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Indications for PGD
Recurrent Miscarriage & Infertility
 Preimplantation
genetic diagnosis (PGD) dramatically improve the chance of a
successful IVF pregnancy in couples where prior IVF failures
have remained unexplained. It has been estimated that over
half of all IVF failures are not able to be explained by an
apparent problem with embryo "quality". For many couples
however, this statistic is quite misleading. Most IVF
centers look very closely at the appearance of embryos under
the microscope as they attempt to determine a "good" or
"high quality" embryo from those of lesser quality.
Generally, embryos are given "good" marks when they
demonstrate an appropriate number of cell divisions at a
given time in their growth cycle, when the individual cells
of the embryo appear to have a uniform size and when there
is an absence of cellular "fragments" that may or may not
represent problems in the growth progress of the embryo.
Recent advances however, have shown that even embryos
receiving the highest ratings from scientists based on their
"normal" or "excellent" appearance under the microscope may,
in fact be highly abnormal and totally incapable of ever
producing a pregnancy. This discovery was brought about by
the addition of preimplantation genetic diagnosis (PGD) to
the tools available to scientists in the IVF laboratory. PGD
has offered physicians and scientists, for the first time
ever, the ability to examine far beyond the superficial
appearance of an embryo. We are now able to examine the most
important internal genetic code of the embryo as well. And
with these new genetic tools, we have come to learn that
some embryos that appear on the surface to be of the highest
quality may carry a genetic code that makes them poor
choices for attempting to establish a healthy pregnancy. We
have also now learned that other embryos that might have
been classified as less than optimal based on their
appearance, and may not have been selected for return to the
mother may in fact be of the finest quality and have ten or
twenty times more chance of producing a healthy pregnancy
than those that would have been selected without the use of
the remarkable new PGD tools. That beauty in an embryo is
more than skin deep has now been confirmed by science. The
technique has also allowed confirmation, for the first time,
of the suspicions of our IVF scientists that simply
observing and grading the appearance of an embryo may fall
far short of being able to provide reliable information to
patients who have failed IVF.
 PGD
is helpful for patients with unexplained infertility,
recurrent miscarriages, unsuccessful IVF cycles, advanced
maternal age, or male factor infertility. In those cases,
the most likely cause is a chromosome abnormality.
Chromosome abnormalities include aneuploidy and structural
abnormalities. Aneuploidy is the most common chromosomal
abnormality. Aneuploidy can occur in both eggs and sperm.
Structural abnormalities include translocations, inversions,
and deletions. Structural chromosome abnormalities can also
be present in eggs and sperm. The transmission of a
chromosome abnormality to an embryo can result in a low
implantation rate, miscarriage or the birth of a baby with a
genetic disorder. Using Fluorescence In Situ Hybridization
(FISH), the scientists in our PGD laboratory can identify
the absence of these specific genetic disorders in each
normal developing embryo. As a result, only those embryos
free of genetic disease will be transferred to the patient’s
uterus so as to increase the chance of conception and
ultimately a healthy baby.
Recurrent First-trimester Pregnancy
Loss
Recurrent pregnancy loss (defined as three or more
miscarriages in a row) affects approximately 1% of the
population. The evaluation of these patients should first
rule out genetic, anatomic, endocrine, and immunologic
causes for recurrent miscarriage. Many doctors will also
test for genetic blood clotting disorders, although this
remains controversial. The medical evaluation recurrent
miscarriage should be individualized, but typically includes
a physical examination; pelvic ultrasonography,
hysterosalpingography, or saline hysterosonography to
evaluate the uterus; complete blood cell count; testing for
thyrotropin, antithyroid antibodies, prolactin, lupus
anticoagulant, anticardiolipin, and antiphosphatidylserine
antibodies; karyotyping (chromosomal analysis) of both
partners; and possibly an
 endometrial
biopsy (biopsy of the lining of the uterus) and screening
for genetic blood clotting disorders.
Approximately 5% to 8% of couples with a history of
recurrent pregnancy loss have an abnormal karyotype, usually
a balanced translocation. A balanced translocation is a
rearrangement of chromosomes in an otherwise normal person
that markedly increases that persons risk of producing
abnormal eggs or sperm, leading to an increased risk for
miscarriage and birth defects. PGD can be performed for
couples with a balanced translocation, allowing them to
implant only chromosomally balanced embryos, thus reducing
their risk of miscarriage. The use of PGD for translocations
is technically more complicated than for aneuploidy.
Patients with a translocation should be referred to a
genetics counselor to review their options. A referral for
PGD at a center with experience in this type of analysis can
then be made if the couple desires it.
 Fertile
couples with repeated miscarriages should be evaluated for
the presence of a chromosomal abnormality. The female or
male partner may be a carrier of a balanced translocation or
be an aneuploid mosaic.
Even after undergoing a complete work-up, many couples have
no identifiable cause for their miscarriages, and therefore
no standard treatment options. Without treatment, couples
with recurrent miscarriage have a 55% to 70% chance of a
successful live birth, depending on how many miscarriages
they have had and whether they have any previous normal
full-term pregnancies. Thus, expectant management with close
follow-up (no treatment or intervention) is a reasonable
option for these patients. For couples desiring a more
aggressive approach, PGD may be offered for significant
reduction (by more than 50%) of the risk of first-trimester
miscarriage due to an abnormal number of chromosomes.
Next :
Unsuccessful IVF Cycles (>2)
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