Diagnosing Pregnancy by Serum Beta-HCG
Serum beta-HCG becomes positive approximately 9 days after conception and a negative serum beta-HCG test essentially excludes the diagnosis of intrauterine or ectopic pregnancy. 1
Detection Threshold and Timing
- Serum beta-HCG can be detected as early as 6 days after presumed conception, making it the earliest reliable marker of pregnancy. 2
- The test becomes positive approximately 9 days after conception, well before a missed menstrual period. 1
- Serum testing is more sensitive than urine testing, with radioimmunoassays detecting levels as low as 5 mIU/mL. 3
Diagnostic Interpretation
Single Measurement Limitations
- A single HCG measurement has limited diagnostic value; serial measurements 48 hours apart provide more meaningful clinical information. 4
- A negative serum beta-HCG essentially excludes both intrauterine and ectopic pregnancy. 1
- Elevated beta-HCG in a nonpregnant patient may indicate miscarriage, ectopic pregnancy, pituitary production, paraneoplastic production, or gestational trophoblastic disease. 1
Correlation with Ultrasound
- At HCG levels of approximately 1,000-3,000 mIU/mL (discriminatory threshold), a gestational sac should be visible on transvaginal ultrasound. 4
- The traditional discriminatory level of 3,000 mIU/mL is more appropriate than historical levels of 1,000-2,000 mIU/mL for predicting gestational sac visibility. 4
- All pregnancies associated with beta-HCG concentrations greater than 300 mIU/mL should be correctly identified by transvaginal ultrasound. 5
Serial Monitoring Protocol
When to Repeat Testing
- Obtain repeat serum HCG measurements every 48 hours (2 days) to assess for appropriate rise or fall. 4
- A viable early intrauterine pregnancy typically shows doubling of HCG levels every 48-72 hours. 4
- Continue serial measurements until HCG rises to a level where ultrasound can confirm intrauterine pregnancy (>1,000-1,500 mIU/mL). 4
Abnormal Patterns Requiring Evaluation
- If HCG levels plateau (defined as <15% change over 48 hours) for two consecutive measurements, further evaluation is needed. 4
- If HCG levels rise >10% but <53% over 48 hours for two consecutive measurements, suspect abnormal pregnancy. 4
- In nonviable pregnancies, HCG fails to rise appropriately or decreases. 4
Critical Pitfalls to Avoid
Assay Interference
- When HCG results do not fit the clinical picture, measure the HCG on a different assay, as different assays have varying sensitivities and may detect different forms of HCG. 4, 6
- Many commercial HCG assays have problems with false-positive or false-negative results due to their ability to detect different HCG isoforms/fragments. 4
- When a false positive is suspected in serum, assessment of urine HCG can be helpful, as cross-reactive molecules in blood that cause false positives rarely get into urine. 4
Clinical Context
- Never defer ultrasound based solely on HCG level being "too low", as ectopic pregnancies can present at any HCG level. 4
- Approximately 22% of ectopic pregnancies occur at HCG levels <1,000 mIU/mL. 4
- Do not use the HCG value alone to exclude the diagnosis of ectopic pregnancy in patients who have indeterminate ultrasound findings. 4
Timing Considerations
- Qualitative urine pregnancy tests can remain positive for several weeks after pregnancy termination because HCG persists in the bloodstream. 7
- Most standard urine pregnancy tests will become negative within 2 weeks after a miscarriage. 7
Special Clinical Scenarios
Pregnancy of Unknown Location
- Perform transvaginal ultrasound immediately, regardless of HCG level, as it is the single best diagnostic modality with 99% sensitivity for ectopic pregnancy when HCG levels are elevated. 4
- About 7-20% of patients with pregnancy of unknown location will later be diagnosed with ectopic pregnancy. 4