C-reactive protein is an acute-phase reactant that increases with trauma or infection. Levels of this protein are lower in patients with ectopic pregnancy than in patients with an acute infectious process. When an infectious process is part of the differential diagnosis, measurement of C-reactive protein may be beneficial (135).
Ultrasonography Improvements in ultrasonography resulted in the earlier diagnosis of intrauterine and ectopic gestations (136). The sensitivity of the β-hCG assay allows the diagnosis of pregnancy before direct visualization by ultrasonography.
The complete examination should include both transvaginal and transabdominal ultrasonography. Transvaginal ultrasonography is superior to transabdominal ultrasonography in evaluating intrapelvic structures. The closeness of the vaginal probe to the pelvic organs allows use of higher frequencies (5–7 mHz), which improves resolution. Intrauterine pregnancy can be diagnosed 1 week earlier with transvaginal than with transabdominal ultrasonography.
Evidence of an empty uterus, detection of adnexal masses and free peritoneal ﬂuid, and direct signs of ectopic pregnancy are more reliably established with a transvaginal procedure (137– 142). Transabdominal ultrasonography permits visualization of both the pelvis and abdominal cavity and should be included as part of the complete ectopic pregnancy evaluation to detect adnexal masses and hemoperitoneum.
The earliest ultrasonographic finding of an intrauterine pregnancy is a small ﬂuid space and the gestational sac, surrounded by a thick echogenic ring, located eccentrically within the endometrial cavity. The earliest normal gestational sac is seen at 5 weeks of gestation with transabdominal ultrasonography and at 4 weeks of gestation with transvaginal ultrasonography (143,144). As the gestational sac grows, a yolk sac is seen within it, followed by an embryo with cardiac activity.
The appearance of a normal gestational sac may be simulated by intrauterine ﬂuid collection, the pseudogestational sac, which occurs in 8% to 29% of patients with ectopic pregnancy (145– 147). This ultrasonographic lucency, centrally located, probably represents bleeding into the endometrial cavity by the decidual cast. Clots within this lucency may mimic a fetal pole.
Morphologically, identification of the double decidual sac sign (DDSS) is the best method of ultrasonographically differentiating true sacs from pseudosacs (148). The double sac, believed to be the decidua capsularis and parietalis, is seen as two concentric echogenic rings separated by a hypoechogenic space. Although useful, this approach has some limitations in sensitivity and specificity—the DDSS sensitivity ranges from 64% to 95% (147). Pseudosacs may occasionally appear as the DDSS; intrauterine sacs of failed pregnancies may appear as pseudosacs.
The appearance of a yolk sac within the gestational sac is superior to the DDSS in confirming intrauterine pregnancy (149). The yolk sac is consistently visible on transabdominal ultrasonography with a gestational sac size of 2 cm and on transvaginal ultrasonography with a gestational sac size of 0.6 to 0.8 cm (150,151). Intrauterine sacs smaller than 1 cm on transabdominal ultrasonography and smaller than 0.6 cm on transvaginal ultrasonography are considered indeterminate. Larger sacs without DDSS or yolk sac represent either a failed intrauterine or ectopic pregnancy.
The presence of cardiac activity within the uterine cavity is definitive evidence of an intrauterine pregnancy. This finding essentially eliminates the diagnosis of ectopic pregnancy because the incidence of combined intrauterine and extrauterine pregnancy is 1 in 30,000.