Posts Tagged ‘ovulation’

Cervix uteri and seven or eight related things

February 7, 2012

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

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

February 2, 2012

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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Much in women’s health revolves around folliculogenesis – from teen age to peri-menopause

November 30, 2011

In this article I sketch for you the usefulness of the Ovulona™ Smart Sensor™ throughout a woman’s life, with particular attention paid to the extremes of the reproductive lifespan.

We outline the significance of the cervical tissue biosensor for a woman’s health management from adolescence (the teen years) to peri-menopause. This schematic diagram is a pictorial synopsis of the multi-purpose utility of the Ovulona throughout most of a woman’s lifetime.

Ovulona throughout a woman's life

As you recall from prior posts on this blog, FIV™ stands for FOLLICULOGENESIS IN VIVO™, which translates as the sequence of menstrual cyclic records that will be captured and stored (automatically saved) in the Ovulona during normal use by a woman at home. The data is available for transfer to healthcare providers’ Ovulograph™ for medical uses during the reproductive years.

The reproductive age is officially defined as 14 to 44 but we’d encourage, for health reasons, to chop off a few years at both ends from the actual reproductive (high end) or sex-exploration activities (low end). When folliculogenesis – i.e. menstrual cycling – ceases in menopause, hormone therapy and cervical tissue health screening are the two components of menopause and post-menopause health management, to which the Ovulona is applicable.

In this article, I address very briefly (tweetingly!) the two “boundary conditions” of said reproductive years.

I’ll deal with the young boundary condition, i.e. adolescence or teen age, in the style popular nowadays especially at that stage of life . That is, I let speak a few tweets.

When you look at the tweetingly referenced papers (click the short URLs below), you will see how the teen cramp sufferer needs our Ovulona. That’s because she must take the anti-inflammatory medication before the ovulation-linked pain hits, otherwise the med would not work. She – or is it you? – must be able to anticipate ovulation. You need the Ovulona. The timing is crucial, similar to the right timing for conception purposes… (Recommended reading: http://endometriosis.org/treatments/painkillers/ = http://to.ly/6ZsS in the #NSAIDs tweet below).

If it’s menstrual bleeding (not ovulation) that pains you, the Ovulona will tell you when you expect that – whether it is ovulation + 14 days or, probably more likely at this young age, ovulation + irregular number of days. You’ll then see on the display your recorded min and max, with respective probabilities the more accurate the longer you’ve used the Ovulona. That’s this app’s meaning of Smart Sensor™ for you! (And that is because we don’t track just this or that hormone in your pee! Or your BBT, or your signs…)

As for the STD screening aspect of those young years, indicated in the pictorial synopsis above, I refer you to the recent posts in this blog; and the sex ed use of the Ovulona – or rather its recorded data and their discussions in classes – is self-explanatory.

But then there is the subject of chemical contraception, the Pill. So, here, a couple of tweets.

A teenage girl has a #dilemma . With the #Pill she brings on herself a significantly earlier #menopause & likely difficulty to #conceive when desired http://to.ly/5f2W

#Menstrual #cramps are bad but don’t allow them – by taking the #Pill – to cause you the much worse #pain of TTC #infertility http://to.ly/5f2W    [TTC = Trying To Conceive. That’s the phrase and acronym used by people who have difficulty getting pregnant.]

http://to.ly/5f2W Even with just 3-15 months of #contraceptive #pill use you suffer greater loss of S crypt cells than can be replaced. Then difficult TTC is likely [S crypts are part of the microscopic structure of the cervical epithelium, of the tissues.]

Here now are those few tweets referring to dysmenorrhea, the menstrual pain which causes so much suffering and so many lost hours at school and/or at work. In this day and age!

#NSAIDs against #endometriosis pain http://to.ly/6ZsS Since you must take the meds BEFORE expected #cramps you need our Ovulona tool to anticipate ovulation http://to.ly/MJS [NSAIDs = Non-Steroidal Anti-Inflammatory Drugs]

@bioZhena/fertility    http://to.ly/MJS Why most girls get cramps What goes on there Why & what’s PCOS See it with Ovulona [Obese girls tend to grow into women with PCOS = Poly Cystic Ovary Syndrome, the cause of major killer diseases, and often causing infertility.]

Folliculogenesis #InVivo for Why Do Most Girls Suffer With #dysmenorrhea #cramps http://to.ly/MJS #womenshealth #diagnostic #medicaldevice

Ovulona for etiology & management of  #dysmenorrhea Why do teen girls suffer with #cramps?   http://to.ly/MJS #pharma #medtech #medicaldevice [etiology = the cause or origin of a disease]

Re: etiology of adolescent #dysmenorrhea Prostaglandin theory & treatment known since the 1980s. Why are period cramps still so bad?

I leave you and this “boundary condition for Ovulona’s use” with two Google Insights graphs. Look here how the worldwide interest level in the subject of period cramps has been increasing since 2004.

Period cramps worldwide searches from 2004 by Google Insights

Period cramps worldwide searches from 2004 by Google Insights

Don’t ask me why the recorded public interest is emanating from those particular English-speaking countries and not from numerous others, and look for details at http://www.google.com/insights/search/#cat=0-45&q=period%20cramps&cmpt=q (you can change the selected parameters and observe the effect of the changes).

I merely note the periodicity developing in the data in recent years on top of the clear upward trend, the periodicity indicative of highest interest in summertime (such as in July 2011 as captured in the screen shot in the illustration)…

This trend is, of course, the same in the next graph, where I added dysmenorrhea (red) for comparison. That’s a difficult word, so it is not as much searched on as the colloquial cramps – except for, if you look closely, in (Southeast)Asia.

Period cramps & dysmenorrhea worldwide searches since 2004 by Google Insights

I’ll now use one more tweet to segue into the other end of the span of reproductive years.

#estrogen can be a good medication but we need #personalizedmedicine tools. We must measure & titrate #hormone uptake http://t.co/CeCsWgn

The following illustration shows that we at bioZhena have the technology with which to do that, i.e. a tool with which to adjust treatment to suit a given female patient.

The illustration is a graph of the effects of estrogen and progesterone monitored with our technology in an ovariectomized pig. Ovariectomy is the removal of the ovaries. It is the animal equivalent of surgical hysterectomy, which causes surgical menopause since the reproductive system no longer produces said sex hormones, the sex steroids estrogen and progesterone.

In the illustrated experiment, the steroids were later given to the animal (after recovery from surgery), and the result was that progesterone drove the sensor signal down versus estrogen drove it up (as seen in FIG. 5 below, excerpted from our patent portfolio). This is a useful finding, for example for monitoring the effects of hormone replacement therapy (HRT). 

Graph of estrogen and progestagen effects on porcine cervix

Graph of estrogen and progestagen effects on porcine cervix

We also have the proof of the concept generated by a menopausal woman, using a Premarin treatment in that experiment (Premarin is an estrogen medication used for treating the symptoms of menopause including hot flashes, vaginal dryness, etc.). The data was used in another patent in our portfolio.

Background on menopause, HRT and bioZhena can be found in the early blog post at https://biozhena.wordpress.com/2007/12/18/menopause-hrt-and-biozhena/ .

Experts advocate that women in their 30s and 40s should look at menopause now. Health maintenance depends on diagnostic tools. We propose that the preparation for menopause be done – in a simple quick daily routine – by systematically monitoring the Ovulona menstrual cyclic profile, and how it changes over the years. How it responds to pregnancy and birth, to things like diet, exercise, various ills, various medications, stress… in the particular woman user, not some statistical average. For evidence-based personalized health care.

That’s the broader meaning and the purpose of the folliculogenesis cyclic profile generated by the Ovulona. It’s not merely (“merely”!) for helping to get pregnant or for avoiding pregnancy without chemicals, as is illustrated and described in “Pregnancy and birth control how-to by bioZhena” at this Photobucket site. In the third graphic, on this page, see the follicular waves that relate to follicular age, i.e. how fast is menopause approaching, after pregnancies were successfully achieved and then regulated in this Ovulona-guided manner.

This is because the cervix monitors the physiological inputs after conception and after pregnancy just like it does the monitoring before fertilization and before birth. We pick up the diagnostically useful information from this key female organ. We speak of end organ effects.

For a still broader perspective, including symptometric monitoring correlated with folliculogenesis, go to “Far more than a tool for reproductive management”.

STOP PRESS

And after all that, 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/

Saint Nicholas Day, his legend, and our modern day’s prematurity, EDD calculation, gestational age, problem with LMP

December 8, 2010

Could high prevalence of prematurity be a consequence of motherhood not being the top job held by society in high esteem? A modern paradox.

December 5 is the eve of St. Nicholas Day, the patron Saint of many people, cities and countries – including the largest one [ http://en.wikipedia.org/wiki/Saint_Nicholas#Deeds_and_miracles_attributed_to_Saint_Nicholas ]. St. Nicholas is remembered and celebrated in similar ways in some countries, rewarding well-behaved children but not the misbehaving ones… Which is why St. Nicholas, known as Svaty Mikulas, visits the children at home, in certain parts of Central Europe, in the evening along with an Angel and a Devil (Cert). The Saint asks the parents about the kids’ conduct…

Josef Lada_Mikulas, andel a cert

Josef Lada - Mikulas doma

Josef Lada – Mikulas doma

I share with you a depiction of the tradition drawn by Josef Lada in the troubled 1930s, an idyllic tradition of an industrial people, which they keep to this day…

Besides numerous miracles, this most popular of Saints was and is reputed for gift-giving (hence the commercialized Santa Claus transformation morphing St. Nicholas  with a Western or Northern European Father Christmas later on in the month of December).

There are numerous legends about Saint Nicholas’ miracles and his deeds of help. Perhaps the most famous one is about the three daughters of an impoverished man who could not afford a proper dowry for them, dowry being an ancient habit, the original purpose of which “was to provide ‘seed money’ or property for the establishment of a new household” – and we are now talking about the 300s CE [Christian Era].

The saint Bishop of Myrna saved the girls from the fate of slavery and prostitution by secretly dropping “three purses (one for each daughter) filled with gold coins through the window opening into the man’s house”, which gift made the young girls “eligible” again. It is also said that he dropped the gift down the chimney where stockings were hanging “over the embers to dry, and that the bag of gold fell into the stocking”. That’s beside the point because we are not discussing Santa of Christmas, but rather we are remembering St. Nicolas of December 6.

Jan_Steen_Het_Sint_Nicolaasfeest, The Feast of St. Nicholas

Jan_Steen_Het_Sint_Nicolaasfeest,                               The Feast of St. Nicholas

In those times many, many centuries ago, the chief purpose of young women’s life was motherhood, naturally within a marriage, hence the said dowry habit. In our times, many things have changed, including, unfortunately, young women’s attitude towards motherhood. Well, not just young women’s attitude…

Motherhood must be held in high esteem to reverse the trend reflected by an outcry in tweeter-sphere that’s a part of life nowadays: “I never felt marginalized as a woman until I became a mother”. Now this is very sad. Sad for society since the opposite should be the case.

Motherhood is the most important “job” in the world, and this is not some cute old-fashioned thought. Women bear enormous responsibility for the health of the nation, of humankind. Society should pamper them. Meaning: Society should be organized based on the recognition of Mother Nature’s design, which design – with the optimal years for motherhood in the early twenties – does not go away only because nowadays we can do all kinds of things – including octuplet pregnancies at grandmotherly age.

One consequence of the referenced changes is the currently common delays in getting married, and especially delays in bringing children into the world, starting a family. In other words, the unfortunate consequence is motherhood in later years of life than Nature intended. And then there are other consequences. Among them, prematurity.

Lou Beach, Preggers

Lou Beach, Preggers

@DrJenGunter not too long ago tweeted on prematurity, the most common cause of infant morbidity and mortality in the U.S.: “I just wrote a book on prematurity. Personal and professional experience”. See The Preemie Primer: A Complete Guide for Parents of Premature Babies–from Birth through the Toddler Years and Beyond [Paperback], Jennifer Gunter MD (Author) at http://www.amazon.com/Preemie-Primer-Complete-Premature-Babies/dp/0738213934/

Here is a citation [from http://www.preemieprimer.com/ ]:

My son Victor has dystonic cerebral palsy. He weighed 843 g at birth and had a grade 2 IVH. The bleed resolved in the NICU without hydrocephalus.

He is seven years old now. He is very stiff and is so shaky on a bicycle that we have given up trying for now. He couldn’t stand on one foot until he was 5. It took a very long time for him to get the hang of swimming and at the age of seven he is by no means a fish, but I feel if he were to fall in a pool he could keep his head above water. His digestive tract is very affected, but we have figured out ways to minimize these issues. It took countless hours of OT and thousands of hours of him practicing, but his writing is beautiful and God know where he gets his spelling ability from. He hopscotches like a pro. He is reading a grade level ahead. All without a CT scan or an MRI.

Based on his exam and his problem areas I am sure his cerebellum is a mess. In fact, I wonder if I would have pushed him so hard if I had seen a brain scan before we left the NICU?

“What we know about prematurity” is reviewed by the March of Dimes Campaign at http://www.marchofdimes.com/Mission/prematurity_indepth.html .

Today more than 1,400 babies in the United States (1 in 8 [= 12.5%]) will be born prematurely. Many will be too small and too sick to go home. Instead, they face weeks or even months in the newborn intensive care unit (NICU). These babies face an increased risk of serious medical complications and death; however, most, eventually, will go home. … In fact, the rate of premature birth increased by more than 20 percent between 1990 and 2006. … The rate fell to 12.3 percent in 2008 from 12.7 in 2007, a small but statistically significant decrease.

Why women deliver early? In nearly 40 percent of premature births, the cause is unknown. However, researchers have made some progress in learning the causes of prematurity. Studies suggest that there may be four main routes leading to spontaneous premature labor.”

Štyrský, Marriage

Štyrský, Marriage

Do refer to the referenced article for more about the four main causes:

  1. Infections and/or inflammation.
  2. Maternal or fetal stress.
  3. Bleeding.
  4. Stretching.

And then there is this: These four routes are not the only things to consider. Other factors, such as multiple pregnancy, inductions and cesarean sections, can also play a role. (Mostly man-made factors, we note. I say “mostly” because some multiple pregnancies happen also to women who did not get pregnant through the Artificial Reproductive Technologies… )

Prematurity is bad for infant, parents, and public health. We at bioZhena propose to contribute to the reduction of its prevalence, by making the FOLLICULOGENESIS IN VIVO™ [FIV™] technology available for routine use by women and their physicians. As a particular example, in relation to the referenced other factors, we propose to make it possible to compute the Expected Date of Delivery (EDD) based on the expectant mothers’ folliculogenesis data.

The idea is to get away from the gestation calculation popularized about 200 years ago in 1812 by a Dr. Naegele, for whom the 40 weeks or 10 lunar months rule of obstetrics is named. This rule of 280-day gestation assumes that the mother ovulates on day 14 of a 28 day menstrual cycle, which the readers of bioZhena’s Weblog know that it is an unrealistic assumption.

America in 1812, the time of Dr. Naegele’s 200 years of fame

America in 1812, the time of Dr. Naegele’s 200 years of fame

Napoleon & carabiniers_in_front_of_Moscow_1812

Napoleon & carabiniers_in_front_of_Moscow_1812

Allegedly*, it was Dr. Hermanni Boerhaave, in his time a highly respected academic physician, botanist and chemist, who read in the Bible that pregnancy should last 10 lunar months. He is said to have formulated – in the 1700s – a way of calculating the expected date of delivery (EDD).

Thus, expectant mothers get EDD today based on the myth of the baroque-era Boerhaave … Yet, already Aristotle taught that “the human fetus is expelled … at any period of pregnancy …; moreover, when the birth takes place in the eighth month, it is possible for the infant to live.”

The gist of the bioZhena hypothesis is this: The EDD can be projected quite well from ultrasonic measurements of the unborn baby’s head and body size, but for a more convenient, affordable and consequently more practical solution, we propose to seek a correlation between the Ovulona FIV™ attributes such as cycle length and the EDD/EDC. Importantly, this will be done by using the date of insemination, which will be easily – electronically – recorded by the user of the Ovulona™ as an integral part of the routine.

Trying to be fair or considerate to the women’s healthcare classics, I report an obgyn.net paper at http://www.obgyn.net/fetal-monitoring/fetal-monitoring.asp?page=cotm/9807/cotm_9807 . It is titled “’Back to the Future’ for Hermaani Boerhaave, or, ‘A rational way to generate ultrasound scan charts for estimating the date of delivery’” by Dr David J R Hutchon, Consultant Obstetrician, Memorial Hospital, Darlington, England. This is about the ultrasound approach, and he comments that: QUOTE “the approach mimics, in modern terms, the method originally formulated by Boerhaave. … If Boerhaave had had an ultrasound scanner, his paper might have read something like, ‘It is proved by numerous observations that 99 out of 100 births occur 22 weeks (at 18 weeks gestation) after the biparietal diameter of the fetus is 40mm’ (Fig 1).”

Besides his Figure 1, I also share Mr Hutchon’s (a British medical doctor, when Consultant, becomes Mr again) Fig. 2, “Regression analysis showing line fit plot. The number of days between scan and delivery has been converted to conventional gestation by subtracting from 280. The lower and upper dotted lines represent delivery at 42 and 37 weeks respectively.” QUOTE UNQUOTE.

Gestation age vs. crown rump length by DJR Hutchon

Gestation age vs. crown rump length by DJR Hutchon

Gestation vs. biparietal diameter by Hutchon

Gestation vs. biparietal diameter by Hutchon

Biparietal diameter is the (outer – inner) measurement of the fetal skull echo. Crown-rump length (CRL) is the measurement of the length of human embryos and fetuses from the top of the head (crown) to the bottom of the buttocks (rump). In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization. These are the Wikipedia reported definitions. The two weeks between 9 and 11 assume the “regular” length of the menstrual cycle, which is a theoretical assumption that could very likely be incorrect in practice, in the given woman and in the given last cycle of hers (because regularity is a myth, too). Well, look at the scatter in the data points, it’s telling.

In addition to the convenience, affordability and practicality of the bioZhena approach, do not overlook the feature that the data will be personal to the given woman, and the measurement will not refer to LMP. It will not rely on the woman’s recollection of her last menstrual period (instead, it will refer to the last electronically recorded intercourse); and it will not subject the baby to unnecessary ultrasound radiation.

For more on the topic, try under Gestation in the Alphabet of bioZhena https://biozhena.files.wordpress.com/2007/11/aaee-the-alphabet-of-biozhena.pdf (or https://biozhena.wordpress.com/2007/11/28/the-alphabet-of-biozhena/ ). See also the discussion under Parturition, where we express the expectation that parturition management will be revolutionized by the introduction of the Ovulona into obstetric and gynecological practice.

Anderle - Pasek 06

Anderle – Pasek 06

Summary Definitions [quoted from http://www.righthealth.com/topic/Fetal_Age ]:

Gestation is the period of time between conception and birth, during which the fetus grows and develops inside the mother’s womb.

Gestational age is the time measured from the first day of the woman’s last menstrual cycle [LMP] to the current date. It is measured in weeks. A normal pregnancy can range from 38 to 42 weeks.

Infants born before 37 weeks are considered premature. Infants born after 42 weeks are considered postmature. (Note: 42 x 7 = 294).

Especially with the challenged menstrual cycles that are particularly irregular in length, referencing the LMP in the reckoning can easily introduce a significant error. Perhaps that is why the above summary definition of normalcy is 38 to 42 weeks but prematurity is “before 37 weeks”? (A week here, a week there…) Read also the earlier post https://biozhena.wordpress.com/2008/01/11/about-the-edd-andor-edc-issue-and-a-request-for-input-from-readers/ .

Tomáš Císarovský  - Kukátko

Tomáš Císarovský – Kukátko

280 may have been in the Bible, but it ain’t necessarily right. We’ll see whether 266 is, and whether it is a worldwide constant, which is doubtful. If for no other reason, global constancy is doubtful because it was reported from India that “Mean gestational age at the onset of labour for women native to the area of study was 272 days (standard deviation 9 days). Pregnancies beyond a duration of 280 days showed significantly increased perinatal morbidity.” (Referencing the above righthealth.com definitions, we see 294 – 280 = 14. A week here, a couple of weeks there…)

Well, 272 – 14 = 258. Not 266, and that number is of interest because per Encyclopedia of Childhood and Adolescence, ”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” (article Gestation Period and Gestational Age).

And then you have the oprah.com article, which asks, “Will the labor start naturally on time, or will the baby be so late that induction or Caesarean section is necessary?”: http://www.oprah.com/relationships/Is-Pregnancy-Really-40-Weeks-Long . While debating the validity of the word “necessary” is not the point here, the author there refers to data from studies that concluded greater than 280 days due dates (288 days in one study), of which one study was in Sweden.

A hypothesis can be that hot climates may lead to lower gestation periods than cold climates. This would be a hypothesis based on two data points and a common sense for “the babies taking longer when it’s cold outside”… We’ll want to compare, say, data from Inuits and Lapps on the one hand with data from equatorial Africa and Philippines and/or Indonesia on the other. Logically, we’ll control for factors known or suspected as being involved, such as those four main causes listed above – and age, parity and other factors already explored by people such as Mittendorf in the 1980s.

Kupka - Creation de l homme

Kupka – Creation de l homme

The idea is that routine use of the Ovulona will provide for an equivalent of the above-referenced 38-week (266 days) calculation, which is available to the women receiving IVF or artificial insemination. The data will be personal and the geography of the birth will be noted (as well as ethnicity), with data sooner or later coming from all corners of the world.

Capturing and working with the fertilization date should, by and of itself, be an improvement over the current way of EDD/EDC assessment. An improvement over the paradox of modern obstetrics and gynecology handling the most important aspect of reproduction by means of some biblical myth, and having become more and more interventionist probably at least in part because of that myth. Reference a recent tweet: Maternity Care In America Rife With Systematic Failures l Being #Pregnant http://su.pr/2j91wY “most people don’t know normal birth”. This refers to the medical staff.

That these thoughts are sensible, and that the chief problem is the LMP, is supported by ultrasound studies such as “Gestational age and induction of labour for prolonged pregnancy” by Jason Gardosi, Tracey Vanner, and Andy Francis (Perinatal Research, Audit and Monitoring, Department of Obstetrics and Gynaecology, Queen’s Medical Centre, Nottingham, UK) in British Journal of Obstetrics and Gynaecology, July 1997, Vol. 104, pp. 792-797 – [http://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.1997.tb12022.x/pdf].

Citing from this study of more than 24.5 thousand pregnancies: Menstrual dates [LMP data] systematically overestimated gestational age at term when compared with scan dates… suggesting that most pregnancies which are considered ‘prolonged’ according to menstrual dates are in fact mis-dated. The median gestational age for induced labours was 286 days by last menstrual period but only 280 days by scan, and most (71.5%) inductions done post-term (> 294 days) according to menstrual dates were not post-term if scan dates alone are used to calculate the gestational age.“

This study was a retrospective analysis of computer files of 24,675 pregnancies delivered in a teaching hospital between 1988 and 1995.

Here is their graphical summary of distribution of deliveries as a function of gestational ages by ultrasound scan dates.

Deliveries vs. gestational ages by ultrasound scan dates

Deliveries vs. gestational ages by ultrasound scan dates

Their most explicit statement in support of our conviction and plan is this citation: “Even if the date of the last menstrual period is recalled with accuracy, delay in ovulation can result in over-estimation of the true gestational age, which results in an apparent prolongation of pregnancy.” The authors also cite a 1972 paper in American Journal of Obstetric and Gynecology in support of the just cited statement.

The Gardosi et al. paper concluded: Regardless of obstetric and maternal views of the advantages and disadvantages of routine induction policies, our results suggest that most post-date inductions are unwarranted on the basis of gestational age. The incidence of prolonged pregnancies can be considerably reduced by establishing dates by ultrasound alone.

Needless to say, a similar graph for deliveries in India would show the spontaneous labor peak earlier (272 days by one study in tropical Manipal) while a Scandinavian graph would be shifted in the opposite direction; both were referenced above.

I’ll be darned if the introduction of the Ovulona into the gestation arena should not bring some order and peace (as opposed to the mess and anxieties of today). As I wrote in the conclusion of the related January 11, 2008 article: It is perfectly realistic a vision that, in future, an expectant mother’s EDD and/or EDC will be assessed based on her folliculogenesis (FIV™) data.

The EDD/EDC will be computed automatically and provided by her own Ovulona Smart Sensor™. And no Saint Nicholas miraculous assistance will be required by the future users – although we will not write here the same for bioZhena.

———

* I write “allegedly” because I spent many an hour looking for evidence of truth in this allegation, only to find the Dutch man an impressive medico-scientific mind and an impressive likeable character – but no evidence of the biblical dogma ascribed to him. As I write this note, I am going once more through the tedious but interesting Dr. Boerhaave’s “Academical lectures on the theory of physic” of AD 1744. The man’s fame and authority was such that “a Chinese mandarin, seeking advice, addressed his letter to ‘Boerhaave – Europe’, and it was delivered”. See http://books.google.com/books?id=QTUVAAAAQAAJ&printsec=frontcover&dq=Hermanni+Boerhaave+1744&source=bl&ots=NCeCN4gLdd&sig=SoUA_WS6iSkh2A8WpBX7S4o54Uw&hl=en&ei=ebP-TP2WBIX2tgO12-mvCw&sa=X&oi=book_result&ct=result&resnum=4&ved=0CB8Q6AEwAw#v=onepage&q&f=false

Instant detection of pregnancy and of Early Pregnancy Loss, EPL – the adversary of Trying To Conceive, TTC – especially after age 25

November 11, 2010

Early Pregnancy Loss is also known as #stillbirth or #miscarriage, or Early Embryonic Mortality (EEM), and the Ovulona™ is a tool of evidence-based personalized medicine.

After the optimum fertility age of the early twenties, achieving motherhood gets more difficult. It becomes even more essential than before to know your three fertile days, during which – and only during which – conception can occur.

The simple basic principle is: Fertility status detection must be easy and reliable. PLUS early pregnancy detection is really important, and it should be built-in, an integral part of the conception-aiding tool.

Why? Because:

1) early in pregnancy the conceived baby would be harmed by some of the medications taken by the woman, e.g. by a psychiatric medication with teratogenic effect (harmful to the fetus, causing a congenital disorder);

and 2) because of the annual 600,000 miscarriages – per CDC statistics – out of the 6 million US births, which means that at least some 10% of pregnancies are lost to early pregnancy loss (EPL), miscarriage, stillbirth.

Many EPLs go unnoticed. The EPL is a part of the TTC [Trying To Conceive] or subfertility/infertility problem. Our Ovulona monitor of FOLLICULOGENESIS IN VIVO™ is the prospective solution for managing the problem.

The Ovulona™ detects the 3 fertile days for conception, and it will also automatically detect pregnancy immediately upon conception. Similar to early pregnancy loss — its detection is the inverse of pregnancy detection, which both involve the follicular waves. Like this:

Follicular waves disappear = pregnancy detected

versus

waves reappear in early pregnancy =  early pregnancy loss detected.

Furthermore, the cyclic profile data captured by the Ovulona can be used by your healthcare provider to assess what is going on, and provide more effective help.

DIFFICULT USE OF EXISTING OPKs [Ovulation Prediction Kits] is shown in the following tweet by a @WannaBeMom: “1st month using opk. Do the lines usually start light and then get darker day by day or do they ever go back & forth b4 ovulation?”

Our electronic device will take the WannaBeMoms into a different world of baby-making.

Honey is Sweeter than Blood by Salavador Dali, 1941

Honey is Sweeter than Blood by Salavador Dali, 1941

For a woman in her 30s who has had a miscarriage or even two or three, “any delay in attempting conception could further decrease the chances of a healthy baby”, says CNN reporting on a medical study, http://www.cnn.com/2010/HEALTH/08/05/miscarriage.try.again.asap/ .

Study: Women who conceive within six months of miscarriage reduce risk of another.”

November 2016 review and meta-analysis (data on more than a million women): “With an Inter Pregnancy Interval of less than 6 months, the overall risk of further miscarriage and preterm delivery  were significantly reduced.”

These are fundamental principles.

And another principle, not brought up by the CNN or by the study itself, is that a tool for monitoring the early stage of pregnancy for EPL is most desirable. We’d say, mandatory. The Ovulona device monitors (or tracks the process of) folliculogenesis in vivo, which includes the follicular waves that occur after ovulation. The waves disappear upon conception because the reproductive system does not go into another menstrual cycle – it’s pregnant.

In case of EPL, Early Pregnancy Loss (miscarriage), the waves will come back. Early Pregnancy Loss, or Early Embryonic Mortality, is quite a common sad experience of many of us.

The essential point made here is that the woman’s and her physician’s decisions should be guided by the folliculogenesis cyclic profile (and/or its distortion due to distress of any kind). The woman and her doctor should not make decisions or pass recommendations working in the dark, and the data, on which any decision should be based, must be personal to the given patient.

That’s what the Ovulona from bioZhena is for. Personalized medicine. Evidence based medicine.

Automatic pregnancy detection is inherent in the Folliculogenesis In Vivo™ cyclic profile (follicular waves disappear).

This is a screen shot of one of my narrated slides about “what’s going on here” – view (and hear) the slide at https://biozhena.files.wordpress.com/2015/07/single-slide-unprecedented-wealth-of-info-narrated.pps.

Note specifically that: The follicular waves, which occur after ovulation [when the body prepares for the next menstrual cycle], cannot remain in place after fertilization succeeds and conception takes place [because the post-ovulation regime change is even more profound]. That is the principle of instant detection of pregnancy. As opposed to the waiting for the HPT [Home Pregnancy Test] result.

HCG or Human Chorionic Gonadotropin laboratory signature

HCG or Human Chorionic Gonadotropin laboratory signature of the biomarker – detected in a pregnant woman’s urine about 2 weeks into her pregnancy by a HPT home-use urine test – as a color change (into which color the HPT reduces the illustrated complex lab signature)

Should the conceptus [product of conception, early embryo] be lost to EEM, Early Embryonic Mortality (miscarriage), the follicular waves come back to be seen by the Ovulona. That’s the principle of early detection of the miscarriage, and of detecting the return of the non-pregnant condition.

Trying to conceive again should be based on the personal FIV™ [FOLLICULOGENESIS IN VIVO] cyclic profile data generated by the woman trying to have a baby. This is a principle of evidence-based medicine. Personalized medicine.

Entre Les Trous De La Memoire by Appia

The Ovulona is intended to help people such as those writing in a forum as follows:

My partner and i started trying for a baby in jan And Concieved in the first month. Unfortunately in march at 8 weeks I had a miscarriage. We have been trying since with no luck. Could something be wrong. Please help this is really getting me down. http://www.netdoctor.co.uk/interactive/discussion/viewtopic.php?t=57881&f=5

We got pregnant the first cycle with both my ds and dd. I am most likely moving to cycle #11 with this baby. We did conceive on the second cycle of trying with baby #3 but we miscarried a week later. Nothing since then. I’m not sure why this time is taking so much longer. http://www.mothering.com/discussions/showthread.php?p=16029816

Can anyone advise? My daughter has been trying to get pregnant for several years. Her husband is fine. My daughter has now been asked to go for a scan which scared the life out of me (you automatically think something is horribly wrong). Can someone tell me what the scan is about – what sort of scan is it? http://www.netdoctor.co.uk/interactive/discussion/viewtopic.php?t=31528&f=5

The information contained in the folliculogenesis cyclic profile, as illustrated in the slide captured above, is meaningful and can help the healthcare provider to answer questions such as these.

Trying to conceive, TTC, or the frustration of sub-fertility & infertility

November 9, 2010

Existing approaches to TTC, Trying To Conceive, are not satisfactory – and cannot be, without FOLLICULOGENESIS IN VIVO™

Here is the premise: To #conceive a #pregnancy the couple must absolutely do their TTC in the woman’s #fertile time, which is a window of 3 days: https://biozhena.wordpress.com/2010/05/25/difficult-conception-tied-to-pregnancy-complications-addressed/ . The unspoken corollary is that advancing age does not help, and neither do things that pollute our life, that is all those various stressors.

Besides which, you need to know not only when your ovulation is approaching but also that it actually occurs. No guessing, no mere assuming that it does, or that it did.

Human ovulation caught on camera by Dr Donnez

Human ovulation caught on camera by Dr Donnez

This photo of the ovulation event is unique, and it clearly cannot be the answer to the necessity of knowing that ovulation occurs in the menstrual cycle of interest to you. Also unique is that the Ovulona™ will do the determination of ovulation for you automatically – in your hands, at your convenience, with no discomfort. It’s one part of the FOLLICULOGENESIS IN VIVO™ simple self-monitoring procedure with the Ovulona™. In doing so, you’ll gather and automatically store in the device data of diagnostic significance to your healthcare providers. Your physician’s decisions should be guided by the folliculogenesis cyclic profile. Yours, too.

Here now, how TTC people need our Ovulona: Disgusted with peeing on a stick, writes stressed out, frustrated, messed up @socalledttclife: “On to IUI #4 we go” [IUI = Intra Uterine Insemination procedure], http://ow.ly/351yf .

She blogs: “…Progesterone supps suck. No, really, Crinone is now numero uno on my most hated list right there behind peeing on a stick and betas. It totally MESSED with my head this cycle. It made me crampy, it gave me headaches, it delayed my period—ALL of the things that are usually early pregnancy symptoms. Damn you, Crinone!”

This is one example and one reason why a month ago the following tweeting dialog took place: RT @resolveorg What’s the one thing you wished the public knew about #infertility?

bioZhena’s answer = Before #fertility #drugs, try right timing http://to.ly/5dUR . Definitely! Read on.

Quite apart from the fact that even the artificial reproductive procedures such as said IUI have to be performed at the right time in the patient’s cycle to have a chance succeeding. Before undergoing the “heroic procedures” of Artificial Reproductive Technologies [ARTs], explore the normal natural approach, and – naturally – you need a reliable timing tool to know when exactly your 3-day fertile window occurs. Good thing you are still this side of 35, although it would be much better if you were this side of 25. Or 30, at least. But that’s water under the bridge… unfortunately.

Water under the bridge… How many bridges?

Water under the bridge… How many bridges?

Per Google Alert, Today’s TTC Trying To #Conceive forum has 4 results that are symptomatic of the TTC world – and how that world needs our Ovulona diagnostic tool with essential folliculogenesis data for the physicians:

1. Conceiving in our 20s http://www.mothering.com/discussions/showthread.php?p=16007861

2. healthy excersise while TTC – TTC- Trying to conceive Group so im a gymaholic… Before I go to my GP again with yet another silly question, what do you girls think, with your experience and knowledge, about my standard work out ‘plan’ below? Is this too much while TTC? … Thoughts? Please don’t make me not do it 😦

social.kidspot.com.au/topic.php?topic_id=8490

3. First time TTC with clomid and really nervous, any suggestions?? Forum · PCOS Treatments and Conditions · Infertility and Trying to Conceive; First time TTC with clomid and really nervous, any suggestions? …
www.soulcysters.net/showthread.php?t=317229&page=2

4. Pregnancy Forum UK : UK Pregnancy Forum Parenting and Baby forum …
hey all i had a positive opk on fri am but this morning days later had twinges on left hand side which feel like op is it possible that i have only just …
178.19.113.123/viewtopic.php?f=8&t=114228&view…

#PCOS patients should monitor folliculogenesis & the effects of any treatment on it. See http://to.ly/MJU , and for what it is go to http://to.ly/757m , and see how an obgyn physician related to the technology even early on when it was still in a rather crude prototype form: http://to.ly/vG0 .

As we expressed earlier in this blog:

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.

#Obese peri-pubertal girls may have hyperandrogenemia which can be forerunner of #PCOS: http://to.ly/6PrK .

Not all #women with #PCOS have difficulty achieving #pregnancy, but anovulation is a common problem: http://to.ly/5mjs .

#PCOS problems are more about #prevention of diseases due to PCOS = #endometrial #cancer #diabetes #heart disease #strokes: http://to.ly/5mjs . Per @JoshGitalis : Insulin resistance is an underlying biochem. imbalance in not only type 2 #diabetes, but #CVD, #hypertension, #PCOS, and colon/breast cancer.

RT @kevinmd Too many young children are medicated with powerful #drugs http://goo.gl/fb/xXu5q – Too many #women too. Will this ever be seen as abuse?

Durer, Albrecht - The Temptation Of The Idler (or The Dream Of The Doctor)

Durer, Albrecht – The Temptation Of The Idler (or The Dream Of The Doctor)

Difficult #conception is tied to #pregnancy complications: http://to.ly/4Fih #fertility TTC #conceive #womenshealth . Read also: http://to.ly/6ahN .

#Natural vs. #Clomid in Dr. Randine Lewis: From #Infertility to Motherhood, http://to.ly/60v6 . Wrote the #medical doctor:

“I was experiencing hormonal problems. My joints ached, I had lower back and knee pain, I had to urinate frequently, I had night sweats, I was experiencing hair loss and my periods were extremely irregular and sometimes nonexistent.

A medical work-up revealed my estrogen and progesterone levels were alarmingly low, resulting in my inability to conceive. The doctor recommended that I take Clomid, a drug designed to hyperstimulate a woman’s ovaries to produce more eggs, thus increasing the chances of pregnancy. This advice seemed wrong to me; what about the underlying problem? Was it not unwise to hyperstimulate my ovaries when the problem obviously resided in my whole hormonal system?”

Now, put that in context with More About Clomid, Serophene, Clomiphene citrate or Clomifene, http://to.ly/5dUr . Why popping pills is not the best.

Is #ovulation enough to #conceive? http://to.ly/4Fih . Not really. You have to satisfy 4 factors, 4 prerequisites:

1. good health,

2. right insemination timing,

3. fertilization works,

4. embryo lives, is not lost to early embryonic mortality.

#Stress can do unwanted things to #women & #menstrual cycles: http://to.ly/yBk . Check this out. Sub-fertility can result.

30% of women or couples cannot get pregnant

Every year past the optimal fertile age of early twenties is making things harder – on would be mom, on baby, on healthcare system, on humankind.

Consequences of conception difficulties should not be taken lightly. See why.

STOP PRESS

And now, for a more explicit and detailed info, go to the 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/

How follicular waves will be used for early detection of pregnancy, and for early detection of miscarriage, EPL – to TTC again asap

August 25, 2010

In this post we talk again about the feature introduced in an earlier post, https://biozhena.wordpress.com/2010/01/10/about-the-added-bonus-of-folliculogenesis-monitoring-automatic-pregnancy-detection .

This time we focus on the importance of the utilization of the follicular waves not only for practically instant pregnancy detection, but also for a similarly early detection of miscarriage or early pregnancy loss (EPL, also known as spontaneous abortion, SAB). Refer to Early Pregnancy Loss,  http://emedicine.medscape.com/article/260495-overview . Note: Chief Editor is Professor Lee P. Shulman, MD, FACOG – one of bioZhena Corporation’s Board of Medical Advisors.

Sonography scene. Some contrast vis-à-vis the Ovulona™!

Sonography scene.   Some contrast vis-à-vis the home-use Ovulona™!

Excerpted from said Medscape overview: Early pregnancy loss is unfortunately the most common complication of human gestation, occurring in at least 75% of all women trying to conceive. Most of these losses are unrecognized and occur before or with the next expected menses. Of those that are recognized, 15-20% are spontaneous abortions (SABs) or ectopic pregnancies diagnosed after the pregnancy is clinically recognized.

The incidence of spontaneous miscarriage is 10-15%, whereas the rate of recurrent miscarriage is 3-5%. Approximately 5% of couples trying to conceive have 2 consecutive miscarriages, and approximately 1% of couples have 3 or more consecutive losses.

Early pregnancy loss is defined as the termination of pregnancy before 20 weeks’ gestation or with a fetal weight of below 500 g. An article in http://www.cnn.com/2010/HEALTH/08/05/miscarriage.try.again.asap/ summarized the conclusion that “any delay in attempting conception could further decrease the chances of a healthy baby”.

This is a fundamental concept. Further they write, with reference to the original BMJ publication, “Study: Women who conceive within six months of miscarriage reduce risk of another… The women who conceived within six months also had better overall outcomes. They were about 10 percent less likely to have a C-section or a preterm delivery, and about 15 percent less likely to have a baby of low birth weight than the women who waited up to a year.”

This is a highly suggestive conclusion, implying the need to know as soon as possible. The sooner the better for attaining happiness.

Angelo Bronzino - Allegory_of_Happiness, 1564

Angelo Bronzino – Allegory_of_Happiness, 1564

Another fundamental principle, not brought up by CNN or by the study itself, is that a tool for automatic monitoring of the early stage of pregnancy to watch out for EEM [Early Embryonic Mortality] is desirable, to put it mildly. Our Ovulona™ device is perfect for that. The Ovulona monitors folliculogenesis in vivo, which includes the follicular waves occurring after ovulation. The waves disappear upon conception (the pregnant system does not go preparing for another menstrual cycle, which the follicular waves signify).

The follicular waves disappear as soon as conception takes place and the woman is in early stages of pregnancy. In case of miscarriage, the waves will come back. The point made here is that the woman’s and her obgyn’s decisions about trying for pregnancy again should be guided by diagnostic data. The data on which any decision should be based must be personal to the given patient – not based on statistical outcomes of studies such as the one referenced above.

That’s what the Ovulona™ from bioZhena is for, the tested and the putative uses of which are discussed throughout the bioZhena’s Weblog.

For a pictorial overview with a written narrative, you can go to http://to.ly/VCF (http://s755.photobucket.com/user/vaclavkirsner/library/Second%20album/Pregnancy%20and%20birth%20control%20how-to%20by%20bioZhena?sort=2&page=1 ) and peruse the 6 pictures with brief written explanations of the basics of FIV™, the ovulographic™ monitoring of folliculogenesis in vivo™.

This one of the 6 illustrations, http://to.ly/1k9L, is about “what’s going on here”.  In other words, what is FOLLICULOGENESIS IN VIVO™, the mechanism of the cyclic profiles, the mechanism of menstrual cycles as detected (and passed on to the Ovulona sensor) by the cervix uteri. Should you want to listen to my spoken narrative, click on the image or on the link below.

wealth-of-information-inherent-in-cyclic-profile-signature

The unprecedented wealth of information inherent in the FIV™ cyclic profile

https://biozhena.files.wordpress.com/2016/11/single-slide-narrated-best-wealth-of-info-in-menstrual-cycle-profile-signature.pps

The bottom line is this: The multitude of repeatable features of the cyclic pattern makes it possible to determine the boundaries of the fertile window for every individual menstrual cycle.

A key distinction of our technique is that the “dynamic range” of the cyclic profile data (the vertical span) is the same in all cycles and in all women. This – in addition to the repeatable features of the pattern – facilitates electronic interpretation of the data. Only the timing of the various features varies from cycle to cycle, and we work with that.

The cyclic pattern exhibits a number of well-defined peaks and troughs, with the first post-menstruation minimum (or trough, nadir) occurring typically already on cycle day 6, 7 or 8. That’s the selection stage of folliculogenesis (which follows on the stage of recruitment, days 1 – 5). The signal then rises to a maximum (long-term predictive peak, driven by the maturation of the dominant follicle), the highest reading level of the cycle. Over the next several days, the readings fall toward the minimum before the short-term predictive peak. We have found the ovulation-marker minimum after this short-term predictive peak to correlate with urinary LH and FSH peaks (hormones).

Based on data, we interpret the ovulation marker to be an instantly detected effect of the steroid hormone switch that occurs at ovulation (estrogen to progesterone dominance). The follicular waves, which occur after ovulation [when the non-pregnant system prepares for the next menstrual cycle], cannot remain in place after conception takes place [the regime change is even more profound].

That is the principle of instant detection of pregnancy. Should the conceptus be lost to EEM, Early Embryonic Mortality (miscarriage), the follicular waves come back. That’s the principle of early detection of miscarriage also known as spontaneous abortion [SAB], and of detecting and monitoring the return of the non-pregnant condition.

059q Book of hours

059q Book of hours

Trying to conceive again should be based on the personal FIV™ [FOLLICULOGENESIS IN VIVO™] data generated by the patient, that is, by the woman trying to conceive. This is a principle of evidence-based medicine. Personalized medicine.

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/

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

June 27, 2010

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

Emeritus Professsor Erik Odeblad

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

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

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

Jan Amos Komenský (Comenius) Says Farewell to...

Jan Amos Komenský (Comenius) Says Farewell to…

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

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

Prof. Erik Odeblad's sketches from www.woombeuskadi.org...4_erik_odeblad(secrecion_cervix).pdf 13 February 2008

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

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

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

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

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

  • S crypts produce S mucus, which forms string-like channels and provides transport (“swimming lanes”) for sperm cells. (“Produces a wet, lubricative sensation at the vulva.” That’s for the NFP sympto-thermal method use, the Billings method and/or the Creighton Model NaProEducation Technology method, the classical NFP or FAM – the latter, Fertility Awareness Method, publicized by Ms. Toni Weschler’s 2002 book Taking Charge of Your Fertility .)
  • L crypts produce L mucus, which eliminates low-quality sperm and provides a structure to support what he calls the S and the P mucus. P is a reference to the so-called Peak mucus of NFP or FAM.
  • G crypts produce G mucus, which is “an impenetrable gestagenic mucus formed in the lowest cervical crypts. Prevents sperm entry to the cervix and is part of the immune system which protects the woman’s reproductive system from infection.” A remark from dictionary.com: gestagen (jěs’tə-jən, -jěn’) n. A substance, such as a steroid hormone, that affects the uterus in a manner similar to progesterone. And a remark from a scientific commentator: This G mucus is characterized by the oxidized state of the mentioned redox couples, causing cross-linking in the glycoprotein mucin, which prevents microbes including sperm from entering. Visualize this as closed -S—S- gates (as opposed to the open gate form -SH   HS- of the “reduced” state of the redox couples; “reduced” meaning “electronated and hydrogenated”, the opposite of “oxidized”).
Mondrian_Evolution

Mondrian_Evolution

There are three fundamental principles at work.

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

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

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

Now, then.

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

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

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

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

50% / 25 years = 2% per year.

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

Profile crypts baseline never pregnant never on the Pill

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

Representative profile of cervical crypts

(percentage of cervix occupied by active crypts)

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

This is a baseline profile.

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

Cervix of a 20 year old virgin

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

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

Mucus secretions

Schematics of cervical mucus secretions

Key to colors:

Blue         = S mucus

Yellow     = L mucus

Red          = G mucus

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

Pink         = Z granules

Professor Odeblad’s explanatory notes:

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

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

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

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

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

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

2. Slow-down of atrophy aging by pregnancy:

Profile crypts 4x pregnant

Profile of cervical crypts of a 4x pregnant woman

Representative profile of cervical crypts

(percentage of cervix occupied by active crypts)

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

Pregnancy – S crypt diminution rate from Odeblad’s graph

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

30% / 25 years = 1.2% per year.

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

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

Profile of cervical crypts of a woman on the Pill

Representative profile of cervical crypts

(percentage of cervix occupied by active crypts)

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

Pill – S crypt diminution rate from Odeblad’s graph

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

60% / 25 years = 2.4% per year.

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

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

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

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

This is double the baseline rate of cervical atrophy.

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

Three concluding remarks by Prof. Odeblad:

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

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

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

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

Comment on implications for treatments of certain symptoms

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Laodamia

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

June 25, 2010

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)

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. 1506.

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.

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

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

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

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.

June 23, 2010

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/ ).

30% of women or couples cannot get pregnant

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_large

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, 1938

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.

Dali - Geopoliticus Child Watching the Birth of the New Man (1943)

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 .

Sleep by Salvador Dali, 1937

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

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…)


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