PGS: Important Components Of Chromosome Testing
Published: 12/11/2015
ACFS strongly believes that chromosome testing alone is not the sole reason
for our significantly improved success rates. Although, it is overwhelmingly
the most important component, without the "best" eggs, an excellent
embryo/blastocyst culture system, an excellent
freeze-thaw program (vitrification),
excellent trophectoderm biopsy techniques using
laser and
uterine transfer techniques, the team at ACFS does not think that they would
get the same results.
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ACFS strongly believes that every woman is genetically pre-determined to
make a certain amount of eggs on each stimulation cycle.Because of age,
reproductive function gets hammered, mainly because of
chromosome abnormalities,
not because ACFS cannot get you good
day 5 blastocysts. That is why it
is important to be aggressive in
COH (controlled ovarian hyperstimulation)
to get the most and best number of eggs possible; because only some
embryos will make it to blastocysts, than only some will be
chromosomally normal.
If not stimulated appropriately/aggressively you may still get a lot of
eggs but they may be of poor quality producing "poor" quality
embryos that may or may not develop to the blastocyst stage. Even if they
develop into a blastocyst (day 5 embryo) they may be
"incompetent" and not implant and/or have a
higher risk of miscarriage (not related to being chromosomally abnormal).
Alternately, if not stimulated appropriately, you will get fewer eggs than
you are genetically pre-determined to make; and they may also be of
decreased quality, either not fertilizing and/or producing poor quality
embryos that do not implant. ACFS believes that
understimulation is a one of the most important factors
in why a woman has an unsuccessful IVF cycle.
There is of course the concern about
OHSS or ovarian hyperstimulation syndrome. In its severe form, you can be hospitalized and are "very"
sick. OHSS can be avoided by not getting the patient pregnant; in other
words,
cryopreserve or freeze (vitrification)
all the embryos, and later transfer than in a subsequent cycle. Also, by
not transferring the embryos the woman can be placed on medications that
will significantly abate the symptoms of OHSS. Because of the fear of
OHSS, some clinics
back off stimulation, or will "coast" the patient or increase
the amount of medication if not responding well. ACFS respectfully
disagrees with this approach and feels that these cycles should be
canceled rather than trying to "rescue" the cycle and
re-stimulated in a subsequent cycle.
This thinking may support ACFS speculation that "conservative"
stimulation protocols may lead to aneuploidy or chromosome
abnormalities.And supports ACFS thinking about not under-stimulating
patients and to maximize their genetic potential, whatever it is.
Also, ACFS data shows that pregnancy rates are decreased if you transfer
embryos back in a fresh physiologically overstimulated cycle. You may than
ask, "than don't physiologically overstimulate me". The
problem is if you are not mildly "overstimulated", you may not
make the "best" quality eggs/embryos.
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ACFS no longer does day 3 embryo biopsy and a fresh embryo transfer. ACFS
published a study in June 2011
showing that 64% of day 3 biopsied embryos that make "nice"
looking blastocysts but that come back chromosomally abnormal, if
re-biopsied on day 5, "self-correct" and are chromosomally normal.
Also, it has been shown that embryos like group culture and if biopsied on
day 3 have to be separated and kept in their own individual culture dishes
in order to keep tract. It would also mean a fresh transfer in a potentially
physiologically "overstimulated" cycle. And since only the
"best of the best" embryos make it to day 5; if embryos do not
make it to the blastocyst stage (stage 5) than no biopsy is done and the
patient not only knows the answer sooner rather than waiting for the results
of the day 3 biopsy; but also saves a considerable amount of money by not
doing a transfer.
ACFS has not done day 3 transfers in the last 4-5 years with or without
chromosome testing.
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But than you may ask, "is a
frozen or cryopreserved cycle as good as a fresh cycle?"
In ACFS experience, a frozen cycle is better than a fresh cycle.
Why? For three reasons. First, you do
not want to put embryos back in a "physiologically"
overstimulated cycle (having adverse effects on endometrial receptivity
and endometrial DNA patterns); second, only the
"best of the best" embryos survive the freeze-thaw process; and
third, it significantly decreases (or can eliminate) the
risk of OHSS. This is based on the assumption that your ART laboratory
operates at a high level of excellence. ACFS was not able to say this 5-6
years ago, but if your embryos were not able to reach the blastocyst stage
(day 5) in ACFS-ART laboratory culture system, than they would not have
made it in you if they were transferred. The same is true of frozen
embryos, if they do not survive the
freeze/thaw process (vitrification)
at ACFS than they would not have survived in a fresh transfer. There are
clinics that disagree with these conclusions but the overall experience at
ACFS is quit the opposite. Recent reports in the literature (ESHRE, July
2012) support ACFS conclusions. Initial meta-analysis on this subject
indicates that the chance of a clinical pregnancy is approximately 30%
higher when all the embryos are
frozen or cryopreserved
(vitrification) for later transfer than with fresh embryo transfer. We
have not done a day 3-embryo transfer for the last 4-5 years; and as shown
from our data above, we feel very comfortable with our freeze/thaw (or
vitrification) program which is a very critical part of doing
PGS-chromosome testing.
This also works out quite well because if you are doing
chromosome testing, the
embryos are cultured out to
day 5 or the blastocyst stage,
than biopsied. Since you do not get the results in time to do a fresh
transfer, all the
embryos are cryopreserved and
transferred in a subsequent cycle (FET-frozen embryo transfer); thus avoiding transferring them back in a "physiologically"
overstimulated cycle and also avoiding the risk of
OHSS. Two very
important advantages.
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ACFS knows what it is asking, that women not do a fresh transfer and wait to
do a
FET or frozen embryo transfer. The goal however, "is not to see how fast we can do the
procedure" but to maximize the chances of getting pregnant on the first
attempt at IVF. ACFS' data clearly supports this premise. Even if a
couple is not doing
chromosome testing, they
should consider not doing a fresh transfer in a physiologically
overstimulated cycle,
cryopreserve all their embryos and
subsequently do a
frozen embryo transfer (FET)
the following cycle. Most folks than say, "but data shows that fresh is
better than frozen". Actually, in ACFS experience this is not accurate.
Why? Because in a regular IVF cycle without chromosome testing,
the "best" looking embryos (morphologically normal)
are transferred in that fresh cycle and the "remaining" embryos
are than cryopreserved. Statistically, however, "these remaining
embryos" tend not to be the "best embryos" (hence, why they
were frozen instead of transferred). Subsequently, when doing a future
FET with these "lesser
quality" embryos, pregnancy rates are not as good. In contrast, if ALL
the embryos had been frozen, and
only the ones that survived the freeze-thaw process were transferred,
pregnancy rates would be as good, if not higher, than a fresh transfer.
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The "easy" job at ACFS is to get good day 5 blastocysts, even in
reproductively older women. ACFS is very good at that and can control the
whole thing-from
ovarian stimulation (COH),
fertilization using ICSI, blastocyst culture developing the
embryos to day 5, the
freeze-thaw process (vitrification)
and uterine transfer. Where we "lose" control is whether or not
the embryos are chromosomally normal. That is out of ACFS control.
Therefore, it is ACFS thinking, "If you can not control it than
maximize it".
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A very important component of
chromosome testing (PGS) is
the skill and expertise of the embryologist doing the biopsy. There are only
a limited number of embryologists that had the expertise and experience to
safely and effectively do day 5 blastocyst biopsies with
laser.
ACFS embryologist has done over
1500 blastocyst biopsies without harming a single embryo.
This is not the kind of procedure that you would want done by someone
that does not do it on a regular basis.
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ACFS also recommends that reproductively older women, in addition to doing
chromosome testing, also consider doing two stimulation cycles. The first
cycle would be to only get eggs which would be
cryopreserved (vitrification) and
than let the patient get her period. In one or two months, she would
stimulate again. Than, the eggs from the first stimulation cycle would be
thawed and along with the fresh eggs from the second stimulation cycle, and
all be fertilized; only paying one
ICSI charge, one
advance culture (blastocyst) charge,
one TE biopsy and
chromosome charge. The
advantage of doing this is that as women get reproductively older they make
less eggs/embryos that advance to day 5 blastocysts and that are
chromosomally normal. By doing two stimulation cycles, you get twice as many
eggs/embryos that have a chance to reach the blastocyst stage and be
chromosomally normally; thus increasing pregnancy rates and decreasing
costs. This all depends on the ART-IVF lab having an excellent
egg vitrification or vitrification
program. ACFS data shows that egg vitrification or freezing is as good as
using fresh eggs.
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ACFS does not transfer using ultrasound guidance and has data showing that
it is not necessary. By not using ultrasound guided uterine embryo transfer,
it is much more comfortable for the patient by not having 32-40 oz. of water
in the bladder and having a large speculum in the vagina while someone is
pushing down abdominally on your bladder. ACFS did an internal study
approximately 8 years ago and showed the uterine embryo transfer (ET) with a
mock transfer first was actually more successful than ultrasound guided ET.
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ACFS does not do this for money. We do
chromosome testing (PGS) at
our cost because we want all patients to consider doing PGS with their
IVF cycle. Hopefully, by a
patient getting pregnant on their first attempt, ACFS loses money by not
doing multiple attempts at either a fresh and/or multiple
FETs (frozen embryo transfer). If there are no remaining chromosomally normal embryos, ACFS losses
it's
freezing fees and storage fees.
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Is ACFS biased with its IVF success rates? Absolutely, we are. But it is
biased solely in favor of the patient. We do not think that any woman would
knowingly want to transfer chromosomally abnormal embryos. By knowing that
you have chromosome normal day 5 blastocysts that survived the freeze-thaw
process, ACFS is absolutely biasing the results. But that's a good
thing.
WHAT DO YOU THINK WILL HAPPEN IF YOU TRANSFER TWO NICE LOOKING DAY 5
BLASTOCYSTS THAT ARE CHROMOSOMALLY COMPETENT AND HAVE SURVIVED THE FREEZE-THAW
PROCESS WITH AN UNEVENTFUL UTERINE TRANSFER?