Category Archives: hCG


Biodegradable Pregnancy Tests? What’s the big deal?

Recently, there was a buzz in the pregnancy testing world because a company called Lia Diagnostics received pre-market approval from the FDA for the first biodegradable pregnancy test that can be flushed down the toilet. When I excitedly emailed my co-blogger David about this, he said “Is that something that is really important to women?” This is a good question. Today I’d like to discuss why I think this type of product is important and take a look at the 510(K) premarket notification which is publicly available.

First, why is a flushable home pregnancy test important? One of the things that initially made home pregnancy devices attractive when they were first marketed back in the 1970’s is privacy.  They can be used in your own home. No need to go to a doctor or health center to find out if you are pregnant. You are the first to know in the privacy of your own home. However for some women, achieving privacy, even where they live, is difficult. Being able to flush the device down the toilet allows women to truly achieve privacy. No one will know the results or that the testing was even done.

The other reason that a flushable pregnancy device is important is environmental. Pregnancy devices are made from plastic and end up in land-fills. This is a huge burden on our environment and can no longer be ignored in the US or in developing countries, where these devices are also used. Imagine the environmental impact this device could have if it set a trend for other home pregnancy devices and other biomedical products to become biodegradable.  I feel that for this reason alone, this is a major milestone.

One thing that was not talked about in the press (and I could not find on the Lia website) is whether the packaging is also biodegradable & flushable. This will be key to achieve true privacy & environmental friendliness. In my laboratory, we do studies on pregnancy devices. Here I have included some photos of the trash we generated from just one study. As you can see, a great deal of that trash is packing material. This needs to be flushable and biodegradable too in order to achieve the company's goals of privacy & environmental friendliness.

Packaging trash

Six devices
Six devices

Trash generated from one of our home pregnancy device studies (property of Ann M. Gronowski)

Next, let’s take a look at the 510(K) pre-market notification for the Lia Pregnancy test. Lia compared their device to the OSOM hCG urine test. Our lab has studied the OSOM device in the past. In the summary document they show that the device can detect 100% of samples with an hCG concentration of 22 IU/L and 50% of samples at 14 IU/L. This is similar to other over-the counter devices on the market. Using 153 urine samples, the Lia device showed 100% concordance with the OSOM device. The device showed no cross reactivity with LH up to 500 IU/L and FSH & TSH up to 1000 IU/L. They evaluated the hook effect (something that can cause a false-negative result) up to 500 IU/mL (500,000 IU/L) which is good. They also checked for a hook due to hCG β-core fragment and showed no effect up to 500,000 pmol/L, which is a concentration at which we have previously demonstrated the OSOM device to give false negative results.

The Lia pregnancy test is scheduled to be available for purchase in mid-2018. Based on the data submitted to the FDA it sounds very promising. I hope that this novel product will induce other medical device companies take note and start to manufacture more biodegradable products.

How Early Can Pregnancy Be Detected?

Calendar_2“How early can pregnancy be detected?” is a question we are asked all the time. The short answer is, “It depends.” Let’s answer this question one step at a time.

First, the most common way to detect early pregnancy is by measuring the hormone human chorionic gonadotropin (hCG). If an egg is fertilized, the developing embryo will attach to the lining of the uterus around 6-12 days after ovulation. This is called implantation.  The hormone hCG is produced by trophoblastic cells (the outer layer of the embryo) after implantation. It takes several days for hCG to be detectable in blood or urine. hCG production increases very rapidly with serum concentrations doubling every 1-1.5 days in the first 8-10 weeks of pregnancy. So, detecting pregnancy first depends on how quickly implantation occurs.

Second, it depends on the sample in which hCG is measured; blood or urine. Urine concentrations of hCG are almost always lower than serum concentrations. In addition, urine concentrations of hCG can be affected by fluid intake. If large amounts of fluids are ingested (think Big Gulp)  then urine concentrations will be more dilute. This is why first morning urine samples are often recommended because this urine is usually the most concentrated of the day since people don’t tend to drink anything during the sleeping hours. The amount of water in blood is more regulated that that of urine and generally does not change, even after ingesting large amounts of liquid. Therefore, use of a blood sample will generally detect pregnancy earlier than use of urine. 

Third, it depends on the method used to detect hCG; qualitative or quantitative. Qualitative devices are those that can be purchased over-the-counter to detect hCG in urine. They are also used in hospitals and doctor offices. These devices generally have cutoffs for positivity that vary from about 20-50 IU/L. The cutoff varies widely by brand. Interestingly, we have shown that the devices used at home are often more sensitive than the devices used in the hospital!!  We have previously blogged about this topic. Quantitative hCG assays are performed using blood samples in laboratories and are much more analytically sensitive than qualitative assays. Most quantitative hCG assays can detect hCG at concentrations of 2 IU/L and some can go as low as 0.1 IU/L. Therefore, quantitative assays will be able to detect pregnancy earlier than qualitative assays.

Fourth, when the clinical sensitivity of an hCG test for diagnosing pregnancy is determined, it is usually determined as a function of the number of days relative to the expected day of the menstrual period (EMP). How early an hCG test can detect pregnancy depends on how the EMP is estimated. Most women estimate EMP by counting 28 days from the first day of the last menstrual period (LMP). This 28-day cycle includes the approximate 14 days between first day of menses and ovulation (called the follicular phase) and the approximate 14 days between ovulation and the day before the next menstrual period (called the luteal phase). However, the length of menstrual periods varies between women. Studies have shown that most of the variation occurs in the follicular phase.Therefore, the most accurate way to estimate the EMP is by measuring 14 days from ovulation as estimated by detecting a dramatic rise in the concentration of luteinizing hormone (LH), commonly referred to as the LH surge. Using 14 days from the LH surge can detect 100% of pregnancies by the EMP, as opposed to using 28 days from LMP which did not detect 100% of pregnancies until 7 days after EMP.  By measuring serum hCG, 100% of pregnancies can be detected by EMP and nearly all pregnancies can be  detected by 3 days before EMP. 

In summary, how early pregnancy can be detected depends on many factors. In some cases pregnancy can be detected more than 3 days before EMP. Virtually all pregnancies should be detected by one week after EMP.

Personalized medicine during pregnancy

Pregnancy dnaPersonalized medicine can be defined as customized disease prevention therapies and drug treatment protocols based on knowledge of an individual’s unique genetic makeup, metabolic profile and clinical presentation. So far, personalized medicine has focused on the prevention and treatment of conditions affecting adults such as cancer and cardiovascular disease.  However pregnancy is a unique situation where the unique characteristics of two individuals are being assessed: mother and infant. Remarkably few studies have addressed the therapeutic implications of recent advances in genetic technologies for the fetus. Focus has been more on prenatal diagnosis than on fetal treatment. As molecular technologies advance and costs decrease, targeted genetic testing and even whole genome sequencing of the fetus are likely to become more available. This brings with it a number of ethical issues especially as it relates to testing of the infant. For instance, there are questions of informed consent, confidentiality of results, the clinical significance of genetic polymorphisms and decisions to terminate pregnancy on the basis of these test results.

Nonetheless, there have been some interesting advances in personalized medicine, for both mother and fetus, during pregnancy. This is the focus of an upcoming symposium at the AACC meeting to be held tomorrow, July 29th, at 10:30 am in Atlanta, Georgia.  

Predicting Response to Drugs:  Sixty-four percent of women in the US are prescribed more than one drug during pregnancy (excluding vitamins). A better understanding of how drugs are metabolized during pregnancy and how they affect the fetus is clearly needed. Cytochrome P450 is the predominant class of oxidative enzymes that catalyze many types of drugs. Interestingly, the expression of a number of P450 genes is altered during pregnancy. Most notably, CYP1A2 has been shown to be decreased by 65% by the 3rd trimester. In the past several years, several studies have examined the ability to predict a woman’s response to drugs used during pregnancy, like tocolytics and anti-emetics, based on their genotype. A study by Haas, et. al. demonstrated that CYP3A5 high-expressing women had lower circulating concentrations of Nifedipine, a common tocolytic. A study by Lehmann, et. al. demonstrated that a genotype for serotonin receptor subunits 5-HT3A and 5-HT3B may play a role in hyperemesis severity and response to anti-emetics. This type of genotyping is not yet ready for prime time, but it holds promise for better utilization of medications during pregnancy.

Assessing the Fetus: We have blogged previously about cell free fetal DNA (cffDNA) in maternal blood and its utility in predicting fetal trisomy. cffDNA can also be used to assess fetal Rhesus D (RhD) status. This method can be used to determine the fetal RhD genotype when the mother has clinically significant alloantibody to the D antigen AND the father is heterozygous for RhD or is not available for testing. Testing such as this is useful because instead of treating all RhD-negative women with RhD immunoglobulin, treatment can be targeted to mothers that carry RhD-positive fetuses. This type of approach can conserve supplies of therapeutic anti-D, prevent unnecessary administration of a human-derived blood product to a vulnerable patient group, and avoid subjecting RhD-positive infants to intensive antenatal monitoring to predict and treat fetal anemia. Interestingly, despite the fact that the American College of Obstetricians and Gynecologists support the use of cffDNA for RhD assessment, it is not a widely used clinical tool in the United States.

Predicting Viability: Not all personalized medicine is genetic. Personalized medicine can also be used to guide treatments. With this in mind, there are several publications that suggest novel uses for hCG testing. The first takes advantage of “semi-quantitative” urine hCG devices. These devices are similar to home pregnancy devices, but they essentially contain multiple detection strips with different cutoffs that can give the reader a rough estimate of the urine hCG concentration (>25, >100, >500, >2000 or >10,000). Several studies have examined the use of these devices in a home setting following medical abortion as a replacement for clinic follow-up. If the woman is able to demonstrate decreasing hCG concentrations at home, she can avoid a return visit to the clinic. This can reduce the burden on the healthcare setting, but it could also help women for whom getting to a clinic is difficult because of work or family commitments or who live in a remote geography. Both studies demonstrate that use of semi-quantitative hCG devices in this setting had 100% sensitivity to detect unsuccessful abortions. The second interesting use for hCG measurement is in the prediction of fetal viability. Several studies have suggested that urine and serum concentrations of hyperglycosylated hCG (hCG-H) are low in women with pregnancy failure. These studies suggest that measurements of serum or urine hCG-H to detect failed pregnancy is 60-70% sensitive and 97-100% specific (links here and here). These studies are small and there is not currently a readily accessible assay for hCG-H, but it is intriguing to think about the possibility of a test that could distinguish viable from non-viable pregnancies especially in an emergency setting when physicians are making treatment decisions and have to take into account potential risks to the fetus.

Finally, an hCG blood test that can be performed at the point-of-care

Testing urine samples for the presence or absence of hCG is commonly performed in hospitals and clinics for the rapid assessment of a woman's pregnancy status. This topic has been discussed several times in this blog (see here and here).

Urine hCG tests are hugely popular because they can be performed near the patient and they are granted waived status by the Clinical Laboratory Improvement Amendments.

However, urine is not a suitable sample type for pregnancy assessment for many reasons, such as:

  • Urine hCG tests are prone to false-negative results.
  • hCG becomes detectable in the urine after it appears in the blood, so urine tests are not as sensitive as blood hCG tests.
  • Urine tests provide a positive/negative results whereas blood tests provide a quantitative concentration.

Because of these limitations, in particular the risk of false negative results, I've often said that urine hCG testing is inappropriate in healthcare delivery settings. Blood tests for hCG are much more reliable but they take longer to produce results because of the time required for sample transport and processing by a centralized laboratory.

Finger StickAt long last, a rapid, quantitative blood test for hCG is finally available in the US from Abbott Point of Care, Inc. on their i-STAT instrument. Naturally, people will want to know how the test performs and we recently published a paper on the analytical performance of the test.

We evaluated the test using whole blood and plasma (the sample types that were cleared for use) as well as serum. Overall, the test works quite well in all sample types and is suitable for use in healthcare settings. It provides the reliability of laboratory blood-based hCG testing but with the convenience of point-of-care testing.

There are two important limitations to note:

  1. The analytical measuring range of the i-STAT hCG test is limited to 5-2,000 IU/L. While this is similar to the measuring ranges of many laboratory hCG tests, the instruments used in labs can automatically dilute and re-test samples that have a high hCG concentration, something that the i-STAT is unable to do. When tested with the i-STAT, a sample with an hCG concentration greater than 2,000 IU/L will be reported as such. While this type of result indicates that hCG is present in the blood, not having an absolute concentration will be insufficiently informative in some clinical situations.
  2. The test is susceptible to the high-dose hook effect at an hCG concentration somewhere between 400,000 and 600,000 IU/L. This means that when a sample with an extremely high hCG concentration is tested, the result can be falsely decreased. However, even though the result is falsely decreased, it is still very likely to be interpreted as "positive" and the risk of a false-negative result is extremely remote.

This type of test is long overdue in the US. The use of urine hCG testing to determine a woman's pregnancy status is fraught with difficulties and is known to cause harm to patients. Despite their problems, urine hCG testing won't be going away any time soon but the availability of a test that performs hCG blood tests close to the patient is a step in the right direction.

False negative pregnancy tests: the story continues

This post was written by Robert D. Nerenz, PhD, an assistant professor at the University of Kentucky, in Lexington.

Neg pregnancy testIn previous posts, we have discussed false negative pregnancy test results caused by hCG beta core fragment (hCGβcf), the predominant form of hCG found in urine after six weeks of pregnancy. False negative pregnancy tests can result in undesirable outcomes (including loss of pregnancy) if inappropriate treatment is given. In a recent study evaluating the performance of devices used in a hospital setting, 9 of 11 devices were found to be susceptible to false negative results when used to test urine solutions containing hCGβcf concentrations observed in normal pregnancy.

After our study was published, we were frequently asked whether these devices actually performed poorly in clinical practice or if the results we observed only occurred in a controlled laboratory environment. To address this question, we searched the database of medical device malfunctions reported to the FDA (Manufacturer and User Facility Device Experience, or MAUDE) to find reports of false negative pregnancy test results in a clinical setting. Using the search term “MAUDE pregnancy false negative” we found 707 reports between 2000 and 2014 that described false negative urine hCG results in women shown to be pregnant at the time of testing. 91 different POC hCG devices were described from 14 manufacturers, including 10 of the 11 devices evaluated in our initial screening study.

Based on the description in the MAUDE report, we subdivided the false negatives by potential cause. In 433 reports the cause of the false negative result was unknown.  132 were likely because the hCG concentration was so low that it was below the limit of detection for the test device. Of these 132, nine were associated with adverse events. We also found 142 reports that were likely due to hCGbcf hook effect and ten (or 7%) of those were associated with adverse events, including delayed prenatal care, delayed treatment of ectopic pregnancy, performance of inappropriate imaging studies and even surgery leading to loss of pregnancy. In addition to the reports documented on the FDA website, it is virtually certain that many more false negative results have occurred and have gone unreported to the FDA.

The fact that false negative pregnancy test results occur relatively frequently in clinical practice was an important finding because it highlighted the limitations of currently available devices and emphasized that this problem is not limited to one or two devices. Rather, the fact that the vast majority of pregnancy test devices performed poorly in our study and were reported to generate false negative results in clinical practice indicates that this is a much larger problem.

To decrease the occurrence of false negative pregnancy test results, contributions from multiple different groups will be required. First, the FDA should insist that device manufacturers market devices that generate positive results in all pregnant women, including those with high urine concentrations of hCGβcf. Second, clinicians at large hospitals should request that pregnancy testing be performed on serum using a quantitative assay, especially in patients with abdominal pain, vaginal bleeding or other symptoms that strongly suggest the patient might be pregnant. Quantitative serum assays can generate results in less than an hour, can detect lower concentrations of hCG than point-of-care test cartridges and are not affected by hCGβcf because hCGβcf is not present in serum. Lastly, laboratorians should work to decrease the time required to generate test results in order to make quantitative testing more appealing to clinicians. At institutions where urine point-of-care testing must be performed, laboratorians should evaluate all available options and select the device that provides an optimal combination of sensitivity and lack of susceptibility to interference caused by elevated concentrations of hCGβcf.

Unfortunately, currently available pregnancy test devices present a risk to patients. It is our hope that a coordinated effort from the FDA, manufacturers, clinicians and laboratorians will eliminate that risk.

Improved Qualitative Pregnancy Devices

In the past, we have blogged about false negative urine qualitative hCG tests in both point-of-care (POC) hospital devices and over-the-counter (OTC) devices due to the presence of high concentrations of hCGbcf. We feel this represents a real problem for patients and clinicians trying to diagnose pregnancy and could results in harm to mother and/or fetus.

It is our understanding that the FDA is requiring device manufacturers to address this problem in any new devices going through the FDA approval process. However, it is up to manufacturers if they want to voluntarily change their existing devices. Hence we have urged manufacturers to modify their devices to eliminate false negatives due to hCGbcf.

Recently, we were made aware of two manufacturers that had apparently modified their qualitative pregnancy devices: The Cen-Med Elite Plus One-Step Pregnancy Test (a hospital POC device) and the First Response Early Result OTC device (an over-the-counter device). In order to evaluate these modifications we compared the old and new devices using the screening test we have developed previously.   Our results demonstrated that indeed, the new version of each device perform better than the previous version.  Both original devices demonstrated significantly diminished signal when 500 pmol/L hCG was tested in the presence of 500,000 pmol/L hCGbcf. However the modified devices gave faint or clear positive signals in the presence of the same hCG concentrations (see figure). Figure for Blog
It is clear that improvement of qualitative urine hCG devices is possible and we encourage all manufacturers to design devices that are not inhibited by hCGbcf. 

The hCG discriminatory zone in ectopic pregnancy: does assay harmonization matter?

Ectopic_Pregnancy_DiagramEctopic pregnancy is a potentially life threatening complication of pregnancy. It occurs when the embryo implants outside the uterine cavity, most commonly in the fallopian tube. Common symptoms include nausea, abdominal pain, and slight vaginal bleeding. Approximately 2% of all pregnancies are ectopic pregnancies and they require emergency treatment to either prevent rupture of the fallopian tube or treat a woman with a ruptured ectopic pregnancy.

Diagnosis of an ectopic pregnancy requires the exclusion of a normal, intrauterine pregnancy. This is often facilitated by the use of transvaginal ultrasound (TVUS) to visualize the location of the yolk sac or embryo, which should be able to be seen by the end of the 6th week of gestation. However, such precise dating is often not available for patients that seek medical attention with symptoms of ectopic pregnancy and so hCG testing is often used as a surrogate marker for gestational age. The serum hCG result is interpreted against the “hCG discriminatory zone.” This is the hCG concentration that, once exceeded, means that the embyro should be large enough for TVUS to always detect it. However, it is inappropriate to diagnose a patient with an ectopic pregnancy even if no embryo is observed in the uterus when the hCG concentration has exceeded the discriminatory zone. 

The hCG discriminatory zone is commonly described as an hCG concentration between 1,500 and either 2,000, 2,500 or 3,000 IU/L. Guidelines from the American College of Obstetricians and Gynecologists define it as 1,500 to 2,000 IU/L.

The management of patients with a suspected ectopic pregnancy would be easier if hCG assays were harmonized, meaning that, regardless of the assay used to measure the hCG concentration, the results would be equivalent. In other words, it would be ideal if a sample tested for hCG on one manufacturer’s test platform was equivalent to the result obtained from another manufacturer’s test platform. Unfortunately, hCG assays are not harmonized, yet many clinicians are unaware of this limitation.

Along with colleagues, I recently published the results of a study that evaluted if the lack of hCG test harmonization would affect the interpretation of an hCG result with regards to the hCG discriminatory zone. The findings confirmed that there was, indeed, a lack of harmonization between 7 commonly used hCG assays. However, when we calculated what the expected hCG discriminatory zone should be for the different assays, all of them, with one exception, would have been within 9% of the frequently cited hCG discriminatory zone cutoffs of 1,500 to 3,500 IU/L. That amount of variation is very reasonable and is not cause for alarm. The single exception was an hCG assay for which a discriminatory zone of 2,000 to 4,900 IU/L would be estimated to be equivalent. We concluded that, despite significant differences in hCG concentrations across different hCG tests, an hCG result within a discriminatory zone of 1,500–3,500 IU/L could be used without regard to a specific assay for all but one commonly used hCG test.

Watch a short video of me explaining this study!

Examination of eleven hospital hCG devices for false negative results

Beckman Icon 20In previous blog posts we have discussed false negative urine hCG tests due to high concentrations of hCG beta core fragment (hCGβcf), the predominant form of hCG found in urine after six weeks of pregnancy. High concentrations of hCGβcf saturate either one or both of the antibodies used in the test. This hCG variant effect prevents the development of a positive signal and generates a negative result despite the presence of intact hCG in the urine sample being tested.

The original studies were performed by adding increasing concentrations of purified hCGβcf to a urine sample obtained from a pregnant woman. The problem with this approach is that the relative abundance of hCG, hCGβcf and other hCG variants in the urine that may affect device performance vary between women. A standardized method, using defined concentrations of hCG, is needed to evaluate the performance of currently available devices.

In a recent publication, we describe a screening method that can be easily used to examine the effect of hCGβcf and have used this method to test eleven POC hospital urine hCG devices.

First, a wide range of purified hCG and hCGβcf concentrations were combined to prepare 2 solutions:

  • Solution A: 500 pmol/L (171 IU/L) intact hCG with 0 pmol/L hCGβcf and
  • Solution B: 500 pmol/L intact hCG with 500,000 pmol/L hCGβcf

These solutions were tested on two hCG devices, the results of which helped to define a screening method:  

Each device is tested with the two solutions and the intensity of the test bands are compared. If Solution B shows a lighter test band than solution A, then the device is susceptible to false negatives with hCGβcf.

Using these two solutions we compared the performance of 11 hospital urine hCG devices

  • SP hCG Combo Rapid Test, Cardinal Health
  • OSOM hCG Combo Test, Genzyme Diagnostics
  • hCG Combo, Alere
  • ICON 20 hCG, Beckman Coulter
  • ICON 25 hCG, Beckman Coulter
  • Elite Plus hCG, Cen-Med
  • Clinitest hCG Pregnancy Test, Siemens
  • hCG Urine Test, McKesson
  • QuickVue+ One-Step hCG Combo Test, Quidel Corporation
  • QuPID One-Step Pregnancy Test, Stanbio Laboratory
  • Sure-Vue Serum/Urine hCG-Stat, Fisher HealthCare

Interestingly, we found that only 2 devices were acceptable (i.e. not affected by the hCG variant effect). These were the Beckman Icon 20 (shown above) and the Alere hCG Combo devices. By contrast, the Genzyme OSOM and Cen-Med Elite Plus hCG devices were the most susceptible to false negative results due to hCGβcf (OSOM shown below). The remaining seven were moderately affected.


The paper also demonstrated that devices that gave the strongest signal with hCGβcf alone were those that were least likely to show a false negative effect.

The screening method can be used by device users and manufacturers to evaluate hCG devices for inhibition by hCGβcf. We hope that the results of this study will help healthcare providers make informed decisions about which hCG devices to select, especially in medical centers that are unable to perform rapid, quantitative measurements of hCG in serum.

However, while the availability of hCG test devices that are not affected by hCGβcf is certainly reassuring, quantitative serum measurement of hCG should still be the test of choice when available.

The history of pregnancy tests

HCG croppedIf you are interested in hCG, like we are, you might be interested in a recent paper, in Clinical Chemistry, by Dr. Glenn Braunstein entitled "The long gestation of the modern home pregnancy test."

Dr. Braunstein is one of the researchers that helped develop the first radioimmunoassay specific for hCG in the 1970's and is a leader in the field of hCG.

In his paper, Dr. Braunstein reflects on the history of urine pregnancy tests.  He explains that there is actually a description of a pregnancy test in ancient Egyptian papyrus writings. In that test, women urinate on wheat and barley seeds. If neither grows the woman is not pregnant. If the barley grows it will be a male and if the wheat grows it will be a female!

The first bioassay was described in 1927 by the German scientists Ascheim and Zondek who demonstrated ovarian stimulation in mice when they were injected with the urine from pregnant women. After that, there were many bioassays developed to detect pregnancy. Apparently these had analytical sensitivities of between 100-18,000 IU/L and they took 2-9 days to get a result!

The first radioimmunoassay for hCG & LH (leuteinizing hormone) was described in 1966 by Midgley.  Its analytical sensitivity was very high by today’s standards (175 IU/L) but, of course, it recognized both hCG and LH and it took 3 days to perform. The similarity between hCG and LH was a real problem. It was not until Dr. Braunstein, together with Dr. Judith Vaitukaitis, developed new antibodies that were specific to the hCG beta subunit that an hCG-specific assay was developed. With this assay, they were able to detect pregnancy as early as 7.5 days after fertilization and they were able to develop reference intervals for serum during pregnancy.

The first home pregnancy test marketed in the U.S. was the e.p.t.® ("Early pregnancy test") in 1977. It was described as a "private little revolution" because it allowed women to determine if they were pregnant in the privacy of their own home with no one else knowing. Today, pregnancy tests account for $228 million dollars in annual sales and take up considerable shelf space at retail stores with different brands and styles (see photo).  

For further reading, another great reference for the history of the pregnancy test was created by the NIH library and can be found here.

A rapid pregnancy test without using urine? Not so fast.

The rapid assessment of pregnancy status is important in urgent health care settings. Determining if a Tube of blood woman is pregnant or not is necessary to:

  • Determine if symptoms such as abdominal pain, vaginal bleeding, and/or vomiting are due to pregnancy;
  • Prevent fetal exposure to sources of radiation (x-ray, CT, scan, etc);
  • Prevent the administration of teratogenic medication.

In many health care setting, qualitative urine hCG testing is often used to quickly determine a woman's pregnancy status. Several posts on this blog have discussed the limitations of this type of testing (see here and here for some background). We have often advocated for the use of quantitative serum hCG testing over qualitative urine testing for this purpose but there are some logistical challenges with quantitative serum testing:

  • The use of a blood sample requires its collection and transport to a central laboratory.
  • Once received in the lab, a blood sample has to be centrifuged to separate the serum (the liquid part of the blood that is actually tested) from the blood cells.
  • Both of the above steps increase the amount of time needed to perform the test and report the result to the physician.

Although many qualitative hCG tests used in health care settings can be used with either urine or serum, qualitative serum testing is impossible to perform at the point-of-care. This is because obtaining serum requires centrifugation of the whole blood and centrifugation can't practically be done outside of a laboratory.

Recognizing that hCG tests performed on blood samples are generally better than thosed performed on urine, physicians are sometimes tempted to use whole blood (instead of serum) as the sample type for qualitative hCG testing at the point-of-care. An example of this type of use is described here.

That report describes the use of whole blood instead of urine or serum for the qualitative detection of hCG in a patient with a ruptured ectopic pregnancy. This was what I call a VBI: a Very Bad Idea. It is so wrong that two colleagues and I wrote to the journal that published the report to let them know it was a VBI.  Basically, we pointed out that:

  • Using whole blood instead of serum or urine was a modification of the intended use of an FDA-approved test and as such was against the law without appropriate validation experiments.
  • The peer-reviewers and journal editors failed to recognize that their report was in conflict with federal and state regulations and the report's publication essentially recommends the promotion of an unauthorized practice with serious patient safety risks.
  • Involving laboratory professionals to help identify solutions for clinical dilemmas involving laboratory tests is always a smart idea.

In response to our criticism, the authors replied with this:

"Physicians' judgment is relied upon to determine when benefit to the patient outweighs the risk of inaccuracy of unapproved use."

In other words they essentially said "we can do anything we want, regardless of regulations, when we act according to our best judgement."

How convenient. How utterly ignorant. How potentially dangerous.

Sadly, this type of mis-information is widespread. A website called "Emergency Physicians Monthly: The Indpendent Voice for Emergency Physicians" featured an article titled "Stat Pregnancy Test…Without Urine?" in September 2013. This article encourages the use of using whole blood for qualitative hCG testing and even provides a "Quick Trick" section on how to perform the test. This is grossly negligent on their part. I note that under the "Tips" section the author writes:

"Be sure to wait at least 5 minutes when using whole blood in the kit. It sometimes takes a while." (emphasis is mine)

Hmmmm, might someone want to define what "a while" is?

I think my opinion on this matter is evident. If reliable results are to be obtained and utilized for patient care decisions, clinical laboratory tests must be performed using validated methods (including the type of sample tested). To deviate from established protocols without guidance from laboratory professionals is a VBI.