Beta-HCG

Background

• Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced by the syncytiotrophoblast of the placenta
• Detected in maternal serum as early as 6-8 days after ovulation
• The beta subunit is specific to hCG and is what is measured by pregnancy tests (qualitative = urine, quantitative = serum)
• In normal early pregnancy, serum hCG approximately doubles every 48-72 hours, peaking at 8-11 weeks of gestation

Indications

• Confirm pregnancy
• Evaluate for ectopic pregnancy in patients with abdominal pain or vaginal bleeding
• Serial monitoring to assess viability of early pregnancy
• Evaluate for gestational trophoblastic disease (e.g., molar pregnancy)
• Evaluate for possible miscarriage or pregnancy of unknown location

Expected Levels by Gestational Age

B-HCG levels over time.

Estrogen, progesterone, beta-hcg levels throughout pregnancy.

Gestational Week	Minimum (mIU/mL)	Maximum (mIU/mL)
3	5	50
4	5	426
5	18	7,340
6	1,080	56,500
7-8	7,650	229,000
9-12	25,700	288,000
13-16	13,300	254,000
17-24	4,060	165,400
25-40	3,640	117,000
Postpartum (4-6 wks)	NA	<5

• Values represent approximate ranges and vary by laboratory and assay method
• Wide range of normal values at any given gestational age; a single value should not be used alone to determine viability

Repeat Levels

Repeat B-hCG Levels

Pregnancy Type	B-hCG Change
Normal	Minimum expected rise depends on initial hCG value: Initial hCG <1,500 mIU/mL: minimum 49% rise in 48hrs Initial hCG 1,500-3,000 mIU/mL: minimum 40% rise in 48hrs Initial hCG >3,000 mIU/mL: minimum 33% rise in 48hrs hCG typically doubles approximately every 48-72 hours in early pregnancy Rate of rise slows after hCG reaches approximately 6,000-10,000 mIU/mL
Ectopic	Increases or decreases more slowly than expected ("plateau") Approximately 21% of ectopic pregnancies have a normal hCG rise
Miscarriage	Expected to decline >21-35% in 48 hrs

• A single hCG level cannot reliably distinguish intrauterine from ectopic pregnancy
• The discriminatory zone (typically 1,500-3,500 mIU/mL depending on institution) is the hCG level above which a gestational sac should be visible on transvaginal ultrasound

Interpretation Pearls

• hCG >1,500-3,500 mIU/mL (institutional discriminatory zone) without an intrauterine pregnancy on transvaginal ultrasound should raise suspicion for ectopic pregnancy
• Very high hCG levels (>100,000 mIU/mL) should raise concern for gestational trophoblastic disease
• A plateau in hCG levels (rise <49% or decline <21% in 48 hrs) is suggestive of a pregnancy of unknown location and may represent ectopic or nonviable intrauterine pregnancy
• hCG levels may remain detectable for 4-6 weeks after miscarriage or completion of a pregnancy
• Heterophilic antibodies can cause false-positive results (hook effect); consider serial dilutions if clinical picture does not match hCG level

Causes of Elevated hCG

• Intrauterine pregnancy (most common)
• Ectopic pregnancy
• Gestational trophoblastic disease (molar pregnancy)
• Recent pregnancy loss or termination (residual hCG)
• Exogenous hCG administration
• Germ cell tumors
• Peri-menopausal pituitary hCG production (usually low levels <14 mIU/mL)

See Also

• Pregnancy (main)
• Vaginal Bleeding Pregnant (less than 20wks)
• Ectopic pregnancy
• Maternal Vitals and Labs in Pregnancy
• Miscarriage
• Gestational trophoblastic disease