What Women Know, And What They Want To Know About Their Fertility Status

There: What Women Know

There is no device in the marketplace today that would tell you, in plain English, “today is your fertile day 1” – meaning that sex today is likely to lead to pregnancy. And from our clinical trial results you will know that the pregnancy conceived on this first of the fertile days is likely to be a male fetus, a boy.

There is no such device on the market that would subsequently confirm the pregnancy within days – when, after ovulation on fertile day 3, you would no longer register the usual follicular waves. Your Ovulona device would interpret that as pregnancy detected, because that is how the biology works.

There is no device out there that would detect the only 3 days in each menstrual cycle during which – and only during which – pregnancy can result from insemination, whether natural or artificial. The other fertility monitors cannot detect either delayed ovulation (which happens due to stress) or when ovulation does not occur at all. In fact, they do not detect ovulation, they just guess at it.

This bears repeating. There is no device out there that would detect the only 3 days in each menstrual cycle during which – and only during which – pregnancy can result from insemination, whether natural or artificial. The other fertility monitors cannot detect either delayed ovulation (which happens due to stress) or when ovulation does not occur at all. Because they do not detect ovulation, they merely assume its occurrence due to the particular hormonal marker of their choice. But no single hormone, even if it were detected with the accuracy of laboratory methods, determines the fertile window including ovulation. It’s much more involved than that.

Here: What Women Want To Know

Only scarcity of funds keeps us from a device doing all those things not available today.

Our personal self-diagnostic device, the Ovulona™, will tell the woman in plain English (or any other language) whether today is one of the three days on which she can become pregnant.

http://biozhena.files.wordpress.com/2009/10/fertile-window1.jpg?w=600

Fertile window

How? We’ll have the woman-user monitor at home the process that causes menstrual cycles and is fundamental to women’s health. The use is very simple, just like a tampon, but only for a few seconds (about 20) to obtain the result, with an instant display of the result.

Primary use is for reproductive management – that is aiding the achievement of pregnancy, and fertility-awareness based non-invasive birth control. But there is much more, including an automatic screening for cervical cancer, management of PMS/PMDD and management of hormone therapy, to name just a few useful applications that come with the core technology.

We show the working of the prototyped product using the graphs of the measurement results plotted against the days of the menstrual cycle. The graphs produce cyclic profiles descriptive of the nuances of the monitored menstrual cycles. None of the old techniques can do that.

These cyclic profiles have important characteristics: 1. The cyclic profile has numerous repeatable features. 2. The range of readings is the same in different cycles and, importantly, also in different women. 3. The profile features are interpretable, and are due to the biological process that causes the menstrual phenomena (folliculogenesis). The significance of these profiles goes beyond reproductive management.

To wit: Ours is a unique and disruptive technology. (As such, not readily funded by the established financing channels, and we are seeking well matched financial partners that will not run the project to the ground.)

http://biozhena.files.wordpress.com/2009/10/fertile-window-for-birth-control.jpg?w=600

Fertile window for birth control

For a better insight, visit http://biozhena.wordpress.com/about/about-biozhena-tech-pitch, and the other posts on this blog [ http://biozhena.wordpress.com/ ], and check out http://www.linkedin.com/in/vaclavkirsner.

Before you go, see this, to get a sense of what is going on here:

http://biozhena.files.wordpress.com/2009/10/baseline-cycles-interpreted.jpg?w=600

Baseline cycles interpreted

Parties with an interest relevant to bioZhena Corporation will be provided with more confidential information upon request (email: vaclavkirsner@yahoo.com).

Far more than a tool for reproductive management

On symptometric monitoring correlated with folliculogenesis: Why it is essential for effective diagnosis in women’s healthcare

The purpose of this article is to bring to your attention the big picture. That is the fact that the potential impact of the bioZhena technology goes beyond reproductive management. We illustrate how we mean it when we invoke the vision that the Ovulona device will become a friendly routinely-used companion tool with numerous diagnostic ramifications for women everywhere.

The natural interest of the woman-user in being in charge of her reproductive life leads to the possibility of using the information gathered in the process for additional medical purposes, some not so obviously connected with the menstrual cycle signature. (The Ovulona cyclic profile is the signature.)

You will follow the discussion here better if you peruse the bioZhena weblog article, listed under Pages and titled, What is symptometric? What is the meaning of “symptometric data”? The answer in a nutshell: Symptometry means symptoms quantified and charted.

Now for a possible application. You probably do realize that there are gender differences in how patients respond to therapy, and you do not need reminding that cardiovascular disease is a big problem for women’s health, far from killing mainly male victims.

In this context we hint at an electronic interface that will function to navigate through a menu that provides for a daily registration of quantified symptoms by means of one of the standard medical symptometric inventories such as the Calendar of Premenstrual Experiences (COPE), or the Daily Record of Severity of Problems (DRSP), etc. This will replace the paper forms used today.

The DIU will facilitate electronic recording of quantified symptoms

By design, the symptometric data will be correlated with the Ovulona data on folliculogenesis – and will be far better than the old, inefficient and costly, paper-using procedures of yesteryear (those did not employ any folliculogenesis correlation, of course). No need to invoke the evolving societal developments in general healthcare policy towards cost-effectiveness, etc.

A recent health news headline declares: “More evidence that depression is hard on the heart”, and here is the synopsis: Severe depression may silently break a seemingly healthy woman’s heart. Doctors have long known that depression is common after a heart attack or stroke, and worsens those people’s outcomes. Monday, Columbia University researchers reported new evidence that depression can lead to heart disease in the first place [http://channels.isp.netscape.com/news/story.jsp?floc=ne-story-9-l9&idq=/ff/story/0001%2F20090310%2F0629929017.htm&sc=1500 03/10/09 06:29 © Copyright The Associated Press].

The issue is not the reported “big surprise: Sudden cardiac death seemed more closely linked with antidepressant use than with the depression symptoms the women reported. That might simply mean that women who used antidepressants were, appropriately, the most seriously depressed, cautioned lead researcher Dr. William Whang. But he said the finding merited more research” [loc. cit.].

The issue is that not only more research but all routine women’s health practice requires the knowledge of how symptoms relate to (correlate with) the course of the menstrual cycle or, more accurately put, the course of folliculogenesis.

For an illustration, refer to Premenstrual syndrome (PMS) and PMDD

Effective therapy requires this (differential diagnosis), and our technology will do three things for public health:

1. Enable routine quantitative recording of symptoms,
2. Correlate symptoms with the underlying folliculogenesis process, and
3. Allow for individualization of therapy (titrate medication doses for individuals).

This is one of the examples of non-reproductive applications of the bioZhena planned products; this is simply a reminder that the core product, the Ovulona™ for reproductive management, is far from the only planned product offering.

The Ovulona™ is the core product with various diagnostic ramifications within the bioZhena Fertility and Health Awareness System™.

The Ovulona is not another ovulation kit, my dear

Reply to Jennifer K. who wrote: How is this different from the other ovulation kits on the market today? It seems very similar to products I have seen before. QUOTE UNQUOTE

Actually, Jennifer, you are mistaken. There is no such thing available to you in the marketplace today.

None of the ovulation kits – which the Ovulona™ is not – or any other fertility-status monitor on the market today has the required accuracy to determine fertile day 1, fertile day 2, and fertile day 3 (ovulation, the last day of the fertile window).

All the existing techniques only guesstimate the approach of ovulation, and none of them can detect ovulation separately from predicting it. They detect neither the first day nor the last day of your brief fertile window.

Let’s try to illustrate this with the following graphical comparison of the Ovulona 3-day fertile window versus the fuzzy and much wider, uncertain window indicated by one of the old techniques. (In this case it was the so-called Peak mucus method but LH kit and BBT yielded similarly wide and fuzzy fertile periods, that is the days on which intercourse resulted in pregnancy.)

Ovulona 3-day fertile window versus old methods

Because in the Old Method ovulation was only guessed at, a fuzzy fertile period obtained.

Fuzzy and long. Wrong.

There is no device in the marketplace that would tell you, in plain English, “today is your fertile day 1” – meaning that sex today is likely to lead to pregnancy. And from our clinical trial results you will know that the pregnancy conceived on this first of the fertile days is likely to be a male fetus, a boy.

There is no device that would subsequently confirm the pregnancy within days – when, after ovulation on day 3, you would no longer register the usual follicular waves – and your Ovulona device would interpret that as pregnancy detected, because that is how it works.

There is no device out there that would detect the only 3 days in each menstrual cycle during which – and only during which – pregnancy can result from insemination, whether natural or artificial. The other fertility monitors cannot detect either delayed ovulation (which happens due to stress) or when ovulation does not occur at all.

There is no device that would, in the event of pregnancy, calculate for you the scientifically predicted EDD, Estimated Delivery Date, so as to spare you the nerves, hassles and expenses associated nowadays with premature trips to the maternity ward and related hardships. Hardships suffered by expectant mothers because of the old non-scientific way the doctors guesstimate and frequently mismanage the EDD today.

There is no other device that would enable you to avoid the expense and hassle of trying to become pregnant with the help of the costly Artificial Reproductive Technologies when your dominant follicle maturation is not happening – which is only detectable with our folliculogenesis-tracking little device for home use.

Your gynecologist, your family doctor – or your psychiatrist if you suffer badly with PMS – does not have the benefit of the folliculogenesis cyclic profiles stored in the Ovulona memory for better diagnosis and better treatment than you can get today.

There is no other technology that would – automatically and without bothering you at all – keep track of whether your cervical tissues are healthy, and would issue a warning only when detecting tissue aberration several months in a row (to spare you the anxieties and expenses associated with the Pap smear cervical cancer tests’ false positives).

There is no technology as yet available to all women worldwide with all these empowering features at a perfectly affordable cost.

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

EDD stands for Estimated Date of Delivery, while EDC stands for Estimated Date of Confinement. The bioZhena thinking, in one brief sentence, is: Aim to replace stochastic with deterministic, which is also the purpose of our eukairosic^TM diagnostic tools.

The medical position on 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 postterm 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 articles 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.

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 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 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 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.

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… That evidence exists for gestational length variability with ethnicity (or race) has also been noted [International Journal of Epidemiology 2004, Volume 33, Number 1, pp. 107-113 ].

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. [Private at vaclavkirsner at yahoo.com, please, if you prefer to communicate privately.]

There actually would seem to be a fairly good basis for this attempt at an online inquiry (or survey), in preparation for an introduction of a tool with which to study the subject further. -

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!

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

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

With our eurokairosic^TM diagnostic tools, we generally aim to determine the right time, and in the case at hand we would like 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 try to replace the LMP/Naegele-based approach with a hard data-based technique, applied to each and by each Mom individually.

Again, your comments and answers to the questions above would be very useful. Public or private input would be appreciated. [Private at vaclavkirsner at yahoo.com, please, if you prefer private.]

 

Parturition means birthing (birth) and dystocia a difficult one

And what is a parturition alarm?

 

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

/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:

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. Well, check out Figuring Your Due Date, too – from the Midwife Archives, listed also in the Blogroll, on the right (at the top of the blog).

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 only after that with any concerns of perinatal medical professionals.

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. [Private at vaclavkirsner at yahoo.com --- should you prefer private communication.]

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

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.

 

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

 

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

“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 Ovulona^TM 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

——————————————————————————————

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.

——————————————————————————————-

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.

…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 cycle – Indian 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

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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.

 

 

 

Stress and fertility

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 position 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 there!

Just remember, this is no Alphabet of Ben Sira!

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

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, as 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. For visualization see http://images.google.com/images?hl=en&q=ovarian+follicles&btnG=Search+Images&gbv=2

Results obtained with our Ovulona prototypes to date lead to the conclusion that the technique appears to detect such phenomena as referred to by Dr. Ferin. This is not so much or merely the different rates of follicular maturation in different menstrual cycles, but more seriously 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.

This is the detection of Ferin’s “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 [LPD], anovulation, and amenorrhea may develop” – and, indeed, we have seen the LPD, the extended follicular phase and short luteal phase, and various other aberrations in the cyclic profiles of different women over the years.

bioZhena is basically involved with non-pathological stress responses through monitoring certain end-organ effects. 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 to date is compelling.

For a hint of this, refer to these 5 slides: Five slides selected for bioZhena weblog

Watch them in the slide show mode. To get out of the slide show, you jerk the mouse… remember? (Remember this from the earlier Cervix post /2007/12/16/cervix-uteri-and-seven-or-eight-related-things/?)

You might read the Speaker Notes for the slides, too… (written for you!)

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). 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 luteal-phase 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):

A woman’s history of amenorrhea and/or of ovarian cysts is pertinent to the case of 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 – in slides 1 and 2 – 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.

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.

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

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.

 

The Ovulona^TM 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.

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

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”

 

 

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.

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 dystrophic 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, in particular, requires to ascertain whether the symptoms are unique to the premenstrual 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 once the primary care fails) utilizes nothing better than the discredited calendar-based rhythm method rather than a rigorous technique for ovulation detection.

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 might 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 Ovulograph^TM 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.

 

Two examples of ovulographic correlation of symptoms (symptometric data, here the COPE scores) and folliculogenesis (Ovulona data) 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 http://biozhena.wordpress.com/what-is-symptometric/.

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

 

 

In the first example, the cumulative COPE score rose on day 13, which was 3 days before ovulation (day 16), and we noted that this was a case of an irregular cycle with a delayed ovulation. In the second example, the COPE score rose on day 17, which was 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 was post-ovulatory. Only the second example (documented post-ovulation rise of the COPE score) appears to be a classical case of PMS.

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.

 

Cervix uteri and seven or eight related things

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

Not included in The Alphabet as yet is the motto found in the header of this blog. Rerum Naturare Feminina.

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

Linguistic advice would be welcome on the correct way of referencing women in the plural. (Women’s Natural Thing.)

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 test to evaluate patients whose Pap smear screening produced abnormal cytological smear results. For more details see http://lib-sh.lsumc.edu/fammed/atlases/colpoat.html .

 

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.

 

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):

 

 

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 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 – click to open a larger PDF version of the image

 

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.

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.

In case of interest, the reader’s appreciation of the Ovulona’s diagnostic performance can be reinforced by viewing the following set of 5 slides.

 Selected slides for bioZhena’s weblog

The PowerPoint slide attachment opens in their Normal mode (normally used for creating and editing the slides). The slides are animated and should be viewed in the Slide Show mode — accessed via the View button on upper left, selecting Slide Show on the drop-down menu.

Browse through the slides either by left-clicking on each slide or by using the down-arrow key (to the right of the main keyboard, at bottom edge). You can browse back by means of the up-arrow key.

To get out of the Slide Show mode, move mouse quickly (jerk it), which causes a button to appear in left bottom corner of the Slide Show screen; click it and select End Show.

Alternatively, you can select the Speaker Notes, which contain additional information about the data.

 

Natural Family Planning and Fertility Awareness – not the old “Rhythm method”!

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

Natural family planning (NFP):

This refers to several different methods for spacing, postponing, avoiding or enhancing the possibilities of conception, without any chemical or physiological alterations of the reproductive system (female or male). NFP, therefore, is not merely a birth prevention method but is also utilized to increase the chances of becoming pregnant.

Natural family planning research has shown that among the advantages of the NFP practice is that the required discipline enhances the sexual relationship and dialogue, and that there is a reduction of “dominant attitude” in both men and women practising NFP. Contemporary methods are sometimes referred to as ‘fertility awareness’ (FA) since they are ultimately based on awareness of symptoms of fertility that are readily recognizable or measurable by any woman. Other people distinguish between NFP and FA in terms of the fertile phase: NFP users abstain whereas FA users employ a barrier method of contraception during the fertile phase. In any case, NFP and FA are distinct from the older ‘calendar’ methods such as Ogino-Knaus (the so-called ‘rhythm’ method).

The American College of Obstetricians and Gynecologists (ACOG) refers to “family planning by periodic abstinence” and explains that this is [QUOTE] another name for the method of birth control that used to be called ‘rhythm method’ or ‘safe period’. More recently it has also been called ‘natural family planning’ or ‘fertility awareness’. It isn’t a single method but a variety of methods. Each is designed to help a couple find out which days during a woman’s menstrual cycle she is likely to be fertile or able to become pregnant [END OF QUOTE]. Ref.: http://www.medem.com/search/article_display.cfm?path=\\TANQUERAY\M_ContentItem&mstr=/M_ContentItem/ZZZ48OI527C.html&soc=ACOG&srch_typ=NAV_SERCH .

While the proponents of NFP warn that, without further expenditures on education, NFP will remain a fringe method in the U.S., the American College of Obstetricians and Gynecologists advises the public that [QUOTE] periodic abstinence is quite an effective means to prevent an unwanted pregnancy [END OF QUOTE].

A more detailed and informed article is in American Family Physician, Nov 1, 1995 by John H. Geerling [ http://findarticles.com/p/articles/mi_m3225/is_n6_v52/ai_17558662 ] who writes that “studies have reported that women who practice methods of natural family planning do so for health reasons, and because the methods are natural and do not require the use of chemicals”. He also writes that: “Effective use of natural family planning requires teaching beyond that which physicians can provide during a typical office visit. Therefore, physicians who wish to provide natural family planning as an option to their patients need to establish working relationships with persons who are qualified to instruct patients in the various methods of natural family planning.”

The Ovulona^TM from bioZhena is designed to make NFP/FAM easily accessible to anyone. Scientific Family Planning^TM and/or Scientific Fertility Awareness^TM are the putative names for our approach, SFP^TM and SFA^TM.

FAM (fertility awareness method):

A method of determining a woman’s fertility status through self-assessment of certain fertility signs: waking temperature (also called the basal body temperature or BBT), cervical fluid, and cervical position. While NFP users abstain, FAM users apply one of the barrier methods of contraception for vaginal intercourse during the “unsafe days” of a woman’s fertile phase.

“Rhythm” method:

Also called the calendar method, it has been discredited because of two factors: its unwarranted assumption of regularity of menstrual cycles, and the long period of abstinence demanded by it. The method’s one-time well-known status has caused a skeptical bias in America to all NFP or FAM methods, although they are very different.

The calendar or “rhythm” method is useless (and silly), unlike NFP or FAM. The reader may be aware of another nickname for the “rhythm method”… If so, you also understand that the above-referenced ACOG is confused when they talk of “another name for the method of birth control that used to be called ‘rhythm method’”. This sort of confusion is sadly not unique, including in the medical circles, and we reference other instances in some other entries in The Alphabet ( /2007/11/28/the-alphabet-of-biozhena/ ).

Fetal sex pre-selection – the fundamentals

For this and the various related concepts and terms, see the Alphabet of bioZhena at

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

 

Fetal sex pre-selection:

Here is the underlying principle: Out of the 46 chromosomes (23 pairs), the last pair is the sex chromosome. It is of the XX type in the female and XY type in the male. The ovum (egg) has X type chromosomes only, while 50% of the sperm have X chromosomes and 50% have Y chromosomes. If an X sperm fertilizes the egg, this results in an XX combination, which is a female offspring. If a Y sperm fertilizes the egg, the result is an XY combination and a male child.

According to http://www.fertility-docs.com/fertility_gender.phtml , “the selection of gender has been a quest of couples for as far back as recorded history allows. Early drawings from prehistoric times suggest that sex selection efforts were being investigated by our earliest ancestors. Later history shows intense interest in sex selection by early Asian (Chinese), Egyptian and Greek cultures. This is followed by documented scientific efforts beginning in the 1600s to sway the chances of achieving a pregnancy by a variety of methods…” QUOTE UNQUOTE

Two approaches to sex selection have been demonstrated in the current scientific literature. One approach employs the tools and methods of assisted reproductive technologies (ARTs), manipulating the genetic material of the sperm prior to artificial insemination, so as to facilitate fertilization by the selected one of the two genders of the spermatozoa. The other approach attempts to enhance the probability of conceiving the desired gender by appropriate timing of the conception event with respect to ovulation. This is a highly controversial subject despite the fact that a substantial body of work on it has been published.

Thus, a 2001 publication by respected experts from a premier infertility treatment institute (G.Hodgen et al., see below) has put forward evidence that male spermatozoa (Y-chromosome-bearing sperm) live longer than female spermatozoa (X-chromosome-bearing).

This is consistent with earlier findings by Auckland, New Zealand researchers that boys tend to be conceived earlier in the fertile period than girls (the earlier conception requires a longer lifetime of the sperm). This was discussed in our two previous posts: /2007/12/02/regarding-fetal-sex-preselection/ and /2007/12/03/fetal-sex-preselection-illustrated/ .

A 1991 Johns Hopkins University meta-analysis of six NFP studies concluded that the data showed “a statistically significant lower proportion of male births among conceptions that occur during the most fertile time of the cycle”, meaning near ovulation. Indeed, the Auckland study by Professor John France’s group found that 65% of male infants were conceived 2 to 5 days before ovulation while “71% of the born girls were conceived from intercourse timed between 1 day before to 1 day after the estimated time of ovulation”. See the referenced previous posts.

Notes:

1) Hodgen et al. paper on different survival times of X and Y sperm:

Andrologia, Volume 33 Issue 4 Page 199 – July 2001
Differential binding of X- and Y-chromosome-bearing human spermatozoa to zona pellucida in vitro
Q. Van Dyk, M. C. Mahony and G. D. Hodgen

 

2) We might refer to the second, the correct-timing, approach to fetal sex pre-selection as eukairosic. This [Eukairosic™] with reference to http://www.perseus.tufts.edu/cgi-bin/lexindex?lookup=kairo/s〈=Greek

kairos III. more freq. of Time, exact or critical time, season, opportunity… … …

 

 

Fetus:

 

The organism that develops from the embryo at the end of about seven weeks of pregnancy and receives nourishment through the placenta. Fetus, plural fetuses:

1. The unborn young of a viviparous vertebrate having a basic structural resemblance to the adult animal. Viviparous: Giving birth to living offspring that develop within the mother’s body. Most mammals and some other animals are viviparous. Vertebrates have a backbone or spinal column.

2. In humans, the unborn young from the end of the eighth week after conception to the moment of birth, as distinguished from the earlier embryo. [From Latin fetus, offspring.]

Embryo:

The embryo is the organism that develops from the pre-embryo, and begins to share the woman’s blood supply about nine days after fertilization. Approximately one-half of all human embryos are abnormal [ http://www.columbialabs.com/html/crinwom/infertility/fertilization.htm ]. QUOTE: “There is fortuitously a biologically based selection bias against abnormal human embryos. A signal is obviously recognized by the mother, which helps explain why so many embryos fail to implant. An abnormal embryo that manages to implant is often miscarried in the first 10 weeks of pregnancy. Early miscarriages are almost always the result of abnormal development of the fetus. This is why progesterone is not usually recommended for threatened abortion. It is only if the physician can confirm, using ultrasound, that the fetus is viable, will he prescribe progesterone to help maintain the pregnancy.”

Veterinary fetal sex pre-selection:

A similarly high level of interest in embryo sexing (fetal sex pre-selection, or sex ratio) exists in the livestock industries, and researchers have experimented with the timing of insemination method. A tool such as the bioZhena Corporation’s BioMeter is indispensable for this approach to embryo sexing, because of the required accuracy and precision of the timing. The controversy in the veterinary literature is a clear evidence that timing the insemination merely with respect to estrus is not good enough. The timing must be with respect to ovulation. The BioMeter, which detects ovulation as well as anticipating it, should make it possible to investigate questions such as whether different species have different lifetimes of the sperm. It should be possible to establish what kind of a distribution of sperm lifetimes there may be within a species. (See also under Timing of insemination.)

The 2001 book Biotechnology in Animal Husbandry (R. Renaville & A. Burney, editors, Kluwer Academic Publishers) has a chapter on Sex Preselection in Mammals. The abstract states: Since a long time, sex preselection has been a goal of the dairy and meat industry to increase the rate of response to selection, to reduce the cost of progeny [offspring or descendants] testing for elite males, and to produce desired specialized and genetically superior offspring. The authors write: In animal husbandry, pre-selection of sex prior to conception will dramatically impact a farmer’s productivity and income, because in each of the chosen target industries there is a strong preference for one sex over the other. For example, the dairy industry must have females to produce milk whereas the beef industry prefers males for their higher quality and lower cost of production. Sex pre-selection is one of the most sought after biotechnologies of all times.

In a section on Factors Affecting Sex Ratio, the experts write: Considerable folklore particularly in humans has arisen regarding preconception methods to manipulate animal sex ratio. The authors point out that conventional wisdom holds that steroid hormones play no role in sex predetermination in mammals, and it is only after gonadal differentiation that steroids sculpt the characteristics, which distinguish males from females. They also write that, for a number of years, the time of insemination or mating during estrus has been believed to influence the sex ratio of offspring, and they review various conflicting reports in several animal species. One kind of these results, in cows, indicates that the sex ratio may be affected by the maturational state of the oocyte [egg] at the time of insemination (yielding sex ratio 0.7 when inseminated immediately after, and 2.5 when inseminated 8 hours after polar body extrusion, which basically refers to ovulation timing). In their Conclusion, the experts again point out that “economics dictate that livestock producers are under increasing pressure to produce a given number of progeny of the desired sex.”

The results of sex pre-selection experiments depend on the state of the ovulating egg and of the sperm. This may depend on whether a given father belongs into a sub-population of males with long or short sperm lifespan. Whether there is such a thing as this kind of categorization within a species can only be established by means of a tool such as the Ovulona/BioMeter.

This holds for all species, including Homo Sapiens, of course, and public health statistics make such categorization actually quite likely. In the U.S., the sex ratio (number of males born per 1000 females) has declined from 1.052 in 1983 to 1.049 in 1999, having been as low as 1.047 twice in the late nineties. Interestingly, this decline is evidently due to the decline in the white race (from 1.057 to 1.052, through as low as 1.049) whereas for the black race the sex ratio has actually increased over those years (from 1.028 to 1.031, through as high as 1.036) [web reference: http://www.infoplease.com/ipa/A0005083.html ].

All this is suggestive of a likely strong reason why people will want to use the bioZhena [eukairosic] products, and the application will not even need to be advertised.

Infertility and A.R.T. or Assisted Reproductive Technologies

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

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

 

 

Infertility:

Clinical infertility is the inability of a couple to achieve a pregnancy or to carry a pregnancy to term after one year of unprotected intercourse. If the difficulty to conceive lasts less than a year, the condition is referred to as reduced fertility or sub-fertility (see the previous post at /2007/12/14/sub-fertility-or-reduced-fertility/ ). Clinical infertility is classified further into male infertility, female infertility, couple infertility, and unexplained infertility. Studies have shown that in the past 50 years the quality and quantity of sperm has dropped by 42% and 50% respectively. In the past 20 years the decrease in sperm counts has occurred at a rate of 2% annually. For further information refer to Xeno-estrogens (see the Alphabet of bioZhena at /2007/11/28/the-alphabet-of-biozhena/ and the web reference therein).

In the U.S. alone, of the 6.7 million women with fertility problems in 1995, 42% had received some form of infertility services. The most common services were advice and diagnostic tests, medical help to prevent miscarriage, and drugs to induce ovulation [Fam. Plann. Perspect. 2000 May-Jun;32(3):132-7].

 

 

 

A Glossary of Infertility Terms and Acronyms published by the InterNational Council on Infertility Information Dissemination is available at http://www.inciid.org/glossary.html .

 

 

ART or Assisted Reproductive Technologies:

 

Also referred to sometimes colloquially as the “heroic procedures”, they are used to treat infertility patients. ART refers to all techniques involving direct retrieval of oocytes (eggs) from the ovary. They are: artificial insemination (AI), IVF (in vitro fertilization), TET (tubal embryo transfer), ZIFT (zygote intra-fallopian transfer), GIFT (gamete intra-fallopian transfer), ICSI (intra-cytoplasmic sperm injection), blastocyst transfer and other infertility treatments, such as IUI (intra-uterine insemination), assisted hatching (AZH), and immature oocyte maturation (IOM).

Web reference: http://www.ebiztechnet.com/cgi-bin/getit/links/Health/Reproductive_Health/Infertility/Education/Assisted_Reproductive_Technologies/

 

 

Sub-fertility or Reduced Fertility

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

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

Subfertility (THE INITIAL TARGET OF BIOZHENA):

A state of less than normal fertility but not as bad as clinical infertility. Also called reduced fertility, it refers to the inability to conceive for more than about 4 months but not more than a year (which then becomes classified as clinical infertility, the inability to conceive after a year of unprotected intercourse). It is estimated that as many as one in six couples (17%) have difficulty in conceiving the number of children they want when they want them.

Again: Research suggests that between 14 and 17 percent of couples are affected by subfertility at some time during their reproductive lives. In fact, only eight out of 10 couples trying for a baby do get pregnant within 12 months. For approximately 10 percent of couples, pregnancy will still not have occurred after two years (clinical infertility). Sometimes the label of subfertility is used for couples who have had regular unprotected sexual intercourse for all of two years without conception taking place. This is a reflection of the fact that subfertility is becoming more and more commonplace.

According to one source ( http://www.womens-health.co.uk/ ), even for a healthy fertile couple, the ‘per month’ success rate (conception rate) is only around 15-20%, “so it is not at all uncommon to take some months to conceive”. Overall, around 70% of couples will have conceived by 6 months (a 30% subfertility rate). 85% conceive within 12 months (a 15% subfertility rate, “for the less impatient”). And 95% will be pregnant after 2 years of trying (technically, this is a conservatively estimated infertility rate of 5% – c.f. the 10% referenced above; or, this statistic might be perhaps considered the subfertility rate for the angelically patient). The monthly success rate in this population is 8%, and this statistic drops progressively as time goes on.

As for possible causes of difficulty to conceive, alcohol consumption, even in small amounts, can reduce a woman’s chance of conceiving by more than 50 percent, and smoking “…drastically reduced fertility in our sample”, as wrote a team from the Baltimore-based Health Care Financing Administration, in a report published in “Fertility and Sterility” (1998; 70: 632-637).

In terms of help, many people believe that fertility drugs, even when effective, remove conception from the intimate relationship between the partners, which means that it is to some extent beyond their control. Besides this loss of control, there are drawbacks and disadvantages to all forms of medically assisted conception. Some of them have potentially serious long-term effects. Consequently, many couples prefer to avoid these risks.

Women who describe overcoming infertility with the help of alternative therapists went to them because they had been offered drugs to induce ovulation but were reluctant to take them, when they learned of the possible side effects. Disturbing reports have appeared about the long-term as well as short-term effects of assisted conception. Increased miscarriage levels and premature and multiple births are not only very distressing but have considerable cost implications, both personally and societally (i.e., this is a public health issue). Babies born prematurely, or in multiple births, are at a disadvantage from the start. There are also some reports of increased rates of ovarian cancer in women who have taken fertility drugs, and of cancer in the babies of mothers who have had ovulation induced by drugs.

Subfertile couples are naturally interested in methods and tools that can help them to overcome the difficulty to conceive. 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.

With the mentioned statistics of the fertile-age women suffering from the subfertility problem, this is a truly large opportunity in a constantly renewing and growing market. We are talking about 9 or 10 or even 18 million women in the USA alone – or quite possibly many more, taking into account all the impatience and demand for instant gratification in people today; plus about 50% of the 10 million of clinically infertile US couples, that is those who cannot afford the very costly ART treatments. [A.R.T. = Assisted Reproductive Technologies.]

This is the initial, early-stage, mission of bioZhena Corporation: To provide a definitive timing aid to couples experiencing difficulties in conceiving a baby. See also the entry for the Ovulona, where it is explained that, in this situation of reduced fertility, the basic problem is the proper timing of the intercourse.

 

Four fertility-related terms and concepts

For others, see the Alphabet of bioZhena at /2007/11/28/the-alphabet-of-biozhena/

Fertile phase or fertile window:

The days of the menstrual cycle, during which sexual intercourse or insemination can result in pregnancy. It includes several days leading up to and including ovulation. The exact number of the fertile days is not known. It is currently “officially” believed to be 6 days, although evidence shows that there are only 3 days of high probability of conception (while the other three days are likely due to inadequate methods of ovulation monitoring used in earlier studies). The unequivocal determination of the fertile window is a pivotal task for bioZhena. See also the previous post: /2007/12/03/fetal-sex-preselection-%e2%80%93-illustrated/

The fertile window is an empirical factor, which should be consistent with the fertilizable lifetimes of the gametes (the egg and the sperm). Those are also uncertain but currently accepted figures are up to 12 (or maybe 24) hours for the egg, and at most 3 days for the sperm. (These times must overlap, of course; they are not additive.) The historically excessive length of the officially recognized fertile phase has always been due to the absence of definitive diagnostic means. Some years ago, a reviewer of a federal grant application wrote to reject the proposal on the basis that the officially recognized required period of abstinence was about two weeks, which is impractical…

Fertility (or Fertility Status):

The female of any mammalian species, including the human female, can conceive only during a very limited period of time (a window of only a few days, arguably 3), and only if all conditions are perfect. The fertile window occurs repeatedly at intervals that are more or less regular (28 + or – 9 days or so) but their variability is substantial to the extent that planned pregnancy is a challenge. A normal healthy couple will statistically take at least 3 or 4 months to conceive, even if the concept of the fertile window is known to them. An increasing percentage of couples experience difficulties in achieving pregnancy, and reproductive specialists have found that a large percentage of women had no idea of when they could conceive.

FAM (Fertility Awareness Method):

A method of determining a woman’s fertility status through self-assessment of certain fertility signs: waking temperature (also called the basal body temperature or BBT), cervical fluid, and cervical position. While NFP users abstain, FAM users apply one of the barrier methods of contraception for vaginal intercourse during the “unsafe days” of a woman’s fertile phase. NFP stands for Natural Family Planning.

Fertilization:

The joining of an egg and sperm. More accurately, fertilization is the union of a spermatozoal nucleus, of paternal origin, with an egg nucleus, of maternal origin, to form the primary nucleus of an embryo. It is the fusion of the hereditary material of two different sex cells, or gametes, each of which carries half the number of chromosomes typical of the species.

Although sperm can swim several millimeters per second, their trip to and through the fallopian tubes is assisted or facilitated by muscular contraction of the walls of the uterus and the tubes. There is also evidence that the egg releases a chemical attractant for sperm. In any case, sperm may reach the egg within 15 minutes of ejaculation. The trip is also fraught with heavy mortality. An average human ejaculate contains several hundred million sperm but only a few hundred complete the journey. And of these, only one will succeed in entering the egg and fertilizing it. Fertilization begins with the binding of a sperm cell to the outer coating of the egg (called the zona pellucida). Enzymes, released by the acrosome at the tip of the sperm head, digest a path through the zona and enable the sperm to enter the cytoplasm of the egg.

For fascinating details, explore the developmental biology site http://zygote.swarthmore.edu/chap4.html . You will see, e.g., a photo showing the “sun in the egg”: the microtubules (stained with fluorescent antibodies to tubulin) radiating from the centrosome associated with the male pronucleus and reaching towards the female pronucleus. “This vivid image conveyed the discovery of the moment at which a new life was formed. The metaphor expressed awareness that the force of natural powers was greater than the sum of two cells.”

Then, you can read up on Homunculus: Historiographic Misunderstandings of Preformationist Terminology, an essay by Clara Pinto-Correia, abstracted from her forthcoming book, The Ovary of Eve. This essay examines the association of the term “homunculus” with the “little man” that some of the leading spermists located inside the head of the spermatozoon during the rise of theories of reproduction in the seventeenth century. You can further find out that there is “a history of speculation about sex determination that views women as incomplete males… about the notion that women are almost-men whose development or evolution is truncated… how textbooks claimed that maleness means mastery, the Y-chromosome over the X, the medulla over the cortex, androgen over estrogen…”

The Ovulona™

 

This is the putative trade name of the women’s health version of the bioZhena device, as opposed to the animal version (see the BioMeter entry in the Alphabet of bioZhena). An earlier prototype was once referred to as the Ovulon but the feminine-gender name is surely more appropriate.

Now a citation: A remarkable property of the cervix is the extreme sensitivity to the effect of estrogen and progestogens. Changes in the composition and properties of cervical secretions have been used for many years as an in vivo biologic assay for sex steroids. How well put, on page 564 of the compendium “Human Reproduction: Conception and Contraception”, edited by E.S.E. Hafez and T.N. Evans, Harper & Row Publishers, 1973.

In the Epilogue, Professor Hafez further states that “…the fertile period of the menstrual cycle is not more than 4 days, and probably less”. He also says: “Unfortunately, accurate detection of this fertile period is difficult, due to individual variation in the length of the menstrual cycle and frequency of ovulation, and to the absence of clinical signs of ovulation.”

We cite him here because the books edited by Hafez were explored at the inception of this project, and because all these referenced facts of life were the premises for the inception of the project and for the development of the intellectual property.

You may almost view the cited reference to the remarkable property of the cervix as a definition of the bioZhena innovation. “Accurate detection of the fertile period” is the operative phrase, and it is what eludes the various alternative methods and products. We all know that those products have not solved the fundamental diagnostic problem of woman- or mankind.

We have, and here is a schematic diagram of how:

The origination of the Ovulona (and/or BioMeter) technology was a response to this basic human need on the part of a husband and wife pair of scientists. On the one hand, we struggled with the newly experienced pain of an apparently sterile marriage. But we also realized that we were conceivably in a position to help ourselves by combining our respective professional resources.

It all goes back to the postulate, by the ever so pragmatic female of the species, that before any of the more or less bothersome medical procedures should be undertaken, the basic problem of proper timing (of the conceptive intercourse, insemination) must be conquered.

This is how the project came about, and everything else followed. (The reader will understand that the postulated principle holds for every couple.) And let’s be explicit about the fact that “everything else” includes not only the broad applicability of the ensuing tissue biosensor.

That “everything else” also includes the realization that we are monitoring folliculogenesis (the maturation of the egg in the ovarian follicle). And it includes, more importantly, the crucial capability to detect ovulation and not just predicting it.

Although we could not really be clear about this until Chiara Benedetto, M.D. sent us the results of measurements (with an early prototype) of her carefully selected baseline-type subjects, the Ovulona provides not only a short-term anticipation of ovulation but also an earlier long-term prediction signal.

 

 

The cyclic profile features are briefly discussed in the Post Script, below.

This long-term predictive peak really has no counterpart among the various other methods of fertility monitoring. Its position ahead of ovulation apparently depends on the rate of maturation of the dominant follicle in the given menstrual cycle, and it correlates with the length of the menstrual cycle. None of this would have been apparent from the early in-house longitudinal study, since the study involved a non-baseline subject. In non-baseline cycles, which are common in real life, even the luteal (post-ovulation) phase often is not constant… and various other deviations occur from the ideal case descriptions in medical textbooks.

Data to date indicate that the long-term warning of the upcoming ovulation event occurs comfortably early for the practice of natural family planning (NFP). Consequently, we are in a position to claim progress over the 1973 statement in the Hafez Epilogue, which stated that “the long-term prediction of ovulation by at least 6 days seems to be difficult and, as yet, unsolved” (loc. cit. page 711).

The capability to anticipate ovulation well in advance, and to then detect ovulation independently of the predictive signals, is unique to the bioZhena technology.

This unique capability results from the mode of action, further discussed in the Alphabet of bioZhena under Modus operandi (MO). See also under Mysterious conceptions – or the non-existence thereof. From the MO also follows the broad applicability of the technology, which is another feature that distinguishes the Ovulona from any other product addressing fertility status and ovulation monitoring. For a potential impact of the technology on public health, see under Sexually transmitted diseases, and also under Cervical cancer and under Smoking.

It could be argued that the greatest aspect of the bioZhena project is the idea of introducing – via the affordable personal fertility monitoring method – a general, routinely usable, women’s health tracking and diagnostic tool, with the potential to impact on several important areas of public health. We have every intention to make this argument, and we plan to put it into practice.

 

Post script

Here is another (larger, easier to read at Zoom 150%) rendition of the data:

Three baseline cycles from Turin study

The cyclic pattern exhibits a number of well defined peaks and troughs: The first repeatable feature is the first post-menstruation minimum occurring typically on day 6, 7, or 8 (driven by the selection of the dominant follicle). The signal then rises to a maximum (the long-term predictive peak), which is driven by the maturation of the dominant follicle.

This 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). <!–[endif]–>

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.

The post-ovulation (luteal phase) peaks and valleys have only recently been interpreted as due to the follicular waves (preparing for the next menstrual cycle). The follicular waves are a recent discovery in women [Baerwald AR, Adams GP, Pierson RA, Fertil. Steril. 2003 Jul;80(1):116-22, “A new model for ovarian follicular development during the human menstrual cycle”], which now adds a significant diagnostic use to the luteal-phase part of our cyclic profile (re: menopause, aging).

 

BIOZHENA’S MISSION: A HEALTH TOOL FOR EVERY WOMAN

Far more than a tool to aid achieving pregnancy

 

bioZhena vision explained

 

 

 

Our vision is to create a product that practically every woman will want to use. The woman of the 21st century is envisaged to become accustomed to using her daily Ovulona self-check about as routinely as she is using her lipstick or her toothbrush.

The Ovulona™ will be useful to the point of becoming an essential tool of women’s health management, both at home and, if need be, for the provider in the doctor’s office. Accordingly, the Ovulona will be supremely user-friendly and affordable for everyone.

 

 

 

 

Go to bioZhena vision explained

 

 

The Elevator: Swiss VC/PE deal-maker offers bioZhena to their investors

The Elevator, “The Magazine for a Wealth of Opportunity”, December 2007

 

This post is about the integral and unavoidable aspect of project development – seeking development capital. The title could conceivably read “From Switzerland With Love”, if a play on words were intended. Such as the name of The Elevator magazine is a reference to the phrase “elevator pitch”, a standard concept in the venture capital/private equity arena (meaning a very brief introductory pitch of the investment proposition; The Elevator articles are naturally somewhat more extensive than that).

The editor of The Elevator reviewed and published bioZhena after we responded to their invitation, “Seeking Deals to Fund”, http://www.linkedin.com/pub/0/456/786 .

The Elevator (“The Magazine for a Wealth of Opportunity”) is an impressively produced electronic magazine, attached. On page 3, the editor writes: “…since our first issue in March 2006 we have reviewed over 300 projects and retained 60 of them as features. More than 10,000 individuals have seen The €levator ; we’ve had a great diversity of projects, much interest and several deals closed over the past 12 months. … I invite all our readers to become active members of our investor’s forum …“.

On page 35 appears the following claim: OUR TEAM OF EXPERTS PROVIDES ACCESS TO THE BEST SOLUTIONS IN PRIVATE EQUITY, ASSET MANAGEMENT AND VIP ADVISORY.

Here are the headlines from the magazine’s title page, featuring a partial list of contents, and bioZhena is one of these featured listings:

• How to open your own fund. An introduction by the experts of JP Fund Services
• bioZhena. The turnkey technology for birth control
• VentureLab. The professional matching platform
• The Village Barbados. Prime Luxury Retreat seeking USD 31 million

The interesting thing about this presentation of bioZhena, by the Geneva-area international business VC/PE deal-maker, is their risk scale. We see a scale with 6 colors, from green and light green, through yellow, then light pink and dark pink, and finally the highest risk level is red.

The editor indicates the risk level of the bioZhena proposition as between light green and yellow (or level 4 on a scale of 1 to 11). This is the same as that of the real estate deal “The Village Barbados”, and it is better than the level 5 [yellow] risk level of the VentureLab deal, and it compares favorably with the various other listings in this December issue of the Elevator. Only the Yacht Club Mediterranean and the Castellan, New York real estate deals are assessed with lower risk levels, 2 and 1 respectively.

It is also interesting that bioZhena’s risk level is assessed the same as that of DealFlow, Toronto – “a television series that captures the drama and sport of global business as seen through the eayes of dealmakers”. DealFlow “is currently seeking US$620,000 in a US$875,000 Private Placement Offering of Convertible Preferred shares at US$20.00 per share”.

bioZhena’s investment opportunity is described as follows:

Investment Volume: Up to $ 15 Million (current Offering for $3M plus 1-year $3M Warrant)

Est. Return on Investment: 100%+

Est. Duration: Approx. 3 Years

Minimum Investment: $250,000 or a portion thereof at Company’s discretion

 

Ref.:

The Elevator, “The Magazine for a Wealth of Opportunity”, December 2007

Fetal sex preselection – illustrated

Fetal sex preselection – illustrated

In the document attached to this post, we say:

The following illustration is adapted from one of our slides. Here is the slide:

The three-day fertile window how-to

View the slide in the Slide Show mode, as there is animation.

The attachment opens in their Normal mode. Click View on upper left and select Slide Show.

The slide indicates how it works or rather how it will work when the smart Ovulona™ is launched in the marketplace. The data were generated in a clinical study performed with our early prototype, and show the morning and evening cyclic profiles from one of the baseline subjects studied by the gynecologist Dr. Benedetto of the University of Turin, Italy.

And here is, in a nutshell, the clinical trial evidence of the 3-day fertile window:

This is a replot of their data whereby the outlier data points were considered to in fact belong to the counts of the three days of high birth counts, the outliers having been due to their inaccurate and unreliable methods of guessing at ovulation.

 

More details are in the attached file: Fetal sex preselection – illustrated

This is a detailed description of the origin (including the best clinical trial evidence available to date) of the 3-day fertile window.

The 3-day window of high conception probability is unequivocal (there is no doubt that the data show that window). The low birth counts on the flanks of this 3-day group are data point outliers due to errors in the investigators’ guessing the ovulation day. The 3-day group of high birth counts is there whether we simply ignore the outliers or add them to this group. This is no unreasonable massaging of the data because the investigators’ methods of estimating ovulation timing are well known to have high error bars associated with their ovulation-day estimation.

.

Regarding fetal sex preselection

A new friend, interested in the bioZhena technology and venture proposition, has written to me:

“One question that I’ve gotten is around the accuracy of sex selection. I know this is (or can be) a controversial subject. My wife and I (parents of 3 boys) tried using one of the methods in a book to have a girl on our second try. It didn’t work, obviously, and our son decided to come on his own. Could you please tell me more about that part of the test. I understand it in theory but probably it will need to go into clinicals to validate the claim – right?”

I responded fairly promptly, but without details such as the references and especially some graphics, and without expressing serious doubt about my friend’s book and the advice they had drawn from it. This was my response:

Of course, sex preselection is a controversial subject. Most important, though, is that you understand that this is not our initial product offering; it is merely a well justified expectation (speculation), which requires a study and investment, just like the early cervical cancer diagnosis as well as the birth control uses of the Ovulona technology.

What we have for immediate market introduction is the Ovulona as a tool for aiding conception, as previously passed by the FDA, and that did not include any fetal sexing claims.

…

[NFP = Natural Family Planning; FAM = Fertility Awareness Method]

We will introduce SFP, Scientific Family Planning. SFA, Scientific Fertility Awareness. All four ™-designated.

For your immediate understanding of this particular fetal sexing implications of the bioZhena technology, you presumably are aware of slide 4. Now I summarize for you where this comes from. Namely, I paraphrase from a detailed white paper, which is available for study upon request, if interested:

…a 1992 publication by John T. France et al., reporting data from 55 pregnancies (and births). The study was based on data whereby only one coitus per fertile period occurred, and three different markers were used to estimate the time of ovulation.

The stringency of the study design by France et al. went so far as to exclude 29% of pregnancies from the birth sex ratio evaluation in terms of timing of conception with respect to ovulation, because of more than one act of intercourse during the fertile period. Significantly, the birth sex ratio was 0.50 for this excluded group but far from 0.50 for the good study population.

The results of the France et al. study were as follows: Of the 34 male infants born, 65% were conceived 2 to 5 days before ovulation, and 71% of the born girls were conceived from intercourse timed between 1 day before to 1 day after the estimated time of ovulation. However, there was a great uncertainty about the actual ovulation day because in only 9% of the cases did the three ovulation markers agree with each other. In 68% of the cycles, agreement was within +/-1 day. The peak cervical mucus marker was one while the other two markers were the onset of the LH surge, and the basal body temperature rise.

Hoping that this mildly specialist language is not just mumbo jumbo to you, the key to this is your understanding that until the emergence of our device there has not been a definitive tool for this; that is, not only predicting but also detecting ovulation – and everything else follows from this simple fact.

The France et al. study was the best, better than some others, but even France et al. did not do everything right. For example, John France was not able to share those 9% of cases where the three methods, which they wisely used (to make up for the absence of a definitive tool), coincided in terms of the day of ovulation. Those 9% could have given us a better, almost definitive baseline. (5 definitive cases, if coincidence of three unreliable methods amounts to definitiveness. 5 = 9% of 55.)

K., this slip into details has been due to your scientific education and the personal level of your prior involvement with the subject, which presumably makes for an appreciation not necessarily to be found elsewhere, in other people.

Having quoted the question and answer verbatim, my next post will attempt to improve the answer (the answer to what may well be a burning question in numerous minds) with the illustrations and explanations.

The Alphabet of bioZhena — Abeceda bioŽeny

THE ALPHABET OF BIOZHENA WITH CLICKABLE TABLE OF CONTENTS

The Alphabet of bioZhena

A glossary of biomedical terms for bioZhena Corporation

 

 

The glossary-and-primer of bioZhena is attached; click on one of the links above.

In THE ALPHABET we expand on – and explain the meaning of – the one brief sentence: We have invented the new technology of ovulography™, fundamental to women’s health and lifestyle.

Ovulography is bioZhena’s proprietary technology for monitoring folliculogenesis in vivo. To tell the woman user, which are the three days when she can become pregnant (and the rest of the month when she cannot). And there is more, much more, which is what THE ALPHABET OF BIOZHENA is about.

This glossary/primer of bioZhena Corporation is no Alphabet of Ben Sira — an anonymous work, which has been dated anywhere from the seventh to the eleventh century, and which tells the story of the conception, birth, and early education of the prophet Ben Sira.

There were twenty-two stories (mimicking the twenty-two letters of the Hebrew alphabet) to answer the questions posed by the Babylonian king Nebuchadnezzar. Apart from being notable for the story of Lilith, the primordial first wife of Adam, what makes this ancient text particularly unique and fascinating is its irreverent tone … And, we get to learn of the angels who are in charge of medicine: Snvi, Snsvi, and Smnglof!

For more information on the ancient and irreverent Alphabet of Ben Sira, go to http://www.google.com/search?q=Alphabet%20of%20Ben%20Sira !

 

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And now, as the ancients would say, remotum joco (roughly, “joking aside”):

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A simple description and pictorial representation of the female reproductive organs is available at the American Medical Association’s web site “Atlas of the Body: Female Reproductive Organs”: http://www.medem.com/MedLb/article_detaillb.cfm?article_ID=ZZZ8QKJ56JC&sub_cat=2

A more detailed treatment of Sexual Reproduction in Humans is given in http://www.ultranet.com/~jkimball/BiologyPages/S/Sexual_Reproduction.html

For a particularly enjoyable, stimulating and informative source on the intimate geography of womanhood, reach for Natalie Angier’s Pulitzer Prize winning book “Woman – An Intimate Geography”, Houghton Mifflin Company, 1999, ISBN 0-395-69130-3. An excellent background read for the appreciation of bioZhena. But read Mysterious conceptions, under M.

 

For all that, go to one of the attached files: The Alphabet of bioZhena in PDF format. THE ALPHABET OF BIOZHENA WITH CLICKABLE TABLE OF CONTENTS is more convenient than the PDF version that does not have the clickable table of contents.

Hello world!

This is our alternative or introductory About. Written as a post when getting into this blogging, getting the hang of it here… Thank you to WordPress.com. Please do visit the About page, for a more informative introduction to bioZhena.

In one brief sentence: We have invented the new technology of ovulography™, fundamental to women’s health and lifestyle.

We have a personal fertility status monitor for home use by women, and a data management system for physicians who can receive the folliculogenesis data from their patients.

Our personal self-diagnostic device, the Ovulona™, tells the woman in plain English whether today is one of the three days that she can become pregnant.

How? We monitor the process that causes menstrual cycles and is fundamental to women’s health. Primary use is for reproductive management: birth control and aiding the achievement of pregnancy. But there is much more, including an automatic screening for cervical cancer, management of PMS/PMDD and management of hormone therapy, to name just a few uses that come with the core technology.

To wit: Ours is a unique and disruptive technology.

Only this Ovulona device can provide to the woman at home the interpreted fertile status results in plain language for an immediate use, and provide data of unequaled accuracy. This is why ours is the only diagnostic tool that can be used for birth control.

Only our technology can perform an automatic cervical cancer screen in the background, free of anxiety, discomfort and high cost (as associated with the Pap smear). We also plan to incorporate a therapeutic function into the Ovulona device. All this will add to the consumer appeal of our core product line, already well documented.

bioZhena is a medical consumer electronic technology developer, with a significant intellectual property. We plan on having a marketable product ready within 7 months of funding, and profitability within 2 – 3 years. Adequate funding is referenced here…