End of the year, and trying to get pregnant

Now, at the end of the year, …

“…Josef Lada did far more than illustrate the Hasek’s Good Soldier Svejk novel, and his idealized paintings of carol singers and family gatherings are, for many in this country, an enduring symbol of Czech Christmas.” http://www.radio.cz/en/section/curraffrs/josef-ladas-paintings-an-enduring-symbol-of-czech-christmas/pictures/obrazy/lada-josef/vanoce.jpg

…the stat counters monitoring the visits to the posts of bioZhena’s Weblog show something that I want to share with you. Namely: The most visited blog posts at this time of the year are those addressing the issues involved in trying to conceive (the flip side of natural birth control). Those blog articles exhibit distinctly higher viewing statistics than the stats of the posts on other topics of reproductive health – whereby some of those topics exhibit a different seasonality of increased interest.

If you wish to put this in context and review the situation out there, outside of bioZhena’s Weblog, read the attached paper Google evidence of increasing prevalence of subfertility.

A couple of examples of the bioZhena’s Weblog titles most visited at this time of the year:

The fallacy of ovulation calculators, calendars and circulating-hormone detectors = https://biozhena.wordpress.com/2012/02/13/the-fallacy-of-ovulation-calculators-calendars-and-circulating-hormone-detectors/ Don’t let them lead you by the nose with likely this and probable that! You need to know for sure.

Critique of birth control efficacies in NFP as published by Marquette University researchers = https://biozhena.wordpress.com/2010/03/23/critique-of-birth-control-efficacies-in-nfp-as-published-by-marquette-university-researchers/ Comments on a report of two studies http://www.usccb.org/prolife/issues/nfp/cmr_winter-spring09.pdf – they report on what we will call peri-ovulation methodologies.

Some women email me, while some “like” certain Ovulona pages or bioZhena’s Weblog posts.

Citing from one such email: “I am a 41 year old nulliparous woman in good health (with a few minor issues). I have been TTC for 1 year without success and came across Ovulona by accident during a Google search for how to optimise my fertility.”  TTC stands for Trying To Conceive, a standard acronym in the community of sub-fertility sufferers. Or even infertility sufferers – those who have not conceived while trying for longer than a year. (Re: Medical definitions of sub-fertility and infertility.) Nulliparous means no children, medical adjective for women having no previous births.

You know, my dear reader, that the optimal age for conception and motherhood is 20 to 24 years, after which fertility starts declining, and it drops a lot after 35 years of age. Should this be news to you, read The perils of IVF, of ARTs, of giving birth at old maternal age . “About epigenetic evidence that should make you think twice+ before you contemplate In Vitro Fertilization and think that having a baby can wait. The bottom line? Be a young mother!”

And from another reader’s email: “Please let me know if there is any way to buy an Ovulona or to use one for trial purposes.”

In response, I can only explain – apologetically, suppressing frustration – that we do not have any Ovulona units available because we have not yet manufactured the marketable product, due to lack of capital. Then, attempting a little more positive note, I remind the would-be Mums about what some experts call “focused intercourse” – that is focusing on trying to hit the fertile window. In the absence of the Ovulona, this must be done preferably with more than one of the several available methods (several, because they are unreliable, inaccurate – don’t rely on any one of them alone). And I urge you to also avoid stress…

Although the old imperfect methods (including instrumental monitoring of urine samples and/or of the BBT) give only inaccurate estimates, they should help to focus on the right time when the probability of conception exists. Outside of the fertile window you don’t have a chance to conceive.

Here is to illustrate two such imperfect methods in comparison with ours (where our Ovulona not only anticipates but also detects ovulation, which detection is all important): https://biozhena.wordpress.com/2007/12/16/cervix-uteri-and-seven-or-eight-related-things/marquette-comparison-with-lh-kit-and-peak-mucus-2/ .

In this record of a 42-years old woman, our device detected delayed ovulation on cycle day 17, while two other methods estimated ovulation from day 16 to day 18. This lack of precision and accuracy is not at all good for natural birth control and/or for trying to achieve fetal gender pre-selection (= trying to conceive specifically a boy or specifically a girl). But, with such inaccurate methods, which are available now before we bring the Ovulona into the market, you can see here that you might be fortunate and hit on at least a part of the fertile window. In this example (because of the ovulation delay), the LH-indicated days 16 and 17 were fertile days because the sperm are viable for about 3 days. Perhaps even day 18 may have been a fertile day, if the ovum (egg) lived long enough, and depending on when exactly on day 17 the detected ovulation occurred (morning or evening?). Such uncertainties will be removed by properly designed experiments with the properly designed Ovulona.

This record from a comparative study shows how the old ovulation prediction methods are unreliable, because the two used here predicted ovulation for 3 different days – but the record may also serve to illustrate for you that (and how) you may be lucky and hit at least one of the fertile days. Here, in this record, ovulation was detected – not merely anticipated – by the Ovulona prototype. It was detected on the day of the second urinary LH indication, which is here one day before the esoteric Peak mucus of NFP aficionados; they did not use the BBT in this study. None of the old techniques detects ovulation: they predict it or, in the case of the BBT, indicate that ovulation has occurred.

There are only 3 days in each menstrual cycle during which pregnancy can occur, and it will if you are fortunate. The 3 fertile days are the day of ovulation plus the two days immediately before ovulation.

I’ll now write a long sentence full of the word “trying”, with several connotations. Repeat after me (and grasp what follows): Trying to determine the 3 days of the fertile window without the Ovulona is pretty much impossible, but trying for it – or at least some of it – is better than trying completely in the dark.

That’s because the 3-day fertile window varies, it does not stay put on certain days of the menstrual cycle from one cycle to the next. Check out this earlier bioZhena post for evidence that this is so. See evidence generated by other experts years or rather decades ago – when they hoped that microcomputer-assisted basal body temperature [BBT] monitoring would solve the problem.

From a graph such as the one above, it is evident that to determine the fertile days before ovulation is more difficult than estimating the last fertile day, which is the day of ovulation. This difficulty is a well recognized fact, and it’s not a matter of whether ovulation is or is not delayed by stress of one kind or another. The stress-caused delay (or even complete suppression) of ovulation is one of the things that complicate management of reproductive life.

Now for the encouragement: Maybe, the idea of not being completely at the mercy of chance when trying to conceive a baby, might even help you to be less stressed out about it at a time when celebrating the end of the year (and looking back and looking forward – along with all that Christmas rush) leads to an increased level of stress anyway.

Josef Lada’s idyllic take on Christmas activities in the countryside and in the city, that is to say, in Czechoslovak towns of his day. There, a fish meal on Christmas Eve was and still is one of the traditions, although the country is now two (and good friends). The fishy thing was apparently based on the belief that fish scales symbolize the prospect of money next year to the eater. Maybe some of us should not have turned our nose up about this fish thing… Then the capital for the Ovulona might not have been so slow coming! Mea culpa, mea maxima culpa!

Perhaps the focus idea may help you not to be stressed out about the thing which is supposed to be pleasurable and not a chore. Suppose that between now and some time in January/February (in the course of the long winter evenings, “za dlouhych zimnich veceru”) you’ll get your focusing organized. You surely will get over the holidays, too… Then, with a bit of happiness, relaxation and luck, come next October you will have the kind of happiness you wish for! And you’ll thus contribute to the birth/delivery statistics for October…

Josef Lada’s calendar illustration for October (c. 1940s)

In this picture, Josef Lada illustrated, long time ago, the characteristics of the month of October. Among them is the rut of the elk, which had given the month its name in the artist’s language. Way back, in those days – the pre-contraceptive Pill days, years and centuries – the difficulty to become pregnant was not a widespread phenomenon, and Mums were  younger than many are nowadays.

The evolution of subfertility and infertility (as a big-time societal phenomenon) in the U.S. is summarized based on data from http://www.infoplease.com/ipa/A0005074.html#ixzz2GBMSkUKy  [Information Please® Database, © 2007 Pearson Education, Inc.] in the next post.

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…).

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’.

Stress and fertility

Please click through to the 2019 revision of this post at

https://biozhena.wordpress.com/stress-and-fertility-fertile-window-ovulation/

How stress affects the inherently narrow fertile window

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

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

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

Just remember, this is no Alphabet of Ben Sira!

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

Stress and the menstrual cycle

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

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

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

 

 

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

 

 

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

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

Stress and the Ovulona^TM

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

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

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

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

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

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

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

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

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

 

 

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

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

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

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

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

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

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

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

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

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

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

References as excerpted from our White Paper:

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

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

Terminology reminder:

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

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.