Establishing a diagnosis
The laboratory report of the PGD chromosome screening will
have a table (shown below) that lists the embryo number and
the number of signals observed for each chromosome. After
the list of observed signals for each chromosome, the
individual result for the cell and, finally, the embryo will
be listed to aid in decision making.
Normal embryos show two signals for the numbered chromosomes
and either 2 X chromosomes (female) or 1 X and 1 Y
chromosome (male). Abnormal embryos show a numerical
abnormality of a single chromosome i.e. trisomy (three
copies), monosomy (1 copy) or nullisomy (no copies). Embryos
are said to have complex abnormalities if more than a single
chromosome is abnormal. These embryos are also called
chaotic, and are the most frequently seen abnormalities,
comprising half of all abnormal embryos. This type of
complex abnormality arises when an already abnormal embryo
encounters additional abnormal cell divisions resulting in
an almost random distribution of chromosomes in subsequent
cells. Embryos with this type of chromosome abnormality will
not produce ongoing pregnancies.
In order to obtain results of the biopsy, the cell removed
must contain a nucleus, as the nucleus contains the genetic
information necessary for testing. If the cell removed has
no nucleus or if the nucleus ruptures during the extraction
or fixation process, that cell cannot be scored for
chromosome problems. As embryos are actively dividing,
sometimes the biopsied cell contains two nuclei (as the cell
was preparing to divide). Most often, embryos which contain
such ?binucleate? cells are abnormal. Both of these
situations may not allow a PGD result to be interpretable
for that particular cell. This is one of the reasons we try
and take two separate cells to analyze whenever possible.
Those embryos considered to be unaffected on the basis of
the PGD testing will then be available to be transferred
into the woman's uterus or cryopreserved for future use.
The establishment of a diagnosis in PGD is not always
straightforward. The criteria used for choosing the embryos
to be replaced after FISH results are not equal in all
centres. In some centres only embryos are replaced that are
found to be chromosomally normal (that is, showing two
signals for the gonosomes and the analysed autosomes) after
the analysis of one or two blastomeres, and when two
blastomeres are analysed, the results should be concordant.
Other centres argue that embryos diagnosed as monosomic
could be transferred, because the false monosomy (i.e. loss
of one FISH signal in a normal dipoloid cell) is the most
frequently occurring misdiagnosis. In these cases, there is
no risk for an aneuploid pregnancy, and normal diploid
embryos are not lost for transfer because of a FISH error.
Moreover, it has been shown that embryos diagnosed as
monosomic on day 3 (except for chromosomes X and 21), never
develop to blastocyst, which correlates with the fact that
these monosomies are never observed in ongoing pregnancies.
Accuracy and Interpretations