bioZhena venture

bioZhena’s technology platform is bound to revolutionize women’s healthcare with diagnostic tools for women and their doctors & payers.

Empower women with clear menstrual cycle data vs. drugging healthy women & the iatrogenic consequences.

This is the first (sex-life management) application providing a superior (definitive) tool with which to tackle the ever-growing difficulty of getting pregnant when planned. And using the same tool for hormone-free, non-interventional, pregnancy avoidance. And, making available the 5th vital sign menstrual cycle profile signature to physicians when needed, for better diagnosis and management of health issues.

Also unprecedented and important for public health is our way of monitoring inconspicuously at the same self-check time the woman’s cervical health – at home. This will work in the background of the primary process, not bothering the user unless a tissue aberration is detected consistently several months in a row. This way of innocuous screening, and its affordability, should significantly improve on the Pap smear screening test.

Explore the few slides including the links in some of them: https://biozhena.wordpress.com/wp-content/uploads/2017/03/new-mostly-narrated-slides-2017-03e2.pps

.

But perhaps – especially if you are a male reader – you may feel that a daily (or almost daily) insertion for the quick self-check is too much to expect of a woman keen on knowing her daily fertility status plus the additional benefits of the routine?

Then our next generation telemetric cervical ring iteration of the same smart sensor is the answer for you. She and her doctor will have a choice.

See the image of a slide and click it to view the slide, grasp the significance:

https://biozhena.wordpress.com/wp-content/uploads/2017/05/single-slide-friendly-tech-with-cervical-ring-ovulograph.pps

.

But then my gynecology colleague would argue that the other major healthcare front is even more important. Namely, our way of providing to the women’s healthcare professionals access to the menstrual cycle vital sign longitudinal records, which Dr. Kim likened to the cardiologists’ ECG recordings – but with the important advantage of being affordably and routinely generated by patients at home (and saved in the sensor).

This other major front is providing to the healthcare system the means of obtaining a handle on the management of gynecologic and obstetric medical issues that require better diagnostic evidence for more effective and preventative therapies. In brief, we are answering the call and challenge to “Improve the methods and criteria to assess ovulatory dysfunction” (per R.S. Legro MD, 2013), and more.

Current modalities to diagnose preterm labor cannot detect the early biochemical changes of the cervix which result in dilation that leads to preterm births. Once the advanced signs of preterm labor are found, remedies to stop it are often futile and always costly for the healthcare system ($26B annually in USA alone), and frequently have adverse long-term consequences for the prematurely-born child and the family.

https://biozhena.wordpress.com/wp-content/uploads/2014/11/impedence-beyond-cervical-length.pdf

.

The bioZhena technology will alert the women-users and their healthcare providers on a timely basis to the onset of pregnancy-related conditions such as normal and preterm labor. And the immediate detection of pregnancy, whether intended or unintended, is automatic with the primary routine use of the home-use smart sensor. That is a notable advantage over the current home pregnancy tests!

.

Summing up, read an overview Feasibility of the Planned Range of Ovulona™ Applications

https://biozhena.wordpress.com/wp-content/uploads/2014/11/feasibility-of-the-planned-range-of-ovulona-applications1.pdf

.

And here is now the financial pro forma aspect of bioZhena’s breakthrough non-interventional approach to women’s healthcare.

5-year pro forma assuming $6M funding (5-year Business Plan Summary Financial Projections)

Or, better,

10-year projections:

Minimum Viable Product Scenario (MVS) and Full Value Scenario (FVS)

For better legibility click https://biozhena.wordpress.com/wp-content/uploads/2016/09/comparison-mvs-cf-fvs.pps

.

From bioZhena’s pitch on EquityNet:

Women’s personal sex-life management tool for the Information Age.

Generating diagnostic vital-sign profiles for doctors and payers.

This first app of proprietary cervical sensor has FDA clearance.

Income from it will support further breakthrough applications.

.

The gist of the bioZhena women’s healthcare breakthrough is this:

We monitor the brain – sex organs feedback loop.

Nobody else does.

.

See the illustration below. Grasp the significance: The market offers you anything other than what’s needed, which is the monitoring of the feedback brain – ovary interactions.

“To mitigate the startup investment risk, the first app is an already FDA-cleared electronic fertility monitor for women at home…

Our electronic technology platform is bound to revolutionize women’s healthcare with diagnostic tools for women and their doctors & payers.

… will provide for non-interventional reproductive management, aiding conception and natural birth control without hormones, and automatically detecting pregnancy – planned or accidental. …

We will offer early detection of cervical cancer and other STDs as a built-in screen performed innocuously in the privacy of one’s home – automatically in the background of the primary monitoring…

Ovulona™ tracks the female reproductive cycle via the end-organ effect of the brain-ovary feedback loop on the uterine cervix. Numerous benefits ensue…”

.

This is a screen shot of slide 4 from a 5-slide set https://lnkd.in/ed9yXUX

(slides take a few moments to open).

.

Contra Nescience Contra Insouciance (SM 2015)

The Home Page of bioZhena’s Weblog offers further particulars (click the link, which translates as “Against Ignorance Against Indifference”)

.

And yours truly bioZhena founder seeks a well-matched management partner of either gender.

.

About atrophy, reproductive aging, and how it’s really not nice to fool Mother Nature – or with

I have taken it upon myself to popularize Prof. Erik Odeblad’s classic findings about the biophysics of the tissues and secretions of cervix uteri, and how they translate into reproductive physiology and hence to reproductive medicine – at home and in the doctor’s office.

  Emeritus Professor Erik Odeblad    “The cervix is a precision organ as complex as the eye”

My ulterior motive is that I want to be understood when harking back to the British commercial’s exclamation that warned about too arrogant an attitude towards Mother Nature. Or, maybe I aim at the wisdom of the saying (“It’s not nice to fool Mother Nature!”) to be appreciated particularly within the given field of endeavor and/or endeavour – that is, reproductive management. Even if it were only in a segment of it.

In the Alphabet of bioZhena (which is no Alphabet of Ben Sira, though we model on it somewhat), https://biozhena.wordpress.com/wp-content/uploads/2007/11/aaee-the-alphabet-of-biozhena.pdf , there is an entry about Atrophy and what it does to a woman as years go by, how “atrophy of mucosal surfaces takes place, accompanied by several problems.”

Jan Amos Komenský (Comenius) Says Farewell to…

In this blog post I focus on aging – and thus atrophy – of the cervix, leaving aside the inevitable corresponding phenomena in other parts of the reproductive system.

The focus on the cervix is due to bioZhena’s focus on the cervix… which in our scheme of things is the supreme monitor of the complex reproductive goings on that Mother Nature designed in order to cope with all that complexity. After you’ve read the Alphabet article on atrophy, you might scroll down to the entry there about the cervix, which will take you also through cervical cancer and cervical mucus, besides a couple of other things cervical. That will or would be a nice preparation for, or introduction to, what follows.

Two sketches by Emeritus Professor Erik Odeblad to illustrate his saying, “The cervix is a precision organ as complex as the eye”. Click (right-click) on the image to see the details. And read on about the details. The fine structure of the cervical canal wall, schematized on the right, is based on examination of mucus samples obtained with a suction syringe from the various parts of the cervical canal of human volunteers for physico-chemical examination.

When, at the inception of the project, we decided to focus on the given part of the anatomy, Erik Odeblad’s work logically and inevitably became a part of the background. He used the NMR (nuclear magnetic resonance) technique of physical chemistry to perform the complicated investigation of cervical mucus, and he produced the classical evidence for the difference between the “fertile” mucus macromolecules that allow the passage of the sperm, and the “infertile” cross-linked glycoprotein molecular network that does not. (To this day I remember his usage of “undulations”…)

In fact, this early information, which involved the thiol-disulfide (sulphydryl-disulphide) redox couples in the glycoprotein macromolecule, had much to do with our early hypothesis of the mechanism of our measurements. Never mind that his work was in the context of the subjective self-examination used in NFP, which did not work for the female member of the team! Had it worked for her, there would probably not be any Ovulona™ for monitoring folliculogenesis in vivo (FIV™ – which has utility well beyond fertility status determination)!

With atrophy being the general biological aspect of aging (and with the initially very large number of ova or eggs in the young female’s ovaries decreasing as she matures and ages), the cervix similarly “undergoes a natural process of development and aging. The surface area of the cervix that is given over to the mucus secreting glands [“crypts”] gradually diminishes with age.”

Odeblad defines three types of the (endo)cervical glands, which he (and others too e.g. Embryology.CH and Eurocytology.EU since at least the 1970s) calls the “crypts”:

• S crypts produce S mucus, which forms string-like channels and provides transport (“swimming lanes”) for sperm cells. (“Produces a wet, lubricative sensation at the vulva.” That’s for the NFP sympto-thermal method use, the Billings method and/or the Creighton Model NaProEducation Technology method, the classical NFP or FAM – the latter, Fertility Awareness Method, publicized by Ms. Toni Weschler’s 2002 book Taking Charge of Your Fertility .)

• L crypts produce L mucus, which eliminates low-quality sperm and provides a structure to support what he calls the S and the P mucus. P is a reference to the so-called Peak mucus of NFP or FAM.

• G crypts produce G mucus, which is “an impenetrable gestagenic mucus formed in the lowest cervical crypts. Prevents sperm entry to the cervix and is part of the immune system which protects the woman’s reproductive system from infection.” A remark from dictionary.com: gestagen (jěs’tə-jən, -jěn’) n. A substance, such as a steroid hormone, that affects the uterus in a manner similar to progesterone. And a remark from a scientific commentator: This G mucus is characterized by the oxidized state of the mentioned redox couples, causing cross-linking in the glycoprotein mucin, which prevents microbes including sperm from entering. Visualize this as closed -S—S- gates (as opposed to the open gate form -SH   HS- of the “reduced” state of the redox couples; “reduced” meaning “electronated and hydrogenated”, the opposite of “oxidized”).

Mondrian_Evolution

There are three fundamental principles at work.

1. Natural baseline aging, and this is fundamental – a more or less linear decrease in the number of all three kinds of these glands or crypts, at somewhat different rates: S the fastest, L somewhat slower, G slower still.

2. Slow-down of the aging atrophy by pregnancy.

3. Acceleration of the aging atrophy by the Pill [and/or by other endocrine-active compounds, EACs – this is a logical extrapolation, speculative, but must be assumed].

Now, then.

1. Natural baseline aging, fundamental – a more or less linear decrease in the number of all three kinds of these glands or crypts:

“The number of S crypts decreases from teen age. They are first replaced by L crypts starting at the base of the cervix. Later G crypts replace the L crypts.”

Thus, from Odeblad’s graph [rate reckoned from 15 yrs old to 40 yrs old]:

S crypt baseline decrease or diminution (or atrophy) rate:

50% / 25 years = 2% per year.

At 50 years old, S crypts are at some 10%.

Profile of cervical crypts of a baseline woman – never pregnant & never on the Pill

Representative profile of cervical crypts

(percentage of cervix occupied by active crypts)

for a woman who goes through life without pregnancy or use of the Pill.

This is a baseline profile.

Here is Erik Odeblad’s schematic of the crypts on the surface of the cervical canal:

Carefully mapped lateral wall of the cervix of a 20 year old virgin           (reported by Emeritus Professor Erik Odeblad, Department of Medical Biophysics, University of Umeå, S-90187, Umeå, Sweden)

This is Professor Odeblad’s artist’s impression of cervical mucus secretions:

Schematics of cervical mucus secretions

Key to colors:

Blue         = S mucus

Yellow     = L mucus

Red          = G mucus

Green      = P mucus of which there are several sub-types

Pink         = Z granules

Professor Odeblad’s explanatory notes:

Z granules – the enzyme in the Z granules combines with the P mucus to create a liquefying effect.

P mucus – there are a number of sub-types of this mucus, the most relevant for fertility are P2 and P6. P2 could be present as early as the beginning of the fertile phase possibly having a role in liquefying the G mucus. P6 is mostly confined to the upper part of the cervix, occurring close to the Peak of fertility, and having a role in conveying sperm. It creates a very wet and lubricative sensation at the vulva.

F mucus – comes from the cells scattered throughout the length of the cervical canal and has no known special function.

For a recent evidence of four different morphological mucus types, namely L, S, P and G, see “Morphological characterization of different human cervical mucus types using light and scanning electron microscopy” by M. Menárguez, L.M. Pastor and E. Odeblad, Human Reproduction, Vol. 18, No. 9, 1782-1789, September 2003 –  http://humrep.oxfordjournals.org/cgi/content/full/18/9/1782

Citation: “The distribution of crypt zones in the cervix depends on age, number of pregnancies and use of contraception. In a non-pregnant woman, aged 25–30years and not having used contraception, the cervix averages 22 mm in length and 6 mm in diameter at ovulation. The crypt distribution starting from below and moving upwards is as follows: the G crypts dominate in the lowest 4–5 mm; then there is a zone of L crypts occupying the next 9–10 mm; this is followed by the S zone, for 5–6 mm; and the highest 3–4 mm contains the P crypts.”

When you read the paper, you detect that he has a very special knack for sampling the respective mucus types from the said crypts. Hat off! Work with human experimental subjects is no stroll in the park, to put this mildly.

2. Slow-down of atrophy aging by pregnancy:

Profile of cervical crypts of a 4x pregnant woman

Representative profile of cervical crypts

(percentage of cervix occupied by active crypts)

for a woman who goes through life with four pregnancies and no use of the Pill.

Pregnancy – S crypt diminution rate from Odeblad’s graph

[4 pregnancies, no Pill, rate reckoned from 15 yrs old to 40 yrs old]:

30% / 25 years = 1.2% per year.

At 50 years old, S crypts are at some 20%.

3. Acceleration of atrophy aging by the Pill [and/or by other endocrine-active compounds, EACs – a logical extrapolation]

Representative profile of cervical crypts

(percentage of cervix occupied by active crypts)

for a woman who goes through life without pregnancy and uses the Pill for 10 years

Pill – S crypt diminution rate from Odeblad’s graph

[no pregnancy, Pill for 10 years (18 to 28 yrs old), rate reckoned from 15 yrs old to 40 yrs old]:

60% / 25 years = 2.4% per year.

At 50 years old, S crypts are at some 5%.

This includes the slow down of the diminution gradient during the last 12 years of no Pill.

Compare this with diminution/atrophy rate during the 10 years on the Pill:

65% – 25% = 40% / 10 years = 4% per year.

This is double the baseline rate of cervical atrophy.

It’s more than 3 times higher than the pregnancy-slowed atrophy rate.

Three concluding remarks by Prof. Odeblad:

“Regression when taking the Pill is different for estrogen-dependent crypts (L and S) and progesterone-dependent crypts (G) which may in part overdevelop.”

“The study of the effects of contraceptive pills on the cervix is a difficult task. A considerable amount of work is required for each patient and the time required spans many years, up to 10 years or more. Many women also want to change to other pills or to other methods of contraception, or perhaps now want to become pregnant. It also happens that some pills are withdrawn from the market. To these difficulties are added the normal age changes in the cervix and the dynamic processes which are of constant occurrence. After 3 and up to 15 months of contraceptive pill use, there is a greater loss of the S crypt cells than can be replaced.” (“Some Notes on the Cervical Crypts”, Dr E. Odeblad, Bulletin of the Ovulation Method Research and Reference Centre of Australia, Vol 24 No 2 June 1997, p31)

Citations and graphics reproduced from http://www.billings-ovulation-method.org.au/act/cervix/ageing.shtml .

“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 .

Comment on implications for treatments of certain symptoms

For example, the suggested method [Weschler, Toni (2002). Taking Charge of Your Fertility (Revised ed.). New York: HarperCollins. p. 52] of thinning cervical mucus to help achieve pregnancy by taking the OTC expectorant drug guaifenesin, which is thought to act by increasing the volume and reducing the viscosity of secretions.

The drug is also used to treat the symptoms of primary dysmenorrhea [severe uterine pain during menstruation ] where another treatment of choice is combined oral contraceptives [COCs]. Such treatments are administered to adolescents as well as to mature women because dysmenorrhea is a very common and serious problem (25% of women and up to 90% of adolescents ).

In both cases, the expectorant and the contraceptives are administered without knowledge of their mechanism of action in the given problem. Focus is on treating symptoms, not the underlying causes. The patient is the detector of any effect. How does the expectorant drug use correlate with the secretions of the different types of cervical mucus on the one hand, and with the folliculogenesis cyclic profile on the other? Is there any connection? If not, what does the drug do to the different crypts? And what the COCs do to them?

Is the expectorant so selective that it might do the right thing? Reduce type G? Enhance type S mucus? Does oxidation of the guaifenesin help reduce the cross-linked mucin type G in the cervical canal? As simple and pretty as that? (Even prettier if guaifenesin were not to be an EAC, an endocrine-active compound … which inactivity does not look likely – http://www.who.int/ipcs/publications/en/ch3.pdf .)

Would it not be nice to have a rationale for how the small guaifenesin molecule can have a good effect on both sub-fertility/infertility and dysmenorrhea?

Could it be that guaifenesin works bioelectrochemically in the same oxidation-reduction (redox) manner on the enzyme cyclooxygenase in the prostaglandin cascade, which is a cascade of redox reactions – producing an anti-inflammatory effect that translates as suppression of pain? (On a personal note, why not capitalize here at least conceptually on our ancient Wellcome Research Labs work, even before receiving – presumably – the first pension money from Glaxo Smith Kline?)

It’s easier to contemplate in general the effect of the contraceptive drug, which will presumably depend on the contents of the estrogenic and gestagenic components (modeling on Odeblad’s findings)…

Is there a connection between pain, cervix and ovaries, ovarian reserves? Maybe an abnormal depletion of, via ovarian cysts? Will the number of follicular waves and/or other features in the Ovulona cyclic profile – and correlated with ultrasound and MRI – show any such abnormality? Might the Ovulona be useful for diagnosis here, convenient, simple (inexpensive)? Wouldn’t that be nice?

Is cyclooxygenase inhibition detected by the cervix, does it show in the cyclic profile? Does said prostaglandin synthesis inhibition alter the number of follicular waves – while reducing the pain?

Answers to questions like these are needed. Keep in mind that ovulation is an inflammatory process, and since we detect it in the cyclic profile, it is reasonable to pose the above prostaglandin theory questions about the COX-2 (cyclooxygenase) inhibition.

Summarizing Odeblad’s results and the take-home message:

Baseline outcome of cervical S crypts aging: S crypts down to 20% at 40 years of age. Here you have the reason why mature age leads to sub-fertility and to infertility.

Atrophy slow-down effect of 4 pregnancies: S crypts down to 40% at 40 years of age. Here you see Mother Nature’s design in action. Pregnancy slows down the inherent rate of cervical aging (atrophy, deterioration). Naturally, this is not to argue for 4 pregnancies per lifetime – it’s merely how the effect was made measurable.

Atrophy acceleration effect of 10 years on the Pill: S crypts down to 10% at 40 years of age. Here is why it’s not nice to fool Mother Nature, why it’s not good to mess with her design. The Pill is an archetypal anthropogenic Endocrine-Active Compound [man-made EAC], and it was brought up in the previous post how there are very many of these EACs, all insulting the female body and health, some – like chemical contraceptives – by design.

While the story of Laodamia and Protesilao is touching, I merely want to ask that girls, ladies and their physicians do not moon the messenger.

STOP PRESS

And now, go and check out the 2012 post “The fallacy of ovulation calculators, calendars and circulating-hormone detectors” at https://biozhena.wordpress.com/2012/02/13/the-fallacy-of-ovulation-calculators-calendars-and-circulating-hormone-detectors/

More About Clomid, Serophene, Clomiphene citrate or Clomifene

Why popping pills is not the best. This chemicalization of life is a form of enslavement.

Expanding on the previous post, I reiterate what I left off with. It is advisable – and safer – to go about TTC, Trying To Conceive, without the use of chemicals, especially man-made chemicals – and note that herbal preparations are chemicals too. Monitoring (measuring) the effects of anything [any drug] you ingest is basically a must, if you do not play “Russian roulette” with yourself, your offspring, your family.

There is no such thing as a “magic bullet”, and every drug has side effects. It is advisable – and safer – to go about TTC by mastering the natural “right time” approach. The medical establishment has approved of it for birth control, even if not all medical schools teach it. (Go figure.)

Of course, this is the era of popping pills, but it might also be the tail of the era, if web 2 social networking and all that is really here to stay… (Please don’t say, “you wish” about the tail!) The pressure of big pharma advertizing is what makes for said era. In the Middle Ages, they who were accessible to the then lobbying pressures, had things like the Crusades, witch-hunts, and stuff like that. Now, there are different pressures and more customers accessible to them…

An Angel Leading the Crusaders to Jerusalem - Gustave Doré (1832 - 1883)

But, back to Clomid, clomiphene, now spelled clomifene. This http://www.early-pregnancy-tests.com/clomid.html is one of the many websites about the drug. It warns that “…in the case of clomid and FertilityBlend/FertilAid, the product makers do state that clomid should not be taken with herbal products…”.

Looking at the chemistry of the non-steroidal ovulatory stimulant Clomid (or clomifene), http://to.ly/5dn2, and keeping in mind the inevitable occurrence of metabolic biochemistry (drug transformation in the body of the patient), one finds this title:

Stilbenoids: Resveratrol, Tamoxifen, Diethylstilbestrol, Combretastatin, Pterostilbene, Clomifene, Stilbenoid, Combretastatin A-4, Kobophenol A – at http://to.ly/5dm1.

Simply put, these medicinal compounds are differently substituted stilbenes (http://to.ly/5dQa = chemically modified stilbenes [stilbene being an ethene double bond with phenyl groups on both carbon atoms of the double bond]). Here is the pharma business in a nutshell: The different substituents (or modifiers attached to the stilbene molecule) impart different electronic, electrochemical, biochemical and physiological activities. That’s what the pharmaceutical industry explores in or with their products.

Albrecht Durer - Christ among the Doctors. AD 1506.

Then, we have a search for triphenyl ethylene stilbene http://to.ly/5dkt . Some of the search results are as follows – with particular reference to the fourth one below the recumbent woman (where anthropogenic means “caused or produced by humans”, and endocrine, of course, pertains to an endocrine gland or its secretion into blood or lymph):

OESTROGENS AND PRO-OESTROGENS RELATED TO STILBENE AND TRIPHENYLETHYLENE http://joe.endocrinology-journals.org/cgi/content/abstract/3/1/168 . “It has recently been shown [Emmens, 1941, 1942] that oestrogensmay be divided into two classes—those which act directlyor with changes that can be effected locally…” (Yes, shown in the forties.)

Estrogens and antiestrogens I: physiology and mechanisms of action …, Volume 1 (1999) http://to.ly/5dkx . “The most prominent drug amongst these compounds is tamoxifen…”

1993: RU 486—A Decade on Today and Tomorrow http://www.nap.edu/openbook.php?record_id=2203&page=71 . “The development of RU 486¹ (Figure B1.1), the first efficient antiprogestin, may be seen as a result…this meeting, which merged science (hormone research) and the cause des femmes… it became clear that the available contraceptive methods did not completely meet the needs of women and their families; nor would they alone have a sufficient demographic impact… Mifepristone (RU 38486)…”

Albrecht Durer - Draughtsman Drawing a Recumbent Woman. 1525. Woodcut.

Chemistry of Natural and Anthropogenic Endocrine-Active Compounds http://to.ly/5dkG . “…endocrine active compounds comprise both naturally occurring substances and man-made chemicals, and their chemical structures are surprisingly diverse… Phytoestrogens, Industrial Chemicals… The stilbene-type agents diethylstilbestrol (DES), E,E-dienestrol and meso-hexestrol were synthesized in the late 1930s and are among the first man-made estrogens used for human treatment… banned today…  The phenolic A ring of steroidal estrogens has long been considered a prerequisite for estrogenicity… also of paramount importance for the high estrogenic activity of DES and other stilbene-type compounds… it has been observed that numerous other phenols exhibit hormonal activity… potential endocrine disruptors, viz., alkylphenols and bisphenols… prototype of bisphenols is bisphenol A (BPA, Fig. 12), used in large amounts for the production of polycarbonate plastics and epoxy resins… Polychlorinated biphenyls (PCBs) are among the most persistent and ubiquitous environmental pollutants. Whereas the PCBs themselves have no or at best marginal estrogenicity, significant hormonal activity may be entailed to these molecules by hydroxylation [22].”

Albrecht Durer - The Martyrdom of the Ten Thousand. AD 1508

To help make some sense of the above, let the editor of Annals of Internal Medicine (http://to.ly/5dnr ) say this: “…in the field of synthetic substitutes for the female sex hormones, the essential point is the establishment of the fact that estrogenic activity is not exclusively a property of compounds structurally similar to the natural hormones [that is, possessing the phenanthrene nucleus]… a number of simpler substances having estrogenic properties…”

So, again, there is no “magic bullet”, there are inevitable side effects, associated with lack of specificity (the scientific term for “no magic bullet”).

Specific Clomid warnings are, for example, at emedzone site (.com/clomid-brand-tabs-aventis-pharma-p-149.html). To cite: The regimen in which Clomid should be used depends on the individual condition… and if HCG was used mid-cycle or not.

Albrecht Durer - The Dresden Altar. AD 1496

Clomid Warnings

Clomid can cause disturbed vision and blurred vision and therefore should be used with caution…

For those women who are planning to get pregnant, be warned that taking Clomid may result [in] multiple births and this may be harmful to the mother and to the fetus as well. (Note: Multiple births are also a very big problem for public health.)

Clomid may also be not advised for patients with the following medical conditions (note: these are conditions that may have caused the difficulty to conceive in the first place):

• Endocrinal disorders

• Thyroid problems

• Live[r] diseases

• Ovarian cysts and enlargement

• Polycystic ovarian syndrome

• Uterine fibroids

• Any other chronic illnesses

• Endometrial carcinoma

• Vaginal bleeding

If you have any of the above-mentioned diseases, your doctor may advise you not to take Clomid or will significantly alter your dosage.

Clomid is also not advised for pregnant women as it is a drug in the pregnancy category X and may cause birth defects when taken by pregnant women.

Clomid is also not advisable for nursing mothers as it passes into the breast milk and may cause harm to the nursing infant. END QUOTE.

Albrecht Durer - Durer's Wife Agnes

In addition, the use of fertility drugs may be associated with an increased chance of developing ovarian cancer, although there is an ongoing controversy over this: http://to.ly/5dmf , http://www.wordiq.com/definition/Ovarian_cancer .

Such are the reasons why popping pills is not the best. Not to attack big pharma, but all this chemicalization of life is a form of enslavement. More insidious than the slavery that was abolished centuries ago, more subtle. First, make them buy a drug that causes such and such side effects including the least spoken of, the premature aging of the cervix http://to.ly/5dMb ; the ensuing problems are then tackled with other drugs (like clomifene), and on and on it goes.

Let’s contemplate with Albrecht’s wife Agnes why it should be that too many pregnancies were the problem before chemical contraception, whereas today… Today, sub-fertility and infertility are on the up and up, while contraceptive failure statistics are in the picture, too, showing that about half of all pregnancies in the U.S. are unplanned, and that mature population of America uses surgical sterilization for birth control.

This is a man-made problem. See the next post about accelerated atrophy of vital cervical tissues (crypts) due to the man-made problem called the Pill (About atrophy, reproductive aging, and how it’s really not nice to fool Mother Nature – or with). And see the December 2011 post about Difficult to conceive – Google evidence that pregnancy complications and trying-to-conceive concerns shot up after the Pill launch in 1960s (this article reiterates and simplifies the take-home message put forward in the atrophy – aging – Mother Nature post; and two paintings of the Rape of Europa are showed there, too…).

About Clomid, Serophene or, generically, clomiphene citrate. A critical look, part 1.

In relation to folliculogenesis, the mechanism of menstrual cycling, which we monitor in vivo – to get away from drugs as much as possible.

Last night I re-tweeted this:

RT @FertilAidAmy What is Clomid…? http://blog.fairhavenhealth.com/ = it’s NOT recommended to take it for >6 cycles, and it causes decreased fertile mucus

Then I found that there is no entry about Clomid in the Alphabet of bioZhena. Yet, Clomid is a very frequently administered medication for women with difficulty conceiving, “prescribed to women that are trying-to-conceive to induce ovulation. Clomid is often prescribed to women with irregular cycles that either experience irregular ovulation or don’t ovulate at all” (http://blog.fairhavenhealth.com/ ).

Clomid was also involved in a peculiar episode when a business-incubator director took me once to a local hospital’s young lady gynecologist thinking that, because she was written about in the local newspaper, she was just right for bioZhena Corporation’s quest for good people and/or “strategic allies”. Instead, the take of the young physician, who took several calls from upstairs during the “interview”, was something along the lines, “I don’t see what’s in it for me with your technology. When they [subfertility sufferers] come to us, we put them on Clomid, and that’s that…”.

Dali - Longlegs

Well, let’s look at what the “that’s that” is about. The referenced tweet mentioned, within the allowed 140 characters, two features. One, that Clomid should not be taken for more than 6 menstrual cycles. And two, that it is known to reduce the amount of the all-important fertile mucus, which is the cervical mucus form occurring only during the run up to ovulation. This essential temporary change is for the purpose of opening the cervical canal for the penetration of the sperm and, in fact, for what is called the capacitation of the sperm. At all times outside of the fertile window, the fertile mucus is replaced by the protective type of cervical mucus, which prevents the entry of microbes including sperm into the uterus and beyond.

For a concise overview of this essential mucus, read the article Cervical mucus (under C) in the Alphabet of bioZhena, at  https://biozhena.wordpress.com/wp-content/uploads/2007/11/aaee-the-alphabet-of-biozhena.pdf . There we cite a noted expert on the subject, Dr. Erik Odeblad, and the gist of his message is: “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 estrogens, and the Pill causes atrophy of these crypts. Fertility is impaired since the movement of sperm cells up the canal is reduced.”

You can imagine that this will have something to do with the reason why the woman becomes a patient and is now prescribed the fertility drug.

One other thing about the drug is the issue of the official “10-per-cent possibility that Clomid could produce twinning”, described by a physician’s blog post at KevinMD.com about “one of the largest malpractice awards in Canadian history. At issue is how the patient understood the discussion of the risks of Clomid”: http://to.ly/5cE7 .

Sublime moment by Salvador Dali

Clomid is the brand name for the fertility drug clomiphene citrate. Clomiphene citrate may also be sold under the brand name Serophene or as the generic version called clomiphene citrate (http://to.ly/5cIc ).

Here is a bit more scientific take on how it works, cited from Wikipedia (http://en.wikipedia.org/wiki/Clomifene ):

Therapeutically, clomiphene is given at day 2 of menses [menstruation]. By that time, FSH level is rising steadily, causing development of a few follicles [in the ovary].

Let’s interject a clarification: This timing is called the recruitment stage of folliculogenesis, during which LH induces an “angiogenesis” factor from the theca cells, increasing the blood supply and estrogen synthesis by the recruited cohort of follicles.

The term “selection” indicates the reduction of the recruited group of follicles down to the species-characteristic ovulatory quota, which in women and related primates is one. Selection is the culmination of recruitment on day 6 ± 1. “Typically only one of the two ovaries sponsors recruitment and selection of the single dominant follicle, which is destined for ovulation.” We detect the selection stage as the first marker in our ovulographic™ (or folliculogenesis in vivo™) cyclic profile. Refer to the bioZhena tech pitch page http://to.ly/xE6 and/or to http://to.ly/MJU , http://to.ly/MWl .

Back to the language of the Wikipedia article: Follicles in turn produce the estrogen, which circulates in serum. Clomiphene acts by inhibiting the action of estrogen on the pituitary [gland, or hypophysis, in the brain]. [It] binds to estrogen receptors and stays bound for long periods of time.

This prevents normal receptor recycling and causes an effective reduction in hypothalamic estrogen receptor number. As a result, the body perceives a low level of estrogen… Since estrogen can no longer effectively exert negative feedback on the hypothalamus, GnRH secretion becomes more pulsatile, which results in increased pituitary gonadotropin (FSH, LH) release. Increased FSH level causes growth of more ovarian follicles, and subsequently rupture of follicles resulting in ovulation. END OF QUOTE.

Salvador Dali - Geopoliticus Child Watching the Birth of the New Man

From another Wikipedia article, about GnRH (http://en.wikipedia.org/wiki/GnRH ):

At the pituitary, GnRH [Gonadotropin Releasing Hormone (synthesized and released from neurons within the hypothalamus )] stimulates the synthesis and secretion of the gonadotropins, (that is) follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These processes are controlled by the size and frequency of GnRH pulses, as well as by feedback from androgens and estrogens. Low-frequency GnRH pulses lead to FSH release, whereas high-frequency GnRH pulses stimulate LH release. …the frequency of the pulses varies during the menstrual cycle, and there is a large surge of GnRH just before ovulation.

To reiterate, Clomiphene acts by inhibiting the natural action of estrogen on the pituitary gland in the brain, interfering with – or, shall we say, altering, manipulating – the process of folliculogenesis. Women’s health revolves around folliculogenesis and its complex control mechanism by the brain and by the ovaries.

To give you a sense of said complexity of the biology we are working with when we monitor folliculogenesis in vivo, we cite the specialist, Dr. Ernst Knobil: “The mechanism is believed to involve the circhoral* clock of the hypothalamic GnRH pulse generator, on which the circamensual** ovarian clock is obligatorily dependent”. [*Occurring cyclically about once an hour, pulses from the brain; ** about once a month.] From Knobil’s memorial lecture The Wisdom of the Body Revisited, available online at http://physiologyonline.physiology.org/cgi/content/full/14/1/1 .

During the reproductive years, pulse activity is critical for successful reproductive function as controlled by feedback loops. Cited in conclusion from the Wikipedia GnRH article referenced above. (The Wikipedia also has an article about the cervix and cervical mucus, at http://en.wikipedia.org/wiki/Cervical_mucus#Cervical_mucus .)

15- Word(le) greetings from bioZhena's follicular waves

A wordle is a toy for generating “word clouds” from text.

In this case the entire bioZhena’s Weblog as it was in November 2009 — 15 most prevalent words.

It is advisable – and safer – to go about TTC, Trying To Conceive, without the use of chemicals, especially man-made chemicals, and note that herbal preparations are chemicals too. Monitoring (measuring) the effects of anything you ingest is basically a must, if you do not play “Russian roulette” with yourself, your offspring, your family.

The above wordle, the “greetings from bioZhena’s follicular waves”, is a reminder that, before resorting to the chemical route, the innocuous “right time” approach is indicated (because it does not go against – it goes with – the natural biology of the body).

Have you noticed that the powerful Clomid is an estrogen agonist/antagonist? (Acting like estrogen or against estrogen. Tricky, yes? You bet. Or play roulette…)

Far more than a tool for getting pregnant and for pregnancy avoidance

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 obvious in the context of the menstrual cycle signature. The Ovulona cyclic profile is the signature of the menstrual-cycle vital sign.

To enlarge the image, click https://biozhena.wordpress.com/wp-content/uploads/2009/03/menstrual-cyclic-profile-signature-of-the-hpg-feedback-mechanism.jpg   The H-P-G feedback loop (F) gives rise to the menstrual cyclic profile signatures.

Now peruse https://biozhena.wordpress.com/wp-content/uploads/2019/03/wealth-of-info-elucidation-silent-3-slides-animated-ed.pdf

You will follow the discussion here better if you review 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, and the data from any number of months stored in the device will be transferred to the patient’s healthcare provider(s). The longitudinal record of menstrual cyclic signatures provides a new means of patient profiling.

The DIU will facilitate electronic recording of quantified symptoms. Below we show the planned transformation of the Ovulona into a semi-permanently worn cervical ring telemetric device.

See the image better in slide 4 of QUICK INTRO 4 SLIDES at Friendly Technology and Next Generation Design

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 requirements 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™.

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

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

Parturition alarm:

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

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

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

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

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

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

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

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

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

Parturition:

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

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

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

Indubitably, due dates are a little-understood concept:

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

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

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

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

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

Dystocia or birthing difficulty:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 ‘To know what is to be known’.

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.

 

The Ovulona™

This is the putative trade name of the women’s health version of the bioZhena core product, 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 – at the time when it received its FDA 510k clearance – but the feminine-gender form of the name is surely more appropriate (with the a at the end of the name, the Ovulona).

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 stated that “…the fertile period of the menstrual cycle is not more than 4 days, and probably less”.

He also said: “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 beginning 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 possible definition of the bioZhena innovation. Definition of the basic primary application of the invention. Accurate detection of the fertile period is the operative phrase, and it is what eludes the various alternative, already marketed, methods and products. I refer to them as the peri-ovulation methods. We all know that those products have not solved the fundamental diagnostic need of woman- or humankind. 

We have, which is why we can talk about a non-hormonal, non-chemical, non-barrier, non-surgical pregnancy avoidance as well as pregnancy aiding – by timing intercourse with respect to ovulation. Here is a schematic diagram of how (stripped of precision):

.

For more on how this will work for you, view the slide The three-day fertile window how-to (to exit the slide, just click on it. You can also view this by clicking on the image below).

In this animation, with the “try for” indicators, we reference the outcome of a France et al. study of fetal gender pre-selection superimposed on the menstrual cyclic profile generated by our device in a small clinical trial. Morning and evening monitored data were compared to BBT temperature data of the same subject of the pilot study. You might notice how the data suggests the progress of folliculogenesis between the AM and the PM hours.

Click image to view The three-day fertile window how-to (to exit the slide, just click on it).

.

And now, let me insert a fast-forward from the time this post was written in December 2007.

Here is the shortest possible summary introduction of the Ovulona device for women’s personal tracking of fertility with concurrently screening cervical health. 3 slides with some links https://biozhena.wordpress.com/wp-content/uploads/2018/03/ovulona-from-startup-version-to-cervical-ring-implementation.pps

For further particulars, try this bioZhena intro in 10 mostly narrated slides https://biozhena.wordpress.com/wp-content/uploads/2016/12/new-set-v7-narrated-slides-edec16.pps

How the Ovulona^TM will help women’s physicians to better help their patients is shown in this slide: https://www.linkedin.com/feed/update/urn:li:activity:6489235834502463488

Cervical health screening, pregnancy monitoring and other applications will be introduced while generating revenues with the already FDA-cleared minimum-value application of the core Ovulona^TM product.

.

The Smart Ovulona™ will interpret the daily measurement data for display on the screen of the device in plain language such as FERTILE DAY 1 or PREGNANCY DETECTED or SEE DOCTOR ABOUT CERVIX.

But that is only the beginning. The fertile window determination is the basic or primary application of the Ovulona, our core product with numerous diagnostic ramifications within the bioZhena Fertility and Health Awareness System™.

The various topics for utilization of the Ovulona are discussed in the posts of this blog, reflecting the broad applicability of our technology of FOLLICULOGENESIS IN VIVO™ beyond reproductive management. See, for example, Much in women’s health revolves around folliculogenesis – from teen age to peri-menopause .

Although we do not disclose and I do not blog about all the significant uses of at-home monitoring of the cervix uteri, another example is discussed in the post “Far more than a tool for getting pregnant and for pregnancy avoidance. (On symptometric monitoring correlated with folliculogenesis: Why it is essential for effective diagnosis in women’s healthcare)”. This is a hint at how the technology can help physicians to better help their female patients.

Explore the blog’s Table of Contents. In one of the articles you will read how another Emeritus Professor (Erik Odeblad) influenced the inception and development of the bioZhena project by his work, which influence was memorably captured in his apt saying,

“The cervix is a precision organ as complex as the eye”.

There you have it, the basic tenets of bioZhena and our focus on the cervix uteri.

.

---

---

.

For further particulars, read on.

The origination of the Ovulona (and/or BioMeter) technology was a response to a 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 knowledge 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 (i.e. of 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.

The said “everything else” also includes the realization that, by interfacing with the cervix, we are monitoring folliculogenesis (the maturation of the egg in the ovarian follicle). And it includes, most importantly, the crucial capability to detect ovulation and not just predicting it. Last but not least, “everything else” also includes the appreciation of the unprecedented impact the monitoring of fertility status via the uterine cervix has on the quality and broad applicability of the menstrual cycle profile.

Better than so many words, let me offer you a picture, a shorthand representation of what the bioZhena ectocervix monitor is involved with, how the menstrual cycle profile records come about – the neuroendocrinological mechanism. Do note well the words in lieu of the figure caption.

Here are 447 words in lieu of a caption for the composite image:

The ovulographic monitoring of folliculogenesis in vivo is believed to capture the fine-tuning effects on folliculogenesis of the direct neural control via ovarian and uterine innervation and the acute effects of local (autocrine and paracrine) modulatory actions.

Neither of those effects can be detected by the systemic peripheral variables such as the BBT or the urinary levels of hormones monitored by the commercially available home-use technologies.

See https://biozhena.wordpress.com/wp-content/uploads/2019/01/Single-slide-How-the-Ovulona-will-help-physicians.pdf for how this will help physicians to better help their female patients. See how Ovulona anticipates failure to ovulate in a healthy woman, and how Ovulona detects delayed ovulations in asynchronous cycles that happen to many healthy women. These occurrences are where the neurological effects are suspected to play a role.

.

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

This was subsequently confirmed by another proof-of-concept study with non-baseline subjects at the Natural Family Planning clinic at Marquette University (Wisconsin – Dr. Richard Fehring and associates). See the Fehring and Schlaff paper with a Note about further insight into the published results.

.

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

To be clear, the long-term predictive peak 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.The other methods predicting ovulation all monitor hormone markers in general circulation (after clearance into other body fluids), which is too remote, indirect, hence the no counterpart statement of fact.

None of this would have been apparent from the early in-house longitudinal study, since the study involved a non-baseline subject (and then another). In non-baseline cycles, which are common in real life, even the luteal (post-ovulation) phase quite often is not the theoretical 14 days long… and various other deviations occur from the “ideal” (simplified) case descriptions found in medical textbooks.

Data to date indicate that the long-term warning of the upcoming ovulation event occurs sufficiently 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.

This broad applicability is another feature that distinguishes the Ovulona from any other product addressing fertility status and, as they in fact do, merely estimating (guessing at) ovulation.

For a potential impact of the technology on public health, see in the Alphabet under Sexually transmitted diseases, and also under Cervical cancer and under Smoking. You can also find articles on these topics in this blog’s Table of Contents (TOC). The TOC is clickable and provides descriptive snippets about the blog articles. As an example, see the blog post “Smoking affects the menstrual cyclic profile as captured by the Ovulona™, monitoring might help with smoking-cessation” .

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 – with support of a well-matched investor. That is why the plan to transform the Ovulona into the (semi) permanently worn telemetric cervical ring.

---

Post script

Here is a larger, easier to read, rendition of the Figure with the data (choose either a silent graph or a narrated animation):

Three baseline cycles from Turin study and/or the same as an annotated slide narrated by yours truly

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.

At this point I share with you the explanation of the long-term predictive peak by reference to the picture of the baseline cycles that we are now well familiar with. The picture is annotated with labels and short-hand elucidation of the features under discussion.

.

For better legibility, click the image, view a slide show version.          The URL is: https://biozhena.wordpress.com/wp-content/uploads/2016/12/wealth-of-info-elucidation-of-domin-folli-peak-3-slides.pps

 R… Recruitment on days 1 to 5 ± 1 (data captured usually only after blood flow – due to hygiene concerns).

S… Selection on day  6 ± 1.

GC+TC E2up… Dominant Follicle Maturation: Granulosa and Theca Cells produced Estradiol  (E2) rises, which drives the signal up; Dominant Follicle also initiates expression of LH Receptors.

GC P4up… After the appearance of LH Receptors, the preovulatory Granulosa Cells secrete Progesterone (P4), which drives the signal down. (That’s also why the ovulation marker is a trough, the lowest minimum in the menstrual cyclic profile.)

Ref.: Page 39 of 23rd Edition of Williams OBSTETRICS © 2010, 2005, 2001 by The McGraw-Hill Companies, Inc. (www.gums.ac.ir/Upload/Modules/Contents/asset39/williams23.pdf)

Above: Elucidation of the long-term ovulation-predictive dominant follicle peak (December 2016)

The long-term predictive dominant follicle peak 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 dominance).

Note that the corresponding basal body temperature (BBT) curve rises, to the post-ovulatory higher level, after the ovulation marker. This indicates, to the extent that the BBT can be relied on, that ovulation had, indeed, occurred. The planned sonographic (ultrasound) investigations will confirm this correlation with a better accuracy.

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 relatively 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 diagnostic usefulness to the luteal-phase part of our cyclic profile – for example re: menopause, aging, which is a use of the waves invoked by the cited authors.

Our understanding of the implication for early detection of pregnancy came in due course. Very early detection, essentially instant – no waiting for two weeks for the absent menstrual bleeding and for a detectable concentration of hCG in the urine!

See https://biozhena.wordpress.com/2010/11/11/instant-detection-of-pregnancy-and-of-early-pregnancy-loss-epl-the-adversary-of-trying-to-conceive-ttc-especially-after-age-25/ for the article “Instant detection of pregnancy and of Early Pregnancy Loss, EPL – the adversary of Trying To Conceive, TTC – especially after age 25”.

Early Pregnancy Loss (EPL) is also known as stillbirth or miscarriage, or early embryonic mortality, and the Ovulona™ will enable the user to try conceiving again as soon as possible, in order to avoid recurrent EPL miscarriage (since it is now known that the sooner conception occurs after the EPL, the better the chance of success).

Should you wish to talk with me on the phone or via Skype, please email me first to schedule the call. My email is: vaclav at biozhena dot com

.