2009 Vienna - European Society of Human Genetics

Prenatal and perinatal genetics
objective case management. It is especially valuable in genetic diseases
with low penetrance, late onset conditions and cancer predispositions.
P05.49
medical outcome of children born after PGD for HLA matching
M. L. Bonduelle, S. Desmyttere, W. Verpoest, H. Van de Velde, M. De Rycke,
I. Liebaers;
UZBrussel, Brussel, Belgium.
PGD (Preimplantation Genetic Diagnosis) with HLA (Human Leukocyte
Antigen) matching allows to select unaffected, HLA compatible
embryos to cure an affected sibling. Data on 27 pregnancies conceived
after PGD-HLA between 2004 and 2008 are reported. Children
were examined at the age of 2 months, 1 and 2 years at our centre to
analyse the medical outcome.
The PGD-HLA procedure was applied to 175 cycles for 65 couples.
Indications were Beta thalassemia, Severe Combined Immune Deficiency
syndrome, Wiskott Aldrich syndrome, Fanconi Anemia, Acute
Lymfatic Leukemia, Sickle cell anemia, Duncan’s syndrome, Acute
Myeloid leukemia, hyper IgM syndrome, Diamond-Blackfan anemia.
These treatments resulted in 79 transfers, 27 pregnancies (3 biochemical,
5 miscarriages, 5 still ongoing) and 14 deliveries (1 twin, 13
singletons). Outcome data are missing for one child. Four boys and 10
girls had a mean birth weight of 3256 ± 637 grams (2300 to 4650 gr) at
a mean term of 38.3 ± 1.6 weeks (36 to 42 weeks). One girl had a left
eye congenital cataract. Three siblings underwent a successful transplantation
of haematopoietic cells. One affected child died before the
birth of the HLA compatible sibling. Another ill child was transplanted
with bone marrow from an allogenic donor while awaiting the birth of
the HLA compatible sibling. The other affected children have as yet
not been transplanted.
Children born after PGD-HLA appear to be in good health. These preliminary
data will be further evaluated in a larger long-term follow-up
study including medical and psychological outcome of child and family.
P05.50
Polar body diagnosis for female translocation carriers applied
during conventional iVF treatment
M. Maurer 1 , T. Ebner 2 , C. Duba 1 ;
1 Humangenetische Untersuchungs- und Beratungsstelle, Landes- Frauen- und
Kinderklinik, Linz, Austria, 2 IVF-Kinderwunschabteilung, Landes- Frauen- und
Kinderklinik, Linz, Austria.
Objective: Carriers of reciprocal and Robertsonian translocations
are faced with increased reproductive risks depending on the chromosomes
which are involved in the chromosomal rearrangements.
According to the restrictive legal situation in Austria, preimplantation
genetic diagnosis is limited by law to polar body diagnosis (PBD).
Polar body diagnosis was therefore offered and used to identify balanced/normal
and unbalanced oocytes.
Materials/Methods: Polar body diagnosis using FISH (fluorescence
in-situ hybridisation) was performed for 9 couples with the female carrying
a translocation during conventional IVF cycles. We used translocation
specific combinations of distal and proximal probes to the
breakpoint, which allowed differentiation of unbalanced and balanced
oocytes.
Results: Polar body diagnosis was performed for 14 cycles of translocation
diagnosis (7 cycles for reciprocal; 7 cycles for Robertsonian
translocations).
After PBD only 19 % of oocytes were diagnosed as normal/balanced
and 81 % showed an unbalanced chromosomal content. From 14 cycles
performed, only 4 cycles (28,6 %) had euploid oocytes available,
71,4 % showed solely aneuploid oocytes.
Conclusion: In this study, we found a higher than average aneuploidy
rate in oocytes of female translocation carriers. Interestingly, patients
with Robertsonian translocations showed more euploid oocytes than
carriers of reciprocal translocations. The high rate of chromosomally
unbalanced oocytes lead to the conclusion, that for carriers of maternal
translocations who already need IVF treatment for infertility, polar
body diagnosis is a valuable additional selection tool. Screening for
imbalance in cases with increased risk of viable chromosome abnormality
might help to decrease miscarriages and pregnancy termination
after prenatal diagnosis.
P05.51
Preimplantation Genetic Diagnosis: international Regulatory
Approaches
B. Knoppers1,2 , T. Nguyen1 ;
1 2 Centre for Public Law, Montreal, QC, Canada, Canada Research Chair in
Law & Medicine, Montreal, QC, Canada.
In the last decade, innovations in reproductive genetic testing and human
genomic research have altered the policy and legal approaches
surrounding reproductive choices. Innovations in both prenatal diagnosis
(PND) and preimplantation genetic diagnosis (PGD) provide
prospective parents with information regarding phenotypic or genetic
traits, health status and the sex of their offspring. This information
has important implications for reproductive decision-making yet, reproductive
choices must be weighed against broader ethical, legal or
social issues particular to each diagnostic procedure. Contradictory
views and opinions abound in different countries creating an inconsistency
in the manner in which PND and PGD are regulated. This
is due to the presence or absence of universal health care systems
and to demographic, cultural or socio-economic factors that underlie
different regulatory approaches. The aim of this article is to provide
an analysis of current laws and policies regarding PND and PGD and
the regulatory trends in sixteen different countries: Australia, Belgium,
Canada, China, France, India, Israel, Japan, Netherlands, New Zealand,
Singapore, Switzerland, South Africa, Spain, United Kingdom
and the United States. Our analysis shows that, despite the similarities
between PND and PGD in terms of their uses and outcomes,
PND is progressively considered part of routine prenatal care while
the various uses of PGD, although expanding, are being heavily scrutinized
resulting in the tendency for greater regulatory oversight by the
majority of countries surveyed. Such scrutiny requires making explicit
both the reasons for additional indications for PGD and the justifications
for prohibitions, if any.
P05.52
Preimplantation Genetic Diagnosis for complex chromosome
rearrangements
P. Gosset 1 , M. Fradin 1 , C. Retter 1 , M. Schillinger 1 , M. Minz 2 , F. Vialard 3 , S.
Viville 1 ;
1 SIHCUS-CMCO, Schiltigheim, France, 2 Centre Cytogénétique - Diagnostic
Pré Natal, Laboratoire Clément, Le Blanc-Mesnil, France, 3 Laboratoire Biologie
de la Reproduction et Cytogénétique, CHI Poissy Saint Germain, Poissy,
France.
Chromosomal rearrangements are relatively common: around 1 individual
out of 1000 is carrying a Robertsonian translocation, 1/1000 a
balanced reciprocal translocation, 1/10000 an inversion.
The probability of having a couple where both member is carrying
such an abnormality is around 4.4 by million, i.e. around 50 couples in
age to procreate in France.
Preimplantation Genetic Diagnosis (PGD) is offered to patients having
a risk to transmit a genetic disease to their offspring.
PGD is frequently used for single chromosomal rearrangement, using
fluorescence in situ hybridisation techniques (FISH) on embryo’s cell
nuclei.
In case of complex chromosomal rearrangement (CCR) PGD faces
two major difficulties, I) the chances of having an unaffected embryo
are low, II): technical difficulties are increased to diagnose all possible
unbalanced karyotypes in embryos.
Two couples having PGD for CCR are presented here:
- Couple 1: 45,XY,der(14;21)(q10;q10) and 46,XX,inv(10)(p13q11.2)
- Couple 2: 45,XY,der(15;21)(q10;q10) and 46,XX,t(1;9)(q25;q34.1)
Chances for having balanced embryos were estimated as sufficient to
offer PGD to these couples.
We described here the development of specific FISH techniques for
these PGDs, allowing an accurate analysis in a short time compatible
with the necessity to rapidly replace embryos into uterus.
PGD resulted in pregnancy for each couple, but one terminated in
spontaneous abortion.
This work supports the idea that PGD can be efficiently offered to
couples with complex chromosomal indications if I) the proportion of
expected balanced embryos is sufficient and II) a reasonable number
of oocytes can be obtained by ovarian stimulation.