Beta-HCG

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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[1]
  • 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[2]

Indications

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[3]
  • 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:[2][4]
    • 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[5]
Miscarriage
  • Expected to decline >21-35% in 48 hrs[6]
  • A single hCG level cannot reliably distinguish intrauterine from ectopic pregnancy[7]
  • 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[8]

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[8]
  • Very high hCG levels (>100,000 mIU/mL) should raise concern for gestational trophoblastic disease[9]
  • 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[10]

Causes of Elevated hCG

See Also

References

  1. ↑ Wilcox AJ, Weinberg CR, Wehmann RE, et al. Measuring early pregnancy loss: laboratory and field methods. Fertil Steril. 1988; 49(3):481-485. PMID 3342901.
  2. ↑ 2.0 2.1 Barnhart KT, Sammel MD, Rinaudo PF, et al. Symptomatic patients with an early viable intrauterine pregnancy: HCG curves redefined. Obstet Gynecol. 2004; 104(1):50-55. PMID 15229000.
  3. ↑ Cole LA. New discoveries on the biology and detection of human chorionic gonadotropin. Reprod Biol Endocrinol. 2009; 7:8. PMID 19171054.
  4. ↑ Barnhart KT, Guo W, Cary MS, et al. Differences in serum human chorionic gonadotropin rise in early pregnancy by race and value at presentation. Obstet Gynecol. 2016; 128(3):504-511. PMID 27500347.
  5. ↑ Silva C, Sammel MD, Zhou L, et al. Human chorionic gonadotropin profile for women with ectopic pregnancy. Obstet Gynecol. 2006; 107(3):605-610. PMID 16507930.
  6. ↑ Doubilet PM, Benson CB, Bourne T, Blaivas M. Diagnostic criteria for nonviable pregnancy early in the first trimester. N Engl J Med. 2013; 369(15):1443-1451. PMID 24106937.
  7. ↑ Murray H, Baakdah H, Bardell T, Tulandi T. Diagnosis and treatment of ectopic pregnancy. CMAJ. 2005; 173(8):905-912. PMID 16217116.
  8. ↑ 8.0 8.1 Connolly A, Ryan DH, Stuber AR, Postma HJ. Reevaluation of discriminatory and threshold levels for serum beta-hCG in early pregnancy. Obstet Gynecol. 2013; 121(1):65-70. PMID 23262929.
  9. ↑ Soper JT. Gestational trophoblastic disease. Obstet Gynecol. 2006; 108(1):176-187. PMID 16816073.
  10. ↑ Cole LA. Phantom hCG and phantom choriocarcinoma. Gynecol Oncol. 2006; 100(2):271-280. PMID 16169064.
  11. ↑ Snyder JA, Haymond S, Parvin CA, et al. Diagnostic considerations in the measurement of human chorionic gonadotropin in aging women. Clin Chem. 2005; 51(10):1830-1835. PMID 16099937.
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