CHR Update

The following articles represent an Update on CHR activities. If you want further information on any of these articles, please email Tom Weidner.




December 2008

We want to start our monthly UPDATE wishing all of our patients, colleagues and other readers a Very Happy Holiday Season and a Healthy and Prosperous New Year 2009. Recognizing the difficult economic times we are in, it seems more than ever important to maintain optimism and a positive outlook. As a famous philosopher once said (quoted over and over by many of our parents), “as long as we are healthy …!”

In contrast to many other medical specialty areas, most of our patients are, fortunately enough, in a traditional physical sense, healthy. They often suffer terribly emotionally for not being able to conceive, but they (and we) are lucky not to face life and death situations, which represent the daily routine for many of our colleagues in other medical specialties.

We, of course, do not want to minimize the stress infertility patients are under. It is considerable! But we all understand that even stress is a relative phenomenon: while it always could be better (i.e., less), this may also be the time to recognize that it always could be worse. We consider it our responsibility at CHR to keep our patients’ stress level to a minimum, and, therefore, are always grateful if you, - our patients -, tell us how we can do even better.

In the meanwhile we want to reemphasize that, in contrast to many other programs, we do not close the center for the holidays. We do understand that many of our patients have to receive medical care under insurance plans expiring at the end of the year. We also already noted in the November UPDATE our discount program for uninsured patients, who qualify under income ceiling. If there are other things we can do, please let us know!

Contact us about financial assistance

ASRM Meeting, San Francisco

As we already anticipated in last month’s UPDATE, CHR broke all records at this year’s Annual Meeting of the American Society for Reproductive Medicine (ASRM) in San Francisco. With 11 oral and poster presentations and one additional video presentation, we, very clearly, were in the top one percent of institutions (world-wide) in visibility. With Drs. David H. Barad and Kutluk Oktay, in addition, chairing menopause and fertility preservation sessions that attracted very large attendance, CHR was present everywhere.

Learn more about Fertility Preservation options at CHR's IFP

Maybe most rewarding was, however, the feedback we received from colleagues from all over the world, who, in previously unprecedented numbers, now have embraced the dehydroepiandrosterone (DHEA) protocol, developed at CHR for women with diminished ovarian reserve, elevated FSH levels and/or simply advanced female age. Both Dr. Barad and Dr. Gleicher were approached by physicians from many different countries, who wanted to share their “DHEA success stories.”

Dr. Ed Ryan from Toronto, Canada, who had previously collaborated with CHR on a report on decreased miscarriage rates after DHEA supplementation (the abstract was presented at the 2006 ASRM Meeting and a manuscript is in press), reported his center’s gender experience after DHEA supplementation. Like we here at CHR, he has observed a considerable shift towards male offspring after DHEA supplementation. This was also the observation made by Dr. Mamas, an investigator from Athens, Greece, who this year reported his center’s DHEA success in Fertility and Sterility (2008 Mar 3. [Epub ahead of print]). He communicated his center’s gender finding in a conversation with Dr. Gleicher, CHR’s Medical Director. It thus increasingly appears that CHR’s initial observation that DHEA supplementation shifts the gender balance towards more males may, indeed, be correct.

Learn more about CHR's DHEA program

The FMR1 (fragile X) gene

Readers of our monthly UPDATEs, and/or of our quarterly newsletter CHR VOICE, will know that one of the major research projects that CHR has been pursuing over the last two years has been the association between the FMR1 gene and ovarian function. CHR investigators presented some of these data at the ASRM meeting in San Francisco and approximately half a dozen papers, describing this research, are in press or have already electronically appeared. The most exciting finding, defining a previously unknown function of the gene in regards to ovarian function is, however, currently only in preparation stages for submission for publication. Because of prepublication restrictions that most prestigious journals impose on unpublished data, we are currently not in the position to go into further details. Only so much; wait and see!

We, however, can offer a brief update in regards to already publicly presented data. Here are the key points: The FMR1 gene represents a snippet of genetic material on the X chromosome. It has historically attracted considerable attention because it is a gene made up of so-called CGG (nucleotide) triple repeats, which have the potential to “expand.” This means that within one generation, the number of CGG triple repeats may increase to a significant degree. If these repeats reach 55-200, a so-called premutation range is reached. If over 200 repeats are present in an individual, he/she has the so-called full mutation. Especially males who have premutation or full mutations are at significant risk for severe neurological and/or psychiatric disorders. Male premutation carriers are at risk of developing a severe neurodegenerative disorder at middle age, while the full mutation in males is the most well-known genetic cause of autism and mental retardation.

Severity of these neurological and psychiatric findings, of course, makes it worthwhile to screen mothers (who transmit the genetic risk to offspring), and potentially affected individuals, in attempts to prevent transmission into future generations and in order to reach accurate diagnoses, where the condition is already present.

Investigators at CHR have now, however, defined an additional purpose of this gene. It quite apparently is also involved in regulating ovarian reserve. This was demonstrated by building on some data reported in the ‘90s, when investigators demonstrated that a majority of humans possess 29-30 CGG repeats, while smaller minorities show either higher or lower numbers. Higher CGG repeats, especially at premutation ranges, had historically been associated with increased risk towards premature ovarian failure (early menopause). Taking these observations as stepping stones, CHR investigators initially demonstrated that increasingly larger CGG repeats increasingly predisposed patients towards prematurely diminished ovarian reserve (premature ovarian senescence).

This then raised the obvious next question: What decreasingly low CGG repeats mean in regards to ovarian reserve? This question was answered in one of the oral presentations, given by Dr. Gleicher, at ASRM in San Francisco, and currently already in press as a full length publication. As the investigators were able to demonstrate, lower counts, in an almost identical fashion to higher counts, also predispose towards premature ovarian senescence.

It, thus, appeared that the CGG peak of 29-30 might represent a “normal” range in regards to the regulatory function the FMR1 gene exerts over the ovaries, while higher and lower counts denote risk towards premature decline in ovarian reserve; i.e., premature ovarian senescence or premature ovarian aging (POA), as we have come to call the earlier stages of the process.

We are going to end the story here, but wait for more exciting news from CHR in regard to the FMR1 (fragile X) gene in the near future. Our research in this area is continuing on a very aggressive pace and we hope in the very near future also to be able to announce specific clinical benefits for our patients that may arise from this research.

Read more about advances in treating POA

Further honors for CHR’s Medical Director

We already have extensively written about the invitation CHR’s Medical Director, Dr. Gleicher, received to give the Patrick Steptoe Memorial Lecture to the British Fertility Society on Wednesday, January 7, 2009. We also noted that he was, in addition, invited to give the following day a shorter lecture on "Unexplained Infertility" to the same body.

Now Dr. Masoud Afnan arranged in addition a “stomp the professors” follow up meeting on Friday and Saturday, January 9 and 10, at which Dr. Gleicher and Prof. Richard Fleming will be the two guest professors. In addition to answering a myriad of directed questions from the audience, Dr. Gleicher will also present two additional lectures; one on “The effects of DHEA in women with diminished ovarian reserve,” and a second one on “The FMR1 (fragile X) gene as a fertility test.”

Dr. Gleicher was invited to join the international Advisory Board of a new website, www.IVF-Worldwide.com (currently under construction), which aims to become the largest and most comprehensive IVF-focused professional website for the IVF field.

Learn more about the IVF program at CHR

Dr. Gleicher was invited by Serono Symposia International to participate in a conference with the title “New Frontiers in Fertility,” which will take place February 13-14, 2009 in Lisbon, Portugal. He was asked to give a presentation with the title “Can we positively affect follicular recruitment,” which will primarily concentrate on CHR’s DHEA experience.

Dr. Gleicher was also again, like in 2008, invited to present a talk at the Annual Meeting of the Jordanian Society for Fertility and Genetics, which will meet April 8-10, 2009 in Amman, Jordan. The topic of his talk will be “Can we treat ovarian aging?” and will also primarily concentrate on CHR’s DHEA experience, which is increasingly used as an example for new programs all around the world.

Considering the upcoming holidays, we very likely will publish an UPDATE in January of 2009 only if there is really important news to report. Otherwise, look for these pages again in February 2009.

Until then, stay healthy and warm, and remember that there is always somebody on the other end of the line at CHR who is ready to answer your phone call or e-mail.

We wish everybody a Wonderful 2009.

- The CHR Staff

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PREVIOUS UPDATES

We will continue posting periodic UPDATES when there is news to report from CHR. So, continue looking for them! These are exciting times at CHR, and we thank you for your interest in our work.

Last Updated: October 19, 2011