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

May 2008

A very busy April, behind us, we are preparing for an even busier May and June. May 15 is the deadline for abstract submissions to this year’s ASRM meeting in San Francisco and we already submitted six abstracts and still have a number more to go. Abstracts always represent the first presentation of new research results to the public, in this case, of course, colleagues. They, therefore, usually offer only preliminary results and much of the materials presented in abstract format at scientific meetings, therefore, never make it into formal publications as peer reviewed full length papers.

At CHR, however, it has been always our policy to present only rather definite results at scientific meetings. Most of our abstracts, therefore, do end up being published in full length manuscript formats. This year is a very good example: Even though we are still very early in the year, CHR authors already have seven (7) full length papers published in peer reviewed medical journals (for detail see Table). Most of them had originally started as abstracts and then, quickly, were expanded to full manuscript length. Acceptance as a manuscript in a prestigious medical journal, of course, significantly validates the published research beyond data just published in abstract format.

New manuscripts accepted and published

(1) Gleicher N. Missed immunological opportunities in pregnancy (Editorial)
Expert Rev Clin Immunol 2008;4:1-3
(2) Gleicher N. Graft-versus-host disease and immunologic rejection: implications for diagnosis and treatments of pregnancy complications.
Expert Rev Obstet Gynecol 2008;3:37-49
(3)Weghofer et al. The impact of LH-containing gonadotropins on diploidy rates in preimplantation embryos: long protocol stimulation.
Hum Reprod 2008;23:499-503
(4) Gleicher et al. Preimplantation genetic screening: “established” and ready for prime time? (Editor’s Corner)
Fertil Steril 2008; 89:780-8
(5) Gleicher et al. A pilot study of premature ovarian senescence: I. Correlation of triple CGG repeats on the FMR1 gene to ovarian reserve parameters FSH and anti-Müllerian hormone.
Fertil Steril 2008; doi:10.1016/j.fertnstert. 2008.01.098*
(6) Gleicher et al. A pilot study for premature ovarian senescence: II. Different genotype and phenotype for genetic and autoimmune etiologies.
Fertil Steril 2008; doi:10.1016/j.fertnstert.2008.01.099*
(7) Gleicher and Barad. Twin pregnancy, contrary to consensus, is a desirable outcome in infertility.
Fertil Steril 2008; doi:10.1016/j.fertnstert.2008.02.160*
* Indicates that paper has so far only appeared in electronic format in print

In addition to the manuscripts listed in the table, which already have appeared in print, at least four (4) more are in press, and are expected to appear in print within days to weeks, and at least half a dozen additional manuscripts, are currently under review at various prestigious medical journals. CHR thus not only produces quite remarkable amounts of research data, but those research efforts usually quickly, as a testimonial to the quality of the research performed at CHR, find their way into prestigious medical journals.

Reprints of all manuscripts published by CHR authors are obviously available to the readers of the CHR UPDATE. If you are interested in receiving a reprint, please contact us at chrjournal@thechr.com or call 312-876 1506.

In our June CHR UPDATE we will, once again, discuss new insights from ongoing research efforts at CHR. This month, we, however, want to concentrate on a number of recent developments in the general medical literature, deserving of our attention.

Does DHEA improve cognitive function in women?

All persistent readers of the CHR UPDATE will by now be eminently familiar with the mild male hormone dehydroepiandrosterone DHEA. Investigators at CHR have been using this hormone now for a number of years very successfully in women with diminished ovarian reserve (DOR), whether their ovarian impairment is due to advanced age or premature ovarian aging (POA). In doing so, we have been able to demonstrate that in such women DHEA supplementation has quite remarkable beneficial effects (see Table 1), which all can be summarized as rejuvenating ovarian function.

During all that time of DHEA use at CHR, we have carefully monitored side effects of the medication and have been impressed by how rarely even the most common side effects, such as oily skin, acne and hair loss, seem to occur.

We, however, have been even more surprised that quite often what we really heard were anything but side effects; indeed, many more patients than complained about side effects, commented to us how much better overall DHEA supplementation makes them feel. Table 2 summarizes some of the specifics.

Now comes a study, reported in the prestigious Journal of Clinical Endocrinology and Metabolism (Davis et al. 2008; 93:801-8), in which investigators from Australia report that DHEA appears to improve cognitive functions in women. Specifically, they noted that higher endogenous DHEA levels are independently and favorably associated with executive function, concentration and working memory. It seems our patients knew all along what they were talking about!

Contact us for more on DHEA and premature ovarian aging.

IVF in Europe and the USA: A world apart?

In two papers published in Human Reproduction (Gleicher et al. 2006;21:1945-50) and Fertility and Sterility (Gleicher et al. 2007;87:1301-5), Drs. Gleicher and Barad were probably the first to point out the considerable differences in IVF pregnancy rates between US and European programs, with the USA experience offering patients dramatically higher overall pregnancy rates, though also higher multiple pregnancy rates. While the message initially was not very well received by European colleagues, their attitude now seems to have finally come around.

A lead article in the January issue of Focus in Reproduction, the official monthly magazine of ESHRE, the European counterpart of ASRM (January 2008, pp28-33), mostly offered information from an interview with Dr. Gleicher (and even his photo) on the topic, and CHR’s two above noted publications were widely quoted.

That Europeans have started to take these outcome differences seriously can also be deducted from the fact that a special symposium on the topic has been scheduled for the coming Annual Meeting of ESHRE, which this year will take place in Barcelona, Spain. Dr. Gleicher was, indeed, invited to join the faculty of speakers for this symposium.

Practice patterns have been diverging between Europe and the USA for quite some time. A more regulated environment in Europe has led to lower multiple pregnancy rates but also to dramatically lower pregnancy success with IVF and, therefore, to much higher cycle utilization. Europe has also been leading in efforts to avoid twin pregnancies and has attempted to do so at practically all cost. This has led to the active promotion of single embryo transfer (s-ET), in Belgium, for example, even mandated by law.

s-ET, of course, reduces pregnancy chances in comparison to 2-embryo transfer (2-ET). The increasing utilization of s-ET in Europe can, therefore, be predicted to lead to further reductions in pregnancy chances and, at least in the short term, to a further increasing par in pregnancy rates between Europe and the USA.

The aggressive pursuit of s-ET has primarily been based on the argument that singleton pregnancies have lower complication rates in mothers and offspring than twin deliveries. Drs. Gleicher and Barad in a just very recently published paper demonstrated, however, that these assumptions are statistically incorrect (Gleicher and Barad. Fertil Steril 2008; doi:10.1016/j.fertnstert.2008.02.160) Since most infertile women under treatment are planning on more than once child, a treatment cycle leading to a singleton delivery will have to be followed by a second such cycle in order to give this patient the desired two children. In contrast, a patient would be a mother of two in only one twin pregnancy. A correct statistical analysis can, therefore, not compare outcomes between one singleton and one twin pregnancy, but has to consider outcomes of one twin gestation in comparison to two singleton deliveries. When this is done, twin pregnancies no longer demonstrate higher risk profiles and/or costs than singletons.

Even though going against widely prevailing opinions, these data are practically undisputable. CHR’s recently published study, thus, pulls the rug from under the principal argument in favor of s-ET and will with great likelihood, therefore, be subject to very active discussion at this year’s ESHRE and ASRM meetings. Stay tuned; twins may again come into fashion, after all!

Contact us for a pre-ivf consultation.

Fertility Preservation

Much has recently been written in these pages on fertility preservation. In view of much hype in the lay media, especially surrounding oocyte (egg) freezing, we just want to point out that recently The American College of Obstetricians and Gynecologists (ACOG) has added its opinion to the topic by publishing a formal ACOG Committee Opinion on the issue of ovarian tissue and oocyte cryopreservation. We are quoting from the abstract of this opinion (Obstet Gynecol 2008; 111 (May):1255-6):

As more young women are cured of cancer with chemotherapy and radiotherapy, which can be gonadotoxic, interest is growing in treatments that may preserve fertility. IVF with cryopreservation of embryos is currently the best option for fertility preservation when treatment for cancer is anticipated. Ovarian tissue cryopreservation and oocyte cryopreservation are two options with potential. Although these methods are developing rapidly, their use as a means to have a child after cancer treatment MUST BE CONSIDERED INVESTIGATIONAL AND OFFERED ONLY WITH APPROPRIATE INFORMED CONSENT IN A RESEARCH SETTING AND UNDER THE AUSPICIES OF AN INSTITUTIONAL REVIEW BOARD.

We have really nothing to add to this opinion except to announce that CHR was just licensed by New York State’s Department of Health to cryopreserve ovarian tissue under the center’s tissue banking license and will be receiving specimens from Sloan Kettering Memorial Cancer Center in New York City and Westchester Medical Center in Valhalla.

Contact Us

To find out more about the Center for Human Reproduction, or to learn more any of our infertility solutions, please contact us.

- The CHR

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