Ovulatory dysfunction

The ovulatory dysfunction obgyn specialist’s concerns:

‘Ovulatory dysfunction’ bears the imprimatur of a succinct medical diagnosis, but what does it really mean and above all, how do you diagnose it, especially in women with a normal menstrual history?

Although we have multiple measures in our modern toolbox: ultrasound for daily follicular monitoring, hormonal assays of serum, urine and saliva (some for instance LH available over the counter to our patients), and even, heaven forbid, an endometrial biopsy; these are expensive, invasive and labor intensive for both physician and patient to document, and often lacking in evidence-based cutoffs.

We are likely to assume that a woman is ovulating regularly if her menstrual cycle length is 21–35 days (thanks to classic studies of Treolar et al. (1967) which were based on menstrual diaries collected on the back of a postcard, beginning in young women recruited during their college years and then collected over their lifetimes)… but what does it really mean and above all, how do you diagnose it…?

This is cited from “The quality of ovulation is strained in normal women” by Richard S. Legro, Human Reproduction, Vol.28, No.6 pp. 1446–1447, 2013. Read the editorial at https://academic.oup.com/humrep/article/28/6/1446/604215/The-quality-of-ovulation-is-strained-in-normal

The bioZhena answer (and my imprimatur) is this: You diagnose it with the help of bioZhena’s menstrual cycle ovulographic^TM profiling, the menstrual cycle signature  profiles recorded longitudinally at home. Also referred to as the technology of Folliculogenesis In Vivo^TM.

And the thought is this: You do not just assume, in evidence-based medicine. That is why we bring the technique of diagnostic-information rich cyclic profiles recorded longitudinally by women at home.

I am referring here to Richard Legro having written further: The bottom line is that the most common clinical practice to screen for ovulatory dysfunction is a menstrual history. Much of our knowledge of the normal length of the menstrual cycle and the effects of age on the menstrual cycle comes from the classic studies of Treloar et al. (1967) … We are likely to assume that a woman is ovulating regularly if her menstrual cycle length is 21–35 days (thanks to Treloar).

But then let’s ponder on this:

Here is a good example of cycle length variability of a woman who charted over a hundred of her menstrual cycles: Fig. 1 in Biostat (2010) http://biostatistics.oxfordjournals.org/content/11/4/741.full

Dr. Legro discussed the diagnostic difficulties and concluded his editorial by referring to the expert panel from the recent NIH sponsored Evidence-Based Methodology Workshop on PCOS that recommended in their final report to ‘Improve the methods and criteria used to assess ovulatory dysfunction’

(http://prevention.nih.gov/workshops/2012/pcos/docs/PCOS_Final_Statement.pdf).

He wrote: I concur, though like them I am lacking in a specific test or method.

bioZhena’s Folliculogenesis In Vivo^TM (FIV^TM) provides the needed method.

Our FIV technology tracks the menstrual cycle folliculogenesis mechanism via the end-organ effect of the brain-ovary feedback interactions on the uterine cervix.

Folliculogenesis-In-Vivo tracks the end-organ effects of brain – ovary interactions; it works with cycles challenged by asynchrony of brain and ovarian pacemakers, which hinders ovulation. Folliculogenesis is not merely a process involving hormonal signals – it is a process of integration of all neuroendocrinological inputs, which the cervix monitors. And the Ovulona^TM (and prospectively the telemetric Halo™ cervical ring) monitors the cervix.

Here we show the menstrual cycle profile data generated by our core product, the Ovulona^TM, the data to be provided to the user’s physician via the Ovulograph^TM.

For better legibility of the contents, view and hear three slides at https://biozhena.files.wordpress.com/2018/02/wealth-of-info-elucidation-3-animated-slides-2-narrated.pps

Or click on the composite image to bring up three slides in PDF format via this link: https://biozhena.files.wordpress.com/2019/01/ovulona-anticipates-and-detects-ovulation-3-slides.pdf

For the left-side part of the image, click: https://biozhena.files.wordpress.com/2018/03/ovulona-from-startup-version-to-cervical-ring-implementation.pps

For the right-hand side part, click: https://biozhena.files.wordpress.com/2007/12/hypothalamus-p-g-feedback-and-innervation-panorama.jpg

The monitored menstrual cyclic pattern exhibits a number of well defined peaks and troughs, with the first post-menstruation minimum (or trough, nadir) occurring typically on day 6, 7, or 8. The signal then rises usually over several days to a maximum (the long-term predictive peak), the highest reading of the cycle. Over the next several days, the readings fall toward the minimum before the short-term predictive peak (predictive of imminent ovulation).

Thus, in the shown 30 days long cycle, the long-term predictive peak is 8 days wide. It is followed by the usually narrow short-term predictive peak (3 days wide in  unperturbed baseline cycles), 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 dominance switch that occurs at ovulation (estrogen dominance to progesterone dominance).

Note that the corresponding basal body temperature (BBT) curve rises to the post-ovulatory higher 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.

It was important that Dr. Benedetto carefully selected baseline subjects for the independent pilot trial (at the First Gynecology Clinic, University of Turin, Italy). Even in these baseline subjects, the classical BBT “biphasic profile” is unreliable. The belated rise of the BBT3 curve (the data points of the 27 years old subject) is clearly noticeable (see slide 2 of 3 in the above-shown  https://biozhena.files.wordpress.com/2019/01/ovulona-anticipates-and-detects-ovulation-3-slides.pdf), and it is symptomatic of the uncertainty inherent in the basal body temperature measurements (because the BBT responds also to other variables besides ovulation).

Click on the image to view the slide

How the features of the menstrual cyclic profile relate to folliculogenesis is explained in slide 3 of the Friendly Technology – Wealth of Information slide set (https://biozhena.files.wordpress.com/2017/02/friendly-technology-wealth-of-information-510k-vltava-fda-nih-e.pps), and more details about the tracking of the dominant follicle are explained in the slide at https://biozhena.files.wordpress.com/2017/02/wealth-of-info-elucidation-of-domin-folli-peak-single-slide.pps (see the clickable image just above).

Now read this: How the Ovulona will help physicians to better help their patients (and there is of course more, such as the management of anovulation, with prevalence of over 30% of “clinically normal menstrual cycles”, often associated with infertility and the related ills):

Click on the image to view the PDF slide page with clickable links: https://biozhena.files.wordpress.com/2019/01/Single-slide-How-the-Ovulona-will-help-physicians.pdf

Our resolve to deliver on this promise was expressed in a now-lost tweet, which too referenced and paraphrased Dr. Legro’s concluding line (…let the advice of Antonio, the Merchant of Venice, guide our investigative efforts: ‘My ventures are not in one bottom trusted, nor to one place’):

Not Merchant of Venice, bioZhena’s ventures ARE in one bottom trusted, ARE to one place.

Ovulona’s first guinea pig, meet the Bard’s first love!  🙂 A facetious reference to the first tester of the proto-Ovulona without whom none of this would have come about…

Anne Whateley by Giovanni Antonio Boltraffio (Italian High Renaissance painter, ca.1466-1516)

(Anne Whateley, Shakespeare’s First Love. Not his wife, Anne Hathaway, “who married the Bard after he got her pregnant and eventually got a second-best bed in his will in return, a sure sign of spite.”)