Home Monitoring with the ClearPlan Easy Fertility Monitor for Fertility Awareness

Transcription

1 The Journal of International Medical Research 2001; 29 (Suppl 1): 14A 20A Home Monitoring with the ClearPlan Easy Fertility Monitor for Fertility Awareness K MAY Research and Development, Unipath Ltd, Bedford, UK* Many couples planning a pregnancy have had to gauge the best time for sexual intercourse from subjective indications, e.g. cervical mucus changes, or retrospective information, e.g. temperature and calendar methods. Between women, and within a woman, there are considerable variations in menstrual cycle length and underlying hormonal patterns. Although fertility test kits are available, most still rely on visual interpretation by the user. A new combination of immunochemical testing and computing technology is now available in the ClearPlan Easy Fertility Monitor. This paper describes the features of this accurate, simple-to-use, home-based fertility monitor, which gathers data on hormonal patterns and takes account of the individuality of menstrual cycles in women. These data and information about other events, such as sexual intercourse, can be stored in the monitor and accessed by the couple and their medical professional for retrospective review. The monitor is useful for couples who have just started trying to conceive, or those who have been planning a pregnancy for some time. KEY WORDS: CLEARPLAN EASY FERTILITY MONITOR; POTENTIAL FERTILITY; OVULATION; URINARY LUTEINIZING HORMONE; URINARY ESTRONE GLUCURONIDE Introduction For the majority of couples, their desire and ability to conceive a child is now governed as much by personal choice as by biological and hormonal factors. Data on the hormonal indicators of Peak Fertility have been acquired and are discussed elsewhere in this supplement. 1 For the couple planning a pregnancy, however, the ability to time *Dr May is currently Vice President of Research and Development for Inverness Medical Ltd, Inverness, UK. ClearPlan Easy TM Fertility Monitor is a trademark owned by or licensed to the Unilever group of companies. sexual intercourse at the optimum phase of the menstrual cycle is often based on retrospective information. For example, calendar calculations are based upon previous cycle lengths, and this information is used to predict the most probable time of ovulation during the current cycle. Some methods are prospective (e.g. monitoring changes in cervical mucus) but still rely on subjective interpretation by the user. 2 4 Developing a simple immunochemical test that provides an accurate, objective and personal profile of hormone changes 14A

2 throughout the menstrual cycle has been a research goal since hormonal indicators of ovulation were first described. 5 7 Such a device has now become available and is marketed as the ClearPlan Easy Fertility Monitor. The monitor is a new, simplified, hand-held instrument that provides objective indication of the days when conception is more likely to occur by monitoring estrone-3- glucuronide (E3G) and luteinizing hormone (LH) in early-morning urine samples to delineate the fertile period. Other ovulation detection kits available only check the levels of LH, whereas the ClearPlan Easy Fertility Monitor checks both LH and E3G levels. The new monitor provides a personalized estimate of the fertile phase and is appropriate for all couples who are planning a pregnancy. This paper describes the technology behind the monitor s development, its use as a homebased aid to conception and its potential application in a clinical setting. Urinary hormone monitoring with the ClearPlan Easy Fertility Monitor The ClearPlan Easy Fertility Monitor comprises an effective urine collection and test system (using disposable test sticks) and an electronic monitor that reads and interprets test results. The system is an extension of the rapid assay technology that has been successfully employed in the *Clearblue Easy TM is a trademark owned by or licensed to the Unilever group of companies. Clearblue Easy * and ClearPlan Easy tests for pregnancy and ovulation prediction. Software built into the ClearPlan Easy Fertility Monitor allows it to use the information gained from the test results to monitor changing hormone levels and determine the fertile status on each day of the cycle. URINE TEST STICKS Each test stick is a disposable unit that collects an early-morning urine sample and simultaneously detects the presence of LH and E3G within the sample. Inside the plastic casing of the test stick are two key raw materials; the first, which is partly protruding from the sampling end of the plastic casing, is a hydrophilic, non-woven wick supported on a mylar backing. When held in the urine stream the protruding part of the wick collects a sample for testing. Figure 1 shows the test stick with part of the wick protruding. The wick inside the casing holds LH and E3G antibodies bound to blue latex particles. Still inside the plastic casing, further away from the sampling end of the test stick, is the test strip. This is a nitrocellulose membrane on which antibodies for LH and an E3G conjugate are deposited at two different test zones within the test stick window The LH assay is a sandwich assay (Fig. 2A). After sampling, urine travels up the wick by capillary action and mobilizes the latex-bound LH antibody, which binds to any LH present in the sample. The urine carries this LH complex to the test zone where the LH binds to a second antibody immobilized on the test FIGURE 1: A test stick is used to analyse the presence of LH in a urine sample 15A

3 FIGURE 2: (A) The luteinizing hormone (LH) assay is a sandwich assay, whereby any LH present in urine binds to latex particles that are then carried to the test zone. (B) LH then binds to an immobilized antibody, forming a sandwich and producing a blue line if LH is present in the urine (positive test). Increasing amounts of urinary LH cause a stronger blue line to appear. (C) If the test is negative, the mobile latex particles cannot bind at the test zone, therefore no blue line appears strip. This forms a sandwich, producing a blue line (LH test line, Fig. 2B). In the absence of LH, the latex-bound antibody cannot bind at the test zone and no blue LH test line appears (Fig. 2C). The intensity of the blue line is directly proportional to the concentration of LH in the sample. The E3G assay is a competitive assay (Fig. 3). At the same time, urine traveling up the wick mobilizes the latex bound E3G antibody, which binds to any E3G present in the sample. When this complex reaches a second test zone it is unable to bind to the E3G conjugate and no blue E3G test line is formed FIGURE 3: (A) The estrone-3-glucuronide (E3G) assay is a competitive assay. While the urine travels along the test strip, the latex bound E3G antibody is also mobilized. (B) Unlike the luteinizing hormone (LH) assay, this complex is unable to bind to the E3G conjugate at the test zone. A high urinary concentration of E3G leads to a pale blue (or absent) line. (C) A blue line does form if little or no E3G is present in the sample. A higher color intensity indicates a lower E3G concentration 16A

4 (Fig. 3B). In the absence of E3G, the latex-bound E3G antibody binds directly to the E3G conjugate immobilized in the test strip and a blue E3G test line forms (Fig. 3C). The intensity of the blue line is indirectly proportional to the concentration of E3G in the sample. ELECTRONIC MONITOR Determination of the test result through visual assessment of the test-line color alone is a subjective technique that relies on the user s interpretation. The ClearPlan Easy Fertility Monitor removes user interpretation and brings a new level of objective measurement into home-based fertility monitoring. The monitor, shown in Fig. 4, uses an optical reading mechanism to measure the intensity of the line and by application of a rule set (monitor algorithm) can determine changes in the hormone levels. The monitor is a battery-operated, selfcalibrating, electronic device. When the monitor is switched on, prior to reading a test, it checks the conditions of the optics and makes any allowances for any dirt detected when reading the test. It will then notify the user, via the display, that the optics require cleaning. In addition, when the monitor measures the intensity of the blue lines formed in the test stick, it makes allowances for the base transparency of the test stick by making additional measurements where no dye is present. The wick end of the test stick is held in the first morning-urine stream for 3 s. After sampling, the plastic cap is replaced on the test stick and it is inserted into a slot in the monitor. The test stick is illuminated from one side and light is detected at the other side by a series of photodetectors in the test stick window region. A signal at each of the LH and E3G test zones is calculated that represents the fraction of light absorbed by each of the test lines. A strong line has a high signal, and a weak line a low signal. The monitor uses these measurements to determine the changes in the urinary hormone levels. FIGURE 4: The ClearPlan Easy Fertility Monitor, which uses an optical reading mechanism to measure the intensity of lines in the test zone 17A

5 How to use the monitor When the user s menstrual period starts during the night or early in the morning, on rising she firmly presses the button marked M on the monitor for 5 s. If her period starts later in the day, the user presses the M button on the following morning. Once the M button is pressed, the monitor registers this as the first day of the user s menstrual cycle by showing an m and 1 on the display screen, and indicates that this is a time of Low Fertility by showing one bar on the screen. The user looks at the monitor each morning to check when urine tests are required. For the first cycle, the monitor will request a test on day 6 and after cycle 1 the monitor will adapt the start of testing to the individual s cycle. There is a 6-h testing window, from 3 h before to 3 h after the time that the M button was pressed on day 1, which enables the user to test her urine during a time-period convenient to her; the only constraint is that an earlymorning urine specimen must be used for each test because this provides a reliable measurement of both LH and E3G. By setting the M button on day 1 at 09.00, the user can test her first urine of the day between and for the duration of the cycle. The user checks the monitor display every morning to see if a test is requested. To undertake a test she holds a test stick in her urine stream for 3 s. She then places the cap over the sampling end and inserts the test stick into the monitor for analysis. The test stick should be inserted in the monitor within 15 min of completing the test. The monitor display emits a flashing test stick symbol for 5 min to indicate that analysis is under way, and at the end of this time the monitor asks for the stick to be removed. Once the test stick has been removed the monitor displays the fertility status for that day. The monitor will request one test each day for up to a total of 10 or 20 consecutive days. In cycle 1 the first test is requested on day 6, and in each subsequent cycle the start of testing may vary between days 6 and 9 as it is optimized to the user s cycles using information collected by the monitor. In the majority of cycles the monitor will request only 10 tests, however if the mid-cycle LH surge is not detected during the first 10 tests a second set of 10 tests is requested. Determination of fertility status The system will delineate three levels of fertility according to changes detected in the levels of LH and E3G. Low Fertility is displayed on the monitor s screen when the hormones are at a baseline level. Low Fertility will be displayed from day 1 of a woman s cycle until rises above the baseline levels are detected. The change from Low Fertility to High Fertility is triggered by detection of elevated E3G levels. The change from High Fertility to Peak Fertility is triggered by the detection of an LH surge. Peak Fertility is displayed on the day of the LH surge and on the following day. After this, High Fertility will be displayed for 1 day prior to a return to Low Fertility. Data have been obtained from laboratory analysis of daily urine samples with the monitor. A total of 352 cycles, contributed by 90 women for up to 5 cycles, were tested. The majority of cycles showed 1 5 days of High Fertility prior to Peak Fertility. On a cycle-bycycle basis this percentage increased from 66% in cycle 1 to 76% in cycle 2 (when the monitor had begun to learn about the volunteer s cycle and the testing regime was optimized accordingly). Clinical information In addition to being able to know the daily fertility status, another option is available. The ClearPlan Easy Data Transfer System 18A

6 has been developed to allow information stored by the monitor to be transferred to a computer for use and display by the user or her medical professional. By inserting a data card (similar in size to a credit card) into the slot at the back of the monitor, a copy of the monitor s memory is made. By using a datacard reader connected to the computer loaded with the supporting software, these data can be transferred to a PC for display and storage. The display shows a retrospective record of the user s cycles including daily fertility status, cycle start dates, cycle lengths and number of tests requested and completed. An example display is shown in Fig. 5. An additional facility permits useful information on events, such as sexual intercourse, to be recorded using a second type of card. These data can also be displayed in conjunction with the cycle information. In order to maintain an up-to-date record of all the available monitor data, information should be transferred after every 2 cycles of use. Conclusions For all couples trying to conceive, the ClearPlan Easy Fertility Monitor can tell them on which days sexual intercourse is most likely to lead to conception, objectively and accurately. For couples experiencing difficulty conceiving, use of the ClearPlan Easy Fertility Monitor in conjunction with the ClearPlan Easy Data Transfer System offers an opportunity for sharing information stored by the monitor with medical professionals, as a first step in the diagnosis and treatment of infertility. The ClearPlan Easy Fertility Monitor keeps a File Card User Name: User Reference: Help Cycle 1, Start: 4 April 1998, Length: 29 days Clearplan Data Transfer System Key Low High Peak Esmerelda Smith Test Done Test Not Done Event First Card Use Time: 23:00 Date: 25 September Cycle: 2, Start: 3 May 1998, Length: 27 days Cycle: 3, Start: 30 May 1998, Length: 31 days FIGURE 5: A typical record of the user s menstrual cycle displayed when the ClearPlan Easy Data Transfer System is used 19A

7 record of the user s Low, High and Peak fertility management tool, not a small Fertility days and cycle lengths for up to the laboratory, and it does not store quantitative previous 6 menstrual cycles. Using the hormone information, but the system does ClearPlan Easy Data Transfer System, this provide accurate, objective information for information can be made available to the couples trying to conceive, which can be medical professional for assessment. The shared with a medical professional for those ClearPlan Easy Fertility Monitor is a seeking advice or intervention Cambridge Medical Publications References 1 Spieler JM, Collins WP: Potential fertility defining the window of opportunity. J Int Med Res 2001; 29 (Suppl 1): 3A 13A. 2 Collins WP: Indicators of potential fertility: scientific principles. In: Natural Contraception Through Personal Hormone Monitoring (Bonnar J, ed). New York: The Parthenon Publishing Group, 1996; pp Royston JP: Basal body temperature, ovulation and the risk of conception with specific reference to lifetimes of sperm and egg. Biometrics 1982; 38: Royston JP: Identifying the fertile phase of the human menstrual cycle. Stat Med 1991; 10: WHO Task Force for Methods of Determination of the Fertile Period: Temporal relationships between ovulation and defined changes in the concentration of the plasma estradiol-17 beta, luteinizing hormone, follicle-stimulating hormone and progesterone. I: Probit analysis. Am J Obstet Gynecol 1980; 138: WHO Task Force on Methods for Determination of the Fertile Period: Temporal relationships between ovulation and defined changes in the concentration of the plasma estradiol-17 beta, luteinizing hormone, follicle-stimulating hormone and progesterone. II: Histologic dating. Am J Obstet Gynecol 1981; 139: WHO Task Force on Methods for Determination of the Fertile Period: Temporal relationships between indices of the fertile period. Fertil Steril 1983; 39: 647. Address for correspondence Dr K May Inverness Medical Ltd, Beechwood Park North, Inverness IV2 3ED, UK. 20A