Clin Chem Lab Med 2011;49(8):xxx-xxx ? 2011 by Walter de Gruyter • Berlin • New York. DOI 10.1515/CCLM.2011.211
Article in press - uncorrected proof
The untility of six over-the-counter (home) pregnancy tests
Laurence A. Cole*
Department of Obstetrics and Gynecology, USA hCG
Reference Service, University of New Mexico,
Albuquerque, NM, USA
Background: The home pregnancy market is rapidly evolv-
ing. It has moved from detection of pregnancy on the day
of missed menstrual bleeding, to detection claims 4 days pri-
or. It is moving from all manual tests to digital tests, with a
monitor reading the bands and informing women they are
pregnant. A thorough study is needed to investigate the
validity of claims and evolving usefulness of devices.
Methods: Studies were proposed to examine the sensitivity
and specificity of home tests and their abilities to detect preg-
nancy. Methods examined the abilities of tests to detect
human chorionic gonadotropin (hCG), hyperglycosylated
hCG, free b-subunit, a mixture of these antigens in 40 indi-
vidual early pregnancy urines and 80 individual early preg-
Results: Using a mixture of hCG, hyperglycosylated hCG
and free b-subunit typical for early pregnancy, the sensitivity
of the First Response manual and digital tests was 5.5 mIU/
mL, while the sensitivities of the EPT and ClearBlue brand
manual and digital tests was 22 mIU/mL. On further evalu-
ation, the First Response manual and digital tests both detect-
ed 97% of 120 pregnancies on the day of missed menstrual
bleeding. The EPT manual and digital devices detected 54%
and 67% of pregnancies, respectively, and the ClearBlue
manual and digital devices detected 64% and 54% of preg-
Conclusions: First Response manual and digital claim
)99% detection on the day of missed menses. The results
here suggest similar sensitivity for these two tests. The EPT
and ClearBlue manual and digital test make similar )99%
claims, the data presented here disputes their elevated claim.
The first home pregnancy test was EPT (1). Since then,
devices have undergone many changes, including the adap-
tion of an immunometric assay format (2). Currently, manual
*Corresponding author: Laurence A. Cole, Department of
Obstetrics and Gynecology, USA hCG Reference Service,
MSC10-5580, University of New Mexico, Albuquerque,
NM 87131, USA
E-mail: email@example.com, firstname.lastname@example.org
Received October 28, 2010; accepted March 13, 2011
tests are interpreted as a faint test line present on a device
showing pregnancy. Digital devices, in contrast, display
‘‘yes’’ or ‘‘no’’ or ‘‘pregnant’’ or ‘‘not pregnant’’ on an
This article examines the advantages and disadvantage of
different home pregnancy tests available in the USA and
Western World today, and their utility in detecting pregnancy.
This article compares digital and manually read home preg-
nancy tests. It also examines the claim that devices can detect
pregnancies 4 days prior to missed menstrual bleeding. This
article focuses on the manual and digital devices First
Response, EPT and ClearBlue Easy, the principal devices
used today (3). An extensive study is described describing
the sensitivity of devices for detection of hCG and specificity
for detecting human chorionic gonadotropin (hCG), hyper-
glycosylated hCG and the free b-subunit. The abilities of
over-the-counter devices to detect pregnancy in 120 urines
in the days leading up to and following the time of missed
menstrual bleeding are carefully assessed.
Materials and methods
Collection of urine by the USA hCG Reference Service was con-
ducted according to a protocol approved by the Human Research
Review Committee at the University of New Mexico (Protocol 04-
132). All results from this study were accumulated and analyzed in
an Microsoft Excel 2007 spreadsheet (Microsoft, Richmond, WA,
The Siemens Immulite assay has been shown to equally detect hCG,
hyperglycosylated hCG, hCG free b-subunit, and nicked hCG (3,
4), and to function equally well in analyzing serum and urine sam-
ples (5, 6). From multiple studies performed using this test cali-
brated against WHO 4th IS, 1 ng/mL of this standard has always
read as 11 mIU/mL, 2 ng/mL as 22 mIU/mL, 5 ng/mL as 55 mIU/
mL, and 10 ng/mL as 110 mIU/mL. Similarly, using this automated
assay, 1 ng/mL of our hyperglycosylated hCG standard C5 has
always read as 11 mIU/mL, 2 ng/mL as 22 mIU/mL, 5 ng/mL as
55 mIU/mL, and 10 ng/mL as 110 mIU/mL. As such, we consider
1 ng/mL of hCG or hyperglycosylated hCG to be the equivalent of
11 mIU/mL of hCG (3–6). Similarly, hCG b-subunit standard
(WHO 1st RR), 1 ng/mL has always yielded 18 mIU/mL in the
Siemens Immulite test, and 2 ng/mL as 36 mIU/mL, 5 ng/mL
as 90 mIU/mL, and 10 ng/mL as 180 mIU/mL. Thus, we consider
1 ng/mL of hCG b-subunit to be the equivalent of 18 mIU/mL. On
a molar basis, considering the molecular weights of b-subunit and
hCG, the b-subunit value should be 36,700%22,200 or 1.65=
greater than the hCG value, 1.65=11s18. This shows that these
conversion factors, 11= and 18= are molar equivalents (5, 6).
Cole: Home pregnancy tests
Article in press - uncorrected proof
Innovation Ltd. However, Inverness Medical Innovations
Ltd. calibrates their home pregnancy test based on the LH
peak plus 17 days, or 4 days longer than that shown by
scientific investigation. This may explain the lack of sensi-
tivity, shown here, of their tests to detect pregnancy on the
actual day of a missed menstrual period, LH peak plus
Overall our conclusion is that early pregnancy over-the-
counter pregnancy test methods need to detect the three
important early pregnancy ingredients, hCG, hyperglycosy-
lated hCG and free b-subunit equally. A test specifically
designed for detecting early pregnancy, making claims of
detection 4 days prior to the day of a missed menstrual peri-
od, must also be highly sensitive for detecting hCG-related
molecules. While these criteria are seemingly met by First
Response manual and digital, they are clearly not met by
EPT and ClearBlue devices based on the 120 pregnancies
examined here. EPT and ClearBlue make the claims, such
as ‘‘more than 99% accurate,’’ ‘‘no other brand is more
accurate’’ and ‘‘used 4 days before the expected period’’
seemingly with FDA approval. However, these claims are
not supported by our study of 120 pregnant women.
Care is needed in purchasing over-the-counter pregnancy
tests. Claims made by ClearBlue and EPT easy, such as
)99% accuracy on the day of a missed menstrual period,
and by ClearBlue for use 4 days prior to missing menses are,
based on Study 5 and 6, without foundation. The claims
made by First Response devices for detection of all preg-
nancies on the day of missing menstrual bleeding, while
slightly off, may however, be considered valid. This study is
the largest and most comprehensive study of over-the-count-
er tests ever published, examining urine spiked with hCG,
hyperglycosylated hCG, free b-subunit, and a mixture of all
three, and 120 individual urines from pregnant females.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that
there are no conflicts of interest regarding the publication of this
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
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