I received this comunication from the American Society for Reproductive Medicine

MEETING ANNOUNCEMENT  —The Adequacy of Assisted Reproductive Technology Oversight

Monday, December 14, 2009

In a docinthemachine exclusive first I am excited to share with you a new endometriosis scoring staging system that is the first ever to predict a patients chance of getting pregnant without IVF.

The EFI or endometriosis fertility index was just presented by Dr David Adamson, a fertility specialist at the 38th annual Global Congress on Gynecologic Minimally Invasive Surgery– the annual meeting of the AAGL in Florida.  As a fertility specialist and surgeon myself it was starred on my agenda not to miss as a highlight of the entire congress.  Here’s all the details of his presentation and the scoring system.

Here’s my podcast interview with the lead author Dr Adamson just after he gave his talk at the 38th AAGL Global congress in Orlando

 

 Dr David Adamson Endometriosis Fertility Index Podcast with Docinthemachine.com [17:12m]: Play Now | Play in Popup | Download

BREAKING NEWS

In a docinthemachine exclusive first I am excited to share with you a new endometriosis scoring staging system that is the first ever to predict a patients chance of getting pregnant without IVF.

The EFI or endometriosis fertility index was just presented by Dr David Adamson, a fertility specialist at the 38th annual Global Congress on Gynecologic Minimally Invasive Surgery– the annual meeting of the AAGL in Florida.  As a fertility specialist and surgeon myself it was starred on my agenda not to miss as a highlight of the entire congress.

Why Its Important: Every staging system up to now were made by committee trying to guess what would be an important factor– but none have ever directly predicted a patient’s chance of pregnancy– they main thing they need to know. This study was mathematically devised and DOES the allow a patient to know her direct chance of having a baby after surgery!!!

In this post I’ll review his findings and share the scoring forms and data.  My next post will be an exclusive  podcast interview I just did with the author of the importance of this major breakthrough. The paper is being released today as “in press” in the journal “Fertility and Sterility” of the ASRM (here’s the link) — but you’ll need a membership to access it.  I’ll post the final pubmed links when it comes out in print.

Background- What’s endometriosis? Endometriosis is a devastating disease where the cells that normally line the uterus and grow each month in preparation for a baby grow abnormally outside the uterus on it surface or on the tubes ovaries or other internal organs.  These cells bleed cyclically each month internally an cause inflammation resulting in pain, infertility , and damage to other organs.  It affects 5% of the population who have no symptoms but up to 25-33% of women with infertility or pelvic pain.  A valuable resource is the endometriosis association who I work with frequently.

Lead Author–is my friend collegue and mentor from a distance Dr David Adamson.  He’s and ob gyn fertilit specialist who is on the faculty of both UCSF and Stanford and who specializes in both fertility and reproductive surgery — he’s served as president of both our fertility society ASRM and our surgical society AAGL.

The Results– Predicting Fertility:  Chances of pregnancy by Stage

Here’s the latest installment of the docinthemachine podcast.  In this installment I review new FDA device approvals and then present an interview about HD technology for entertainment and medicine with Bob Ott (vice president of broadcast and professional audio/video products for Sony Electronics) recorded at the National Association of Broadcasters (NAB).

 

 docinthemachine november 2009 [19:35m]: Play Now | Play in Popup | Download

Since its inception docinthemachine has focused on sharing a vision of how technology can transform medicine.  I am excited to expand my postings and analysis of all things related to fertility diagnosis and treatment.  As most of you are aware I am a board certified reproductive endocrinologist — which is an Ob Gyn with addition training and expertise in infertility.  i am currently the Medical and Scientific Director at Gold Coast IVF in Syosset, NY.  When I first started DITM I planned on setting up a second blog solely focused on infertility.  With the efforts required to post here and continue my clinical practice and research that idea sat on my “to do” list.  I have frequently posted on fertility topics here nonetheless.

After some sould-searching and planning and discussions with my good friends and fellow med bloggers Nick Genes and Gene from Medgadget  I have decided to jut add all that content here to docinthemachine.  While it does not have a sexy-fertility name its a part of me that has a fantastic group of readers…  Everyone I spoke with unanimously agreed to just expand the content here!

So stay tuned for more fertility related posts in the days to come. 

Many are reporting today that a woman on Long Island gave birth to rare identical triplets.  She actually gave birth at one of my main hospitals and I know her Ob.  The story goes on to say she had IVF but only one embryo was replaced.  I was not her treating fertility doctor.  However, this event raises and important fact.  More and more fertility specialists are turning to a technique called blastocyst transfer.  Here we let the embryo grow and additional 2 days in the dish in the lab.  Instead of transferring it on day 3 we let it grow until day 5 (occasionally 6).  By letting them grow more each embryo that survives has a greater chance of implanting.  Therefore we can transfer less of them, reduce the risk of multiples (usually!) and keep pregnancy rates high.  The risk is if the embryos are not very strong then none may survive.

Why this may be the cause:   It has been know for some time that when we use this technique the rate of identical twins (ie a single embryo splits into two) is significantly great – up to 5% or so.  Therefore it makes perfect sense that the rate of identical triplets could rise as well.  Since a single embryo was transferred they say- this is usually done in blastocyst cases.

Countless sources are reporting on the “three parent embryo” created as a potential treatment for infertility.  What has not been reported is that ther is an almost 10 year history of unreagulated human experimentation in this arena which led to a rare federal ban on specific fertility treatments.  Is this hope, hype or dangerous human experimentation?  Read on to see!

Background- what are mitochondria?  Mitochondria are tiny primite organisms that millions of yers ago became incorporated into human cells.  They exisit in every cell but have their own unique genetic material. They function as the engines of the cell providing energy for metabolism.  I wrote an review of how they got there and what they do that you can read here.  In short mitochondria have their own DNA (similar to that of bacteria) and reproduce independently of the cell in which it is found.  We now have a symbiotic relationship with them.  

First - the details receontly reported by the BBC.  Diseases of the function of mitochondria exist.  “About one in every 6,500 people is affected by such conditions, which include fatal liver failure, stroke-like episodes, blindness, muscular dystrophy, diabetes and deafness.”  Details of their human experiment:  Scientists in the UK experimented on 10 embryos left over after IVF fertility treatments.  They microsurgically removed the nucleus, containing the embryo’s DNA  and implanted it into a donor egg whose DNA had also been removed. The donor egg while missing its DNA still contained its mitochondrial DNA.  They watched these embryos grow in the petri dish for 6 days. 

Therefore the resulting embryo will have the DNA of the donated nucleus but the mitochondrial DNA of the host cell- curing and potentially eradicating - the mitochondrial illness. 

This is not the first time this has been done.  The fertility treatment history of human experimentation on this:  While I was teaching at Yale Medical one of my partners and mentors in the fertility department (Dr David Keefe) was actively pursuing research on mitochondrial dysfunction as a cause of human infertility.  At that time a few fertility doctors in the US theorized that one cause of human reproductive aging was accumulated damage to the mitochondria in the egg. They thought the genes of the egg could be healthy but the rest of the egg that supports its become faulty.  They experimented with a technique called cytoplasmic transfer.  Using a microscopic needle tiny drops of fluid were sucked out of a donor’s egg and injected into that of an older infertile woman hoping to breath new energy and life into it.   Unfortunately most research groups found it did not seem to offer any benefit.

Reasons why it likely did not work:

1. using minute drops of fluid from a donor egg into a recipient is just not enough to correct the metabolic problem or defect
2. my collegues at Yale found that the mitochondria in the egg is often tightly joined to the nucleus so the cytoplasmic transfer did not move enough of them
3. a huge proportion of age related egg defects are related to nuclear not mitochondrial DNA defects.

The federal government banned this treatment in 2001.  Some feared that chromosomal abnormalities and birth defects could result if there were three people’s DNA in one embryo.  Federal officials decided that any method involving the transfer of genetic materials without the fusion of egg and sperm requires the oversight and involvement of the Food and Drug Administration.  The US legislation leading to the FDA taking jurisdiction over human eggs sperm and embryos is a whole other topic to be covered in later posts.   A brief overview of this from Rodger Gosden (who I know and respect as a leading reproductive biologist) is posted here from 1999 when this treatment was at its heyday with references justifying its use from mouse research.

The next brouha using the technique in humans in 2003:   Related research on nuclear transfer was again presented at the annual ASRM meeting in San Antonio in 2003.  I was in the audience for the talk and remember it well.  One of the researchers was an American out of NYU Dr Jaime Grifo who also used to be in my ex-department at Yale.  He is also a repected researcher who I know well.  Unable to perform the research in the US- the experiment was performed in China.  as reported here and here 

Researchers at Sun Yat-sen University in Guangzhou implanted three embryos in the womb of a 30-year-old infertile woman… A triplet pregnancy resulted, they announced at the annual meeting of the American Society for Reproduction Medicine in San Antonio, Texas this week. One of the foetuses was “reduced” to ensure the viability of the pregnancy, but the other two died anyway at 24 and 29 weeks.

With this technique, called nuclear transfer, the doctors fertilised an egg from their patient and an egg from a donor. Two embryos resulted. The nucleus of both women’s embryos was extracted, and the patient’s genetic material was inserted into the empty “eggshell” of the other embryo which, however, contained mitochondria with the other woman’s DNA. The procedure gives the infertile woman’s embryo the healthy mitochondria it needs to develop — but it also results in a child with genetic material from one father and two mothers.

Dr Grifo has maintained that he was an advisor and did not partake in the actual experiment.  NYU issued a statement that if the research was performed in China their IRB did not have oversight (different than my department where all work I did anywhere fell under the IRB as a faculty member).  I have never asked him his take on this but do respect him and strongly do not believe he is someone who would knowingly break the law or do what he felt was wrong.

Nonetheless- the ASRM responded with a moratorium on any future presentations on cloning (whether this was cloning is a whole other debate- many feel not). 

The technique is still undergoing related research:  I chair the video committe of the American Societry for Reproductive Medicine (ASRM) the largest international fertility research society.   Just this past year we accepted a video presentation on how to technically perform the procedure from a research team in Japan.  The paper- Embryonic Development Following the Nuclear Transfer of In Vitro Matured Metaphase-II Oocytes into Enucleated Freshly Ovulated Metaphase-II Oocytes by Tanaka and collegues investigated the possibility of repairing either mitochondrial diseases or female infertility due to ooplasmic deficiency and abnormalities. They demonstrated embryonic development following the nuclear transfer of in vitro matured metaphase-II oocytes into enucleated freshly ovulated metaphase-II oocytes and concluded it could be applied to the treatment of mitochondrial diseases or female infertility due to ooplasmic deficiency and abnormalities. 

More is certainly to come. 

A new study published today in the BMJ showed that the use of accupuncture boosted IVF success rates 65%.  They used the statistical tool called meta-analysis.  Here several small research studies each showing a possible effect are combined to create a virtual huge study that can demonstrate the clear power of an intervention. 

The full report can be read here.  They found a 65% increase in pregnancy rates.  Using another mathematical tool they found that for every 10 women having IVF one additional will become pregnant. 

How it can work:  There are several theories.  One is the accupuncture could increase blood flow to the uterus and help implantation.  Another is that it could relax the uterine muscles.  We have also known for some time anyhting that causes tiny uterine contractions (such as poor embryo transfer techniques) can lead to expulsion of the precious microscopic embryos out of the uterus.   

Some Fertility specialists have been using this approach:  I have been offereing accupuncture to my IVf patients at Gold Coast IVF for years since a German study initially reported benefits. 

They missed some studies showing negative effects: I was at the Annual meeting of the American Society for Reproductive Medicine in October in Washington DC.  There was a lead study there that showed accupuncture dramatically reduced pregnancy rates.  Had this been included in the BMJ study their results would have been less positive.  The study was conducted by friends of mine at a well known Seattle fertility center.  One possible explanation is that they made the patients get right up after their procedures and drive across town in traffic to get the accupuncture and stress levels were huge - another known negative factor.  They also did not use the standard needle placement of earlier studies. 

Good old MSNBC is reporting a story today that heavy cell phone usage leads to lowered sperm counts in men. Before you throw them out the window there are some serious flaws with the study. They report: “In a study of 361 men seen at their infertility clinic, researchers at the Cleveland Clinic found an association between the patients’ cell phone use and their sperm quality.”

On average, the more hours the men spent on their cell phones each day, the lower their sperm count and the greater their percentage of abnormal sperm.

The study comes out of the Cleveland Clinic from a fertility group I know very well and was published in Fertility and Sterility. MSNBC is not correct that this is the first such study, there are in fact two others previously.

The authors write on the general risks of cell phone use that they “operate between 400 MHz and 2000 MHz frequency bands and emit radiofrequency electromagnetic waves (EMW). Reports of potential adverse effects of radiofrequency EMW on brain, heart, endocrine system, and DNA of humans and animals are widely reported in the literature.” If routine use has clear clinical risks remains unclear.

What the study shows: Cell phone users groups showed a decrease in sperm count, motility,viability, and normal morphology with the increase in daily use of cell phones.

Their Overall Results Data:

Why You Should Not Worry Yet: There are some significant problems with the study. First the differences seen may not be clinically relevant nor even lead to infertility. Second they relied on self-reporting of past usage of cell phones (hey bud - thanks for the sperm specimen- can you tell me how many minutes you used last month?). third, cell phones drastically differ in the radiation they emit so it does not make sense that the effect would not be brand specific. Also thanks to the inverse square law the radiation from the phone falls off by hte square of the distance to the organ. I do not know about you but when I speak on my cell phone I tend to keep my testicles a bit far from the phone.

The Biggest problem: The association does not mean causation. We have known for years that very prolonged sitting in a hot car, obesity, smoking, and possibly stress can adversely affect sperm numbers and function. I guarantee you that the guys talking on their cell phones for 4-6 hours a day are more likely in the car, yelling at the driver next to them with a cigarette hanging in the mouth and a big mac on the seat next to them then calmly doing yoga while sipping vitamin water and eating a salad.

Studies in animals have not shown any direct toxic effects.

Quote of the Day: In reviewing the limitations of the animal studies I would have guessed it was really hard to get the rats to talk on their cell phones for 4-6 hours a day. They are such busy little animals scurrying about looking for food all the time and their paws are so little to hold a blackberry. The authors however point out: “it is impractical to compare a rat model to humans because of its small testicular size, nonpendulous scrotum, and the fact that its testis can migrate.” No need to say any more…

Scientists in the UK have successfully tricked stem cells from a female to develop into sperm.  If these cells are functional then the possibility exists for an “all-female” baby to be made from the cells of a same sex female couple.  This is the next step forward from a group that earlier did the same thing with cells from a man.

This study was reported in the British Telegraph Newspaper.  They listed it as embryonic stem cells from a female human embryo - they are likely wrong - as I read the report it appears to be cells isolated from an adult female human bone marrow. 

This same group from Newcastle University led by Prof. Karim Nayernia reported last year that they had made a sperm from the bone marrow of an adult man.  I reported on this research in my previous post Babies Without Men and how it opened the possibility of making sperm from a female and creating a female-female baby.  The details of the original project, ethical and genetic risks  and  heated (and sometimes nasty) debate on lesbian-lesbian parenthood are here.

He now reports that he has repeated the experiment and made the sperm from the marrow cells of a female.  The work has not yet been published not subjected to peer review. 

I previously reported that I think there is a ticking genetic time bomb here due to imprinting errors.  The genes that come from your mother and father are in some cases marked as such genetically and one copy may be shut off.  In some cases only the gene from mom is active in others only the one from dad.  This new process may mess with this system - and imprinting errors are known to cause genetic diseases in some cases.  In fact, the telegraph reports of some “problems”

Prof Nayernia showed the potential of the method in 2006, when he used sperm derived from male embryonic stem cells to fertilise mice to produce seven pups, six of which lived to adulthood, though the survivors did suffer problems.

They also report it could be used to make eggs from a gay man’s cells “a gay man to donate skin cells that could be used to make eggs, which could then be fertilised by his partner’s sperm and placed into the uterus of a surrogate mother.”

While they also report he is seeking permission to create a baby in this way, the UK is very restrictive on new reproductive technologies.  They have a law- the 1990 Human Fertilisation and Embryology Act- that restricts what can and cannot be done.