Lab Interpretation: Positive hCG in women

ALGORITHM — 

Human chorionic gonadotropin (hCG) is measured primarily to detect pregnancy and, less frequently, to distinguish among a viable intrauterine, nonviable intrauterine, and extrauterine pregnancy (algorithm 1). It is also used to diagnose and monitor gestational trophoblastic disease (GTD) and germ cell tumors.

PREGNANCY

Detection

●Serum – Qualitative serum pregnancy tests typically detect hCG levels of 5 to 10 milli-international units/mL, while a high-sensitivity, quantitative serum beta-hCG assay can measure hCG values as low as 1 to 2 milli-international units/mL. hCG is secreted into the maternal circulation after implantation, which may occur 6 to 10 days after ovulation. This is the earliest that hCG can be detected with an ultrasensitive quantitative serum test.

●Urine – Most urine pregnancy tests are less sensitive than serum and are only qualitative, detecting hCG beginning at a level of 20 to 50 milli-international units/mL. In addition, the median hCG concentration is higher in serum than in urine. Therefore, very early in pregnancy, a serum pregnancy test may be positive while the urine pregnancy test is still negative. Tests on urine are adequate for diagnosis of a suspected pregnancy in women who have missed a menstrual period, especially when there is time to follow an initial negative test with a second test a week later.

●Home pregnancy test – Most home pregnancy tests are based on measuring hCG in urine. Positive results on a home-based test should be confirmed in most patients. Options include an office-based hCG test or another definitive finding (eg, Doppler confirmation of fetal cardiac activity, sonographic visualization of the pregnancy, uterine size consistent with dates). Confirmation is not required prior to first trimester medication termination. (See "Clinical manifestations and diagnosis of early pregnancy" and "First-trimester pregnancy termination: Medication abortion", section on 'Telemedicine and hybrid models'.)

False-positive pregnancy tests are rare and may be due to (table 1):

●Operator error in performing or interpreting the test, particularly with home pregnancy tests.

●Biochemical pregnancy (ie, recent pregnancy loss very soon after implantation).

●Exogenous hCG administered as part of infertility treatment or for athletic performance. Exogenous hCG should be cleared by two weeks postinjection.

●hCG secretion from a neoplasm (eg, GTD, ovarian germ cells tumors).

●Pituitary hCG secretion, typically in perimenopausal and postmenopausal women.

●Interference with the assay by antianimal antibodies, anti-hCG antibodies, or other substances (eg, high doses of biotin). In this setting, serum test is positive but urine test is usually negative.

Medications do not generally cause false-positive pregnancy tests, unless the medication contains hCG, high doses of biotin, or, rarely, certain antibodies. (See "Clinical manifestations and diagnosis of early pregnancy".)

For women with a presumptive normal pregnancy, counsel regarding pregnancy options. Begin or continue routine prenatal care. A standard panel of laboratory tests is typically obtained on every pregnant woman at the first prenatal visit. (See "Prenatal care: Initial assessment", section on 'Standard panel'.)

Additional testing may be necessary in women at risk for specific conditions (eg, thyroid disease, diabetes). (See "Prenatal care: Initial assessment", section on 'Selective screening'.)

Evaluation of concerning symptoms — For women who have symptoms suggestive of abnormal pregnancy (eg, uterine bleeding, pelvic or adnexal pain, severe nausea and vomiting), perform clinical assessment for ectopic pregnancy, pregnancy loss, or GTD.

Obtain:

●Serum quantitative hCG (if not performed as the initial pregnancy test)

●Transvaginal ultrasound (TVUS) examination

For women with significant first trimester vaginal bleeding (more than spotting), also obtain complete blood count (CBC) and, if indicated, type and screen (assessing for anemia and alloimmunization risk). If Rh-, anti-D immune globulin may be indicated, unless the pregnancy is very early or the vaginal bleeding is clearly due to a nonplacental, nonfetal source (eg, vaginal laceration). (See "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation".)

Women with a positive hCG and/or an acute abdomen or hemodynamic instability may have intra-abdominal hemorrhage from a ruptured ectopic pregnancy and should have emergency evaluation and treatment. (See "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Hemodynamically unstable patients'.)

●Normal intrauterine pregnancy detected – If a normal intrauterine pregnancy (IUP) is detected on TVUS and the serum hCG is within the normal range for gestational age, this excludes most cases of ectopic pregnancy or GTD. In rare cases, both an intrauterine and ectopic pregnancy may coexist. There is no role for serial monitoring of hCG concentration once the presence of a normal intrauterine singleton or multiple gestation has been established by ultrasound imaging. Continue routine prenatal care. (See "Prenatal care: Initial assessment" and "Prenatal care: Second and third trimesters".)

●Normal intrauterine pregnancy not detected – If a normal IUP is not detected, possibilities include:

•An early normal pregnancy

•Nonviable IUP

•Ectopic pregnancy

•GTD (less common)

Findings on physical examination, serial quantitative hCG levels, and TVUS help guide further evaluation and management. (See "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Diagnostic evaluation' and "Hydatidiform mole: Epidemiology, clinical features, and diagnosis", section on 'Pelvic ultrasound' and "Gestational trophoblastic neoplasia: Epidemiology, clinical features, diagnosis, staging, and risk stratification", section on 'Pelvic ultrasound' and "Pregnancy loss (miscarriage): Terminology, risk factors, and etiology".)

If ultrasound does not detect an IUP, the gestation may be too early to be visualized on ultrasound or it may be extrauterine. The serum quantitative hCG level at which a gestational sac should be visualized by TVUS if an IUP is present (discriminatory zone) is often considered to be 2000 milli-international units/mL; however, the threshold varies by laboratory and institution, and some data suggest that an IUP may not be visible until a higher level is reached (3510 milli-international units/mL).

•An hCG concentration greater than the discriminatory zone (approximately 2000 to 3510 milli-international units/mL) combined with absence of an IUP on TVUS strongly suggests ectopic pregnancy. An extraovarian adnexal mass is the most common ultrasound finding in ectopic pregnancy. (See "Ectopic pregnancy: Clinical manifestations and diagnosis".)

•If hCG is less than the discriminatory zone and the patient is hemodynamically stable, repeat quantitative serum hCG every two days for at least three serial measurements to determine trajectory of hCG, which will determine the next step:

-Counsel patient regarding symptoms of ruptured ectopic pregnancy (severe or persistent abdominal pain, increased vaginal bleeding).

-Ensure patient can see a clinician within two days and be compliant with blood draws (otherwise, send to emergency department).

•If the pregnancy is undesired, uterine aspiration can expedite diagnosis and management. If villi are present, an IUP was present. If no villi are present and the hCG decreases quickly, no additional treatment may be needed. If no villi are present and the hCG does not decrease, an ectopic pregnancy is likely.

MONITOR GERM CELL TUMORS — 

Ovarian germ cell tumors are often associated with hormonal or enzymatic activity (table 2). Although the definitive diagnosis is made by histology at time of surgical excision, the diagnosis is strongly suggested preoperatively by the presence of an adnexal mass on pelvic imaging and an elevated level of an associated tumor marker (eg, hCG, alpha-fetoprotein [AFP]). Tumor markers are monitored regularly as part of post-treatment surveillance. (See "Treatment of malignant germ cell tumors of the ovary", section on 'Post-treatment surveillance' and "Ovarian germ cell tumors: Pathology, epidemiology, clinical manifestations, and diagnosis", section on 'Tumor markers'.)

REFERENCE RANGE — 

hCG should be undetectable in nonpregnant women and in men. The serum hCG concentration doubles approximately every 29 to 53 hours during the first 30 days after implantation of a viable IUP. The concentration of hCG peaks at 8 to 10 weeks of gestation, with a peak ranging from 20,000 to 100,000 milli-international units/mL in a pregnancy with a single fetus. The levels decrease to a plateau in the second and third trimesters and then slowly decline towards term. Interpretation of a specific test result should be based upon the reference range reported with that result.

CITATIONS — 

The supporting references for this content are accessible in the linked topics.