The perils of IVF, of ARTs, of giving birth at old age – part 2

Tidbits from a debate at LinkedIn group The Life Science Executive Exchange, about DANGERS OF IN VITRO FERTILIZATION. Since many of you will not be members of said group, I make bits from the discussion available in this way, for the interested reader. And I offer Google Ngram evidence for why I was justified to exclaim, “Damn the bloody Pill”.

Politely put as: Perish the Pill! The drug (aka Oral Contraceptive Pill, OCP, and its various modifications) created the problem that too many solve with IVF and other ARTs (= In Vitro Fertilization and other Artificial Reproductive Technologies). People debate hotly burdening future generations with debt – but we don’t seem to care about burdening them with health consequences of the daft but so prevalent postponement of motherhood until it’s too late.

In January 2017 it is appropriate to add one other angle to the concern about as yet unproven but possible consequences of artificial reproduction. When “sperm are injected directly into an unfertilized egg, [the ART procedures] are bypassing nature’s way of eliminating defective sperm…” Dr. Gagneux told the American Association for the Advancement of Science in Washington. “The concern is that by by-passing female choice (or filter) at the level of sperm selection, we might produce embryos that contain risk factors that we would otherwise not have.”

Thus reported in popular media (http://www.independent.co.uk/news/science/ivf-use-could-be-storing-up-health-problems-biologist-warns-a6875876.html?platform=hootsuite), while in one of their scientific publications Eillen Tecle and Pascal Gagneux write in specialist language about “female choice, whereby females actively select more advantageous sperm… based on the glycocalyx variability as a metric of sperm quality… Evidence exists for selective processes by cervical mucus…  retention of sperm with compromised chromatin in the cervical mucus… remains to be formally investigated” (http://onlinelibrary.wiley.com/doi/10.1002/mrd.22500/full).

And now back to the LinkedIn debate about the epigenetic concern regarding IVF and other ARTs.

Vanya Loroch:

“…our behavior impacts directly the health of our descendants. Not much to do with Darwin, by the way (for those who do not know what epigenetics is all about). …

The issues we face today in our world are often so complex that lay people CANNOT blindly trust experts (IVF protocols or FUKUSHIMA are two very different examples… but maybe not that different, come to think about it). If we want a better world for our children, it may be absolutely essential to build a trans-disciplinary knowledge and society where lay people are educated ENOUGH to throw the right questions at the experts and make informed decisions together.

Agnes Boulloche – L’Education

WE NEED REAL UNIVERSAL LIFE SCIENCE EDUCATION FOR ALL (what 99% of the people are getting is a sad joke). If we fail to achieve this, utter irrationality (e.g. the GMO debate in Europe) or worse (unnecessary suffering) are bound to happen, again and again.”

Patrick Courtney:

“Why is the GMO debate in Europe utter irrationality?”

Vanya Loroch:

“…I have a very short answer. When European citizens are asked whether a tomato contains DNA, the majority (65%, I believe) answer NO – ref. below. These frightening numbers are going down but very slowly… If the GMO debate is a citizen debate, as IT SHOULD BE, 65% of the citizens cannot be rational about it because they lack even the most basic understanding of the workings of a living cell. …”

References:
1. Eurobarometer survey. See for example: http://genome.wellcome.ac.uk/doc_WTD021020.html
2. A wealth deferred: the politics and science of Golden Rice. Erin Baggott . Harvard International Review/Fall, 2006

Paul Stinson:

“What rubbish. Are you telling me that Swiss scientists in 2011 studying IVF results (from what years?) are being taken seriously? I am familiar with a couple that had IVF treatment in Johannesburg in 1991 and their twin sons are today Varsity Squash team members in an Ivy League school. Vascular dysfunction? I doubt it.”

Vanya Loroch:

“If it is rubbish, it is peer-reviewed rubbish and it took several years to peer-review it.

And the outcome is that the publisher (Circulation, Journal of the American Heart Association – Impact factor almost as good as the impact of Science[top US journal]) took the study and the results seriously enough to publish it. 65 healthy kids born thanks to IVF + lab model on mice all show the same issues: epigenetic alterations + abnormal vascular structure and function, similar to what some type I diabetics have (or worse). Maybe rubbish to you, but data are always data. By the way, vascular dysfunction doesn’t mean one can’t excel in sports. It’s a risk factor, not a disease!

If interested, read the paper or at least the abstract, eg. Conclusions: Healthy children conceived by ART display generalized vascular dysfunction. This problem does not appear to be related to parental factors, but to the ART procedure itself. http://circ.ahajournals.org/content/early/2012/03/13/CIRCULATIONAHA.111.071183.abstract?goback=.gde_72923_member_103918763

And remember that hydrogenated fats were promoted by the medical experts in the seventies and eighties as a healthy alternative to animal fats. To err is human….”

[My added comment: The royal physicians of the British King George V recommended cigarette smoking as a healthy and useful activity – in second decade of 1900s. How many decades before the change of heart?]

Romer A. Gonzalez-Villalobos:

“I personally think that it is too early to jump into any conclusions. Science is self correcting; let’s wait and see if other studies support these findings.”

Vanya Loroch:

“I agree that we certainly don’t have the full picture, but the mouse IVF model the team developed replicates faithfully the epidemiological findings in the children.

The vascular damage in IVF can be fully prevented by including melatonin during the in vitro step.

This vascular damage is passed on to F1 mice. The methylation of promoter regions in key genes needed for vasculogenesis and arteriogenesis was shown to be altered, and butyrate fed to the IVF mice prevented the transmission of the dysfunctional artery phenotype to the offspring.

Agnes Boulloche – Dessins

In other words, very different experimental techniques to characterize the phenomenon all say the same thing: epigenetic alterations at the time when gametes/early embryo are suspended in synthetic media, in vitro.

Science is self-correcting, but that is not necessarily true for human health. For me (and I have no potential conflict of interest with anyone or anything), the results of the human and mouse studies are more than enough to declare an immediate moratorium on IVF and ICSI until this issue of epigenetic alterations is solved. Of course this is unlikely to happen. I only hope that the health of all the IVF kids will not be adversely affected by what has been seen.”

My comment: He has an omission in the above statement in that the concern – about the epigenetic consequences for health of subsequent generations of the offspring – is not expressed. It’s not merely or even mainly about the IVF kids. Do see the BBC movie to grasp this – referenced in part 1: The Ghost in your Genes (at http://www.youtube.com/watch?v=toRIkRa1fYU ). 5 video clips of some 9 minutes or so each. The epigenetic consequences last for generations.

Meanwhile, here is evidence for how it all came about, why the problem arose in the first place. Before the introduction of the contraceptive Pill, IVF did not exist. Are you familiar with the word iatrogenic?

Ngram 9: in vitro fertilization, IVF, the Pill, OCP
http://books.google.com/ngrams/graph?content=in+vitro+fertilization%2CIVF%2Cthe+Pill%2C+OCP&year_start=1960&year_end=2008&corpus=0&smoothing=5
When you enter phrases into the Google Books Ngram Viewer, it displays a graph showing how may times those phrases have occurred in a corpus of books (here English-language books) over the selected years (here 1960 to 2008). The N numbers (or the number of phrase occurrences relative to all books) for the four topics are on the same scale indicated on the vertical axis. The graph shows that the number of books about the Pill (green) goes up after the Pill launch in the early 1960s and, after leveling off in late 1970s, it starts declining. Meanwhile, the number of books on OCP (Oral Contraceptive Pill, yellow curve) grows as the OCP term becomes more and more used in medico-scientific literature, leveling off in the 1990s and then declining (similar to the green curve of the Pill). The number of books on IVF (red) has grown well above the book numbers on the other terms or phrases, including “in vitro fertilization” (blue), which was understandably at first somewhat more frequent than “IVF” but from early 1980s “IVF” has been the preferred term and thus the number of books about IVF by far exceeds those on the other three terms/topics.
Whether ”IVF” or “in vitro fertilization”, it is clear from this Ngram that books on the subject did not exist before chemical contraception was introduced in the 1960s.
This is possibly seen more easily below in Ngram 10, which only shows the data for books on IVF (blue) and for books about the Pill (red), same as in Ngram 9. Books about the Pill appear and grow in numbers in the 1960s while IVF books only appear and their volume grows fast some 10 years later. Another decade later, the IVF book numbers far exceed those about the Pill. Also significantly, the IVF book volume does not exhibit a declining trend.

Ngram 10: IVF and the Pill

The Pill was never a good medication, if only because pregnancy is not a disease. It’s always been a drug of convenience, and we don’t even have to go into the eugenic intentions of Mrs. Sanger, without whom her “magic pill” of a drug would not have come about. A drug of convenience is akin to recreational drugs.

Instead of messing with women’s reproductive biochemistry and physiology, healthcare and public health should have focused, and should focus now, on behavioral reproductive management. (As in: You want to feel good? Go for a run, raise your endorphins and burn some calories – but don’t do drugs. Same difference with the Pill. Don’t bust up your cervical physiology with the Pill, making for your infertility. You won’t need to worry about Clomid, IVF etc. if you watch your age, too.) But now back to the discussion of Dangers of In Vitro Fertilization.

Heber Hammon:

“This was a very interesting and sobering article. I have been surprised at the reaction of the medical profession regarding it. I think the epigenetic system needs to be studied closely. I suspect the recent autism epidemic is caused to a high degree by malfunction of the epigenetic processes. We have learned that nutrition plays an important role. I follow IVF from the perspective of animal science. I have not seen any health issues resulting from embryo transplanting either from embryo flushing or implanting after IVF. The discussion here is informative on many levels.”

Mike Kelly:

“As a follower of IVF science for many years I do not understand how you can make a statement that melatonin will alleviate the symptoms discovered. I sense some lack of scientific verity.”

Vanya Loroch:

“Mike, this is not a “statement”, it is an experimental finding made by the team in their mouse IVF model. They were the first ones to be surprised.

The finding is the following: the inclusion of melatonin in the culture media (the in vitro step) normalized DNA methylation of the embryos; it prevented in particular the dysmethylation of the promoters of genes needed for arteriogenesis, and it also prevented mesenteric endothelial dysfunction and arterial hypertension.

This finding is in mouse IVF so far. Extrapolating to humans is the usual issue.

Melatonin *is known* to play an (important?) role in regulation of ovarian function, it plays a favorable role in oocyte maturation and it improves fertilization rates. This is well documented. A Pubmed search (“melatonin in vitro fertilization”) or even Google will point you to the relevant literature.

My comment for you here:

For confirmation see search http://isearch.avg.com/search?cid={6AE0129D-5975-485B-BB40-4646A7CCE716}&mid=a0d3a7b6b0f32c95be0fb17758cc560e-b42e229379060869383d6811e0f2b34960104ea5&ds=AVG&lang=us&v=10.2.0.3&pr=fr&d=2012-02-14%2019:21:29&sap=dsp&q=melatonin+in+vitro+fertilization

Citing from the first search result (J Pineal Res. 2000 Jan;28(1):48-51): Melatonin increased the fertilization rate significantly… Furthermore, a significant increase in the rate of embryos reaching the four-cell stage, the eight-cell stage, and blastulation, was observed. [Quantitative data are omitted by me here.]

From a related citation (Endocr Res. 2010 Jan;35(1):17-23): Melatonin is capable of improving the developmental capacity of ovine, porcine and bovine embryos in vitro. … The in vitro development of mouse two-cell embryos significantly benefited from treatment with melatonin in a concentration-dependent manner…

Derek Donohue:

”Plenty of facts and data exist to support this finding.

I’d encourage everyone to look at this from a standpoint of a discipline with a longer history and larger dataset – horse breeding. Fact is people pay far more to breed a champion racehorse than they do to breed a human. Yet this high dollar industry, far pre-dating the human fertility industry, is fraught with failure and error. Only a handful of legacy champions have ever been bred in countless attempts.

Furthermore, issues surrounding sperm and egg viability have yet to be overcome by even the most modern science.

Emotions and energy in the chaos aesthetic by Viktor Sheleg
http://www.sheleg-gallery.com/sheleg2/index1.htm
or http://ego-alterego.com/wp-content/uploads/2011/07/40881_111467795583097_100001596316201_102626_6451116_n.jpg

We are only now coming to full understanding of the scope of genomic function occurring within sperm, including their genetic expression to environmental stressors. The experts in that field agree this is likely at the root of historically disappointing fertilization rates from frozen equine sperm. But we’ve only just begun to even look at it. [Interjecting my comment: With our technology, they could avoid semen freezing and bring the stallion to the mare at the right time in her estrous cycle, even trying for the desired fetal sex.]

With this in mind, I am fully open to believing that we don’t have the full understanding of the entire topic of human fertility that we like to believe we do.

Which of you can tell me how frozen human sperm samples are thawed? In the equine world it is dunked in a 50C water bath for up to 5 minutes. This, despite the fact that millions of years of evolution have put the testes outside of the body because even temps of 37C are stressful to sperm. This common mammalian attribute has remained constant ahead of many other evolutionary changes in countless species. Yet, despite this glaring evidence, this egregiously unscientific practice is the widely accepted standard in a discipline with a six figure buy in.

Can any of you really vouch for the quality of donated human sperm when half million dollar equine sperm is handled so haphazardly? Does anyone really claim to already know that donor sperm is not similarly genetically compromised by environmental stressors even when we are just now realizing that the possibility exists? Resting in self assurance of that which is known, while ignoring all that is not known, that is not the way to advance scientific understanding.

We’ve barely just started looking at the genetic impacts of IVF practices inside of eggs and sperm despite long understanding that we are asking them to function the same under totally foreign conditions.

Keep in mind, the question is not can you put an egg and sperm together in a dish and get a viable offspring. The question is can you produce the same quality offspring at the same rate as the real thing. To be convinced that we can, when we’ve only begun exploring the most fundamental factors, that is not a rational or fact based position. Especially when we cannot even follow nature’s multimillion year example of how to handle sperm.

I’m willing to accept these results, encourage further study, and endeavor to understand the how and why in the interest of improving outcomes. END QUOTE

MARINA RICHTEROVÁ – Golgota, Hommage a P. Bruegel, 1998 and The Juliet, 2000
From http://www.gallery.cz/gallery/en/Vystava/1999_01/Ramec_V.html

This concludes the selection from the referenced LinkedIn discussion at The Life Science Executive Exchange, titled DANGERS OF IN VITRO FERTILIZATION.

I close with the words with which I opened part 1 of this topic about epigenetic evidence that should make you think twice before you contemplate In Vitro Fertilization and mainly before you think that having a baby can wait. The bottom line? Be a young mother!

The perils of IVF, of ARTs, of giving birth at old maternal age

About epigenetic evidence that should make you think twice+ before you contemplate In Vitro Fertilization and think that having a baby can wait. The bottom line? Be a young mother!

I lighten up this very serious topic by announcing that an unusually early hummingbird scout has arrived here in the Front Range of northern Colorado Rocky Mountains yesterday morning! And the tiny hummie is here today, too! In fact, two of them, the green-back variety!

But on Friday, it was a sad coincidence when, after I “shared” on Facebook the picture of a certain baby in need of a heart transplant, later in the day I happened on a related news. And I tweeted the allowed 140 characters thus: #Infertile #TryingToConceive Warning & clear explanation http://to.ly/cTP3 #IVF protocols seriously flawed – induce epigenetic damage.     

Sarah Christie, Facebook – Share this! If she gets 1,000 shares she gets her heart transplant for free.
http://www.facebook.com/photo.php?fbid=388139167870098&set=a.318579008159448.96351.100000220538357&type=1&ref=nf

In the above-linked summary of a Swiss study about children born by Artificial Reproductive Technology [ART] procedures, “ART children were found to have … a significantly higher risk of cardiovascular disease at a young age.”

Note: “Vascular dysfunction is related to ART per se rather than to parent-related factors. Oxidative stress may represent an underlying mechanism”. Cited from: “Systemic Vascular Dysfunction in Children Conceived by Assisted Reproductive Technologies” http://spo.escardio.org/eslides/view.aspx?eevtid=33&id=976 by Rimoldi SF, Sartori C, demarche SF, Stuber T, Garcin S, Duplain H, Germond M, Scherrer U, Allemann Y.

See also: “Systemic and Pulmonary Vascular Dysfunction in Children Conceived by Assisted Reproductive Technologies”, Circulation 2012; CIRCULATIONAHA.111.071183 published online before print March 20 2012 by Urs Scherrer et al. – http://circ.ahajournals.org/content/early/2012/03/13/CIRCULATIONAHA.111.071183.abstract : “…children conceived by ART display generalized vascular dysfunction. This problem does not appear to be related to parental factors, but to the ART procedure itself.”

This Circulation 2012 online article also summarizes the background, as follows: “Assisted reproductive technology (ART) involves the manipulation of early embryos at a time when they may be particularly vulnerable to external disturbances. Environmental influences during the embryonic and fetal development influence the individual’s susceptibility to cardiovascular disease raising concerns regarding the potential consequences of ART on the long-term health of the offspring.”

And it is apparently even worse.

According to a position statement by European Society for Human Reproduction and Embryology (ESHRE), http://www.eshre.eu/binarydata.aspx?type=doc&sessionId=2zn3zp4523tjjg45tnjhaev1/Birth_defects_position_papers.pdf QUOTE:

“Children from couples who get pregnant after assisted reproduction techniques (ART), like IVF/ICSI, have a 40-50% increased risk for a birth defect.

A similar increased risk has been reported for subfertile couples who get pregnant spontaneously after a prolonged time period. This increased risk seems thus mainly be due to parental characteristics from the infertility status and not to the treatment given. A recent case-control study from USA has confirmed these findings.” END QUOTE.

Vanya Loroch, PhD is the author of the summary referenced in the tweet above, in the opening sentence about epigenetic damage due to IVF. Readers will benefit from watching his last listed reference, The Ghost in your Genes (at http://www.youtube.com/watch?v=toRIkRa1fYU ).  As Dr. Loroch writes, it is a fascinating BBC show on the topic of human epigenetics. I would say, the movie should be a mandatory infotainment (viewing) material for all teenagers and young adults.

Vanya also provides a micro-primer on epigenetic alterations, which I recommend. It is at the mentioned http://www.loroch.ch/blog/public/danger-ivf-summary-findings (= the above-cited tweet’s short URL: http://to.ly/cTP3 ).

Intuition – Gil Bruvel
http://www.liveinternet.ru/tags/surrealism/page7.html

As one of the scientists there contemplates, in the last part of the film, this new epigenetic insight will make you think about being a guardian of your genome – for the sake of the future offspring of your offspring, not just for your own health’s sake. The environmental impact on the health of future generations (yes, in plural) is demonstrated there in a clear way, with very little scientific jargon and much BBC quality.

Incidentally, how the in vitro in IVF causes the epigenetic switch (damage) is shown there, too. Highly recommended. They don’t even mention uniparental disomy (UPD) as I do, below! After you’ve watched the movie, you’ll put it in context, for sure. Especially you, the female “uniparent”!

I’ve written previously about delayed parenting or, rather, mothering: 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 (ref.: https://biozhena.wordpress.com/2010/05/25/difficult-conception-tied-to-pregnancy-complications-addressed/ ). “High-risk pregnancies are more likely in women who have difficulty getting pregnant, with or without help from hi-tech fertility treatments.” That’s citing a specialist medical authority.

In my Facebook Note, titled “Bestia triumphans II and the International Women’s Day. A heresy?”, I put it rather mildly:

Ironically, the consequences of the sexual revolution [i.e., the introduction of the Pill in the 1960s] can only lead to the deterioration of the health of the human lot. The offspring of all those older mothers (and fathers) can hardly be expected to carry an improving human gene pool.

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

One of the references behind this statement is: Am J Med Genet. 2000 Dec 18; 95(5):454-60, “The contribution of uniparental disomy to congenital development defects in children born to mothers at advanced childbearing age”: This study confirms the hypothesis that uniparental disomy is a not negligible cause of congenital developmental anomalies in children of older mothers. QUOTE UNQUOTE.

Brief clarifications:

Uniparental disomy (UPD) occurs when a newborn receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent (http://en.wikipedia.org/wiki/Uniparental_disomy ).

Maternal Age: Women are born with all the eggs they will ever have. Therefore, when a woman is 30 years old, so are her eggs. … Errors can crop up in the eggs’ genetic material as they [the eggs, ova] age over time. Therefore, older women are more at risk of giving birth to babies with chromosome abnormalities than younger women. Since men produce new sperm throughout their life, paternal age does not increase the risk of chromosome abnormalities (http://www.genome.gov/11508982 ).

Jiří Anderle
Láska za lásku / Love for Love
lept, pastel / etching, pastel, 1996
opus 535, 13 x 17 cm 7.400,- Kč / CZK
http://www.galerieart.cz/anderle_vystava_2011- 1990-1999.htm

Heresy or not, I exclaim in the vernacular used during my early adult years in Britain: Damn the bloody Pill!

And, from my even younger years in the “Old Country”, I recall the sadly funny outcry, Lide jsou blbe!, which translates – albeit without rhyming – as: People are imbecile! (daft, idiotic, …). These days, I would not use such language, of course. Not even to those whose job it is to look after healthcare.

The reasons for why I swear at the Pill and other Endocrine Disruptive Chemicals have been discussed previously in this bioZhena’s Weblog. See, for example, 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) . You need the gist of the bad Pill effect, here and now? This is the bottom line: “After 3 and up to 15 months of contraceptive pill use, there is a greater loss of the S crypt cells than can be replaced. … S crypts are very sensitive to normal and cyclical stimulation by natural estrogens, and the Pill causes atrophy of these crypts. Fertility is impaired…” and people wait with having kids until it’s too late.

While the Pill- and other drug-making and the various artificial reproductive technologies are a big business (much like war-making), I continue to try and clarify that natural reproductive women’s health management is a must. Gentlemen, we do have the technology for that. Ladies, quite a few of them, already know. Or at least a few of them do – globally. Look at the Blog Stats and the Flag Counter, on the right margin (of home page or of about page).

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

Regardless of what contraceptive proponents tell you

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

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

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

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

Here we have a comparison of statistics of three phrases:

pregnancy complications (blue),

difficult birth (red), and

trying to conceive (green).

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

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

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

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

Peter Paul Rubens, Allegory of War, c. 1628

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

In a previous bioZhena’s Weblog post, you can see evidence that oral contraceptive use directly and negatively impacts the cervical crypts, which brings about the difficulty to conceive. The bottom line is this: “After 3 and up to 15 months of contraceptive pill use, there is a greater loss of the S crypt cells than can be replaced.” The S crypts are needed for conception.

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

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

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

Lion_Hunt_Mosaic in Pella

zb.jpg

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

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

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

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

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

Edward_Burne-Jones_Maria_Zambaco_1870

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

BONE HEALTH:

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

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

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

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

HEART HEALTH:

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

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

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

Max Beckmann, The rape of Europa (1933)

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

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

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

Atrophy acceleration effect of 10 years on the Pill:

S crypts are down to mere 10% at 40 years of age. Here is why it’s not nice to fool Mother Nature, why it’s not good to mess with her design. Fertility is drastically reduced. The Pill is an archetypal anthropogenic Endocrine-Active Compound [man-made EAC]. It was brought up previously in this blog how there are very many of these EACs, all insulting the female body and health; some – like chemical contraceptives – by design. Having invoked the design, I am reminded that the original designers of the Pill had no idea about contraception – they were pushing the frontiers of steroid chemistry… (not this particular application of one kind of steroids).

Atrophy slow-down or beneficial effect of pregnancies:

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

And again, the bottom line is this: “After 3 and up to 15 months of contraceptive pill use, there is a greater loss of the S crypt cells than can be replaced. …S crypts are very sensitive to normal and cyclical stimulation by natural estrogens, and the Pill causes atrophy of these crypts. Fertility is impaired since the movement of sperm cells up the canal is reduced.” END QUOTE.

In case you’d like to view the Carlo Adelio Galimberti picture accompanying the concluding words, please re-visit the cited earlier post. The concluding words were and still would be: While the story of Laodamia and Protesilao is touching, I merely want to ask that girls, ladies and their physicians do not moon the messenger.

P. S.

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

STOP PRESS

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

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

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.

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

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.

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

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/

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

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

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

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

In the Alphabet of bioZhena (which is no Alphabet of Ben Sira, though we model on it somewhat), https://biozhena.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…

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

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

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

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

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

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

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

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

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

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

Mondrian_Evolution

There are three fundamental principles at work.

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

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

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

Now, then.

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

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

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

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

50% / 25 years = 2% per year.

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

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

Representative profile of cervical crypts

(percentage of cervix occupied by active crypts)

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

This is a baseline profile.

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

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

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

Schematics of cervical mucus secretions

Key to colors:

Blue         = S mucus

Yellow     = L mucus

Red          = G mucus

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

Pink         = Z granules

Professor Odeblad’s explanatory notes:

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

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

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

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

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

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

2. Slow-down of atrophy aging by pregnancy:

Profile of cervical crypts of a 4x pregnant woman

Representative profile of cervical crypts

(percentage of cervix occupied by active crypts)

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

Pregnancy – S crypt diminution rate from Odeblad’s graph

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

30% / 25 years = 1.2% per year.

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

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

Representative profile of cervical crypts

(percentage of cervix occupied by active crypts)

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

Pill – S crypt diminution rate from Odeblad’s graph

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

60% / 25 years = 2.4% per year.

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

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

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

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

This is double the baseline rate of cervical atrophy.

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

Three concluding remarks by Prof. Odeblad:

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

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

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

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

Comment on implications for treatments of certain symptoms

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

STOP PRESS

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