Soft Candy as an Electronic Material Suitable for Salivary Conductivity-Based Medical Diagnostics in Resource-Scarce Clinical Settings.

Soft candy was discovered to be an excellent electronic material and was used to fabricate electrodes for salivary conductivity-based diagnostics. Using a simple molding process, a soft candy (Tootsie Roll) was made into 20 × 20 × 5 mm electrodes with a stable frequency response (0.1-100 kHz). The soft candy electrode-liquid interface circuit model was also developed for the first time. Using 0.01, 0.05, and 0.1 M phosphate-buffered saline and artificial saliva of varying conductivities, the performance of the soft candy (Tootsie Roll) electrode was evaluated. The electrode has a low temperature coefficient of ∼0.02 V/C, and the evaporation-induced mass change during measurement (<3 min) was negligible. Using a trenched surface, a limit of detection (LOD) of ∼1630 µS/cm was obtained and was lower than the saliva conductivity of a healthy adult at ∼3500 µS/cm. Thus, it is suitable for monitoring the ovulation cycle for natural family planning as well as chronic kidney disease diagnosis. Given the ubiquity of soft candy, the simplicity of the molding process, and the negligible medical waste stream, it is a more appropriate approach to diagnostics design for resource-scarce clinical settings, such as those in developing countries. The broader impact of this work will be the paradigm shift of soft candy from food to a new class of edible, moldable, high-resistivity, and stable electronic materials.

Menstrual cyclicity is predictably unpredictable.

"Time moves slowly but passes quickly" - Alice Walker.

An inexpensive smartphone-based device for point-of-care ovulation testing.

The ability to accurately predict ovulation at-home using low-cost point-of-care diagnostics can be of significant help for couples who prefer natural family planning. Detecting ovulation-specific hormones in urine samples and monitoring basal body temperature are the current commonly home-based methods used for ovulation detection; however, these methods, relatively, are expensive for prolonged use and the results are difficult to comprehend. Here, we report a smartphone-based point-of-care device for automated ovulation testing using artificial intelligence (AI) by detecting fern patterns in a small volume (<100 µL) of saliva that is air-dried on a microfluidic device. We evaluated the performance of the device using artificial saliva and human saliva samples and observed that the device showed >99% accuracy in effectively predicting ovulation.

Accuracy of a home-based device for giving an early estimate of pregnancy duration compared with reference methods.

OBJECTIVE: To assess a home pregnancy test's accuracy to concurrently detect pregnancy and determine pregnancy duration. DESIGN: Multicenter, prospective study. SETTING: Study sites in the United States. PATIENT(S): Women actively attempting to conceive who have menstrual bleeds (18-45 years). INTERVENTION(S): Volunteers collected early morning urine samples (three or fewer menstrual cycles). Pregnant volunteers underwent ultrasound dating scans. Ovulation day (LH surge +1 day) during pregnancy-resulting cycles was determined by quantitative measurement of LH. Random urine samples were tested with the hCG-measuring pregnancy test from 4 days before the expected period until 4 weeks later. MAIN OUTCOME MEASURE(S): A home pregnancy test's accuracy in determining pregnancy duration compared with ultrasound and ovulation day. RESULT(S): Agreement between pregnancy test results and time since ovulation was 93% (confidence interval [CI], 91.5-94.4). Agreement with ultrasound was dependent on the formula: there was 99% agreement when calculated with adjustment for Hadlock formula bias (Pexsters; CI, 98.2-99.4) or using a nonbias formula (Wu; CI, 98.6-99.6), when ultrasound error was accommodated. Agreement was lower when bias/measurement errors were not accounted for (Wu, 86%, CI, 83.9-88; Hadlock, 80.8, CI, 78.2-83.3). CONCLUSION(S): This home pregnancy test provides an accurate estimation of pregnancy duration in weeks categories, 1-2, 2-3, 3+ weeks since ovulation, thereby showing utility in dating pregnancy.

Efficacy of a new postpartum transition protocol for avoiding pregnancy.

INTRODUCTION: The postpartum period is a challenging time for family planning, especially for women who breastfeed. Breastfeeding delays the return of menses (lactational amenorrhea), but ovulation often occurs before first menses. For this reason, a protocol was developed to assist women in identifying their return of fertility postpartum to avoid pregnancy. METHODS: In this prospective, 12-month, longitudinal cohort study, 198 postpartum women aged 20 to 45 years (mean age, 30.2 years) were taught a protocol for avoiding pregnancy with either online or in-person instruction. A hand-held fertility monitor was used to identify the fertile period by testing for urinary changes in estrogen and luteinizing hormone, and the results were tracked on a web site. During lactational amenorrhea, urine testing was done in 20-day intervals. When menses returned, the monitor was reset at the onset of each new menstrual cycle. Participants were instructed to avoid intercourse during the identified fertile period. Kaplan-Meier survival analysis was used to calculate unintentional pregnancy rates through the first 12 months postpartum. RESULTS: There were 8 unintended pregnancies per 100 women at 12 months postpartum. With correct use, there were 2 unintended pregnancies per 100 women at 12 months. CONCLUSION: The online postpartum protocol may effectively assist a select group of women in avoiding pregnancy during the transition to regular menstrual cycles.

[Sonographical visibility of the corpus luteum in dairy cows]. / Sonographische Darstellbarkeit des Corpus luteum bei der Milchkuh.

OBJECTIVE: The study aimed to evaluate the day from which a corpus haemorrhagicum in the dairy cow after spontaneous or induced ovulation can be visualized using a mobile ultrasound device. MATERIAL AND METHODS: During three uninfluenced control cycles and three cycles in which six cows received a simultaneous treatment with GnRH and PGF2a, either on day 7, 14 or 17 post ovulation, the ovaries were scanned sonographically. In every control cycle a daily ultrasound examination was conducted starting from the 18th day of a cycle, in the treatment cycles beginning from the day of the hormonal treatment. Thus the formation of a new corpus luteum was followed sonographically from the day of ovulation onwards. Concentrations of progesterone were determined on day 1 of any cycle, on the day of hormonal treatment and on the 5 days following the treatment to support the sonographical results through endocrine values. RESULTS: A corpus luteum was visible in 100% of the cases on day 5 of the cycle, regardless of whether it had been a spontaneous or induced ovulation. In the treatment cycles, a sonographically visible luteolysis induced by the hormonal treatment began between 1.3 and 1.8 days after the hormone injection and lasted on average 3.7 days. The day of the cycle on which hormonal treatment was performed had no influence on the occurrence of luteolysis. A central fluid-filled cavity was visible in 33% of the corpora lutea, becoming smaller during luteolysis and disappearing before luteolysis was completed. CONCLUSION AND CLINICAL RELEVANCE: A corpus luteum is sonographically visible on day 5 after ovulation. Ultrasound examinations can be used to confirm induced luteolysis. The formation of a new corpus luteum can be visualised to confirm the success of an induced ovulation.

Monitoring of ovarian activity by measurement of urinary excretion rates of estrone glucuronide and pregnanediol glucuronide using the Ovarian Monitor, Part II: reliability of home testing.

BACKGROUND: The UNDP/WHO/World Bank/Special Programme of Research, Development and Research Training in Human Reproduction (Geneva) set up a study to determine whether it is feasible for women to monitor their ovarian activity reliably by home testing. Daily self-monitoring of urinary hormone metabolites for menstrual cycle assessment was evaluated by comparison of results obtained with the Home Ovarian Monitor by untrained users both at home and in study centres. METHODS: Women collected daily data for urinary estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) for two cycles, then the procedure was repeated in the women's local centre (in Chile, Australia or New Zealand) giving a total of 113 duplicate cycles. The tests were performed without the benefit of replicates or quality controls. The home and centre cycles were normalized and compared to identify assay errors, and the resulting home and centre menstrual cycle profiles were averaged. RESULTS: Reliable mean cycle profiles were obtained with the home and centre excretion rates agreeing to within 36 ± 21 nmol/24 h for E1G and 0.77 ± 0.28 µmol/24 h for baseline PdG values (1-5 µmol/24 h). The cycles had a mean length of 28.1 ± 3.1 days (n = 112; 5th and 95th percentiles: 24 and 35 days, respectively), a mean follicular phase of 14.8 ± 3.1 days (n = 107; 5th and 95th percentiles: 11 and 21 days) and a mean luteal phase length of 13.3 ± 1.5 days (n = 106; 5th and 95th percentiles: 11 and 17 days), calculated from the day of the LH peak. CONCLUSIONS: The study confirmed that the Ovarian Monitor pre-coated assay tubes worked well even in the hands of lay users, without standard curves, quality controls or replicates. Point-of-care monitoring to give reliable fertility data is feasible.

[Calculation of the Pearl Index of Lady-Comp, Baby-Comp and Pearly cycle computers used as a contraceptive method]. / Indeks Pearl'a komputerów cyklu Lady-Comp, Baby-Comp i Pearly stosowanych jako metoda antykoncepcji.

INTRODUCTION: Lady-Comp, Baby-Comp and Pearly cycle computers are medical devices that use sophisticated statistical gathering methods, as well as a comprehensive database, to precisely determine fertile and infertile phases of a menstrual cycle on the basis of everyday basal body temperature measurements. They have been produced and distributed worldwide by Valley Electronics GmbH (Eschenlohe, Bavaria, Germany) for over 25 years. OBJECTIVES: The aim of the study was to calculate the Pearl Index of cycle computers in order to determine their contraceptive effectiveness. MATERIAL AND METHODS: 510 Polish women, randomly chosen from the database of the distributor, who had been using the device for over one year or during 13 menstrual cycles, received the questionnaire. The Pearl Index was calculated as a quotient of the number of unplanned pregnancies and the total number of cycles during which cycle computers were used and the obtained value was then multiplied by 1300. Statistical methods were applied to analyze data from the questionnaires and to calculate the Pearl Index. Unplanned pregnancy odds ratio for women using additionally condoms during the fertile phase of the cycle was also calculated. RESULTS: 139 properly filled questionnaires were the source of data about 3332 cycles. After the initial analysis, 290 cycles were declined because the respondents had not complied with the computer indications and 1021 cycles were declined because the respondents had been using other contraceptive methods at the same time--no unplanned pregnancy was noted in that group. In the investigated group of 2040 cycles of correct cycle computers use, one unplanned pregnancy was observed. Calculated Pearl Index for this group amounted to 0.64; it means, that less than 7 out of 1000 users of cycle computer as a contraceptive method may become pregnant within one year The odds of pregnancy in women using a cycle computer and condoms on fertile days amounted to 1.035%; it means that 1 out of 100 users of the combined methods may become pregnant within one year. CONCLUSIONS: The Pearl Index value of cycle computers is comparable with the Pearl Index of hormonal contraceptives. Cycle computers offer an effective and drug-free method of contraception to all women who wish to limit interventions in their bodily functions and do not want or cannot use other contraceptive methods.

Self-assessment of the cervical pupil sign as a new fertility-awareness method.

This pilot study investigates in a group of 20 healthy volunteers with regular cycles and prior experience in natural family planning methods whether self-assessment of the cervical "pupil sign" is feasible and can be used to detect the preovulatory fertile window. All participants were able to assess the cervical pupil sign. Based on this method, the fertile window lasts on average 3 days, which is significantly shorter and more consistent than when defined on basis of the vulvar mucus method.

Timing clinic visits to phases of the menstrual cycle by using a fertility monitor: the BioCycle Study.

Planning study visits during specific menstrual cycle phases is important if the exposure or outcome is influenced by hormonal variation. However, hormone profiles differ across cycles and across women. The value of using fertility monitors to time clinic visits was evaluated in the BioCycle Study (2005-2007). Women aged 18-44 years (mean, 27.4) with self-reported menstrual cycle lengths of 21-35 days were recruited in Buffalo, New York, for 2 cycles (n = 250). Participants were provided with home fertility monitors that measured urinary estrone-3-glucuronide and luteinizing hormone (LH). The women were instructed to visit the clinic for a blood draw when the monitor indicated an LH surge. The monitor recorded a surge during 76% of the first cycles and 78% of the second cycles. Scheduling visits by using set cycle days or algorithms based on cycle length, such as a midcycle window or a window determined by assuming a fixed luteal phase length, would be simpler. However, even with perfect attendance in a 3-day window, these methods would have performed poorly, capturing the monitor-detected LH surge only 37%-57% of the time. Fertility monitors appear to be useful in timing clinic visits in a compliant population with flexible schedules.

Evaluation of a new approach for the estimation of the time of the LH surge in dairy cows using vaginal temperature and electrodeless conductivity measurements.

The objective of the study was to test the effectiveness of a new type of conductivity sensor, along with vaginal temperature, at identifying the LH peak associated with estrus in dairy cows. Twelve mature non-lactating Holstein-Friesian cows had their estrous cycles synchronized on two occasions, and then data were collected for the following spontaneous cycles. An indwelling electrodeless plastic-coated toroidal conductivity sensor, which also recorded temperature, was placed in the vagina throughout the cycle. Blood samples were collected for LH measurement, and ultrasound scanning used to confirm ovulation. Although there was a relationship between vaginal mucus conductivity measured by the toroidal sensor and the timing of the LH surge, it was not sufficiently robust in individual cows to be able to identify the time of the LH surge. The mean increase in vaginal temperature at estrus was 0.48 degrees C. An algorithm was developed which used the detected individual cow temperature peak to test the relationship with the LH peak. In 16 out of 21 cases where ovulation was confirmed and data existed, the estimated individual peak was within 4h of the LH surge, in three cases it was +/-6h, and in two instances it was early. In conclusion, the temperature algorithm was able to identify the time of the LH surge and thus predict time of ovulation in a way that would allow effective AI, although this result needs to be tested in lactating cows. However, the toroidal conductivity sensing method was not able to produce data of sufficient quality to develop a predictive relationship in individual cows.

Devices for home evaluation of women's health concerns.

PURPOSE: Devices used for home evaluation of fertility, pregnancy, menopause, colon cancer, breast cancer, and urinary-tract and vaginal yeast infections are discussed. SUMMARY: Ovulation-prediction devices monitor natural changes in a woman's body during the menstrual cycle, including changes in basal body temperature, urinary luteinizing hormone, and urinary estrone-3-glucuronide concentrations. Also available are devices that identify changes in the content of sodium chloride and other electrolytes in saliva and cervical-vaginal mucus. Home pregnancy tests are designed to detect human chorionic gonadotropin in the urine. Both urine and saliva tests are available for home evaluation of menopause; the most common devices use urine to measure follicle-stimulating hormone. The saliva tests measure estradiol, progesterone, and testosterone. Devices for home screening for colon cancer use either the guaiac test or the fecal immunochemical test. For aid in breast self-examination, patients may use a simulated-breast product designed to train them to detect lumps or a thin, silicone-containing pad intended to increase the sensitivity of the fingers to abnormalities. Urine-dipstick tests can be used to screen for urinary-tract infection, and a swab or panty liner can be used to detect vaginal pH changes indicative of vaginal yeast infection. Home-based tests may be convenient and economical but also have limitations; pharmacists can help educate patients and clinicians. CONCLUSION: Many devices are available to help evaluate women's health concerns at home.

Increased pregnancy rate with use of the Clearblue Easy Fertility Monitor.

OBJECTIVE: To determine the effect on pregnancy rates through use of the Clearblue Easy Fertility Monitor (CEFM) in women trying to conceive. DESIGN: Prospective study, in which volunteers were randomly assigned either to use or not to use the CEFM. All participants could also use other aids to conception. Data were self-reported by volunteers using daily diaries, supplied and collected by mail. SETTING: Home use, under conditions normally experienced by over-the-counter purchasers of the marketed device. PATIENT(S): Women who were trying to conceive; 653 (CEFM 305, control 348) provided evaluable information. INTERVENTION(S): CEFM was used for two cycles. MAIN OUTCOME MEASURE(S): Cumulative pregnancy rates over two cycles of use. RESULT(S): The cumulative pregnancy rate for 2 cycles was significantly higher in the CEFM group (22.7%) compared with the control group (14.4%). More women who had been trying to conceive for <6 months became pregnant than women who had been trying to conceive for >6 months (odds ratio: 2.67). Previous pregnancy and younger age of partners were also significant prognostic factors, but use of other aids to conception was not. After adjustment for other factors, CEFM use remained a significant factor affecting the chance of conceiving within two cycles (odds ratio: 1.89). CEFM users found the device to be easy/very easy to use (90%) and convenient/very convenient (80%). CONCLUSION(S): Use of the CEFM increases the likelihood of getting pregnant during the first two cycles of use compared with its nonuse, in women who had been trying to conceive for up to 2 years.

Acceptability of a home monitor used to aid in conception: psychosocial factors and couple dynamics.

BACKGROUND: Assessing the psychological acceptability of technologies designed to assist couples in achieving pregnancy is complex. OBJECTIVE: The current study developed measures relating to the impact of one such technology on 52 couples' relationships, their feelings relating to pregnancy status and their feelings about the technology itself. METHODS: Pregnancy status and daily logs of sexual activity were recorded for four menstrual cycles, in addition to the completion of acceptability questionnaires. RESULTS: Baseline acceptability measures were more favorable among couples eventually achieving pregnancy. For couples not becoming pregnant, acceptability declined over time and relationships became more strained. Behavioral data clearly indicated a "targeting" and focusing of sexual activity in response to the information displayed by the monitor. CONCLUSION: Expectations of success, couple disagreements about prior failure and partner communication patterns appear to be related to pregnancy success when using such technology.

Basal body temperature assessment: is it useful to couples seeking pregnancy?

Advanced practice nurses in primary care settings are often asked to give appropriate advice to couples seeking pregnancy. This article examines the issue of basal body temperature (BBT), a time-honored way to establish the presence of ovulatory cycles, and asks if BBT is an outdated recommendation. The article also reviews the benefits and limitations of recommending BBT to couples seeking pregnancy in light of recent fecundity research.

Protocol for determining fertility while breastfeeding and not in cycles.

A protocol was developed and evaluated for nonovulating breastfeeding women to determine potential fertility with an electronic hormonal fertility monitor. The amount of required abstinence (i.e., days of potential fertility) through the first menstrual cycle indicated by the fertility monitor was significantly lower (17% of the total days) compared with the amount of abstinence (50% of the total days) indicated by the self-observation of cervical mucus.

Predicting menstrual migraine with a home-use fertility monitor.

A home-use fertility monitor was used to time perimenstrual prophylaxis in 27 women with menstrual or menstrually related migraine. Cycle length variability was mostly caused by follicular phase variability; the postovulatory luteal phase was relatively constant. The monitor accurately identified ovulation in >90% of cycles, enabling prediction of menstruation and precise timing of perimenstrual prophylaxis. Ninety-seven percent of women found the monitor useful in predicting menstrual migraine attacks.

Estimated maximum failure rates of cycle monitors using daily conception probabilities in the menstrual cycle.

BACKGROUND: A number of menstrual cycle monitors have been developed to detect the fertile window of the menstrual cycle, mainly for contraceptive purposes. Reliable data on most of these systems are still missing but are urgently needed because many women use them and the tested systems differ enormously in price and effectiveness. We suggest a new efficacy estimating method to evaluate cycle monitors prior to full prospective clinical trials. METHODS: Sixty-two women prospectively tested seven cycle monitors and the symptothermal method (STM) of natural family planning (NFP) but not more than two different systems at the same time. The clinical fertile window was determined by detecting the day of ovulation using daily urinary LH measurements and daily ultrasonic folliculometry. This was compared to the fertile phase predicted by the systems. Maximum failure rates were estimated for each cycle monitor and the STM, using the daily conception probability rates taken from the European Fecundability Study. Intercourse was assumed to occur on each of all falsely predicted days of infertility. RESULTS: Sixty-two women with a mean age of 31 years (range: 21-42 years) contributed a total of 122 cycles to this study. Monitors based on the microscopic evaluation of saliva or mucus had many more false infertile days than the other methods based on temperature or hormonal measurements (225 versus 42 days). The maximum unintended pregnancy rates per cycle for temperature computers were estimated to be 0.0134-0.0336, for the hormonal computer 0.1155 and for mini-microscopes 0.2313-0.2369. For the STM of NFP, there were no false infertile days. CONCLUSIONS: The STM of NFP proved to be the most effective contraceptive method to detect the fertile window among all the methods tested. The estimated efficacy of the other cycle monitors range from the temperature computers (upper level) to the hormonal computer (medium level) and the mini-microscopes with very low estimated contraceptive efficacy.

Hormonal monitoring of ovarian activity using the Ovarian Monitor, part I. Validation of home and laboratory results obtained during ovulatory cycles by comparison with radioimmunoassay.

A study was conducted to determine the accuracy and reliability of the Home Ovarian Monitor for measuring estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) during ovulatory cycles as a means of monitoring ovarian activity. Approximately 60 ovulating women in three centres collected timed specimens of urine (3h or more) for a total of six cycles each. The women measured the E1G and PdG excretion per 24h in their urine specimens using the Monitor. A local laboratory using the Monitor also measured the excretion. Urine specimens from 18 to 19 cycles were sent frozen to the WHO Reference Laboratory in London where they were analysed for E1G and PdG by the Monitor and by radioimmunoassay (RIA). The correlation coefficients between the Monitor and radioimmunoassay results obtained in London were better than 0.84 in 80% of the cycles. A urine bias caused the Monitor E1G results to be higher than those obtained by radioimmunoassay but the daily patterns were the same. In 50% of the cycles, this bias caused a delay of up to 3 days in identifying the beginning of the E1G rise compared with radioimmunoassay. Timing of the preovulatory E1G peak and the postovulatory PdG rise agreed within the experimental errors of the two systems. The study confirmed that women using the Monitor at home obtained results that were as accurate as those obtained by laboratory procedures. Careful supervision was required to maintain laboratory levels of quality control and interpretation of results.