A total of 334 couples underwent 561 PGD cycles for 45 different indications (Table I).The mean maternal age was 31.8 ± 4.3 years, ranging from 21 to 44.
The single gene defects investigated included autosomal dominant (34 cycles; 22 couples), autosomal recessive (303 cycles; 191 couples) and X linked disorders (27 cycles; 15 couples). A total of 197 cycles, for 106 couples, were also performed for HLA matching.
Myotonic dystrophy was the most frequent autosomal dominant disease tested (n = 9). β-Thalassemia was the most frequent autosomal recessive disorder (n = 217), followed by cystic fibrosis (n = 40), and Spinal Muscular Atrophy (n = 15). Haemophilia A (n = 6) and Duchenne muscular dystrophy (n = 5%) were the most frequent X-linked disorders investigated.
A total of 4663 embryos were analysed. PCR amplification was successful in 6057 out of 6664 blastomeres (91.0%). Amplification failed for all the markers/loci tested in 607 blastomeres. The efficiency of amplification for the individual genetic conditions ranged from 80.0% to 100%, with an overall amplification rate of 92.4%. The ADO rates varied between the different loci/markers investigated, ranging from 0,0% to 12,9%, with an average ADO rate of 7.5%.
Overall, 4269 (91.6%) embryos were successfully genotyped in the 561 clinical cycles.
Following transfer of 758 embryos, 141 women had positive hCG levels (35.7% pregnancy rate per embryo transfer), 116 of which were confirmed with fetal sacs and heart beat. 25 pregnancies spontaneously miscarried within the first trimester and two ectopic pregnancies were terminated. 38 pregnancies are still ongoing, whereas the others 69 went to term without complications, resulting in the birth of healthy babies.
| Disease |
Gene
|
N. Cycles
|
N. Couples
|
N. of clinical pregnancies
|
N. of pregnancies still ongoing
|
N. of pregnancies delivered
|
| Autosomal Dominant |
|
34 |
22 |
8 |
3 |
5 |
| Charcot Marie Tooth type 1A |
PMP22 |
1 |
1 |
1 |
1 |
0 |
| Congenital fibrosis of extraocular muscles |
KIF21A |
2 |
1 |
0 |
0 |
0 |
| Hand-Foot-Uterus syndrome / Synopolydactlyly |
HOXD13-
HOXA13 |
2 |
1 |
0 |
0 |
1 |
| Holt-Oram Syndrome |
TBX5 |
1 |
1 |
1 |
0 |
1 |
| Huntington |
HD |
3 |
3 |
2 |
1 |
1 |
| Li-Fraumeni Syndrome |
p53 |
2 |
1 |
0 |
0 |
0 |
| Myotonic dystrophy |
DMPK |
9 |
5 |
0 |
0 |
0 |
| Neurofibromatosis type 1 |
NF1 |
4 |
3 |
1 |
1 |
0 |
| Retinoblastoma |
RB1 |
4 |
2 |
0 |
0 |
0 |
| Tuberossclerosis 1 |
TSC1 |
1 |
1 |
1 |
0 |
1 |
| Spastic Paraplegia type3 |
SPG3A |
1 |
1 |
1 |
0 |
1 |
| Torsion dystonia, early onset |
DYT1 |
3 |
1 |
1 |
0 |
2 |
| Von Hippel-Lindau syndrome |
VHL |
1 |
1 |
0 |
0 |
0 |
| |
|
|
|
|
|
|
| Autosomal Recessive |
|
240 |
156 |
55 |
19 |
36 |
| 3-Hydroxyisobutyryl-CoA hydrolase deficiency |
HIBCH |
1 |
1 |
0 |
0 |
0 |
| Cystic Fibrosis |
CFTR |
40 |
30 |
9 |
1 |
7 |
| Congenital adrenal hyperplasia |
CYP21A2 |
3 |
3 |
1 |
1 |
0 |
| Factor VII deficiency |
F7 |
1 |
1 |
1 |
0 |
0 |
| Familial Mediterranean Fever |
MEVF |
2 |
1 |
0 |
0 |
0 |
| Gangliosidosis |
GLB1 |
2 |
1 |
|
|
|
| Homocystinuria |
MTHFR |
1 |
1 |
1 |
1 |
0 |
| Hypomagnesemia |
CLDN16 |
1 |
1 |
0 |
0 |
0 |
| Limb-girdle muscular dystrophy type 2C |
SGCG |
1 |
1 |
0 |
0 |
0 |
| Mevalonic aciduria |
MVK |
1 |
1 |
0 |
0 |
0 |
| Mucopolysaccharidosis Type IIIA - Sanfilippo sindrome A |
SGSH |
5 |
1 |
1 |
1 |
0 |
| Mucopolysaccharidosis type IIIB - Sanfilippo syndrome B |
NAGLU |
1 |
1 |
1 |
1 |
0 |
| Mucopolysaccharidosis Type VI - Maroteaux-Lamy Syndrome |
ARSB |
2 |
1 |
1 |
0 |
1 |
| Neuronal ceroid lipofuscinosis 1 - Batten's disease |
PPT1 |
1 |
1 |
1 |
0 |
1 |
| Niemann-Pick disease |
SMPD1 |
1 |
1 |
1 |
1 |
0 |
| Tay Sachs |
HEXA |
1 |
1 |
0 |
0 |
0 |
| Thalassemia - β |
HBB |
217 |
127 |
31 |
9 |
21 |
| Sickle cell anemia |
HBB |
7 |
4 |
2 |
1 |
1 |
| Spinal Muscular Atrophy |
SMN |
15 |
13 |
5 |
3 |
3 |
| |
|
|
|
|
|
|
| X-linked |
|
27 |
15 |
11 |
2 |
7 |
| Adrenoleukodystrophy |
ABCD1 |
3 |
2 |
1 |
1 |
0 |
| Alpha-Thalassemia mental retardation syndrome |
ATRX |
1 |
1 |
0 |
0 |
0 |
| Charcot Marie Tooth type X |
CMTX |
3 |
1 |
3 |
0 |
1 |
| Chronic granulomatous disease |
CYBB |
1 |
1 |
1 |
0 |
2 |
| Duchenne muscular dystrophy |
DMD |
5 |
2 |
1 |
0 |
1 |
| Fragile - X |
FRAXA |
2 |
1 |
0 |
0 |
0 |
| Glucose-6-phosphate dehydrogenase deficiency |
G6PD |
1 |
1 |
0 |
0 |
0 |
| Haemophilia A |
F8 |
6 |
3 |
3 |
1 |
1 |
| Haemophilia B |
F9 |
3 |
1 |
1 |
0 |
1 |
| Lesch-Nyhan syndrome |
HPRT |
1 |
1 |
0 |
0 |
0 |
| Wiskott-Aldrich Syndrome |
WAS |
1 |
1 |
1 |
0 |
1 |
| |
|
|
|
|
|
|
| Specific traits |
|
197 |
106 |
42 |
14 |
20 |
| SGD + HLA Matching |
Gene + HLA |
159 |
88 |
34 |
11 |
18 |
| HLA Matching only |
HLA |
38 |
18 |
8 |
3 |
2 |
| TOTAL |
561 |
334 |
|
116 |
38 |
69 |