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.

Cervix uteri and seven or eight related things

It seems worthwhile to reblog the December 2007 post about the basics. Including “why the bioZhena technology had to be invented. One way of saying this is: The available means, methods or products, were not good enough. Another way of putting this is to quote from medical literature…”

And then see how none of the methods determined ovulation with the required accuracy to be useful either as a conception aid or especially for birth control.

3-day fertile window with gender preselection vs. inaccurate old methods

Here is how our method (monitoring folliculogenesis in vivo) does it by generating the multi-featured cyclic profile that includes the definitive ovulation marker after the predictive signals, and here is how this compares with the older techniques. See how inaccurate is the ovulation assessment by the older means available to the users of NFP or FAM.

For more about the data in the above illustration, go see another old bioZhena post, “Regarding fetal sex preselection”, at   https://biozhena.wordpress.com/2007/12/02/regarding-fetal-sex-preselection/ .

If you want to learn more about how the Ovulona device does it, go to “About bioZhena Tech Pitch” at   https://biozhena.wordpress.com/about/about-biozhena-tech-pitch/ (inserted here in February 2019).

bioZhena's Weblog

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

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

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

Cervix:

The narrow lower part of the uterus (womb), with an opening that connects the uterus to the vagina. It contains special glands called the crypts that produce mucus, which helps to keep bacteria (and other microbes, including sperm for most of the cycle) out of the uterus and beyond. Sometimes called the neck of the womb, it protrudes into the vagina. The region…

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Stress and fertility: How stress affects the inherently narrow fertile window

This blog post appears as the third result in Google search on “bioZhena” (without the quote marks). The complete title is:

Stress and fertility

How stress affects the inherently narrow fertile window

To read the whole post, click on either of the antique-book images or on Reblogged from bioZhena’s Weblog:

Before you go there, here is a little update. New research into stress and fertility was published since I wrote the blog post in December 2007, and here is a summary of an article titled “Stress puts double whammy on reproductive system, fertility” (see http://esciencenews.com/articles/2009/06/15/stress.puts.double.whammy.reproductive.system.fertility ).

 

QUOTE: The new research shows that stress also increases brain levels of a reproductive hormone named gonadotropin-inhibitory hormone, or GnIH, discovered nine years ago in birds and known to be present in humans and other mammals. This small protein hormone, a so-called RFamide-related peptide (RFRP), puts the brakes on reproduction by directly inhibiting GnRH.

The common thread appears to be the glucocorticoid stress hormones, which not only suppress GnRH but boost the suppressor GnIH – a double whammy for the reproductive system. END QUOTE

 

Unlike any other fertility monitoring technology, bioZhena’s Ovulona™ is a Smart Sensor™ in vivo monitor of folliculogenesis. Unlike any other fertility monitor, the Ovulona is basically involved with the always-present stress responses – through monitoring certain end-organ effects on folliculogenesis. The other techniques monitor only this or that circulating hormone – not good enough. The end-organ effect(s) is what counts.

 

Again, to read the whole post, click on either of the antique-book images or on Reblogged from bioZhena’s Weblog

 

For a 2012 update go to What is the mechanism of stress and how does it affect reproduction. An update. And: Be a young mother! (Ovulona™-related published scientific findings by others about disruption of fertility, about PCOS or Poly Cystic Ovarian Syndrome, how stress suppresses ovulation, about the hypothalamic amenorrhea of stress and postpartum blues/depression, about a CRH placental clock which determines the length of gestation and the timing of parturition and delivery, and the role of CRH in premature labor. How old age affects folliculogenesis as a stressor. Even how acute stress may induce ovulation in women.)

bioZhena's Weblog

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…

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Difficult to conceive – Google evidence that pregnancy complications and trying-to-conceive concerns shot up after the Pill launch in 1960s

Regardless of what contraceptive proponents tell you

On this day when Vaclav Havel passed away. In this post, I come out explicitly with an argument against the use of contraceptive pills and related agents (all Endocrine-Active Compounds [EACs]), because of the serious consequences of the sex steroid chemicals for women’s health. I start with evidence from Google statistics.

It is possible to examine the English-language literature for the frequency of addressing certain topics over a period of time. I already did this in the recent post “Seven billion people – after half a century with the Pill”.

Let’s look at data from Google Ngram Viewer about the statistics of the occurrence of certain topics (such as difficult birth) in all books published in English. The data is obtained via http://books.google.com/ngrams/info – for anyone to examine.

Briefly, when we enter phrases into the Google Books Ngram Viewer, it displays a graph showing how frequently those phrases occurred in a corpus of books (here English-language books) over the selected years (here 1900 to 2000). The data is normalized by the number of all books published in each year.

Here we have a comparison of statistics of three phrases:

pregnancy complications (blue),

difficult birth (red), and

trying to conceive (green).

Ngram 6: pregnancy complications, difficult birth, trying to conceive

The topic of difficult birth exhibits an almost linear growth over the century, even though there are discernible steps in the early years such as the step that followed the plateau (flat portion) lasting from about 1915 to just before 1930, when it “shoots up to catch up with” the overall trend. And, overall, the red curve grows steadily from 1900 to 2000.

In contrast, the blue curve of pregnancy complications and the green curve of trying-to-conceive both shoot up only after 1960, the decade of the introduction of the contraceptive pill. The steep rise in pregnancy complications books (blue) starts soon after 1960. The rise in the number of books about trying-to-conceive (green) starts in mid-1970s and is also distinctly faster than the steady growth over the century of books on difficult birth (red), although it is slower than the pregnancy complications that started going up some ten years earlier.

Of course, the green trying-to-conceive curve is not uninteresting in the early decades of the century, either, if only because it appears that the late Victorians had a significant interest in the topic, much higher than in the other two and especially as compared to pregnancy complications (blue). I’ll leave any discussion of the trend there to others, although the downward trend in the first half of the century would seem consistent with the rise of the birth control movement and with the consequences of two World Wars, and the Great Depression in between.

Peter Paul Rubens, Allegory of War, c. 1628

Those two generations had it tough but, on the other hand, their health, the health of humankind, was not yet assaulted by the sex-steroid chemicals that were introduced in the 1960s.

In a previous bioZhena’s Weblog post, you can see evidence that oral contraceptive use directly and negatively impacts the cervical crypts, which brings about the difficulty to conceive. The bottom line is this: “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.” The S crypts are needed for conception.

To further cite Professor Erik Odeblad: “Complications arising from the use of the Pill are very frequent. Infertility after its use for 7-15 years is a very serious problem. S crypts are very sensitive to normal and cyclical stimulation by natural estrogens, 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.”

This is a serious problem because, according to medical literature, most American women, “approximately 85% of U.S. women will use the OC (oral contraception) for an average of five years.¹ However, women’s OC use, similar to other chronic medications, is often inconsistent and transient.² Reported six-month OC discontinuation rates vary from 18% to 50%.^3,4,5 Unintended pregnancy often follows OC discontinuation” END OF QUOTE. (Am J Obstet Gynecol. 2007 April; 196(4): 412.e1–412.e7)

These data can be read and understood as the double-whammy put on or dealt to American reproductive and public health. That is the high prevalence of trying-to-conceive problems (sub-fertility and infertility) and at the same time the very high rate of unintended pregnancies.

Lion_Hunt_Mosaic in Pella

zb.jpg

While many proponents of chemical contraception minimize or gloss over the side effects of contraceptive chemicals, it is known that “OCPs (oral contraceptive pills) have several known metabolic effects including increased production of clotting factors resulting in increased risk of venous thromboembolism, increased gallstone formation during the first year of use, and increased risk of liver adenomas (Speroff and DeCherney 1993)” – cited from Ther Clin Risk Manag. 2008 October; 4(5): 905–911 (paper from University of Vermont College of Medicine and Reproductive Endocrinology and Infertility, Women’s Health Care Services)

That said, studies mainly focus on side effects such as amenorrhea, the incidence of breakthrough bleeding and spotting, compliance, discontinuation rates or patient satisfaction, headaches, genital irritation, tiredness, bloating, and menstrual pain.

To cite from said medical publication “Evaluation of extended and continuous use oral contraceptives”, Ther Clin Risk Manag. 2008 October; 4(5): 905–911 QUOTE [emphasis mine]:

In a normally menstruating woman who is not taking contraceptive hormones, progesterone is only present in appreciable quantities during the luteal phase of the menstrual cycle [meaning: after ovulation], after the development of the endometrium. When combination OCPs are administered, the effect of the progestational agent takes precedence over the estrogen component in the reproductive tract, and the endometrium demonstrates this progestin effect (Moyer and Felix 1998). The result is a thin, decidualized (transformed) endometrium with atrophied glands that is not receptive to embryo implantation. Progestins also cause thick, impermeable cervical mucus, preventing sperm from reaching the uterine cavity, and also decrease tubal mobility, altering the movement of sperm and oocytes through the fallopian tube (Johnson et al 2007; Rossmanith et al 1997) END OF QUOTE.

This is consistent with the Erik Odeblad findings about the fine structure of the cervical tissues. http://humrep.oxfordjournals.org/cgi/content/full/18/9/1782

Edward_Burne-Jones_Maria_Zambaco_1870

Further to the examples of studies about the mainly short-term effects of chemical contraception, here are examples of published findings about the harmful long-term effects of the sex steroid chemicals administered to healthy women. This is not a systematic review, merely a couple of examples.

BONE HEALTH:

The conclusion of “Effects of Depot Medroxyprogesterone Acetate and 20 μg Oral Contraceptives on Bone Mineral Density” [Obstet Gynecol. 2008 October; 112(4): 788–799]is as follows:

QUOTE Use of very low-dose OCP (Oral Contraceptive Pill) may result in a small amount of bone loss. DMPA (depot medroxyprogesterone acetate) use results in greater bone loss, but this is largely reversible at the spine. Use of very low-dose OCPs after DMPA discontinuation may slow bone recovery.

As a result, the Food and Drug Administration issued a warning in 2004 advising women to limit its use to ≤2 years.

Oral contraception (OC) containing only 20 μg ethinyl estradiol (EE) may also adversely affect bone health, especially if used during adolescence. END OF QUOTE [emphasis mine].

HEART HEALTH:

According to J Clin Endocrinol Metab. Author manuscript; available in PMC 2011 November 9 (Published in final edited form as: J Clin Endocrinol Metab. 2007 August; 92(8): 3089–3094), “whether OCP use in healthy young women is associated with increased CV (cardiovascular) risk is controversial. However, a recent meta-analysis of 14 studies showed that current use of low-dose OCPs increased the risk for myocardial infarction by 84% (37). More data are available regarding CV risk associated with estrogen/progestin use in older women… The Heart and Estrogen/Progestin Replacement Study showed an early increase in events and no benefit overall in women with known CV disease, and the Women’s Health Initiative (WHI) trial demonstrated an increase in CV events in healthy women (38, 39).” END QUOTE.

René Boyvin, The rape of Europa, c. 1545-55

In Greek mythology Europa (Greek Ευρώπη Eurṓpē) was… seduced by the god Zeus in the form of a bull, who breathed from his mouth a saffron crocus^[14] and carried her away to Crete on his back… and so see Wikipedia for the whole story. Oh, and should this not be clear, the metaphor here pertains to the man-made OCP [Oral Contraceptive Pill] accomplishment…

Max Beckmann, The rape of Europa (1933)

Returning to Odeblad’s results on the consequences of the Pill for the cervix uteri, that is on how contraceptive chemicals make it difficult to conceive later – and reiterating the take-home message put forward previously in “About atrophy, reproductive aging, and how it’s really not nice to fool Mother Nature – or with”:

Natural aging of cervical S crypts (= cervical aging of a woman never pregnant and never on the Pill):

S crypts, which are needed for conception, are down to 20% at 40 years of age, at the natural aging rate -2% per year. Here you have the reason why a too mature age leads to sub-fertility and to infertility. My remark: The optimal age for motherhood has always been and always will be the early twenties of a woman’s life.

Atrophy acceleration effect of 10 years on the Pill:

S crypts are down to mere 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. Fertility is drastically reduced. The Pill is an archetypal anthropogenic Endocrine-Active Compound [man-made EAC]. It was brought up previously in this blog how there are very many of these EACs, all insulting the female body and health; some – like chemical contraceptives – by design. Having invoked the design, I am reminded that the original designers of the Pill had no idea about contraception – they were pushing the frontiers of steroid chemistry… (not this particular application of one kind of steroids).

Atrophy slow-down or beneficial effect of pregnancies:

S crypts only down to 40% at 40 years of age. Here you see Mother Nature’s design in action. Pregnancy slows down the inherent rate of natural cervical aging (atrophy, deterioration). The effect of 4 pregnancies was measured in the Odeblad research. This is not to argue for 4 pregnancies per lifetime – it’s merely how the difference between with and without was made more “easily” measurable in the very difficult studies.

And again, the bottom line is this: “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. …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.” END QUOTE.

In case you’d like to view the Carlo Adelio Galimberti picture accompanying the concluding words, please re-visit the cited earlier post. The concluding words were and still would be: 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.

P. S.

Vaclav Havel would smile at the image of “mooning” Laodamia. I smile at the thought of his riding the children’s scooter (kolobezka) along Saint Peter’s heavenly corridors (looking for Olga? Since Pani Dagmar remained down there?). He reportedly did that scooter-running in the “labyrinthine” corridors of Prague Castle…

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.files.wordpress.com/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…)

Folliculogenesis in vivo™ monitoring is far better than current home-use fertility self-help tools

And here is again why

The FIV™-monitoring Ovulona™ is superior compared to existing commercial products in the home-use fertility self-help category, such as the urinalysis hormone (LH) kits or OPKs and their improved electronic iteration, and other such products. Superior on several levels.

Unprecedented user-friendly design coupled with unprecedented accuracy, liberating the user from the vagaries of imperfect ovulation method-based probabilities.

That must be the main one for the TTC [Trying To Conceive] people, but additional attributes are no less significant. Multi-purpose applicability including but not limited to built-in early pregnancy detection and early pregnancy monitoring. That’s to help manage and deal with the inherently high prevalence of early embryonic mortality [EEM], the chief complication of human gestation. (See https://biozhena.wordpress.com/2010/01/10/about-the-added-bonus-of-folliculogenesis-monitoring-automatic-pregnancy-detection .)

When the TTC hurdle is successfully dealt with, the EEM is the next obstacle on the way to overcoming the sub-fertility issue. Just think about this for a moment. The EEM is Mother Nature’s design to deal with problems that quite likely lead to the TTC challenge (aka sub-fertility or even infertility) in the first place…

There is more to the superior attributes of the FIV technology [FIV = Folliculogenesis In Vivo]. Readily thought about is non-invasive natural birth control. The Ovulona is an electronic tool for 21st Century’s NFP and/or FAM. Natural Family Planning and Fertility Awareness Method, both of which we envision under the umbrella of Scientific Family Planning™, SFP™.

Furthermore, once you become aware of how Folliculogenesis In Vivo works, it will be less of a surprise to see that the Ovulona tissue biosensor will also provide a nice and easy cervical cancer screen – and prospectively screening for other pathologies, and their treatment…

Treatment (as opposed to diagnosis), you wonder what that is about? It’s about the vaginal tissues being the most efficient route for administration of medications, and very logical for a topical treatment, wouldn’t you think? Logical and potentially pretty effective for public health, once the tool has become widely used due to its affordability and mass-market acceptance. That’s the vision.

Of course, there are still other applications that the male managers of investment coffers tend to view as women’s issues that are not their concern, such as management of PMS and its debilitating form the PMDD, such as proper evaluation of EDD and EDC (Expected Date of Delivery, and of Confinement), such as hormone therapy and related matters. All these are big issues of public health, the sentiments of said managers of other people’s money notwithstanding.

Now, back to the primary and initial use of the FIV-tracking Ovulona.

Only the Ovulona can determine the three days of the fertile window of opportunity to conceive, unperturbed by the talk out there – by the proponents of the imperfect ovulation measures – about six days, which talk stems from a certain highly publicized and yet flawed study in 1995… A publication (in NEJM) that caused a sensation at the time by shortening the NFP’s prescribed period of abstinence from the previous too long imposition to the less off-putting 6 days).

Detection of the 3 fertile days is possible because the Ovulona monitors the process of folliculogenesis, and it does it by sensing the tissues in the reproductive tract where the site of action is. Where the body integrates and responds to signals from the ovary and from the brain. That is the action, as opposed to the presence of this or that hormone in blood or urine or any other body fluid.

The determination of the three days window is absolutely necessary because only that way can conception be either assisted or avoided with the required accuracy. The existing home-use fertility tracking commercial products cannot do that, and that is why they speak about a longer and fuzzy fertile window. See preceding and older posts in this blog if you want to get a better understanding of all that which is covered by the short word fuzzy. You will also get the long word (peri-ovulation methods) if you delve into the matter that way.

The existing commercial products cannot be used, either, for an attempt at baby gender pre-selection by timing conception with respect to ovulation. They cannot do that because they do not anticipate ovulation accurately and they do not detect ovulation (they merely assume its occurrence).

Joan Miro – Birth World

Consequently, those techniques cannot distinguish between 2 or 3 days before and the day of ovulation. This is to try for a boy or for a girl, respectively, or to TTC, or to avoid conception. The commercially available technologies do not detect ovulation independently of the one predictive element they test for – or two such elements, LH and E2, in the case of the urine-analyzing gadget now sold by Inverness/SPD GmbH. It is not unlike groping in the dark… The other electronic gadget out there, the one offered by Zetek, is tracking indirectly the effect of the same hormone (estrogen) in two body fluids with two probes at two different times during the menstrual cycle. And your old BBT method tracks indirectly the effect of progesterone that you know causes the BBT to go up a bit after ovulation, albeit with a statistical uncertainty of + or – 3 days (and a poor signal to noise ratio at that).

The thing that the old *Imperfect Measures* tools detect is an input in the hormone signaling mechanism they talk about but of which mechanism they monitor merely that one input hormone signal (or two). However, the boundaries of the fertile window are not single hormone events; hormone monitoring (direct or indirect) cannot define the fertile window.

The existing products do not determine the fertile window of 3 days because they monitor this or that remote parameter that only reflects some aspect of the process that culminates in ovulation. They only detect a hormone signal that says “ovulation can happen about now” (LH), or a signal that says “ovulation has occurred” (BBT); or some reflect estrogen (e.g., through saliva appearance). Estrogen elevates before LH but not far enough ahead, and certainly it does not indicate the start of the fertile window nor the end of the window, which is ovulation. A saliva property is a fuzzy detector of estrogen, much like the vaginal fluid’s tactile and visual examination practiced in some circles.

Clock Explosion by Salvador Dali

Significantly, the hormones that anticipate ovulation do not mean that ovulation occurs right away or even at all. They just signal that the body is ready. It is essential to actually detect the occurrence of ovulation independently of prediction, and only our technology does that. Stress often either delays or even prevents ovulation, and only the Ovulona™ detects this. You can again find some earlier posts with more details about this.

There are also earlier posts about the variability of ovulation times from cycle to cycle in the same woman (as well as across a population), and the variability can be more than the width of the fertile window, more than the said 3 days. That 3 day span tends to also be the statistical uncertainty of the old techniques referenced here, plus or minus 3 days.

Serious consequences ensue for the users of the old *Imperfect Measures* techniques, whether employed to achieve pregnancy or to avoid it. Look at the small example from a small test-of-concept study by an independent NFP research-and-teaching group.

In the four recorded cycles of a childless 41-years old patient, the Ovulona prototype captured 3 delayed ovulations out of the 4 recorded cycles. In only one of the four cycles did the LH agree with our ovulation marker while Peak Mucus indication was one day late in that cycle. In the three cycles with delayed ovulation, the delays were:

In cycle 1:  4 days after LH kit positive and 3 days after Peak Mucus.

In cycle 3:  3 days after LH kit positive and 2 days after Peak Mucus.

In cycle 4:  1 day after LH kit positive and 2 days after Peak Mucus.

In another post in this blog, we showed how the test data divides the NFP clinic patients’ results into two categories that we termed regular and irregular (challenged). To avoid confusion with the traditional usage of the term regular/irregular in the context of menstrual cycles, we shall refer to the two categories as ordinary and challenged, respectively. Cycle 2 is an ordinary cycle (with LH and Peak mucus within 1 day of ovulation marker day) versus the other records showing challenged cycles with delayed ovulation.

The other challenged cycles from the study are tabulated below here, and you will note that they are quite numerous even in the small study of just 10 women with 2 cycle records each. Even in that small population of real life women, 45% cycles were challenged. You also see that the ovulation delays occur at any age (here from 19 to 41 years of age), and regardless of parity (that is, regardless of whether the woman has ever borne children or not):

In the table of ovulation days indicated by the three techniques, O stands for the ovulation marker of Ovulona prototype, LH means LH kit (OPK) positive result, and Pk means Peak Mucus result (as taught by NFP teachers).

As noted above, LH and Pk are in all these cycles lower than the O values, which relationship defines the category of challenged cycles (ovulation delayed with respect to given hormone signal). The delays in this small sample from a small pilot study are from 2 days to 4 days with respect to LH, and from 2 to 3 days with respect to Pk; two cycles are without any LH surge detection.

We also note that our self-diagnostic process – while generating the detailed folliculogenesis profile data for optional analysis by the woman’s healthcare provider – is not unpleasant as is urine sampling, and is not cumbersome, confusing or prone to subjective misinterpretation of results as the other technologies tend to be.

We can and we do envisage the Ovulona to become a friendly routine for the women of the 21st century, everywhere. The existing home-use fertility monitoring products could not aspire to play that role. Hormones in body fluids are only of temporary utility for TTC. Against that, FIV (or Folliculogenesis In Vivo) is not only a superior tool for TTC but it goes beyond that first use – to be of unprecedented and unique service in personalized women’s healthcare for years to come.

See earlier posts in this blog about how symptoms (such as PMS symptoms) vary depending on the day of cycle and on the health conditions of any woman. It is known that female patients respond to therapy differently in relation to their menstrual cycle, i.e., in relation to folliculogenesis. That relationship to the FIV profile is THE fundamental guiding principle of personalized medicine for women.

A new era of obstetrics and gynecology in the offing.

Folliculogenesis in vivo for women’s healthcare – the vision  (from Space perspective, courtesy of NASA)

Yes, dear, contingent upon funding…

        STOP PRESS

For more information go to 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/