Preimplantation
genetic diagnosis enables us to identify genetic
diseases prior to embryonic attachment to the uterus
(before pregnancy is established) and eliminates the
need for possible pregnancy termination after
prenatal diagnosis of a genetically affected fetus.
At CRH PGD is available to couples who have a
known genetically transmittable disease, to those
who have had a child with a genetic disease in the
past and to other couples at risk (i.e., advanced
maternal age). Preimplantation genetic diagnosis
should reduce the psychological trauma experienced
by couples who carry a genetic disease, as it allows
intervention before pregnancy is established.
The basic procedure underlying
PGD involves removing a cell from an embryo
resulting from in vitro fertilization, analyzing the
genetic material, and then transferring the embryo
into the uterus if the analysis does not indicate a
the presence of a disease.
Recent knowledge indicates that 60% of embryos have
abnormalities in women older than 35.
Preimplantation genetic diagnosis offers the
potential to screen for embryos with aneuploidy (unusual
number of chromosomes).
Once perfected, the net result should be a decreased
miscarriage rate, increased pregnancy rates and
lower incidence chromosomal anomalies.
At CRH we offer screening for inherited
autosomal
recessive disorders, where the specific gene defect
is identified¶
(i.e., Tay Sachs disease, cystic fibrosis). We also
offer PGD & sex selection to avoid X-linked
disorders§ (i.e., Duchenne's, muscular
dystrophy, Lesch Nyhan syndrome). With some X-linked
disorders (e.g. Duchenne’s muscular dystrophy) the
specific defect can now be identified in a
proportion of families, which means that male
embryos free of the disorder can now be implanted
along with female embryos. PGD has also been used to
test for autosomal dominant conditions£,
the gene predisposing to polyposis coli (and
inherited cancer of the colon) and Marfans
syndrome). As new tests become available this list
will continue to grow.
A further reason for requesting PGD at CRH is when
one partner is at high risk of transmitting a
chromosome anomaly, such as a translocation. Such
couples have often experienced repeated miscarriages
and periods of infertility and are already receiving
assisted conception treatment. For such patients,
PGD may be a way to achieve a successful pregnancy
where they would otherwise have difficulty. In some
instances, PGD may also help individuals at risk of
having a child with severe developmental problems
because of a chromosomal imbalance.
Sexing embryos to avoid X-linked disorders and
testing for age related aneuploidy are indications
for PGD in this center.
The future promise of preimplantation genetic
diagnosis is immense. The number of diseases that
can be detected will dramatically increase with the
aid of the data now being collected for the Human
Genome Project.
The
first step to PGD is creating embryos outside the
body by IVF. A biopsy is then carried out to remove
a cell from the developing embryo, which can be used
to test whether the embryo carries a genetic
disorder. The first and/or second polar body can be
removed and used to determine the genetic status of
the mothers' chromosomes. The genetic diagnosis of
the biopsy cells is attempted using one of two
diagnostic techniques: fluorescent in situ
hybridization (FISH), for chromosome disorders, and
polymerase chain reaction (PCR), for single gene
defects. Tags are used for the particular
chromosomes involved in the translocation (transfer
of part of a chromosome to a new position on the
same or on a different chromosome with resultant
rearrangement of the genes)
so that only unaffected embryos are transferred.
The DNA from a single cell is incubated with primers
which bind close to the gene sequence of interest,
and with the addition of an enzyme, thousands of
copies are made of the relevant section of DNA. The
resulting DNA fragments can be analyzed by a number
of different techniques to determine whether the
single cell was at risk of the genetic disease.
