from
the book How to Have a Baby: Overcoming Infertility
by Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani,
MD.
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What
is PGD ( preimplantation genetic diagnosis) ?
How
is PGD done ?
What is PGD
( preimplantation genetic diagnosis) ?
PGD, or preimplantation genetic diagnosis,
is a new technique, which marries the recent spectacular
advances in molecular genetics and assisted reproductive
technology. Preimplantation genetic diagnosis enables
physicians to identify genetic diseases in the embryo,
prior to implantation, before the pregnancy is established.
PGD was first developed for patients
who were at risk of having children with serious genetic
disorders, which often discouraged them having their
own biological children. These couples are often faced
with attempting a type of "Russian Roulette" to have
children, many times having to confront the difficult
decision to terminate an affected pregnancy.
Consider a woman known to be carrying
an X-linked disease with a 50% risk of an affected male
in each pregnancy. In addition, her daughters have a
50% risk of being carriers, but are unlikely to be clinically
affected. She may not wish to become pregnant if she
has to make decisions about an affected child in a viable
pregnancy. However, she would become pregnant if she
knew she had conceived a daughter, and with preimplantation
diagnosis this possibility becomes a reality. PGD thus
eliminates the need for possible pregnancy termination
after prenatal diagnosis of a genetically-affected fetus.
Research has shown that it is possible
at three days after fertilisation to remove one or two
cells from an 8-10 celled embryo without detriment to
its further development. Embryos were sexed on the basis
of the presence or absence of a DNA fragment specific
for the Y chromosome; in 1990 two sets of twin girls
were born to five couples at risk of passing on an X
linked disorder. Subsequently, a number of babies have
been born after the preimplantation genetics has ruled
out diagnosis of cystic fibrosis, Tay Sachs disease,
Lesch Nyhan syndrome, Duchenne muscular dystrophy and
for diseases carried on the X chromosome.
Sexing the embryo to avoid X linked
disease remains the commonest reason for preimplantation
diagnosis, now optimally carried out by the molecular
cyto genetic technique of FISH (fluorescent in situ
hybridisation) with DNA probes derived from the X and
Y chromosomes.
How
is PGD done ?
How is PGD done? After IVF, on the 3rd day, the 8-cell
embryo is biopsed. to obtain blastomeres (single cells)
for molecular diagnosis. An embryo biopsy is done using
micromanipulators under the visual control provided
by an inverted tissue culture microscope. The embryo
is held in position using a holding pipette, while a
glass needle is used to drill a hole through the zona
pellucida (the shell or the outer layer of the embryo
) using a laser or acid Tyrode's. A single cell is then
removed by gentle suction. The cell (called a blastomere)
is then available for genetic diagnosis.
Fig 1. Embryo biopsy, with a single blastomere being
sucked out from the 8-cell embryo. This will be sent
for analysis.
Analysis of genetic material (DNA) from
a single cell is performed either using a technique
called FISH ( fluorescent in situ hybridisation) or
PCR ( polymerase chain reaction) . FISH utilises fluorescent
probes, which are specific for a given chromosome, and
therefore allows one to screen embryos for chromosomal
normality. PCR allows one to amplify (mutiply ) a selected
DNA sequence of interest, so that it can be analysed.
After the analysis on the single cell, the embryos are
kept in culture and allowed to further divide. Once
the appropriate molecular diagnosis is made, unaffected
embryos can be transferred back into the uterus in the
IVF cycle.
PGD is now also being used in order
to increase pregnancy rates for older infertile women.
One of the reasons older women have a poorer pregnancy
rate is because their embryos are often chromosomally
abnormal, because of the fact they have older eggs (
which may have genetic defects). PGD allows the doctor
to select only the chromosomally normal embryos, so
that only these can be transferred back into the uterus,
resulting in a higher pregnancy rate.
While PGD represents the cutting edge of reproductive
technology, and gives us an idea of what may be possible
for the future, it also raises a number of worries and
concerns, especially in India, where people are worried
that it may be used for sex-selection.
PGD is emotionally a very touchy area,
because not only are we dealing with human embryos -
the very start of new life, but we are studying their
basic blueprint - their genes - the stuff of which humanity
is made. Obviously, this is likely to cause people to
take very strong views on what is right and what is
wrong - so that they start thinking with their hearts
rather than their heads ! Many people confuse PGD with
genetic engineering. A familiar refrain is we shouldn't
be doing any of this because scientists are becoming
too big for their boots - they are trying to play God
by tinkering with the genes , and it is far better that
they leave this entire field well alone, since we will
never be able to understand any of it - it is beyond
human wisdom. This is a common knee-jerk reaction, which
precludes further rational debate.
The other view point is - Why not ?
If man can improve on Nature, then why should he not
try? After all, building a house is simply man's way
of improving on nature - and if we can improve man himself,
then why not? Seen in this light, then studying the
molecular genetics of the human embryo would be the
ultimate goal of all medicine. In the past, doctors
used to treat adults. In the beginning of the 20th century,
we started treating children, and the field of pediatrics
was born. We can now treat the fetus - and the future
patient of the 21st century will be the embryo - this
is a logical progression!
If we allow people to choose when to
have babies; how many to have; and even to terminate
pregnancies if they inadvertently get pregnant, then
why not allow them to select the sex of their child,
if it is possible?
We should allow patients freedom to
choose for themselves - medical technology should empower
them with choices they can make for themselves! A common
criticism against PGD for sex selection is that it will
cause an unbalanced sex ratio. In reality, PGD will
allow couples to balance the sex ratio in their families,
rather than unbalance it! For example, take a couple
with a baby girl, who want to have a second baby. If
they leave things upto chance, half of them will have
a second baby girl - causing unbalanced intrafamily
sex ratios ! PGD will allow them to make sure that they
have a balanced sex ratio in their family, if they so
desire. Seen in this light, PGD is perhaps the ultimate
form of family planning there is!
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