Serious health consequences of delaying pregnancy, and the need for prevention of impaired fertility also known as subfertility and infertility

Simply put: We must talk prevention versus treatment of this health condition, which is not inevitable. On the present large scale, impaired fertility is anthropogenic – where anthropogenic means “caused or produced by humans”. When trying to conceive, it is highly advisable not to delay baby making beyond the optimal age of early 20s, and in any case to practice “focused intercourse”. In that connection (with said focus), “anthropogenic” acquires a positive connotation – even if my introduction is no longer exactly simply put!

Absolute Must: Focus on Fertile Window

The said focus on focused intercourse is an absolute must, and you save yourself a lot of grief that way because there can be no conception outside of the fertile window, whether subfertile or not. This should really be in your mind and in your heart when you are trying to conceive. And if you are, unfortunately, past the optimal age of early twenties, just try and don’t delay pregnancy any longer – for a good reason (or rather for several good reasons)!

To expand on this, let the scene be set by excerpts from a review in a medical journal written already 10 years ago by a consultant in reproductive medicine (director of an assisted conception unit in London): “ABC of subfertility. Extent of the problem”, BMJ 2003 August 23; 327(7412): 434–436 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC188498/).

QUOTE: One in six couples [17%] have an unwanted delay in conception. Roughly half of these couples will conceive either spontaneously or with relatively simple advice or treatment.

Most couples presenting with a fertility problem do not have absolute infertility (that is, no chance of conception), but rather relative subfertility with a reduced chance of conception… so that only 4% remain involuntarily childless. As each couple has a substantial chance of conceiving without treatment, relating the potential benefit of treatment to their chances of conceiving naturally is important…  END QUOTE.

Encouraging (isn’t it?)

This is rather encouraging, isn’t it? The cited reproductive medicine specialist states further that spontaneous conception has about a 30% conception rate in the first month of trying, and the chance then falls steadily to about 5% by the end of the first year. Such statistical pronouncements are just that. The following citation is unarguably meaningful – and we do not gloss over the “timing of intercourse during the natural cycle”.

“The likelihood of spontaneous conception is affected by [= is dependent on] age, previous pregnancy, duration of subfertility, timing of intercourse during the natural cycle, extremes of body mass, and [any] pathology present. A reasonably high spontaneous pregnancy rate still occurs even after the first year of trying. A strong association exists between subfertility and increasing female age. The reduction in fertility is greatest in women in their late 30s and early 40s. For women aged 35-39 years the chance of conceiving spontaneously is about half that of women aged 19-26 years.” QUOTE UNQUOTE.

These things have been covered in the various earlier posts of this blog, with appropriate emphasis on said timing of intercourse during the natural menstrual cycle. That’s because, even if you did have a previous pregnancy and you do NOT have an extreme body mass and/or a pathology causing the difficulty to get pregnant, you (and anyone else) can only conceive during the short fertile period, the so-called fertile window.

… but: “Be a young mother!”

And, I go again as far as urging you, “Be a young mother!” As I said, this earnest recommendation is for a good reason. Because, in addition to what I have told you about before (e.g. in https://biozhena.wordpress.com/2012/04/18/the-perils-of-ivf-of-arts-of-giving-birth-at-old-age-part-2/ ), now see and grasp this:

Serious health consequences of delayed conception are beginning to appear in medical literature; that is, serious consequences for the mother, for the would-be mum.

For example, in a paper titled “Subfertility and risk of later life maternal cardiovascular disease” published in Hum. Reprod. 2012 Feb;27(2):568-75 (http://www.ncbi.nlm.nih.gov/pubmed/22131387). The authors gave this background: “Subfertility shares common pathways with cardiovascular disease (CVD), including polycystic ovarian syndrome [PCOS], obesity and thyroid disorders. Women with prior no or just one pregnancy are at an increased risk of incident CVD when compared with women with two pregnancies.”

They concluded that subfertility among women who eventually have a childbirth is a risk factor for cardiovascular disease. As if we all did not know that even without subfertility adding to it, heart disease is the leading cause of death among women [see http://www.health.harvard.edu/newsweek/Gender_matters_Heart_disease_risk_in_women.htm or literally millions of other web pages].

Jiří Anderle / Jiri Anderle
Bestia triumphans II
lept, měkký kryt / etching, vernis mou
1984, opus 271, 65 x 95,5 cm
http://www.galerieart.cz/prodej_anderle_2.htm
For the “triumphant beast” and Giordano Bruno’s story see http://twitpic.com/8r5lyi

More reasons to prevent subfertility

But there is not just the cardiovascular risk, as if that were not enough! Concerns about cancer risk in connection with subfertility have been raised in medical literature already about a decade ago, such as in the paper “Cancer risk associated with subfertility and ovulation induction: a review” – published in Cancer Causes Control 2000 Apr;11(4):319-44 (http://www.ncbi.nlm.nih.gov/pubmed/10843444).

However, there “the only consistent association observed is an increased risk of endometrial cancer for women with subfertility due to hormonal disorders. While positive findings in some studies on fertility drugs and ovarian cancer risk have aroused serious concern, the associations observed in most of these reports appear to be due to bias or chance rather than being causal.”

So, as always, more investigations are needed but the health concern does not go away. The paper concluded: “To discriminate between the possible carcinogenic effects of various ovulation induction regimens, subfertility disorders, and reproductive characteristics associated with subfertility, future studies should include large populations of subfertile women with sufficient follow-up time.”

Well, the truth is that my purpose – and the purpose of bioZhena Corporation – is to make the population of subfertile women as small as possible, by helping every one of you to determine in every menstrual cycle the very narrow fertile window for your focused intercourse, the fundamental requirement for getting pregnant.

This fundamental requirement you already know, I trust. If not, explore the bioZhena’s Weblog for clarification (you can use Table of Contents at https://biozhena.wordpress.com/table-of-contents-links-to-biozhena-posts/ or try searching the blog by means of the widget in the margin on the home page, shown as Search bioZhena’s Weblog – enter keyword, hit Enter). It is frustrating that one of my recent blog pieces had to be on the subject of only the best that you can do for your fertility awareness in the absence of the Ovulona™ – because our Ovulona is not yet available to you due to our lack of financing (see https://biozhena.wordpress.com/2012/12/14/end-of-the-year-and-trying-to-get-pregnant/ ).

Anthropogenic, iatrogenic

Meanwhile, here is another medical-literature paper, this time about cancer risk of drugs that the healthcare industry uses to help women get pregnant – after helping women to prevent pregnancy with another (the big P) drug, the anthropogenic cause of what experts have called the epidemic of impaired fertility: “Ovulation inducing agents and cancer risk: review of literature” published in Curr Drug Saf. 2011 Sep 1;6(4):250-8 (find the abstract at http://www.ncbi.nlm.nih.gov/pubmed/22129320).

The authors give the following summary: “Over the past decades, the use of ovulation inducing drugs has been increasing. A possible causal link between fertility treatments (especially [the widely used] clomiphene citrate and gonadotrophins) and various types of malignancies, including cancers of female reproductive system, thyroid cancer and melanoma, has been postulated. The majority of the available studies on this subject suffer from methodological limitations, including the small number of outcomes, short and incomplete follow-up, and inability to control for potential confounders.

Concerning ovarian cancer, while early studies led to the suggestion of an association between ovulation inducing agents and increased risk of malignancies, the majority of data do not support a causal link.

An increased risk was recently observed in women giving birth after in vitro fertilization (IVF), but it appeared to be consequential to the infertile status rather than the effect of fertility drugs. More controversial are the results concerning breast cancer with some investigations suggesting an increased risk after exposure to ovulation inducing agents, especially clomiphene citrate, whereas others not supporting this concept. A possible trend towards an increased risk has been reported by some authors for endometrial cancer.

Altogether, current data should be thus regarded as a signal for the need of further studies rather than being definitive in them.” END QUOTE.

After introduction of the anti-conception Pill

I must emphasize and impress on you the fact that subfertility and infertility became a societal problem of increasingly large proportions only after the introduction of the anti-conception Pill. “After 3 and up to 15 months of contraceptive pill use, there is a greater loss of the S crypt cells than can be replaced.” The S crypts of the endocervical canal are needed for conception.

To further cite Professor Erik Odeblad : “Complications arising from the use of the Pill are very frequent. Infertility after its use for 7-15 years is a very serious problem. S crypts are very sensitive to normal and cyclical stimulation by natural estrogens, and the Pill causes atrophy of these crypts. Fertility is impaired since the movement of sperm cells up the canal is reduced. Treatment is difficult.”

You can find more on this in my earlier post, Difficult to conceive – Google evidence that pregnancy complications and trying-to-conceive concerns shot up after the Pill launch in 1960s. (Regardless of what contraceptive proponents tell you.)

MARINA RICHTEROVÁ – Golgota, Hommage a P. Bruegel, 1998 and The Juliet, 2000

(Picture from https://biozhena.wordpress.com/2012/04/18/the-perils-of-ivf-of-arts-of-giving-birth-at-old-age-part-2/marina-richterova-golgota-hommage-a-p-bruegel-1998-and-the-juliet-2000/ )

Ignored. Now, the consequences

I am reminded of an insight expressed on the floor of the US Congress after the Pill made a big impact on society in the 1960s. In 1970, Dr. Hugh J. Davies of Johns Hopkins University told the US Senate in the Nelson Hearings about the contraceptive Pill: “Never before in history have so many people taken such powerful medication with so little information as to its actual and potential risks. …With the introduction of such active ingredients, we are actually setting up a massive endocrinological experiment with millions of healthy women.”

Well, decades later we are reaping the consequences of the massive experiment. Said millions of healthy women are not quite so healthy, are they? It is high time to fix this man-made problem.

In an earlier post I wrote: Iatrogenic medicine kicking Hippocrates where it hurts the most. Was it in the blog piece last-linked above?

How baby-making late in life evolved into subfertility and infertility, difficult conception, too long TTC

Way back, in the pre-contraceptive Pill days, the difficulty to become pregnant was not a widespread phenomenon, and mums were  younger than many are nowadays. If you want to see graphical proof of how the phenomenon came about in the previous century, review the attached paper Google evidence of increasing prevalence of subfertility. Should you not be a subfertility or infertility sufferer, and therefore not familiar with the acronym, TTC stands for Trying To Conceive.

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

In 1940, births to mothers over 29 years old (30 to 49) were apparently almost as numerous as births to mums of the optimal fertility age 20-24: The ratio of 30-49 years old to the optimal-age group was 0.91 [here referred to as ratio a) =  data for 30–34 plus 35–39 plus 40–44 plus 45–49, this sum divided by data for 20–24], and the number of births in the most fertile age group of mums represented 31% of all births in the U.S.

In case you did not check out the above-linked attachment https://biozhena.files.wordpress.com/2012/12/google-evidence-of-increasing-prevalence-of-subfertility.pdf : The high number of 1940 births to older mothers [high ratio a)] is not so surprising in view of the growing number of books on subfertility and infertility in the 1940s, as seen in the respective Google Ngrams shown here and discussed in the attached PDF paper.

Ngram 3: infertility and contraception

In the present analysis of the historical birth rates, the age group of 25-29 is considered kind of neutral (neither optimal nor too old) whereas the 30-34 years old group is included among the too old ages for optimal fertility. This inclusion could be disputed – if we did not face the subfertility/infertility phenomenon, in which age is a significant factor. In any case, excluding the 30-34 age group from the aged-motherhood definition only delays the trend reversal – observed below in 1980 – by a decade.

I interject here a citation from the post referenced and linked at the end of this post, so that you’ll be well aware of the link between conception difficulties and advancing age, and of the adverse effect of the use of the Pill.

QUOTE: People have a hard time accepting that getting pregnant is not as easy as expected, when they finally decide to want a baby – usually way too late, and after her use of the Pill. The drug makes healthy young women in their best years to postpone family- and baby-making, it damages their cervical S-crypts thus causing difficulty to conceive and, by encouraging promiscuous sex life, it has caused an enormous increase in the prevalence of sexually transmitted diseases that also lead to infertility. Not just a double whammy, a triple whammy on womankind.  Sad, sad, sad. … Advanced age of the would-be Mum works against her on account of the Mother Nature’s Probabilistic Rules and Regulations of Baby-Making… END QUOTE.

An obgyn’s article on female subfertility in the Lancet invokes “two main factors that determine subfertility: duration of childlessness and age of the woman”. It is not likely that an obgyn would be as critical of the Pill as yours truly, although there have been exceptions. No further comment on this is needed or offered in this blog post. Instead, I share that another medical article from Britain reported that “the incidence of infertility was 0.9 couples per 1000 general population. The average age of women was 31 years, and the average time attempting conception was 18 months… At 12 months, 27% of all couples in the study achieved a pregnancy spontaneously and a further 9% with treatment.”

Here are the 1940 US birth statistics data from the referenced infoplease.com source:

Year	Total	Under 15	15–19	20–24	25–29	30–34	35–39	40–44	45–49
1940	2,558,647	3,865	332,667	799,537	693,268	431,468	222,015	68,269	7,558

And this is the calculation for the present analysis of the data:

a) 729,310/799,537 = 0.912

(ratio a is the sum of births to age groups from age 30 to age 49 divided by births to age group 20 – 24)

b) 799,537/2,558,647 =  0.312

(ratio b is births to age group 20 – 24 divided by total births in 1940)

By 1950 and 1960, the trend was good because ratio a) declined from 0.91 to 0.86 and then to 0.80 while the number of optimally aged young mothers rose slightly to 32% and then to 33.5%. These pre-Pill years were good years from this perspective, and the trend continued – even after the contraceptive Pill was introduced (in the 1960s), at least initially.

In 1970, there was a drop in the total number of births from the total of 1960 (4,257,850 births) and a dramatic drop in the number of births by aged mothers [ratio a) was 0.47] – and the births by the most fertile age group were up to 38% of all births. As though the contraceptive Pill worked in this sense (but only if we do not look at the significantly increased births by underage girls, especially the under 15)… Here is the 1970 data from the above source:

Year	Total	Under 15	15–19	20–24	25–29	30–34	35–39	40–44	45–49
1970	3,731,386	11,752	644,708	1,418,874	994,904	427,806	180,244	49,952	3,146

Unfortunately, in 1980 – that’s some 20 years after the Pill was introduced – the trend started to reverse while the total births continued to drop (and underage births dropped, too): Ratio a) of the number of aged mothers’ births to the most fertile age group’s births rose to 0.58 and births by the most fertile 20-24 year old mums represented now only 34% of total US births. The bad trend toward older-age motherhood continued.

By 1990, there were even more births to aging mothers than births to the most fertile age group, with ratio a) standing at 1.15 and the number of births to mothers of the optimal age group having dropped to a mere 26%.

The bad trend continued so that in 2000 advanced-age mothers exceeded the optimal-age group with ratio a) at 1.45, and with the optimally aged mums at 25% of total births. The trend continued further so that in 2009 advanced-age mothers exceeded the optimally aged mums by a factor of 1.53 [= ratio a)] and the optimal age group’s births dropped to 24% of total births. Data for 2009 are the most recent available data.

Tamara de Lempicka Quattrocento, 1937

Is the difference between way back and now the reason for one other elevated readership statistic here on bioZhena’s Weblog? It is intriguing to see that during the months of the highest numbers of US births/deliveries (late summer and autumn, well before the year-end Holiday Season), a highly viewed post this year was the one published around the time of Mother’s Day: Why too many young and not so young ladies could NOT receive flowers on Mothers’ Day. Why so many trying-to-conceive, why so much infertility = https://biozhena.wordpress.com/2012/05/14/why-too-many-young-and-not-so-young-ladies-could-not-receive-flowers-on-mothers-day-why-so-many-trying-to-conceive-why-so-much-infertility/ Say thank you to the social and medical advances of the twentieth century – primarily those of chemical birth control, the Pill.

What do you think of all this?

P. S. The Alphabet of bioZhena (glossary/primer) is at https://biozhena.files.wordpress.com/2020/01/aaee-the-alphabet-of-biozhena-011207-with-tracking.pdf

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

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

Stress and fertility

How stress affects the inherently narrow fertile window

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

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

 

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

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

 

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

 

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

 

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

bioZhena's Weblog

Please click through to the 2019 revision of this post at

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

How stress affects the inherently narrow fertile window

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

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

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Major studies decades ago revealed variability of menstrual cycles

But people are still naïve about the basic cause of the difficulty to achieve pregnancy

Sex education at school, its quality or otherwise, is likely to have much to do with fertility problems later in life. Many women (men, too, of course) can use the  keyboard with all their fingers (as well as their thumbs!) but have poor understanding of the basic functioning of their reproductive system.

colonial-classroom.jpg

That ignorance is well known, and is underlying the fertility problems. You should see the pregnancy doctors’ tweets – replying to some incredible questions, and then the talk of various mysteries!

A shining example is this tale of “mysterious conception”. For the whole story see the Alphabet of bioZhena under M, “Mysterious conceptions (OR THE NONEXISTENCE THEREOF)” on page 34 or thereabout, from which I cite:

QUOTE:  It appears that we must dwell on this topic, because of stories and notions propagated in various pertinent circles. This writing has been prompted by page 176 in the excellent 1999 book “Woman” by Nathalie Angier, where the Pulitzer laureate relates the story of the mysterious conception of her only child. Mysterious, because it occurred, she believes and makes her readers believe, outside of ovulation and of the fertile window.

The reason for this entry in the Alphabet of bioZhena is that there is NO SUCH THING AS MYSTERIOUS CONCEPTIONS, there is only lack of information, or ignorance of the facts. We might say, intellectual misconceptions lead to “mysteries” in terms of conception, of babies conceived supposedly when conception was biologically impossible, and vice versa, some women have difficulties conceiving for the same fundamental reason. We shall use Ms. Angier’s case to make this point. UNQUOTE.

To drive the point home, here is an excerpt from John J. McCarthy, Jr. and H.E. Rockette, “Prediction of ovulation with basal body temperature”, Journal of Reproductive Medicine, Volume 31 (No.8), Supplement, 742 – 747, 1986.

Referencing particularly large studies from 1967 and 1977, these BBT experts had this to say all those years ago (and never mind their “prediction” in the cited title whereas the BBT is well known to be no predictor):

QUOTE:  Cycle regularity is often assumed by both women and their physicians. The suggestion, that the BBT graph of the previous cycle can be used to identify the day of ovulation in the current cycle, requires nearly absolute cycle regularity. [However, note this:] The data collected by 1,085 women, who provided at least 6 or more charts each, were studied for cycle length variability. … The cycle length range was more than five days for 56% of the women who submitted 6 graphs, and for 75% of those with 12 graphs. … Absolute regularity was not demonstrated in as few as six cycles. Even when the cycle length that deviated the most was eliminated, less than 1% (8 of 1,085 women) had no variation in cycle length. When the number of cycles was extended to 12, no woman had variability of less than two days in cycle length. END OF QUOTE.

In real life, you realize, no cycle can be eliminated from the experience, and every day matters. Two days are very likely to make the difference between conception and the lack of it. And/or cause an unwanted pregnancy, for that matter.

Middendorf  – On the ball

The above findings are therefore the basis on which we can say quite categorically that nobody is as regular as a metronome (and nobody conceives in an anovulatory cycle), that there is no such thing as absolute regularity, whether 28 days or otherwise.

If you are in the sub-fertile category of people finding it difficult to become pregnant, you are likely to have cycle variability of more than 5 days over those months of your fruitless efforts that define your category. More likely than being one of the 0.74% of the population with no variation in cycle length, which under ideal conditions may also mean no variation in the time of ovulation. Persistent monitoring is well advised.

Why people cannot achieve pregnancy

In many cases – if not most – it is NOT because of clinical infertility.

Basic cause of “apparent” infertility

This article is about the basic cause of most disappointed efforts at achieving pregnancy. The basic cause of the disappointment is that intercourse is had at a wrong time. That is, not during the kairos time of your menstrual cycle, the right time, during which – and only during which – fertilization can occur and result in conception (that may lead to successful pregnancy).

Note that we are not talking here about the relatively few cases of real clinical infertility that are caused by certain organic problems such as, say, blocked fallopian tubes or similar.

We are referring here to what is termed by experts (medically classified) as reduced fertility or sub-fertility. This refers to the predicament of people who cannot achieve pregnancy for too long. We would say that even this terminology is misleading but it is well established in OBGYN medicine, so let’s work with it.

Of course, “cannot achieve pregnancy for too long” is medically expressed more quantitatively by postulating the number of months during which the attempts to conceive a baby turn out to be fruitless, disappointing. (Do we need to add that, as a consequence, what is supposed to be a significant physio-pleasure then often becomes a chore, with the stress only exacerbating the painful disappointment and the actual problem?) Yes, stress enhances the problem.

For many years, the number of months during which unprotected intercourse does not result in pregnancy (and is classified as sub-fertility/reduced fertility) was defined as up to 12 months. For 12 months of fruitless attempts to get pregnant you were sub-fertile, suffering reduced fertility. Only after a year, you became a case of clinical infertility.

More recently, as the prevalence of these problems increases, some medical authorities have extended this period of “advised patience” to as long as 2 years. Only after this extended period of advised patience in trying to conceive would the woman and/or couple be put into the clinically infertile category.

The basic cause of most failed efforts to become pregnant is simply wrong timing, wrong time within the menstrual cycle when the unprotected intercourse occurs with the intent to conceive a baby. This wrong time has much to do to with the continued belief, carried over from earlier times, that most menstrual cycles are “regular”. This is one of the myths. The exact opposite is true.

You can see evidence of that in data from 10 women attending a Natural Family Planning clinic. Differences from -5 to +3 days were recorded in this small sample, and these were differences between ovulation days in just two successive menstrual cycles (where cycle lengths ranged from 23 to 35 days). The variability becomes more extensive when more cycles are reviewed.

In fact, there is no such thing as cycle regularity. It is therefore essential to perform persistent monitoring, as the phrase goes nowadays, to determine the right time for a conceptive intercourse.

It was found decades ago that most women experience changes of even more than five days in the length of their consecutive menstrual cycles, and therefore also changes in the day of ovulation from one menstrual cycle to the next.

This fact of life is basic to the predicament of finding it difficult to achieve pregnancy – because you can get pregnant ONLY during the very narrow fertile window of 3 days; that is the day of ovulation plus the 2 days just before ovulation.

To read more about this, go to  https://biozhena.wordpress.com/the-fertile-window-is-3-days-wide-not-6-which-6-day-belief-originated-in-a-flawed-1995-study/. 

Fact:

Less than 1% of women would be found with no variation at all even for short sequences of only a few menstrual cycles, and absolutely no-one would be regular in twelve cycles. [Ref.: John J. McCarthy, Jr. and H.E. Rockette, “Prediction of ovulation with basal body temperature”, Journal of Reproductive Medicine 31 (No.8), Supplement, 742 – 747, 1986; also – and particularly – see refs. therein to the largest studies, i.e., to R.F. Vollman, “The menstrual cycle”, 1977, and A.E. Troelar et al., “Variation of the human menstrual cycle through reproductive life”, 1967.]

The research involved thousands of BBT [Basal Body Temperature] records obtained from correspondingly high number of women. The research was carried out when the hope was that the then new technology of the micro-computerized thermometer would provide the answer to the quest for a definitive tool for reproductive management. Well, it did not.

The BBT is not the answer, it cannot be. It’s not the solution because it is notoriously unreliable, whether micro-computerized or measured with an ordinary thermometer. Simply put, the BBT is affected by too many things, and it has been found to rise anywhere from 3 days before to 3 days after ovulation, despite the expected rise immediately after ovulation.

Comment:

The sympto-thermal method of NFP practice, also known as the Billings method, gets around the notorious lack of reliability of the BBT by having women perform certain anatomical observations “down there” and observations of the appearance of the fluid wiped off “down there”.

Subjective as this enhancement is, in reviewing a sufficient number of cycle records you would see that it is more likely the sympto- observations than the thermal measurements that, when lucky enough, are associated with recorded pregnancy-test positive. Basically, any of this helps the woman to stay focused, and the lack of accuracy is made up for by an as high frequency of intercourse as practical or desirable. Like shooting in the dark with an automatic weapon… (but then, if there is no target in the dark…)

I got off on this tangent, and should come back to the inherent variability of menstrual cycles and ovulation times in another post. To impress on you that this basic fact of life is particularly important when you are finding it difficult to get pregnant – probably because you are past the most fertile years, which are – or, rather, were – the early twenties of your life.

Parturition means birthing (birth) and dystocia a difficult one

And what is a parturition alarm?

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

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

Parturition alarm:

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

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

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

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

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

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

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

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

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

Parturition:

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

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

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

Indubitably, due dates are a little-understood concept:

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

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

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

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

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

Dystocia or birthing difficulty:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Today is a major anniversary related to the bioZhena enterprise. Namely, a round-number (and not small) birthday of the offspring whose begetting had much, if not everything, to do with the inception of the project.

The biologically educated member of the would-be parental team insisted that medical help would have to be the very last resort, as she did not wish to be poked in and subjected to the various medical procedures available in the country of the proud Albion (that, alas, no longer ruled the waves!), where this awakening was going on. The image of what she resented getting into is telling, and it’s not even the whole story.

Awakening on the part of said couple, who till then took steps to minimize or theoretically avoid getting in the family way, owing to circumstances. As in too many instances the world over, the “awakening” was left until somewhat too late. I do not wish to talk about age specifics, but you probably know that particularly female fertility (more accurately put, fecundity or fecundability) decreases starting around or even before the Christ’s age, and so – in retrospect – it was no great surprise to find that achieving pregnancy was not as simple as expected. At the time, actually, this was a great surprise…

At the time, yours truly was not an expert in the field that deals with certain practicalities of the most important aspect of life, by which many of us mean procreation, reproduction, and its management. I am referring to some insight into the practicalities on the female side of things procreative, which insight was not there at the time – but the better half knew the basic fundamental that I now delight in referencing as eukairosic.

In a nutshell, the word refers to the right time, opportune time – exactly what we are about – the strategic or “right time; the opportune point of time at which something should be done.” A window of opportunity is kairos time.

For more about this, the Wikipedia article can be recommended, at http://en.wikipedia.org/wiki/Kairos . Let’s cite: Kairos (καιρός) is an ancient Greek word meaning the “right or opportune moment,” or “God’s time” [sic; thus said – but this should say “gods’ time”]. The ancient Greeks had many gods, and two words for time, chronos and kairos. While the former refers to chronological or sequential time, the latter signifies “a time in between”, a moment of undetermined period of time in which “something” special happens. What the special something is depends on who is using the word. END QUOTE.

If you visit that article, you will probably understand why I would like to look at the possibility of adopting as our company logo QUOTE a monochrome fresco by Mantegna at Palazzo Ducale in Mantua (about 1510 C.E.) that shows a female Kairos (most probably Occasio)… UNQUOTE.

You will also appreciate that, since we are not theologians, and because “eu-“ is the Greek prefix meaning well or good or true or easy, my choice of the adjective that we want to trademark as descriptive of bioZhena’s wares is eukairosic™.

And so here, for the sake of accurate definition, is one other item from The Alphabet of bioZhena – /2007/11/28/the-alphabet-of-biozhena/

Fecundability and fecundity:

Fecundability is the probability of achieving pregnancy within one menstrual cycle – about 20% or maybe 25% in normal couples [sic; the probability depends on many factors, including age – vide infra, or see below].

Fecundity is the ability to achieve a live birth.

Fecundability is strongly influenced by the age of the partners, and it is maximal at about age 24. There is a slight decline at ages 24 – 30, and a rapid decline after age 30.

The words are derived from Latin fecundus, fecund, from the root of fetus, via Old French fecond. Fecund means fruitful in children, or prolific.

As for the eukairosic diagnostic tools, their utility goes beyond reproductive management. Due to folliculogenesis (menstrual cycling), even things such as administration of medications or certain diagnostic examinations must be performed at the right time within the menstrual cycle…

Scire quod sciendum

fecundoscitus!!! 🙂

Thus spoke the exegete and father of Barnaby and Petrushka, Vaclav Kirsner © 2007

 ‘To know what is to be known’.

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

“When pushed too far, subfertility occurs”

Here is an ad hoc selection of a few abstracts from my files on psychoneuroimmunoendocrinology papers addressing ovulation, reproduction (folliculogenesis).

Abstracts of ad hoc selected papers about stress in reproductive physiology:

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

The first few are representative of animal work, and then several abstracts represent the literature on stress in the human female. In between, let’s display our cyclic profile data on a non-baseline menstrual cycle with delayed ovulation. This record illustrates how our Ovulona^TM device can detect the effect of stress on the course of the menstrual cycle. Non-baseline refers to any real-life female with all the stressors of our daily life, no baseline simplifications of conditions such as we need to try and approach what we would call ideality (at least in physical science we would…).

Should these abstracts turn out to be too stressful, then you may perhaps enjoy better another selection I just came across, Introduction to psychoneuroendocrinology volume: is there a neurobiology of love? http://cogweb.ucla.edu/Abstracts/NeuroLove_98.html

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Highlights:

possible pathway in the regulation of ovulation – stria terminalis to the amygdaloid complex in the monkey (Macaca fascicularis) – J Physiol. 1977

Characteristics of a ventral tract from the bed nucleus of the stria terminalis (BST) to the amygdaloid complex

from BST to the amygdala, and, since the neurones of BST contain estradiol, … this tract may be involved in the regulation of ovulation.

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New data on serotoninergic mechanisms in ovulation in the cyclic female rat – C R Seances Soc Biol Fil. 1979

These results provide support to the specificity of action of serotonin in the control of ovulation in the cyclic rat. They also suggest an interaction of serotonin and oestrogens in this control.

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the hypothalamo-pituitary-gonadal axis in the female rhesus monkey. – Ann N Y Acad Sci. 1993
inhibit the GnRH pulse generator

acute decrease in LH and FSH secretion.

This decrease in gonadotropin release may explain the deleterious effects of stress on the menstrual cycle. However, an acute decrease in gonadotropins following activation of the adrenal axis is not observed in the presence of estradiol.

Thus, during the menstrual cycle, a relative protection against the deleterious effects of acute stress may exist. How potent this protective mechanism is against repetitive stress is not known.

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What is stress, and how does it affect reproduction? – Anim Reprod Sci. 2000

stressors such as milk fever or lameness increase the calving to conception interval by 13-14 days, and an extra 0.5 inseminations are required per conception.

a variety of endocrine regulatory points exist whereby stress limits the efficiency of reproduction

stressors interfere with precise timings of reproductive hormone release within the follicular phase

opioids mediate these effects

there is a level of interference by stressors at the ovary

Reproduction is such an important physiological system that animals have to ensure that they can respond to their surroundings; thus, it is advantageous to have several protein mechanisms, i.e. at higher brain, hypothalamus, pituitary and target gland levels.

However, when pushed too far, subfertility occurs.

…stressors interfere with precise timings…

And the stressors may even cause the Ms. to forget her daily measurement, in spite of which the pattern is discernible and interpretable in terms of “go/no go” or “safe/unsafe” as some may put it; we just say FERTILE or NOT and leave it to the user to decide… And yes, the indication of the fertile day number will also be provided.

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The role of stress in female reproduction: animal and human considerations – Int J Fertil. 1990

Tonic, pulsatile gonadotropin secretion is inhibited by stress and by administered morphine, but morphine does not block the estrogen-induced preovulatory surge in primates.

Accordingly, impaired follicular development appears to be the most common cause of reproductive dysfunction attributable to stress in the human female

must take into consideration the many differences between the hormonal responses to stress in the human and laboratory animals.

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Development of the hypothalamic-pituitary-ovarian axis – Ann N Y Acad Sci. 1997

Onset of puberty is associated with a greater increase in LH pulse amplitude than frequency

Only after the steep early pubertal increase in LH, ovarian steroidogenesis is activated, with increases in androgen and estrogen secretion. Under further FSH stimulation, follicular growth and maturation proceed. The first menstrual cycles are mostly anovulatory for 1 to 2 years. Luteal phase insufficiency is common the first five years after menarche.

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Hypothalamo-pituitary-gonadal axis in control of female reproductive cycle – Indian J Physiol Pharmacol. 2001

Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus is pivotal to the regulation of reproductive physiology in vertebrates. The characteristic periodic secretion of gonadotropin releasing hormone (GnRH) from the medial basal hypothalamus (MBH), at the rate of one pulse an hour is essential for the maintenance of the menstrual cycle. These pulses are due to oscillations in the electrical activity of the GnRH pulse generator in the MBH.

The GnRH pulse generator is under the influence of an assortment of interactions of multiple neural, hormonal and environmental inputs to the hypothalamus. Hence, a number of conditions such as stress, drug intake, exercise, sleep affect the activity of this pulse generator.

Any deviation of normal frequency results in disruption of normal cycle. The cycle can become anovulatory in the hypothalamic lesions

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Influence of the ovarian cycle on the central nervous system – Ther Umsch. 2002

In general, estradiol and testosterone exert a stimulatory, progesterone an inhibitory effect on neuronal activities which are mediated by excitatory (e.g. glutamate, aspartate), and inhibitory amino acids (e.g. GABA) and neuropeptides (e.g. beta-endorphin), respectively.

The pulse amplitudes are primarily influenced by estradiol, but neuropeptide Y, neurotensin and noradrenaline contribute to their preovulatory enhancement.

Despite of this, up to 20% of ovulatory cycles do not show any rise in body temperature.

It could be demonstrated that performance on tests of articulatory and fine motor skills are enhanced in the late follicular phase as compared to the menstruation phase, while spatial ability was better during menses. Estrogens may influence mood and well-being in a favorable manner, while in predisposed women progesterone may cause symptoms of premenstrual syndrome.

Somatic complaints (back pain, abdominal pain, breast tenderness) which are highest before and during menstruation, are probably associated with a lowered pain threshold due to a fall in the beta-endorphin levels in the CNS.

FOR A 2012 UPDATE SEE https://biozhena.wordpress.com/2012/05/28/what-is-the-mechanism-of-stress-and-how-does-it-affect-reproduction-an-update/

Stress and fertility

Please click through to the 2019 revision of this post at

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

How stress affects the inherently narrow fertile window

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

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

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

Just remember, this is no Alphabet of Ben Sira!

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

Stress and the menstrual cycle

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

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

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

 

 

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

 

 

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

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

Stress and the Ovulona^TM

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

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

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

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

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

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

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

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

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

 

 

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

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

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

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

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

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

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

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

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

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

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

References as excerpted from our White Paper:

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

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

Terminology reminder:

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

Cervix uteri and seven or eight related things

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

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 around the cervical protrusion is known as the vaginal fornix. The sanitary vaginal tampon is inserted so as to reach into the posterior fornix. Likewise the bioZhena sensor. As simple as that.

The cervix is the gateway to the uterus and has a lot of important and challenging roles. It must allow the passage of either sperm (or penis, in some species) at copulation, prevent the entrance of microorganisms before and particularly during pregnancy, and expel the neonate and placenta at parturition (birth). It is a muscular tube that has a very dynamic role in both the menstrual cycle and in forming a tight seal during pregnancy, but opening to form a broad passageway at birth. The multitude of physiological roles of this gateway has caused it to become an important element or focus of the bioZhena technology.

Cervical mucus:

The fluid secreted by the inner walls of the cervical canal and exuded by the cervix. The amount and the properties of the fluid change depending on the phase of the menstrual cycle, e.g., from practically nonexistent during the so-called dry days early in the cycle to the relatively copious amounts of clear slippery fluid during the fertile days.

Cervical mucus is essential for the ability of the sperm to function properly: sperm survival and sperm transport within the woman’s reproductive system are critically dependent upon the presence of a healthy mucus.

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

Cervical mucus method:

A method of determining a woman’s fertility by observing changes in her cervical mucus. The Billings ovulation method and the Creighton model ovulation method are both cervical mucus methods.

Cervical palpation:

Feeling the cervix with the middle finger of the thus trained woman-user of FAM or NFP to determine cervical position. This is not a widely used procedure, and is not involved in the Billings and Creighton ovulation methods.

Cervical position:

Three facets of the cervix (its height, softness and the size of its opening, the cervical os) assessed for fertility significance by specially trained users of this method of NFP or FAM. Not many of those around…

Colposcope:

A viewing instrument with a bright light and magnifying lens that is used to examine the vagina and cervix stained with special solutions. Colposcopy: Examination of the vaginal and cervical epithelia by means of a colposcope. [Greek kolpos, vagina, womb + -scopy, suffix that signifies viewing; seeing; observation: as in microscopy. From Greek -skopi, from skopein, to see.] Colposcopy is the diagnostic procedure to evaluate patients whose Pap smear screening produced abnormal cytological smear results.

Billings Ovulation Method (BOM):

An NFP method in which the fertile days are identified exclusively by observations of cervical fluid at the vaginal opening. Developed by the Australian Drs. John and Evelyn Billings. An international survey in 1987 indicated that at least 50 million couples were using the method, and the number is said to be increasing from year to year. It has also been estimated that 80% of natural family planning world-wide is now the Billings ovulation method. In 1978 an international conference in Melbourne was attended by delegates from 48 countries. See also the cervical mucus method.

Creighton model ovulation method:

An NFP method of vaginal-cervical mucus self-evaluation according to criteria developed by Thomas Hilgers, M.D. at St. Louis and Creighton Universities. The criteria are called the vaginal discharge recording system (VDRS) and require that women check for the mucus by wiping the outside of their vaginas with bathroom tissue, checking the mucus for color, stretch and consistency. The last day of mucus that is either clear on appearance, stretches an inch or more, and/or causes the sensation of lubrication is called the peak mucus day. The method is similar to the Billings ovulation method.

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bioZhena’s method of monitoring the cervix:

And then we have the bioZhena method, with the Ovulona inserted briefly just like a tampon applicator, and taking a reading of the fertility status (most of the time NOT FERTILE = cannot conceive; only 3 days of fertility in each menstrual cycle):

The DIU is or will be an auxiliary add-on

 

 How the Ovulona will be transformed into a (semi-) permanently worn cervical ring obviating daily insertion is shown in slide 4 of QUICK INTRO 4 SLIDES at

Friendly Technology and Next Generation Design

The natural interest of women in being in charge of their reproductive life leads to the possibility of using the information gathered in the process for additional medical purposes. The Ovulona cyclic profile is the signature of the menstrual-cycle vital sign, which is the result of the illustrated interaction between the female brain and the ovaries – the so-called Hypothalamus-Pituitary-Gonad Feedback Loop (F). (This editing added here in 2016.)

To enlarge the image, click https://biozhena.files.wordpress.com/2009/03/menstrual-cyclic-profile-signature-of-the-hpg-feedback-mechanism.jpg

The H-P-G feedback loop (F) gives rise to the menstrual cyclic profile signatures captured by the bioZhena technology.

Here is why the bioZhena technology had to be invented. One way of saying this is: The available means, methods or products, were not good enough. Another way of putting this is to quote from medical literature, as follows.

A symposium on ovulation prediction in the treatment of infertility covered all the phenomena known to be associated with ovulation [reference 9]. Moghissi, who discussed more than 20 measurable parameters that vary during the menstrual cycle, stated the following [reference 8]: “Mid-cycle mucorrhea, ferning, spinnbarkeit, lowered cell content, and viscosity of cervical mucus are used commonly in ovulation detection and as an index of the estrogenic response of cervical epithelium. However, these changes extend over several days … (These changes) do not necessarily indicate ovulation, and are merely an index of the optimal amount of circulating estrogen…”.

In brief, none of the methods determined ovulation with the required accuracy to be useful either as a conception aid or especially for birth control. Here is how our method (monitoring folliculogenesis) does it by generating the multi-featured cyclic profile that includes the definitive ovulation marker after the predictive signals, and here is how this compares with the older techniques. See how inaccurate is the ovulation assessment by the older means available to the users of NFP or FAM (spread over 3 days):

Marquette comparison with LH kit and Peak mucus – right click on the link to open a larger PDF version of the image.

In this example, our device detected delayed ovulation while the LH ovulation kit indicated positive for ovulation on two days (not just one) and the mucus assessment (Creighton method) indicated positive one day later. The LH was positive the day before as well as on the day of the ovulation marker (day 17), while the Peak mucus day indicated ovulation one day after the ovulation marker day.

The spread of 3 days is not acceptable, but it is actually quite typical of the uncertainty associated with these older techniques. You know what that means, don’t you, because you know that every day matters. Their lack of accuracy and precision renders the older techniques not good enough – which is where we started.

Cited references:

[8] Kamran S. Moghissi, “Cervical mucus changes and ovulation prediction and detection”, Journal of Reproductive Medicine 31 (Number 8), Supplement, 748 – 753, 1986.

[9] Stephen L. Corson, guest editor, “Ovulation Prediction in the Treatment of Infertility. A Symposium”, Journal of Reproductive Medicine 32 (Number 8), Supplement, 739, 1986.

Review and listen to 3 narrated slides summarizing the bioZhena technology. Contemplate the importance of the cervix uteri.