1. VIEWS AND REVIEWS
Introduction:
Preimplantation genetic screening
is alive and very well
David R. Meldrum, M.D.
Reproductive Partners Medical Group, Redondo Beach, California
Aneuploidy screening of all chromosomes (preimplantation genetic screening) at each stage of embryo development, the techniques
available, and the advantages and disadvantages of each technique are reviewed. (Fertil Steril
2013;100:593–4. 2013 by American Society for Reproductive Medicine.)
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Because many couples have de-layed
starting their families un-til
the woman is in her late 30s
or early 40s, the percentage of embryos
with aneuploidy can exceed 60%, re-sulting
in a high proportion of futile
transfers and a risk of miscarriage that
can be R40%. In countries and states
where IVF is covered financially, cou-ples
still drop out of treatment because
of their inability to cope with repeated
failures. We are in great need of tech-niques
that can identify embryos with
the capacity to result in a healthy
newborn, make the process more effi-cient,
and keep intensive failed cycles
to a minimum. These techniques will
allow us to increase the number of cy-cles
with transfer of a single embryo,
thereby minimizing pregnancy compli-cations
and maximizing neonatal
outcomes.
The profound impact of nonviable
pregnancies on our IVF couples is pain-fully
apparent to all of us, but it has not
received sufficient emphasis because
until now prevention was not clearly
possible. However, as series of 24-chro-mosome
preimplantation genetic
screening (PGS) have now appeared in
abstracts and in early publications it
is apparent that the rate of miscarriage
is running at about 5%–10%, a remark-able
but not unexpected finding. We all
want to avoid establishing a pregnancy
where the couple observes heart motion
and progressive fetal growth only to see
it stop, followed by surgery or miscar-riage.
Losing up to 6 months from their
attempts at conception is also very sig-nificant,
particularly for older couples,
and the saved expense goes a long
way toward offsetting the costs of PGS.
The revolutionary technologies
that now allow us to confirm that all
24 chromosomes are normal are thor-oughly
reviewed by Alan Handyside,
who was the first in the world to
perform preimplantation genetic diag-nosis.
He has nicely contrasted the
pros and cons of the various techniques
that are available and has described
them in readily understandable terms.
Markus Montag has described the
earliest point at which the genetic con-tributions
of the oocyte and the sperm
can be viewed (biopsy of the first and
second polar bodies). This technique is
more commonly being used in Europe,
where a large multicenter trial is under-way.
Richard Scott has contrasted the
pros and cons of biopsy of cleaved em-bryos
compared with sampling tro-phectoderm
cells from the blastocyst.
Although there are some advantages
to polar body biopsy, it is clear that
owing to the complexities of polar
body formation, errors can occur,
including designating an embryo as
abnormal when the resulting conceptus
is normal. Regarding biopsy of the
cleaving embryo, multiple studies
have documented that biopsy reduces
viability of the embryo. Those studies
were generally restricted to couples
having good-quality embryos. For
those patients whose embryos are of
insufficient quality to recommend
further culture to the blastocyst, biopsy
is likely to compromise their develop-ment
even more. For such couples,
less invasive techniques, such as polar
body biopsy or time-lapse imaging of
embryo development may be more
appropriate.
Received June 21, 2013; accepted July 16, 2013; published online August 2, 2013.
D.R.M. has nothing to disclose.
Reprint requests: David R. Meldrum, M.D., Reproductive Partners Medical Group, 510 N. Prospect
Ave., Suite 202, Redondo Beach, California 90277 (E-mail: drmeldrum@gmail.com).
Fertility and Sterility® Vol. 100, No. 3, September 2013 0015-0282/$36.00
Copyright ©2013 American Society for Reproductive Medicine, Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.fertnstert.2013.07.1968
VOL. 100 NO. 3 / SEPTEMBER 2013 593

2. VIEWS AND REVIEWS
If we accept our current understanding that blastocyst
biopsy does not appear to affect embryo viability and gives a
high rate of diagnostic accuracy, our remaining challenges are
to decide for whom it is best suited, to optimize the number
and quality of blastocysts for biopsy, and to decide whether
transfer should be in the same cycle or at a delayed time when
the endometrium is not altered by the ovarian stimulation.
The risk of multiple pregnancies appears to be greatest in
our best responders to stimulation who produce a good num-ber
of high-quality blastocysts. By choosing those IVF cycles
for PGS, elective single-embryo transfer (eSET) can be recom-mended,
resulting in a marked decrease of twins and higher-order
multiple pregnancies. Bill Schoolcraft has described his
group's experience with PGS in couples having a mean
maternal age of 38 years having delayed eSET following
comprehensive chromosome screening (CCS) (4), with an
ongoing pregnancy rate of 60%, a rate significantly higher
than for women having delayed eSET based on morphology
alone. Of course, the cumulative pregnancy rate would have
to be compared between the two groups to assess whether
the addition of CCS increased the chance of achieving a viable
pregnancy overall. However, even if we accepted that the cu-mulative
delivery rate might be equal, the avoidance of futile
transfers, miscarriages, and maternal and neonatal complica-tions
due to multiple pregnancies and even due to transfer of
multiple embryos that result in singleton deliveries, would
more than justify the additional expense of CCS. Each indi-vidual
IVF program will have to decide along with each
couple how many blastocysts are needed to warrant biopsy.
In some instances, such as with recurrent spontaneous abor-tion,
a couple might even choose to have only one or two em-bryos
biopsied to minimize the risk of miscarriage or an
ongoing chromosomally abnormal fetus.
Blastocyst biopsy requires a highly refined laboratory
environment to achieve good success. As just three examples:
5% oxygen has been shown to increase the rate of blastocyst
development and implantation, and nonhuman studies have
documented more cells per blastocyst; for those couples not
having intracytoplasmic sperm injection it has been shown
that a brief exposure of the sperm to the oocyte for 2 hours
achieves improved embryo quality and implantation; even
the number of incubators relative to the number of cycles
will optimize embryo quality by allowing a culture environ-ment
with the fewest perturbations. The factors responsible
for producing a high-quality laboratory are far beyond
what can be covered here.
Finally, is fresh or delayed transfer preferable following
CCS? Richard Scott has demonstrated excellent success with
fresh transfer by having an on-site genetics laboratory. How-ever,
studies have been accumulating showing that delayed
transfer yields superior implantation rates, even with a slow
freezing technique (5), and improved pregnancy outcomes
by avoiding the effects of ovarian stimulation on placental
development, which may make this last question moot.
Trophectoderm biopsy with CCS and delayed transfer
promises to be a major advance for older women to achieve
optimal success and for the best maternal and neonatal out-comes
for the resulting pregnancy. All of these benefits
should translate into further success by reducing dropouts
from treatment because of inability to cope with failure,
including the profound emotional toll of losing a prized
pregnancy.
594 VOL. 100 NO. 3 / SEPTEMBER 2013