Serial hCG levels are usually required when the results of the initial ultrasonography examination are indeterminate (i.e., when there is no evidence of an intrauterine gestation or extrauterine cardiac activity consistent with an ectopic pregnancy). When the hCG level is less than 2,000, doubling time helps to predict viable intrauterine gestation (normal rise) versus nonviability (subnormal rise). With normally rising levels, a second ultrasonography examination is performed when the level is expected (by extrapolation) to reach 2,000 mIU/mL. Abnormally rising levels (less than 2,000 mIU/mL and less than 50% rise over 48 hours) indicate a nonviable pregnancy. The location (i.e., intrauterine versus. extrauterine) must be determined surgically, either by laparoscopy or dilation and curettage. Indeterminate ultrasonography results and an hCG level of less than 2,000 mIU/mL is diagnostic of nonviable gestation, either ectopic pregnancy or a complete abortion. Rapidly falling hCG levels (50% over 48 hours) occur with a completed abortion, whereas with an ectopic pregnancy levels rise or plateau.
A single hCG measurement has limited usefulness because there is considerable overlap of values between normal and abnormal pregnancies at a given gestational age. The ectopic pregnancy site and hCG level do not correlate (112). Many patients in whom the diagnosis of ectopic pregnancy is being considered are uncertain about their menstrual dates. A single hCG level may be useful when measured by sensitive enzyme immunoassays that, if negative, exclude a diagnosis of ectopic pregnancy. Measurement of a single level may be helpful in predicting pregnancy outcome after timed conceptions using advanced reproductive technology. If the hCG level is more than 300 mIU/mL on day 16 to 18 after artificial insemination, there is an 88% chance of a live birth (113). If the hCG level is less than 300 mIU/mL, the chance of a live birth is only 22%. A single hCG level may facilitate the interpretation of ultrasonography when an intrauterine gestation is not visualized. An hCG level greater than the ultrasound discriminatory zone indicates a possible extrauterine pregnancy. Determination of serial hCG levels may be needed to differentiate an ectopic pregnancy from a completed abortion. Further tests are required for patients in whom ultrasonography examination results are inconclusive and hCG levels are below the discriminatory zone.
Serum Progesterone The mean serum progesterone level in patients with ectopic pregnancies is lower than that in patients with normal intrauterine pregnancies (114,115). However, in studies of more than 5,000 patients with first-trimester pregnancies, a spectrum of progesterone levels was found in patients with both normal and abnormal pregnancies (35,116,117). About 70% of patients with a viable intrauterine pregnancy have serum progesterone levels higher than 25 ng/mL, whereas only 1.5% of patients with ectopic pregnancies have serum progesterone levels higher than 25 ng/mL, and most of these pregnancies exhibit cardiac activity (35,116,117).
A serum progesterone level can be used as an ectopic pregnancy screening test for both normal and abnormal pregnancy, particularly in settings in which hCG levels and ultrasonography are not readily available. A serum progesterone level of less than 5 ng/mL is highly suggestive of an abnormal pregnancy, but it is not 100% predictive. The risk of a normal pregnancy with a serum progesterone level of less than 5 ng/mL is about 1 in 1,500 (118). Serum progesterone measurements alone cannot be used to predict pregnancy nonviability.