From the Guidelines
A serum pregnancy test can be negative while a urine pregnancy test is positive due to the differences in sensitivity and specificity of the tests, as well as the timing of the tests, with urine tests sometimes detecting lower levels of human chorionic gonadotropin (hCG) than serum tests 1. The discrepancy between serum and urine pregnancy tests can be attributed to several factors, including:
- Timing of the tests: Urine pregnancy tests can detect hCG earlier than serum tests, especially if the serum test is qualitative rather than quantitative.
- Dilution effects: hCG may be more concentrated in urine than in blood, particularly in early pregnancy or if the woman is well-hydrated.
- Technical factors: Laboratory errors, improper test handling, or different sensitivity thresholds between tests can also contribute to the discrepancy.
- Medical conditions: Certain conditions, such as pituitary dysfunction or neoplasia, can cause elevated hCG levels unrelated to pregnancy, leading to false positive urine tests 1. It is essential to note that a serum hCG value greater than 5 mIU/mL is generally considered indicative of pregnancy, but values of 5 mIU/mL or less may occur in healthy nonpregnant patients 1. In cases where a serum pregnancy test is negative and a urine pregnancy test is positive, repeating both tests in 48-72 hours is recommended to clarify the true pregnancy status, as hCG levels should approximately double every two days in early viable pregnancies.
From the Research
Possible Reasons for Negative Serum Pregnancy Test with Positive Urine Pregnancy Test
- Early gestational age: According to 2, early gestational age is a common factor contributing to false-negative urinary hCG testing results. If the pregnancy is still in its early stages, the hCG levels may not be high enough to be detected by the serum test.
- β-core hook effects: 2 also mentions β-core hook effects as a factor that can lead to false-negative urine hCG test results. However, this effect can also occur in serum tests, although it is less common.
- Structural heterogeneity of hCG: As explained in 3, hCG exists in biological fluids as a mixture of different isoforms. This structural heterogeneity can affect the measurement of hCG in serum and urine, leading to discrepancies between the two tests.
- Sensitivity of the tests: The sensitivity of the serum and urine tests can also play a role in the discrepancy. 4 discusses the use of hCG measurement in detecting pregnancy and the problems of false-positive and false-negative pregnancy tests.
Analytical and Clinical Aspects of hCG Measurement
- hCG can be measured quantitatively in serum or urine, with the latter also using qualitative and rapid immunoassays 3.
- The advantages and limitations of assessing hCG in urine and serum are discussed in 3, highlighting the debate on whether serum or urine tests are preferred for establishing a diagnosis of pregnancy.
- 5 provides information on normal early pregnancy serum hCG levels and vaginal ultrasonography findings, which can be useful in understanding the relationship between hCG levels and pregnancy viability.
Other Factors to Consider
- Individual variation in hCG results: 4 mentions the extreme variation in individual hCG results, which can complicate pregnancy detection.
- Delayed implantation: 4 also discusses the problem of false-negative pregnancy tests due to delayed implantation.
- Heterophilic antibodies: 4 mentions the problem of false-positive pregnancy tests due to heterophilic antibodies.