PGD in Italy: 1PB Testing
genetic diagnosis by 1PB testing only provides
information about the maternal genotype; it cannot be
used in cases of paternally derived autosomal dominant
Preimplantation HLA matching (Verlinsky et al., 2001;
Fiorentino et al., 2004, 2005; Van de Velde et al.,
2004), to conceive a healthy child who could become a
future umbilical cord blood donor of hematopoietic stem
cells for the treatment of existing affected sibling,
would be not possible.
To perform an indirect linkage analysis-based diagnosis,
a family pedigree must be obtained and DNA from family
members (existing children of the couples, maternal
parents or DNA obtained from previous prenatal
investigations) should be tested to determine which
allele combination is associated with the maternal
mutation. Hence, the technique will not be applicable
for de novo mutations and in those cases where relatives
are unavailable or unwilling to cooperate.
The high rate of heterozygosity found in 1PBs (56.2% and
61.1%, for CF and ?-thalassemia genes, respectively)
greatly reduces the number of oocytes available for
selection because no assertion on the status of the
corresponding oocytes could be made. The probability of
a crossing over occurrence is a function of the distance
of the gene from the centromere. Since βT and CF genes
are located in the telomeric region of their
chromosomes, the reported high recombination rates were
widely expected. However, a more centromeric location of
other genes (e.g. DMD, SMN1, ATRX, PMP22, etc.) could
result in a lower recombination rate, providing a
greater number of oocytes available for ICSI.
A poor ovarian response to hormonal hyperstimulation, is
also known to have a major impact on the number of the
retrievable oocytes and, consequently, on the number of
oocytes available for analysis, reducing the chance of
finding mutation-free oocytes to be fertilised.
Therefore, several IVF cycles may be necessary to obtain
a pregnancy and a live birth.
The achievement of a high fertilization rate also
represents a critical factor, and the consequences of a
delayed ICSI on fertilization rate should be evaluated.