Posts Tagged ‘Ovulona’

About the EDD and/or EDC issue, and a request for input from readers

January 11, 2008

EDD stands for Estimated Date of Delivery, while EDC stands for Estimated Date of Confinement (the time of going to hospital for the delivery, “the lying-in of a woman in childbed“).

Seasonality of Google Searches Bears Out These Thoughts And Plans

August and July, October and/or September are the months of the season of most births in the U.S. And Mums-To-Be are rather anxious about the timing of the pregnancy-to-birthing process, gestation.

Just see how, well ahead of the upcoming birth time, the interest in the search term “gestation” peaks every year in April, give or take a month. You can see it at https://www.google.com/trends/explore?date=2004-12-31%202017-01-18&geo=US&q=gestation (search terms: United States, 12/31/04 – 1/18/17, All categories, Web Search). I’ll expand on the seasonality aspect below, after I share some thoughts and plans.

The bioZhena thinking, in one brief sentence, is this: Aim to replace stochastic with deterministic, which is the purpose of our eukairosicTM diagnostic tools. Then the E in EDD and EDC will stand for EXPECTED.

‘Expected’ based on a measured data based computation, as opposed to a subjective recall based physician’s guess. Because, as I say in the very last sentence at the end of this article: Your approaching EDD and EDC are not normalized/relative like those in the statistical graph …

The medical position on the current status of obstetrics can be characterized by the following two papers.

1) Theory of obstetrics: an epidemiologic framework for justifying medically indicated early delivery

[BMC Pregnancy Childbirth. 2007 Mar 28;7:4. Joseph KS, Perinatal Epidemiology Research Unit, Department of Obstetrics & Gynaecology, Dalhousie University, Halifax, Nova Scotia, Canada]

QUOTE: Modern obstetrics is faced with a serious paradox. Obstetric practice is becoming increasingly interventionist … Whereas … mortality declines exponentially with increasing gestational duration, temporal increases in medically indicated labour induction and cesarean delivery have resulted in rising rates of preterm birth and declining rates of post-term birth. … [This] provides a theoretical justification for medically indicated early delivery and reconciles the contemporary divide between obstetric theory and obstetric practice. END QUOTE.

And 2) A re-look at the duration of human pregnancy

[Singapore Med J. 2006 Dec;47(12):1044-8. Bhat RA and Kushtagi P, Department of Obstetrics and Gynaecology, Kasturba Medical College, Manipal, India]

QUOTE: The duration of human pregnancy is arbitrarily taken as 280 days (40 weeks). Foetuses are considered to be at high risk once pregnancy goes beyond the expected date of confinement. … Conclusion: Mean gestational age at the onset of labour for women native to the area of study was 272 days (standard deviation 9 days). Pregnancies beyond a duration of 280 days showed significantly increased perinatal morbidity. It is suggested that there is a need for determining the length of gestation and to compile gestation-wise incidence of … neonatal morbidity indicators for different populations. END QUOTE.

Related medical publications are here.

I will rely on the birthing specialist, Janelle Durham, to verbalize for you the status quo in this aspect of the homo sapiens experience – below. First,

Gestation Period, Gestational Age and OvulonaTM

Per Encyclopedia of Childhood and Adolescence, article Gestation Period and Gestational Age ,

” a gestation period of thirty-eight weeks (266 days) is calculated for women who are pregnant by a procedure such as in vitro fertilization or artificial insemination that allows them to know their exact date of conception.”

The Ovulona women’s healthcare and self-care device from bioZhena will provide to the woman user a very simple means to record the day of any intercourse as a part of her record of the menstrual cyclic profile. In every cycle, whether pregnancy is planned or not. This must become a part of the routine. The information will be electronically recorded along with the daily or almost-daily measurement data inherent in the use of the Ovulona.

With that menstrual cycling history data, this intercourse-timing information will be available for use by the woman’s physician(s). And in due course (contingent on funding) the cervical ring transformation of the Ovulona will remove the need for daily insertion…

Therefore, the routine use of the Ovulona (and of the internally worn HaloTM cervical ring) will provide for an equivalent of the above-referenced 38-week (266 days) calculation available to the women receiving IVF or artificial insemination. This alone should be an improvement on the current way of EDD/EDC assessment. In this context, an investigation should be undertaken into the question of whether any inference can be drawn from the woman’s menstrual cycle history prior to the conceptive (baby-making) intercourse.

Any comments on this would be welcome, even about anecdotal or subjective or tentative observations that may be available. However non-scientific, however tentative, however uncertain an individual answer or input from you may be…

Questions

Questions such as: What evidence is available in medical literature (or maybe in unpublished records?) about the outcomes of the IVF or artificial insemination pregnancies, i.e. about their documented gestation periods? Does the 38 weeks projection work? Always? If not always, can anything be correlated with any deviation?

Has anyone looked at whether there may be an effect of geography in terms of hot vs. cold climate on gestation periods of natives? And perhaps even at whether a gestation-period difference may arise in data at a well-selected locale between winter and summer deliveries (of course only natural, not “medically indicated early deliveries”)?

The complicating effect of first versus subsequent pregnancy has already been noted, of course… That evidence exists for gestational length variability with ethnicity (or race) has been noted, too:

“122,415 nulliparous women with singleton live fetuses at the time of spontaneous labour, giving birth in the former North West Thames Health Region, London, UK. Results: The median gestational age at delivery was 39 weeks in Blacks and Asians and 40 weeks in white Europeans.” [International Journal of Epidemiology 2004, Volume 33, Number 1, pp. 107-113 ].

I am happy to observe that this outcome is not counter-intuitive (because women with ancestors in hot climates seem to tend to shorter gestational age at delivery than those who can be presumed to originate from colder climate conditions).

Conceivably, such a preliminary info, which I am after here, is not forthcoming — and we shall have to try and gather even these preliminary data in a systematic manner when the time comes, but no question asked, nothing learned… Public or private input would be appreciated. (I wrote this request here in 2008.)

Although focused on the very serious complication in pregnancy, A Balancing Act: Ideal Delivery Timing & Chronic Hypertension by Eva Martin, MD is an example of the kind of information that we will need when setting out to start the adaptation of our technology to the challenge of assessing and managing EDD/EDC. Retweeting her piece, I tweeted in April 2017: This is why when the monitoring will better assess EDD/EDC >abandon old Naegele rule.

Dr. Martin has a few videos online on the subject of due dates, and here is one of them (~2 minutes): How to Calculate Your Due Date After A.R.T. –  https://www.youtube.com/watch?v=G4OCSwxTEIg  (in a nutshell: Fertilization + 266 days [38 weeks] as we already noted above, with reference to the Encyclopedia of Childhood and Adolescence).

There in any case does seem to be some, perhaps fairly good, basis for this attempt at a preparation for an introduction of a tool for definitive assessment of EDD and EDC.

Due Dates Paper by Ms. Durham

According to the due dates paper by Janelle Durham, written for Certification with Birth Education in January, 2002 , QUOTE: “some women are aware of when they ovulate, either based on formal methods and record-keeping such as daily temperature checks, or on physical symptoms such as mild pain upon ovulation, or observation of changes in vaginal mucus. Many women know the dates when conception was possible, because they know the dates when they had intercourse during their most recent menstrual cycle.

Due dates can be calculated based on these dates, but many physicians prefer to calculate it from date of last menstrual period. They may only calculate from conception date if conception was medically managed and supervised through techniques such as artificial insemination.

Based on date of last normal menstrual period.

Due dates are typically calculated based upon the date the last menstrual period began, according to the mother’s report. Naegele’s rule assumes that ovulation occurred 14 days after LMP, which is only the case for women with 28 day cycles. Some caregivers will ask their patients for a history of menstrual cycles so that they can adjust this number, as appropriate, for cycles of different lengths or irregular cycles.

It’s also important to consider: recent use of oral contraceptives, and their possible effect on ovulation date; inaccurate memory about when the last period occurred, the possibility of interpreting post-conception ‘spotting’ as a light period, and unrecognized pregnancy losses. These issues all complicate due date prediction, and it’s estimated that nearly 25% of infants who would be classified as preterm birth on the basis of the last normal menstrual period are not preterm. (Cited in Health Canada)” END QUOTE.

At this point, let me translate the one brief sentence I wrote at the top into a less specialist language. Ms. Durham shows a statistical distribution of gestation periods applicable to any woman, and that is the approach I labeled stochastic, because of its statistical nature. I admit, the word is harking back to the days of my postgrad phys chem endeavors, which were mostly endeavours at the time. 🙂 We could also say, probabilistic – two syllables longer, though!

Gestational Age at Birth vs. Weeks since LMP

http://transitiontoparenthood.com/ttp/birthed/duedatespaper.htm

Janelle Durham, for Certification with Birth Education NW. January, 2002.

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Our Goal – Your Comments

With our eurokairosicTM diagnostic tools, we generally aim to determine the right time, and in the case at hand we propose to provide for a much less fuzzy assessment of the EDD and EDC. After all, precedent exists in the A.R.T. arena, and prerequisites, too, to some extent at least.

In a nutshell: Let’s replace the LMP/Naegele-based approach with a hard data-based technique, applied to each and by each Mom individually.

Again, your comments on and/or answers to the questions above would be useful. Public or private input would be appreciated. [Private to: vaclav@biozhena.com please.]

In any case, for more on this topic see a related post published on December 8, 2010: Saint Nicholas Day, his legend, and our modern day’s prematurity, EDD calculation, gestational age, problem with LMP. We show there data from a study of more than 24.5 thousand pregnancies demonstrating that “most (71.5%) inductions done post-term (> 294 days) according to LMP dates were not post-term if ultrasound scan dates alone are used to calculate the gestational age.”

Vision

It is perfectly reasonable a vision that, in future, an expectant mother’s EDD and/or EDC will be assessed based on her folliculogenesis in vivo (FIV™) data which will include the electronic record of every sexual intercourse. The EDD/EDC will be computed automatically and provided by her own Ovulona Smart Sensor™.

So that, for example, a woman in and native to (or perhaps with ancestry from) a hot climate region might automatically obtain her EDD of 39 weeks when she electronically registers her day of intercourse on her Ovulona. Versus 40 weeks for a white European, consistent with the knowledge base noted above and assuming its validation.

No more uncertainties as in the LMP-based estimation. The bell-shape curve of distribution (such as the Janelle Durham graph above) will be replaced by personalized specifics.

Seasonality of EDC Searches on Google

On June 1, 2015 (at about the time of the year when, statistically, most American expectant mothers are about the last trimester away from their Estimated Date of Delivery and of Confinement) I add the following illustration. It appears to suggest why in May and June each year for the last 6 years there is always a noticeable increase in the viewing statistic of this blog post that you are reading. The interest in the subject of the due dates is up.

Seasonality of Search Google Trends for search term “EDC” 2009 - 2015

See the image better as Single slide – Google Trends for EDC Search 2009 – 2015 e

Check the trend for yourself by moving from the screen shot image to the actual graph online via the link http://v.gd/c2MOyR i.e. http://www.google.com/trends/explore#cat=0-45&q=edc&geo=US&date=1%2F2009%2078m&cmpt=q&tz= . Once online, the Google graph shows (with cursor put on data for different months) the counts of US searches for EDC in the different months. You can change the range of the time period via the Time button, and the country of interest via the Country button. The numbers represent search interest relative to the highest point on the chart. At the time of writing this, it was the number of searches in June 2014 (assigned the maximal relative value of 100).

Move the cursor along the graph to see the values for other months within the examined period. You’ll see the EDC value of 100 in June 2014; in June 2013 the US peak was at 72 counts. The worldwide trend is much like the US trend because the statistics are driven by the overwhelming majority of American searches. E.g. the May 2015 count worldwide is only higher by 7 more searches than the US value of 48; in June 2014 the worldwide count was the same 100 as the US while in June 2013 the worldwide count was 20 counts higher than the US count of 65.

That’s as of June 3, 2015. Might this change later? Well, click http://www.google.com/trends/explore#cat=0-45&q=edc&geo=US&date=1%2F2009%2082m&cmpt=q&tz=Etc%2FGMT%2B6 and see the graph as of September 12, 2015, which does show the June 2015 peak indubitably.

The worldwide count can be obtained via the Country button on the Explore bar in Google Trends (USA was selected here). The data are normalized, relative numbers – you can read up on it… It’s a Google algorithm.

And here now is a January 6, 2017 update of the Google Trends EDC results, showing that the June peak (in search activity for EDC) continues to be there; in June 2016 it stood at 88 while in June 2015 it was 89, as found by placing the cursor on the peak in the online graph (only one data point can be screen-printed as in the image here) – the URL is below the image:

google-trends-edc-12-31-08-to-12-31-16

https://www.google.com/trends/explore?cat=45&date=2008-12-31%202016-12-31&geo=US&q=edc

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Dear Reader,

Your approaching EDD and EDC – if indeed their coming up is the reason why you are reading this – are not normalized or relative values like those in the statistical graph

— and good luck, all the best from bioZhena!

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Parturition means birthing (birth) and dystocia a difficult one

January 9, 2008

And what is a parturition alarm?

For these and other entries, see the Alphabet of bioZhena at

https://biozhena.wordpress.com/2007/11/28/the-alphabet-of-biozhena/

Parturition alarm:

This is a concept that has to do with the need to know when labor or delivery is beginning, because the birthing female may be in need of help.

At the time of writing the first Alphabet draft more than five years ago, an Internet search produced only one such technology, a pressure-sensing girth, suitable for the horse breeder only, because it utilizes the fact that the horse mare lies on her side only in the process of parturition. To illustrate, we borrow a nice picture from a more recent publication found in today’s search on parturition alarm, which search still shows a preponderance of equine innovations:

Equine birth alarm

In the originally noted publication, reference was made to some other method that would detect the emergence of the amniotic sac or of the foal from the vulva (vaginal orifice) but that was not a satisfactory solution. In the horse-breeding arena, about 5-6% of births require help. Various approaches to the birth alarm solution have been attempted.

These days, there are quite a few patents etc. found in the parturition alarm search. And even 5 years ago, a patent from New Mexico University should have been found because their intra-vaginal parturition alarm patent (basically for cows) was published in 1987.

In human obstetrics, where most births take place in hospitals, determining the right time of confinement would be very beneficial. bioZhena (and/or its sister company, bioPecus) will investigate our vaginal sensor technology – suitably modified – with a view to developing a parturition alarm applicable to any mammal.

Also relevant in this context is the implication of the Ovulona making available the menstrual cycle (folliculogenesis) data over many months or cycles before conception. This will enable a more accurate anticipation of the EDD, Expected Date of Delivery. You will understand this better below, under Parturition. I highly recommend that you check out Figuring Your Due Date, too – from the Midwife Archives.

Let us put it this way: Since this is the bioZhena blog (and not bioPecus, for veterinary tools), the EDD issue must be addressed first, before any parturition alarm developments. Because we are primarily concerned with the Rerum Naturare Feminina.

And it would still be of great interest to hear from an expert Latinist about the correct way of saying this in plural, the Natural Thing of Women, the Women’s Natural Thing…

This being a reference to /2007/12/16/cervix-uteri-and-seven-or-eight-related-things/ .

Parturition:

The process of giving birth; childbirth. [From Late Latin parturitio, from Latin parturitus, past participle of parturire, to be in labor.]

Parturition is illustrated at http://www.mhhe.com/biosci/esp/2001_saladin/folder_structure/re/m2/s5/ .

The illustration’s legend indicates that physicians usually calculate the gestation period (length of the pregnancy) as 280 days: 40 weeks or 10 lunar months from the last menstrual period (LMP) to the date of confinement, which is the estimated date of delivery of the infant [EDD].

Indubitably, due dates are a little-understood concept:

“Truth is, even if you know the exact date when you ovulated, you still can only estimate the baby’s unique gestational cycle to about plus or minus two weeks” [ http://www.gentlebirth.org/archives/dueDates.html ]. Why should that be? Because of the variability of your menstrual cycle lengths? (They vary even if you do not think so).

Statistically, the gestation time for human babies has a mean of 278 days and a standard deviation of 12 days, an uncomfortably large spread. The old Naegele Rule of a 40-week pregnancy was invented by a Bible-inspired botanist Harmanni Boerhaave in 1744 and later promoted by Franz Naegele in 1812. It is still believed to work fairly well as a rule of thumb for many pregnancies. However, the rule of thumb also suggests: “If your menstrual cycles are about 28 days, quite regular, and this is not your first child, your physician’s dating is probably fine. If your cycles are longer or irregular, or if this is your first child, the due date your physician has given you may be off, setting you up for all kinds of problems” (induction, interventions, C-section among them).

This is where the bioZhena technology can be expected to provide help, making it possible to reckon the EDD with recorded menstrual cycle (folliculogenesis history) data rather than merely with the LMP + 280 days. This, once properly researched, may be expected to have a significant impact on obstetric management. — Any comments?

It is ironic that, in this age of technological medicine, American women worry about their birthing process not being allowed to take its own natural course on account of an ancient method of predicting the EDD.

Ironically, the 40 week dogma – which is the gestational counterpart of the unacceptable calendar method of birth control (the so-called “Vatican roulette”) – does not reconcile the 295+ days of the 10 lunar months; and yet, at the same time, the U.S. has an unusually high perinatal death rate, resulting from high statistics of too early (preterm) labor. Quid agitur? See also under Gestation.

Dystocia or birthing difficulty:

Dystocia is difficult delivery, difficult parturition. From Latin dys-, bad, from Greek dus-, ill, hard + Greek tokos, delivery. Calf losses at birth result in a major reduction in the net calf crop. Data show that 60% of these losses are due to dystocia (defined as delayed and difficult birth) and at least 50% of these calf deaths could be prevented by timely obstetrical assistance. The USDA web site http://larrl.ars.usda.gov/physiology_history.htm is apparently no longer there but when it was it indicated that an electronic calving monitor was being developed to determine maternal and fetal stress during calving. These studies are important since they are leading the way for developing methods to reduce the $800 million calf and cow loss that occurs each year at calving in the USA’s beef herds.

In analogy with the superiority of in vivo monitoring of folliculogenesis versus tracking behavioral estrus (heat), in vivo monitoring of the progress towards parturition must be a priori a more promising approach.

The telemetric version of the BioMeter – the animal version of the Ovulona technology – will hopefully provide a tool for these efforts. Once tested on animals, human use will be a logical extension of the endeavor. (Or endeavour, should it take place in Europe! Smiley…)

Comment about the EDD and/or EDC issue, and request for input:

Again, EDD stands for Estimated Day of Delivery, while EDC stands for Estimated Day of Confinement.

Per Encyclopedia of Childhood and Adolescence, article Gestation Period and Gestational Age [ http://findarticles.com/p/articles/mi_g2602/is_0002/ai_2602000272 ], ” a gestation period of thirty-eight weeks (266 days) is calculated for women who are pregnant by a procedure such as in vitro fertilization or artificial insemination that allows them to know their exact date of conception.”

The Ovulona device from bioZhena will provide to the woman user a very simple means to record the day of any intercourse. In every cycle, whether pregnancy is planned or not. This must become a part of the routine. The information will be electronically recorded along with the daily or almost-daily measurement data inherent in the use of the Ovulona. With that menstrual cycling history data, this intercourse-timing information will be available for optional use by the woman’s physician(s).

Therefore, the routine use of the Ovulona will provide for an equivalent of the above-referenced 38-week (266 days) calculation available to the women receiving IVF or artificial insemination.

This alone should be an improvement on the current way of EDD/EDC assessment.

In addition, an investigation should be undertaken into the question of whether any inference can be drawn from the woman’s menstrual cycle history prior to the conceptive intercourse. Any comments on this would be welcome, even about anecdotal or subjective or tentative observations that may be available already. However non-scientific, however tentative, however uncertain an individual answer or input from you may be…

E.g., do women with more or less regular cycles tend to exhibit a regular gestation period, and vice versa?

And, certainly, what evidence is available in medical literature (or maybe in unpublished records?) about the outcomes of the IVF and/or artificial insemination pregnancies, i.e., about their documented gestation periods? Does the 38 weeks projection work? Always? If not always, can anything be correlated with any deviation?

Do women with distinctly irregular menstrual cycles tend to have non-regular gestation periods?

The complicating effect of first versus subsequent pregnancy has already been noted, of course…

Conceivably, there is no such preliminary info available, and we shall have to try and gather even these preliminary data in a systematic manner, but – no question asked, nothing learned… Public or private input would be appreciated.

Birthday, and how it relates to the bioZhena enterprise – eukairosic™ diagnostic tools

December 28, 2007

Today is a major anniversary related to the bioZhena enterprise. Namely, a round-number (and not small) birthday of the offspring whose begetting had much, if not everything, to do with the inception of the project.

The biologically educated member of the would-be parental team insisted that medical help would have to be the very last resort, as she did not wish to be poked in and subjected to the various medical procedures available in the country of the proud Albion (that, alas, no longer ruled the waves!), where this awakening was going on. The image of what she resented getting into is telling, and it’s not even the whole story.

Woman in stirups sketch

Awakening on the part of said couple, who till then took steps to minimize or theoretically avoid getting in the family way, owing to circumstances. As in too many instances the world over, the “awakening” was left until somewhat too late. I do not wish to talk about age specifics, but you probably know that particularly female fertility (more accurately put, fecundity or fecundability) decreases starting around or even before the Christ’s age, and so – in retrospect – it was no great surprise to find that achieving pregnancy was not as simple as expected. At the time, actually, this was a great surprise…

At the time, yours truly was not an expert in the field that deals with certain practicalities of the most important aspect of life, by which many of us mean procreation, reproduction, and its management. I am referring to some insight into the practicalities on the female side of things procreative, which insight was not there at the time – but the better half knew the basic fundamental that I now delight in referencing as eukairosic.

In a nutshell, the word refers to the right time, opportune time – exactly what we are about the strategic or “right time; the opportune point of time at which something should be done.” A window of opportunity is kairos time.

For more about this, the Wikipedia article can be recommended, at http://en.wikipedia.org/wiki/Kairos . Let’s cite: Kairos (καιρός) is an ancient Greek word meaning the “right or opportune moment,” or “God’s time” [sic; thus said – but this should say “gods’ time”]. The ancient Greeks had many gods, and two words for time, chronos and kairos. While the former refers to chronological or sequential time, the latter signifies “a time in between”, a moment of undetermined period of time in which “something” special happens. What the special something is depends on who is using the word. END QUOTE.

If you visit that article, you will probably understand why I would like to look at the possibility of adopting as our company logo QUOTE a monochrome fresco by Mantegna at Palazzo Ducale in Mantua (about 1510 C.E.) that shows a female Kairos (most probably Occasio)… UNQUOTE.

You will also appreciate that, since we are not theologians, and because “eu-“ is the Greek prefix meaning well or good or true or easy, my choice of the adjective that we want to trademark as descriptive of bioZhena’s wares is eukairosic™.

And so here, for the sake of accurate definition, is one other item from The Alphabet of bioZhena – /2007/11/28/the-alphabet-of-biozhena/

Fecundability and fecundity:

Fecundability is the probability of achieving pregnancy within one menstrual cycle – about 20% or maybe 25% in normal couples [sic; the probability depends on many factors, including age – vide infra, or see below].

Fecundity is the ability to achieve a live birth.

Fecundability is strongly influenced by the age of the partners, and it is maximal at about age 24. There is a slight decline at ages 24 – 30, and a rapid decline after age 30.

The words are derived from Latin fecundus, fecund, from the root of fetus, via Old French fecond. Fecund means fruitful in children, or prolific.

As for the eukairosic diagnostic tools, their utility goes beyond reproductive management. Due to folliculogenesis (menstrual cycling), even things such as administration of medications or certain diagnostic examinations must be performed at the right time within the menstrual cycle…

Scire quod sciendum

fecundoscitus!!! 🙂

Thus spoke the exegete and father of Barnaby and Petrushka, Vaclav Kirsner © 2007

 ‘To know what is to be known’.

What is the mechanism of stress, and how does it affect reproduction?

December 27, 2007
“When pushed too far, subfertility occurs”
Here is an ad hoc selection of a few abstracts from my files on psychoneuroimmunoendocrinology papers addressing ovulation, reproduction (folliculogenesis).

Abstracts of ad hoc selected papers about stress in reproductive physiology:

What is the mechanism of stress, and how does it affect reproduction?

The first few are representative of animal work, and then several abstracts represent the literature on stress in the human female. In between, let’s display our cyclic profile data on a non-baseline menstrual cycle with delayed ovulation. This record illustrates how our OvulonaTM device can detect the effect of stress on the course of the menstrual cycle. Non-baseline refers to any real-life female with all the stressors of our daily life, no baseline simplifications of conditions such as we need to try and approach what we would call ideality (at least in physical science we would…).

Should these abstracts turn out to be too stressful, then you may perhaps enjoy better another selection I just came across, Introduction to psychoneuroendocrinology volume: is there a neurobiology of love? http://cogweb.ucla.edu/Abstracts/NeuroLove_98.html

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Highlights:

possible pathway in the regulation of ovulation – stria terminalis to the amygdaloid complex in the monkey (Macaca fascicularis) – J Physiol. 1977

Characteristics of a ventral tract from the bed nucleus of the stria terminalis (BST) to the amygdaloid complex

from BST to the amygdala, and, since the neurones of BST contain estradiol, … this tract may be involved in the regulation of ovulation.

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New data on serotoninergic mechanisms in ovulation in the cyclic female rat – C R Seances Soc Biol Fil. 1979

These results provide support to the specificity of action of serotonin in the control of ovulation in the cyclic rat. They also suggest an interaction of serotonin and oestrogens in this control.

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the hypothalamo-pituitary-gonadal axis in the female rhesus monkey. – Ann N Y Acad Sci. 1993
inhibit the GnRH pulse generator

acute decrease in LH and FSH secretion.

This decrease in gonadotropin release may explain the deleterious effects of stress on the menstrual cycle. However, an acute decrease in gonadotropins following activation of the adrenal axis is not observed in the presence of estradiol.

Thus, during the menstrual cycle, a relative protection against the deleterious effects of acute stress may exist. How potent this protective mechanism is against repetitive stress is not known.

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What is stress, and how does it affect reproduction? – Anim Reprod Sci. 2000

stressors such as milk fever or lameness increase the calving to conception interval by 13-14 days, and an extra 0.5 inseminations are required per conception.

a variety of endocrine regulatory points exist whereby stress limits the efficiency of reproduction

stressors interfere with precise timings of reproductive hormone release within the follicular phase

opioids mediate these effects

there is a level of interference by stressors at the ovary

Reproduction is such an important physiological system that animals have to ensure that they can respond to their surroundings; thus, it is advantageous to have several protein mechanisms, i.e. at higher brain, hypothalamus, pituitary and target gland levels.

However, when pushed too far, subfertility occurs.

Non-baseline cycle with delayed ovulation

…stressors interfere with precise timings…

And the stressors may even cause the Ms. to forget her daily measurement, in spite of which the pattern is discernible and interpretable in terms of “go/no go” or “safe/unsafe” as some may put it; we just say FERTILE or NOT and leave it to the user to decide… And yes, the indication of the fertile day number will also be provided.

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The role of stress in female reproduction: animal and human considerations – Int J Fertil. 1990

Tonic, pulsatile gonadotropin secretion is inhibited by stress and by administered morphine, but morphine does not block the estrogen-induced preovulatory surge in primates.

Accordingly, impaired follicular development appears to be the most common cause of reproductive dysfunction attributable to stress in the human female

must take into consideration the many differences between the hormonal responses to stress in the human and laboratory animals.

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Development of the hypothalamic-pituitary-ovarian axis – Ann N Y Acad Sci. 1997

Onset of puberty is associated with a greater increase in LH pulse amplitude than frequency

Only after the steep early pubertal increase in LH, ovarian steroidogenesis is activated, with increases in androgen and estrogen secretion. Under further FSH stimulation, follicular growth and maturation proceed. The first menstrual cycles are mostly anovulatory for 1 to 2 years. Luteal phase insufficiency is common the first five years after menarche.

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Hypothalamo-pituitary-gonadal axis in control of female reproductive cycleIndian J Physiol Pharmacol. 2001

Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus is pivotal to the regulation of reproductive physiology in vertebrates. The characteristic periodic secretion of gonadotropin releasing hormone (GnRH) from the medial basal hypothalamus (MBH), at the rate of one pulse an hour is essential for the maintenance of the menstrual cycle. These pulses are due to oscillations in the electrical activity of the GnRH pulse generator in the MBH.

The GnRH pulse generator is under the influence of an assortment of interactions of multiple neural, hormonal and environmental inputs to the hypothalamus. Hence, a number of conditions such as stress, drug intake, exercise, sleep affect the activity of this pulse generator.

Any deviation of normal frequency results in disruption of normal cycle. The cycle can become anovulatory in the hypothalamic lesions

—————————————————————————————–

Influence of the ovarian cycle on the central nervous system – Ther Umsch. 2002

In general, estradiol and testosterone exert a stimulatory, progesterone an inhibitory effect on neuronal activities which are mediated by excitatory (e.g. glutamate, aspartate), and inhibitory amino acids (e.g. GABA) and neuropeptides (e.g. beta-endorphin), respectively.

The pulse amplitudes are primarily influenced by estradiol, but neuropeptide Y, neurotensin and noradrenaline contribute to their preovulatory enhancement.

Despite of this, up to 20% of ovulatory cycles do not show any rise in body temperature.

It could be demonstrated that performance on tests of articulatory and fine motor skills are enhanced in the late follicular phase as compared to the menstruation phase, while spatial ability was better during menses. Estrogens may influence mood and well-being in a favorable manner, while in predisposed women progesterone may cause symptoms of premenstrual syndrome.

Somatic complaints (back pain, abdominal pain, breast tenderness) which are highest before and during menstruation, are probably associated with a lowered pain threshold due to a fall in the beta-endorphin levels in the CNS.

FOR A 2012 UPDATE SEE https://biozhena.wordpress.com/2012/05/28/what-is-the-mechanism-of-stress-and-how-does-it-affect-reproduction-an-update/

Stress and fertility

December 22, 2007
Please click through to the 2019 revision of this post at
https://biozhena.wordpress.com/stress-and-fertility-fertile-window-ovulation/

How stress affects the inherently narrow fertile window

Stress can do unwanted things to a woman and her menstrual cycle. In a nutshell, stress can make a woman completely infertile in this menstrual cycle (e.g., LPD, see below), or it can change the timing of her fertile window (the time of ovulation included) within the menstrual cycle. Any of this can cause problems and lead to more stress…

The medical term is stress response, and it refers to the overall reaction of the organism to any adverse stimulus, whether it be of physical, mental or emotional kind, internal or external. The purpose is to adapt to challenge, and this goes on all the time. (C’est la vie! Real life is a never-ending series of stress responses.) Should the compensating reaction of the organism be inadequate or inappropriate, a pathological disorder may result.

The HPA axis, the immune system and the sympathetic nervous system are involved in the stress response. Don’t get stressed by some undecipherable abbreviations or unknown words — look up The Alphabet of bioZhena, you may find it or them in there!

Just remember, this is no Alphabet of Ben Sira!

( /2007/11/28/the-alphabet-of-biozhena/)

021r from The Book of Urizen

Stress and the menstrual cycle

“It is a matter of conventional wisdom that perturbations in the external or internal environments – that is stress – can interfere with the normal course of the menstrual cycle.” To further quote the expert, “disturbances in the menstrual cycle occur in response to exercise and physical demands, stress and emotional demands, and diet and nutritional demands” [citation below, ref. 17].

As Michel J. Ferin writes, with reference to the brain component of the female reproductive control system, “with minimal reduction in (GnRH) pulse frequency, small undetected defects in the follicular maturation process may occur, whereas with a higher degree of pulse inhibition the follicular phase may be prolonged, and luteal phase deficiency, anovulation, and amenorrhea may develop.”

A micro-glossary: The follicular maturation process is also called folliculogenesis. GnRH is a brain-produced hormone involved in folliculogenesis. A maturing follicle is a small, protective sac, gland, or cluster of cells in the ovary, in which an egg (ovum) develops towards ovulation, in order to have a chance to be fertilized.

 

What is folliculogenesis - like EKG

 

And here is for you a baseline picture of how our folliculogenesis-in-vivo technique captures the course of folliculogenesis in baseline subjects (healthy and chemically clean i.e. no medication, less than 35 years old). Take your time to study the wealth of information particularly in the right-hand part of the image (use the linked slide):

 

 

For better legibility, click on the image. For more detail (presented in a PDF of 3 slides better viewed – incl. presenter notes – in Firefox, not in Chrome), go to:  https://biozhena.files.wordpress.com/2019/03/wealth-of-info-elucidation-silent-3-slides-animated-ed.pdf .  For the animation and narration of the first two slides, go to: https://biozhena.files.wordpress.com/2018/02/wealth-of-info-elucidation-3-animated-slides-2-narrated.pps (again, Firefox works while Chrome does not, at least here for me).

As for the scientific background of our work:  https://biozhena.files.wordpress.com/2007/12/what-is-stress.pdf is an ad hoc selection of a few abstracts from my files in (or before) 2007 on papers addressing ovulation, reproduction, folliculogenesis and stress. I referred to said area of biomedical science as psychoneuroimmunoendocrinology. Your perusal of the material with my markings (highlights) will help you understand the significance of the bioZhena technology for women’s healthcare and self-care. (The footer in the document shows obsolete email and physical addresses.)

Stress and the OvulonaTM

As introduced above, our electrochemical sensor of the ectocervix, the OvulonaTM, is a smart tissue biosensor for women’s reproductive self-help. It records menstrual cycle vital sign  signature data for OBGYN, PRIMARY CARE, RE and other healthcare providers’ use when needed.

Results obtained with our Ovulona prototypes lead to the conclusion that the technique appears to detect such phenomena as referred to by Dr. Ferin.

This is not merely the detected different rates of follicular maturation in different menstrual cycles, but even more significantly the delayed ovulations in those cycles where it takes longer than 1 day to reach the ovulation marker trough (minimum), as observed in some non-baseline subjects’ cyclic profiles. And the unprecedented  detection of the absence of dominant follicle maturation, which makes the woman infertile in the present menstrual cycle. Click on the composite image below for a better resolution of the contents.

Short luteal phase and LPD examples of the Ovulona(TM)'s diagnostic power

Here (in the upper image) is the detection of Ferin’s “minimal reduction in (GnRH) pulse frequency, small undetected defects in the follicular maturation process may occur”.

Whereas (lower image), “with a higher degree of pulse inhibition the follicular phase may be prolonged, and luteal phase deficiency [LPD], anovulation, and amenorrhea may develop” – and, indeed, we have seen the LPD, the extended follicular phase and short luteal phase, and other aberrations in the cyclic profiles of different women over the years.

bioZhena’s technique is basically detecting non-pathological stress responses in menstrual cycles through monitoring cervical end-organ effects. Pathological stress responses are captured as well.

Abnormal cyclic patterns of the end-organ effects may serve as an early warning of pathological disorders. This remains to be systematically investigated. Anecdotal evidence in non-baseline cyclic profiles is compelling.

For a hint of how this came about, including samples of data from two pilot studies by independent investigators testing our prototypes, refer to these five  slides (they take a few moments to open; some browsers such as Firefox seem better for it): Five slides selected for bioZhena weblog

The five slides are as old as the text of the original blog post, so perhaps a recent more detailed explanatory illustration (clickable for better legibility) might be in order:

 

Ovulona detects delayed ovulation

 

For better legibility of the contents and for links to the references, see the PDF of the slide shown in the image: https://biozhena.files.wordpress.com/2019/01/single-slide-ovulona-detects-delayed-ovulation-w.-links.pdf  (You can enlarge the contents using the browser zoom, or use the PPS slide show version of the slide (it takes a few moments to open): https://biozhena.files.wordpress.com/2019/01/single-slide-ovulona-detects-delayed-ovulation-w.-links.pps)

In general, the non-baseline cyclic profiles present certain quantitative deviations from baseline: e.g., their post-ovulation (luteal) phase can be not of the normal length of about 14 days (12 to 16) as in one of the illustrated cycles above. In such abnormal cycles with short luteal phases (<11 days, observed more often in older women), there is a lack of synchrony due to a mismatch between the ovarian steroids and the pituitary peptides [S.K. Smith et al., J. Reprod. Fert. 75:363, 1985].

Here is an example of a non-baseline cyclic profile of a woman with a short luteal phase (8 days); for comparison, the woman’s BBT profile in the same cycle is also shown:

Short luteal phase cyclic profile

A woman’s history of amenorrhea and/or of ovarian cysts is pertinent to the case of abnormally short luteal phase, but so is stress and its effect on the GnRH hormone generator in the hypothalamus of the brain, which affects the output of the pituitary peptides.

For example, it is known in a general way that norepinephrine and possibly epinephrine in the hypothalamus increase the GnRH pulse frequency. Conversely, the endogeneous opioid peptides, the enkephalins and beta-endorphin, reduce the frequency of the GnRH pulses. These interactions are particularly important at the time of the “mid-cycle” LH surge, affecting its timing and intensity [W.F. Ganong, Review of Medical Physiology, 17th edition, Appleton & Lange, 1995, Chapter 23].

The slow rate of descent of the Ovulona signal – seen in slides 1 and 2 of the 5 slides  above – descent from the short-term predictive peak to the ovulation marker trough (minimum) is a useful diagnostic feature that is indicative of an extended period of time required for the two “clocks” (the circhoral and the circamensual) to become synchronized as a precondition of ovulation.

Activation of the hypothalamus-pituitary-adrenal (HPA)-axis by physical, chemical, and psychological perturbations is known to result in elevated levels of serum corticosteroid hormones. Corticosteroids are the principal effectors in the stress response and are thought to be responsible for both adaptational and maladaptational response to perturbing situations. They have profound effects on mood and behavior, and affect neurochemical transmission and neuroendocrine control.

Stress double whammy

Cortisol, the predominant corticosteroid in primates, is often regarded as the “stress hormone” and consequently serves as a marker of stress. Cortisol can be measured in blood, urine, and saliva. For information about the adrenal gland and stress, go to http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/adrenal/index.html .

We logically mentioned stress in the post on Sub-fertility (or Reduced Fertility), in the following reminder. The endocrinologist professor Brown may be quoted:

“Failing to conceive when wanted is stressful and therefore favours infertility. It should be remembered that, apart from a few conditions such as blocked fallopian tubes, absent sperm and continued anovulation, most couples will conceive eventually without help. However, the modern expectation is one of immediate results, and the main function of assisted reproduction techniques is therefore to shorten the waiting time for conception.”

To which we would add that bioZhena aims to offer a more affordable and safer alternative to the A.R.T. approach. Besides offering to women’s healthcare providers the diagnostic technique with the capabilities outlined in the foregoing.

References as excerpted from our White Paper:

[17] Michel J. Ferin, “The menstrual cycle: An integrative view”, Chapter 6 in [2], pages 103 – 121.

[2] Eli Y. Adashi, John A. Rock, and Zev Rosenwaks, editors, “Reproductive Endocrinology, Surgery, and Technology”, Lippincott – Raven, 1996.

Terminology reminder:

Luteal phase is the phase after ovulation. Follicular phase is the phase before ovulation. Referencing the phases of the menstrual cycle. Amenorrhea = abnormal absence of menstrual bleeding. GnRH = gonadotropin releasing hormone. See The Alphabet of bioZhena at /2007/11/28/the-alphabet-of-biozhena/

MENOPAUSE, HRT, AND BIOZHENA

December 18, 2007

For these and other terms, see the Alphabet of bioZhena at /2007/11/28/the-alphabet-of-biozhena/

You’ll find much more there under Menopause, HRT, and bioZhena.

Klimt’s Medicine mural

The OvulonaTM is an individual woman’s health monitoring tool, primarily responsive to her steroid hormone profile. As such, it may be expected to become useful for the management of menopause, and specifically for the individualization of HRT (hormone replacement therapy) or for the monitoring of the effects of any alternative approach to menopause management. See also under Hot flushes (or flashes) and under End-organ effect, below.

The concept of individualization of HRT has to do with the adjustment of hormone dosages, so as to minimize the drugs’ harmful side effects. The bioZhena technology is an objective and quantitative monitor of the effects of steroid hormones – whether endogeneous or exogeneous (own-body-generated versus administered). On this basis, it is expected to be a meaningful tool for menopause management, both in the hands of health providers as well as conceivably in the hands of the end-users themselves. Besides causing the Ovulona to become a widely used personal tool for women’s health management in the reproductive years, there is a good chance that the technology will naturally extend its usefulness into the post-reproductive years.

Hormone replacement therapy (HRT):

The use of synthetic hormones, particularly estrogen, to replace the menopausal woman’s diminished naturally self-generated supply of hormones. Prescribed to alleviate menopausal symptoms such as hot flushes, as well as to prevent osteoporosis. Menopause and HRT – initially as “estrogen replacement” or unopposed estrogen – did not come into vogue as a topic of concern for the medical profession until the 1960s, when chemical contraception was introduced.

It is interesting to note that in countries in Asia and South America, where women eat either wild yams or soybeans, which are sources of progesterone, the term “hot flush” does not even exist in their languages. They also rarely suffer from the host of female problems presently plaguing Western women.

It is a fact that an estimated 40 to 50 million American women are now 50, the approximate average age of menopause onset. We believe that the Ovulona will be useful in menopause management in general, and personalization of HRT in particular. The latter has to do with the minimization of side effects of HRT. With respect to that, note that the risk of developing breast cancer, particularly the lobular subtype, is elevated with ‘recent long-term’ use of hormone replacement therapy. This according to a report published in the February 2002 issue of the Journal of the American Medical Association.

For more details, see Another study implicates HRT in breast cancer at http://www.lef.org/whatshot/2002_02.htm (and also http://news.bbc.co.uk/1/hi/health/3018930.stm, or google on HRT report risk of developing breast cancer).

See this April 2007 article at http://www.kaisernetwork.org/daily_reports/rep_index.cfm?DR_ID=44377, which states that as a result of said report, millions of women ceased use of the drugs. Prescriptions for HRT declined by at least 38% in 2003 and by an additional 20% in 2004. Researchers found that in 2003 and 2004, 30,000 fewer women developed breast cancer than would have been predicted by previous trends, and the incidence of breast cancer reached its lowest rate since 1987. Researchers estimate that 16,000 fewer cases of breast cancer are being diagnosed each year because of the decline in HRT use, but experts argue that HRT should not be discontinued or abandoned.

HOT FLUSHES (OR FLASHES):

During the menopausal years, many women experience severe multiple symptoms, to a greater or lesser extent, depending on the individual. In fact, 70% of women experience hot flushes within 3 months of a natural or a surgical menopause. With some, the menopausal impact of estrogen deprivation can go unnoticed. The hot flush – or, medically, the vasomotor flush – is viewed as the hallmark of the female climacteric, experienced to some degree by most menopausal women.

The term is descriptive of a sudden reddening of the skin on the head, neck and chest, which is accompanied by a feeling of intense body heat and often by profuse perspiration. The duration varies from a few seconds (about 30) to several minutes, and rarely an hour or so. The episode ends usually in profuse sweating and a cold sensation. The hot flush frequency may be from rare to recurrent every few minutes, and the flushes are more pronounced at night or during times of stress. The disturbance of sleep results in fatigue, which may in turn lead to irritability, poor concentration, impaired memory, and other deterioration of quality of life. The vasomotor flushes are less frequent and less intense in a cool environment such as in winter months in the northern hemisphere. They can occur in pre-menopause, and are a major feature of post-menopause, lasting in most women for one or two years, but in as many as 25 – 50% of women for longer than 5 years. Unlike other aspects of menopause, hot flushes lessen in frequency and intensity with advancing age.

The physiology of the hot flush is still not well understood, but it apparently originates in the hypothalamus (in the brain) and is brought about by the decline in estrogen at menopause. Vasomotor flushes appear to result from a sudden lowering of the hypothalamic thermoregulatory set point. Activation of cutaneous vasodilation (increased blood flow into skin vasculature) causes an increased peripheral blood flow and thus heat loss, leading to a fall in core temperature. There are hormonal consequences as follows: About 3 to 6 minutes after the flush onset, epinephrine increases in blood (but not norepinephrine), and corticotropin acutely rises 5 minutes after the flush onset, leading to increases in cortisol (15 minutes), androstenedione (15 minutes) and dehydroepiandrosterone, DHEA (20 minutes). While luteinizing hormone (LH) increases and peaks about 12 minutes after the onset, growth hormone also rises, about 30 minutes after the flush. On the other hand, estrogen levels, as well as prolactin, FSH and TSH (follicle-stimulating and thyroid-stimulating hormones) remain stable during hot flushes.

The flush may be preceded by palpitations or headache, and is often accompanied by weakness, faintness, or vertigo. It is understood in gynecology that 10 to 25% of women report hot flushes before menopause, and that women are often treated unnecessarily with estrogen for this relatively common psychosomatic symptom.

In brief, the flush is not a release of accumulated body heat but is a sudden inappropriate excitation of heat release mechanisms. Its relationship to the LH surge and temperature change within the brain is not well understood. It is understood that the flushes are a consequence of the withdrawal of estrogens, rather than of hypoestrogenism (low estrogen levels) per se. The discontinuation of administered estrogens may also precipitate hot flushes, which may also be caused by the infertility drug clomiphene citrate (a nonsteroidal inhibitor of estrogen receptors in the brain).

Obese women tend to be less troubled by hot flushes (because they are less hypoestrogenic).

An estimated 40 to 50 million American women are now 50, the approximate average age of menopause onset, and so it is not surprising that there is much discussion about whether hormone replacement therapy (HRT, see above) causes breast cancer or whether natural hormone creams are effective. The average woman experiencing the onset of menopause can get lost in all the controversies — especially if she is already losing her normal composure because of distressing hot flushes and night sweats.

The bioZhena technology is expected to become a useful tool for the management of menopause, and specifically for the individualization of HRT or for the monitoring of the effects of any approach to menopause management. The concept of individualization of HRT has to do with the adjustment of hormone dosages, so as to minimize the drugs’ harmful side effects.

Alternative approaches include various uses of plant products with natural estrogenic and anti-estrogenic effects that balance and augment the body’s hormone levels. For example, in The Hot Flash Cookbook (Chronicle Books, 1997), author Cathy Luchetti shares her thoroughly researched and tested nutritional solutions for relief of menopausal symptoms. In “No More Hot Flashes!” ( http://216.205.123.2/whatshot/whatshot45.shtml ), Luchetti is quoted saying, “I couldn’t accept the very idea of HRT. I have never believed in pill-popping or other synthetic approaches to health. Yet, I had to do something, because I felt as if my once-dependable body and upbeat attitude were being chiseled away, bit by bit. And being a historian, I kept recalling all the Victorian stories of menopause that ended with the woman becoming ‘unhinged by the change of life.’ I refused to accept that as my fate.”

Luchetti’s words may be considered symptomatic of the attitude of many women today, and bioZhena is in tune with these changing attitudes. Unfortunately for some, though, with addiction and consumerism being what they are, some of our “thoroughly modern Millies” (pun intended) find it almost impossible to recognize that “…to try for hot-flash relief, you should avoid certain foods if you can — especially spicy foods, caffeine, and sweets. Drinking alcohol can also trigger hot flashes”. For those, there exist some over-the-counter herbal supplements “for ridding oneself of hot flashes and other menopausal symptoms”.

As an objective and quantitative monitor of the effects of endogeneous or exogeneous (own-body-generated versus administered) steroid hormones, the bioZhena technology is expected to be a meaningful tool for menopause management, both in the hands of health providers as well as conceivably in the hands of the end-users themselves. This is a logical expectation because some women, especially those still having menstrual cycles, have apparently found that nutritional supplements (such as Dong Quai or Licorice Root) actually aggravated their symptoms. The proponents of these supplements argue that some of the herbs “don’t agree with every woman” and that it is necessary to “give it time and carefully observe its effects in your body.” As in any other situation, a good diagnostic tool is a highly advisable proposition.

Michelangelo’s Sybille de Cummes

End-organ effect:

A concept of biomedicine, which has to do with monitoring of the effects of stimuli, usually chemical stimuli such as drugs, on a biological system, that is either a part of or the complete body of an animal, or a human subject. While the fate of a chemical compound can be monitored by detecting it in body fluids (blood, urine, saliva, etc.), it can also be monitored by measuring the effect on a certain part of the body, called the end organ because the stimulus ends up there. The same applies to stimuli and reactions that the body generates by itself. bioZhena explores electronic monitoring of end-organ effects.

Premenstrual syndrome (PMS) and PMDD

December 17, 2007

For these and other terms, see the Alphabet of bioZhena at /2007/11/28/the-alphabet-of-biozhena/

The bioZhena technology is useful beyond the fertility-tracking primary purposes

(i.e., beyond aiding conception and aiding birth control).

“PMS is one of the most common disorders treated by reproductive endocrinologists”

The Book of Urizen

PMS is a combination of emotional, physical, psychological, and mood disturbances that occur after ovulation and normally end with the onset of the menstrual flow. The symptoms include abdominal bloating, breast tenderness, headache, fatigue, irritability, anxiety, and depression.

Why is this serious?

At least 30% of menstruating women experience distressing premenstrual symptoms that compel them to seek their doctor’s help, and as many as 60% to 75% of women experience some of the PMS symptoms. Of these, about 2% to 10% experience severe problems and functional impairment, which is called the premenstrual dysphoric disorder or PMDD.

According to the PMS expert, Dr. Joseph Mortola, PMS is one of the most common disorders treated by reproductive endocrinologists. Diagnosis depends on prospective recording of symptoms, and a documented symptom-free interval during the follicular (premenstrual) phase of the menstrual cycle.

PMS/PMDD is an entity that must be distinguished from (and treated differently than) anxiety disorders and depression. However, the research is still in its infancy. According to Dr. Mortola, the realization of the effectiveness of certain new drugs such as the GnRH analogs combined with estrogen/progestin replacement therapy is an important area for future research, where the optimal dosages of replacement therapy have yet to be determined. This is similar to the situation with perimenopausal HRT.

Therapeutic treatment of PMDD requires to ascertain whether the symptoms are unique to the premenstrual (post-ovulation) phase or not. This is to differentiate PMDD from clinical depression, for proper treatment. Current medical practice (both primary care and particularly psychiatry, which steps in afterward in some of the difficult cases) utilizes nothing better than the discredited calendar-based rhythm method rather than a rigorous technique for ovulation detection.

Needed: Differential diagnosis

Effective medical help for female patients requires differential diagnosis, for which the recorded symptoms must be correlated with the progress of the menstrual cycle (folliculogenesis). This correlation has not been available up to now and the diagnostician can only guess at how the scores of symptoms relate to the course of the menstrual cycle (folliculogenesis).

Differential diagnosis is essential because a clinical study found that more than 75% of patients presenting with the complaints of PMS had another condition that either could account for the symptoms or that required correction before an accurate diagnosis of PMS could be made [Mortola, JF: “Issues in the diagnosis and research of premenstrual syndrome”, Clin. Obstet. Gynecol. 35:587-598, 1992].

The physician user of our OvulographTM technology will have the benefit of working with accurate and comprehensive data on each patient’s menstrual cycle history, and will be in a better position to provide effective help.

How OvulographTM will help

Two examples of ovulographic correlation of symptoms (symptometric data, here the COPE scores) and folliculogenesis (Ovulona probe readings) can be seen below and – along with the answer to What is the meaning of symptometric data – in the document on the accompanying Page “What is symptometric?” at https://biozhena.wordpress.com/what-is-symptometric/.

Ovulographic correlation of folliculogenesis and symptometric data – click to open a clear PDF version of the image

Ovulographic Correlation of Folliculogenesis and Symptometric Data

In the first example, the cumulative COPE score rises on day 13, which is 3 days before ovulation (day 16), and we note that this is a case of an irregular cycle with a delayed ovulation. In the second example, the COPE score rises on day 17, which is 2 days after the day of ovulation (day 15).

We observe that, in the first example, in the absence of the Ovulona probe data, the “traditional” method of counting back 14 days from the first day of menstrual bleeding (namely, to day 12) would lead to the wrong conclusion that the score rise on day 13 is post-ovulatory.

Only the second example (documented post-ovulation rise of the COPE score) appears to be a case of PMS.

“Psychiatric instruments” will become women’s healthcare tools

COPE score refers to the well known “psychiatric instrument”, the Calendar of Premenstrual Experiences (COPE), described in a paper by Beck LE, Gevirtz R, Mortola JF: “The predictive value of psychosocial stress on symptom severity in premenstrual syndrome”, Psychosom. Med. 52:536, 1990.

The bioZhena technology should have a positive effect in the PMS/PMDD arena.

Two key words are pertinent in this context, namely psychoneuroendocrinology (or even psycho-neuro-immuno-endocrinology) and the much shorter psychosomatic, as in psychosomatic medicine.

See also “On the importance of symptometric monitoring” https://biozhena.wordpress.com/about/about-biozhena-tech-pitch/importance-of-symptometry/ .

Cervix uteri and seven or eight related things

December 16, 2007

For these and other terms, see the Alphabet of bioZhena at /2007/11/28/the-alphabet-of-biozhena/

Rerum Naturare Feminina. A Woman’s Natural Thing. In the lingua franca of the ancients.

The reader of this bioZhena’s Weblog article will or should be well aware that a woman’s menstrual cycle lengths are quite variable, as is the timing of her ovulation within those menstrual cycles. For evidence of this variability, see another blog post at https://biozhena.wordpress.com/2010/03/07/variability-of-menstrual-cycles-and-of-ovulation-timing/ (opens in new tab/window). Our focus on the cervix uteri is clarified below in this article.

Cervix:

The narrow lower part of the uterus (womb), with an opening that connects the uterus to the vagina. It contains special glands called the crypts that produce mucus, which helps to keep bacteria (and other microbes, including sperm for most of the cycle) out of the uterus and beyond. Sometimes called the neck of the womb, it protrudes into the vagina. The region around the cervical protrusion is known as the vaginal fornix. The sanitary vaginal tampon is inserted so as to reach into the posterior fornix. Likewise the bioZhena sensor. As simple as that.

The cervix is the gateway to the uterus and has a lot of important and challenging roles. It must allow the passage of either sperm (or penis, in some species) at copulation, prevent the entrance of microorganisms before and particularly during pregnancy, and expel the neonate and placenta at parturition (birth). It is a muscular tube that has a very dynamic role in both the menstrual cycle and in forming a tight seal during pregnancy, but opening to form a broad passageway at birth. The multitude of physiological roles of this gateway has caused it to become an important element or focus of the bioZhena technology.

Cervical mucus:

The fluid secreted by the inner walls of the cervical canal and exuded by the cervix. The amount and the properties of the fluid change depending on the phase of the menstrual cycle, e.g., from practically nonexistent during the so-called dry days early in the cycle to the relatively copious amounts of clear slippery fluid during the fertile days.

Cervical mucus is essential for the ability of the sperm to function properly: sperm survival and sperm transport within the woman’s reproductive system are critically dependent upon the presence of a healthy mucus.

To quote a noted expert, Professor Erik Odeblad: “Complications arising from the use of the Pill are very frequent. Infertility after its use for 7-15 years is a very serious problem. S crypts are very sensitive to normal and cyclical stimulation by natural oestrogens, and the Pill causes atrophy of these crypts. Fertility is impaired since the movement of sperm cells up the canal is reduced. Treatment is difficult.” He also wrote: “After 3 to 15 months of contraceptive pill use, there is a greater loss of the S crypt cells than can be replaced … A pregnancy rejuvenates the cervix by 2-3 years, but for each year the Pill is taken, the cervix ages by an extra year.” Web reference:http://www.billings-ovulation-method.org.au/act/pill.html .

Cervical mucus method:

A method of determining a woman’s fertility by observing changes in her cervical mucus. The Billings ovulation method and the Creighton model ovulation method are both cervical mucus methods.

Cervical palpation:

Feeling the cervix with the middle finger of the thus trained woman-user of FAM or NFP to determine cervical position. This is not a widely used procedure, and is not involved in the Billings and Creighton ovulation methods.

Cervical position:

Three facets of the cervix (its height, softness and the size of its opening, the cervical os) assessed for fertility significance by specially trained users of this method of NFP or FAM. Not many of those around…

Colposcope:

A viewing instrument with a bright light and magnifying lens that is used to examine the vagina and cervix stained with special solutions. Colposcopy: Examination of the vaginal and cervical epithelia by means of a colposcope. [Greek kolpos, vagina, womb + -scopy, suffix that signifies viewing; seeing; observation: as in microscopy. From Greek -skopi, from skopein, to see.] Colposcopy is the diagnostic procedure to evaluate patients whose Pap smear screening produced abnormal cytological smear results.

Billings Ovulation Method (BOM):

An NFP method in which the fertile days are identified exclusively by observations of cervical fluid at the vaginal opening. Developed by the Australian Drs. John and Evelyn Billings. An international survey in 1987 indicated that at least 50 million couples were using the method, and the number is said to be increasing from year to year. It has also been estimated that 80% of natural family planning world-wide is now the Billings ovulation method. In 1978 an international conference in Melbourne was attended by delegates from 48 countries. See also the cervical mucus method.

Creighton model ovulation method:

An NFP method of vaginal-cervical mucus self-evaluation according to criteria developed by Thomas Hilgers, M.D. at St. Louis and Creighton Universities. The criteria are called the vaginal discharge recording system (VDRS) and require that women check for the mucus by wiping the outside of their vaginas with bathroom tissue, checking the mucus for color, stretch and consistency. The last day of mucus that is either clear on appearance, stretches an inch or more, and/or causes the sensation of lubrication is called the peak mucus day. The method is similar to the Billings ovulation method.

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bioZhena’s method of monitoring the cervix:

And then we have the bioZhena method, with the Ovulona inserted briefly just like a tampon applicator, and taking a reading of the fertility status (most of the time NOT FERTILE = cannot conceive; only 3 days of fertility in each menstrual cycle):

Ovulona™

The DIU is or will be an auxiliary add-on

 

 How the Ovulona will be transformed into a (semi-) permanently worn cervical ring obviating daily insertion is shown in slide 4 of QUICK INTRO 4 SLIDES at

Friendly Technology and Next Generation Design

The natural interest of women in being in charge of their reproductive life leads to the possibility of using the information gathered in the process for additional medical purposes. The Ovulona cyclic profile is the signature of the menstrual-cycle vital sign, which is the result of the illustrated interaction between the female brain and the ovaries – the so-called Hypothalamus-Pituitary-Gonad Feedback Loop (F). (This editing added here in 2016.)

Menstrual cyclic profile signature of the HPG feedback mechanism

To enlarge the image, click https://biozhena.files.wordpress.com/2009/03/menstrual-cyclic-profile-signature-of-the-hpg-feedback-mechanism.jpg

The H-P-G feedback loop (F) gives rise to the menstrual cyclic profile signatures captured by the bioZhena technology.

Here is why the bioZhena technology had to be invented. One way of saying this is: The available means, methods or products, were not good enough. Another way of putting this is to quote from medical literature, as follows.

A symposium on ovulation prediction in the treatment of infertility covered all the phenomena known to be associated with ovulation [reference 9]. Moghissi, who discussed more than 20 measurable parameters that vary during the menstrual cycle, stated the following [reference 8]: “Mid-cycle mucorrhea, ferning, spinnbarkeit, lowered cell content, and viscosity of cervical mucus are used commonly in ovulation detection and as an index of the estrogenic response of cervical epithelium. However, these changes extend over several days … (These changes) do not necessarily indicate ovulation, and are merely an index of the optimal amount of circulating estrogen…”.

In brief, none of the methods determined ovulation with the required accuracy to be useful either as a conception aid or especially for birth control. Here is how our method (monitoring folliculogenesis) does it by generating the multi-featured cyclic profile that includes the definitive ovulation marker after the predictive signals, and here is how this compares with the older techniques. See how inaccurate is the ovulation assessment by the older means available to the users of NFP or FAM (spread over 3 days):

Marquette comparison with LH kit and Peak mucus – right click on the link to open a larger PDF version of the image.

Marquette comparison with LH kit and Peak mucus

In this example, our device detected delayed ovulation while the LH ovulation kit indicated positive for ovulation on two days (not just one) and the mucus assessment (Creighton method) indicated positive one day later. 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 spread of 3 days is not acceptable, but it is actually quite typical of the uncertainty associated with these older techniques. You know what that means, don’t you, because you know that every day matters. Their lack of accuracy and precision renders the older techniques not good enough – which is where we started.

Cited references:

[8] Kamran S. Moghissi, “Cervical mucus changes and ovulation prediction and detection”, Journal of Reproductive Medicine 31 (Number 8), Supplement, 748 – 753, 1986.

[9] Stephen L. Corson, guest editor, “Ovulation Prediction in the Treatment of Infertility. A Symposium”, Journal of Reproductive Medicine 32 (Number 8), Supplement, 739, 1986.

Review and listen to 3 narrated slides summarizing the bioZhena technology. Contemplate the importance of the cervix uteri.


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