The American College of Medical Genetics along with
the American College of Obstetrics and Gynecology
has recommended that all couples of reproductive age
who are considering establishing a pregnancy be
offered genetic testing for carrier status for
multiple genetic diseases. Testing potential parents
for carrier status of genetic diseases is not a
novel concept, but with the completion of the Human
Genome Project, the DNA sequence information for
many single gene disorders has rapidly grown and is
now allowing for the detection of multiple
mutations.
Carriers of genetic disease do not manifest the
disorder themselves, but if both parents are
carriers of the same mutation, their child will have
a significant chance of suffering from a serious
genetic disease. The most common of these disorders
have an autosomal recessive mode of inheritance
where statistically 25% of children born to a couple
who are both carriers will actually have the
disease, 25% will not have the disease or even be
carriers, and 50% will be carriers of the gene but
will usually have no symptoms of the actual disease
in question.
Without parental genetic testing, parents can be
shocked to learn that they have a child with a
serious or even fatal disease because the parents
themselves are healthy individuals who happen to be
asymptomatic carriers of a mutant version of a
critical gene. Testing of parents prior to
conception is the only way to know if your pregnancy
will be at increased risk of resulting in a child
with one of these inherited disorders. If both
partners are determined to be carriers of a specific
abnormal gene, there are actions that can be taken
to dramatically improve the chances of having a
child without the genetic abnormality. Couples who
present to an infertility clinic specifically to be
evaluated for single gene abnormalities often have
no barriers to conceiving. They are candidates for
preimplantation genetic testing solely to eliminate
the risk of having a child born with one of these
serious or fatal conditions.
In the past, there was only one way to perform
accurate genetic testing on prospective parents:
patients have their blood drawn for a serum
karyotype, or chromosome analysis. This test allows
the physician to confirm that each partner has a
normal number of chromosomes and that there are no
obvious gross abnormalities within those
chromosomes. This type of testing does not, however,
enable the physician to screen for specific genetic
diseases. Until recently, that could only be
accomplished through the performance of
individualized genetic tests, a very expensive and
arduous process. In addition, this process was
further complicated by the fact that only a small
number of genetic diseases could actually be
screened before the process became prohibitively
expensive.
Due to tremendous advances in genetic science, two
new types of genetic testing are now available. One
involves the collection of saliva from each partner.
Each sample can be screened for over 109 different
autosomal recessive genetic disorders for a
reasonable fee. In the event that only one partner
is found to carry the gene for an autosomal
recessive disorder, there is no chance that the
couple’s children can actually have the disease in
question; the worst outcome possible would be that a
child could be an asymptomatic carrier of the
abnormal gene – just like the affected parent. In
the event that each partner has a genetic defect
involving the same gene, i.e. they are both
carriers, then there would be a one in four chance
that any resulting offspring would actually have the
disease in question. There would be a one in two
chance that any offspring would be a carrier of the
disease, and therefore asymptomatic, and there would
be a one in four chance that any offspring would be
totally unaffected. The primary advantages of this
particular test are that it is performed on saliva,
rather than blood, it screens for a large number of
diseases very efficiently, and it is relatively
inexpensive.
The other type of test actually looks at pieces of
genes, rather than any whole gene or chromosome.
Through the testing of tissue obtained from either a
cheek swab or blood from each partner, 200-300,000
small DNA fragments representing pieces of each
known gene can be evaluated. When an embryo
resulting from in vitro fertilization is produced,
the DNA from each embryo can be evaluated and
screened as well. Not only can this testing
determine whether each embryo has the normal number
of chromosomes, but in addition the source of any
identified genetic abnormality can be accurately
identified. In other words, in the event that an
embryo turns out to be chromosomally abnormal, this
testing can determine whether the abnormality came
from the egg or from the sperm. This is very helpful
in cases of recurrent miscarriage or in cases of
repetitive in vitro fertilization failure when
couples are struggling to determine whether they
should continue to proceed with treatment using
their own gametes or whether they should consider
using either donor sperm or donor oocytes.
An example that we commonly see at TFC is a couple
with a history of recurrent miscarriage who has a
completely normal basic evaluation. They decide to
proceed with IVF using this new testing procedure.
Although several of their embryos on Day 3 look
normal, the embryo biopsies show that, in fact, each
embryo is chromosomally abnormal. In the past, we
would be unable to answer the basic question of what
they should do next. By default, many fertility
specialists would recommend the use of donor eggs –
without actually knowing if that was the source of
the problem. Now with this testing, our physicians
can confidently determine whether the defect
originates in the egg or the sperm, and using this
information, they can help our couples determine the
appropriate next step in their treatment.
These two new technologies represent a major advance
in the field of genetics and offer our patients new
hope for achieving their dream of a healthy family.
