Rethinking the rate of rise in β-hCG. The oft-quoted maxim that ectopic pregnancy or impending miscarriage is associated with a rise in β-hCG of less than 66% in 48 hours arose from a 1981 study that included only 20 women and that was based on an 85% confidence interval (CI).20 A recent study of 287 women suggests that the minimal expected rise in 2 days for a viable intrauterine pregnancy (based on a 99% CI) should be at least 53%.21
Combining β-hCG levels and ultrasound findings to improve diagnosis. Because the exact gestational age is often unknown in women presenting with features of ectopic pregnancy, the β-hCG level is used to determine whether a gestational sac can be identified on ultrasound. With a β-hCG level of 6500 mIU/mL, a gestational sac should be visible on abdominal ultrasound in the uterus of a woman with an intrauterine pregnancy; the sac should be absent in ectopic pregnancy. This β-hCG level is designated the discriminatory zone.22
With a high-resolution transvaginal ultrasound (TVUS), the gestational sac of a normal single intrauterine pregnancy should be visible at a β-hCG level above 1000–1500 mIU/mL, depending on equipment and technical expertise.2,7 In multiple gestations the discriminatory zone is observed to be above 2300 mIU/mL.2 Various ultrasonography findings have been combined with β-hCG levels to more accurately diagnose ectopic pregnancy (TABLE 2 and FIGURE).
Serial β-hCG measurements. If TVUS findings are indeterminate, serial measurements of β-hCG levels at 48-hour intervals may be useful in managing suspected ectopic pregnancy. Dart et al17 found that a rise in β-hCG level of 66% or more was usually associated with a viable intrauterine pregnancy, though 22% of women in that study had an ectopic pregnancy. Mol et al13 found similar results using a cutoff of a β-hCG level rise of 50% or more; 35% had an ectopic pregnancy. Increases in the β-hCG level less than these cutoffs almost always indicated an abnormal pregnancy, and about half of these women had an ectopic pregnancy.13,17 Also a fall in the β-hCG level by less than 50% was almost always associated with an abnormal pregnancy, but only 19% of these women had an ectopic pregnancy. 13,17 Alternatively, decreases in β-hCG level of greater than 50% reduced the chance that patients had an ectopic pregnancy to less than 3%.13,17
Scope of the problem
Ectopic pregnancy is defined as the implantation of the fertilized egg that occurs outside the uterine cavity. It is practically synonymous with tubal pregnancy, as 97% occur in the Fallopian tube.6,23 Ectopic pregnancy occurs in 2% of all pregnancies in the United States, affecting more than 100,000 patients each year. It is a leading cause of pregnancy-related death in the first trimester,2 with a yearly monetary impact of greater than 1 billion dollars. The incidence has increased almost six-fold since 1970 due to delayed child-bearing, rising prevalence of sexually transmitted diseases, and sterilization procedures.6
FIGURE
Diagnostic protocol with high sensitivity and specificity for ectopic pregnancy
* Other than midline suprapubic cramping.
† Risk may be higher in presence of these factors: previous EP, tubal surgery, tubal disease detected by hysterosalpingogram or laproscopy, diethylstilbestrol exposure, sterilization, intrauterine device.
‡ Progesterone is useful only when TVUS is indeterminate.
§ β-hCG level for criterion should be based on local values at which IUP visible on TVUS.
|| TVUS should be repeated when β-hCG has risen above the discrimination zone.
¶ Only 2/170 patients in this category had EP; therefore, D&C is safe but may not be cost-effective.11
β-hCG, beta-human chorionic gonadotropin; EP, ectopic pregnancy; TVUS, transvaginal ultrasound; OB/GYN, obstetrician/gynecologist;
IUP, intrauterine pregnancy; D&C, dilation and curettage.
Serum progesterone levels may have limited usefulness. Serum progesterone measurements are not considered accurate enough to diagnose ectopic pregnancy.24 However, progesterone levels may be helpful if they are either very high or very low. Levels less than 22 ng/mL have a sensitivity of 100% for ectopic pregnancy.25 Only 5 of 1615 patients (0.3%) in 13 studies with progesterone levels below 5 ng/mL had a viable intrauterine pregnancy.24 By establishing the low likelihood of a viable intrauterine pregnancy, serum progesterone measurements may also be useful when β-hCG levels have reached 1000–1500 mIU/mL and the TVUS is equivocal.25
When D&C may help. Dilation and curettage (D&C) is an option for patients with an indeterminate ultrasound result and progesterone levels less than 5 ng/mL, as it can rule out an ectopic pregnancy with only a small chance of interrupting a viable intrauterine pregnancy. The presence of chorionic villi rules out an ectopic pregnancy. In the absence of villi, if β-hCG levels subsequently plateau or increase, it is presumptive of ectopic pregnancy. Chorionic villous sampling by pipelle curette has both insufficient sensitivity and predictive value in diagnosing ectopic pregnancy, and should not be considered a substitute for D&C.26