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.

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.

[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.

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.

Menstrual cyclicity is predictably unpredictable.

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

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.

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.

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.

Ovulation prediction by monitoring salivary electrical resistance with the Cue Fertility Monitor.

The purpose of this study was to investigate the potential relationship between the salivary electrical resistance, as measured by the Cue Fertility Monitor, and the time of ovulation. Twenty-seven cycles in 18 volunteers were analyzed. A slight correlation could be demonstrated between the day of salivary electrical resistance peak and the day of luteinizing hormone (LH) peak. However, the changes in salivary electrical resistance values, arranged to the day of LH peak, were not statistically significant. The days of salivary electrical resistance peak in relation to the day of LH peak were not reproducible in individual women. The apparent relationship between the day of salivary electrical resistance peak and the day LH peak might be explained by the methodology used. It is concluded that measuring the salivary electrical resistance is of no use in predicting the day of ovulation.

Ovulation prediction by monitoring salivary and vaginal electrical resistance with the PEAK Ovulation Predictor.

We investigated the ability of the PEAK Ovulation Predictor to predict the expected date of ovulation in 21 infertile, spontaneously ovulating women. A nonsignificant correlation (R = 0.15; P = .51) existed between the predicted date of ovulation and the day of the serum LH peak. A moderately strong correlation (R = 0.61; P less than .01) was observed between the day of the salivary electrical resistance peak and that of the serum LH peak. However, the serum LH peak occurred between 4-9 days after an identified peak in salivary electrical resistance. Twice-daily urine LH testing correlated strongly with both the serum LH peak (R = 0.93; P = .0001) and the ultrasound-detected day of ovulation (R = 0.81; P = .0001). A statistically significant peak in the mean salivary or vaginal electrical resistance on a particular day relative to the day of the serum LH peak could not be demonstrated. When identified, the nadir in vaginal electrical resistance occurred no earlier than 2 days before the serum LH peak and thus may mark the endpoint of the fertile period for natural family planning methods. We conclude that, whereas the PEAK Ovulation Predictor is of little value in accurately predicting ovulation, measurements of salivary and vaginal electrical resistance may be helpful in timing inseminations. However, for detection of the serum LH surge, twice-daily urine LH testing demonstrated a stronger correlation and narrower frequency distribution than did those determinations based on electrical resistance.

A new method for predicting and confirming ovulation.

Evaluation of a method for predicting and confirming ovulation by measurement of vaginal and salivary electrical resistance (VER and SER) was the purpose of this study. Eighteen menstrual cycles from 13 subjects were analyzed. A clearly defined nadir in VER at day 0, the day of the luteinizing hormone (LH) peak, followed by a pronounced increase the following day was observed. A peak in SER was consistently observed 5 to 6 days before day 0. The correlation coefficient (r) between the cycle day of the SER peak and cycle day of the LH peak was 0.94. After the peak in SER, values were low for several days but increased 1 to 2 days before the LH peak. Results indicate that monitoring of SER and VER may provide the basis for a simple method for predicting and confirming ovulation.

Prediction of ovulation with the use of oral and vaginal electrical measurements during treatment with clomiphene citrate.

This study was undertaken to evaluate the usefulness of measuring salivary and vaginal electrical resistance in monitoring ovulation induced by clomiphene citrate (CC). Data from 28 cycles of 12 women treated with CC were compared with those of 18 cycles of 13 women who were ovulating spontaneously. Patterns of salivary readings in CC and spontaneous cycles were similar and showed a preovulatory peak 6.2 (mean) days before the luteinizing hormone peak. The trend in vaginal readings for CC cycles differed from that of spontaneous ovulations in that the values were depressed during and shortly after CC therapy. Occurrence of the periovulatory nadir and subsequent rise was common to both groups. The rise in vaginal readings CC cycles occurred within 24 hours of the luteinizing hormone peak in 88% of cases. Retrospective analysis showed that, based on this method, artificial insemination would have been timed appropriately in 25 of 27 cycles or in every cycle, depending on the protocol used. The results indicate that the method is equally useful for predicting and confirming ovulation in cycles in which CC was used to induce ovulation as it is in spontaneous cycles.

Evaluation of "Determine; The OvuTest" as a device for identifying optimal time for conception.

The device known as "Determine; The OvuTest" (Ventco Medical Trading Company, Montreal, Quebec, Canada) was appraised for its stated function of determining the optimal time for human conception by detecting the presence of the protein, uteroglobin (UTG), in cervical mucus. Twenty volunteers used the device daily through three cycles in which ovulation was indicated by rise in basal body temperature and/or elevated levels of luteinizing hormone. No correlation was found between the instrument readings and time of ovulation. When tested in vitro, it did not distinguish the presence of UTG. When vaginal flushings, containing cervical mucus, were analyzed for UTG by double immunodiffusion, no lines of precipitation were observed. We conclude that "Determine; The OvuTest" does not identify the approximate time of ovulation and therefore is not a reliable aid to conception. It does not detect UTG, and periovulation cervical mucus does not contain UTG.

Therapeutic donor insemination: the impact of insemination timing with the aid of a urinary luteinizing hormone immunoassay.

The records of 120 patients undergoing therapeutic donor insemination were reviewed to determine if the use of the enzyme immunoassay of urinary luteinizing hormone (LH) to plan inseminations decreased the number of cycles required to achieve conception. All inseminations were performed with fresh semen. Patients in group 1 (n = 26) utilized urinary LH testing in addition to basal body temperature (BBT) and cervical mucus examinations to time their inseminations, while inseminations in group 2 (n = 94) were timed with only BBT and cervical mucus examinations. The monthly fecundability of patients in group 1 was 0.13, whereas the monthly fecundability of patients in group 2 was 0.11. The mean number of inseminations was 1.4 and 1.6 per cycle for groups 1 and 2, respectively. There were no significant differences between groups 1 and 2 in regard to the number of cycles required to achieve conception. The use of a urinary LH immunoassay for insemination timing offers no benefit over conventional methods of timing (BBT, cervical mucus) when fresh donor semen is used.

Validity of the Bioself 110 fertility indicator.

The Bioself 110 (Bioself Canada, Inc., Montréal, Québec, Canada) is an electronic computerized thermometer designed to identify the fertile and infertile phases of the menstrual cycle. The purpose of this study was to evaluate the validity of the device by comparing it with a reference method, the Ovustick (Monoclonal Antibodies, Inc., Mountain View, CA) luteinizing hormone (LH) surge detection kit. The Bioself 110 identified the 6-day fertile period in 86.4% of 220 cycles studied and 5 fertile days in 93.2%. The Bioself 110 correctly identified the postovulatory infertile phase in 93.3% of 178 cycles. On average, the device identified 10.9 fertile days and 10.6 postovulatory "safe" days per cycle. It was concluded the device would be a useful aid to couples trying to conceive or prevent pregnancy.

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.

Correlation of Ovutron readings and the basal body temperature (BBT) with serum sex-hormone and luteinizing hormone levels.

Prior studies have produced conflicting results about whether a change in electric potential occurs at the time of ovulation. This study was undertaken to determine whether the Ovutron, a digital voltmeter which displays the sign and magnitude of voltage measured when the index fingers are applied to the electrodes, would produce a mix in polarity, some positive and some negative voltages, with 5 consecutive measurements preceding ovulation. This device was used daily in 10 normally ovulating women to determine whether such a mix in polarity occurred during the menstrual cycle and its relationship to the corresponding daily measurements of luteinizing hormone, total immunoreactive estrogen (IRE) and progesterone heralding and confirming ovulation. In addition, the Ovutron readings were compared to the basal body temperature (BBT) measurements. In 8 of 10 women studied with the Ovutron device, a mix in polarity was observed in 2 of 3 consecutive days preceding ovulation and was associated in all but 2 subjects with a 50 pg/ml/day incremental increase in IRE. By comparison, only 4 of the 10 subjects had a "classic" biphasic BBT curve. This novel device should be evaluated in a large group of women employing these and other additional parameters (e.g., ultrasonography) in order to determine its efficacy and whether it has a role in the treatment of infertility as well as contraception.

Evaluation of the Lady Free Biotester in determining the fertile period.

Small hand-held microscopes have been developed for self-observation of salivary ferning patterns to detect the fertile time of a woman's menstrual cycle. The purpose of this study was to evaluate one such microscope, the Lady Free Biotester, by comparing it with the self-observation of cervical-vaginal mucus and with the self-detection of luteinizing hormone (LH) in the urine. Twelve natural family planning teachers (average age 34.6 years) observed their cervical-vaginal mucus, tested their urine for LH, and observed salivary and cervical-vaginal mucus ferning patterns (with the Lady Free Biotester) for two menstrual cycles. Data indicated that there was a strong correlation between the LH in the urine and the peak in self-observed cervical-vaginal mucus ferning (r = 0.99, p < or = 0.001) and salivary ferning (r = 0.98, p < or = 0.001). However, it was difficult to assess the beginning and end of the fertile time based on the salivary ferning patterns. Further testing of salivary ferning patterns is recommended before widespread use of these devices for family planning.

PIP: Several small, hand-held microscopes have been developed and marketed for self-observation of ferning patterns in either saliva or cervical-vaginal mucus to detect the fertile period of a woman's menstrual cycle. This study evaluated the Lady Free Biotester microscope, which detects salivary ferning patterns, by comparing its performance with that of self-observation of cervical-vaginal mucus through the Creighton model vaginal discharge recording system and self-detection of luteinizing hormone (LH) in urine with an OvuQuick kit. 12 US natural family planning teachers (mean age, 36.7 years) practiced all three methods for two menstrual cycles. There was a strong correlation between urinary LH and the peak observed in cervical-vaginal mucus ferning (r = 0.99; p 0.001) and salivary ferning (r = 0.98; p 0.001). However, there was no discernible beginning or end to fertility as determined by salivary or cervical-vaginal ferning. In many cases, ferning days were found throughout the cycle. Until more definitive tests with salivary ferning patterns are conducted, it is recommended that the hand-held microscopes be used only in connection with other tested markers of fertility.

Contraceptive application of the Bioself fertility indicator.

The Bioself fertility indicator is a hand-held electronic device that combines the basal body temperature and calendar methods for planning or preventing pregnancy. A study was undertaken in three centers in the province of Québec, Canada, to evaluate the Bioself device as a contraceptive aid. Eighty-three women were recruited; they accumulated 745 cycles of use. Six unplanned pregnancies occurred from unprotected intercourse during the fertile phase of the cycle, as indicated by the Bioself device. The pregnancy rate was 9.02 per 100 women-years and the one-year discontinuation rate was 32.5%. The low pregnancy rate is attributed to the women's experience in natural family planning, reinforced, in 51% of the cycles, by protection from additional barrier methods. It was concluded that the Bioself device is an effective contraceptive aid for couples who are aware of the pros and cons of natural family planning and desire a noninvasive means of contraception.