging. In these patients, an increase in median days to diagnosis and EP rupture was revealed, although the latter did not reach statistical significance.
We are not able to determine the cause of this delay in diagnosis. An inflection point may provide the practitioner reason to recompare the observed hCG curve to the standard curve, thus delaying action, or it may be some innate characteristic of the EP itself. Interestingly, women with inflection point(s) presented with lower median hCG values. This may be partly responsible for delayed EP diagnosis, given that hCG levels are correlated with TVS accuracy in visualizing EP (7
). Although we recognize that the total number of inflection events is relatively small, this is one of the largest studies of EPs and the evaluation of inflection points is an important novel investigation.
Importantly, the overlap demonstrated between EP curves and IUP or SAB curves was evident when we evaluated two consecutive hCG measurements, at presentation and after an inflection point of the relevant curves. This may imply that EP misclassification as a viable IUP or SAB could occur at any time during evaluation, independent of which consecutive hCG values we choose to compare. When evaluating a pregnancy of unknown location, practitioners must not be reassured by hCG curves that fit the pattern of IUP or SAB after an inflection point.
Stratifying our results by race and ethnicity may aid in better understanding the EP clinical and epidemiologic phenomena. National trends may not accurately represent EP-related statistics in certain geographic areas, especially where rapidly growing and culturally diverse populations live (17
). In this context, converging evidence points out that African Americans have higher EP incidence and mortality ratio (3
). Data on Hispanics are sparse. According to a study in California, Hispanics have the lowest EP rate among all racial and ethnic groups; however, the percentage of ruptured EPs in Hispanics is similar to that of African Americans (17
It has traditionally been thought that socioeconomic parameters such as limited access to health care and lower educational attainment may account for racial and ethnic disparities in EP mortality or severe complication rate (3
). Less health insurance coverage, failure of women to recognize early pregnancy signs and symptoms, or lack of EP awareness may impede early prenatal care (3
). It should be stressed that in our study, African Americans and Hispanics did not exhibit any significant difference in hCG values at presentation or gestational age at diagnosis, compared with the remaining population.
In light of our findings, the explanation of the higher EP mortality ratio in African Americans is intriguing. As we demonstrated, a unique hCG pattern in African Americans with EP marked by increased inflection point rate may exist, contributing to delayed diagnosis and, thus, enhancing EP rupture risk. There is very little available literature demonstrating differences in hCG curves by race, whether at one point in time or changes over time. Two groups have reported that hCG values may be higher among African Americans in the first trimester than white patients (19
), and this is an area for future research. The substantiation of our observation by larger studies is mandatory before definite conclusions are drawn.
In summary, these data confirm that no one unique pattern in hCG curves can be derived from EPs. Although the rate of change can often be used to distinguish an EP from an IUP or an SAB, EP may mimic both diagnoses in at least 27% of cases. The presence of inflection points is highly predictive of an EP but was associated with a delay in diagnosis with a greater percentage of rupture. The sole use of hCG surveillance to recognize or to rule out an EP raises major concerns about its safety and efficacy and should be avoided. Particular diligence is needed in patients with inflection points in their curves, especially the African American population.