The following articles represent an Update on CHR activities.
If you want further information on any of these articles, please
email Tom
Weidner.
It is a reflection of how busy the summer of 2008 is evolving
that we this year are not taking a summer break in publishing
monthly UPDATEs. There is simply too much going on and
here are some of the highlights:
Oldest patient ever with DHEA pregnancy
Readers of UPDATEs will recall that, a while back, we set
the goal of crossing the threshold of female age 46 years in
establishing pregnancies. We are now very pleased to report
that not only have we, indeed, crossed this threshold, but we
have even come close to age 47. We recently discharged into
obstetrical care a 46 year and 9 months old female, who
spontaneously had conceived after 6 weeks of DHEA, while
waiting to start an IVF cycle after the usual 2 months of DHEA
supplementation. This case represents so far the oldest female
with a DHEA pregnancy established at CHR and probably one
of the oldest females in the world to conceive after any form of
infertility treatment.
Learn more about DHEA at CHR
We are also pleased to report that others in the world are also
finally starting to report on DHEA. In a so far only electronically
published report from Greece in Fertility & Sterility (2008) Mamas
and Mamas (doi:10.1016.j.fertnstert. 2007.11.055), the authors
report on five DHEA conceptions, - a rather small number, of
course, in comparison to CHR’s experience. The report was,
nevertheless, quite remarkable because two of the pregnancies
were achieved in women with initial baseline FSH levels above
100mIU/mL. Their report, therefore, suggests that DHEA
supplementation may not only be successful in establishing
pregnancies in older women with diminished ovarian reserve and younger women with premature ovarian aging (POA), but
also in women with outright premature ovarian failure (POF).
CHR, therefore, is in the process of initiating a clinical trial
of DHEA in POF patients.
Our Toronto, Canada, based colleagues (Ryan E., et al) also
will soon publish their DHEA experience, which mimics ours
very closely. An abstract from their center was just accepted
for the upcoming Annual ASRM Meeting in San Francisco (see below) and these data will, therefore, also appear in Fertility & Sterility.
Also, View Dr. Gleicher's appearance on The Early Show on CBS, 8/4/08 where he discusses CHR's DHEA program.
A brief report from ESHRE
CHR Medical Director, Norbert Gleicher, MD, and Andrea
Weghofer, MD, Ph.D, represented CHR at this year’s Annual
ESHRE Meeting in Barcelona, Spain. While the weather was
very hot and humid, the meeting nevertheless attracted a
record crowd of over 7,000 participants (probably the largest
attendance ever at any ESHRE or ASRM meeting). And there
was a lot to do!
Dr. Gleicher had been invited to speak at two special symposia
during the meeting, both held in the central convention hall
in front of thousands of attendees. The first, organized by
FERRING, addressed the importance of LH/hCG stimulation
vs. FSH-only stimulation in IVF. The second symposium,
organized by IBSA in the same venue the following day, dealt
with the IVF outcome difference between the U.S. and Europe.
And while both of these symposia (and especially the second)
attracted fierce debates, neither reached the decibel level of
one of CHR’s oral abstract presentations.
Drs. Gleicher and Weghofer presented two oral and one poster
presentations with CHR data. Even before its formal oral
presentation, an abstract presented by Dr. Gleicher had become
a centerpiece of attention, primarily for the British press. In this
abstract Dr. Gleicher presented evidence that the widely held
belief that twin pregnancies represent higher risk outcomes
for infertility patients than singletons was mistaken. (A detailed
manuscript has been published electronically: Gleicher N and
Barad D. Twin pregnancy, contrary to consensus, is a desirable
outcome in infertility. Fertil Steril doi:10.1016/j.fertnstert.20
08.02.160). Since such an allegedly higher risk profile is the
principal argument for the recent widely propagated concept
of single embryo transfer (s-ET), establishing the higher risk
profile as incorrect pulls the rug from under proponents of wide
s-ET utilization.
Read more about CHR's IVF treatment plans
Practically all U.K. papers of significance reported Dr. Gleicher’s
presentation. The reason for this special attention in the U.K.
was the British Embryology Authority’s decision, only a week
earlier, to mandate the increased use of s-ET in attempts to
reduce national twin pregnancy rates. Obviously, not a very
well thought-through policy and just another example why
government regulation of medical care never works.
View samples of the media coverage in response to Dr. Gleicher's ESHRE presentation.
Government regulation of fertility care is, however, especially
dangerous; Focus on Reproduction, the monthly official
ESHRE magazine, in its May 2008 issue, reported that Italy’s
first official evaluation of Law 40 (mandating new IVF policies
for the country) found a decline in ART pregnancy rates. Dr.
Gleicher and other speakers noted in the ESHRE symposium
on differences in IVF outcomes between the U.S. and Europe that
more intensive government interventions in Europe were one of
the reasons for so much poorer pregnancy rates in Europe than
in the U.S. Dr. Gleicher also noted in his presentation that such
interventions very frequently overlook the infertility patient’s
basic right to strive for maximal pregnancy chances.
New definitions for Infertility and Recurrent
Pregnancy Loss
The Practice Committee of the ASRM recently published new
definitions, which are worthwhile to comment on: The first important modification is the definition of infertility as a disease.
It is further defined by failure to achieve pregnancy in 12, or
more, months of unprotected intercourse. The most important
modification may, however, lie in the recommended timing for
diagnostic intervention. It now states that earlier evaluation [than
after 12 months] may be justified based on medical history and
physical findings and is warranted after 6 months for women
over age 35.
Recurrent pregnancy loss is now also defined as a disease,
but distinct from infertility. It is further defined by [only] two or
more failed pregnancies and already at that point merits careful
review as to whether specific evaluations may be appropriate.
Both new recommendations thus practically advance the time of
appropriate diagnostic and therapeutic interventions. It seems
high time for such a formal decision! Competent physicians
have followed these definitions for years.
Please contact us for more on Premature Ovarian Aging.
Annual ASRM Meeting 2008
We three months ago in the UPDATE announced a record
nine abstract submissions from CHR to the upcoming Annual
ASRM Meeting, which this year will take place November 10 -12 in San Francisco, CA. We are now pleased to report that
an unprecedented eight, out of nine, submissions have been
accepted for presentation. And this doesn’t even include a
number of additional abstracts on which CHR staff collaborated,
but which were submitted from collaborating institutions. For
example, as already noted earlier, our Toronto colleagues
(Ryan et al) also had an abstract accepted, summarizing their
DHEA outcome experiences.
In collaboration with this group, one of the CHR abstracts that
was accepted reports on the unusually low miscarriage rate
in pregnancies, established after DHEA supplementation.
CHR’s and Toronto’s combined data demonstrates an
approximately 50-80% reduction in expected age-specific
miscarriage rates, strongly suggesting that DHEA
supplementation may reduce aneuploidy (chromosomal
abnormality) rates.
CHR in the Media
The Early Show, CBS
CHR Drs. Norbert Gleicher and
David Barad appeared on “The Early Show” on Aug. 4, 2008 in a
series entitled Medical Miracles. Dr. Gleicher described the process that has led to CHR's groundbreadking work with DHEA. Video
Newsweek Magazine
Dr. Kutluk Oktay met with the national magazine to share the
story of a cancer patient who, thanks to one of Dr. Oktay’s
innovative techniques, became pregnant and had a child after
undergoing cancer treatments. The story appeared in the Aug.
4 issue of Newsweek.
Article
New CHR Publications
Having passed the mid-year point, it is once again time to list
CHR publications, which so far have appeared during 2008, either
electronically or in print. Interested readers of this UPDATE are
welcome to order reprints of any of these articles either by e-mail
(editorial@thechr.com) or by calling 312-876-1506.
(1) Gleicher N. Missed immunological opportunities in pregnancy. 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 A et al. Does autoimmunity play a role in the
pathophysiology of premature ovarian aging? RBM Online
2008;16:830-4
(4) Weghofer A et al. The impact of LH-containing gonadotropins
on diploidy rates in preimplantation embryos: long protocol
stimulation. Hum Reprod 2008;23:499-503
(5) Gleicher N and Barad D. Arguments against elective single-embryo
transfer. Expert Rev Obstet Gynecol 2008; 3:481-6
(6) Gleicher N et al. Preimplantation genetic screening: “established”
and ready for prime time? Fertil Steril 2008; 89:7808
(7) Gleicher N and Barad D. Single versus twin embryo implantation:
Evidence, cost-effectiveness, and patient satisfaction. Gynecol &
Obstet 2008;13:77-83
(8) Gleicher N 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
doi:10.1016/j.fertnstert.2008.01.098
(9) Gleicher N et al. A pilot study of premature ovarian senescence: II.
Different genotype and phenotype for genetic and autoimmune
etiologies. Fertil Steril 2008; doi:10.1016/j.fertnstert.2008.01.099
(10) Singer T et al. Correlation of antimüllerian hormone and baseline
follicle-stimulating hormone levels. Fertil Steril 2008; doi:10.1016/
j.fertnstert.2008.03.034
(11) Gleicher N and Barad D. Twin pregnancy, contrary to consensus,
is a desirable outcome in infertility. Fertil Steril 2008; doi:10.1016/
j.fertnstert.2008.02.160
(12) Oktay K et al. Safety of fertility preservation by ovarian stimulation
with letrozole and gonadotropins in patients with breast cancer: A
prospective controlled study. Journal of Clinical Oncology 2008;
doi: 10.1200/JCO.2007.14.8700
(13) Oktay K et al. Can GnRH analogues preserve gonadal function
without preserving fertility? Oncologist 2008 May; 13(5):615-7
(14) Oktay K and Cil AP. Who is the best candidate for oocyte
cryopreservation research? Fertil Steril 2008 Apr 26 [Epub ahead
of print]
(15) Oktay K et al. Terminal kinase regulates G2/M transition through a
mechanism upstream of Aurora-B. Cell Cycle 2008 Feb 15; 7(4);
533-541 [Epub ahead of print]
(16) Oktem O and Oktay K. Stem cells: a perspective on oocytes. Ann
N Y Acad Sci 2008 Apr; 1127:20-6
(17) Oktem O and Oktay K. The Ovary: Anatomy and function
throughout human life. Ann N Y Acad Sci 2008 Apr; 1127:1-9
(18) Oktem O and Oktay K. Preservation of menstrual function
in adolescent and young females. Ann N Y Acad Sci. 2008
Jun;1135:237-243
(19) Oktay K and Sonmezer M. Gonadotropin-releasing hormone
analogs in fertility preservation-lack of biological basis? Nat Clin
Pract Endocrinol Metab. 2008 Jul 15. [Epub ahead of print] PMID:
18628732 [PubMed - as supplied by publisher]
(20) Oktay K and Sonmezer M. Chemotherapy and amenorrhea: risks
and treatment options. Curr Opin Obstet Gynecol 20:408-415 2008
Wolters Kluwer Health | Lippincott Williams & Wilkins 1040-872X
PMID: 18574230 [PubMed - as supplied by publisher]
In addition, six manuscripts are already in press, which means that they
have been accepted for publication, but have not yet appeared, and
another 10 are currently under review. In other words, we anticipate
another record year for CHR publications!
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