Category Archives: hCG

hCG

Pregnancy testing in the Emergency Department: a physician’s perspective


Today's post is by a guest author, Ian Schwartz, M.D. Dr. Schwartz is an assistant professor of emergency medicine at the Yale University School of Medicine and the former medical director of the adult emergency department at the Yale-New Haven Hospital in New Haven, CT. Here, he provides his perspective on determining a patient’s pregnancy status in an emergency setting and describes the possible consequences of erroneous hCG test results.

EmergencyThe practice of emergency medicine is a daily challenge for providers in the field. Patient histories are varied and nuanced and no two cases are ever the same.  In the hectic, chaotic and over-flowing hallways of the emergency department (ED), providers (not surprisingly) look to hang on to objective evidence in order to come up with diagnoses and treatment plans.

Experienced providers realize, of course, that a diagnosis is usually a best guess. For the majority of patients, emergency room doctors are simply synthesizing a few facts and ideas into a coherent explanation for the symptoms that brought the patient to the ED.

The challenge is that even those elements that we call facts are, themselves, nuanced. Every ED doctor has had the experience of staring at a chest x-ray and debating whether the patient had pneumonia or some fluid in their lungs. X-ray interpretation is literally dealing in shades of grey.

As opposed to evaluating X-rays, laboratory test results would appear to be much more objective. The lab provides a discrete test result along with a reference interval for defining what is considered to be “normal.” For most health care providers the validity and accuracy of most test results go unquestioned. Yes, that patient absolutely has elevated calcium. Yes, this patient is anemic. Decisions for further testing, treatment and disposition are often made based solely on these test results.

Emergency providers (and others who practice evidence-based medicine), think in terms of odds and probability. That is, they think about the likelihood of a disease. Some examples: the likelihood of a blood clot in the lungs given a patient’s risk factors or the 30-day likelihood of a heart attack if a patient with chest pain is sent home. Each ED doc has his or her own acceptable “miss rate” for a given condition.

However, when it comes to pregnancy testing that sort of calculation and prediction simply doesn’t enter the mind of most ED providers. The pregnancy test is often considered to be the one single binary (yes/no) test that they can actually rely on.

Most emergency departments perform qualitative hCG tests using a urine sample to determine a woman’s pregnancy status. The tests are similar to those that can be purchased over-the-counter and performed at home. The person performing the test will be handed the urine sample, perform the test, and (hopefully) chart that result into the medical record and (hopefully) alert a nurse or other care provider of the result.

A provider sees this result and takes the appropriate action. There is usually no second thought about the quality of the test result. If it’s negative then the patient with abdominal pain is not pregnant and the physician can get the CT scan of the abdomen instead of the ultrasound. A negative result is also a license to order antibiotics, pain medications, and other drugs without concern for possible fetal harm. The urine hCG test is the standard way we define pregnancy in the emergency department and it gives the green (or red) light to treat the patient as not pregnant (or pregnant).

There is a problem with this type of reliance: the urine hCG test, itself, is simply not good enough to tell us whether or not a patient is pregnant.

Here are a few facts that most ED providers are unlikely to know about hCG testing:

  1. hCG appears in blood before urine, sometimes up to 5 days earlier.
  2. The claimed analytical sensitivity of most qualitative urine hCG tests is 25 IU/L whereas the quantitative blood assays are sensitive to 1-2 IU/L (commonly pregnancy is defined by greater than 5 IU/L).
  3. Even though common qualitative urine tests claim 99+% accuracy in determining pregnancy status, a recent study suggests that they are actually only 99% sensitive at an hCG concentration of 150-225 IU/L.
  4. There is a potential window of 3 to 7 days during the first trimester of pregnancy where a quantitative blood test will detect hCG while the qualitative urine test might not.
  5. Ectopic pregnancies can occur at hCG concentrations below what is detectable by current qualitative methods.
  6. In one study of over 11,700 urine samples, 69 (0.5%) of ED hCG test results were erroneous due to documentation errors, inherent deficiencies in qualitative tests or because the hCG concentration was below the level of detection.

So what are some real-world consequences of not using the most accurate hCG test at our disposal? If we believe a patient with abdominal pain is not pregnant (when in fact they are) we order CT scans of the abdomen looking for appendicitis or other abdominal diseases. That CT scan just delivered 10 mSv of radiation to the mother and fetus and doubled the risk of the fetus developing a childhood cancer (1 in 1,000). Or we just ordered Motrin, a medication known to cause neural tube defects and a variety of heart defects. And we have just increased the risk of miscarriage two and a half fold.

In a later post, I will address the erroneous belief that qualitative urine hCG tests are quicker to result than quantitative blood tests. However regardless of speed, ED’s across the country are utilizing a test that does not deliver the accuracy that most providers believe they are getting. This is a fact that should be quite troubling to all of us considering the number of urine pregnancy tests that performed each day. How many erroneous results are we are unknowingly receiving and what is the potential harm that is being done to a fetus in its most fragile period of growth?

False Negative Pregnancy Tests Still a Real Problem in Home and Hospital Devices


Neg pregnancy testWe have blogged in the past about false negative pregnancy tests due to hCG beta core fragment (hCGbcf).   After about 5 weeks of pregnancy (i.e. 3 weeks after the expected period) concentrations of hCGbcf, in urine, are higher than all other forms of hCG. Our group has shown previously that the concentration of hCGbcf can saturate one of the antibodies used in the point-of-care hospital pregnancy kits. As a result, test shows a negative result. The variant hook effect can be confirmed if testing shows a positive result after diluting the sample. This phenomenon is referred to as the "variant hook effect" and was reported to the FDA in 2009.

Recently, our group took this observation one step further and examined over-the-counter home pregnancy devices to see if they were subject to the same problem.  We examined six over the counter devices and selected two that seemed to be most affected by the variant hook effect. We then compared those two devices to the hospital device that we had made our original observations in four years ago, and to a hospital device that we thought performs best when compared to various other hospital pregnancy devices. Not surprisingly, we found that the over-the-counter home pregnancy devices are also subject to the variant hook effect. However, what was a surprise was that the hospital pregnancy devices were more affected by hCG beta core fragment than the home pregnancy devices!  Furthermore, despite the fact that the variant hook effect was reported to the FDA in 2009, manufacturers have not changed their devices to avoid this problem. To hear more about this paper you can listen to a podcast describing the findings.

Our laboratory is currently working to better define how much hCGbcf is required to cause the variant hook effect. We hope that this will help manufacturers to produce devices that avoid false negative results. In the meantime, several things need to be done:

  1. Physicians, nurses, and other health care professionals need to be educated about this problem-especially in the hospital setting.
  2. The variant hook effect should be made clearly visible in pregnancy test package inserts and they need to state that when a false negative is suspected, a simple dilution can yield a positive result if the patient is truly pregnant. This is very important for centers that have no alternative way of testing for pregnancy.
  3. Finally, in my opinion, quantitative serum hCG testing should be the preferred pregnancy test in centers where it is available. Serum testing is not subject to the variant hook effect because hCGbcf is not present in serum. Furthermore, quantitative serum assays are much more sensitive than the qualitative assays.

Detecting hCG in urine: how low is low enough?


A recent post on this blog described the inability of qualitative point-of-care (POC) hCG tests to detect hCG when it was present in urine or serum at a concentration that should, according to the test manufacturer, always be detected. The inability of these devices to detect hCG is a serious concern.

A false-negative result from a home pregnancy test can be initially disappointing if a pregnancy is desired or a temporary relief if it is not. By contrast, a false-negative result in the health care setting can result in serious harm to the fetus if a patient who is assumed to not be preganant undergo interventions that are potentially harmul to the pregnancy.

A recent case report has been published that, like other reports, emphasizes the limitations of qualitative urine hCG testing. The case describes a young woman who required radioactive iodine therapy for Grave's disease. Importantly, this young woman was also recently pregnant. That fact would likely not have been discovered had the physician relied on a qualitative urine hCG test. Fortunately, the laboratory had performed a quantiative urine hCG test (note that quantitative hCG tests using urine may be performed by the lab but the results are reported as qualitative (e.g. yes or no) and not the actual hCG concentration) which was interpreted as "positive" because the measured hCG concentration was greater than the lab's cutoff of less than or equal to 5 IU/L (it was 12 IU/L). A serum hCG test performed the same day produced a result 15 IU/L (not pregnant=less than or equal to 5 IU/L). Two days later a repeat serum hCG test produced a result of 147 IU/L confirming that she was in the very early stages of pregnancy. 

As has been noted in this blog in the past (here and here), urine hCG testing is commonly performed in the health care setting because it is convenient. However, the problems with urine hCG tests are so numerous (see here and here) that urine hCG testing should not be relied upon to determine a patient's pregnancy status.

The authors of the case described above correctly point out that the detection thresholds of most qualitative urine hCG tests are stated to be 20–50 IU/L (recent evidence suggest these cutoffs are not always accurate). Further, they call for more sensitive qualitative urine hCG tests in order to decrease the number of false-negative hCG results in the health care setting and suggest that a detection threshold of 5 IU/L (which is the same threshold used for interpreting quantitative serum hCG tests) should be used. Interestingly, this conclusion is similar to the one my group suggested in regards to qualitative serum hCG testing.

I am in complete agreement that when it comes to the detection of early pregnancy, hCG tests that are capable of accurately detecting and/or measuring hCG are required. Currently, this means that serum hCG tests should be used exclusively, in the health care setting, for this purpose. To rely on less sensitive tests and less accurate urine hCG tests is a disservice to our patients.

Wanted! A sensitive qualitative hCG test.


Today’s post is by a guest author, Dina N. Greene, Ph.D. Dr. Greene is a Scientific Director at Northern California Kaiser Permanente Regional Laboratories in Berkeley, CA. She discovered that qualitative hCG tests may not be as analytically sensitive as we all have come to believe and she shares her observations here. A report of her work has been published in Clinica Chimica Acta.
Neg pregnancy test
The assessment of very early pregnancy (from conception until about two weeks following the
expected menses) is dependent on the detection of hCG in serum or urine. In health care settings a urine sample is often the specimen of choice because it is convenient and usually easy to obtain.

When urine samples are tested for hCG they are most frequently tested using qualitative (yes/no) point-of-care (POC) devices. This type of testing is attractive because it is performed close to the patient and the test results can be obtained within minutes. In general, when challenged with urine or serum containing hCG these devices work well. However, what was not known was how sensitive these devices are for detecting very early pregnancy. That is, could pregnancy be ruled out if a qualitative POC test was negative?

To answer that question we completed a study that took a systematic approach to this question by testing urine and serum specimens collected from patients that spanned a wide range of hCG concentrations with two commonly used POC devices.

While many concentrations of hCG were represented in these samples, we purposefully skewed the specimens so that a large percentage (~30%) had concentrations of hCG expected to be seen only in very early pregnancy. The results were surprising.

We found was that the devices did not always detect hCG at the lowest detectable concentration claimed by the manufacturer (20 IU/L for urine and 10 IU/L for serum). In fact, we had many false-negative results when the urine concentration of hCG was as high as 200 IU/L or the serum hCG concentration was as high as 50 IU/L. We further showed that the urine specimens were collected from patients that were at approximately 4 weeks’ of gestation which, if calculated from the day of the last menstrual period, is close to the day of expected menses.

Anecdotally, medical providers at some institutions have recognized this phenomenon. If a sexually active woman is unsure of her pregnancy status, and the POC urine hCG test result is negative, the provider may encourage the patient to return for retesting in a few days. Alternatively, if the patient’s pregnancy status must be known urgently, the provider may collect a blood sample for quantitative serum hCG testing performed in the laboratory to confirm the negative POC test result.

Interestingly, the package insert of one qualitative hCG POC device used in our study states “If a negative result is obtained, but pregnancy is suspected, another sample should be collected and tested 48-72 hours following.” Most other hCG POC devices provide a similar disclaimer. Although it is empirically recognized that false-negative results are possible in early pregnancy, most individuals (health care professionals and consumers alike) assume that this corresponds to the period of gestation that precedes hCG production. What our study showed is that hCG is present in the urine and serum of these women, but the concentration is too low for the POC devices to always detect reliably.

False-Positive Results in Point-of-Care Ovulation Prediction Devices Due to Very Low Concentrations of Human Chorionic Gonadotropin


Point of care devices which detect luteinizing hormone (LH) are used to predict ovulation and time intercourse in women who are trying to get pregnant. Women attending fertility clinics also commonly use these devices to time intrauterine insemination.  Although the hormones LH and hCG share 80% structural homology, cross reactivity in quantitative (laboratory) LH and hCG assays has not been a problem for many years due to the use of very specific antibody pairs. Many physicians and laboratorians assume that that specificity holds true for qualitative (home) devices as well.

Recently, a women undergoing fertility treatment at our institution detected a positive LH surge using an over the counter LH device despite the fact that she was later found to be pregnant. This made us ask the question "Could the over-the-counter ovulation kits cross react with hCG?"  Therefore, we undertook a study where we added purified hCG to saline and tested three home ovulation prediction devices [Clear Blue® (Swiss Precision Diagnostics, Geneva, Switzerland), First Response® (Church & Dwight, Princeton, NJ), and Walgreens® (Inverness Medical (now Alere), Waltham, MA)]. We found that all the devices we tested returned false positive results at hCG concentrations ranging from 10 to 10,000 mIU/mL.

The concentration of hCG at which devices were positive varied by brand. Both Clear Blue and Walgreens were clearly positive at hCG concentrations of 100 mIU/mL! Clear Blue was positive at an hCG concentration of 10 IU/L! Walgreens turned positive between 50 and 100 mIU/mL, and First Response turned positive between 5,000 and 10,000 mIU/mL. The LH concentration that caused positive results also varied by device brand (Table). Only Clear Blue was definitively positive at 50 mIU/mL of LH. First Response and Walgreens turned positive between 50 and 100 mIU/mL of LH.

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These devices may produce false positive results in women who are very early in pregnancy. At our institution, the reference interval for hCG in the first three to four weeks of pregnancy is 9 to 130 mIU/mL. Package inserts for some devices contain a cautionary statement that results obtained during pregnancy or administration of certain drugs including hCG may produce misleading results; however, it is clear that most physicians and laboratorians are unaware of the any potential cross-reactivity. This data is being presented at the American Association of Clinical Chemistry (AACC) meeting (Wednesday July 31, 2013, Poster B50) in Houston, and will be published in full later this year in Clinical Biochemistry doi.org/10.1016/j.clinbiochem.2013.07.017.

Fertility clinics and physicians that rely on home LH devices to detect an LH surge for the timing of intrauterine insemination should be aware that early pregnancy may cause false positive results on LH devices. Fertility clinics in particular should instruct their patients to use home LH devices with minimal hCG cross-reactivity.

TMI? A home hCG test that detects pregnancy and estimates weeks since conception


CalendarI'm beginning to wonder what could possibly come next. Last month, Swiss Precision Diagnostics (via its Procter & Gamble partner) unveiled its newest product in consumer diagnostics: the Clearblue Advanced Pregnancy Test with Weeks Estimator. This urine hCG test determines pregnancy status but also provides an estimate of the number of weeks since ovulation. The device has been cleared by the FDA and will be availabe in the US in September, 2013.

It works like other qualitative urine hCG tests but the body of the device contains two test strips that capture and detect the hormone in the urine sample. Detection of hCG is accomplished by the appearance of a colored band at a specific location on the test strip.

One test strip is designated "high sensitivity" and can detect a low concentration of hCG (detection limit of 10 IU/L). This test strip determines pregnancy status (pregnant or not pregnant). The other test strip has "low sensitivity" and detects higher concentrations of hCG and is used to estimate the number of weeks since conception. An optical reader housed within the device determines the color intensity of the test strips and a digital display reports the results as 1) Not pregnant; 2) Pregnant 1-2 weeks; 3) Pregnant 2-3 weeks; or 4) Pregnant 3+ weeks. The device reports an invalid result if there is a malfunction due to the device itself or operator error.

Clearblue with Estimator

Note that the weeks estimate is based on hCG concentration which is not how a pregnancy is usually dated. Physicians calculate gestational age by the day of the last menstrual period (LMP) so the device's estimate will be about 2 weeks less than one based on the LMP.

In its press release, Procter & Gamble states that the test is "more than 99 percent accurate in detecting pregnancy from the day of the expected period, and it is approximately 93 percent accurate in estimating how many weeks based on time since ovulation." I wanted to know what studies were done to support those claims but I received no response when I reached out to the individual at Procter & Gamble identified in the press release. However, there are some data included in the FDA's decision summary:

  • An early pregnancy study was conducted using 100 urine samples collected from non-pregnant women expecting to become pregnant. These samples were collected on days -6 to 1+ relative to the day of expected period. 99.0% of the devices gave a "pregnant" result by day zero (the day of the expected period).
  • A clinical study was conducted using samples from 153 volunteers with singleton pregnancies to evaluate performance of the “Weeks Estimator” feature compared to actual gestational age (method not identified). Agreement of “Weeks Estimator” with actual gestational age ranged from 45-99% (bold-faced emphasis is mine).

The bolded statement above is ambiguous but it likely is supposed to mean that the device is accurately able to estimate the true week of gestational age 45-99% of the time. If so then there are several questions that need to be answered. For example, what was the source of the range? Was it derived from different studies or from different gestational ages? What was the median gestational age? Is the device more accurate at certain gestational agess? Also, the range doesn't indicate how inaccurate the device can actually be. That is, when it is wrong how wrong is it? 1 week, 2 weeks, 3 weeks, or even more?

Given that the "Weeks Estimator" is highly variable, it is likely that Procter & Gamble will include language (similar to what the FDA stated) to caution the consumer that "the 'Weeks Estimator' is meant solely as an estimate for the consumer and is not intended as a substitute for a doctor’s clinical diagnosis. The ‘Weeks Estimator’ is not intended for multiple pregnancies. The estimate provided by the device may be inaccurate in these cases."

From a practical perspective, while women may want/need to know when they conceived, this is not the device to accomplish the job. It seems to provide highly variable information that, at best, is just a curiosity. Procter & Gamble says “confirming pregnancy is a life-changing moment in any woman’s life, and it sparks so many immediate questions like 'when did I get pregnant?'" True, but necessary? I'm not convinced.

Should there be a critical value for hCG test results?


UrgentA short while back, a colleague asked Ann and me if we were aware of any need to have a critical value for hCG tests.  Our colleague had been asked by a physician to implement one in his laboratory because the physician had “missed” a molar pregnancy diagnosis due to her being unaware of the hCG test result that had been performed by the lab.  The physician argued that if the lab had notified her that the hCG result was very elevated, it would have alerted her to the fact that this patient may have had an abnormal pregnancy.

Seems reasonable enough, right?  Maybe not.

Let’s first consider the definition of a “critical result.”  Strictly speaking, a critical result is a test result above (or below) a pre-determined cutoff that, if observed, would require immediate medical attention due to the threat of an adverse event (e.g. death) to a patient.

The selection and use of critical results is a giant issue in healthcare laboratory medicine.  Doctors order all kinds of tests on many different patients every day.  The results of those tests are most often delivered electronically through the use of integrated data networks.  The lab performs a test, reports the result via a computer network where it is delivered to the physician.  While the test result is likely to be informative to the care and treatment of a patient, the doctor doesn’t necessarily have to immediately know about the result.  A cholesterol test is a good example.  The result is informative and may guide treatment decisions but the decision to initiate or modify treatment isn’t urgent so the doctor doesn’t need any special notifications.  As such, it would be highly unusual for a lab to have a critical result notification in place for a cholesterol test.

Now consider a result of a blood glucose test.  There can be very serious medical problems if the concentration of glucose is too high (e.g. greater than 450 mg/dL) or too low (e.g. less than 50 mg/dL).  As such, labs have critical results for glucose.  If the concentration exceeds the critical cutoff then the healthcare provider is immediately notified so that appropriate interventions can take place to prevent medical harm to the patient.

While these two are examples are clear-cut, many others are not.  The result is that the lab struggles to find answers to several questions such as 1) What tests are considered “critical?” and 2) What is (are) the cutoff(s) to be used for tests that make the list?  The answers to these questions aren’t trivial.  If the list of tests includes those that aren’t truly critical to patient care then lab personnel spend a lot of time calling results of tests to doctors.  The same thing happens if the cutoffs aren’t selected appropriately.  Furthermore, not only are lab personnel affected, so too are the doctors whose time from caring for their patients is consumed answering those phoned results.

It’s not unusual for a physician to request that the lab add a test to the critical result list.  Frequently this occurs when the physician fails to notice a test result and made an inappropriate decision as a result.  That was the case with the molar pregnancy patient.  A molar pregnancy is an abnormal pregnancy without a viable fetus that usually results in a very elevated hCG concentration, often much higher than that seen in a normal pregnancy.  Women with molar pregnancies have to be treated to prevent potential malignant disease from developing.

While that may seem like a good reason for having a critical hCG test result it’s actually not.  That’s because there isn’t a single, useful hCG concentration above which a molar pregnancy can be easily differentiated from a normal pregnancy.  Some molar pregnancies have hCG concentrations that are more typical of normal pregnancies and some normal pregnancies can have hCG concentrations that are as elevated as they are with molar pregnancies.  There is too much overlap between the two types of pregnancies for an effective hCG cutoff to be established for use as a critical value.  The use of one would be chaotic and would likely result in extreme confusion between doctors, laboratories, and patients.  And in the delivery of any type of healthcare, confusion is definitely not a good thing.

Is the qualitative serum pregnancy test obsolete?


I’ve written several times about qualitative hCG tests in this blog.  As a reminder, qualitative tests can be performed using urine or serum samples.  Urine tests can be performed close to the patient or even at home because the urine sample requires no special processing.  However, when serum is the test really can’t be performed at home or at the point-of-care because the blood sample has to be centrifuged to first obtain the serum and centrifugation is usually only performed in the clinical laboratory.  Notably, clinical labs are often able to do quantitative hCG testing on serum, too.

So, if a lab can do qualitative and quantitative hCG testing on serum, why not just offer one test instead of two?  In other words, might the qualitative test be considered obsolete?  My lab recently published a study that addressed that question.

To answer that question we surveyed several hundred doctors and the survey results revealed the following:

  1. When requesting serum hCG tests, 49% of physicians preferred to order a qualitative rather than a quantitative test even though they believed quantitative tests were more accurate.
  2. Physicians preferred qualitative tests because they believed that they received the test results faster.

However, when we examined the turnaround time data, that last point was not supported.  There are a few definitions of turnaround time to consider.  Doctors consider it to be the time it takes to get a result after the sample is collected while laboratorians consider it to be the time it takes to produce the result after they receive the sample.

By the lab’s definition, qualitative tests were performed more rapidly than quantitative tests but there were no differences using the doctors’ definition of turnaround time.  That’s because the time it takes to transport the sample to the laboratory is known to contribute the most to delays in the total testing process.  So, although physicians believed they get results from qualitative tests more quickly, it doesn’t seem to be the case.

We also compared the analytical sensitivities of the two types of tests.  The qualitative test that we used had a claimed detection limit of 25 IU/L.  That is, a sample with an hCG concentration above 25 IU/L should produce a positive result.  Of the samples that gave a positive result, about 20% had an hCG concentration that was <25 IU/L which indicated that the qualitative test was more analytically sensitive than we expected it to be.  In my opinion, that’s a good thing.

Because we determined the actual pregnancy status of all the patients with a positive result, we were also able to determine how well the qualitative and quantitative tests performed at determining pregnancy status.  Both tests did quite well and showed high sensitivity and specificity.  That is, there were very few false-negative or false-positive results.  From a clinical perspective, a false-negative result is more concerning than a false-positive one because a pregnant patient who is incorrectly identified as not being pregnant risks being exposed to a medical intervention that could harm the fetus.  The false-negative rate was lowest, only 0.1%, when the qualitative test was evaluated against pregnancy status and the detection threshold of 25 IU/L.  The performance of the quantitative serum hCG test was identical.  So, both the qualitative and quantitative serum hCG tests do a very good job at ruling-out a possible pregnancy.

So, given this evidence, I would conclude that while qualitative hCG tests could be replaced by quantitative tests, there is really no compelling reason to do so.

Is it time to abandon the hCG discriminatory zone?


I've written about ectopic pregnancy a few times now (see this and this).  The use of hCG testing in the evaluation of a woman with a suspected ectopic pregnancy is invaluable.  For many years doctors have relied upon the concept of a "discriminatory zone."  That is, an hCG concentration above which an intrauterine pregnancy should always be visible using transvaginal ultrasound.  The hCG concentration that is often used as the discriminatory zone is between 1,000 and 2,000 IU/L.  If no fetus is seen then the woman may receive treatment for a presumed ectopic pregnancy.

Early recognition and treatment of an ectopic pregnancy is critical because it is a leading cause of maternal death in the first trimester.  Ectopic pregnancies are terminated by the use of the drug methotrexate or surgery.  Methotrexate is a folic acid antagonist and a powerful teratogen that causes malformations in a developing fetus.  The use of methotrexate has increased substantially in the last few years because it has fewer risks and is less expensive than surgery.  However, methotrexate is sometimes given to women with an erroneous diagnosis of ectopic pregnancy which results in the loss of a viable pregnancy or the delivery of infants with birth defects.

Two recent reports have shown a spotlight on this problem:

  • The first study reported the outcomes of 8 pregnancies that were incorrectly diagnosed as ectopic and in whom the mother was treated with methotrexate.  Sadly and unsurprisingly, all 8 pregnancies had terrible outcomes.  Two pregnancies resulted in severely malformed infants.  One was liveborn at 37 weeks and had Tetralogy of Fallot, pulmonary atresia, congenital scoliosis, 7 ribs on left side and 11 ribs on right side, and a single kidney.  The other was stillborn at 30 weeks and had Tetralogy of Fallot, horseshoe kidney, and a single umbilical artery.  The other 6 pregnancies were aborted, 3 spontaneously and 3 deliberately.
  • The second study addressed the reliability of the hCG discriminatory zone by evaluting 202 patients that met the following criteria: 1) a transvaginal sonogram showing no intrauterine pregnancy; 2) an hCG test performed on the same day as the ultrasound; 3) documentation of a subsequent viable intrauterine pregnancy.  80% had an hCG concentration less than 1,000 IU/L (well below the discriminatory zone), in 9% it was between 1,000 and 1,499 IU/L, in 6% it was between 1,500 and 1,999 IU/L, and in 5% it was 2,000 IU/L or greater (above the discriminatory zone).  The highest hCG concentration observed was 6,567 IU/L.

While the idea of an hCG discriminatory zone is an appealing one, it is clearly not something that can be relied on to make an important therapeutic decision.  The authors of the second study (above) concluded exactly that and recommend using follow-up sonography and serial hCG testing in hemodynamically stable patients before treating for presumed ectopic pregnancy.

        FDA and FTC Crack Down on hCG Diet Products


        HCG photo
        Although the hCG diet is slightly outside of the realm of The Pregnancy Lab, we have discussed it in the past because we get questions about it all the time. Don't even consider doing this diet to shed your extra holiday pounds. On December 6, 2011, the FDA and Federal Trade Commission issued warnings to a number of companies ordering them to stop selling their homeopathic hCG products.  The warning letter states that, it is unlawful to "advertise that a product can prevent, treat, or cure human disease unless you possess competent and reliable scientific evidence". In addition, the FDA says a 500-calorie diet by itself is pretty risky. You can get gallstones and develop other health problems from such severe restrictions on what you eat.

        If you are considering this or any diet a good resource is an article by American Dietetic Association.