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Hum. Reprod. Advance Access originally published online on September 19, 2005
Human Reproduction 2006 21(1):3-21; doi:10.1093/humrep/dei292
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Published by Oxford University Press 2005 on behalf of the European Society of Human Reproduction and Embryology.

ESHRE PAGE

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, 2 Centre for Medical Genetics, University Hospital and Medical School of the Dutch-speaking Brussels Free University (Vrije Universiteit Brussel, VUB), Laarbeeklaan 101, 1090 Brussels, Belgium, 3 PGD working group Maastricht, Department of Clinical Genetics, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands, 4 Genetics and IVF Institute, 3020 Javier Road, Fairfax Virginia, 22031, USA, 5 Shady Grove Centre for Preimplantation Genetics, 15001 Shady Grove Road, Suite 400, Rockville, Maryland, 20850, USA, 6 Service de la Biologie de la Reproduction, SIHCUS-CMCO, 19, Rue Louis Pasteur, BP120, 67303 Schiltigheim, France, 7 Center for Reproductive Medicine, Academic Medical Center, Fertility Laboratory (A1-229), Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands 8 Department 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, 9 Laboratory of Medical Genetics, University of Athens, St Sophia’s Children’s Hospital, 11527 Athens, Greece, 10 Sanatorium Repromeda, Vinicni 235, 615 00 Brno, Czech Republic and 11 Melbourne IVF, 320 Victoria Parade, 3002 East Melbourne VIC, Australia

12 To whom correspondence should be addressed: joyce.harper{at}ucl.ac.uk


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 General remarks
 Appendix. Centres that...
 Acknowledgements
 References
 
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
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 General remarks
 Appendix. Centres that...
 Acknowledgements
 References
 
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, 1999Go), the second included cycles from September 1998 to May 2000 (ESHRE PGD Consortium Steering Committee, 2000Go), the third was from May 2000 to May 2001 (ESHRE PGD Consortium Steering Committee, 2002Go) and the fourth included data from May 2001 to December 2001 (Sermon et al., 2005Go). 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, 1999Go, 2000Go, 2002Go; Sermon et al., 2005Go). The second set is data collection V. The FileMaker Pro 6TM (FP6) database was used for the last two data-set collections.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 General remarks
 Appendix. Centres that...
 Acknowledgements
 References
 
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 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)Go.


    Results and discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 General remarks
 Appendix. Centres that...
 Acknowledgements
 References
 
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 Mendelian disorders remained the same. Duchenne muscular dystrophy, haemophilia A and fragile X syndrome were the most frequent referrals for X-linked disorders, CF/CBAVD, {beta}-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).


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Table I. Referrals according to indication

 

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Table II. Referrals for chromosomal disorders

 

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.


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Table III. Reasons for preimplantation genetic diagnosis (PGD)

 

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 IIV, 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.


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Table IVa. Overall cycle data collection I–IV

 

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Table Va. Preimplantation genetic diagnosis (PGD) for chromosomal abnormalities, data collection I–IV

 

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Table VIIa. Cycles performed for single gene disorders using PCR, data collection I–IV

 

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Table VIIIa. Cycles performed for preimplantation genetic screening, data collection I–IV

 

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Table IXa. Preimplantation genetic diagnosis (PGD) for social sexing, data collection I–IV

 


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Table IVb. Overall cycle data collection V

 


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Table Vb. PGD for chromosomal abnormalities, data collection V

 


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Table Vc. Chromosomal abnormalities analysed, data V (for web-based version only)

 


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Table VIa. Sexing only for X-linked disease using PCR or FISH, data collection I–IV

 


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Table VIb. List of indications for which sexing was performed, data collection I–IV

 


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Table VIc. Sexing only for X-linked disease using PCR or FISH, data collection V

 


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Table VId. List of indications for which sexing has been performed, data collection V

 


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Table VIIb. List of indications for monogenic diseases listed as other in Table VIIa, data collection I–IV

 


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Table VIIc. Cycles performed for single gene disorders using PCR, data collection V

 


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Table VIId. List of indications for monogenic diseases listed as other in Table VIIc

 


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Table VIIIb. Cycles performed for preimplantation genetic screening, data collection V

 


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Table IXb. Preimplantation genetic diagnosis (PGD) for social sexing, data collection V

 
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 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.

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 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., 2005Go). In this data collection, acid Tyrode’s was used for zona drilling more than the 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 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), {beta}-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., 2005Go). 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 {beta}-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.

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 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 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 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 these different reports that the pregnancies obtained after PGD are quite comparable to those obtained after ICSI (Bonduelle et al., 2005Go), 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).


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Table Xa. Evolution of pregnancy, data collection I–IV

 

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Table XIa. Complications in clinical pregnancies (total n = 92 patients), data collection I–IV

 

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Table XIIa. Method of delivery and gestational age, data collection I–IV

 

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Table XIIIa. Data on live-born children, data collection I–IV

 

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Table XIVa. Congenital malformations and neonatal complications at birth, data collection I–IV

 


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Table Xb. Evolution of pregnancy, data collection V

 


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Table XIb. Complications in clinical pregnancies (total n = 61 patients), data collection V

 


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Table XIIb. Method of delivery and gestational age, data collection V

 


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Table XIIIb. Data on live-born children, data collection V

 


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Table XIVb. Congenital malformation and neonatal complications at birth, data collection V

 
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.


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Table XVa. Confirmation of diagnosis per fetal sac, data collection I–IV

 


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Table XVb. Confirmation of diagnosis per fetal sac, data collection V

 
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 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 follow-up, 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 XIIbXIVb).

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, 1991Go). 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 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 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
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 General remarks
 Appendix. Centres that...
 Acknowledgements
 References
 
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.

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 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., 2005Go). 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.


    Appendix. Centres that contributed data to collection V
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 General remarks
 Appendix. Centres that...
 Acknowledgements
 References
 
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 Porto-Hospital 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).


    Acknowledgements
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 General remarks
 Appendix. Centres that...
 Acknowledgements
 References
 
We would like to thank ESHRE for its continuing support of this work and to all participating centres.


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 General remarks
 Appendix. Centres that...
 Acknowledgements
 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.[Abstract/Free Full Text]

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.[Abstract/Free Full Text]

ESHRE PGD Consortium Steering Committee (2000) ESHRE Preimplantation Genetic Diagnosis (PGD) Consortium: data collection II (May 2000). Hum Reprod 15,2673–2683.[Abstract/Free Full Text]

ESHRE PGD Consortium Steering Committee (2002) ESHRE Preimplantation Genetic Diagnosis (PGD) Consortium: data collection III (May 2001). Hum Reprod 17,233–246.[Abstract/Free Full Text]

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.[Abstract/Free Full Text]

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.[Abstract/Free Full Text]

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.[Web of Science][Medline]

Submitted on August 1, 2005; accepted on August 8, 2005.


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