Human Reproduction Vol.21, No.1 pp. 3–21, 2006
doi:10.1093/humrep/dei292
Advance Access publication September 19, 2005.
ESHRE PGD Consortium data collection V: Cycles from
January to December 2002 with pregnancy follow-up to
October 2003
J.C.Harper1,12, K.Boelaert2, J.Geraedts3, G.Harton4, W.G.Kearns5, C.Moutou6,
N.Muntjewerff3, S.Repping7, S.SenGupta1, P.N.Scriven8, J.Traeger-Synodinos9,
K.Vesela10, L.Wilton11 and K.D.Sermon2
1
UCL Centre for PGD, Department of Obstetrics and Gynecology, University College London, 86–96 Chenies Mews, London
WC1E 6HX, UK, 2Centre for Medical Genetics, University Hospital and Medical School of the Dutch-speaking Brussels Free University
(Vrije Universiteit Brussel, VUB), Laarbeeklaan 101, 1090 Brussels, Belgium, 3PGD working group Maastricht, Department of Clinical
Genetics, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands, 4Genetics and IVF Institute,
3020 Javier Road, Fairfax Virginia, 22031, USA, 5Shady Grove Centre for Preimplantation Genetics, 15001 Shady Grove Road,
Suite 400, Rockville, Maryland, 20850, USA, 6Service de la Biologie de la Reproduction, SIHCUS-CMCO, 19, Rue Louis Pasteur,
BP120, 67303 Schiltigheim, France, 7Center for Reproductive Medicine, Academic Medical Center, Fertility Laboratory (A1-229),
Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands 8Department of Cytogenetics, and Center for Preimplantation Genetic Diagnosis,
Guy’s and St Thomas’ NHS Foundation Trust, Guy’s Hospital, St Thomas Street, London SE1 9RT, UK, 9Laboratory of Medical
Genetics, University of Athens, St Sophia’s Children’s Hospital, 11527 Athens, Greece, 10Sanatorium Repromeda, Vinicni 235,
615 00 Brno, Czech Republic and 11Melbourne IVF, 320 Victoria Parade, 3002 East Melbourne VIC, Australia
12
To whom correspondence should be addressed: joyce.harper@ucl.ac.uk
The fifth report of the ESHRE PGD Consortium is presented (data collection V). For the first time, the cycle data
were collected for one calendar year (2002) in the following October, so that data collection was complete for pregnancies and babies. The data were collected using a Filemaker Pro database and divided into referrals, cycles, pregnancies and babies. There are currently 66 active centres registered with the consortium; however, the data
presented here were obtained from 43 centres and included 1603 referrals, 2219 cycles, 485 pregnancies and 382
babies born. The cycle data were divided into preimplantation genetic diagnosis (PGD) for inherited disorders
(including chromosome abnormalities, sexing for X-linked disease and monogenic disorders), aneuploidy screening
(PGS) and the use of PGD for social sexing. Data collection V is compared with the previous cumulative data collection (I–IV), which comprised 4058 PGD/PGS cycles that reached oocyte retrieval.
Key words: aneuploidy screening/preimplantation genetic diagnosis/embryo biopsy/PGS/PGD
Introduction
The ESHRE PGD Consortium was established in 1997 and one
of the aims was to collect detailed data on referrals, PGD/PGS
cycles, pregnancies and babies born. There are currently 66
active centres registered with the consortium. This includes
almost all active European Centres and additionally centres
from Australia, Argentina, Israel, Korea, Taiwan and USA.
Four sets of data have previously been published. The initial data
collection included PGD cycles performed up to September 1998
(ESHRE PGD Consortium Steering Committee, 1999), the second
included cycles from September 1998 to May 2000 (ESHRE PGD
Consortium Steering Committee, 2000), the third was from May
2000 to May 2001 (ESHRE PGD Consortium Steering Committee,
2002) and the fourth included data from May 2001 to December
2001 (Sermon et al., 2005). This is the first set of data that relates to
cycles performed in a complete calendar year (January to December
2002) and is referred to as data V. Data VI (January to December
2003) has been collected since December 2004 and is currently
being processed. Cycle data are now collected in the October for the
previous calendar year so that data collection is complete for pregnancies and babies. In this report, two sets of data are presented.
The first set, referred to as data collection I–IV, comprise the cumulative data collections from the previous reports (ESHRE PGD
Consortium Steering Committee, 1999, 2000, 2002; Sermon et al.,
2005). The second set is data collection V. The FileMaker Pro 6™
(FP6) database was used for the last two data-set collections.
Materials and methods
Data collection
Data I–III were collected using paper copy or Excel spreadsheets.
Data IV and V were collected using a FileMaker Pro 6 database
Published by Oxford University Press 2005 on behalf of the European Society of Human Reproduction and Embryology.
3
J.C.Harper et al.
designed by C.Moutou, which contained the following tables: referrals, cycles, pregnancies and babies born. Details of the forms used
and how the database works were described in Sermon et al. (2005).
Results and discussion
The results are shown in the tables and only highlights and
important trends are discussed in the text. Sixty-six active centres are currently registered with the consortium. For 2002, 43
centres contributed data (see Appendix), whereas 11 failed to
do so. Seven centres are new members of the consortium and
five had not started their PGD activity in 2002.
Clinical pregnancy rates (presence of a fetal heart) are
expressed as a percentage of the cycles that reached oocyte
retrieval (% per OR) and as a percentage of cycles that had an
embryo transfer procedure (% per embryo transfer). Additionally the % implantation rate (percentage of fetal heart beats out
of the total number of embryos transferred) for cycles of data
collection V are presented.
Referral data V
In line with past developments, referrals for chromosomal disorders increased and were the most frequent reason for referral
(Table I). The vast majority of referrals were for aneuploidy
screening (Table II). Compared to the previous data collections
there were fewer referrals for reciprocal and Robertsonian translocations. The number of referrals for monogenic disorders
(‘Autosomal recessive’ and ‘Autosomal dominant’ in Table I) did
not change and the most frequent referrals in each group of MenTable I. Referrals according to indication
Data collection
Chromosomal (numerical/structural)
X-linked
Autosomal recessive
Autosomal dominant
Mitochondrial
Two indications
Y-chromosome deletion
Social sexing
Unknown
III–IV
V
1703
397
374
316
6
11
3
68
74
1150
109
102
111
1
2
4
4
120
Table II. Referrals for chromosomal disorders
Data collection
III–IV
Structural chromosomal aberrations
Reciprocal translocation
Robertsonian translocation
Inversion
Deletion
Numerical chromosome aberrations
Aneuploidy risk
47,XXY; 47,XYY
Sex chromosomal mosaicism
Male meiotic abnormalities
Other
Unknown
4
delian disorders remained the same. Duchenne muscular dystrophy, haemophilia A and fragile X syndrome were the most
frequent referrals for X-linked disorders, CF/CBAVD, β-thalassaemia and spinal muscular atrophy (SMA) were the most frequent referrals for autosomal recessive disorders, and
Huntington’s disease and myotonic dystrophy were the most frequent autosomal dominant referrals. There were three referrals
for HLA testing, two of these because of Fanconi anaemia and
one in combination with sickle cell disease. It is interesting to
note that there were only four referrals for social sexing. This is a
discrepancy with the number of cycles reaching OR for social
sexing, which was 72. However, in 120 cases the reason for referral was unknown (i.e. the data were not provide by the centre).
Table III gives the reasons for PGD. Since a couple might
have indicated more than one reason, the total is >100%. In
comparison to previous collections, genetic risk and previous
termination of pregnancy (TOP) have remained at the same
level, while genetic risk and objection to TOP have decreased.
Genetic risk and sub- or infertility has increased together with
age-related aneuploidy screening, i.e. PGS.
Data on cycles
Table IVa shows the cumulative data for collections I–IV. A
total of 2000 cycles reached the stage of oocyte retrieval (OR)
for PGD (chromosome abnormalities, sexing for X-linked disease and monogenic disorders), 1570 had an embryo transfer
procedure (77% per OR) and clinical pregnancy rates of 18% per
OR and 23% per embryo transfer procedure were obtained.
These data are broken down in Tables Va, VIa and VIIa. A total
of 1876 reached the stage of OR for PGS in data I–IV, 1342 having an embryo transfer procedure (71%) and clinical pregnancy
rates of 18% per OR and 25% per embryo transfer procedure
were obtained. These data are broken down in Table VIIIa. A
total of 182 cycles reached OR for social sexing, 131 cycles produced embryos of the desired sex and clinical pregnancy rates of
24% per oocyte retrieval and 34% per embryo transfer procedure
were obtained. These data are broken down in Table IXa.
Looking overall at these 4058 cycles that reached oocyte
retrieval, ICSI was used in the majority of cases. Acid Tyrode’s
drilling was performed in more cycles than drilling using the
laser, and cleavage stage aspiration was still the most commonly
used biopsy method. Data has been obtained for 54 060 oocytes.
Table IVb shows data collection V. A total of 2219 cycles
was started. For PGD, 936 cycles were started, 868 reached
Table III. Reasons for preimplantation genetic diagnosis (PGD)
V
372
141
20
6
126
70
8
4
1060
28
33
20
6
17
882
13
11
11
13
12
Data collection
Genetic risk and previous TOP
Genetic risk and objection to TOP
Genetic risk and sub- or infertility
Genetic risk and sterilization
Age-related aneuploidy
Other
III–IV
V
448 (15)
856 (29)
655 (22)
19 (0.6)
982 (33)
379 (13)
134 (8.4)
309 (19.3)
482 (30.1)
10 (0.6)
987 (61.6)
384 (24.0)
Values in parentheses are percentages.
Some couples had more than one reason for PGD, hence the total is >100%.
TOP = termination of pregnancy.
ESHRE PGD Consortium data collection V
Table IVa. Overall cycle data collection I–IV
Indication
Number infertile
Female age
Cycles to OR
Cancelled after OR before IVF/ICSI
Assisted reproduction treatment
IVF
ICSI
IVF + ICSI
Frozen
Frozen and ICSI
Cancelled ICSI
Unknown
Cancelled after OR
Cycles to PGS/PGD
FISH
PCR
Zona breaching
AT drilling
Laser drilling
Mechanical
Unknown
Biopsy method
Polar body biopsy
Cleavage aspiration
Cleavage extrusion
Cleavage flow displacement
Unknown
Embryology
COC
Inseminated
Fertilized
Biopsied
Successfully biopsied
Diagnosed
Transferable
Transferred
Frozen
Clinical outcome
Cycles to embryo transfer
HCG positive
Positive heart beat
[clinical pregnancy rate (%) per
OR/% per embryo transfer]
PGD
Table IVb. Overall cycle data collection V
PGS
PGD-SS
Total
577
33
2000
4
1774
35
1876
0
19
35
182
0
2370
35
4058
4
278
1684
1
9
3
3
18
88
1908
1070
838
355
1463
10
4
1
109
67
0
5
1
43
77
1799
1799
0
0
14
168
115
53
742
3214
11
18
5
3
61
179
3875
2984
891
1291
507
96
14
1140
533
61
65
19
106
43
0
2450
1146
200
79
11a
1831a
51
2
16
70a
1519a
143
16
52
0
125
43
0
0
81a
3475a
237
18
68
27 397
23 621
17 088
13 005
12 708
11 106
4374
3211
633
24 374
20 930
15002
11 008
10 760
9045
3625
2932
436
2289
2030
1411
1193
1109
1016
469
304
128
54 060
46 581
33 501
25 206
24 577
21 167
8468
6447
1197
1570
458
362
(18/23)
1342
431
336
(18/25)
131
56
44
(24/34)
3043
945
742
(18/24)
PGD (preimplantation genetic diagnosis) column includes PGD for
chromosome abnormalities, sexing for X-linked disease and PGD for
monogenic disorders; PGS = aneuploidy screening; PGD-SS = PGD
for sex selection.
a
Four cycles had polar body biopsy and cleavage stage biopsy.
OR = oocyte retrieval; AT = acid Tyrode’s. COC = cumulus-oocyte complexes.
OR, 603 had an embryo transfer procedure (69% per OR) and
clinical pregnancy rates of 18% per OR and 25% per embryo
transfer procedure were obtained. These data are broken down
in Tables Vb, VIc and VIIc. A total of 1211 cycles was performed for PGS, of which 1202 reached OR and 846 had an
embryo transfer procedure (70% per OR) and clinical pregnancy rates of 16% per OR and 23% per embryo transfer procedure were obtained. These data are broken down in Table
VIIIb. A total of 72 cycles reached OR for social sexing.
Embryos were transferred in 61 cycles and a clinical pregnancy
rate of 21% per OR was obtained. These data are broken down
in Table IXb.
As above for data I–IV, in data V ICSI, acid Tyrode’s drilling
and cleavage stage aspiration were the most common methods
used. Data are presented on 26 747 oocytes.
Indication
Total cycles
Number infertile
Female age
Cycles cancelled before OR
Cycles to OR
Cancelled after OR before IVF/ICSI
Assisted reproduction treatment
IVF
ICSI
IVF + ICSI
Unknown
IVF + frozen
ICSI + frozen
Unknown and frozen
Cancelled after OR
Cycles to PGS/PGD
FISH
PCR
Zona breaching
AT drilling
Laser drilling
Mechanical
Biopsy method
Polar body biopsy
Cleavage aspiration
Cleavage extrusion
Embryology
COC
Inseminated
Fertilized
Biopsied
Successfully biopsied
Diagnosed
Transferable
Transferred
Frozen
Clinical outcome
Cycles to embryo transfer
HCG positive
Positive heart beat
[clinical pregnancy rate (%) per
OR/% per embryo transfer]
Implantation rate (fetal hearts/
embryos transferred) (%)
PGD
PGS
PGD-SS
Total
936
417
32
68
868
2
1211
1120
38
9
1202
0
72
22
36
0
72
0
2219
1559
35
77
2142
2
91
760
2
156
1038
3
1
0
4
4
61
251
1859
5
1
1
19
4
124
2016
1686
330
11
2
73
793
507
286
51
1151
1151
0
1
4
2
0
72
28
44
412
349
32
668
467
16
0
6
66
1080
822
114
14
745
34
108
962
81
5
67
122
1712
182
11 558
9732
7151
5363
5290
4727
1711
1169
160
14 187
11 909
8321
6541
6472
5991
2211
1528
251
1002
742
480
396
396
351
183
145
21
26 747
22 383
15 952
12 300
12 158
11 069
4105
2842
432
603
198
152
(18/25)
846
271
198
(16/23)
61
22
15
(21/25)
1510
491
365
(17/24)
15
17
14
16
PGD (preimplantation genetic diagnosis) column includes PGD for
chromosome abnormalities, sexing for X-linked disease and PGD for
monogenic disorders.
OR = oocyte retrieval; AT = acid Tyrode’s; COC = cumulus–oocyte
complexes; PGS = aneuploidy screening; PGD-SS = PGD for sex selection.
Chromosomal abnormalities
Tables Va–c summarizes the 733 and 474 cycles collected for
data collections I–IV and V respectively. Table Vc lists the
karyotypes for which PGD was offered in data V and can be
found in the electronic version of the paper available at
Human Reproduction online (http://humrep.oxfordjournals.org/).
Overall there was very little difference between the two data
collections. Reciprocal translocation was the most frequent
class of chromosome aberration; ICSI was the predominant
mode of fertilization; acid Tyrode’s with cleavage aspiration
was the predominant sampling method. A global average of
14.7 and 13.7 COC per OR cycle was collected for the I–IV
and V data collections respectively; the fertilization rate (73
and 74%), the proportion of successfully biopsied embryos
which gave a diagnosis (90 and 91%), the proportion of
5
J.C.Harper et al.
Table Va. Preimplantation genetic diagnosis (PGD) for chromosomal abnormalities, data collection I–IV
Indication
Robertsonian Robertsonian Reciprocal, Reciprocal,
Sex chromosome Other
translocations, translocations, male carrier female carrier abnormalities
male carrier
female carrier
Total cycles
120
Number infertile
96
Female age
33
Cycles cancelled before OR
4
Cycles to OR
116
Cancelled after OR before IVF/ICSI
0
Assisted reproduction treatment
IVF
7
ICSI
107
IVF + ICSI
0
Frozen
0
ICSI and frozen
2
Cancelled after IVF/ICSI
3
Cycles to PGD
113
Zona breaching
AT drilling
85
Laser drilling
28
Mechanical
0
Biopsy method
Polar body biopsy
1
Cleavage aspiration
111
Cleavage extrusion
1
Cleavage flow displacement
0
Embryology
COC
1714
Inseminated
1452
Fertilized
999
Biopsied
647
Successfully biopsied
630
Diagnosed
522
Transferable
196
Transferred
165
Frozen
4
Clinical outcome
Cycles to embryo transfer
93
HCG positive
26
Positive heart beat
22
Clinical pregnancy rate (%) per OR/% per embryo transfer 19/24
Total
110
38
32
2
108
0
182
66
33
5
177
1
162
35
32
3
159
0
103
90
34
4
99
3
56
20
33
2
54
0
733
345
32
20
713
4
14
92
1
0
1
2
106
28
147
0
1
0
6
170
50
108
0
1
0
1
158
9
87
0
0
0
3
93
19
35
0
0
0
3
51
127
576
1
2
3
18
691
74
29
3
137
26
7
134
16
8
49
20
24
36
11
4
515
130
46
4
102
0
0
0
166
3
1
3
147
7
1
0
93
0
0
0
50
1
0
8
669
12
2
1652
1368
1005
800
780
708
199
171
13
2806
2404
1805
1449
1417
1304
289
249
7
2525
2189
1666
1420
1391
1292
287
251
0
1074
876
645
479
475
420
192
140
13
715
635
426
343
330
299
123
88
2
10486
8924
6546
5138
5023
4545
1286
1064
39
88
27
21
19/24
120
26
20
11/17
120
27
21
13/18
74
21
12
12/16
41
15
13
24/32
536
142
109
15/20
OR = oocyte retrieval; AT = acid Tyrode’s; COC = cumulus–oocyte complexes.
successfully biopsied embryos with a transferable result (26 and
25%), and the clinical pregnancy rate per OR (15 and 15%)
were similar.
The relatively low pregnancy rates are likely to reflect
that the low proportion of embryos with a transferable
result limits the choice of embryo for transfer (∼1 in 4
embryos biopsied for all classes of chromosome aberration,
and only 1 in 5 embryos for reciprocal translocation cycles
in particular).
Sexing for X-linked disease
Table VIa shows the cumulative data I–IV for sexing only for
X-linked disease using FISH and PCR. On average, 13.5
oocytes were collected per OR. FISH was used in the majority
of cycles (n = 421) compared to PCR (n = 65). The majority of
patients was fertile (88%). IVF was used in 10 cycles where
the diagnosis was done by PCR. The consortium recommends
that when PCR is used, ICSI should be performed to prevent
paternal contamination (Thornhill et al., 2005). In this data collection, acid Tyrode’s was used for zona drilling more than the
6
laser. The biopsy was successful in 96% of embryos and in
89% of embryos successfully biopsied a diagnosis was
obtained. Of these embryos, 36% of embryos were diagnosed
as transferable and 77% cycles which reached OR resulted in
an embryo transfer procedure. Overall clinical pregnancy rates
of 19% per OR and 24% per embryo transfer procedure were
obtained. Table VIb shows the indications for which sexing
only was performed. This was mainly for haemophilia A (98
cycles), Duchenne muscular dystrophy (87 cycles), followed
by X-linked mental retardation and retinitis pigmentosa (24
cycles each).
Table VIc shows the data from collection V for sexing only
cases for X-linked disease using FISH and PCR. The most
common indication in this group was Duchenne muscular dystrophy (36 cycles), followed by haemophilia (22 cycles) and
Becker muscular dystrophy (nine cycles) (Table VId). A total
of 127 cycles were in this group, with 118 cycles going to
oocyte retrieval with an average of 12.6 oocytes per retrieval.
The embryos in this group were mainly diagnosed using FISH
(97%). The biopsy was successful in 99% of embryos biopsied
ESHRE PGD Consortium data collection V
Table Vb. PGD for chromosomal abnormalities, data collection V
Indication
Total cycles
Number infertile
Female age
Cycles cancelled before OR
Cycles to OR
Cancelled after OR before IVF/ICSI
Assisted reproduction treatment
IVF
ICSI
IVF + ICSI
Unknown + frozen
ICSI + frozen
Cancelled after IVF/ICSI
Cycles to PGD
Zona breaching
AT drilling
Laser drilling
Mechanical
Biopsy method
Cleavage aspiration
Cleavage extrusion
Embryology
COC
Inseminated
Fertilized
Biopsied
Successfully biopsied
Diagnosed
Transferable
Transferred
Frozen
Clinical outcome
Cycles to embryo transfer
HCG positive
Positive heart beat
Clinical pregnancy rate (%) per OR/% embryo transfer
Number of fetal hearts
Implantation rate (fetal hearts/embryos transferred) (%)
Robertsonian
translocation,
male carrier
Robertsonian
translocations,
female carrier
Reciprocal,
male carrier
Reciprocal,
female carrier
Sex chromosome
aneuploidy
Other
Total
73
64
36
4
69
0
57
32
33
3
54
0
125
82
34
6
119
0
146
67
34
9
137
0
41
37
33
1
40
2
32
21
33
2
30
0
474
303
33
25
449
2
2
65
1
0
1
8
61
11
42
0
0
1
5
49
11
105
0
0
3
13
106
24
108
0
0
5
16
121
5
32
0
1
0
4
34
10
20
0
0
0
1
29
63
372
1
1
10
47
400
41
20
0
35
12
2
66
33
7
82
38
1
19
13
2
26
2
1
269
118
13
59
2
45
4
98
8
117
4
34
0
29
0
382
18
954
810
574
382
373
328
132
93
10
620
517
399
342
340
305
101
73
9
1684
1428
1060
841
831
746
161
136
4
1920
1671
1279
1005
996
920
183
152
17
583
467
320
217
208
194
97
62
6
391
347
253
190
187
173
48
40
12
6152
5240
3885
2977
2935
2666
722
556
58
42
14
12
17/29
16
17
37
14
11
20/30
13
18
73
24
16
13/22
17
13
84
22
16
12/19
19
13
28
10
8
20/29
9
15
19
3
3
10/16
5
13
283
87
66
15/23
79
14
OR = oocyte retrieval; AT = acid Tyrode’s; COC = cumulus–oocyte complexes.
and 93% of the embryos biopsied were diagnosed. A transfer
was achieved in 84% of the cycles which went through PGD,
with an average of 1.9 embryos transferred in each cycle. The
overall clinical pregnancy rate was 20% per OR and 25% per
embryo transfer, with an implantation rate of 17%.
Monogenic disease
Table VIIa summarizes the cumulative data I–IV for PGD of
specific monogenic diseases. A breakdown is only presented
for the most common disorders. The most common autosomal
recessive diseases were cystic fibrosis (247 cycles), β-thalassaemia (103 cycles), spinal muscular atrophy (66 cycles) and
sickle cell anaemia (15 cycles). The most common autosomal
dominant diseases were myotonic dystrophy (160 cycles),
Huntington’s disease (87 cycles) and Charcot–Marie–Tooth
disease (18 cycles). The most common specific diagnosis of
X-linked diseases were for fragile X (38 cycles), haemophilia A
(16 cycles) and Duchenne muscular dystrophy (26 cycles). Table
VIIb lists the diseases which are included under ‘other’. A total
of 909 cycles was started: 829 resulted in OR, 681 resulted in
embryo transfer procedures (82%) and clinical pregnancy rates
of 20% per oocyte retrieval and 25% per embryo transfer procedure were obtained.
Important points to note from data I–IV are that only 59%
of embryos were diagnosed as transferable for recessive disorders, instead of the expected 75%. IVF was used as the
method of fertilization in 26 cycles, again in contradiction to
recent recommendations (Thornhill et al., 2005). Acid Tyrode’s
drilling was used in the majority of cases with cleavage stage
aspiration.
Table VIIc summarizes data collection V. The same most
common autosomal recessive and dominant disorders and
specific diagnosis of X-linked diseases are found, as shown in
Table VIIa. Overall there was an average of 13 oocytes collected per OR, biopsy was successful in 99%, diagnosis was
possible in 85% of embryos successfully biopsied, and 21% of
cycles to OR resulted in a clinical pregnancy. Table VIId lists
the diseases for data V which are included under ‘other’.
Important points to note from data V are that five cycles
had IVF instead of ICSI and laser drilling was the most common method used. Nineteen per cent of embryos tested for
7
J.C.Harper et al.
Table Vc. Chromosomal abnormalities analysed, data V (for web-based version only)
Female indication
Cycles
Female indication
Cycles
45,X/46,XX
45,X/47,XXX
45,X/47,XXX/46,XX
45,X/47,XXX/48,XXXX
45,XX,der(13;14)(q10;q10)
45,XX,der(13;15)(q10;q10)
45,XX,der(13;21)(q10;q10)
45,XX,der(13;22)(q10;q10)
45,XX,der(14;21)(q10;q10)
45,XX,der(15;21)(q10;q10)
45,XX,der(21;22)(q10;q10)
46,X,del(X)(p22.1)
46,X,der(X)t(X;Y)(p22.3;q12)
46,XX,del(22)(q11.2q11.2)
46,XX,ins(1;13)(p13;q13q22),t(3;6)(p12;p23)
46,XX,inv(2)(p25q34)
46,XX,inv(3)(p26 q13.2),t(13;20)(q31;p12)
46,XX,inv(8)(p21.3q11.2)
46,XX,inv(8)(p23.1q11.2)
46,XX,inv(9)(p11q13)
46,XX,inv(10)(p15q11.2)
46,XX,inv(11)(p15.3q24.2)
46,XX,inv(18)(p11.23q11.2)
46,XX,t(1;5)(q23;p13.1)
46,XX,t(1;9)(p36.3;q34)
46,XX,t(1;10)(q12;q11.2)
46,XX,t(1;10)(q25;p11.2)
46,XX,t(1;12)(p31;p13)
46,XX,t(1;13)(p36.3;q12.3)
46,XX,t(1;14)(p22;q24)
46,XX,t(1;15)(q42;q22.1)
46,XX,t(1;19)(q32.1;q13.1)
46,XX,t(1;21)(p22;q21)
46,XX,t(1;22)(p36.3;q11.2)
46,XX,t(2;3)(q12;q25)
46,XX,t(2;4)(p22.2;q33)
46,XX,t(2;6)(p21;q25.1)
46,XX,t(2;10)(q21;q26)
46,XX,t(2;11)(q37.2;p12)
46,XX,t(2;12)(q35;q24.1)
46,XX,t(2;13)(p16;q31)
46,XX,t(2;13)(q23;q33)
46,XX,t(2;13)(q36;q22)
46,XX,t(2;14)(q21.3;q24.3)
46,XX t(2;15)(p13;q22)
46,XX,t(2;15)(p15;q24)
46,XX,t(2;15)(q33;q11.2)
46,XX,t(2;16)(q37;p11.2)
46,XX,t(2;18)(p11.2;p11.3)
46,XX,t(2;18)(q31;q23)
46,XX,t(2;19)(q37.3;q13.1)
46,XX,t(2;22)(p10;p10)
46,XX,t(3;7)(q23;q31)
46,XX,t(3;10)(q26.2;q21.21)
46,XX,t(3;14)(q13.2;q11.2)
46,XX,t(3;15)(q22;q21)
5
1
8
1
39
7
5
1
3
2
1
1
1
3
1
1
1
1
1
6
1
1
2
1
2
1
1
3
3
1
1
1
3
1
2
1
2
1
1
1
1
1
2
3
1
1
1
2
1
1
1
1
1
3
1
3
46,XX,t(3;16)(p25;q22)
46,XX,t(3;17)(p23;q23)
46,XX,t(4;5)(q33;p15.31)
46,XX,t(4;8)(p16.1;p23.1)
46,XX,t(4;8)(q21.3;p21.3)
46,XX,t(4;15)(p16;p13)
46,XX,t(4;15)(q31.3;q22.1)
46,XX,t(4;17)
46,XX,t(4;18)(q24;p11.3)
46,XX,t(5;13)(q33;q22)
46,XX,t(6;7)(q15;q15)
46,XX,t(6;12)(p11;q11)
46,XX,t(6;19)(p22.1;q13.1)
46,XX,t(7;9)(q21;q34)
46,XX,t(7;10)(q11.2;q26)
46,XX,t(7;12)(p10;p10)
46,XX,t(7;13)(q31.3;q21.3)
46,XX,t(7;14)(p11;q13)
46,XX,t(7;14)(q11.23;q22)
46,XX,t(7;15)(p10;q10)
46,XX,t(7;15)(p14;q11.2)
46,XX,t(7;16)(q21.2;q23)
46,XX,t(7;21)(p10;q10)
46,XX,t(7;22)(p13;q11.2
46,XX,t(8;11)(p21;p15)
46,XX,t(8;12)(q11.2;q12)
46,XX,t(8;13)(q24.1;q22)
46,XX,t(8;19)(q21.3;q12)
46,XX,t(9;10)(p13;q22)
46,XX,t(9;11)(p21.3;q14.1)
46,XX,t(9;13)(q12;p13)
46,XX,t(9;15)(q34;q22)
46,XX,t(9;16)(q34;p12)
46,XX,t(10;13)(q22;q14)
46,XX,t(10;15)(q23;q15)
46,XX,t(10;16)(q24.2;p13.3)
46,XX,t(10;17)(p10;p10)
46,XX,t(10;18)(q?21;q?12)
46,XX,t(11;17)(p15.3;q11.2)
46,XX,t(11;18)(p14;q23)
46,XX,t(11;22)(q23.3q11.2)
46,XX,t(11;22)(q25;q12)
46,XX,t(12;15)(q24,1;q24)
46,XX,t(12;20)(q15;p11.2)
46,XX,t(12;21)(q15;q22)
46,XX,t(13;18)(p11;q11.2)
46,XX,t(13;21)(q14;q21)
46,XX,t(13;21)(q22;q11.2)
46,XX,t(14;18)(q23;q21.1)
46,XX,t(14;18)(q24.2;p11.21)
46,XX,t(14;18)(q24.3;q21.3)
46,XX,t(14;22)(q24;q13)
46,XX,t(19;22)(q13.4;q11.2)
Robertsonian female
Reciprocal female
3
1
2
1
2
1
1
1
4
1
1
1
2
1
1
3
3
2
2
3
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
4
2
1
1
11
1
1
1
3
1
1
2
3
2
1
1
1
1
3
Male indication
Cycles
Male indication
Cycles
45,X,del(Y)(q11.2q11.2),der(13;14)(q10;q10)
45,XY,der(13;14)(q10;q10)
45,XY,der(13;15)(q10;q10)
45,XY,der(13;21)(q10;q10)
45,XY,der(13;22)(q10;q10)
45,XY,der(14;15)(q10;q10)
45,XY,der(14;21)(q10;q10)
45,XY,der(15;21)(q10;q10)
45,XY,der(21;22)(q10;q10)
45,XY,inv(9)(p11q13),der(13;14)(q10;q10)
46,X,del(Y)(q11.2)
46,X,inv(Y)(p11q12)
1
45
2
2
1
1
14
2
2
1
2
1
46,XY,t(5;20)(q33;q13.3)
46,XY,t(6;9)(q23;q23)
46,XY,t(6;10)(p11;p15)
46,XY,t(6;11)(p22.2;q13.1)
46,XY,t(6;13)(p22;q14.2)
46,XY,t(6;15)(q27;q12)
46,XY,t(6;20)(p21.3;q13.3)
46,XY,t(7;13)(p21;q21.1)
46,XY,t(7;16)(q22;q22)
46,XY,t(8;9)(p21;q22)
46,XY,t(8;10)(q13;p13)
46,XY,t(8;11)(p21.1;p14.2)
8
1
1
1
1
1
1
1
2
2
1
1
1
ESHRE PGD Consortium data collection V
Table Vc. Continued
Male indication
Cycles
Male indication
46,X,t(Y;18)(q12;p11.2)
46,XY,-21+,der(21;21)(q10;q10)
46,XY,del(9)(?)
46,XY,ins(7;6)(q22;q25.1q27)
46,XY,inv(1)(p31.2q23)
46,XY,inv(9)(p11q13)
46, XY.ish t(2q;17q)(210E14-,B37c1+;B37c1-,210E14+)
46,XY,t(1;2)(q25;q23)
46,XY,t(1;3)(q44;q21)
46,XY,t(1;4)(p32;q25
46,XY,t(1;4)(q31;q35)
46,XY,t(1;5)(q41;q33)
46,XY,t(1;6)(p13.3;p22.2)
46,XY,t(1;7)(p22;q35)
46,XY,t(1;9)(p13.3;p13)
46,XY,t(1;11)(p12;q12)
46,XY,t(1;13)(q21;q11)
46,XY,t(1;14)(q21;q32)
46,XY,t(1;15)(q21;p11.2)
46,XY,t(1;16)(p31;q22)
46,XY,t(1;17)(p34;q25)
46,XY,t(1;18)(p32;q23)
46,XY,t(1;19)(q33;p11)
46,XY,t(2;8)(p22;p23.1)
46,XY,t(2;8)(q35;q11.2)
46,XY,t(2;11)(q11.2;q23.1)
46,XY,t(2;13)(p16;q31)
46,XY,t(2;15)(q32;q26)
46,XY,t(2;17)(q33;p11.2)
46,XY,t(2;18)(p23;q23)
46,XY,t(2;20)(p10;q10)
46,XY,t(2;22)(q37;q13)
46,XY,t(3;5)(p13;p15.1)
46,XY,t(3;6)(q25;q23)
46,XY,t(3;6)(q26;q23)
46,XY,t(3;6)(q27.1;q21.1)
46,XY,t(3;7)(p14;q34)
46,XY,t(3;7)(q26.2;p14)
46,XY,t(3;14)(q25;q32.3)
46,XY,t(3;19)(p21;p13)
46,XY,t(4;8)(p16;q22.2)
46,XY,t(4;12)(p16;q22)
46,XY,t(4;22)(q21;q13.3)
46,XY,t(5;6)(q35;p21.3)
46,XY,t(5;7)(q33;q22)
46,XY,t(5;8)(q3.1;q1.3)
46,XY,t(5;10)(p13;q23)
1
1
1
1
1
3
1
1
1
1
1
6
1
1
1
1
1
1
1
1
1
1
1
2
1
1
2
2
1
1
1
3
2
1
1
1
1
1
1
1
1
1
3
2
2
1
1
46,XY,t(8;11)(q21;q21)
46,XY,t(8;14)(q21.2;q11.2)
46,XY,t(8;14)(q22.1;q31)
46,XY,t(8;20)(p23.1;q13.1)
46,XY,t(8;21)(p21.1;q22.3)
46,XY,t(9;11)(q21.1;p14.3)
46,XY,t(9;12)(p21;q13.1)
46,XY,t(9;12)(p24;p11.2)
46,XY,t(9;13)(p22;q12.3)
46,XY,t(9;13)(p23;q21.1)
46,XY,t(9;13)(q33;q12)
46,XY,t(9;14)(q32;p11.2)
46,XY,t(10;12)(p13;p13.3)
46,XY,t(10;17)(q22.1;q21.3)
46,XY,t(10;19)(p11;p11)
46,XY,t(10;19)(q21.2;p13.3)
46,XY,t(11;12)(q13;p13)
46,XY,t(11;16)(p15;q12)
46,XY,t(11;19)(p11.2;q13.1)
46,XY,t(11;22)(?;?)
46,XY,t(11;22)(q23;q34)
46,XY,t(11;22)(q23.3;q11.2)
46,XY,t(12;16)(p11.2;p13.1)
46,XY,t(13;14)(q21;q21)
46,XY,t(13;18)(?;?)
46,XY,t(14;15)(q32.1;q13)
46,XY,t(14;17)(p?;q?)
46,XY,t(14;20)(p11.2;q11.2)
β-thalassaemia and HLA typing were diagnosed as suitable for
transfer which is almost exactly the expected percentage.
Preimplantation genetic screening (PGS)
The cumulative data for PGS from collections I–IV are shown
in Table VIIIa; the breakdown is for cycles with one indication, i.e. advanced maternal age (AMA), recurrent miscarriage
(RM), recurrent IVF failure (RIF) and severe male factor
(SMF). Cycles with two indications are included in the ‘other’
column. In data collection V (Table VIIIb), the data have been
divided to reveal multiple indications, e.g. AMA and RIF. The
use of PGS continues to increase with a total of 1990 cycles in
data collections I–IV and 1211 cycles in data collection V
alone. In data collections I–IV, there was about the same
number of cycles for RIF and AMA, but in the most recent data
there were 418 cycles for AMA and only 275 for RIF.
Cycles
1
1
2
1
2
1
1
2
1
2
3
1
1
3
1
1
1
2
2
1
4
6
2
2
2
1
1
1
46,XY,t(15;22)(p11.2;q12)
46,XY,t(18;21)(p10;p10)
47,XXY
47,XXY/46,XY
47,XY,+der( 15)
47,XYY
Robertsonian male
Reciprocal male
1
1
14
3
1
6
3
3
Miscellaneous
Cycles
45,XY,der(14;21)(q10;q10) and 45,XX,der(13;14)(q10;q10)
2
Technical outcomes were good for all cycles. For data collection V, >6500 embryos were biopsied and in 99% of cases
this was successful. FISH analysis resulted in a diagnosis on
93% of embryos and 37% were chromosomally normal and
suitable for transfer.
The overall pregnancy result was 16% per OR and this
ranged from 12% for AMA to 33% for SMF. A closer look at
the cycle parameters of these two groups offers some explanation for the difference in pregnancy results. It is not surprising
that the AMA group had the highest mean maternal age of 41
years. The SMF group had the lowest mean maternal age of 32
years. The AMA group fared poorly compared to the SMF
group with fewer oocytes collected per PGS OR (9.6 versus
15.2), fewer embryos biopsied per PGS OR (4.4 versus 6.4)
and fewer embryos that were genetically suitable for transfer
(31 versus 36%). Of those that had PGS, fewer AMA than
SMF patients had a transfer (60 versus 86%) and those that did
9
J.C.Harper et al.
Table VIa. Sexing only for X-linked disease using PCR or FISH, data
collection I–IV
Total cycles
Number infertile
Female age
Cycles cancelled before OR
Cycles to OR
Assisted reproduction treatment
IVF
ICSI
Cancelled after OR
Cycles to PGD
Zona breaching
AT drilling
Laser drilling
Mechanical
Biopsy method
Cleavage aspiration
Cleavage extrusion
Embryology
COC
Inseminated
Fertilized
Biopsied
Successfully biopsied
Diagnosed
Transferable
Transferred
Frozen
Clinical outcome
Cycles to embryo transfer
HCG positive
Positive heart beat
Clinical pregnancy rate (%) per
OR/embryo transfer (%)
Table VIb. List of indications for which sexing was performed, data
collection I–IV
FISH
PCR
Total
421
51
33
22
399
65
0
31
6
59
486
51
33
28
458
115
284
20a
379
10
49
1b
58
125
333
21
437
236
119
24
50
0
8
286
119
32
374
5
54
4
428
9
5354
4819
3420
2579
2490
2251
768
588
157c
808
627
501
412
376
286
152
119
56d
6162
5446
3921
2991
2866
2537
920
707
213e
305
92
70
18/23
48
22
16
27/33
353
114
86
19/24
a
Twenty-seven embryos from two cycles frozen before biopsy due to
hyperstimulation.
b
Twenty embryos frozen before biopsy.
c
Eleven cycles with embryos frozen without biopsy or after failed diagnosis
included.
d
Thirteen cycles with embryos frozen without biopsy or failed diagnosis
included.
e
Twenty-four cycles with embryos frozen without biopsy or after failed
diagnosis included.
OR = oocyte retrieval; PGD = preimplantation genetic diagnosis; AT = acid
Tyrode’s; COC = cumulus–oocyte complexes.
had fewer embryos transferred (1.6/embryo transfer versus 2.0/
embryo transfer). These differences would make a significant contribution to the lower pregnancy rate observed in the AMA group,
particularly when outcomes are expressed per oocyte retrieval.
This year centres were asked how they define AMA, RIF,
RM and SMF. For AMA, the majority of clinics defined this as
age >37 or >38 years, but several defined this as >35 years. For
RIF, the majority of clinics defined this as three or more failed
embryo transfer procedures (sometimes the definition adds
‘with good quality embryos’) or >10 embryos replaced. However, some clinics defined this as just two failed embryo transfer procedures. The majority of clinics defined RM as three
previous miscarriages (sometimes the definition adds ‘consecutive’). However, one clinic defined this as four previous miscarriages and several just as two previous miscarriages. Severe
male factor included many definitions; azoospermia, severe
oligoasthenoteratozoospermia, macrocephalic sperm, Klinefelter
10
Indication
Number of cycles
Haemophilia A
Duchenne muscular dystrophy
X-linked mental retardation
Retinitis pigmentosa
Adrenoleukodystrophy
Becker muscular dystrophy
Wiskott–Aldrich syndrome
Incontinentia pigmenti
Y deletion
Ornithine transcarbamylase deficiency
Myotubular myopathy
Hunter syndrome
Hydrocephalus
Agammaglobulinaemia
Fabry disease
Charcot–Marie–Tooth disease
Chronic granulomatous disease
Menkes’ disease
FG syndrome
X-linked autism
Löwe syndrome
Ectodermal dysplasia
Choroideraemia
Alport syndrome
Kallman syndrome
Lesch–Nyhan syndrome
Epilepsy
Coffin–Lowy syndrome
Barth syndrome
Ataxia
BRCA 1
Hypospadias
Exep macrosom males
Golabi–Rosen syndrome
Renal agenesis
Haemophilia B
Inversion X
Norrie disease
Skewed X inactivation
Sulphatidosis
Othersa
Total
98
87
24
24
23
17
13
13
11
10
9
9
9
9
8
7
6
6
6
6
5
4
4
2
2
2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
58
486
a
Others include cycles with unknown or unclear indications.
syndrome, males whose semen analysis did not fulfil the WHO
criteria, testicular sperm extraction patients, altered male meiosis, altered FISH results, non-obstructive azoospermia, Y chromosome microdeletion and immature spermatids. The
Consortium recognizes that there needs to be consistency in
these definitions for the purposes of data analysis and this will
be addressed in the future.
Social sexing
Table IXa summaries data I–IV for social sexing. A total of
182 cycles was started, with only 19 patients being infertile. Of
182 cycles reaching OR, 1109 embryos were successfully
biopsied and 304 diagnosed as transferable. A total of 131
cycles reached embryo transfer with a clinical pregnancy rate
of 24% per OR and 34% per embryo transfer.
Table IXb summarizes data V for social sexing. A total of 72
cycles was started, of which 22 included PGS. Only 22 patients
ESHRE PGD Consortium data collection V
Table VIc. Sexing only for X-linked disease using PCR or FISH, data
collection V
FISH
Total cycles
Number infertile
Female age
Cycles cancelled before OR
Cycles to OR
Assisted reproduction treatment
IVF
ICSI
ICSI + frozen
Both IVF and ICSI
Cancelled after OR
Cycles to PGD
Zona breaching
AT drilling
Laser drilling
Mechanical
Biopsy method
Cleavage aspiration
Cleavage extrusion
Embryology
COC
Inseminated
Fertilized
Biopsied
Successfully biopsied
Diagnosed
Transferable
Transferred
Frozen
Clinical outcome
Cycles to embryo transfer
HCG positive
Positive heart beat
Clinical pregnancy rate (%) per
OR/% per embryo transfer
Implantation rate (fetal heart
beats/embryos transferred) (%)
PCR
Total
124
28
33
9
115
3
0
28
0
3
127
28
9
118
23
90
1
1
8
107
0
3
0
0
0
3
23
93
1
1
8
110
63
44
0
0
1
2
63
45
2
104
3
2
1
106
4
1433
1234
902
713
705
654
255
169
22
55
35
25
19
19
19
8
8
0
1488
1269
927
732
724
673
263
177
22
89
29
23
20/26
3
0
0
0
92
29
23
20/25
29/158a (18)
0
29/166a (17)
a
Eleven embryos transferred removed from calculation due to lack of information regarding the number of FHB in pregnancies resulting from the transfer of
those embryos.
OR = oocyte retrieval; PGD = preimplantation genetic diagnosis; AT = acid
Tyrode’s; COC = cumulus oocyte complexes.
were infertile. The mean maternal age was 36 years. No cycles
were cancelled prior to OR. A total of 1002 oocytes was collected, and 396 embryos were successfully biopsied. In 93% of
cycles, the zona was breached by mechanical means; and the
most used biopsy method was cleavage extrusion. In 61% of
cycles PCR was used and in 39% FISH was used. In 11 cycles,
embryos of the required sex were not obtained and the patients
did not have an embryo transfer procedure. No clinical pregnancies were obtained in the combined social sexing and PGS
group. For the cases where FISH was used, a clinical pregnancy rate of 50% was obtained. For the cases where PCR was
used, a clinical pregnancy rate of 27% per OR and 29% per
embryo transfer procedure was obtained. An overall implantation rate of 14% was obtained.
Pregnancies and babies
In the four former data collections (I–IV), detailed data on
648 pregnancies have been collected. It is now clear from
Table VId. List of indications for which sexing has been performed, data
collection V
Indication
Number of cycles
Duchenne muscular dystrophy
Haemophilia A + B
Becker muscular dystrophy
Y deletion
Retinitis pigmentosa
Adrenoleucodystrophy
Menkes’ disease
Inversion X
X-linked mental retardation
Unknown
Alport
Hunter’s disease
Chronic granulomatous
Lowes
OTC
Falizaeus–Merzbacher
X-linked myotublar
Hoyeraal–Hreidarrson
Austism
Fragile X
Sex chromosome mosaicism
Opitz–Kaveggia
X-linked haemophagocytic
Wiscott–Aldrich
Klienfelter syndrome
CMT
X-linked chondrodysplasia
X-linked retinoschisis
LHON mitochondrial
Total
36
22
9
7
6
6
6
4
3
3
3
2
2
2
2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
127
OTC = ornithine transcarbamylase; CMT = charcot marie tooth disease;
LHON = leber hereditary optic neuropathy.
these different reports that the pregnancies obtained after
PGD are quite comparable to those obtained after ICSI
(Bonduelle et al., 2005), giving a first indication that embryo
biopsy is not detrimental to the course and outcome of pregnancy (Table Xa). As in ICSI, no particular complication
stands out, and the most important problem remains the
multiplicity, causing most of the morbidity and mortality
(Table XIa). With the introduction of single embryo transfer
policies in many countries, this problem will decrease in the
future. The most frequent mode of delivery was Caesarean
section (Table XIIa), both for the singletons as for the twins
and triplets, and baby characteristics (birth weight, length,
gestational age at delivery) and malformations at birth are
again quite similar to the characteristics of ICSI babies
(Table XIIIa, XIVa).
The most important factor for PGD in data collection I–IV
was the risk of misdiagnosis (Table XVa). Due to the complexity of the data, it is not possible to calculate the error rate
per fetal sac: several babies have been tested more than once,
e.g. with a prenatal diagnosis, and with a physical examination at birth. It is important, however, to take note of the
misdiagnoses that occurred, and to try and find the cause of
the misdiagnosis. In this way, future misdiagnosis can be
avoided.
For data V, whereas 494 cycles ended in a positive HCG,
only 485 pregnancies were reported. Fifteen pregnancies were
lost for follow-up after the cycle, and for 17 positive HCG, no
11
12
103
47
33
12
91
0
90
0
1
0
7
84
78
6
0
0
0
83
1
0
1219
1050
660
473
463
355
174
159
20
78
29
24
26/31
12
202
0
0
5
8
211
148
56
3
4
2b
194b
11
6
2901
2528
1762
1413
1395
1188
741
405
161
187
58
46
21/25
β-Thal
247
75
33
28
219
CFc
Autosomal recessive
53
15
14
23/26
752
625
440
364
363
299
185
121
8
0
47
9
0
33
16
7
0
1
57
0
4
0
6
56
66
5
34
4
62
SMA
14
3
1
7/7
247
189
139
95
94
83
54
37
28
0
14
0
0
9
5
0
0
0
15
0
0
0
1
14
15
3
36
0
15
SC
8
3
1
13/13
145
119
106
83
83
62
34
23
0
0
8
0
0
8
0
0
0
0
8
0
0
0
0
8
8
0
32
0
8
EB
107
25
21
15/20
1728
1521
1116
766
757
634
272
213
19
0
127
3
2
78
52
0
2
0
138
3
0
3
12
132
160
11
33
16
144
DM1
68
15
12
15/18
1065
935
673
451
443
380
177
111
33
0
75
0
3
35
40
0
3
0
78
0
0
3
3
78
87a
5
32
6
81
HD
9
3
1
10/11
111
93
82
78
78
61
32
25
0
0
10
0
0
10
0
0
0
1
9
0
0
0
0
10
10
7
28
0
10
AP
Autosomal dominant
9
4
4
24/44
209
176
137
67
66
55
23
17
3
0
15
0
0
2
13
0
0
0
17
0
0
0
2
15
18
0
33
1
17
CMT
3
0
0
0
20
15
11
10
10
8
4
4
0
0
3
0
0
0
3
0
0
0
3
0
0
0
0
3
3
0
33
0
3
ACH
10
2
2
20/20
112
97
79
64
63
58
36
25
4
0
10
0
0
8
2
0
0
0
10
0
0
0
0
10
10
0
32
0
10
MS
21
6
6
26/29
348
293
208
164
164
138
93
54
31
0
23
0
0
15
8
0
0
2
21
0
0
0
0
23
26
1
66
3
23
DMD
23
6
6
17/26
296
270
192
132
131
117
52
36
6
0
30
0
2
11
19
0
2
2
32
0
0
2
4
32
38
14
36
2
36
FRAXA
Specific sex-linked
11
4
3
19/27
176
154
113
72
71
41
28
25
4
0
15
1
0
15
0
1
0
6
9
0
1
0
0
16
16
0
28
0
16
Haem
80
29
26
28/33
1420
1186
903
644
638
545
263
185
64
1b
80b
5
3
40
38
7
3
2
86
0
1
5
6
88
102
13
33
8
94
Other
681
202
167
20/25
10749d
9251
6621
4876
4819
4024
2168
1440
381
3b
734b
30
16
490
258
18
14
26
775
3
7
18
49
780
909
181
33
80
829
Total
CF = cystic fibrosis (various mutations); β-thal = β -thalassaemia; SMA = spinal muscular atrophy; SC = sickle-cell anaemia; EB = epidermolysis bullosa; DM1 = myotonic dystrophy; HD = Huntington’s disease;
AP = amyloid polyneuropathy, MS = Marfan’s syndrome; CMT = Charcot–Marie–Tooth disease; ACH = achondroplasia; FRAXA = fragile-X syndrome; DMD = Duchenne muscular dystrophy (specific);
Haem = haemophilia; OR = oocyte retrieval; AT = acid Tyrode’s; COC = cumulus–oocyte complex.
a
Includes three HD with exclusion.
b
Three cycles had both polar body biopsy and cleavage stage biopsy.
c
One cycle for two indications: cystic fibrosis and fragile X syndrome.
d
Eight cycles with missing data.
Total cycles
Number infertile
Female age
Cycles cancelled before OR
Cycles to OR
Assisted reproduction treatment
IVF
ICSI
Cancelled ICSI
Frozen
Unknown
Cancelled after OR
Cycles to PGD
Zona breaching
AT drilling
Laser drilling
Mechanical
Unknown
Biopsy method
Polar body biopsy
Cleavage aspiration
Cleavage extrusion
Unknown
Embryology
COC
Inseminated
Fertilized
Biopsied
Successfully biopsied
Diagnosed
Transferable
Transferred
Frozen
Clinical outcome
Cycles to embryo transfer
HCG positive
Postive heart beat
Clinical pregnancy rate (%) per OR/% per embryo transfer
Indication
Table VIIa. Cycles performed for single gene disorders using PCR, data collection I–IV
J.C.Harper et al.
ESHRE PGD Consortium data collection V
Table VIIb. List of indications for monogenic diseases listed as other in Table VIIa, data
collection I–IV
Indication
No. of cycles
Cycles without indication
21-Hydroxylase deficiency
Adrenoleukodystrophy
Agammaglobulinaemia
Alport syndrome
Adult polycystic kidney disease
BRCA1
Carbohydrate-deficient glycoprotein syndrome type 1A
Central core disease
Crouzon syndrome
Familial adenomatous polyposis coli (Gardner syndrome)
Fanconi anaemia
Gaucher disease
Glucose-6-phosphatase deficiency
Gorlin syndrome
HLA typing
Hunter syndrome (MPS II)
Hyperinsulinaemic hypoglycaemia PHH1
Infantile neuronal ceroid lipofuscinosis
Junctional epidermolysis bullosa
Lesch–Nyhan disease
Medium chain acyl-CoA dehydrogenase deficiency
MELAS (mitochondrial myopathy, encephalopathy, lactacidosis, stroke)
Metachromatic leukodystrophy
Neurofibromatosis
Oral–facial–digital syndrome type 1
Ornithine transcarbamylase deficiency
Osteogenesis imperfecta type I
Osteogenesis imperfecta type IV
Pelizaeus–Merzbacher disease
Retinoblastoma
RhD sensitization
Rhizomelic chondrodysplasia punctata
Skewed X inactivation
Skin fragility syndrome
Spinal and bulbar muscular atrophy
Spinocerebellar ataxia type 7
Stickler syndrome
Tay–Sachs disease
Tuberous sclerose
Tyrosinaemia
Von Hippel–Lindau disease
Waardenburg syndrome
Y deletion
ZFX/ZFY for sexing only
Total
7
2
5
1
4
1
1
3
3
2
4
1
5
1
2
3
1
1
2
1
1
1
2
1
3
3
2
3
4
1
1
4
2
1
2
1
1
3
4
3
1
3
1
3
2
102
data were reported (five centres). Thirteen pregnancies were
reported without a cycle, and 10 pregnancies were a result
from a previous frozen cycle and are thus not included in the
cycle database. The overall pregnancy data V are similar to the
data from previous data collections: multiplicity is still a major
cause of complications, morbidity and mortality and measures
taken to avoid multiplets are still not transpiring in the data
(Tables Xb, XIb, XIIb). No particular complication or malformation stands out (Table XIIIb).
Of the 325 pregnancies in data collection V that ended in the
birth of at least one baby, four deliveries were lost to followup, and no data were submitted on seven deliveries. Data were
submitted on 314 deliveries. Data collection V is not remarkable concerning the babies born: all baby characteristics such
as weight at birth, malformations and neonatal complications
are comparable to data submitted in earlier data collections
(Tables XIIb–XIVb).
No misdiagnosis was reported for data collection V. However, it is noted that three de novo reciprocal translocations
were reported out of a total of 476 fetal sacs (1/159). In comparison, on a large series of prenatal diagnosis, a prevalence of
1/2000 amniocenteses was found (Warburton, 1991). This is
the first report of a cluster of de novo reciprocal translocations.
Whether this is coincidence, or due to better follow-up of pregnancies and babies and reporting, will have to be investigated
over the longer term (Table XVb).
An attempt was made to calculate the singleton live birth
rates per OR (ideally live birth rates per started cycle should be
13
14
38 (3)
22 (0)
34 (36)
3 (0)
35 (3)
0
35 (3)
0
5 (0)
30 (3)
17
13 (3)
0
0
28 (3)
2 (0)
487 (62)
376 (53)
256 (35)
182 (29)
181 (29)
163 (26)
114 (5)
70 (1)
16 (4)
29 (1)
13 (0)
10 (0)
29/34 (0)
18 (0)
26 (0)
3
66
0
6
63
19
42
2
1
59
3
837
747
555
365
364
304
161
95
12
52
17
13
19/25
12
13
β-Thal (β-thal + HLA)b
77
32
33
8
69
CFa
Autosomal recessive
24
8
5
20/21
6
12
360
262
181
137
135
120
79
51
9
0
21
4
10
12
3
0
24
1
0
25
27
4
33
2
25
SMA
8
3
3
30/38
2
13
116
98
55
42
41
33
18
15
5
2
8
0
4
4
2
0
10
0
0
10
12
3
32
2
10
SCc
29 (5)
9 (0)
6 (0)
14/21 (0)
9 (0)
19 (0)
566 (74)
449 (61)
318 (47)
248 (39)
241 (39)
190 (38)
74 (13)
47 (9)
3 (1)
4 (0)
35 (5)
3 (0)
11 (0)
28 (5)
3 (0)
2 (0)
42 (5)
0
44 (5)
53 (6)
8 (1)
34 (32)
9 (1)
44 (5)
HD (HDexcl)d
31
12
8
21/26
8
15
492
440
325
208
205
178
83
53
3
3
33
0
7
26
3
1
38
0
3
36
43
9
34
4
39
DM1
Autosomal dominat
2
1
1
25/50
1
25
88
68
59
33
33
28
12
4
2
0
4
0
0
4
0
0
4
0
0
4
4
0
31
0
4
CMTe
3
0
0
0
0
0
40
34
21
14
14
12
6
5
0
0
3
0
0
3
0
0
4
0
1
3
4
0
34
0
4
ACH
11(1)
5(0)
4(0)
27/36 (0)
5 (0)
21 (0)
219 (7)
157(4)
121(4)
95(4)
91(3)
81(2)
58(1)
24(1)
9(0)
0
15 (1)
0
7
8(1)
0
0 (0)
15 (1)
1 (0)
14(1)
16 (1)
4
31(28)
1 (0)
15 (1)
DMD (BMD)f
2
2
2
100
2
40
32
28
21
9
9
7
5
5
0
0
2
0
2
0
2
0
0
2
2
0
34
0
2
Haem
Specific sex-linked
6
3
2
17/33
1
10
142
110
84
61
61
46
15
10
4
1
11
0
2
9
1
0
12
0
0
12
13
0
35
1
12
FRAXA
24
9
9
27/38
9
20
396
336
257
188
185
160
82
46
12
3
29
3
26
3
1
32
0
33
36
3
34
3
33
Others
228
82
63
21/28
73
17
3918
3223
2339
1654
1631
1388
726
436
80
14
257
12
80
186
17
5
295
1
18
283
335
86
33
34
301
Total
CF = cystic fibrosis (various mutations); β-thal = β-thalassaemia; SMA = spinal muscular atrophy; SC = sickle-cell anaemia; DM1 = myotonic dystrophy; HD = Huntington’s disease; CMT = Charcot–Marie–Tooth
disease; ACH = achondroplasia; FRAXA = fragile-X syndrome; DMD = Duchenne muscular dystrophy (specific); BMD = Becker muscular dystrophy (specific); Haem = haemophilia; OR = oocyte retrieval; AT = acid
Tyrode’s; COC = cumulus–oocyte complexes.
a
Includes one cycle for two indications: CF and social sexing.
b
Cycles for β-thalassaemia and HLA typing in parentheses.
c
Includes two cycles for sickle cell and β-thalassaemia.
d
HD by exclusion.
e
Includes one cycle for X-linked dominant inheritance.
f
Cycles for BMD in parentheses.
Total cycles
Number infertile
Female age
Cycles cancelled before OR
Cycles to OR
Assisted reproduction treatment
IVF
ICSI
Frozen
Cancelled after OR
Cycles to PGD
Zona breaching
AT drilling
Laser drilling
Mechanical
Biopsy method
Polar body biopsy
Cleavage aspiration
Cleavage extrusion
Embryology
COC
Inseminated
Fertilized
Biopsied
Successfully biopsied
Diagnosed
Transferable
Transferred
Frozen
Clinical outcome
Cycles to embryo transfer
HCG positive
Positive heartbeat
Clinical pregnancy rate (% per OR/% per embryo transfer)
Number fetal hearts
Implantation rate (fetal hearts/embryos transferred) (%)
Indication
Table VIIc. Cycles performed for single gene disorders using PCR, data collection V
J.C.Harper et al.
ESHRE PGD Consortium data collection V
Table VIId. List of indications for monogenic diseases listed as other in Table VIIc
Indications
No. of cycles
Adrenoleukodystrophy
Alport syndrome
BRCA1
Canavan disease
Central core disease
Epidermolysis bullosa simplex
Familial ademonatous polyposis (Gardner syndrome)
LCHAD
Lesch–Nyhan disease
Multiple exostoses
Norrie’s disease
Ornithine transcarbamylase deficiency
Osteogenesis imperfecta type I
PDH deficiency
Polycystic kidney disease
Retinoblastoma
Rhizomelic chondro dysplasia punctata
Spinocerebellar ataxia 3 (SCA3)
Spinocerebellar ataxia 7 (SCA7)
Severe combined immunodeficiency
Stickler syndrome
Von Hippel–Lindau
Total
1
2
5
2
3
1
3
1
1
1
1
1
1
1
1
4
1
1
2
1
1
1
36
LCHAD = long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.
Table VIIIa. Cycles performed for preimplantation genetic screening, data collection I–IV
Indication
Total cycles
Number infertile
Female age
Cycles cancelled before OR
Cycles to OR
Assisted reproduction treatment
IVF
ICSI
IVF + ICSI
Frozen
Frozen and ICSI
Unknown
Cancelled after OR
Cycles to PGS
Zona breaching
AT drilling
Laser drilling
Mechanical
Unknown
Biopsy method
Polar body biopsy
Cleavage aspiration
Cleavage extrusion
Cleavage flow displacement
Unknown
Embryology
COC
Inseminated
Fertilized
Biopsied
Successfully biopsied
Diagnosed
Transferable
Transferred
Frozen
AMA
Recurrent miscarriage Recurrent IVF failure
Severe male factora
No indication Other
Total
625
596
40
1
624
285
229
36
8
277
642
637
36
12
630
65
65
32
1
64
54
53
33
1
53
229
194
35
1
228
1900
1774
35
24
1876
128
490
1
0
0
5
25
599
39
235
2
0
0
1
3
274
120
476
6
4
1
23
38
592
1
63
0
0
0
0
4
60
11
42
0
0
0
0
0
53
56
157
1
0
0
14
7
221
355
1463
10
4
1
43b
77
1799
354
209
23
13
198
68
7
1
394
151
10
37
7
46
7
0
38
10
5
0
149
49
9
14
1140
533
61
65b
51c
472c
57
7
13
7
251
14
1
1
7
499
42
6
38
0
33
26
1
0
3
49
1
0
0
2
215
3
1
0
70c
1519c
143
16
52
6933
6143
4427
3580
3523
2815d
582d
971d
92
4134
3467
2495
1916
1827
1461d
527d
465d
44
8708
7479
5395
3495
3440
3186d
1219d
881d
196
952
735
464
326
320
263
129
104
10
699
628
467
365
346
215d
195d
113d
7
2948
2478
1754
1326
1304
1105d
490d
398d
87
24 374b
20 930
15 002
11 008
10 760
9045d
3142d
2932d
436
15
J.C.Harper et al.
Table VIIIa. Continued
Indication
AMA
Recurrent miscarriage
Recurrent IVF failure
Severe male factora
No indication
Other
Total
Clinical outcome
Cycles to embryo transfer
HCG positive
Positive heart beat
Clinical pregnancy rate (%) per OR/%
per embryo transfer
440
130
103
17/23
223
74
61
22/27
416
118
86
14/21
51
21
19
30/37
48
18
17
32/35
164
70
50
22/30
1342
431
336
18/25
a
These data were not extracted from data I–III.
Several cycles had incomplete results.
One cycle had cleavage stage biopsy and polar body biopsy.
d
Several cycles from one centre had no information on the number of embryos diagnosed, number of embryos diagnosed as transferable, but patients did have
embryos transferred. In these cases, undiagnosed or abnormal embryos were transferred.
AMA = advanced maternal age; OR = oocyte retrieval; AT = acid Tyrode’s; COC = cumulus–oocyte complexes.
Other: includes data with two indications.
b
c
Table VIIIb. Cycles performed for preimplantation genetic screening, data collection V
Indication
Total number of cycles
Number infertile
Female age
Cycles cancelled before OR
Cycles to OR
Assisted reproduction treatment
IVF
ICSI
IVF + ICSI
Unknown
Frozen embryos
IVF + frozen
ICSI + frozen
Cancelled after OR
Cycles to PGS
Zona breaching
AT drilling
Laser drilling
Mechanical
Biopsy method
Polar body biopsy
Cleavage aspiration
Cleavage extrusion
Cleavage flow displacement
Embryology
COC
Inseminated
Fertilized
Biopsied
Successfully biopsied
Diagnosed
Transferable
Transferred
Frozen
Clinical outcome
Cycles to embryo transfer
HCG positive
Positive heart beat
Clinical pregnancy rate (%) per OR/% per
embryo transfer
Number of fetal hearts
Implantation rate (fetal hearts/embryos transferred) (%)
AMA
AMA +
AMA + RIF Recurrent
RIF
miscarriage
miscarriage
SMF
No
Other
indication
418
394
41
2
416
43
36
40
2
41
129
114
40
0
129
198
190
36
2
196
275
256
35
1
274
101
101
32
1
100
13
10
33
0
13
34
19
35
1
33
1211
1120
38
9
1202
69
345
1
0
9
32
0
0
33
94
1
0
13
182
0
0
23
249
1
1
1
98
0
0
5
8
0
0
3
30
0
0
156
1038
3
1
0
1
21
395
0
0
3
38
0
1
2
127
0
1
6
190
0
0
12
262
0
1
5
95
0
0
1
12
0
0
1
32
0
4
51
1151
211
177
7
18
20
0
84
42
1
135
54
1
145
115
2
52
43
0
4
8
0
19
8
5
668
467
16
18
342
35
0
20
18
0
0
46
81
0
0
5
172
13
0
17
225
20
0
0
85
10
0
0
11
1
0
2
28
2
0
108
962
81
0
3974
3323
2315
1826
1802
1694
554
387
34
391
324
192
209
208
199
64
49
9
1311
1116
795
739
733
710
229
163
36
2529
2119
1484
1101
1094
994
352
255
33
3892
3322
2343
1732
1715
1596
672
433
99
1524
1241
851
645
638
541
228
163
32
137
117
80
70
67
66
30
20
1
429
347
261
219
215
191
82
58
7
14187
11909
8321
6541
6472
5991
2211
1528
251
237
71
48
12/20
28
6
5
12/18
96
22
18
14/19
135
49
37
19/27
227
74
50
18/22
82
38
33
33/40
12
2
2
15/17
29
9
5
15/17
846
271
198
16/23
57
15
8
16
21
13
51
20
66
15
44
27
2
10
8
14
AMA = advanced maternal age; RIF = repeated implantation failure; SMF = severe male factor; OR = oocyte retrieval; AT = acid Tyrode’s;
COC = cumulus–oocyte complexes.
16
Total
257
17
ESHRE PGD Consortium data collection V
Table IXa. Preimplantation genetic diagnosis (PGD) for social sexing, data
collection I–IV
Table IXb. Continued
FISH
Method for sexing
Total cycles
Number infertile
Female age
Cycles cancelled before OR
Cycles to OR
Assisted reproduction treatment
IVF
ICSI
Frozen
Frozen and ICSI
Cancelled after OR
Cycles to PGD
Zona breaching
AT drilling
Laser drilling
Mechanical
Biopsy method
Cleavage aspiration
Cleavage extrusion
Embryology
COC
Inseminated
Fertilized
Biopsied
Successfully biopsied
Diagnosed
Transferable
Transferred
Frozenb
Clinical outcome
Cycles to embryo transfer
HCG positive
Positive heart beat
Clinical pregnancy rate (%)
per OR/% per embryo transfer
FISH
PCR
Unknown
118
18
35
0
118
59
0
34
0
59
5
1
35
0
5a
182
19
35
0
182a
102
13
3
0
3
115
4
52
2
1
6
53
3
2
0
0
5
0
109
67
5
1
14
168
9
106
0
10
0
43
0
0
0
19
106
43
115
0
10
43
0
0
125
43
1379
1343
972
840
766
700
287
166
93
887
668
428
353
343
316
182
138
35
23
19
11
0
0
0
0
0
0c
2289
2030
1411
1193
1109
1016
469
304
128
90
37
35
30/39
41
19
9
15/22
0
0
0
0
131
56
44
24/34
a
One natural cycle included.
Eleven cycles with embryos frozen without biopsy or failed diagnosis included.
c
Three embryos frozen without biopsy were not included.
OR = oocyte retrieval; AT = acid Tyrode’s; COC = cumulus oocyte complexes.
b
Table IXb. Preimplantation genetic diagnosis (PGD) for social sexing, data
collection V
FISH
SS only
Total cycles
Number infertile
Female age
Cycles cancelled before OR
Cycles to OR
Assisted reproduction treatment
IVF
ICSI
Frozen
IVF + frozen
ICSI + frozen
Unknown + frozen
Cancelled after OR
Cycles to PGD
Zona breaching
AT drilling
Laser drilling
Mechanical
Biopsy method
Cleavage aspiration
Cleavage extrusion
PCR
PCR
Total
Total
Total
SS + PGS
6
0
31
0
6
22
6
38
0
22
44
16
36
0
44
72
22
36
0
72
2
4
0
0
0
0
0
6
1
21
0
0
0
0
0
22
1
36
0
1
4
2
0
44
4
61
0
1
4
2
0
72
0
6
0
0
0
22
0
0
44
0
6
66
5
1
0
22
0
44
5
67
Embryology
COC
Inseminated
Fertilized
Biopsied
Successfully biopsied
Diagnosed
Transferable
Transferred
Frozen
Clinical outcome
Cycles to embryo transfer
HCG positive
Positive heart beat
Clinical pregnancy rate (%)
per OR/% per embryo transfer
Implantation rate (fetal hearts/
embryos transferred)(%)
SS only
SS + PGS
84
78
50
36
36
32
16
12
6
301
210
128
100
100
83
24
23
1
617
454
302
260
260
236
143
110
14
1002
742
480
396
396
351
183
145
21
6
3
3
50/50
14
4
0
0/0
41
15
12
27/29
61
22
15
21/25
15
14
33
0
PGS = aneuploidy screening; SS = social sexing; OR = oocyte retrieval;
AT = acid Tyrode’s; COC = cumulus–oocyte complexes.
Table Xa. Evolution of pregnancy, data collection I–IV
Pregnancies
FISH cycles
PCR cycles
Subclinical pregnanciesa
Clinical pregnancies
Singletons
Twins
Triplets
Quadruplet
First trimester loss
Miscarriage
Extrauterine pregnancy
Vanishing twins/triplets
Ongoing pregnancies >12 weeks
Second trimester loss
Miscarriage
TOP after misdiagnosisc
TOP after amniocentesisd
Reductione
Reduction of multiple pregnancies
Quadruplet to twin
Triplet to twin
Triplet to singleton
Twin to singleton
Normal evolution
Lost to follow-up
Deliveries
Singletons
Twins
Triplets
No. of pregnancies
No. of fetal sacs
648
485/648
163/648
53/648
595
417/595
149/595
28/595
1/595
67/595
62/595
5/595
803
528
16/528
10/528b
4/528
2/528
512
33/512
479
350/479
120/479
9/479
803
417/803
298/803
84/803
4/803
111/803
71/803
5/803
35/803
692
23/692
16/692b
4/692
2/692
1/692
10/692
2/692
5/692
2/692
1/692
659
42/659
617
350/617
240/617
27/617
a
Subclinical pregnancy defined as pregnancy without any other clinical signs,
but positive serum HCG.
b
One triplet: fetal reduction, followed by amniocentesis and loss of remaining
twin at 16 weeks (one fetal sac counted in reduction, two in miscarriage, one
second trimester pregnancy loss after miscarriage counted).
c
TOP = termination of pregnancy. One misdiagnosis for sexing, FISH, female
fetus, indication social sexing; one misdiagnosis for β-thalassaemia, PCR; one
misdiagnosis for myotonic dystrophy, PCR, one misdiagnosis after PGS,
karyotype 45,X.
d
Trisomy 18 after amniocentesis, indication for PGD parent carrier of reciprocal translocation not involving chromosome 18; one polymalformation.
e
One misdiagnosis for sexing, PCR, indication Duchenne, twin pregnancy, selective termination of male fetus. Cycle done in 1996, Y-specific amplification only.
17
J.C.Harper et al.
Table Xb. Evolution of pregnancy, data collection V
Pregnancies
FISH cycles
PCR cycles
Subclinical pregnancies
Clinical pregnancies
Singletons
Twins
Triplets
Quadruplet
Unknown
First trimester loss
Miscarriage
Vanishing twins
Extrauterine gestation
Ongoing pregnancies (>12 weeks)
Second trimester loss
Miscarriage
TOPe
Reduction of multiple pregnancies
Triplet to twin
Triplet to singleton
Quadruplet to twin
Normal evolution
Singletons
Twins
Triplet
Lost to follow-up
Singletons
Twins
Triplets
Deliveries
Singletons
Twins
Triplets
Table XIa. Continued
No. of
pregnancies
No. of
fetal sacs
485
398/485a
88/485a
113/485
372
277/372
85/372
8/372
1/372
1/372
31/372
26/372c
476
389/476a
88/476a
476
277/476
170/476
24/476
4/476
(1)/476b
46/476
29/476
11/476
6/476
430
13/430
11/430
2/430
8/430
2/430
4/430
2/430
409
258/409
142/409
9/409
9/409
6/409
0/409
3/409
400
252/400
142/400
6/400
5/372d
341
10/341
8/341
2/341
331
258/331
71/331
3/331
7/331
6/331
0/331
1/331
325
252/325
71/325
2/325
Complication
Singletons
(n = 65
patients)
Intrauterine death
Intrauterine growth retardation
OHSS
Oligohydramnios
Placenta accreta
Placenta praevia
Polyhydramnios
Pre-eclampsia and hypertension
Premature rupture of the membranes
Preterm contractions
Preterm dilatation
Preterm labour
Psychological problems
Pyelonephritis
Toxoplasmosis maternal problem of
asphyxia and shock lung
Twin to twin transfusion
Total
Twins
(n = 24
patients)
Triplets
(n = 3
patients)
0
6
1
1
3
4
0
8
0
18
1
13
1
1
0
2
1
0
1
0
0
1
4
5
7
2
7
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
92
1
36
0
3
HELLP = haemolysis, elevated liver enzymes, low platelet count; OHSS =
ovarian hyperstimulation syndrome.
Table XIb. Complications in clinical pregnancies (total n = 61 patients), data
collection V
Complication
Incidence
Singletons
(n = 45
patients)
a
One fetal sac was tested with FISH and PCR.
Number of fetal heartbeat (FHB) not known; counted further as one FHB.
c
One miscarriage after amniocentesis.
d
One heterotopic gestation continued as singleton after reduction of extrauterine gestation at 6 weeks.
e
One termination of pregnancy (TOP) for cystic hygroma, failed karyotype,
one TOP for Turner mosaic at amniocentesis.
Incidence
Twins
(n = 13
patients)
Triplets
(n = 3
patients)
b
Table XIa. Complications in clinical pregnancies (total n = 92 patients), data
collection I–IV
Complication
Incidence
Singletons
(n = 65
patients)
Abortion risk
Abruptio placentae, retroplacental
haematoma
Anaemia
Bleeding
Cerclage
Chorioamnionitis
Diabetes mellitus
Oedema
Extrauterine pregnancy followed by
salpingectomy
Gastrointestinal problems
HELLP syndrome
Idiopathic thrombocytopeny
18
Twins
(n = 24
patients)
Triplets
(n = 3
patients)
1
4
0
0
0
0
1
13
3
2
4
1
1
0
2
0
0
2
0
0
0
0
2
0
0
0
0
1
3
1
0
0
0
1
0
0
Abruptio placentae, retroplacental
haematoma
Antepartum haemorrhage
Bleeding
Cholestase
Diabetes mellitus
Oedema
Emesis
Gastrointestinal problems
HELLP syndrome
Intrauterine growth retardation
OHSS
Pregnancy-induced hypertension
Placenta praevia (+ bleeding)
Pre-eclampsia and hypertension
Premature rupture of the membranes
Preterm contractions
Preterm dilatation
Preterm labour
Twin to twin transfusion
Uterine bleeding post-partum
Total
2
1
13
0
4
1
12
2
3
0
1
1
3 (+3)
4
0
11
2
4
0
1
65 (+3)
0
0
0
1
0
1
0
4
0
0
1
1
0
0
2
0
6
2
2
0
0
20
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
0
3
HELLP = haemolysis, elevated liver enzymes, low platelet count; OHSS =
ovarian hyperstimulation syndrome.
calculated but this is impossible because of the obvious underreporting of cancelled cycles). Only fresh cycles and pregnancies with information up to and shortly after birth were taken
into account. Of the 1993 selected cycles, 455 resulted in a
positive HCG, 112 of which were biochemical pregnancies. Of
ESHRE PGD Consortium data collection V
Table XIIa. Method of delivery and gestational age, data collection I–IV
No. delivered
Method of delivery
Vaginal
Caesarean
Vaginal and Caesarean
Unknown
Term at delivery
Preterm
Term
Unknown
Total
Singletons
Twins
Triplets
479
350
120
9
204
227
1
47
177
145
0
28
27
74
1
18
0
8
0
1
116
321
42
46
280
24
64
39
17
6
2
1
Table XIIb. Method of delivery and gestational age, data collection V
No. of deliveries
Method of delivery
Vaginal
Caesarean section
Vaginal + Caesarean section
Unknown
Gestational age at delivery
Preterm
At term
Unknown
Total
Singleton
Twin
Triplet
325
252
71
2
129
158
0
38
117
110
0
25
11
47
0
13
1
1
0
0
71
153
101
31
140
81
38
13
20
2
0
0
Table XIIIa. Data on live-born children, data collection I–IV
Total no. of children born
Sex
Male
Female
Unknown
Mean birthweight (g)
Singletons
Twins
Triplets
Unknown
Mean birth length (cm)
Singletons
Twins
Triplets
Unknown
608
241
332
35
2900
3266
2477
1756
48
50
47
44
241/573
332/573
n = 534
n = 319
n = 194
n = 21
n = 74
n = 322
n = 219
n = 97
n=6
n = 286
Table XIVa. Congenital malformations and neonatal complications at birth,
data collection I–IV
Malformations
No data available
No malformations
Total malformations
Major malformations at birth
Bilateral clubfoot
Chylothorax
Cleft lip and palate
Congenital hip luxation
Cystic mass abdomen
Exencephalia
Fryns syndrome, neonatal death
Hydrocephaly
Large cavernous haemangioma
Pes equinovarus
Phocomelia and pulmonary deficiency
Prune belly syndrome and stillbirth
Stillborn at 28 weeks (no details)
Unilateral intrauterine torsio testis
Minor malformations
ASD
Bilateral hydrocoele
Capillary haemangioma
Cryptorchidy
Mongolian spot
Pyelourethral junctional stenosis
Sacral dimple
Syndactyly digit iv–v
Uniumbilical artery
Neonatal complications
No data available
No neonatal complications reported
Neonatal complications reported
Stay at NCU (<1 week to 1 months)
Intrauterine death at 31 weeks,
prematurity in two other children
Apnoea
Dysmature
Feeding problems
Fryns syndrome and neonatal death
Gastro-oesophagal reflux
Neonatal deaths <7 days
Pneumothorax
Prematurity and neonatal complication
(intubation, NCU)
Prune belly syndrome in one twin and
prematurity in the other twin (28 weeks)
Respiratory problems
Stillborns
177/608
403/431
28/431
1 singleton
1 twin
1 singleton
1 singleton
1 twin
1 twin
1 singleton
1 singleton
1 singleton
1singleton
1 singleton
1 twin
1 twin
1 singleton
1 twin
1 singleton
2 singletons, 2 twins
1 singleton
1 singleton
2 twins
1 singleton
2 singletons
1 singleton
169/608
389/439
50/439
3 singletons, 2 twins
3 triplets (1 pregnancy)
1 twin
6 twins (3 pregancies)
2 twins (2 pregnancies)
1 singleton
1 singleton
3
1 twin
5 singletons, 5 twins, 6 triplets
2 twins
1 singleton, 2 twins
4 twins, 2 singletons
Table XIIIb. Data on live-born children, data collection V
Total children born
Sex
Male
Female
Unknown
Mean birth weight (g)
Singletons
Twins
Mean birth length (cm)
Singletons
Twins
Mean head circumference
Singletons
Twins
Apgar scores
Good
Poor
382
169
203
10
3240
2350
(n = 225/247)
(n = 110/132)
49
47
(n = 133/247)
(n = 56/132)
34
32
(n = 106/247)
(n = 45/132)
188/189
1/189
Numbers in parentheses indicate the number of newborns for whom information is available out of the total number of newborns.
the remainder, four pregnancies were lost to follow-up, 32
were lost during pregnancy, and a total of 378 babies were
born from 307 deliveries. These were 238 singletons (all live
born), 134 twins (one stillborn) and six triplets (three stillborn).
This results in a live birth rate of 15% per OR (307/1993) and a
singleton live birth rate per OR of 12% (238/1993).
General remarks
Due to the large amount of work the data collection involves,
this data collection is 1 year behind its expected publication
date. The Steering Committee of the Consortium are striving to
ensure that data are published within a year of collection. It is
planned that data VI (2003) will be published before the end of
2005 and data VII in 2006.
19
J.C.Harper et al.
Table XIVb. Congenital malformation and neonatal complications at birth,
data collection V
Table XVa. Confirmation of diagnosis per fetal sac, data collection I–IV
Method
No malformation data available
No malformation
Singletons
Twins
Triplet
Babies with malformation
Major
Absence of corpus callosum, hemivertebra
Absence of corpus callosum, kidney dilatation,
growth retardation
Laryngomalacia, receding chin, strawberry naevus
Ventricular septum defect
Ventricular septum defect, retrognatia
Bilateral cryptorchidia
Cleft lip and palate, pulmonary atresia
Cleft lip and palate, tetralogy of Fallot
Cleft lip, cardiopathy, short femur
Pulmonary hypoplasia
Minor
Congenital hip luxation
Heart murmur
Hydrops fetalis
Pre-auricular tags
Pyelo-urethral junction stenosis
Sacral dimple
Single umbilical artery, disappearing hip luxation
Unknown
No neonatal data available
No neonatal complications
Singletons
Twins
Triplet
Neonatal complications
Bronchopulmonar dysplasia
Growth retardation, mental retardation
Infection (1 meconium aspiration sepsis)
IUGR due to HELLP syndrome
Neonatal care, tube feeding 1 week
Dysmaturity
Hypoglycaemia
Hypoglycaemia and feeding problems
Neonatal care
Prematurity
Neonatal death
Cleft lip, cardiopathy, short femur
Pulmonar hypoplasia
Stillborn at 22 weeks
Stillborn at 25 weeks
25/382
338/382
226/247
109/132
3/3
19/382
1 singleton
1 singleton
1 singleton
1 singleton
1 singleton
1 twin
1 twin1
1 twina
1 twin
1 twin
1 singleton, 1 twin
1 singleton
1 twin
1 singleton
1 twin
1 singleton
1 singleton
1 singleton
45/382
314/382
215/247
96/132
3/3
23/282
1 singleton
1 singleton
3 singletons
1 singleton
1 singleton
2 twins
1 twin
1 twin
1 singletonc, 3 twinsb
2 twins
1 twin
1 twin
2 twins
2 twins
a
Two babies from the same twin.
Two babies from the same twin.
c
Singleton with ventricular septum defect and retrognatia.
b
For the first time we have expressed the clinical pregnancy rates per embryo transfer procedure and also the
implantation rates. Furthermore, we have presented preliminary results for live birth rates per OR. For data collection
VI, we intend to publish live birth rates per oocyte retrieval
and per embryo transfer procedure broken down for each
indication.
It appears that since 1997 there have been no major changes
in the methodologies applied to most stages of the PGD/PGS
procedure. Technology has facilitated some minor modifications, e.g. in mode of zona drilling, with laser drilling
becoming increasingly frequent. It is encouraging that no
misdiagnoses were reported between January and December
2002, but disappointing that the overall pregnancy rates
20
Prenatal diagnosis
FISH
CVS
Amniocentesis
Ultrasound
Unknown
Total
PCR
CVS
Amniocentesis
Ultrasound
Unknown
Total
Postnatal diagnosis
FISH
Karyotype miscarriage
Karyotype postnatal
Physical examination
Total
PCR
DNA test miscarriage
DNA test postnatal
Sweat test
Physical examination
Karyotype
Karyotype + DNA
Unknown
Total
Result
n
Normal
Abnormal
40
179
8
3
230
40
176
7
3
226
0
3a
1b
0
4
53
32
4
2
91
53
26
3
2
84
0
6c
1d
0
7
16
31
97
144
7
30f
95
132
9e
1g
2h
12
2
17
4
2
2
1
1
29
2
16
4
1
2
1
1
27
0
1i
0
1j
0
0
0
2
Prenatal diagnosis: FISH fetal sacs tested = 230/602; PCR fetal sacs tested =
91/201; total prenatal testing = 321/803.
Postnatal diagnosis: total FISH sacs/babies tested = 143/602; total PCR
sacs/babies tested = 29/201; total postnatal testing = 172/803.
a
Two misdiagnoses: sexing, female fetus, social sexing (terminated): PGS:
45,X (terminated). Trisomy 18 after PGD for reciprocal translocation.
b
Polymalformation on ultrasound, normal karyotype, terminated.
c
Six misdiagnoses: XL Duchenne (selective reduction of one affected embryo
of twin pregnancy), β-thalassaemia (terminated), myotonic dystrophy
(terminated), cystic fibrosis (born), XL retinitis pigmentosa (born), amyloid
polyneuropathy (born).
d
Echogenic bowel at ultrasound, misdiagnosis for cystic fibrosis, born.
e
One trisomy 3, one trisomy 15, two trisomy 16, one trisomy 22, one mosaic
trisomy 22, one monosomy X, 47,XY,+D(3), one misdiagnosis
47,XX,+der(22)t(11;22)(q23.3;q11.2)mat; parent carrier balanced
translocation.
f
One baby born with Fryns syndrome had a karyotype (normal result).
g
One misdiagnosis, trisomy 21 after aneuploidy screening.
h
One baby with Fryns syndrome, one baby with prune belly syndrome
(both normal karyotype).
i
One CF carrier twin pregnancy: on PGD both diagnosed as homozygote
normal.
j
One twin after PGD for CF: one misdiagnosis, one healthy.
CVS = chorionic villous sampling.
remained low. The consortium will continue to collect data to
support long-term evaluation of PGD/PGS and to promote
good practice.
In 2005, the consortium published detailed guidelines on
PGD and PGS (Thornhill et al., 2005). Our aim is to update
these guidelines on a regular basis.
In 2005, a protocol for a long-term follow-up of PGD babies
born has been prepared and it is hoped that most of the centres
registered with the consortium will be involved in this important study.
ESHRE PGD Consortium data collection V
Table XVb. Confirmation of diagnosis per fetal sac, data collection V
Method
Prenatal diagnosis
FISH
CVS
Amnio
Ultrasound
Total
PCR
CVS
Amnio
Ultrasound
Total
Postnatal diagnosis
FISH
Karyotype miscarriage
Karyotype postnatal
Physical examination
Total
PCR
Karyotype miscarriage
Physical examination
DNA test postnatal
Total
Result
n
Normal
Abnormal
9
79
90
178
9
77
89
175
0
2a
1b
3
13
15
0
28
13
14
0
27
0
1c
0
1
9
16
168
193
4d,e
15g
168
187
5f
1h
0
6
1i
5
0
0
0
0
1
5j
7k
13
7
13
Prenatal diagnosis: FISH fetal sacs tested: 178/389; PCR fetal sacs tested: 28/
88; total prenatal testing: 206/476.
Postnatal testing: FISH fetal sacs/babies tested: 193/389; PCR fetal sacs/
babies tested: 13/88; total post-natal testing: 205/426.
a
46,XX,t(1;5)(q43;q13) de novo after PGD for 46,XY,t(1;11)(p12;q12) (born),
45,X[10]/46,XX[55] after PGS for repeated IVF failures (termination of
pregnancy).
b
Cystic hygroma, karyotype failed, PGD for 45,XX,der(13;21)(q10;q10).
c
46,XX,t(8;9)(p?23;p12) de novo after PGD for Duchenne muscular dystrophy.
d
Normal karyotype in a fetus with multiple malformations.
e
After amniocentesis with normal karyotype.
f
46,X,inv(Y)(p11q12); trisomy 16 after PGS with PB1 analysis;
45,XX,der(7)t(7;15)(p14;q11.2),-15 de novo; 47,XX,+9, trisomy 22.
g
Three twins with polymalformations (see Table XIV) had a normal karyotype.
h
46,XX,t(1;5)(q43;q13) de novo already seen in prenatal.
i
After amniocentesis.
j
One baby (PGD for DMD) had FISH + PCR, diagnosis confirmed by physical
examination and amnio.
k
Three for CF, two for SMA, one for SC and one for β-thal.
CVS = chorionic villous sampling.
Acknowledgements
We would like to thank ESHRE for its continuing support of this work
and to all participating centres.
References
Bonduelle M, Wennerholm UB, Loft A, Tarlatzis BC, Peters C, Henriet S,
Mau C, Victorin-Cederquist A, Van Steirteghem A, Balaska A, Emberson
JR and Sutcliffe AG (2005) A multi-centre cohort study of the physical
health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception. Hum Reprod 20,413–419.
ESHRE PGD Consortium Steering Committee (1999) ESHRE Preimplantation
Genetic Diagnosis (PGD) Consortium: preliminary assessment of data from
January 1997 to September 1998. Hum Reprod 14,3138–3148.
ESHRE PGD Consortium Steering Committee (2000) ESHRE Preimplantation
Genetic Diagnosis (PGD) Consortium: data collection II (May 2000). Hum
Reprod 15,2673–2683.
ESHRE PGD Consortium Steering Committee (2002) ESHRE Preimplantation
Genetic Diagnosis (PGD) Consortium: data collection III (May 2001). Hum
Reprod 17,233–246.
Sermon K, Moutou C, Harper J, Geraedts J, Scriven P, Wilton L, Magli M-C,
Michiels A, Viville S and De Die C (2005) ESHRE PGD Consortium data
collection IV: May–December 2001. Hum Reprod 20,19–34.
Thornhill AR, deDie-Smulders CE, Geraedts JP, Harper JC, Harton GL,
Lavery SA, Moutou C, Robinson MD, Schmutzler AG, Scriven PN, Sermon KD
and Wilton L (2005) ESHRE PGD Consortium Best Practice Guidelines for
Clinical Preimplantation Genetic Diagnosis (PGD) and Preimplantation
Genetic screening (PGS). Hum Reprod 20,35–48.
Warburton D (1991) De novo balanced chromosome rearrangements and extra
marker chromosomes identified at prenatal diagnosis: clinical significance
and distribution of breakpoints. Am J Hum Genet 49,995–1013.
Submitted on August 1, 2005; accepted on August 8, 2005
Appendix. Centres that contributed data to collection V
Argentina: Fecunditas, Buenos Aires (Roberto Coco); Australia: Melbourne IVF, Melbourne (Leeanda Wilton), University of Adelaide,
Dept of Ob/Gyn, Adelaide (Nicole Hussey); Belgium: Centre for
Medical Genetics, Vrije Universiteit Brussel, Brussels (Karen Sermon),
Infertility Centre, Ghent University Hospital, Ghent (Josiane Van de
Elst), Leuven Insititute for Fertility and Embryology, Leuven,
(Gunther Van Kerkhoven), Hopital Erasme, Université Libre de Bruxelles, Brussels (Serena Emiliani); Denmark: Aarhus University Hospital, Aarhus (Johnny Hindkjaer); Finland: Helsinki University Central
Hospital, Helsinki (Christel Hyden-Granskog), AVA-Clinic, Tampere
(Paivi Salin) ; France: Service de la Biologie de la Reproduction,
SIHCUS-CMCO, Strasbourg (Stéphane Viville); Germany: University of Bonn, Bonn (Marcus Montag), Centre for Gynecological
Endocrinology, Reproductive Medicine and Human Genetics,
Regensburg (Andreas Hehr); Greece: IVF and Genetics, Athens
(Elena Kontogianni); Laboratory of Medical Genetics, University of
Athens, St. Sophia’s Children’s Hospital, 11527 Athens, Greece
(Emmanuel Kanavakis and Joanne Traeger-Synodinos); Italy: SISMER,
Bologna (Luca Gianaroli), Reproductive Medicine, European Hospital,
Rome (Marcello Iacobelli), HERA-UMR, Catania (Sandrine
Chamayou); Israel: The Danek Gertner Institute of Human Genetics, Sheba Medical Center (Ayala Aviram-Goldring), IVF Unit,
Hadassah Medical Organisation, Jeruzalem (Alex Simon), Tel-Aviv
Sourasky Medical Center, Tel-Aviv (Yuval Yaron); Korea: Cha
General Hospital, Seoul (Sook Hwan Lee and Mi-Kyung Chung);
Samsung Cheil Hospital, Seoul (Inn Soo Kang); The Netherlands:
Erasmus Medical Center, IVF lab, Rotterdam (Elena Martini),
Center for Reproductive Medicine, Academic Medical Center,
Amsterdam (Sjoerd Repping), PGD Working Group Maastricht,
Maastricht (Edith Coonen); Portugal: Faculty of Medicine of PortoHospital Sao Joao, Porto (Filipa Carvalho); Spain: Instituto Dexeus,
Barcelona (Anna Veiga), Unitat de Biologia Cel.lular, Univ. Autonoma
Barcelona, Barcelona (Josep Santalo), Instituto Valenciano de Infertilidad, Valencia (Carmen Rubio), Fundacion Jimenez Diaz, Madrid
(Esther Fernandez); Sweden: Karolinska Hospital, Stockholm (Elisabeth
Blennow); Sahlgrenska Hospital, Goteborg (Charles Hanson); Taiwan:
Chang Chung Memorial Hospital and Medical College, Tao-Yuan
(Chun-Kai Chen); Turkey: American Hospital, Istanbul (Nesrin
Ercelen); UK: University College London, London (Joyce Harper),
Center for Preimplantation Genetic Diagnosis, Guy’s and St Thomas’
NHS Foundation Trust, London (Peter Braude), Hammersmith
Hospital, London (Stuart Lavery), School of Biology, University of
Leeds (Marc Robinson); USA: Baylor College of Medicine, Houston,
Texas (Sallie McAdoo), Genetics and IVF Insitute, Fairfax,
Virginia (Gary Harton), Shady Grove Centre for Preimplantation
Genetics, Rockville, Maryland (William Kearns); Jones Institute for
Reproductive Medicine, Norfolk, Virginia (Sue Gitlin).
21