What does a positive urine beta-human chorionic gonadotropin (bHCG) test but repeatedly negative quantitative serum beta-human chorionic gonadotropin (bHCG) tests indicate?

From the Guidelines

A positive urine beta-human chorionic gonadotropin (bHCG) test with repeatedly negative quantitative serum bHCG tests typically indicates a false-positive urine result. This discrepancy occurs because urine tests are less specific than serum tests and can be affected by several factors, such as the presence of protein or blood in the urine, certain medications, medical conditions that produce hCG-like substances, or laboratory error 1. The most recent and highest quality study on the topic of acute pelvic pain in the reproductive age group suggests that transvaginal ultrasound (TVUS) is the most useful method to evaluate the endometrium, early pregnancy, and adnexa 1. However, in the context of a positive urine bHCG test with repeatedly negative quantitative serum bHCG tests, the focus should be on resolving the discrepancy between the urine and serum test results rather than immediately proceeding to imaging studies. Some key points to consider include:

• The higher specificity of serum tests due to their ability to detect the exact concentration of bHCG rather than just its presence, making them the gold standard for confirming pregnancy 1.
• The potential for false-positive urine results due to various factors, which can be assessed by evaluating the urine hCG, as cross-reactive molecules in the blood that cause false positives rarely get into the urine 1.
• The role of TVUS in evaluating patients with suspected ectopic pregnancy, with a positive likelihood ratio of 111 for the finding of adnexal mass without an intrauterine pregnancy on TVUS, making it the single best diagnostic modality for this purpose 1. Given the information provided and the focus on morbidity, mortality, and quality of life, the most appropriate next step would be to consider the urine test result as potentially false-positive and rely on the serum test results for confirmation of pregnancy, especially when multiple negative serum results are available. If pregnancy is still suspected despite negative serum tests, a transvaginal ultrasound may be warranted to definitively rule out early pregnancy, taking into account the discriminatory threshold and the patient's clinical presentation 1.

From the Research

Urine bHCG Positive but Quantitative Serum BHCG Repeatedly Negative

• A positive urine beta-human chorionic gonadotropin (bHCG) test but repeatedly negative quantitative serum beta-human chorionic gonadotropin (bHCG) tests can be indicative of several conditions, including a potential ectopic pregnancy or a false positive urine test result.
• According to a study published in 1995 2, the measurement of the maternal serum to cul-de-sac fluid beta-hCG ratio can facilitate the early diagnosis of an ectopic pregnancy in the Fallopian tube, with a diagnostic sensitivity of 95.4% and specificity of 95.2%.
• However, another study from 1993 3 reported a case of ectopic pregnancy with undetectable serum and urine beta-hCG levels, where immunoperoxidase staining of the ectopic trophoblastic tissue revealed beta-hCG production, highlighting the possibility of false negative serum and urine tests.
• A study from 1985 4 found that a negative serum test virtually excludes an ectopic pregnancy, while an empty uterus with an adnexal mass and/or free fluid, along with a positive urine test, gives a high probability of an ectopic pregnancy.
• The use of pregnancy tests, including urine and serum beta-hCG measurements, is widely accepted for diagnosing pregnancy, with high sensitivity and specificity 5.
• A study from 1980 6 demonstrated that beta-hCG can be a useful diagnostic aid for suspected ectopic pregnancy, with no false-negative results reported in patients with ectopic pregnancies, and a negative beta-hCG result ruling out ectopic pregnancy in 100% of cases.

Possible Explanations

• False positive urine test result due to various factors, such as contamination or interference with the test.
• Ectopic pregnancy with low or undetectable serum beta-hCG levels, as reported in some studies 3, 6.
• Other medical conditions that may cause elevated urine beta-hCG levels, such as certain types of cancer or pituitary disorders.
• Laboratory error or variability in test results, which can lead to inconsistent or misleading results.

Clinical Implications

• A positive urine bHCG test with repeatedly negative quantitative serum BHCG tests requires further evaluation and investigation to determine the cause of the discrepancy.
• Clinicians should consider the possibility of an ectopic pregnancy, even with negative serum beta-hCG levels, and perform additional diagnostic tests, such as ultrasound or laparoscopy, to confirm the diagnosis.
• The use of pregnancy tests, including urine and serum beta-hCG measurements, should be interpreted in the context of the patient's clinical presentation and medical history.