Posts Tagged ‘epigenetic’

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

April 18, 2012

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

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

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

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

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.

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

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!

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

April 15, 2012

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.

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 ).

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.

Anderle - Bestia triumphans II

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

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).


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