|
PGD for HLA Matching
 The
procedure was applied to 197 PGD cycles (150 for β-thalassaemia,
19 for ALL, 16 for DBA, 3 for Histiocytosis, 3 for
Adrenoleukodystrophy , 2 for Duncan Sindrome, 1 for Chronic
granulomatous disease, 1 for FANCG, 1 for Wiscott-Aldrich
syndrome and 1 for Mannosidosis-Alpha) performed for 106
couples. A total of 1488 embryos were tested for HLA typing
in combination with a genetic disease, and 329embryos for
HLA typing only (Table 2). A total of 2492 blastomeres was
analysed, in 2292 (92.0%) of which a successful
amplification was obtained (Table 1). Two hundred
blastomeres resulted in the amplification failure for all
the markers/loci tested. The amplification efficiency of the
individual STR markers on blastomeres ranged from 92.2 to
100%, with an overall amplification rate of 98.2%. The ADO
rates varied between the different loci investigated,
ranging from 0.0 to 10.8%
A reliable HLA haplotype was obtained in 2292/2292 (100%) of
the blastomeres with positive PCR results.
Totally, 1704 (93.8%) embryos were diagnosed; however
testing for chromosome 6 copy number revealed 187 (11.0%)
embryos with aneuploidies, including a total of 38 (2.2%)
trisomies, 143 (8.4%) monosomies and 6 (0.4%) uniparental
dysomies, which affected the HLA matching diagnosis for
these embryos (Table 4), leading to a conclusive diagnosis
in only 1517 (89.0%) embryos.
In total, 311 (18.3%) embryos resulted to be HLA matched
with the affected siblings. In the 159cycles of HLA matching
combined a with single gene disorder, although the overall
number of HLA-identical embryos was 259 (18.5%), only 196
(14.0%) resulted also in an unaffected genotype. In the
couples undergoing preimplantation HLA typing without
testing for a causative gene, 52 (17.2%) embryos appeared to
be HLA compatible with the affected children. Recombination
was found in 38 (2.2%) embryos.
Overall 211 embryos were transferred to the patients in 132
of the 197 cycles performed (1.6 + 0.7 on average), and 50
pregnancies were achieved. Eight pregnancies resulted only
biochemical, 11 spontaneously miscarried and one resulted
ectopic, and was then terminated. Thirdy-one ongoing
pregnancies were obtained. The ongoing pregnancy rate was
15.7% per cycle and 23.5% per transfer.
Fourteen pregnancies are still ongoing, while 3 twin and 14
singleton pregnancies, produced the birth of 20 healthy
children, which were confirmed to be HLA identical to their
affected sibling by blood samples HLA testing. Stem cells
collected after delivery from the umbilical cords blood were
transplanted to the affected siblings of 7 couples,
resulting in a successful hematopoietic reconstruction for
all patients.
Number of families treated with
distinct indications for PGD and/or HLA. ongoing
pregnancies. life births and cord blood transplantations (CBTs).
|
Diseases |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
Adrenoleukodystrophy |
3
|
2
|
1
|
50,0 |
0
|
1
|
50,0 |
0
|
1
|
0
|
0
|
0
|
|
β-Thalassemia
|
150
|
81
|
38
|
38,8 |
7
|
31
|
31,6 |
8
|
10
|
13
|
15
|
5
|
|
Chronic granulomatous disease |
1
|
1
|
1
|
100,0 |
0
|
1
|
100,0 |
0
|
0
|
1
|
2
|
0
|
|
Diamond Blackfan Anemia |
16
|
3
|
4
|
36,4 |
1
|
3
|
27,3 |
2
|
1
|
0
|
0
|
0
|
|
Duncan
Syndrome |
2
|
1
|
0
|
0,0
|
0
|
0
|
0,0
|
0
|
0
|
0
|
0
|
0
|
|
FANCG
|
1
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Histiocytosis |
3
|
1
|
1
|
33,3 |
0
|
1
|
33,3 |
0
|
0
|
1
|
1
|
0
|
|
Leukemia |
19
|
14
|
4
|
30,8 |
0
|
4
|
30,8 |
1
|
2
|
1
|
1
|
1
|
|
Mannosidosis-Alpha |
1
|
1
|
0
|
0,0
|
0
|
0
|
0,0
|
0
|
0
|
0
|
0
|
0
|
|
Wiskott-Aldrich Syndrome |
1
|
1
|
1
|
100,0 |
0
|
1
|
100,0 |
0
|
0
|
1
|
1
|
1
|
|
Total
|
197
|
106
|
50
|
37,9
|
8
|
42
|
31,8
|
11
|
14
|
17
|
20
|
7
|
Next :
PGD for Cancer
|
