Normal hCG Levels Throughout Pregnancy
hCG becomes detectable at 6-9 days after conception, peaks between 8-12 weeks of gestation, then steadily declines through week 16 and beyond, with no secondary rise in the third trimester. 1, 2
Early First Trimester (Weeks 0-6)
- hCG becomes detectable in serum approximately 6-9 days after conception, with initial levels rising above 5 mIU/mL to confirm pregnancy 1
- Values of 5 mIU/mL or less may occur in healthy non-pregnant patients 3
- In viable intrauterine pregnancies, hCG rises by at least 53% every 48 hours during early pregnancy, based on the 95% confidence interval for normal rise 1, 4
- At 6 weeks gestation, hCG levels in viable pregnancies demonstrate enormous individual variability, ranging from as low as 1,094 mIU/mL to well over 25,000 mIU/mL 1
Peak Period (Weeks 8-12)
- hCG levels peak between 8-12 weeks of gestation (56-68 days after conception) in normal pregnancy 1, 2
- This peak period correlates with the timing of maximal nausea and vomiting of pregnancy, which typically begins at 4-6 weeks, peaks at 8-12 weeks, and subsides by week 20 1
- hCG levels show significant fluctuations during early pregnancy, with variations that can exceed tenfold, though these variations decrease with advancing gestational age 5
Late First Trimester Decline (Weeks 11-13)
- Free beta-hCG, intact hCG, and hyperglycosylated hCG all decrease by approximately 20-40% from 11 to 13 completed weeks of gestation 1
- The nadir (lowest point) occurs around 18 weeks gestation 2
- At 11 weeks, free beta-hCG performs better than intact hCG for Down syndrome screening (2-3% higher detection rate), while at 13 weeks, intact hCG may perform slightly better (1-2% higher detection) 1
Second and Third Trimesters (Weeks 14-40)
- After peaking at 8-12 weeks, hCG levels show a steady decrease continuing through week 16 and beyond, with no secondary rise in the third trimester 1, 2
- Earlier non-specific immunoassays incorrectly suggested a secondary hCG peak in the third trimester, but modern beta-hCG radioimmunoassays demonstrate this was due to cross-reacting substances, not actual hCG 2
- hCG levels remain detectable throughout pregnancy but at substantially lower levels than the first-trimester peak 2
Critical Clinical Caveats
- Individual variation in hCG levels is enormous—absolute values have poor accuracy for dating pregnancy beyond 6 weeks, and ultrasound dating (not hCG levels) should be used to establish accurate gestational age 1
- The discriminatory level of approximately 3,000 mIU/mL (the level at which a gestational sac should be visible on transvaginal ultrasound) is clinically useful, but this threshold has virtually no diagnostic utility for predicting ectopic pregnancy (positive likelihood ratio 0.8, negative likelihood ratio 1.1) 1
- Management decisions should generally not be made based on a single hCG level—serial measurements 48 hours apart provide more meaningful clinical information 3, 1
- Different hCG assays detect different isoforms (free beta-hCG, intact hCG, hyperglycosylated hCG) with varying sensitivities, so using the same laboratory for serial measurements is recommended 1, 6
- Rarely, elevated hCG levels may be unrelated to pregnancy, such as with pituitary dysfunction or neoplasia 3
Sex-Specific Differences
- hCG concentrations differ based on fetal sex, with high hCG concentrations during the late first trimester (11th-12th week) associated with increased fetal growth amongst female fetuses but not male fetuses 7
- Low hCG concentrations measured in the late first trimester are associated with decreased fetal growth for both male and female fetuses 7