R.J. Fehring and W.D. Schlaff, J. Nurse-Midwifery 43 (2), 117, 1998 Marquette University trial confirmed Turin results – this time with non-baseline subjects (as in real life). Ovulation kit indicates ovulation on 2 days (not just one!) and “Peak mucus” on yet another day – THAT IS NOT GOOD AT ALL ! Data showed superiority over ovulation kit and “Peak mucus” use. This example of non-baseline cyclic profile is from one of the patients at the Marquette NFP Clinic. It has the same features as those we have seen in the baseline cycles from the Turin study of baseline subjects. It also corroborates the evidence obtained in our in-house studies, including the case of a delay of ovulation with respect to the LH and the short-term predictive peak. The Marquette study included both women interested in NFP for birth-control as well those women who sought NFP as a conception aid because of difficulties in conceiving. The authors concluded that the “monitor has potential to be a very useful device to assist in fertility and infertility assessment, therapy, and family planning”. The Marquette study used the digital prototype, Mark 3, which subsequently received the FDA 510(k). The cycle in this example belongs into the category of irregular cycles, with delayed ovulation, further discussed in our white paper. Note also the inaccuracy of ovulation “detection” by the reference methods (the LH kit and Peak mucus). The LH was positive the day before as well as on the day of the ovulation marker (day 17), while the Peak mucus day indicated ovulation one day after the ovulation marker day. The Marquette study did not include ultrasound, which would have helped, and which will be included in our clinical trials. R.J. Fehring and W.D. Schlaff, J. Nurse-Midwifery 43 (2), 117, 1998

This is an example from real-life – not a baseline data from a laboratory See the unprecedented powerful diagnostic capability inherent in the bioZhena cyclic profile This is the long-term predictive peak And here the sensor detects delayed ovulation – in this case delayed by 2 days. No other product can do this for women at home -and for their physicians. The cyclic pattern exhibits a number of well defined peaks and troughs: … the first post-menstruation minimum (or trough, nadir) occurring typically on day 6, 7, or 8. The signal then rises to a maximum (long-term predictive peak), the highest level of the cycle. Over the next several days, the readings fall toward the minimum before the short-term predictive peak. In this cycle with a short luteal phase, which is a recognized gynecological problem, there is also a delay of ovulation. Instead of falling into the ovulation marker trough immediately after the short-term predictive peak, here it takes 3 days. This is the ovarian “I am ready” signal

Different peak sizes show the different speed of maturation of the egg in different menstrual cycles (maturation of dominant follicle) See the unprecedented wealth of information inherent in the bioZhena cyclic profile These are follicular waves preparing for the next cycle. The number of these waves indicates how fast the woman approaches menopause. The cyclic pattern exhibits a number of well defined peaks and troughs: … the first post-menstruation minimum (or trough, nadir) occurring typically on day 6, 7, or 8. The signal then rises to a maximum (long-term predictive peak), the highest level of the cycle. Over the next several days, the readings fall toward the minimum before the short-term predictive peak. Thus, in the recorded 30 days long cycle, the long-term predictive peak is 8 days wide. It is followed by the usually narrow short-term predictive peak, which falls off directly into the trough of the ovulation marker, the lowest reading of the cycle. We have found the ovulation-marker minimum to correlate with urinary LH and FSH peaks, and we view the marker to be an effect of the steroid hormone switch that occurs at ovulation (estrogen to progesterone). Note that the corresponding basal body temperature (BBT) curve rises, to the post-ovulatory high level, after the ovulation marker. This indicates, to the extent that the BBT can be relied on, that ovulation had, indeed, occurred. The planned sonographic (ultrasound) investigations will confirm this correlation with a better accuracy. Note that Dr. Benedetto carefully selected baseline subjects for the trial. Even in these baseline subjects, the classical BBT “biphasic profile” is very unreliable. The belated rise of the BBT3 curve (of the 27 years old subject) is clearly noticeable and symptomatic of the uncertainty inherent in the basal body temperature measurements. Ovulation is detected as estrogen control switches to progesterone control This is the ovarian “I am ready” signal

Ovulona’s diagnostic power will save infertility treatment money. Absence of the peaks anticipates failure to ovulate. Ovulona anticipates LPD = Luteal Phase Defect, which often causes failure to conceive – by normal healthy women Ovulona’s diagnostic power will save infertility treatment money. This cannot be matched by ovulation kits or by any other such product. LPD is a well-known problem that often causes failure to conceive by normal healthy women. It is known to be due to the failure to produce the dominant follicle. The Ovulona apparently detects this by the absence of the preovulatory peaks (where the long-term predicitve peak is driven by the maturation of the dominant follicle). Until now, the LPD condition could only be detected too late, by the distortion in the BBT temperature profile, which in LPD shows a collapse instead of the usual elevated temperature plato, normally associated with the occurrence of ovulation.

from proof of concept study Three baseline subjects’ data from trial performed by Gynecologist Clara Benedetto, MD at 1st Gynecology Clinic, University of Turin, Italy Baseline cyclic profiles from proof of concept study The cyclic pattern exhibits a number of well defined peaks and troughs: … the first post-menstruation minimum (or trough, nadir) occurring typically on day 6, 7, or 8. The signal then rises to a maximum (long-term predictive peak), the highest level of the cycle. Over the next several days, the readings fall toward the minimum before the short-term predictive peak. Thus, in the recorded 30 days long cycle, the long-term predictive peak is 8 days wide. It is followed by the usually narrow short-term predictive peak, which falls off directly into the trough of the ovulation marker, the lowest reading of the cycle. We have found the ovulation-marker minimum to correlate with urinary LH and FSH peaks, and we view the marker to be an effect of the steroid hormone switch that occurs at ovulation (estrogen to progesterone). Note that the corresponding basal body temperature (BBT) curve rises, to the post-ovulatory high level, after the ovulation marker. This indicates, to the extent that the BBT can be relied on, that ovulation had, indeed, occurred. The planned sonographic (ultrasound) investigations will confirm this correlation with a better accuracy. Note that Dr. Benedetto carefully selected baseline subjects for the trial. Even in these baseline subjects, the classical BBT “biphasic profile” is very unreliable. The belated rise of the BBT3 curve (of the 27 years old subject) is clearly noticeable and symptomatic of the uncertainty inherent in the basal body temperature measurements.