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.
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.