CHR Update September 2006

As the summer of 2006 is unfortunately reaching its conclusion, we are very pleased to offer another UPDATE on the happenings at CHR. This has, indeed, been a rather eventful summer for our Center. While traditionally characterized by a certain lull in activities, this was not what we experienced this year. Clinically, at least partially driven by many long-distance patients from outside our primary drawing area, the New York Tri-State area (including many overseas patients), we have on many different fronts (and not only clinically) experienced a very busy summer.

TREATMENT OUTCOMES HAVE NEVER BEEN BETTER

This should not come as a surprise since our pregnancy rates have never been better. Our outcome statistics for YTD 2006 are beating all of our prior records and this despite the fact that probably no other fertility center in the nation faces an initial patient population with as unfavorable outcome predictors as we do. Over 80% of our new patients are at, or above age 40 and/or have prematurely aging ovaries (POA) that lead other centers to recommend oocyte donation. In our hands many of these patients still experience success with their own eggs. Indeed, we expect in the very near future one of our papers to appear in the medical journal, Fertility and Sterility (Gleicher and Barad, In press), in which we report a 32% clinical pregnancy in POA women under age 35, who elsewhere had been, mostly, referred into egg donation.

This, of course, does not mean that everybody will be successful. Indeed, in our individual consultations with new patients we place great emphasize on keeping expectations realistic. However, there can be no doubt that, at CHR, women are conceiving on a regular basis with use of their own eggs and ovaries who, elsewhere, had been denied such an option. CHR is, therefore, seen by many as the fertility center of “last resort” before egg donation.

EGG DONATION LIKE NOBODY ELSE

We, nevertheless, of course, still have to recommend oocyte donation to many patients. Indeed, the volume of oocyte donation cycles at CHR has been increasing and, in 2006, has witnessed a significant jump. This is due to a number of reasons: As already mentioned above, we, of course, have the initially probably most unfavorable patient population amongst fertility centers. Even our quite remarkable success with many of these women, this still leaves many others who, in the end, still require donor eggs.

Secondly, CHR’s pregnancy rates in egg donation cycles in 2006 YTD have been nothing but spectacular. We always emphasize that IVF pregnancy rates need to be viewed with caution, whether high, low, or average, because they lend themselves to easy manipulation: If only patients with favorable characteristics are treated, rates will be high, while the opposite will be the case with more unfavorable women. Centers, which transfer more embryos, may artificially increase their pregnancy rates at the expense of creating (high order) multiple pregnancies, which carry significant neonatal risks.

Amongst all IVF statistics, egg donation cycle statistics lend themselves least to manipulation. After all, egg donors are usually similar (they are young and healthy) and most ethically sound programs transfer only 1 or 2 embryos in fresh cycles. Our YTD 2006 clinical pregnancy rate in egg donation cycles of 72% is, therefore nothing but spectacular. We, of course, always want to emphasize that past performances don’t guarantee future performances. However, our record pregnancy rate in egg donation cycles is, as already noted above, this year fully reflective of a record performance of our IVF program in all of its aspects.
A final reason for the growth in our egg donation program is our absolutely unique ability to match practically any, and all, potential recipients within 24-48 hours. Since, like no other IVF program in the nation, CHR has over 150 prescreened oocyte donors, of practically all ethnicities and religions (including rare ethnicities, like Chinese and Indian, and rare religions, like Jewish, Muslim and Hindi), our egg donation program has been attracting patients from all over the world. No other program in the world can offer the egg donor selection we have to offer, and can match recipients as quickly as we can (within 24-48 hours).

HIGH PREGNANCY/LOW HIGH ORDER MULTIPLE PREGNANCY RATES

As noted above, programs which transfer more embryos can, to some extent, improve their pregnancy rates (though, fortunately, this works only up to a certain degree). Transferring more embryos will, however, always increase the multiple pregnancy rates in parallel and this is not a good thing!

We know better than most other programs that infertile couples often prefer a twin pregnancy over a singleton (-and who can blame them, especially after long standing infertility). After all, we were the first to study this many years ago, and published a paper on this subject in the medical journal, Human Reproduction, already in 1995 (Gleicher, et al., Volume 10:1079-84). Since then quite a number of studies by others have confirmed that fertility patients, indeed, express a strong desire for twin pregnancies.
Multiple pregnancies are, however, more risk-prone than singletons. Indeed, the higher the order of the multiple gestation, the higher the risk for premature delivery and the earlier during gestation delivery will take place. Prematurity, in turn, requires prolonged hospital care for newborns and is associated with a high prevalence of adverse short- and long-term health consequences. Professional fertility organizations around the world have, therefore, over the last few years initiated campaigns to reduce the high rate of multiple births, which are the consequence of fertility treatments.

CHR has been on the forefront of this issue for a long time, and long before it became fashionable and subject to media coverage. For example, already in the year 2000 we published a paper on this subject in the prestigious medical journal, The New England Journal of Medicine on this subject (Gleicher et al., 34:2-7). We, however, also recognized from very early on that not all multiple pregnancies should be considered equal. While twin pregnancies undoubtedly carry a higher risk than singletons, their higher risk, especially with good obstetrical care, is relatively minor. If given a choice, and with full informed consent about those risks, we have repeatedly confirmed that most well educated patients will still choose the option of a twin gestation. Considering the overall risk/benefit evaluation of most infertile couples, we support their choice of such a twin pregnancy risk!

 

We, however, are not supportive of taking chances that a triplet (or even higher order pregnancy) be established. Starting with triplets, we strongly feel that the risk of such a pregnancy outweighs its potential benefits. Because we recognized this problem earlier than most of our colleagues, we also have spearheaded (and applied to our patients) new treatment approaches which have greatly reduced the risk of such high order pregnancies. Those included (1) a reduction in ovarian stimulation cycles with fertility drugs, accompanied by intrauterine inseminations (the cause of a large majority of high order multiple pregnancies) and (2) strict limitations of the number of embryos transferred in IVF cycles.

As a consequence, CHR has, as one of only very few national programs, been experiencing above average overall pregnancy rates, with below average high order multiple pregnancy rates, and we are extremely proud of this fact.

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If you would like to read CHR publications on this topic, here is a detailed reference list:

  • Gleicher N, et al., The desire for multiple birth in couples with infertility problems contradicts present
    practice patterns. Human Reproduction 1995; 10:1079-84
  • Gleicher N, et al., Reducing the risk of high order multiple pregnancy after ovarian stimulation with
    gonadotropins. New England Journal of Medicine 2000; 34:2-7
  • Gleicher N, Safety issues in assisted reproduction technology. A rebuttal. Human Reproduction 2003;
    18:17656-66
  • Gleicher N, Is it time to limit IVF transfers to one embryo? Contemporary Obstetrics and Gynecology
    2004; 48:73-85
  • Gleicher N, Barad D, the relative myth of elective single embryo transfer. Human Reproduction 2006;
    21:1337-44)
  • Gleicher N, et al., A formal comparison of the practice of assisted reproductive technologies between
    Europe and the USA. Human Reproduction 2006; 21:1945-50

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DHEA UPDATE

CHR continues to accumulate data on our DHEA experience. We, indeed, expect the publication of one paper imminently (Barad and Gleicher, Human Reproduction; In press). Two other papers on the topic are still under review (the summer break always slows down the submission process to medical journals).
In addition, we expect to see soon publications from other investigators, especially from outside the U.S., since we know of a number of studies, which are already underway.
Indeed, CHR is also in the process of establishing collaborative research projects with centers outside of the U.S., and we hope to be able to announce the first of such collaborative effort with a large European IVF center in the very near future.

An update on CHR’s DHEA experience will be presented at the upcoming Annual Meeting of the ASRM in October in New Orleans, where our abstract has been accepted for oral presentation. A written form of the abstract is in press in Fertility and Sterility
(Barad et al, In press)
. Our experience continues to suggest that DHEA improves egg and embryo numbers, egg and embryo quality, increases pregnancy rates, speeds up time to conception and, most likely, reduces aneuploidy rates of embryos. Moreover, it does all of this with only minimal side effects.

THE RELATIVITY OF FSH LEVELS

Another abstract accepted for oral presentation at the Annual Meeting of the ASRM in New Orleans involves an exciting new research area at CHR. Under the leadership of Dr. Barad, we have now succeeded in defining age-specific normal FSH levels (Barad et al.,Fertility and Sterility, In press). Age-specific FSH levels are a concept of crucial potential importance and here is why:
Most fertility centers consider FSH levels to be normal up to 10 mIU/ml and this cut off is considered appropriate for women of all ages. Yet, at the same time, it has been known for decades that FSH levels increase as women age. A 20-year old patient should, therefore, be expected to have a different FSH (and lower) level from a 40-year old.

Surprisingly, this very simple concept has so far not been reflected in the clinical practice of infertility. Instead, the ovarian function of women of all ages has for decades been judged based on the universal baseline cut off of 10 mIU/ml. We now have determined what normal baseline FSH levels at different ages really should be and, not surprisingly, they are much lower than 10 mIU/ml in younger women. The importance of this finding is very significant because it now facilitates the diagnosis of prematurely aging ovaries (POA) in much easier, and more standardized fashion.

In other words, if a young woman has elevated FSHL levels for her age, even if her levels are still below the historical 10 mIU/ml level, we now can diagnose her with great certainty with POA. The validity of these new age-specific FSHL cut off levels was further confirmed when we were able to demonstrate that they correlate with egg production in IVF cycles. Egg production, of course, also correlates with female age and what constitutes a normal number of retrieved eggs also changes (decreases) with advancing female age.

We predict that age-specific baseline FSH levels (and egg numbers) will revolutionize the practice of fertility care by improving our ability to diagnose women with POA in a more timely fashion, but also by recognizing those older women who still have good ovarian function and, therefore, do not have to be referred into egg donation. A manuscript on this very important research effort is in preparation.

OTHER RESEARCH ACTIVITIES

There is much more research going on at CHR than we can describe in these short pages.
For example, Dr. Gleicher, who also is a well recognized reproductive immunologist, has currently two papers in press, which address immunological issues in reproductive medicine: In a paper in the American Journal of Obstetrics and Gynecology (Gleicher N, In press), he is addressing the similarities between preeclampsia/eclampsia and organ rejection after transplantation, with special emphasis on autoimmune reactions.

In a second paper, which is to appear in the medical journal Autoimmunity (Gleicher et al., In press), he is reporting a study of mother-newborn pairs, where the mothers are known to suffer from autoimmune diseases.

 

And, while Andrea Weghofer, M.D., Ph.D. has returned to her Alma Mater, the University of Vienna, in Austria, she is still actively continuing to cooperate with CHR on a number of research projects, primarily in the area of preimplantation genetic diagnosis (PGD). Indeed, she, too, was selected for an oral presentation at the upcoming Annual Meeting of the ASRM in New Orleans.

The year 2006, so far, not only has brought us the best clinical pregnancy rates we have ever witnessed at CHR, but also shapes up as the most active research year in at least a decade. Indeed, we don’t recall a period when so many CHR papers appeared in prestigious medical journals within such a short time period.

GRANDROUNDS

The Fall-season for or postgraduate educational series of Grandrounds will be starting on September 12, 2006, with a presentation by Edmond Confino, M.D., Professor of Ob/Gyn at Northwestern Medical School in Chicago. Dr. Confino studied many years ago as a resident under Dr. Gleicher at Mount Sinai Hospital in Chicago, and has since gone on to an illustrious academic career in the specialty. We expect, as always, a full house and, therefore, strongly discourage attendance without confirmed reservations.
We will continue posting periodic UPDATES, when there are news to report from CHR. So, continue looking for them! These are exiting times at CHR, and we thank you for your interest in our
work.

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.