Hum. Reprod. Advance Access originally published online on January 21, 2005
Human Reproduction 2005 20(4):928-935; doi:10.1093/humrep/deh702
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Intact HCG, free HCG 
subunit and HCG core fragment: longitudinal patterns in urine during early pregnancy
1 Brooklyn College, The City University of New York, 3 Irving Center for Clinical Research and 6 Department of Obstetrics and Gynaecology, 7 Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, 2 Epidemiology Branch and 4 Biostatistics Branch, NIEHS and 5 WESTAT, Durham, NC, USA
8 To whom correspondence should be addressed at: Epidemiology Branch MD A3-05, National Institute of Environmental Health Sciences (NIEHS), Durham, NC 27709, USA. Email: wilcox{at}niehs.nih.gov
BACKGROUND: Detecting and monitoring early pregnancy depend on the measurement of HCG. Little is known about how production of various forms of HCG may evolve over the earliest weeks of pregnancy, particularly in naturally conceived pregnancies. METHODS: We describe the daily excretion of three urinary HCG analytes during the first 6 weeks post-conception in 37 naturally conceived pregnancies ending in singleton birth. We assayed daily first morning urine samples for intact HCG, free 
subunit and 
core fragment, plus the combined measurement of these HCG forms. We calculated doubling times for each analyte and the inter- and intra-subject day-to-day variation. RESULTS: Intact HCG and the free subunit were initially the predominant forms of HCG, with the core fragment emerging as the predominant form in the fifth week after conception. Intact HCG and the free subunit showed the most day-to-day variability, and were transiently undetectable even 10 days after detection of pregnancy. The most stable estimate of doubling time was provided by the combined measurement of all these forms. CONCLUSIONS: Although intact HCG is usually regarded as the main analyte for detection and monitoring of early pregnancy, it can fluctuate markedly during early pregnancy. This variability could affect pregnancy test results based on early pregnancy urine, and may distort estimates of doubling time. Assays that combine several forms of HCG may be more reliable.
Key words: HCG/longitudinal patterns/pregnancy/urine
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