Abstract

The ninth report of the European Society of Human Reproduction and Embryology Preimplantation Genetic Diagnosis Consortium is presented documenting cycles collected for the calendar year 2006 and follow-up of the pregnancies and babies born until October 2007, which resulted from these cycles. Since the beginning of the data collections there has been a steady increase in the number of cycles, pregnancies and babies reported annually. For data collection IX, 57 centres have participated, reporting on 5858 cycles to oocyte retrieval (OR), along with details of the follow-up on 1437 pregnancies and 1206 babies born. Eight hundred and twelve ORs were reported for chromosomal abnormalities, 133 ORs for sexing for X-linked diseases, 931 ORs for monogenic diseases, 3900 ORs for preimplantation genetic screening and 82 ORs for social sexing. Data IX are compared with the cumulative data for data collections I–VIII.

Introduction

The European Society of Human Reproduction and Embryology (ESHRE) Preimplantation Genetic Diagnosis (PGD) Consortium was established in 1997. Since 1999, eight data collections of PGD for autosomal and sex-linked monogenic diseases and chromosome abnormalities, preimplantation genetic screening (PGS) and social sex selection have been published (ESHRE PGD Consortium Steering Committee, 1999, 2000, 2002; Sermon et al., 2005, 2007; Harper et al., 2006, 2008b; Goossens et al., 2008). This report summarizes data IX collected for the calendar year 2006 and the subsequent pregnancies. As it was reported for the first time in data VIII, data IX also includes the delivery rate for each indication as well as a graph of the pregnancy rates for each centre (Fig. 1).

Figure 1

Clinical pregnancy rates per centre.

Figure 1

Clinical pregnancy rates per centre.

Materials and Methods

Data were collected using a FileMaker Pro 5, 6 or 8 database, consisting of files for cycle, pregnancy and baby records. The submitted data were thoroughly analysed to identify omissions and any ambivalent data. Corrections were requested from the participating centres. Records with insufficient data, e.g. with no cycle or patient identification or no clear indication or from the wrong time period were excluded from the calculations. In-depth corrections and tables were made by expert co-authors. Clinical pregnancies were defined as the presence of one or more fetal hearts at ∼6 weeks gestation. Implantation rate was defined as the number of fetal hearts per 100 embryos transferred. Delivery rate was defined as the percentage of pregnancies with delivery per oocyte retrieval (OR) and per embryo transfer procedure.

Results

The number of centres that become members of the PGD Consortium increases annually. Data from 57 centres were included in this report. The results are represented in tables according to an established layout. Accompanying text is deliberately concise and seven tables are available in an electronic version only: Supplementary Table IIc lists the abnormal karyotypes carried by the patients undergoing PGD; Supplementary Table IIIc lists the X-linked diseases for which sexing was carried out; Supplementary Table IVc lists the monogenic diseases for which PGD was carried out; Supplementary Tables VIIIa (data I–VIII) and VIIIb (data IX) list the complications of pregnancy and Supplementary Tables XIIa (data I–VIII) and XIIb (data IX) list the congenital malformations and the neonatal complications.

An overview of all cycles collected previously in data collections I–VIII is shown in Table Ia, whereas an overview of the current data collection is shown in Table Ib.

Table Ia

Overall cycle data collection I–VIII

Indication PGD PGS PGD-SS Total 
Cycles to OR 62351 9153 497 15 8851 
Number infertile 2417 8169 46 10 632 
Female age 33 37 37 35 
Cancelled before IVF/ICSI 18 20 
ART method     
 IVF 692 920 138 1750 
 ICSI 5401 8009 342 13 752 
 IVF + ICSI 26 144 170 
 Frozen + ICSI + IVF + unknown 801 28 17 1251 
 Unknown 20 50 70 
Cancelled after IVF/ICSI 364 329 16 709 
Cycles to PGS/PGD 5855 8822 481 15 158 
FISH 3317 8822 299 12 438 
PCR 2538 182 2720 
Zona breaching     
 AT drilling 2894 3372 19 6285 
 Laser drilling 2637 4548 119 7304 
 Mechanical 310 837 343 1490 
 Unknown 14 65 79 
Biopsy method     
 PB biopsy 822 10072 10892 
 Cleavage aspiration 54312 72682 137 12 8362 
 Cleavage extrusion 261 472 344 1077 
 Cleavage flow displacement 16 22 38 
 Blastocyst 55 57 
 PB and cleavage 
 Unknown 16 52 68 
Embryology     
 COCs 85 291 109 832 6802 201 925 
 Inseminated 72 516 90 501 5616 168 633 
 Fertilized 51 773 64 086 3852 119 711 
 Biopsied 38 910 51 259 3014 93 183 
 Successfully biopsied 38 283 50 622 2890 91 795 
 Diagnosed 34 294 46 589 2647 83 530 
 Transferable 12 769 16 784 1032 30 585 
 Transferred 8606 12 131 741 21 478 
 Frozen 1678 2303 215 4196 
Clinical outcome     
 Cycles to ET 4535 6597 354 11 486 
 hCG positive 1473 2165 141 3779 
 Positive heart beat 1139 1635 107 2881 
 Clinical pregnancy rate (% per OR/% per ET) 18/25 18/25 22/30 18/25 
Indication PGD PGS PGD-SS Total 
Cycles to OR 62351 9153 497 15 8851 
Number infertile 2417 8169 46 10 632 
Female age 33 37 37 35 
Cancelled before IVF/ICSI 18 20 
ART method     
 IVF 692 920 138 1750 
 ICSI 5401 8009 342 13 752 
 IVF + ICSI 26 144 170 
 Frozen + ICSI + IVF + unknown 801 28 17 1251 
 Unknown 20 50 70 
Cancelled after IVF/ICSI 364 329 16 709 
Cycles to PGS/PGD 5855 8822 481 15 158 
FISH 3317 8822 299 12 438 
PCR 2538 182 2720 
Zona breaching     
 AT drilling 2894 3372 19 6285 
 Laser drilling 2637 4548 119 7304 
 Mechanical 310 837 343 1490 
 Unknown 14 65 79 
Biopsy method     
 PB biopsy 822 10072 10892 
 Cleavage aspiration 54312 72682 137 12 8362 
 Cleavage extrusion 261 472 344 1077 
 Cleavage flow displacement 16 22 38 
 Blastocyst 55 57 
 PB and cleavage 
 Unknown 16 52 68 
Embryology     
 COCs 85 291 109 832 6802 201 925 
 Inseminated 72 516 90 501 5616 168 633 
 Fertilized 51 773 64 086 3852 119 711 
 Biopsied 38 910 51 259 3014 93 183 
 Successfully biopsied 38 283 50 622 2890 91 795 
 Diagnosed 34 294 46 589 2647 83 530 
 Transferable 12 769 16 784 1032 30 585 
 Transferred 8606 12 131 741 21 478 
 Frozen 1678 2303 215 4196 
Clinical outcome     
 Cycles to ET 4535 6597 354 11 486 
 hCG positive 1473 2165 141 3779 
 Positive heart beat 1139 1635 107 2881 
 Clinical pregnancy rate (% per OR/% per ET) 18/25 18/25 22/30 18/25 

OR, oocyte retrieval; AT, acid Tyrode's; COC, cumulus oocyte complexes; SS, social sexing; PGS, preimplantation genetic screening; FISH, fluorescence in situ hybridization; ET, embryo transfer; ART, assisted reproduction technology; PB, polar body.

PGD column includes PGD for chromosome abnormalities, sexing for X-linked disease and PGD for monogenic disorders.

1Includes two cycles with PGD on frozen embryos only. These cycles were not counted in the cycles with OR.

2Twelve cycles had polar body biopsy and cleavage stage biopsy.

Table Ib

Overall cycle data collection IX

Indication PGD PGS PGD-SS Total 
Cycles to OR 1876 3900 82 5858 
Number infertile 661 3135 3797 
Female age (years) 33 36 38 35 
ART method     
 IVF 184 575 767 
 ICSI 1653 3232 74 4959 
 IVF + ICSI 13 81 94 
 Frozen + ICSI + IVF 26 12 38 
Cancelled after IVF/ICSI 108 113 221 
Cycles to PGS/PGD 1768 3787 82 5637 
FISH 894 3784 82 4760 
PCR 867 870 
FISH + PCR 
Zona breaching     
 AT drilling 529 598 1127 
 Laser drilling 1132 2856 12 4000 
 Mechanical 107 333 70 510 
Biopsy method     
 PB biopsy 39 809 848 
 Cleavage aspiration 1636 2825 4465 
 Cleavage extrusion 62 153 78 293 
 Blastocyst 16 16 
 PB and cleavage 15 15 
Embryology     
 COCs 25 560 42 763 1150 69 473 
 Inseminated 21 503 35 897 988 58 388 
 Fertilized 15 819 25 393 721 41 933 
 Biopsied 11 255 20 181 568 32 004 
 Successfully biopsied 11 165 20 001 565 31 731 
 Diagnosed 10 251 18 592 494 29 337 
 Transferable 3775 6596 209 10 580 
 Transferred 2320 4844 119 7283 
 Frozen 631 862 75 1568 
Clinical outcome     
 Cycles to ET 1315 2836 65 4216 
 hCG positive 497 980 20 1497 
 Positive heart beat 403 794 13 1210 
 Clinical pregnancy rate (% per OR/% per ET) 21/31 20/28 16/20 21/29 
 Number of fetal heartbeats 510 999 13 1522 
 Implantation rate (fetal heartbeats/100 embryos transferred) 22 21 11 21 
 Deliveries 362 619 12 993 
 Delivery rate (% per OR/% per ET) 19/28 16/22 15/18 17/24 
 Miscarriages 13 148 162 
 Miscarriage rate (% per clinical pregn–pregn lost to FU)1 19 14 
 Clinical pregnancies lost to FU 30 33 
Indication PGD PGS PGD-SS Total 
Cycles to OR 1876 3900 82 5858 
Number infertile 661 3135 3797 
Female age (years) 33 36 38 35 
ART method     
 IVF 184 575 767 
 ICSI 1653 3232 74 4959 
 IVF + ICSI 13 81 94 
 Frozen + ICSI + IVF 26 12 38 
Cancelled after IVF/ICSI 108 113 221 
Cycles to PGS/PGD 1768 3787 82 5637 
FISH 894 3784 82 4760 
PCR 867 870 
FISH + PCR 
Zona breaching     
 AT drilling 529 598 1127 
 Laser drilling 1132 2856 12 4000 
 Mechanical 107 333 70 510 
Biopsy method     
 PB biopsy 39 809 848 
 Cleavage aspiration 1636 2825 4465 
 Cleavage extrusion 62 153 78 293 
 Blastocyst 16 16 
 PB and cleavage 15 15 
Embryology     
 COCs 25 560 42 763 1150 69 473 
 Inseminated 21 503 35 897 988 58 388 
 Fertilized 15 819 25 393 721 41 933 
 Biopsied 11 255 20 181 568 32 004 
 Successfully biopsied 11 165 20 001 565 31 731 
 Diagnosed 10 251 18 592 494 29 337 
 Transferable 3775 6596 209 10 580 
 Transferred 2320 4844 119 7283 
 Frozen 631 862 75 1568 
Clinical outcome     
 Cycles to ET 1315 2836 65 4216 
 hCG positive 497 980 20 1497 
 Positive heart beat 403 794 13 1210 
 Clinical pregnancy rate (% per OR/% per ET) 21/31 20/28 16/20 21/29 
 Number of fetal heartbeats 510 999 13 1522 
 Implantation rate (fetal heartbeats/100 embryos transferred) 22 21 11 21 
 Deliveries 362 619 12 993 
 Delivery rate (% per OR/% per ET) 19/28 16/22 15/18 17/24 
 Miscarriages 13 148 162 
 Miscarriage rate (% per clinical pregn–pregn lost to FU)1 19 14 
 Clinical pregnancies lost to FU 30 33 

FU, follow-up; SS: social sexing.

PGD column includes PGD for chromosome abnormalities, sexing for X-linked disease and PGD for monogenic disorders.

1Percentage per number of clinical pregnancies minus the number of pregnancies that were lost to FU.

For all indications for PGD/PGS, intra cytoplasmic sperm injection (ICSI) was the most often used method of fertilization, and cleavage stage aspiration was the most commonly used method of biopsy. Overall zona pellucida drilling was more commonly performed using a laser. The mechanical method was used more often for social sexing since the centre that reported the largest proportion of the cycles for social sexing often uses this method.

PGD cycles for chromosomal abnormalities

Tables IIa and IIb summarize the 2712 and 812 cycles to OR collected for data collections I–VIII and IX, respectively. As for previous years, data IX showed that PGD for reciprocal translocations was performed more often than for Robertsonian translocations or other types of chromosome abnormalities. For data IX, 11 411 oocytes were collected, 72% (7056/9794) fertilized, 72% (5062/7056) embryos were biopsied and 99% (5015/5062) embryos were successfully biopsied. Of the embryos successfully biopsied, 94% (4725/5015) gave a diagnostic result, of which only 24% (1126/4725) were transferable. From 812 OR procedures, only 61% (493/812) resulted in an embryo transfer procedure. This is in agreement with previous data showing that a high level of chromosomally abnormal embryos is found in these patients. A positive hCG was obtained in 174 cycles, with a positive heart beat in 141 cycles [17% per OR (141/812) and 29% per embryo transfer (141/493)]. This gave an implantation rate of 22% (178/821). Finally, the delivery rate was 15% per OR (126/812) and 26% per embryo transfer (126/493). There were 14/140 miscarriages (10% per clinical pregnancy) and 1/141 pregnancy was lost to follow-up.

Table IIa

PGD for chromosomal abnormalities, data collection I–VIII

Indication Robertsonian translocation (male carrier) Robertsonian translocations (female carrier)1 Reciprocal (male carrier)2 Reciprocal (female carrier)1 Sex chromosome aneuploidy3 Other Total 
Cycles to OR 450 315 737 768 239 203 2712 
Number infertile 387 155 445 370 214 113 1684 
Female age 34 33 33 33 32 33 33 
Cancelled before IVF/ICSI 12 
ART method        
 IVF 17 50 92 197 22 45 423 
 ICSI 424 257 617 544 208 153 2203 
 IVF + ICSI 16 
 Frozen + ICSI + IVF + unknown 22 20 56 
 Unknown 
Cancelled after IVF/ICSI 28 15 56 63 15 186 
Cycles to PGD 422 300 678 705 217 192 2514 
Zona breaching        
 AT drilling 218 181 403 455 102 104 1463 
 Laser drilling 192 114 246 218 85 65 920 
 Mechanical 12 29 32 30 23 131 
Biopsy method        
 PB biopsy 11 19 
 Cleavage aspiration 401 278 634 641 210 179 2343 
 Cleavage extrusion 18 16 33 39 13 122 
 Cleavage flow displacement 11 
 Blastocyst 10 19 
Embryology        
 COCs 6589 4366 10 673 10 989 3026 2718 38 361 
 Inseminated 5486 3662 9069 9567 2467 2371 32 622 
 Fertilized 3739 2687 6424 7139 1768 1721 23 478 
 Biopsied 2617 2126 5021 5716 1221 1358 18 059 
 Successfully biopsied 2573 2101 4947 5637 1207 1338 17 803 
 Diagnosed 2288 1929 4581 5262 1097 1239 16 396 
 Transferable 888 569 917 1057 501 389 4321 
 Transferred 592 437 762 859 344 279 3273 
 Frozen 108 46 34 60 46 31 325 
Clinical outcome        
 Cycles to ET 331 234 430 470 173 150 1788 
 hCG positive 109 82 125 136 53 39 544 
 Positive heart beat 95 66 94 102 36 33 426 
 Clinical pregnancy rate (% per OR/% per ET) 21/29 21/28 13/22 13/22 15/21 16/22 16/24 
Indication Robertsonian translocation (male carrier) Robertsonian translocations (female carrier)1 Reciprocal (male carrier)2 Reciprocal (female carrier)1 Sex chromosome aneuploidy3 Other Total 
Cycles to OR 450 315 737 768 239 203 2712 
Number infertile 387 155 445 370 214 113 1684 
Female age 34 33 33 33 32 33 33 
Cancelled before IVF/ICSI 12 
ART method        
 IVF 17 50 92 197 22 45 423 
 ICSI 424 257 617 544 208 153 2203 
 IVF + ICSI 16 
 Frozen + ICSI + IVF + unknown 22 20 56 
 Unknown 
Cancelled after IVF/ICSI 28 15 56 63 15 186 
Cycles to PGD 422 300 678 705 217 192 2514 
Zona breaching        
 AT drilling 218 181 403 455 102 104 1463 
 Laser drilling 192 114 246 218 85 65 920 
 Mechanical 12 29 32 30 23 131 
Biopsy method        
 PB biopsy 11 19 
 Cleavage aspiration 401 278 634 641 210 179 2343 
 Cleavage extrusion 18 16 33 39 13 122 
 Cleavage flow displacement 11 
 Blastocyst 10 19 
Embryology        
 COCs 6589 4366 10 673 10 989 3026 2718 38 361 
 Inseminated 5486 3662 9069 9567 2467 2371 32 622 
 Fertilized 3739 2687 6424 7139 1768 1721 23 478 
 Biopsied 2617 2126 5021 5716 1221 1358 18 059 
 Successfully biopsied 2573 2101 4947 5637 1207 1338 17 803 
 Diagnosed 2288 1929 4581 5262 1097 1239 16 396 
 Transferable 888 569 917 1057 501 389 4321 
 Transferred 592 437 762 859 344 279 3273 
 Frozen 108 46 34 60 46 31 325 
Clinical outcome        
 Cycles to ET 331 234 430 470 173 150 1788 
 hCG positive 109 82 125 136 53 39 544 
 Positive heart beat 95 66 94 102 36 33 426 
 Clinical pregnancy rate (% per OR/% per ET) 21/29 21/28 13/22 13/22 15/21 16/22 16/24 

1One cycle included PGS.

2One cycle included SS.

3Four cycles included PGS.

Table IIb

PGD for chromosomal abnormalities, data collection IX

Indication Robertsonian translocation (male carrier)1 Robertsonian translocation (female carrier)2 Reciprocal translocation (male carrier)3 Reciprocal translocation (female carrier)1,4 Sex chromosome aneuploidy3 Other1 Total 
Cycles to OR 161 83 208 260 53 47 812 
Number infertile 112 36 112 92 41 24 417 
Female age (years) 34 34 34 34 33 344 34 
ART method        
 IVF 14 38 64 136 
 ICSI 148 65 164 187 50 35 649 
 IVF + ICSI 12 
 IVF + frozen 
 ICSI + frozen 13 
Cancelled after IVF/ICSI 13 13 52 
Cycles to PGD 152 76 195 247 49 41 760 
Zona breaching        
 AT drilling 55 26 88 113 13 301 
 Laser drilling 91 45 102 127 36 21 422 
 Mechanical 37 
Biopsy method        
 PB 
 Cleavage aspiration 137 68 191 235 48 40 719 
 Cleavage extrusion 14 11 37 
 Cleavage flow 
 Blastocyst 
Embryology        
 COCs 2247 1259 2976 3714 688 527 11 411 
 Inseminated 1899 1080 2515 3280 569 451 9794 
 Fertilized 1283 817 1846 2401 365 344 7056 
 Biopsied 885 549 1343 1721 268 296 5062 
 Successfully biopsied 878 545 1330 1702 264 296 5015 
 Diagnosed 825 513 1255 1592 258 282 4725 
 Transferable 292 143 233 271 106 81 1126 
 Transferred 206 94 173 228 70 50 821 
 Frozen 36 19 19 13 15 18 120 
Clinical outcome        
 Cycles to ET 116 54 112 139 41 31 493 
 hCG positive 47 15 42 46 16 174 
 Positive heart beat 40 12 29 39 15 141 
 Clinical pregnancy rate (% per OR/% per ET) 25/34 14/22 14/26 15/28 26/34 15/23 17/29 
 Number of fetal hearts 52 15 40 46 18 178 
 Implantation rate (fetal hearts/100 embryos transferred) 25 16 23 20 25 13 22 
 Deliveries 38 10 25 33 14 126 
 Delivery rate (% per OR/% per ET) 24/33 12/18 12/22 13/24 26/34 13/19 15/26 
 Miscarriages 14 
 Miscarriage rate (% per clinical pregn–pregn lost to FU) 12 14 15 10 
 Clinical pregnancies lost to FU 
Indication Robertsonian translocation (male carrier)1 Robertsonian translocation (female carrier)2 Reciprocal translocation (male carrier)3 Reciprocal translocation (female carrier)1,4 Sex chromosome aneuploidy3 Other1 Total 
Cycles to OR 161 83 208 260 53 47 812 
Number infertile 112 36 112 92 41 24 417 
Female age (years) 34 34 34 34 33 344 34 
ART method        
 IVF 14 38 64 136 
 ICSI 148 65 164 187 50 35 649 
 IVF + ICSI 12 
 IVF + frozen 
 ICSI + frozen 13 
Cancelled after IVF/ICSI 13 13 52 
Cycles to PGD 152 76 195 247 49 41 760 
Zona breaching        
 AT drilling 55 26 88 113 13 301 
 Laser drilling 91 45 102 127 36 21 422 
 Mechanical 37 
Biopsy method        
 PB 
 Cleavage aspiration 137 68 191 235 48 40 719 
 Cleavage extrusion 14 11 37 
 Cleavage flow 
 Blastocyst 
Embryology        
 COCs 2247 1259 2976 3714 688 527 11 411 
 Inseminated 1899 1080 2515 3280 569 451 9794 
 Fertilized 1283 817 1846 2401 365 344 7056 
 Biopsied 885 549 1343 1721 268 296 5062 
 Successfully biopsied 878 545 1330 1702 264 296 5015 
 Diagnosed 825 513 1255 1592 258 282 4725 
 Transferable 292 143 233 271 106 81 1126 
 Transferred 206 94 173 228 70 50 821 
 Frozen 36 19 19 13 15 18 120 
Clinical outcome        
 Cycles to ET 116 54 112 139 41 31 493 
 hCG positive 47 15 42 46 16 174 
 Positive heart beat 40 12 29 39 15 141 
 Clinical pregnancy rate (% per OR/% per ET) 25/34 14/22 14/26 15/28 26/34 15/23 17/29 
 Number of fetal hearts 52 15 40 46 18 178 
 Implantation rate (fetal hearts/100 embryos transferred) 25 16 23 20 25 13 22 
 Deliveries 38 10 25 33 14 126 
 Delivery rate (% per OR/% per ET) 24/33 12/18 12/22 13/24 26/34 13/19 15/26 
 Miscarriages 14 
 Miscarriage rate (% per clinical pregn–pregn lost to FU) 12 14 15 10 
 Clinical pregnancies lost to FU 

1Five cycles included PGS.

2Two cycles included cystic fibrosis (CF) and one cycle sexing.

3Three cycles included PGS.

4Three cycles include the male partner with a reciprocal translocation, and one cycle with the male partner with a supernumerary chromosome derived from chromosome 15.

PGD cycles for sexing for X-linked diseases

Tables IIIa and IIIb summarize the 924 and 133 cycles to OR collected for data collections I–VIII and IX, respectively. This year, again, fluorescence in situ hybridization (FISH) was the only method used for sexing cycles. For data IX, 1747 oocytes were collected, 72% (1141/1574) fertilized, 75% (851/1141) embryos were biopsied and 99% (844/851) was successfully biopsied. Of the embryos successfully biopsied, 95% (800/844) gave a diagnostic result, of which only 34% (275/800) were transferable (female). From 133 OR procedures, only 74% (98/133) resulted in an embryo transfer procedure. A positive hCG was obtained in 32 cycles, with a positive heart beat in 25 cycles [19% per OR (25/133) and 26% per embryo transfer (25/98)]. This gave an implantation rate of 19% (32/163). These pregnancy rates were slightly lower than in the previous data collections. Finally, the delivery rate was 18% per OR (24/133) and 24% per embryo transfer (24/98). There was 1/25 miscarriage (4% per clinical pregnancy) and no clinical pregnancies lost to follow-up.

Table IIIa

Sexing only for X-linked disease using PCR or FISH, data collection I–VIII

 FISH PCR Total 
Cycles to OR 858 66 924 
Number infertile 168 168 
Female age 33 31 32 
Cancelled before IVF/ICSI 
ART method    
 IVF 221 10 231 
 ICSI 627 56 683 
 IVF + ICSI 
 ICSI + frozen 
Cancelled after IVF/ICSI 531 12 541,2 
Cycles to PGD 803 65 868 
Zona breaching    
 AT drilling 443 52 495 
 Laser drilling 319 322 
 Mechanical 41 10 51 
Biopsy method    
 Cleavage aspiration 762 60 822 
 Cleavage extrusion 34 39 
 Flow displacement 
 Blastocyst 
Embryology    
 COCs 11 300 912 12 212 
 Inseminated 9958 701 10 659 
 Fertilized 6997 556 7553 
 Biopsied 5323 458 5781 
 Successfully biopsied 5194 422 5616 
 Diagnosed 4773 329 5102 
 Transferable 1643 178 1821 
 Transferred 1155 139 1294 
 Frozen 2863 584 3443,4 
Clinical outcome    
 Cycles to ET 641 55 696 
 hCG positive 210 24 234 
 Positive heartbeat 164 17 181 
 Clinical pregnancy rate (%per OR/% per ET) 19/265 26/315 20/265 
 FISH PCR Total 
Cycles to OR 858 66 924 
Number infertile 168 168 
Female age 33 31 32 
Cancelled before IVF/ICSI 
ART method    
 IVF 221 10 231 
 ICSI 627 56 683 
 IVF + ICSI 
 ICSI + frozen 
Cancelled after IVF/ICSI 531 12 541,2 
Cycles to PGD 803 65 868 
Zona breaching    
 AT drilling 443 52 495 
 Laser drilling 319 322 
 Mechanical 41 10 51 
Biopsy method    
 Cleavage aspiration 762 60 822 
 Cleavage extrusion 34 39 
 Flow displacement 
 Blastocyst 
Embryology    
 COCs 11 300 912 12 212 
 Inseminated 9958 701 10 659 
 Fertilized 6997 556 7553 
 Biopsied 5323 458 5781 
 Successfully biopsied 5194 422 5616 
 Diagnosed 4773 329 5102 
 Transferable 1643 178 1821 
 Transferred 1155 139 1294 
 Frozen 2863 584 3443,4 
Clinical outcome    
 Cycles to ET 641 55 696 
 hCG positive 210 24 234 
 Positive heartbeat 164 17 181 
 Clinical pregnancy rate (%per OR/% per ET) 19/265 26/315 20/265 

1Twenty-seven embryos from two cycles frozen before biopsy due to hyperstimulation.

2Twenty embryos frozen before biopsy.

3Eleven cycles with embryos frozen without biopsy or after failed diagnosis included.

4Thirteen cycles with embryos frozen without biopsy or failed diagnosis included.

5Eleven embryos transferred removed from calculations dues to lack of information regarding the number of fetal heart beats in pregnancies resulting from the transfer of those embryos.

Table IIIb

Sexing only for X-linked disease, data collection IX

 FISH Total 
Cycles to OR 133 133 
Number infertile 52 52 
Female age (years) 34 34 
ART method   
 IVF 43 43 
 ICSI 87 87 
 IVF + ICSI 
 IVF + frozen 
 ICSI + frozen 
Cancelled after IVF/ICSI 
Cycles to PGD 129 129 
Zona breaching   
 AT drilling 46 46 
 Laser drilling 79 79 
 Mechanical 
Biopsy method   
 Cleavage aspiration 123 123 
 Cleavage extrusion 
Embryology   
 COCs 1747 1747 
 Inseminated 1574 1574 
 Fertilized 1141 1141 
 Biopsied 851 851 
 Successfully biopsied 844 844 
 Diagnosed 800 800 
 Transferable 275 275 
 Transferred 163 163 
 Frozen 64 64 
Clinical outcome   
 Cycles to ET 98 98 
 hCG positive 32 32 
 Positive heart beat 25 25 
 Clinical pregnancy rate (%per OR/% per ET) 19/26 19/26 
 Number fetal hearts 32 32 
 Implantation rate (fetal heart beats/100 embryos transferred) 19 19 
 Deliveries 24 24 
 Delivery rate (% per OR/% per ET) 18/24 18/24 
 Miscarriages 
 Miscarriage rate (% per clinical pregn–pregn lost to FU) 
 Clinical pregnancies lost to FU 
 FISH Total 
Cycles to OR 133 133 
Number infertile 52 52 
Female age (years) 34 34 
ART method   
 IVF 43 43 
 ICSI 87 87 
 IVF + ICSI 
 IVF + frozen 
 ICSI + frozen 
Cancelled after IVF/ICSI 
Cycles to PGD 129 129 
Zona breaching   
 AT drilling 46 46 
 Laser drilling 79 79 
 Mechanical 
Biopsy method   
 Cleavage aspiration 123 123 
 Cleavage extrusion 
Embryology   
 COCs 1747 1747 
 Inseminated 1574 1574 
 Fertilized 1141 1141 
 Biopsied 851 851 
 Successfully biopsied 844 844 
 Diagnosed 800 800 
 Transferable 275 275 
 Transferred 163 163 
 Frozen 64 64 
Clinical outcome   
 Cycles to ET 98 98 
 hCG positive 32 32 
 Positive heart beat 25 25 
 Clinical pregnancy rate (%per OR/% per ET) 19/26 19/26 
 Number fetal hearts 32 32 
 Implantation rate (fetal heart beats/100 embryos transferred) 19 19 
 Deliveries 24 24 
 Delivery rate (% per OR/% per ET) 18/24 18/24 
 Miscarriages 
 Miscarriage rate (% per clinical pregn–pregn lost to FU) 
 Clinical pregnancies lost to FU 

PGD for monogenic diseases

Tables IVa and IVb summarize the 2599 and 931 cycles to OR collected for data collections I–VIII and IX, respectively. The most common indications for PGD for autosomal recessive diseases were β-thalassemia and/or sickle cell syndromes (82 cycles), plus 28 cycles for β-thalassemia/sickle cell with human leucocyte antigen (HLA) typing, cystic fibrosis (CF) (78 cycles, including 2 cycles for CF and a second indication) and spinal muscular atrophy (SMA) (56 cycles, of which 6 were for SMA and a second indication). Among the autosomal dominant diseases, the most PGD cycles were performed for myotonic dystrophy type I (DM1) [98 cycles, including one cycle also for Duchenne muscular dystrophy (DMD)] and Huntington disease (98 cycles), neurofibromatosis (21 cycles, 3 of which were performed using FISH for the causative micro-deletion) and Charcot-Marie-Tooth (14 cycles). For specific diagnosis of X-linked diseases, the most common indications were fragile X syndrome (75 cycles), DMD and Becker muscular dystrophy (43 cycles and 2 cycles, respectively) and haemophilia A and B (11 cycles). PGD cycles for an additional 81 monogenic diseases were initiated in 296 cycles (included under ‘other’ in Table VIII) and they are listed in Supplementary Table S3. Besides the 28 cycles for β-thalassemia and/or sickle cell syndromes with HLA typing, there were 12 cycles for HLA compatibility typing plus a further 17 cycles for HLA typing along with a specific disorder including one each for adenosine deaminase deficiency, hyper IgM syndrome and Wiscott–Aldrich syndrome, two each for Blackfan–Diamond and Duncan syndrome, three for granulomatous disease and seven for Fanconi anaemia.

Table IVa

Cycles performed for monogenic disorders, data collection I–VIII

Indication Autosomal recessive
 
Autosomal dominant
 
Specific X-linked
 
Other6 Total 
 CF1 β-Thal/SC and β-Thal/SC + HLA SMA and SMA + retinitis pigmentosa2 HLA compatibility DM1 HD and HD exclusion DMD and BMD3 FRAXA4 Haem5   
Cycles to OR 458 340 178 18 393 326 86 159 49 592 2599 
Number infertile 162 135 17 53 52 11 47 79 565 
Female age 34 34 33 35 32 31 34 33 33 33 33 
Cancelled before IVF/ICSI 
Art method            
 IVF 16 38 
 ICSI 434 339 170 18 383 322 79 153 41 576 2515 
 IVF + ICSI 
 IVF + ICSI + frozen 67 237 
 Unknown 18 
Cancelled after IVF/ICSI 18 18 25 10 30 124 
Cycles to PGD 440 322 170 17 365 316 81 152 47 5636 24736 
Zona breaching            
 AT drilling 213 168 68 126 99 32 36 22 171 936 
 Laser drilling 200 149 85 16 227 198 48 102 23 347 1395 
 Mechanical 23 17 10 16 12 42 128 
 Unknown 14 
Biopsy method            
 Polar body biopsy 118 88 88 28 248 638 
 Cleavage aspiration 4038 293 144 16 3498 287 78 1368 458 5158 22668 
 Cleavage extrusion 24 10 24 20 11 100 
 Blastocyst 17 10 34 
 Unknown 21 
Embryology            
 COCs 5970 4902 2434 229 4797 4603 1148 1684 627 8324 34 718 
 Inseminated 5184 4111 1920 208 4131 3855 948 1408 552 6918 29 235 
 Fertilized 3602 2911 1333 144 2989 2675 697 990 392 5009 20 742 
 Biopsied 2743 2091 1017 97 2021 1924 552 665 278 3682 15 070 
 Successfully biopsied 2715 2047 1011 97 2004 1900 532 654 277 3627 14 864 
 Diagnosed 2357 1712 871 94 1711 1642 481 558 228 3142 12 796 
 Transferable 1423 922 549 20 749 734 326 247 131 1526 6627 
 Transferred 777 654 332 16 513 434 170 156 87 900 4039 
 Frozen 279 121 48 66 111 70 24 14 274 1009 
Clinical outcome            
 Cycles to ET 381 282 156 11 294 252 67 100 42 466 2051 
 hCG positive 127 117 50 81 79 24 30 14 168 695 
 Positive heart beat 102 86 41 63 58 21 23 10 127 532 
 Clinical pregnancy rate (% per OR/% per ET) 22/27 25/30 23/26 6/9 16/21 18/23 24/31 14/23 20/24 21/27 20/26 
Indication Autosomal recessive
 
Autosomal dominant
 
Specific X-linked
 
Other6 Total 
 CF1 β-Thal/SC and β-Thal/SC + HLA SMA and SMA + retinitis pigmentosa2 HLA compatibility DM1 HD and HD exclusion DMD and BMD3 FRAXA4 Haem5   
Cycles to OR 458 340 178 18 393 326 86 159 49 592 2599 
Number infertile 162 135 17 53 52 11 47 79 565 
Female age 34 34 33 35 32 31 34 33 33 33 33 
Cancelled before IVF/ICSI 
Art method            
 IVF 16 38 
 ICSI 434 339 170 18 383 322 79 153 41 576 2515 
 IVF + ICSI 
 IVF + ICSI + frozen 67 237 
 Unknown 18 
Cancelled after IVF/ICSI 18 18 25 10 30 124 
Cycles to PGD 440 322 170 17 365 316 81 152 47 5636 24736 
Zona breaching            
 AT drilling 213 168 68 126 99 32 36 22 171 936 
 Laser drilling 200 149 85 16 227 198 48 102 23 347 1395 
 Mechanical 23 17 10 16 12 42 128 
 Unknown 14 
Biopsy method            
 Polar body biopsy 118 88 88 28 248 638 
 Cleavage aspiration 4038 293 144 16 3498 287 78 1368 458 5158 22668 
 Cleavage extrusion 24 10 24 20 11 100 
 Blastocyst 17 10 34 
 Unknown 21 
Embryology            
 COCs 5970 4902 2434 229 4797 4603 1148 1684 627 8324 34 718 
 Inseminated 5184 4111 1920 208 4131 3855 948 1408 552 6918 29 235 
 Fertilized 3602 2911 1333 144 2989 2675 697 990 392 5009 20 742 
 Biopsied 2743 2091 1017 97 2021 1924 552 665 278 3682 15 070 
 Successfully biopsied 2715 2047 1011 97 2004 1900 532 654 277 3627 14 864 
 Diagnosed 2357 1712 871 94 1711 1642 481 558 228 3142 12 796 
 Transferable 1423 922 549 20 749 734 326 247 131 1526 6627 
 Transferred 777 654 332 16 513 434 170 156 87 900 4039 
 Frozen 279 121 48 66 111 70 24 14 274 1009 
Clinical outcome            
 Cycles to ET 381 282 156 11 294 252 67 100 42 466 2051 
 hCG positive 127 117 50 81 79 24 30 14 168 695 
 Positive heart beat 102 86 41 63 58 21 23 10 127 532 
 Clinical pregnancy rate (% per OR/% per ET) 22/27 25/30 23/26 6/9 16/21 18/23 24/31 14/23 20/24 21/27 20/26 

CF, various mutations; β-Thal, β-thalassaemia; SMA, spinal muscular atrophy; SC, sickle-cell anaemia; DM1, myotonic dystrophy type 1; HD, Huntington's Disease; FRAXA, fragile-X syndrome; DMD, Duchenne muscular dystrophy (specific); BMD, Becker muscular dystrophy; Haem, haemophilia.

1Three cycles for two indications: CF and FRAXA; CF and SS, CF + PGS for diabetes insipidus.

2Includes two cycles for SMA and PGS.

3Includes one cycle for BMD and PGS.

4Includes three cycles for FRAX A testing and PGS.

5Includes one cycle for Haem A and PGS.

6Includes one cycle for Tuberous Sclerosis and PGS.

7Two cycles were on frozen–thawed embryos only so they were not counted as cycles with an OR, but were counted as cycles going to PGD.

8Eleven cycles had both polar body biopsy and cleavage stage biopsy.

Table IVb

Cycles performed for monogenic disorders, data collection IX

Indication Autosomal Recessive
 
Autosomal dominant
 
Specific X-linked
 
Other Total 
 β-Thal and/or sickle syndromes1 (+HLA) CF2 SMA3 HLA compatibility (HLA+ specific disease) HD DM14 Neurofibromatosis5 CMT DMD (BMD) Haem A or B6 FRAXA   
Cycles to OR 82 (28) 78 56 12 (17) 98 98 21 14 43 (2) 11 75 296 931 
Number infertile 32 (1) 28 11 28 3 (1) 14 64 192 
Female age (years) 34 32 33 35 32 32 33 30 35 30 33 26 31 
ART method              
 IVF 0 (0) 
 ICSI 77 (28) 78 55 12 (17) 97 98 18 14 41 (2) 11 75 294 917 
 ICSI + frozen 5 (0) 2 (0) 
Cancelled after IVF/ICSI 3 (3) 3 (2) 4 (0) 15 52 
Cycles to PGD 79 (25) 74 53 9 (15) 95 94 21 13 39 (2) 11 68 281 879 
Zona breaching              
 AT Drilling 10 (0) 18 13 0 (6) 43 12 12 (1) 56 182 
 Laser Drilling 66 (25) 53 38 9 (9) 49 71 18 12 25 (1) 54 192 631 
 Mechanical 3 (0) 11 2 (0) 33 66 
Biopsy method              
 PB 0 (0) 24 35 
 Cleavage aspiration 71 (19) 66 51 7 (13) 91 83 16 13 39 (2) 11 63 249 794 
 Cleavage extrusion 2 (0) 19 
 Blastocyst 6 (6) 2 (1) 16 
 PB + embryo 0 (0) 15 
Embryology              
 COCs 1065 (438) 995 860 170 (222) 1269 1171 346 177 587 (24) 132 938 4008 12 402 
 Inseminated 875 (351) 807 661 121 (178) 1039 985 284 155 471 (23) 116 768 3301 10 135 
 Fertilized 661 (236) 592 507 85 (125) 778 726 217 120 372 (20) 92 592 2499 7622 
 Biopsied 547 (174) 424 347 51 (79) 572 514 161 67 221 (18) 61 395 1711 5342 
 Successfully biopsied 532 (174) 423 345 51 (79) 568 513 161 67 220 (18) 61 394 1700 5306 
 Diagnosed 459 (163) 355 287 48 (71) 515 442 150 65 209 (18) 52 353 1539 4726 
 Transferable 274 (17) 225 175 8 (20) 226 182 53 26 122 (10) 29 179 828 2374 
 Transferred 156 (15) 125 81 6 (13) 120 121 32 13 73 (3) 13 107 458 1336 
 Frozen 34 (24) 27 37 2 (15) 57 28 19 (4) 22 156 447 
Clinical outcome              
 Cycles to ET 67 (14) 65 46 4 (8) 80 72 18 36 (2) 52 242 724 
 hCG Positive 33 (3) 28 15 1 (2) 34 30 10 (2) 21 101 291 
 Positive heartbeat 25 (3) 22 14 1 (0) 29 22 9 (1) 18 86 237 
 Clinical pregnancy rate (% per OR/% per ET) 30.37 (11/21) 28/34 25/30 8/25 (0/0) 30/36 22/30 19/22 14/22 21/25 (50/50) 9/11 24/35 29/36 26/33 
 Number fetal heartbeats 38 (4) 27 18 1(0) 34 27 13 (1) 20 109 300 
 Implantation rate (fetal heartbeats/embryos transferred) 24 (27) 22 22 17 (0) 28.3 22 16 15 18 (33) 19 24 23 
 Deliveries 22 (3) 22 10 1 (0) 27 19 9 (1) 16 75 212 
 Delivery rate (% per OR/% per ET) 27/33 (11/21) 28/34 18/22 8/25 27/34 19/26 19/22 14/22 21/25 (50/50) 9/11 21/31 25/31 23/29 
 Miscarriages 2 (0) 0 (0) 10 23 
 Miscarriage rate (% per clinical pregn–pregn lost to FU) 8 (0) 29 14 0 (0) 11 12 10 
Clin pregn lost to FU 1 (0) 0 (0) 
Indication Autosomal Recessive
 
Autosomal dominant
 
Specific X-linked
 
Other Total 
 β-Thal and/or sickle syndromes1 (+HLA) CF2 SMA3 HLA compatibility (HLA+ specific disease) HD DM14 Neurofibromatosis5 CMT DMD (BMD) Haem A or B6 FRAXA   
Cycles to OR 82 (28) 78 56 12 (17) 98 98 21 14 43 (2) 11 75 296 931 
Number infertile 32 (1) 28 11 28 3 (1) 14 64 192 
Female age (years) 34 32 33 35 32 32 33 30 35 30 33 26 31 
ART method              
 IVF 0 (0) 
 ICSI 77 (28) 78 55 12 (17) 97 98 18 14 41 (2) 11 75 294 917 
 ICSI + frozen 5 (0) 2 (0) 
Cancelled after IVF/ICSI 3 (3) 3 (2) 4 (0) 15 52 
Cycles to PGD 79 (25) 74 53 9 (15) 95 94 21 13 39 (2) 11 68 281 879 
Zona breaching              
 AT Drilling 10 (0) 18 13 0 (6) 43 12 12 (1) 56 182 
 Laser Drilling 66 (25) 53 38 9 (9) 49 71 18 12 25 (1) 54 192 631 
 Mechanical 3 (0) 11 2 (0) 33 66 
Biopsy method              
 PB 0 (0) 24 35 
 Cleavage aspiration 71 (19) 66 51 7 (13) 91 83 16 13 39 (2) 11 63 249 794 
 Cleavage extrusion 2 (0) 19 
 Blastocyst 6 (6) 2 (1) 16 
 PB + embryo 0 (0) 15 
Embryology              
 COCs 1065 (438) 995 860 170 (222) 1269 1171 346 177 587 (24) 132 938 4008 12 402 
 Inseminated 875 (351) 807 661 121 (178) 1039 985 284 155 471 (23) 116 768 3301 10 135 
 Fertilized 661 (236) 592 507 85 (125) 778 726 217 120 372 (20) 92 592 2499 7622 
 Biopsied 547 (174) 424 347 51 (79) 572 514 161 67 221 (18) 61 395 1711 5342 
 Successfully biopsied 532 (174) 423 345 51 (79) 568 513 161 67 220 (18) 61 394 1700 5306 
 Diagnosed 459 (163) 355 287 48 (71) 515 442 150 65 209 (18) 52 353 1539 4726 
 Transferable 274 (17) 225 175 8 (20) 226 182 53 26 122 (10) 29 179 828 2374 
 Transferred 156 (15) 125 81 6 (13) 120 121 32 13 73 (3) 13 107 458 1336 
 Frozen 34 (24) 27 37 2 (15) 57 28 19 (4) 22 156 447 
Clinical outcome              
 Cycles to ET 67 (14) 65 46 4 (8) 80 72 18 36 (2) 52 242 724 
 hCG Positive 33 (3) 28 15 1 (2) 34 30 10 (2) 21 101 291 
 Positive heartbeat 25 (3) 22 14 1 (0) 29 22 9 (1) 18 86 237 
 Clinical pregnancy rate (% per OR/% per ET) 30.37 (11/21) 28/34 25/30 8/25 (0/0) 30/36 22/30 19/22 14/22 21/25 (50/50) 9/11 24/35 29/36 26/33 
 Number fetal heartbeats 38 (4) 27 18 1(0) 34 27 13 (1) 20 109 300 
 Implantation rate (fetal heartbeats/embryos transferred) 24 (27) 22 22 17 (0) 28.3 22 16 15 18 (33) 19 24 23 
 Deliveries 22 (3) 22 10 1 (0) 27 19 9 (1) 16 75 212 
 Delivery rate (% per OR/% per ET) 27/33 (11/21) 28/34 18/22 8/25 27/34 19/26 19/22 14/22 21/25 (50/50) 9/11 21/31 25/31 23/29 
 Miscarriages 2 (0) 0 (0) 10 23 
 Miscarriage rate (% per clinical pregn–pregn lost to FU) 8 (0) 29 14 0 (0) 11 12 10 
Clin pregn lost to FU 1 (0) 0 (0) 

CMT, Charcot-Marie-Tooth; NF1, neurofibromatosis type 1.

1Includes two cycles done also with FISH for a Roberstonian translocation.

2Includes two cycles done also with FISH, one for diabetes insipidus (sexing) and the other for PGS.

3Includes five cycles done also for retinitis pigmentosa and one with FISH for PGS (advanced maternal age: AMA).

4Includes one cycle also for DMD.

5Includes three cycles using FISH for a microdeletion.

6Includes ten cycles Haem A and one cycle Haem B.

For data IX, 12 402 oocytes were collected and 75% (7622/10 135) fertilized. ICSI was used in 926 cycles (of which 9 were subsequently frozen) and in vitro fertilization (IVF) in the 5 cycles that were analysed using FISH. For the first time since data collection was initiated, all cycles that were analysed by polymerase chain reaction (PCR) used ICSI for embryo fertilization, as recommended by our best-practice guidelines (Thornhill et al., 2005). A total of 70% (5342/7622) of the embryos were biopsied and 99% (5306/5342) were successfully biopsied. Of the embryos successfully biopsied, 89% (4726/5306) gave a diagnostic result, of which 45% (2374/5306) were transferable. From 931 OR procedures, 78% (724/931) resulted in an embryo transfer procedure. A positive hCG was obtained in 291 cycles, with a positive heart beat in 237 cycles [26% per OR (237/931) and 33% per embryo transfer (237/724)] and 300 fetal hearts, giving an overall implantation rate of 23% (300/1336). These pregnancy rates were notably higher than in the previous data collections. Finally, the delivery rate was 23% per OR (212/931) and 29% per embryo transfer (212/724). There were 23/237 miscarriages (10% per clinical pregnancy) and 2/237 clinical pregnancies lost to follow-up.

Overall, the number of PGD cycles performed for monogenic disorders between January and December 2006 was almost double that of the previous year (data collection VIII), representing a marked increase. However, there were no marked changes with respect to the progress and outcome of cycles, including the embryology, rates of diagnosis and clinical outcome, such as clinical pregnancy and embryo implantation rates (Harper et al., 2008a).

Preimplantation genetic screening

Tables Va and Vb summarize the 9153 and 3900 cycles to OR reported for data collections I–VIII and IX, respectively. For data IX, 42 763 oocytes were collected, 71% (25 393/35 897) fertilized, 80% (20 181/25 393) embryos were biopsied and 99% (20 001/20 181) were successfully biopsied. Of the embryos successfully biopsied, 93% (18 592/20 001) gave a diagnostic result, of which only 36% (6596/18 592) were transferable. From 3900 OR procedures, only 73% (2836/3900) resulted in an embryo transfer procedure. A positive hCG was obtained in 980 cycles, with a positive heart beat in 794 cycles [20% per OR (794/3900) and 28% per embryo transfer (794/2836)]. This gave an implantation rate of 21% (999/4844). These pregnancy rates were similar to the previous data collections. Finally, the delivery rate was 16% per OR (619/3900) and 22% per embryo transfer (619/2836). There were 148/794 miscarriages (19% per clinical pregnancy) and 30/794 clinical pregnancies lost to follow-up.

Table Va

Cycles performed for PGS, data collection I–VIII

Indication AMA AMA + miscarriage1 AMA + RIF1 Recurrent miscarriage Recurrent IVF failure SMF2 No indication Other Total 
Cycles to OR 2747 267 695 1288 2632 799 228 497 9153 
Number infertile 2365 211 639 1012 2588 735 218 401 8169 
Female age 41 41 41 36 35 35 34 35 37 
Cancelled before IVF/ICSI 
ART method          
 IVF 304 40 53 145 223 80 73 920 
 ICSI 2388 218 629 1110 2354 776 133 401 8009 
 IVF + ICSI 44 28 21 16 14 144 
 ICSI + frozen 28 
 Unknown 24 14 504 
Cancelled after IVF/ICSI 125 21 29 100 24 15 329 
Cycles to PGS 2622 246 688 1259 2531 775 220 481 8822 
Zona breaching          
 AT drilling 998 89 230 619 877 268 69 222 3372 
 Laser drilling 1491 117 272 588 1301 441 121 217 4548 
 Mechanical 120 40 186 51 316 66 30 28 837 
 Unknown 13 37 14 654 
Biopsy method          
 Polar body biopsy 2193 66 339 39 308 28 10073 
 Cleavage aspiration 21993 165 328 1153 2055 727 190 451 72683 
 Cleavage extrusion 185 15 21 62 123 47 17 472 
 Cleavage flow displacement 22 
 Blastocyst 
 Unknown 13 38 524 
Embryology          
 COCs 27 782 2494 6489 16 902 35 122 11 621 2736 6686 109 832 
 Inseminated 23 373 2012 4900 13 888 29 005 9396 2329 5598 90 501 
 Fertilized 16 351 1367 3402 10 090 20 792 6423 1640 4021 64 086 
 Biopsied 12 996 1286 3874 7669 16 189 4850 1330 3065 51 259 
 Successfully biopsied 12 847 1283 3825 7553 15 979 4816 1291 3028 50 622 
 Diagnosed 11 681 1220 3649 68265 14 9465 4452 10965 27195 46 5895 
 Transferable 3270 366 1265 25295 56305 1891 6185 12155 16 7845 
 Transferred 2948 269 879 18375 37805 1295 3325 7915 12 1315 
 Frozen 346 41 133 367 794 231 96 295 2303 
Clinical outcome          
 Cycles to ET 1686 167 523 986 2013 658 180 384 6597 
 HCG positive 496 37 105 370 647 282 68 160 2165 
 Positive heart beat 367 22 79 291 484 225 56 115 1639 
 Clinical pregnancy rate (% per OR/% per ET) 13/22 8/13 11/15 23/30 18/24 28/34 25/31 23/30 18/25 
Indication AMA AMA + miscarriage1 AMA + RIF1 Recurrent miscarriage Recurrent IVF failure SMF2 No indication Other Total 
Cycles to OR 2747 267 695 1288 2632 799 228 497 9153 
Number infertile 2365 211 639 1012 2588 735 218 401 8169 
Female age 41 41 41 36 35 35 34 35 37 
Cancelled before IVF/ICSI 
ART method          
 IVF 304 40 53 145 223 80 73 920 
 ICSI 2388 218 629 1110 2354 776 133 401 8009 
 IVF + ICSI 44 28 21 16 14 144 
 ICSI + frozen 28 
 Unknown 24 14 504 
Cancelled after IVF/ICSI 125 21 29 100 24 15 329 
Cycles to PGS 2622 246 688 1259 2531 775 220 481 8822 
Zona breaching          
 AT drilling 998 89 230 619 877 268 69 222 3372 
 Laser drilling 1491 117 272 588 1301 441 121 217 4548 
 Mechanical 120 40 186 51 316 66 30 28 837 
 Unknown 13 37 14 654 
Biopsy method          
 Polar body biopsy 2193 66 339 39 308 28 10073 
 Cleavage aspiration 21993 165 328 1153 2055 727 190 451 72683 
 Cleavage extrusion 185 15 21 62 123 47 17 472 
 Cleavage flow displacement 22 
 Blastocyst 
 Unknown 13 38 524 
Embryology          
 COCs 27 782 2494 6489 16 902 35 122 11 621 2736 6686 109 832 
 Inseminated 23 373 2012 4900 13 888 29 005 9396 2329 5598 90 501 
 Fertilized 16 351 1367 3402 10 090 20 792 6423 1640 4021 64 086 
 Biopsied 12 996 1286 3874 7669 16 189 4850 1330 3065 51 259 
 Successfully biopsied 12 847 1283 3825 7553 15 979 4816 1291 3028 50 622 
 Diagnosed 11 681 1220 3649 68265 14 9465 4452 10965 27195 46 5895 
 Transferable 3270 366 1265 25295 56305 1891 6185 12155 16 7845 
 Transferred 2948 269 879 18375 37805 1295 3325 7915 12 1315 
 Frozen 346 41 133 367 794 231 96 295 2303 
Clinical outcome          
 Cycles to ET 1686 167 523 986 2013 658 180 384 6597 
 HCG positive 496 37 105 370 647 282 68 160 2165 
 Positive heart beat 367 22 79 291 484 225 56 115 1639 
 Clinical pregnancy rate (% per OR/% per ET) 13/22 8/13 11/15 23/30 18/24 28/34 25/31 23/30 18/25 

RIF, repeated implantation failure; SMF, severe male factor.

Other—includes data with two indications and previous abnormal pregnancies.

1These data were not extracted from I–IV.

2These data were not extracted from I–III.

3One cycle had cleavage stage biopsy and PB biopsy.

4Several cycles had incomplete results.

5Several cycles from one centre had no information on the number of embryos diagnosed, number embryos diagnosed as transferable, but patients did have embryos transferred. In these cases, undiagnosed or abnormal embryos were transferred.

Table Vb

Cycles performed for PGS, data collection IX

Indication AMA RIF Recur miscar AMA + RIF AMA + miscar SMF AMA + SMF RIF + SMF Miscar + SMF Oocyte donation Prev abn preg No indication Other Total 
Cycles to OR 1403 748 408 368 132 365 34 45 10 67 25 129 166 3900 
Number infertile 1120 687 153 357 77 308 32 45 47 13 129 161 3135 
Female age (years) 40 30 26 40 40 35 37 35 38 41 35 36 36 36 
ART method               
 IVF 322 61 42 75 23 36 10 575 
 ICSI 1055 670 354 293 107 348 32 44 10 66 24 73 156 3232 
 IVF + ICSI 22 15 16 20 81 
 IVF + frozen 
 ICSI + frozen 
Cancelled post-OR 55 14 11 18 113 
Cycles to PGD 1348 734 397 367 128 363 34 45 10 67 25 111 158 3787 
Zona breaching               
 AT drilling 163 75 88 40 30 149 32 598 
 Laser drilling 1153 555 292 249 70 168 27 44 45 23 76 152 2856 
 Mechanical 32 104 17 78 28 46 22 333 
Biopsy method               
 PB 113 186 11 272 35 11 23 42 44 71 809 
 Cleavage aspiration 1196 507 374 74 84 347 10 45 25 66 86 2825 
 Cleavage extrusion 39 41 12 21 22 153 
Embryology               
 COCs 13 116 9541 4656 3275 1313 5489 357 546 155 940 319 1318 1738 42 763 
 Inseminated 11 267 7873 3923 2661 1051 4516 306 482 122 799 262 1169 1466 35 897 
 Fertilized 7841 5769 2965 1823 771 3113 207 309 67 584 199 743 1002 25 393 
 Biopsied 5914 4629 2215 1902 698 2291 185 308 62 436 136 620 785 20 181 
 Successfully biopsied 5793 4596 2207 1900 698 2289 183 307 62 435 133 615 783 20 001 
 Diagnosed 5361 4313 2109 1722 631 2185 144 268 61 433 129 541 695 18 592 
 Transferable 1780 1637 720 605 184 784 37 80 28 204 51 193 293 6596 
 Transferred 1446 1093 503 518 139 529 431 74 16 106 26 158 193 4844 
 Frozen 207 232 101 38 22 111 73 11 62 862 
Clinical outcome               
 Cycles to ET 891 601 296 291 81 295 27 38 61 16 97 134 2836 
 hCG positive 253 240 125 67 19 119 10 10 37 41 51 980 
 Positive heart beat 190 201 93 61 16 103 10 30 37 38 794 
 Clinical pregnancy rate (% per OR/% per ET) 13/21 27/33 23/31 17/21 12/23 28/35 21/26 22/26 30/37 45/49 20/31 29/38 23/28 20/28 
 Number of fetal hearts 229 265 124 70 19 134 10 13 41 43 40 999 
 Implantation rate (fetal hearts/100 embryos transferred) 16 24 25 14 14 25 23 18 31 39 23 27 21 21 
 Deliveries 149 163 69 38 12 83 25 30 30 619 
 Delivery rate (% per OR/% per ET) 11/17 22/27 17/23 10/13 9/15 23/28 21/26 20/24 30/37 37/41 4/6 23/31 18/22 16/22 
 Miscarriages 36 30 19 20 16 148 
 Miscarriage rate (% per clinical pregn–pregn lost to FU) 19 15 22 34 25 16 10 14 80 19 19 19 
 Clinical pregnancies lost to FU 30 
Indication AMA RIF Recur miscar AMA + RIF AMA + miscar SMF AMA + SMF RIF + SMF Miscar + SMF Oocyte donation Prev abn preg No indication Other Total 
Cycles to OR 1403 748 408 368 132 365 34 45 10 67 25 129 166 3900 
Number infertile 1120 687 153 357 77 308 32 45 47 13 129 161 3135 
Female age (years) 40 30 26 40 40 35 37 35 38 41 35 36 36 36 
ART method               
 IVF 322 61 42 75 23 36 10 575 
 ICSI 1055 670 354 293 107 348 32 44 10 66 24 73 156 3232 
 IVF + ICSI 22 15 16 20 81 
 IVF + frozen 
 ICSI + frozen 
Cancelled post-OR 55 14 11 18 113 
Cycles to PGD 1348 734 397 367 128 363 34 45 10 67 25 111 158 3787 
Zona breaching               
 AT drilling 163 75 88 40 30 149 32 598 
 Laser drilling 1153 555 292 249 70 168 27 44 45 23 76 152 2856 
 Mechanical 32 104 17 78 28 46 22 333 
Biopsy method               
 PB 113 186 11 272 35 11 23 42 44 71 809 
 Cleavage aspiration 1196 507 374 74 84 347 10 45 25 66 86 2825 
 Cleavage extrusion 39 41 12 21 22 153 
Embryology               
 COCs 13 116 9541 4656 3275 1313 5489 357 546 155 940 319 1318 1738 42 763 
 Inseminated 11 267 7873 3923 2661 1051 4516 306 482 122 799 262 1169 1466 35 897 
 Fertilized 7841 5769 2965 1823 771 3113 207 309 67 584 199 743 1002 25 393 
 Biopsied 5914 4629 2215 1902 698 2291 185 308 62 436 136 620 785 20 181 
 Successfully biopsied 5793 4596 2207 1900 698 2289 183 307 62 435 133 615 783 20 001 
 Diagnosed 5361 4313 2109 1722 631 2185 144 268 61 433 129 541 695 18 592 
 Transferable 1780 1637 720 605 184 784 37 80 28 204 51 193 293 6596 
 Transferred 1446 1093 503 518 139 529 431 74 16 106 26 158 193 4844 
 Frozen 207 232 101 38 22 111 73 11 62 862 
Clinical outcome               
 Cycles to ET 891 601 296 291 81 295 27 38 61 16 97 134 2836 
 hCG positive 253 240 125 67 19 119 10 10 37 41 51 980 
 Positive heart beat 190 201 93 61 16 103 10 30 37 38 794 
 Clinical pregnancy rate (% per OR/% per ET) 13/21 27/33 23/31 17/21 12/23 28/35 21/26 22/26 30/37 45/49 20/31 29/38 23/28 20/28 
 Number of fetal hearts 229 265 124 70 19 134 10 13 41 43 40 999 
 Implantation rate (fetal hearts/100 embryos transferred) 16 24 25 14 14 25 23 18 31 39 23 27 21 21 
 Deliveries 149 163 69 38 12 83 25 30 30 619 
 Delivery rate (% per OR/% per ET) 11/17 22/27 17/23 10/13 9/15 23/28 21/26 20/24 30/37 37/41 4/6 23/31 18/22 16/22 
 Miscarriages 36 30 19 20 16 148 
 Miscarriage rate (% per clinical pregn–pregn lost to FU) 19 15 22 34 25 16 10 14 80 19 19 19 
 Clinical pregnancies lost to FU 30 

Recur miscar, recurrent miscarriage; Prev abn preg, previous abnormal pregnancy.

‘Others’ contains also cycles with multiple indications.

1Failed embryos were also transferred.

The main indications were advanced maternal age (AMA) (1403 ORs) and repeated implantation failure (748 ORs). There were still a large number of cycles reported where no indication was given (129 ORs). All indications involving AMA showed a somewhat lower pregnancy rate (between 13 and 21%) in comparison to the other indications, although the pregnancy rates were higher than in previous data collections. Severe male factor showed a relatively high pregnancy rate [28% per OR (103/365)] as did patients where oocyte donation was performed [45% per OR (30/67)]. Patients with no indication had a pregnancy rate of 29% per OR (37/129).

From 3900 cycles, 368 involved the biopsy of only one embryo and 474 involved the biopsy of two embryos. As stated in data VII (Harper et al., 2008a, b), in the majority of cases these embryos should be replaced without biopsy.

For the first time in the data collection, 3 cycles were performed using a PCR-based micro-array, in all other 3784 cycles FISH was used.

The column ‘others’ contains various indications, such as mosaic embryos and single or double embryo transfer, as well as cycles with multiple indications.

The ESHRE PGS Task Force continues in an attempt to set up a multicentre randomized controlled study for PGS. The discussion about the efficacy of PGS is still very much alive and asks for clear answers.

PGD cycles for social sexing

Table VIa and VIb summarize the 497 and 82 cycles to OR collected for data collections I–VIII and IX, respectively. For data IX, 1150 oocytes were collected, 73% (721/988) fertilized, 79% (568/721) embryos were biopsied and 99% (565/568) was successfully biopsied. Of the embryos successfully biopsied 87% (494/565) gave a diagnostic result, of which only 42% (209/494) were transferable (of the desired sex). From 82 OR procedures, only 79% (65/82) resulted in an embryo transfer procedure. A positive hCG was obtained in 20 cycles, with a positive heart beat in 13 cycles [16% per OR (13/82) and 20% per embryo transfer (13/65)]. This gave an implantation rate of 11% (13/119). These pregnancy rates were similar to the previous data collections. Finally, the delivery rate was 15% per OR (12/82) and 18% per embryo transfer (12/65). There was 1/13 miscarriage (8% per clinical pregnancy) and no clinical pregnancies lost to follow-up.

Table VIa

PGD for social sexing, data collection I–VIII

Method for sexing FISH (SS only) FISH (SS + AS)1 PCR Unknown Total 
Cycles to OR 256 47 189 52 4972 
Number infertile 25 16 46 
Female age 35 38 37 35 37 
ART method      
 IVF 117 10 138 
 ICSI 134 38 168 342 
 Frozen 
 Frozen + IVF + ICSI + unknown 12 
Cancelled after IVF/ICSI 16 
Cycles to PGD 252 47 182 481 
Zona breaching      
 AT drilling 10 19 
 Laser drilling 118 119 
 Mechanical 125 47 171 343 
Biopsy method      
 Cleavage aspiration 126 11 137 
 Cleavage extrusion 126 47 171 344 
Embryology      
 COCs 3292 609 2878 23 6802 
 Inseminated 2876 533 2188 19 5616 
 Fertilized 2025 364 1452 11 3852 
 Biopsied 1627 244 1143 3014 
 Successfully biopsied 1530 244 1116 2890 
 Diagnosed 1398 200 1049 2647 
 Transferable 497 62 473 1032 
 Transferred 330 50 361 741 
 Frozen3 123 86 04 215 
Clinical outcome      
 Cycles to ET 184 32 138 354 
 hCG positive 72 11 58 141 
 Positive heart beat 61 39 107 
 Clinical pregnancy rate (% per OR/% per ET) 24/33 15/22 21/28 22/30 
Method for sexing FISH (SS only) FISH (SS + AS)1 PCR Unknown Total 
Cycles to OR 256 47 189 52 4972 
Number infertile 25 16 46 
Female age 35 38 37 35 37 
ART method      
 IVF 117 10 138 
 ICSI 134 38 168 342 
 Frozen 
 Frozen + IVF + ICSI + unknown 12 
Cancelled after IVF/ICSI 16 
Cycles to PGD 252 47 182 481 
Zona breaching      
 AT drilling 10 19 
 Laser drilling 118 119 
 Mechanical 125 47 171 343 
Biopsy method      
 Cleavage aspiration 126 11 137 
 Cleavage extrusion 126 47 171 344 
Embryology      
 COCs 3292 609 2878 23 6802 
 Inseminated 2876 533 2188 19 5616 
 Fertilized 2025 364 1452 11 3852 
 Biopsied 1627 244 1143 3014 
 Successfully biopsied 1530 244 1116 2890 
 Diagnosed 1398 200 1049 2647 
 Transferable 497 62 473 1032 
 Transferred 330 50 361 741 
 Frozen3 123 86 04 215 
Clinical outcome      
 Cycles to ET 184 32 138 354 
 hCG positive 72 11 58 141 
 Positive heart beat 61 39 107 
 Clinical pregnancy rate (% per OR/% per ET) 24/33 15/22 21/28 22/30 

AS, aneuploidy screening.

1These data were not extracted from I–VII.

2One natural cycle included.

3Eleven cycles with embryos frozen without biopsy or failed diagnosis included.

4Three embryos frozen without biopsy were not included.

Table VIb

PGD for social sexing, data collection IX

 FISH (SS only) FISH (SS + AS) Total 
Cycles to OR 40 42 82 
Number infertile 
Female age (years) 35 40 38 
ART method    
 IVF 
 ICSI 34 40 74 
Cancelled after IVF/ICSI 
Cycles to PGD 40 42 82 
Zona breaching    
 Laser drilling 12 
 Mechanical 32 38 70 
Biopsy method    
 Cleavage aspiration 
 Cleavage extrusion 36 42 78 
Embryology    
 COCs 532 618 1150 
 Inseminated 465 523 988 
 Fertilized 337 384 721 
 Biopsied 264 304 568 
 Successfully biopsied 261 304 565 
 Diagnosed 226 268 494 
 Transferable 120 89 209 
 Transferred 67 52 119 
 Frozen 47 28 75 
Clinical outcome    
 Cycles to ET 37 28 65 
 hCG positive 11 20 
 Positive heart beat 13 
 Clinical pregnancy rate (% per OR/% per ET) 17/19 14/21 16/20 
 Number fetal hearts 13 
 Implantation rate (fetal hearts/embryos transferred) 10 12 11 
 Deliveries 12 
 Delivery rate (% per OR/% per ET) 18/19 12/18 15/18 
 Miscarriages 
 Miscarriage rate (% per clinical pregn–pregn lost to FU) 17 
 Clinical pregnancies lost to FU 
 FISH (SS only) FISH (SS + AS) Total 
Cycles to OR 40 42 82 
Number infertile 
Female age (years) 35 40 38 
ART method    
 IVF 
 ICSI 34 40 74 
Cancelled after IVF/ICSI 
Cycles to PGD 40 42 82 
Zona breaching    
 Laser drilling 12 
 Mechanical 32 38 70 
Biopsy method    
 Cleavage aspiration 
 Cleavage extrusion 36 42 78 
Embryology    
 COCs 532 618 1150 
 Inseminated 465 523 988 
 Fertilized 337 384 721 
 Biopsied 264 304 568 
 Successfully biopsied 261 304 565 
 Diagnosed 226 268 494 
 Transferable 120 89 209 
 Transferred 67 52 119 
 Frozen 47 28 75 
Clinical outcome    
 Cycles to ET 37 28 65 
 hCG positive 11 20 
 Positive heart beat 13 
 Clinical pregnancy rate (% per OR/% per ET) 17/19 14/21 16/20 
 Number fetal hearts 13 
 Implantation rate (fetal hearts/embryos transferred) 10 12 11 
 Deliveries 12 
 Delivery rate (% per OR/% per ET) 18/19 12/18 15/18 
 Miscarriages 
 Miscarriage rate (% per clinical pregn–pregn lost to FU) 17 
 Clinical pregnancies lost to FU 

More than 50% of the cycles were for couples who requested a male embryo (47 cycles) rather than a female embryo (35 cycles). This number is slightly lower than in the last data collection (Goossens et al., 2008). There are more males requested than females as a large number of cases are done in the USA where MicroSort® sperm separation is used and is more efficient at selecting X bearing sperm.

Pregnancies and babies

Tables VIIa,VIIb,IXa,IXb,Xa,Xb,XIa,rXIb and Supplementary Tables VIIIa, VIIIb, XIIa and XIIb summarize the pregnancy and baby data. Data IX were comparable to previous data collections. Data IX included 1437 pregnancies which resulted in 1529 fetal sacs (Table VIIb). There were 980 deliveries of 1206 babies. Of the 1292 cycles ending in a pregnancy with a positive heartbeat, follow-up data on 1279 pregnancies were reported. Of the 980 pregnancies reported to have ended with a delivery (total number of babies: 1206), neonatal data on 1183 babies born from 980 deliveries were submitted. The delivery rates per indication are reported in Tables IIb, IIIb, IVb, Vb and VIb. Forty-four percentage of the deliveries were by Caesarean section (431/980) (Table IXb). In 151 cases, the method of delivery was not known.

Table VIIa

Evolution of pregnancy, data I–VIII

 N pregnancies N fetal sacs 
Pregnancies 3158 3345 
 FISH cycles 2535  
 PCR cycles 620  
 FISH + PCR  
Subclinical pregnancies1 554  
Clinical pregnancies 2604 3345 
 Singletons 1903 1903 
 Twins 597 1194 
 Triplets 77 231 
 Quadruplet 16 
 Unknown 23 12 
Lost to FU during first trimester 29 27 
First trimester loss 266 398 
 Miscarriage 2263 250 
 TOP 54 
 Extra-uterine pregnancy 325 19 
 Vanishing twins/triplets  95 
 Reduction of multiple pregnancies  25 
  Quadruplet to twin  
  Triplet to twin  11 
  Triplet to singleton  
  Twin to singleton  
 Unknown 
Ongoing pregnancies >12 weeks 2309 2920 
Second trimester loss 49 102 
 Miscarriage 346 53 
 Miscarriage twin to singleton  
 TOP 157 15 
 Reduction of multiple pregnancies  33 
  Quadruplet to twin  
  Triplet to twin  11 
  Triplet to singleton  14 
  Twin to singleton  48 
Lost to FU during second trimester 779 95 
Deliveries 2183 2723 
 Singletons 1664 1664 
 Twins 498 996 
 Triplets 21 63 
 N pregnancies N fetal sacs 
Pregnancies 3158 3345 
 FISH cycles 2535  
 PCR cycles 620  
 FISH + PCR  
Subclinical pregnancies1 554  
Clinical pregnancies 2604 3345 
 Singletons 1903 1903 
 Twins 597 1194 
 Triplets 77 231 
 Quadruplet 16 
 Unknown 23 12 
Lost to FU during first trimester 29 27 
First trimester loss 266 398 
 Miscarriage 2263 250 
 TOP 54 
 Extra-uterine pregnancy 325 19 
 Vanishing twins/triplets  95 
 Reduction of multiple pregnancies  25 
  Quadruplet to twin  
  Triplet to twin  11 
  Triplet to singleton  
  Twin to singleton  
 Unknown 
Ongoing pregnancies >12 weeks 2309 2920 
Second trimester loss 49 102 
 Miscarriage 346 53 
 Miscarriage twin to singleton  
 TOP 157 15 
 Reduction of multiple pregnancies  33 
  Quadruplet to twin  
  Triplet to twin  11 
  Triplet to singleton  14 
  Twin to singleton  48 
Lost to FU during second trimester 779 95 
Deliveries 2183 2723 
 Singletons 1664 1664 
 Twins 498 996 
 Triplets 21 63 

1Subclinical pregnancy defined as pregnancy without any other clinical signs, but positive serum hCG.

2Number of fetal heart beats not known. Counted further as one fetal heart.

3One miscarriage after amniocentesis.

4TOP, termination of pregnancy. Two TOPs for ancephalocoele, one TOP for social reasons, one TOP of twin with misdiagnosis for CMT disease 1a.

5One heterotrophic gestation continued as singleton after reduction of extrauterine gestation at 6 weeks.

6One 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).

7TOP after misdiagnosis (five): One misdiagnosis for sexing, FISH, female fetus, indication social sexing; one misdiagnosis for β-Thal, PCR; one misdiagnosis for myotonic dystrophy, PCR, one misdiagnosis after PGS, karyotype 45,X; one misdiagnosis for a reciprocal translocation 46,XY,der(15)t(3;15)(q25.1;q26.3). TOP after ultrasound (four): enlarged lateral ventricle, two singletons with cardiopathy, one singleton with tetralogy of Fallot. TOP after amniocentesis, not related to the PGD: trisomy 18, indication for PGD parent carrier of reciprocal translocation not involving chromosome 18; one polymalformation; one cystic hygroma, failed karyotype; one Turner mosaic, one spina bifida.

8One misdiagnosis for sexing, PCR, indication Duchenne, twin pregnancy, selective termination of male fetus. Cycle done in 1996, Y-specific amplification only.

9One misdiagnosis (47,XXX after PGS for RIF) lost to FU.

Table VIIb

Evolution of pregnancy, data IX

 N pregnancies N fetal sacs 
Pregnancies 1437 1529 
 FISH only cycles 1153  
 PCR only cycles 282  
 FISH + PCR  
Subclinical pregnancies1 145  
Clinical pregnancies 1292 1529 
 Singletons 919 919 
 Twins 280 560 
 Triplets 14 42 
 Quadruplet 
 Unknown no sacs 77  
Lost to follow up during first trimester 13 16 
First trimester loss 262 255 
 Miscarriage 191 214 
 TOP 32 
 Extra-uterine pregnancy 13 16 
 Vanishing twins/triplets or miscarriage multiplet  13 
  Twin to singleton  12 
  Triplet to singleton  
  Triplet to twin  
 Unknown 55  
Reduction of multiple pregnancies  10 
 Quadruplet to twin  
 Triplet to twin  
 Triplet to singleton  
 Twin to singleton  
Ongoing pregnancies (>12 weeks) 1017 1258 
Second trimester loss 29 39 
 Miscarriage 23 30 
 TOP 53 
 Miscarriage twin to singleton  
 Twin to twin transfusion 
Lost to follow-up during second trimester 8 13 
Deliveries 980 1206 
 Singletons 760 760 
 Twins 214 428 
 Triplets 18 
 N pregnancies N fetal sacs 
Pregnancies 1437 1529 
 FISH only cycles 1153  
 PCR only cycles 282  
 FISH + PCR  
Subclinical pregnancies1 145  
Clinical pregnancies 1292 1529 
 Singletons 919 919 
 Twins 280 560 
 Triplets 14 42 
 Quadruplet 
 Unknown no sacs 77  
Lost to follow up during first trimester 13 16 
First trimester loss 262 255 
 Miscarriage 191 214 
 TOP 32 
 Extra-uterine pregnancy 13 16 
 Vanishing twins/triplets or miscarriage multiplet  13 
  Twin to singleton  12 
  Triplet to singleton  
  Triplet to twin  
 Unknown 55  
Reduction of multiple pregnancies  10 
 Quadruplet to twin  
 Triplet to twin  
 Triplet to singleton  
 Twin to singleton  
Ongoing pregnancies (>12 weeks) 1017 1258 
Second trimester loss 29 39 
 Miscarriage 23 30 
 TOP 53 
 Miscarriage twin to singleton  
 Twin to twin transfusion 
Lost to follow-up during second trimester 8 13 
Deliveries 980 1206 
 Singletons 760 760 
 Twins 214 428 
 Triplets 18 

1Subclinical pregnancy defined as pregnancy without any other clinical signs, but positive serum hCG.

2One TOP for 47,XY, + 13, one TOP for encephelocele and one TOP for 47,XY, + 21.

3One trisomy 21, one mosaic 46,XY/47,XY, + 18 (misdiagnosis), one Hemivertebrae, hypoplastic cerebellum, hydrocephaly (46,XX), one abnormal chromosome 15, one polycystic kidney.

Table IXa

Method of delivery and gestational age, data collection I–VIII

 Total Singletons Twins Triplets 
No deliveries 21831 16641 4981 21 
Method of delivery     
 Vaginal 920 823 96 
 Caesarian 1059 693 350 16 
 Vaginal and Caesarian 
 Unknown 200 146 50 
Term at delivery     
 Preterm 609 269 325 15 
 Term 1345 1224 119 
 Unknown 228 171 53 
 Total Singletons Twins Triplets 
No deliveries 21831 16641 4981 21 
Method of delivery     
 Vaginal 920 823 96 
 Caesarian 1059 693 350 16 
 Vaginal and Caesarian 
 Unknown 200 146 50 
Term at delivery     
 Preterm 609 269 325 15 
 Term 1345 1224 119 
 Unknown 228 171 53 

1For one twin there was only partial information: pregnancy was reported as a twin, birth and baby as a singleton.

Table IXb

Method of delivery and gestational age, data IX

 Total Singleton Twin Triplet 
No deliveries 980 760 214 
Method of delivery     
 Vaginal 395 346 49 
 Caesarean 431 295 132 
 Vaginal and Caesarean 
 Unknown 151 119 30 
Term at delivery     
 Preterm 289 133 151 
 Term 640 583 57 
 Unknown 51 44 
 Total Singleton Twin Triplet 
No deliveries 980 760 214 
Method of delivery     
 Vaginal 395 346 49 
 Caesarean 431 295 132 
 Vaginal and Caesarean 
 Unknown 151 119 30 
Term at delivery     
 Preterm 289 133 151 
 Term 640 583 57 
 Unknown 51 44 
Table Xa

Confirmation of diagnosis per fetal sac, data collection I–VIII

Method Result
 
 N Normal Abnormal Unknown 
Prenatal diagnosis     
FISH     
 CVS 82 82 
 Amniocentesis 4802 4692 
 Ultrasound 6442 635 82 
 Unknown 
Total 12061 1189 16 
PCR     
 CVS 122 119 
 Amniocentesis 119 108 10 
 Ultrasound 28 25 
 Unknown 
Total 2691 253 15 
Post-natal diagnosis     
FISH     
 Karyo miscarriage 70 34 36 
 Karyo post-natal 109 106 
 Physical examination 911 907 
 Karyo post-natal + physical examination 15 15 
 Unknown 23 23 
 Total 1107 1064 45 
PCR     
 Karyotype miscarriage 
 DNA test miscarriage 
 DNA test post-natal 50 49 
 Sweat test 
 Physical examination 52 51 
 Karyotype 
 Karyo + DNA 
 Karyo + phys exam 
 Algo test 
 Unknown 11 11 
 Total 143 139 
Method Result
 
 N Normal Abnormal Unknown 
Prenatal diagnosis     
FISH     
 CVS 82 82 
 Amniocentesis 4802 4692 
 Ultrasound 6442 635 82 
 Unknown 
Total 12061 1189 16 
PCR     
 CVS 122 119 
 Amniocentesis 119 108 10 
 Ultrasound 28 25 
 Unknown 
Total 2691 253 15 
Post-natal diagnosis     
FISH     
 Karyo miscarriage 70 34 36 
 Karyo post-natal 109 106 
 Physical examination 911 907 
 Karyo post-natal + physical examination 15 15 
 Unknown 23 23 
 Total 1107 1064 45 
PCR     
 Karyotype miscarriage 
 DNA test miscarriage 
 DNA test post-natal 50 49 
 Sweat test 
 Physical examination 52 51 
 Karyotype 
 Karyo + DNA 
 Karyo + phys exam 
 Algo test 
 Unknown 11 11 
 Total 143 139 

CVS, chorionic villus sampling.

1Three fetal sacs had PCR and FISH at PGD.

2Three fetal sacs with abnormalities on ultrasound (enlarged lateral ventricle, cardiopathy, hydrocephalus) with normal result on amniocentesis.

3Two children had unknown check and karyotype.

Table Xb

Confirmation of diagnosis per fetal sac, data collection IX

Method Result
 
 N Normal Abnormal Failed 
Prenatal diagnosis     
FISH     
 CVS 24 231 12 
 Amniocentesis 113 1091 43 
 Ultrasound 329 326 34 
 Total 466 458 8 0 
PCR     
 CVS 23 22 15 
 Amniocentesis 51 51 
 Ultrasound 
 Total 80 79 1 0 
Post-natal diagnosis     
FISH     
 Karyo miscarriage 19 12 76 
 Karyo post-natal 71 71 
 FISH microdeletion 
 Physical examination 231 230 17 
 Total 323 315 8 0 
PCR     
 Physical examination 31 31 
 DNA test post-natal 34 34 
 Sweetest 
 Hearing test 
 Karyo post-natal 
 Total 75 75 0 0 
Method Result
 
 N Normal Abnormal Failed 
Prenatal diagnosis     
FISH     
 CVS 24 231 12 
 Amniocentesis 113 1091 43 
 Ultrasound 329 326 34 
 Total 466 458 8 0 
PCR     
 CVS 23 22 15 
 Amniocentesis 51 51 
 Ultrasound 
 Total 80 79 1 0 
Post-natal diagnosis     
FISH     
 Karyo miscarriage 19 12 76 
 Karyo post-natal 71 71 
 FISH microdeletion 
 Physical examination 231 230 17 
 Total 323 315 8 0 
PCR     
 Physical examination 31 31 
 DNA test post-natal 34 34 
 Sweetest 
 Hearing test 
 Karyo post-natal 
 Total 75 75 0 0 

1Total three miscarriages after normal outcome amniocentesis (one FISH and two PCR), one miscarriage after normal outcome CVS (FISH).

247,XY, + 21 - > TOP (AS maternal age, repeated IVF failure).

39% mosaic XY / XXY (FISH AS), abnormal chromosome 15 and skeletal displasia -> TOP (AS maternal age); Mosaic: 46,XY/47, XY, + 18-> TOP (AS repeated IVF failures); 21 trisomy- > TOP (AS maternal age, repeated IVF failures).

4Encephalocele - > TOP (AS repeated miscarriage); hemivertebrae, hypoplastic cerebellum, hydrocephaly- > TOP; cystic hygroma 1 twin miscarriage- > ongoing singleton (rec. translocation FISH).

57,XY, + 13 ->TOP (PCR: not affected of Zellweger).

6Mosaic 4n/2n (AS oocyte donation recurrent miscarriage); trisomy 20 (AS maternal age recurrent miscarriage); 92,XXXX (AS maternal age repeated IVF failures); 47,XX, + 10 (AS recurrent miscarriages maternal age); 45,X/46,XY (AS oocyte donation); 45,X,t(2;4)(q11.2;q13) (FISH reciprocal translocation); 47,XY,t(11;22)(q23;q11.2), + 16[11]/46,XY,t(11;22)[7] (FISH reciprocal translocation).

7Misdiagnosis after gender selection for XL retinitis pigmentosa: male.

Table XIa

Data on live born children, data collection I–VIII

Total children born  26581 
Sex   
 Male  1161 
 Female  1405 
 Unknown  92 
Mean birthweight (g)   
 Singletons 3220 1481 
 Twins 2374 824 
 Triplets 1815 39 
Mean birth length (cm)   
 Singletons 49 982 
 Twins 46 459 
 Triplets 44 12 
Total children born  26581 
Sex   
 Male  1161 
 Female  1405 
 Unknown  92 
Mean birthweight (g)   
 Singletons 3220 1481 
 Twins 2374 824 
 Triplets 1815 39 
Mean birth length (cm)   
 Singletons 49 982 
 Twins 46 459 
 Triplets 44 12 

1Numbers in the right column indicate the number of newborns for whom information is available.

Table XIb

Data on children born, data collection IX

Total children born 1183  
Sex   
 Male 562  
 Female 559  
 Unknown 62  
Mean birthweight (g)   
 Singletons 3209 (n = 650/741)1 
 Twins 2420 (n = 384/424)1 
 Triplets 2058 (n = 15/18)1 
Mean birth length (cm)   
 Singletons 50.9 (n = 417/741)1 
 Twins 46.7 (n = 226/424)1 
 Triplets 44.0 (n = 3/18)1 
Mean head circumference (cm)   
 Singletons 34.0 (n = 187/741)1 
 Twins 30.7 (n = 82/424)1 
 Triplets 31.4 (n = 3/18)1 
Apgar scores after 1 min3  (n = 362/1183) 
 Singletons   
  Good2 228  
  Poor2 15  
 Twins   
  Good2 109  
  Poor2 10  
 Triplets   
  Good2  
  Poor2  
Apgar scores after 5 min3  (n = 353/1183) 
 Singletons   
  Good2 233  
  Poor2  
 Twins   
  Good2 114  
  Poor2  
 Triplets   
  Good2  
  Poor2  
Apgar scores after 10 min3  (n = 196/1183) 
 Singletons   
  Good2 142  
  Poor2  
 Twins   
  Good2 53  
  Poor2  
 Triplets   
  Good2  
  Poor2  
Total children born 1183  
Sex   
 Male 562  
 Female 559  
 Unknown 62  
Mean birthweight (g)   
 Singletons 3209 (n = 650/741)1 
 Twins 2420 (n = 384/424)1 
 Triplets 2058 (n = 15/18)1 
Mean birth length (cm)   
 Singletons 50.9 (n = 417/741)1 
 Twins 46.7 (n = 226/424)1 
 Triplets 44.0 (n = 3/18)1 
Mean head circumference (cm)   
 Singletons 34.0 (n = 187/741)1 
 Twins 30.7 (n = 82/424)1 
 Triplets 31.4 (n = 3/18)1 
Apgar scores after 1 min3  (n = 362/1183) 
 Singletons   
  Good2 228  
  Poor2 15  
 Twins   
  Good2 109  
  Poor2 10  
 Triplets   
  Good2  
  Poor2  
Apgar scores after 5 min3  (n = 353/1183) 
 Singletons   
  Good2 233  
  Poor2  
 Twins   
  Good2 114  
  Poor2  
 Triplets   
  Good2  
  Poor2  
Apgar scores after 10 min3  (n = 196/1183) 
 Singletons   
  Good2 142  
  Poor2  
 Twins   
  Good2 53  
  Poor2  
 Triplets   
  Good2  
  Poor2  

1Numbers between brackets indicate the number of newborns for whom information is available out of the total number of newborns.

2Good is defined ≥7, poor is defined <7.

3Total number of children about whom at least one AS is reported.

Confirmation of the diagnosis was performed prenatally (546/1529) and/or post-natally (398/1529) (Table Xb). Supplementary Table XIIb shows the abnormalities found during or after the pregnancy. Several abnormalities were found that were not related to the PGD.

This report again confirms that pregnancies and babies born after PGD are very similar to the pregnancies obtained and babies born after ICSI treatment (Bonduelle et al., 2002). In our series, the number of multiple pregnancies remains high (296/1292, 23%). This means 37% (446/1206) of the babies born are part of a multiplet at birth.

Misdiagnoses

Tables XIIIa and XIIIb summarize the misdiagnoses reported for data collections I–VIII and IX, respectively. For data IX, four misdiagnoses have been reported, all after FISH for PGS. The Consortium has published a paper on the possible causes of misdiagnosis in PGD (Wilton et al., 2009).

Table XIIIa

Summary of misdiagnosis from data I–VIII

Indication Method used PND-post-natal Outcome Reported in 
Monogenics     
 DM1 PCR PND TOP 
 β-Thal PCR PND TOP II 
 β-Thal PCR PND TOP VIII 
 Familial amyloid polyneuropathy PCR PND Born IV 
 CF PCR PND Born II 
 CF (one of twins) PCR Post Born IV 
 CMT1A PCR PND Born Cycle reported in V but misdiagnosis in VII 
 SMA PCR Post Born Cycle reported IV but misdiagnosis in VII 
 CMT1A (twins) PCR PND TOP of both twins VII 
 FRAXA PCR PND Born VIII 
Sexing for X-linked disease     
 46,XY in retinitis pigmentosa PCR PND Born IV 
 46,XY in DMD twin PCR PND TOP of one twin III 
 45,X, Haem A FISH PND TOP IV 
 46,XY, Haem A FISH Post Born VIII 
Translocations     
 Trisomy 13 after 45,XY,der(13;14)(q10;q10) FISH Miscarried Miscarried VI 
 47,XX,+der(22)t(11;22)(q23.3;q11.2)mat FISH PND TOP III 
 46,XY,der(15)t(3;15) (q25.1;q26.3)pat FISH PND TOP VII 
PGS     
 Trisomy 16 after 1st PB biopsy only FISH Miscarried Miscarried VI 
 Trisomy 16 after 1st PB biopsy only FISH Miscarried Miscarried 
 Trisomy 16 FISH Miscarried Miscarried VI 
 Trisomy 16 FISH Miscarried Miscarried VI 
 Trisomy 21 FISH Post Born III 
 47,XXX FISH PND Lost to follow-up VII 
Social sexing     
 Requested male but female fetus FISH PND TOP III 
Indication Method used PND-post-natal Outcome Reported in 
Monogenics     
 DM1 PCR PND TOP 
 β-Thal PCR PND TOP II 
 β-Thal PCR PND TOP VIII 
 Familial amyloid polyneuropathy PCR PND Born IV 
 CF PCR PND Born II 
 CF (one of twins) PCR Post Born IV 
 CMT1A PCR PND Born Cycle reported in V but misdiagnosis in VII 
 SMA PCR Post Born Cycle reported IV but misdiagnosis in VII 
 CMT1A (twins) PCR PND TOP of both twins VII 
 FRAXA PCR PND Born VIII 
Sexing for X-linked disease     
 46,XY in retinitis pigmentosa PCR PND Born IV 
 46,XY in DMD twin PCR PND TOP of one twin III 
 45,X, Haem A FISH PND TOP IV 
 46,XY, Haem A FISH Post Born VIII 
Translocations     
 Trisomy 13 after 45,XY,der(13;14)(q10;q10) FISH Miscarried Miscarried VI 
 47,XX,+der(22)t(11;22)(q23.3;q11.2)mat FISH PND TOP III 
 46,XY,der(15)t(3;15) (q25.1;q26.3)pat FISH PND TOP VII 
PGS     
 Trisomy 16 after 1st PB biopsy only FISH Miscarried Miscarried VI 
 Trisomy 16 after 1st PB biopsy only FISH Miscarried Miscarried 
 Trisomy 16 FISH Miscarried Miscarried VI 
 Trisomy 16 FISH Miscarried Miscarried VI 
 Trisomy 21 FISH Post Born III 
 47,XXX FISH PND Lost to follow-up VII 
Social sexing     
 Requested male but female fetus FISH PND TOP III 

PND, prenatal diagnosis. The numbers in the last column indicate the PGD Consortium report number.

Table XIIIb

Misdiagnosis data IX

Indication Method used PND-post-natal Outcome Reported in 
PGS     
 45,X FISH PND Miscarriage Cycle reported in VIII, but misdiagnosis in IX 
 46,XY/47,XY, + 18 FISH PND TOP IX 
 Trisomy 21 FISH PND TOP IX 
 Trisomy 21 FISH PND TOP IX 
Indication Method used PND-post-natal Outcome Reported in 
PGS     
 45,X FISH PND Miscarriage Cycle reported in VIII, but misdiagnosis in IX 
 46,XY/47,XY, + 18 FISH PND TOP IX 
 Trisomy 21 FISH PND TOP IX 
 Trisomy 21 FISH PND TOP IX 

The numbers in the last column indicate the PGD Consortium report number.

Success of individual centres

Figure 1 shows the pregnancy rate for each centre for data IX. The pregnancy rate ranges from 0 to 50% with the average being 21%. Although it could be expected that centres carrying out lower numbers of cycles may have lower rates owing to less experience, the findings indicate that some of the most active centres fall below the average 21% pregnancy rate and even have pregnancy rates lower than some of the centres performing few cycles.

Discussion

This ninth report of the ESHRE PGD Consortium demonstrates, as in previous years, the continuing increase in the number of PGD cycles, with subsequent pregnancies and babies. It must be stated that for these data collection, a large number of PGS cycles from previous years were included. They were part of an ongoing study and could not be reported before. It should be emphasized that the follow-up of pregnancies resulting from PGD cycles, and preferably also babies born, is, as part of good practice, essential to complete. It gives information on the evaluation of the overall procedure and is strongly recommended for all centres involved in PGD. Data collection IX show that more and more centres do their very best to retrieve these data.

The number of centres participating in the data collection of 2006 was much higher compared with 2005 (57 versus 39). We welcomed many new members during the last 2 years. There are still two levels of membership of the Consortium; full membership for centres that submit annual data and associate membership for centres that cannot submit data (including new clinics, IVF units that work with a diagnostic lab that is a member of the Consortium). Associate centres performing PGD must send the summary data.

As always the centres which submit data have access to the raw data, whereas the associate centres will be allowed to participate in the annual Consortium meetings and they are sent the quarterly Consortium newsletter.

Since ESHRE have set up a PGS task force, the work of the PGS working group is complete.

There are four active Consortium working groups and their work is ongoing. The database group is working on simplifying the results of pregnancies and babies as these data are difficult to summarize. A new database is in preparation for the outcome of the transfer of biopsied/thawed embryos. This will only consider embryos that were frozen after biopsy and PGD. The misdiagnosis working group has published a paper on misdiagnosis (Wilton et al., 2009) and is setting up a study of the analysis of untransferred embryos. The accreditation working group ran a workshop on the Quality Management and Accreditation process in PGD clinics and laboratories in 2008 and will run this again in London in 2010. They are preparing a guide to PGD laboratory accreditation. Working towards accreditation is one of the most important issues being discussed by the PGD Consortium. This has been aided by our external quality assurance (EQA) schemes for FISH and PCR. The pilot for the FISH was run in 2008 and was an online scheme plus the submission of a retrospective case. The 2009 FISH EQA will involve the online workup and assessment of two PGD cases. The PCR EQA will involve sending PGD Centres DNA and single cells for analysis, and the pilot will be run in 2009. Good quality management will help centres become more efficient. A new working group on Guideline development and update has been formed. ESHRE has recently developed a set of Guidelines on writing Guidelines which will, of course, be followed to make guideline documents on PGD in the most appropriate way.

Finally, the paediatric follow-up of PGD babies has been launched and the first results are almost ready for analysis.

From the first nine data collections, the Consortium now has detailed data on 21 743 cycles and 3841 babies born after PGD/PGS.

The large amount of detailed information the Consortium has collected is unique, and studies are underway to analyse many aspects of the data in more depth.

Supplementary data

Supplementary data are available at http://humrep.oxfordjournals.org/.

Acknowledgements

The authors would like to thank Paul Scriven for his help in analysing the data on chromosomal abnormalities and for his careful review of the manuscript.

Many thanks also to all of the centres who participated in data collection IX. Argentina: Fecunditas; Australia: Melbourne IVF; Belgium: Department of Embryology and Genetics of the VUB and Centre for Medical Genetics of the Universitair Ziekenhuis Brussels; Hopital Erasme, ULB, Laboratoire FIV; Infertility Centre, Ghent University Hospital; Leuven Institute for Fertility and Embryology; GIFT, ZOL Ziekenhuis; Leuven University Fertility Centre; Brazil: Fertility-Assisted Reproductive Centre, Sao Paolo; Czech Republic: Sanatorium Repromeda; Institute Pronatal, Genetics; Denmark: Centre for Preimplantation Genetic Diagnosis, Aarhus University Hospital, Fertility clinic; Fertility Clinic, University Hospital Copenhagen; Fertility Clinic, University of Odense; Finland: Helsinki University Central Hospital, Department of Obstetrics and Gynaecology/IVF Unit; AVA-Clinic; France: SIHCUS-CMCO, Service de la Biologie de la Reproduction; Institut de biologie, Lab de Biochemie Génétique; Germany: University of Bonn, Department of Obstetrics and Gynaecology, Section of Reproductive Medicine; University Women's Hospital, Kiel; Centre for Gynecological Endocrinology, Reproductive Medicine and Human Genetics; University Clinic of Schleswig-Holstein; Campus Luebeck, Department of Obstetrics and Gynecology; IVF-SAAR; Fertility Center Hamburg; Kinderwunschcentrum München; Greece: University of Athens, St Sophia's Children's Hospital, Laboratory of Medical Genetics; EMBRYOGENESIS, Centre for subfertility studies; India: Krishna IVF Clinic; Israel: Tel-Aviv Sourasky Center; The Danek Gertner Institute of Human Genetic, Sheba Medical Centre; Zohar PGD lab, Medical Genetics Unit, Shaare Zedek Medical Centre; Italy: SISMER; Japan: Otani Women's clinic; Korea: Kwadong University College of Medicine, Cheil General Hospital, Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology and Infertility; Poland: INVICTA Fertility and Reproductive Centre; Portugal: Faculty of Medicine of Porto-Hospital S. Joao, Department of Medical Genetics; Singapore: Centre for Assisted Reproduction (CARE), Singapore General Hospital; Spain: Instituto Dexeus; Instituto Valenciano de Infertilidad; Institut Marquès, Servei de Diagnòstic Genètic Preimplantacional; Instituto de Reproduccion CEFER; Sistemas Genomicos SL Valencia; Centro de Medicina Embrionaria; U.R.H. Garcia del real; Sweden: Department of Clinical Genetics, Karolinska Hospital; Sahlgrenska University Hospital, Department of Obstetrics and Gynaecology; Taiwan: Lin-Kou Medical Centre, Chang Gung Memorial Hospital and Medical College, Department Of Obstetrics and Gynaecology; The Netherlands: PGD working group Maastricht, The Centre for Reproductive Medicine; Department of Obstetrics and Gynaecology, Subdepartment Infertility, and Department of Clinical Genetics; Center for Reproductive Medicine, Academic Medical Center, IVF Laboratory; IVF/Fertility Laboratory, L2VA, Academic Hospital Groningen; Turkey: American Hospital; Acibadem Genetic Diagnosis and Cell Therapy Centre, Acibadem Genel Mudurluk; UK: UCL Centre for PGD, Department of Cytogenetics and Centre for Preimplantation Genetic Diagnosis; Centre for PGD, Assisted Conception Unit, Guy's Hospital; USA: Jones Institute For Reproductive Medicine; Genetics and IVF Institute.

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