RBMOnline - Vol 8. No 2. 229-235 Reproductive BioMedicine Online; www.rbmonline.com/Article/1155 on web 22 December 2003
Report
Thirteen years’ experience of preimplantation
diagnosis: report of the Fifth International
Symposium on Preimplantation Genetics
Dr Anver Kuliev received his PhD in Clinical Cytogenetics from Moscow Research Institute
of Human Morphology in 1969. In 1979 he took the responsibility for the World Health
Organization (WHO)'s Hereditary Diseases Program in Geneva, where he developed the
community-based programmes for prevention of genetic disorders and early approaches for
prenatal diagnosis. He moved to the Reproductive Genetics Institute in 1990, where he
heads the WHO Collaborating Center for Prevention of Genetic Disorders, and scientific
research in prenatal and preimplantation genetics. He is an author on more than a hundred
papers and nine books in the above areas, including three books in the field of
Preimplantation Genetics.
Dr Anver Kuliev
Dr Yury Verlinsky is a graduate, postgraduate and PhD of Kharkov University of the former
USSR. His research interests include cytogenetics, embryology and prenatal and
preimplantation genetics. He introduced polar body testing for preimplantation genetic
diagnosis and developed the methods for karyotyping second polar body and individual
blastomeres. He has published over 100 papers, as well as three books on preimplantation
genetics.
Dr Yury Verlinsky
Anver Kuliev1, Yury Verlinsky
Reproductive Genetics Institute, Chicago, IL, USA
1Correspondence: 2825 North Halsted Street, Chicago, IL 60657, USA
Tel: +1 (773) 472 4900; Fax: +1 (773) 871 5221; e-mail: anverkuliev@hotmail.com
Abstract
Preimplantation genetic diagnosis (PGD) has been further developed into a practical option for avoiding the birth of affected
children, representing an important complement to traditional prenatal diagnosis. More than 1000 unaffected children have
been born after PGD, suggesting the accuracy and safety of the procedure, which is currently also used with the
establishment of potential donor progeny for stem cell treatment of siblings. Together with progress in the establishment of
embryonic stem (ES) cells, this may contribute to the development and application of stem cell therapy. The accumulated
experience of thousands of PGD cycles for poor prognosis IVF patients provides further evidence of the improvement of
clinical outcome, particularly obvious from the reproductive history of PGD patients. A high prevalence of aneuploidies in
oocytes and embryos may affect the accuracy of PGD for single gene disorders, making aneuploidy testing an important part
of PGD for causative genes and preimplantation human leukocyte antigen (HLA) typing. A sequential sampling of both
oocytes and the resulting embryos may improve accuracy of aneuploidy testing and may also allow the detection and
avoidance of transfer of embryos with uniparental disomies. Current developments and application of nuclear transfer and
sperm duplication techniques, and microarray technology, may also contribute to the improvement of PGD and help in the
development of PGD for genetic expression disorders.
Keywords: aneuploidy testing, chromosomal disorders, embryonic stem cells, preimplantation genetic diagnosis, preimplantation
HLA typing, single gene disorders
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Report - Report of the Fifth International Symposium on PGD- A Kuliev & Y Verlinsky
Introduction
With the expanding indications of preimplantation genetic
diagnosis (PGD) and its wider application to assisted
reproduction practices, the annual numbers of PGD cycles
performed in the last two years have almost doubled. More
than 1000 unaffected children have presently been born after
PGD, indicating further improvement in the accuracy and
reliability of this relatively novel procedure (Verlinsky et al.,
2004).
Introduced initially as an alternative to prenatal diagnosis,
PGD has now also become an important complement to the
presently available approaches for prevention of genetic
disorders. Couples at risk for late onset diseases, or diseases
that are not expressed in 100% of cases, or who require HLAmatched progeny previously would not risk a pregnancy
because of the possible need to terminate it if prenatal
diagnosis gave a positive result. Now PGD relieves couples in
these categories of this worry. PGD has also stimulated
improvements in the accuracy of single-cell genetic analysis.
Sufficient progress has been achieved in PGD for aneuploidies
and translocations, as a result of the introduction of novel and
improved techniques. These developments were reviewed at
the Fifth International Symposium, held in Antalya, Turkey on
5–7 June 2003. They are summarized below, with the
emphasis on the following main topics: (i) improvements in
PGD for single gene disorders; (ii) novel techniques for PGD;
(iii) PGD for treatment of siblings requiring stem cell
transplantation and progress in provision of human embryonic
stem (ES) cells; and (iv) PGD impact on reproductive
outcome.
Improvements in PGD for single
gene disorders
230
At least 1500 PGD cycles have been performed for single gene
disorders, resulting in births of more than 300 unaffected
children (International Working Group on Preimplantation
Genetics (IWGPG), 2001; European Society of Human
Reproduction and Embryology (ESHRE) Preimplantation
Genetic Diagnosis Consortium, 2002; Harper, 2003; Verlinsky
et al., 2004). Among a few new conditions for which PGD was
reported were: Kell disease, familial dysautonomia,
facioscapulohumeral muscular dystrophy, Canavan disease,
and Sanjad–Sakati syndrome (Hellani et al., 2003; Malcov et
al., 2003; Marshall et al., 2003; Rechitsky et al., 2003a;
Verlinsky et al., 2003). This experience shows that some of the
problems previously shown to result in misdiagnosis of single
cell genetic analysis, such as contamination by extraneous
DNA contamination or failed amplification, may now be well
controlled, with reliable methods presently available for
avoidance of misdiagnosis. However, some centres still work
on the application of these methods to achieving PGD clinical
outcome (Girardet et al., 2003; Jiao et al., 2003; Moutou et al.,
2003), or concentrate on the development of PGD protocols
(Bermudez et al., 2003; Fiorentino et al., 2003; Piyamongkol
et al., 2003). Considerable progress has also been made in
detecting preferential amplification and allele dropout (ADO),
which may currently be avoided through the application of the
multiplex nested polymerase chain reaction (PCR) analysis,
involving mutation testing simultaneously with a number of
closely linked polymorphic markers (Rechitsky et al., 2001,
2003b; De Vos et al., 2003; Goossens et al., 2000). Available
experience strongly suggests that PGD protocols for single
gene disorders may no longer be appropriate for clinical
practice without a set of closely linked polymorphic markers
tested simultaneously with causative genes.
Because the availability of a sufficient number of closely
linked informative markers cannot be predicted, especially in
some populations or ethnic groups, the introduction of single
nucleotide polymorphisms (SNP) as linked markers has
improved considerably the chance of finding such markers
(Sermon, 2003). The adequate number of informative linked
markers, together with availability of a sufficient number of
fluorochromes and the introduction of real-time PCR,
substantially improves the accuracy of PGD, also making it
possible to detect and avoid misdiagnosis due to
recombination between the gene and markers and
aneuploidies, which also present a potential source for
misdiagnoses. A crossover rate of 4.3% within human
leukocyte antigen (HLA) area has been observed in a recent
experience of preimplantation HLA typing, involving a series
of 330 preimplantation embryos (Rechitsky et al., 2003b;
Verlinsky et al., unpublished data). The fact that aneuploidies
in oocytes and embryos are highly prevalent has also been well
known (Munné, 2002; Kuliev et al., 2003a), but their impact
on the accuracy of PGD has not previously been fully
appreciated. There is, however, no doubt that the accuracy of
PGD may be compromised by copy number of the
chromosome(s) in which the causative gene tested is localized,
which is particularly important in PGD for single gene
disorders offered for patients of advanced reproductive age, in
whom the same biopsied single cell has to be simultaneously
tested for the causative gene and specific chromosome
number. Preliminary data, involving preimplantation HLA
typing of 371 embryos, demonstrated that as many as 6.4% of
the tested cells were aneuploid for chromosome 6, including
2.2% trisomic and 4.2% monosomic embryos, which may
have led to misdiagnosis of HLA alleles, without evaluating
the copy number of chromosome 6 (Verlinsky et al.,
unpublished data). The data suggest that reliable HLA typing,
as well as PGD for single gene disorders, should involve
testing for the copy number and the origin of missing or extra
chromosomes in which the genes tested are localized.
Novel techniques for PGD
As previously demonstrated, the genetic composition of
oocytes may be tested reliably through removal and testing of
the first and second polar bodies (Verlinsky and Kuliev, 2000).
However, no method has been available for testing the
outcome of male meiosis, as genetic analysis destroys the
spermatozoa, making them useless for fertilization. To
overcome this problem, a new technique has been introduced,
allowing the duplication of spermatozoa before genetic
analysis so that one of the duplicated spermatozoa can be used
for testing and the other for fertilization and consequent
transfer of the resulting embryos, provided that the genetic
analysis of the corresponding duplicate shows a normal
genotype (Willadsen et al., 2003). To demonstrate the
reliability of the technique, over 100 human spermatozoa from
chromosomally normal donors, as well as from translocation
carriers, were injected into enucleated mouse oocytes, and the
duplicated cells resulting from an overnight culture were tested
Report - Report of the Fifth International Symposium on PGD- A Kuliev & Y Verlinsky
by fluorescence in-situ hybridization (FISH) to compare the
chromosomal status of both daughter cells. All but 3% of the
haploid cell pairs derived from the normal donors were
identical for the chromosomes tested, while, as expected, a
high proportion of the paired nuclei derived from the
spermatozoa of translocation carriers were chromosomally
unbalanced, suggesting that ooplasm from mature mouse eggs
can support the faithful replication of any human sperm
genome, irrespective of the genotype. Although it is still to be
demonstrated whether human oocytes could duplicate
spermatozoa as faithfully as murine oocytes, the technique
may have important practical implications for PGD of
paternally derived conditions, such as translocations, known to
produce as many as 70% abnormal spermatozoa on average.
The technique also has potential for research purposes, as
shown in preliminary work devoted to the study of mosaicism
(Munné et al., 2003a). Following duplication of human
spermatozoa in cow oocytes, a series of 31 resulting embryos
were cultured up to the 8-cell stage and tested by probes
specific to chromosomes 13, 16, 18, 21 and 22. As many as
16% of the resulting sperm duplicates appeared not to be
identical, which may further be related to the genetic
differences between the donors involved. In fact, one of the
three sperm donors for the above experiment produced mostly
mosaic embryos in two PGD cycles. However, the rate of
mosaicism in sperm duplicates of the three donors involved in
this small series was similar, indicating that the generation of
mosaic embryos, at least in patients previously tested by PGD,
may be related not to the sperm genotype but to the sperm
centrosome (Silber et al., 2002).
There were also developments in the biopsy procedures for
removing samples from oocytes and embryos, which may be
required for improving the accuracy of PGD. For example,
current PGD practice frequently requires removing the sample
from both the oocytes and the resulting embryos, such as in
PGD combined with preimplantation HLA typing, and
combined PGD for single gene and chromosomal disorders. It
is of interest that a preliminary evaluation of the outcome of
such a double biopsy appeared to have no effect on the
viability of the embryos (Magli et al., 2003). The approach has
been applied on a regular basis as a tool for avoiding
misdiagnosis due to mosaicism and has resulted in 26%
pregnancy rate in IVF patients of advanced reproductive age
(38.5 years on average) (Verlinsky and Kuliev, 2003).
Finally, with the current tendency towards blastocyst transfer,
there has been renewed interest in the development of methods
for blastocyst biopsy, as demonstrated by successful PGD
cycles performed by blastocyst biopsy for translocations,
which have resulted in ongoing clinical pregnancies
(McArthur et al., 2003). Although blastocyst biopsy is not yet
a method of choice in many centres, its potential is obvious,
especially for additional testing required to confirm the polar
body or blastomere diagnosis.
There was progress in the development of microarray
technology in examining gene expression profiles of
individual human oocytes and embryos, although no reliable
correlation has been identified between molecular markers and
developmental competence of oocytes and preimplantation
embryos at the present time. By testing the expression profile
of over 8000 genes examined in single oocytes and embryos,
using Affymetrix GeneChip Microarrays, differences in the
expression were evident even between oocytes of the same
developmental stage, which may be due to underlying genetic
differences that contribute to the patient’s phenotype
(Steuerwald et al., 2003). The comparison of embryos at
different stages of development revealed large divergences in
gene expression, so microarray technology may help in
revealing genes that play critical roles in specific infertile
conditions and normal preimplantation development, thus
providing potential targets for diagnosis.
Customized microarray technology is presently being
developed for the testing of chromosomal aneuploidies and
translocations. However, the method is not yet sufficiently
reliable for aneuploidy testing, requiring the improvement of
the detection of ratio changes of 0.5 (Leigh et al., 2003). The
method was applied for testing genomic DNA for gains and
losses of chromosomal material in blocked morulae, showing
different levels of mosaicism and aneuploidy for different
chromosomes (Benkhalifa et al., 2003). Also a prototype
microarray was developed for the detection of Robertsonian
translocations, which may be applied in clinical practice, after
further improvements to whole genome amplification to
reduce loss of heterozygosity on low template DNA (Osborne
et al., 2003).
However, no significant progress was reported in the
application of comparative genome hybridization (CGH) to
PGD. CGH is still a highly labour-intensive procedure,
incompatible with the current laboratory framework of PGD,
even with the efforts to perform it on polar bodies, or to
accelerate the procedure to be completed in 38 h (Wells et al.,
2002; Ozen et al., 2003). Also, despite the expected higher
aneuploidy detection rates detectable by CGH, no significant
differences were reported (Wilton et al., 2003). In the majority
of embryos tested by both FISH and CGH, the results were
reported to be mainly in agreement, although a few
inconsistencies were also reported (Ozen et al., 2003; Trussler
et al., 2003). As for the available CGH clinical experience, it
is still limited to a series of 20 poor prognosis IVF patients,
involving CGH analysis of 141 embryos, which resulted in
pre-selection and transfer of only 20 aneuploidy-free embryos
in 14 cycles, yielding three clinical pregnancies (Wilton et al.,
2003). This suggests that CGH is currently impractical for
clinical application and requires further improvement.
Further progress was achieved in the application of nuclear
transfer techniques for PGD of translocations, with the current
83% success rate of blastomere nucleus conversion into
metaphase. The method has been applied to 89 clinical cycles
for translocation carriers, resulting in the transfer of balanced
or normal embryos in 68 of them, which yielded 22 unaffected
pregnancies (Verlinsky et al., 2002; Cieslak et al., 2003).
Despite previous hopes for using nuclear transfer technology
for producing female and male gametes through haploidization
of somatic cells (Lacham-Kaplan et al., 2001; Tesarik and
Mendoza, 2003), testing of the resulting presumably haploid
cells by FISH analysis revealed chromosomal abnormalities in
all but 5% of cells in preliminary results (Galat et al., 2003).
This may suggest that, despite the feasibility of somatic cell
haploidization by the use of the metaphase II oocyte
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Report - Report of the Fifth International Symposium on PGD- A Kuliev & Y Verlinsky
cytoplasm, its clinical use cannot be considered at the present
time, due to an extremely high aneuploidy rate.
PGD for treatment of siblings
requiring stem cell transplantation
and progress in provision of human
embryonic stem cells
Preimplantation HLA matching has been used during the last 3
years for the pre-selection of mutation-free embryos, which
may also be potential donor progeny for bone marrow
transplantation (Verlinsky et al., 2001; Kuliev and Verlinsky,
2002). Preimplantation HLA genotyping in combination with
PGD was applied in more than two dozen cycles, resulting in
pre-selection and transfer of the HLA-matched unaffected
embryos in 17.5% of the embryos tested, as expected. The
number of requests for performing PGD in combination with
HLA typing has been increasing overall, with the recent
emergence of a considerable proportion of cases involving
preimplantation HLA typing without PGD. For example, in the
presently available experience of 378 PGD cycles performed
in the present authors’ centre in Chicago for 54 different
conditions, including single gene defects, dynamic mutations
and some medically relevant genetic variations, 45 (12%)
cycles have been performed for HLA typing (Rechitsky et al.
2003b; Verlinsky et al., unpublished data). The number of
HLA cycles in this experience was only 4 (0.5%) in 1999,
when preimplantation HLA typing was first introduced,
reaching 23 (19%) in 2002. While the majority of these cases
(32 cycles) were done for preimplantation HLA genotyping in
combination with PGD for causative genes, including
thalassaemia (19 cycles), Fanconi anaemia (9 cycles),
hyperimmunoglobulin M syndrome (2 cycles), X-linked
adrenoleukodystrophy (one cycle) and Wiskott–Aldrich
syndrome (one cycle), 13 clinical cycles have already been
performed for HLA typing without PGD, i.e. with the only
objective of pre-selecting of HLA-matched progeny for
transplantation treatment of siblings with bone marrow
disorders (Verlinsky et al., unpublished data). The latter cycles
resulted in the embryo transfer of the HLA-matched embryos
in 12 cycles, yielding the birth of five HLA-matched healthy
children to become potential HLA-compatible donors for
siblings requiring bone marrow transplantation. The data
provide a realistic option for the couples desiring the
establishment of a pregnancy potentially providing HLAmatched progeny for treatment of an affected family member,
with the prospect of application of the approach to other
inherited or acquired conditions, also requiring HLAcompatible donors for bone marrow transplantation.
232
Although preimplantation HLA typing is still controversial,
and not allowed in certain countries, it has appeared to be so
attractive for couples in need, that they have been prepared to
achieve their goal in providing their affected siblings with
HLA-matched donor progeny even by travelling out of the
country. For example, PGD for genetic disease combined with
HLA typing for sibling bone marrow rescue has been allowed
in the UK, but HLA typing in the absence of high-risk genetic
transmissible disease was not allowed (Braude, 2003). These
couples requested preimplantation HLA typing abroad, which
has presently resulted in the birth of HLA-matched progeny
for their siblings with leukaemia or with sporadic
Blackfan–Diamond anaemia (Verlinsky et al., unpublished
data). Similarly, the law in the UK has condoned the use of
embryos for stem cell research and therapeutic cloning, but
this is still the subject of intense discussion in many other
European countries with a strong lobby for a ban (Braude,
2003).
In addition to the provision of HLA-matched stem cells for
bone marrow disorders, PGD provides a novel source for the
establishment of ES cells (Pickering et al., 2003). Although ES
cells are usually derived from the culture of the inner cell mass
(ICM) of the preimplantation blastocyst, a highly efficient and
original technique was developed for the establishment of ES
cell lines from human embryos of different stages of
preimplantation development, without isolation and culture of
ICM, and has been applied in the establishment of a dozen ES
cell lines (Strelchenko et al., 2003). These ES lines, as well as
other of ES lines established from spare human blastocysts
obtained after PGD for chromosomal disorders, were
characterized as typical pluripotent ES cells and were shown
spontaneously to differentiate in vitro into a variety of cell
types, including neurons and contracted cardiocytes. The
established repository of ES cells is currently used for research
purposes and is also available on request.
As PGD allows genetic characterization of preimplantation
embryos, prior to the formation of ES cells and their directed
differentiation into different ES lineages, this may also
improve the efficiency of the establishment of ES cells, which
still vary greatly between laboratories. Of special relevance is
the identification of factors influencing the differentiation of
human ES cells, which is an essential prerequisite to their
therapeutic application in regenerative medicine. For example,
in the presence of an inhibitor of bone morphogenic proteins
(NOGGIN), human ES cells were reported to form
neurospheres that express classical neuronal markers (Cram et
al., 2003). Under defined culture conditions, neurospheres are
capable of differentiating into a variety of neural cell types,
including astrocytes and oligodendrocytes. The fact that
human ES cells may be induced to differentiate in vitro into
somatic progeny, and that highly enriched cultures of
proliferating neural progenitor cells may be isolated from
differentiating human ES cells, was also reported (Reubinoff,
2003). The neural progenitors were differentiated in vitro into
astrocytes, oligodendrocytes and mature neurons. Following
transplantation to the developing brain, the human neural
progenitors responded to host signals and were capable of
constructing the neuronal and glial lineages. Controlling
differentiation into pure populations of specific neural cells
may eventually form the basis of therapy for some
neurodegenerative disorders and spinal injuries.
PGD impact on reproductive
outcome
An increasing number of centres have been involved in PGD
for chromosomal disorders, including translocations and
aneuploidies. As previously, significant reproductive impact
was demonstrated in PGD for chromosomal translocations.
The experience of more than 500 cycles accumulated at the
present time further confirms the previous observations on a
more than four-fold reduction of spontaneous abortion rate in
translocation carriers, making PGD a preferred option for
Report - Report of the Fifth International Symposium on PGD- A Kuliev & Y Verlinsky
chromosomal translocations over traditional prenatal diagnosis
(Munné, 2002; Verlinsky et al., 2002; Cieslak et al., 2003;
Munné et al., 2003b).
Further evidence has been accumulated on the positive clinical
impact of PGD for aneuploidy, currently performed for
advanced reproductive age, repeated IVF failures and repeated
spontaneous abortions. Overall, the experience of close to
5000 PGD cycles for aneuploidy has been accumulated, with
the majority of cases (approximately 4000 cycles) undertaken
by the PGD centres in Chicago (Kuliev et al., 2003a; Verlinsky
and Kuliev, 2003), St Barnabas, New Jersey (Munné, 2002;
Munné et al., 2002, 2003c), Bologna (Gianaroli et al., 2001,
2003) and Istanbul Memorial Hospital (Kahraman, 2003). The
positive clinical impact of aneuploidy testing has recently been
documented in terms of doubling the implantation rate in IVF
patients of 40 years and older, given a sufficient number of
zygotes for testing (Munné et al., 2003c).
The improvement in reproductive outcome was particularly
obvious from the analysis of the reproductive history of PGD
patients (Gianaroli et al., 2003). Analysing the outcome of the
transfer of 318 FISH normal embryos, an implantation rate of
65.1% in pregnant patients was observed, with a total of 161
clinical pregnancies generated, which resulted in the birth of
153 children from 125 couples and 26 spontaneous abortions,
giving a take-home baby rate of 82.3%. Of 161 couples
involved in the study, 41 were on their first cycle, 14 had
experienced 31 spontaneous pregnancies with 29 abortions
and two deliveries, and there was only one birth in the
remaining 27 couples. A total of 367 cycles were performed in
120 of these couples before undertaking PGD, with 30
pregnancies, five on term and 25 aborted. These couples had
also experienced 50 spontaneous pregnancies, three on term
and 47 aborted. The overall implantation rate derived from
their reproductive experience was 13.0%, and the take-home
baby rate 6.8%. This makes obvious the clinical usefulness of
PGD for aneuploidy for IVF patients with poor reproductive
performance.
The potential of pre-selecting euploid embryos for transfer is
in agreement with the fact that more than half of oocytes and
embryos tested in PGD for poor prognosis IVF patients were
shown to have chromosomal abnormalities. The analysis of
prevalence and types of these anomalies may help to
investigate their origin and improve the accuracy of PGD for
aneuploidies. For example, based on the testing of 8213
oocytes by first and second polar body sampling in PGD for
IVF patients of advanced reproductive age, it was observed
that 53.1% of oocytes had aneuploidies for chromosomes 13,
16, 18, 21 and 22, with 39% of them originating from meiosis
I, 32% from meiosis II, and 29% from both meiosis I and
meiosis II errors (Kuliev et al., 2003a,b). One-third of the
latter errors appeared to be ‘balanced’ for those chromosomes
involved in errors in both meiosis I and meiosis II, but the
follow-up analysis of the embryos resulting from these
‘balanced’ oocytes showed a normal chromosomal set in only
18% of cases, the remaining majority having aneuploidies,
involving the errors for the same or different chromosomes, or
mosaicism. This may suggest that any error in a female
meiosis may lead to a predisposition to further errors at the
cleavage stage, making the resulting embryos useless for
transfer.
The experience currently accumulated by FISH analysis of
thousands of preimplantation embryos further confirms
50–70% prevalence of aneuploidies at the cleavage stage
(Gianaroli et al., 2001, 2003; Munné, 2002; Kahraman, 2003).
As previously demonstrated, at least half of chromosomally
abnormal embryos have mosaicism, which is the major
challenge in improving the accuracy of PGD for aneuploidies.
As the overall prevalence of chromosomal abnormalities in
oocytes and embryos seems to be comparable, suggesting that
mosaic embryos may originate from aneuploid oocytes
through the process known as ‘trisomy rescue’, further
improvement of PGD accuracy may in future require testing of
both oocytes and the resulting embryos. As mentioned
previously, this may be achieved by a sequential biopsy of both
polar bodies and a single blastomere from the resulting
embryo, so that both meiotic and mitotic errors could be
excluded. In addition, information from both the oocyte and
the embryo chromosome sets will make it possible to detect
the potential uniparental disomy cases, which will be evident
from the detection of the normal disomic embryos, originating
from trisomic oocytes. Collecting of this unique information
may also be useful in finding a possible explanation for at least
some of the cases of Beckwith–Wiedemann syndrome (BWS),
reported recently in an association with assisted reproduction
techniques (DeBaun et al., 2003; Maher et al., 2003; Gicquel
et al., 2003). The fact that more than half of IVF patients are
35 years and older, and that more than half of their oocytes
have aneuploidies, avoiding the transfer of the embryos
resulting from these oocytes through PGD for aneuploidies
should be useful, in addition to potentially improving
implantation and pregnancy rates, for avoiding the transfer of
embryos with uniparental disomies, as possible contributors to
the imprinting disorders.
The Inaugural Meeting of the Preimplantation Genetic
Diagnosis International Society (PGDIS) was held during the
Fifth International Symposium on Preimplantation Genetics,
the participants of which became founding members, along
with the participants of the previous 4th International
Symposium on Preimplantation Genetics in Cyprus, 2002. The
6th International Symposium on Preimplantation Genetics will
be organized now by PGDIS and is scheduled for 19–22 May
2005, with the celebration of millions of IVF and thousands of
PGD babies (http://www.pgdlondon.org).
Note: Many of the references quoted in this article refer to the
papers delivered at the Symposium.
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Received 13 October 2003; refereed 7 November 2003;
accepted 14 November 2003.
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