The ESHRE PGD Consortium: 10 years of data collection

Harper, Joyce; Wilton, Leeanda; Traeger-Synodinos, Joanne; Goossens, V.; Moutou, Céline; SenGupta, Sioban; Budak, T. Pehlivan; Renwick, Pamela; Rycke, Martine De; Geraedts, J. P. M.; Harton, G.

doi:10.1093/humupd/dmr052

Cited by 266 publications

(226 citation statements)

References 45 publications

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“…Although PGD can be used for almost all genetic disorders with a recognized mutation, allele dropout (ADO), where one of the two alleles is preferentially amplified and the other allele is amplified under a detectable level, is the primary inherent pitfall of single-cell PCR and can lead to misdiagnoses [17,18]. For autosomal dominant disorders, ADO of the affected allele would cause a serious misdiagnosis for the transfer of an affected embryo.…”

Section: Discussionmentioning

confidence: 99%

“…Although PGD has been applied successfully in the clinic, misdiagnoses discovered by prenatal diagnosis have been reported [2,18]. The European Society of Human Reproduction and Embryology (ESHRE) PGD consortium reported that the misdiagnosis rates of the PCR-based and FISH-based PGD cycles were 0.14 % (13/9317) and 0.06 % (21/34,855), respectively [2].…”

Section: Discussionmentioning

confidence: 99%

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The clinical application of preimplantation genetic diagnosis for the patient affected by congenital contractural arachnodactyly and spinal and bulbar muscular atrophy

Chen

Diao

et al. 2016

J Assist Reprod Genet

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Purpose To investigate the usefulness of preimplantation genetic diagnosis (PGD) for the patient affected by congenital contractural arachnodactyly (CCA) and spinal and bulbar muscular atrophy (SBMA). Methods Multiple displacement amplification (MDA) was performed for whole genome amplification (WGA) of biopsied trophectoderm (TE) cells. Direct mutation detection by sequencing and next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping were used for CCA diagnosis. Direct sequencing of the PCR products and sex determination by amplification of sexdetermining region Y (SRY) gene were used for SBMA diagnosis. After PGD, the unaffected blastocyst (B4) was transferred in the following frozen embryo transfer (FET). Results In this PGD cycle, sixteen MII oocytes were inseminated by ICSI with testicular spermatozoa. Four blastocysts (B4, B5, B10, B13) were utilized for TE cell biopsy on day 5 after ICSI. After PGD, B4 was unaffected by CCA and SBMA. B5 was affected by CCA and carried SBMA. B10 was unaffected by CCA and carried SBMA. B13 was affected by CCA and unaffected by SBMA. B4 was the only unaffected blastocyst and transferred into the uterus for the subsequent FET cycle. The accuracy of PGD was confirmed by amniocentesis at 21 weeks of gestation. A healthy boy weighing 2850 g was born by cesarean section at the 38th week of gestation. Conclusions PGD is a valid screening tool for patienst affected of CCA and SBMA to prevent transmission of these genetic diseases from parents to children.Keywords Congenital contractural arachnodactyly . Spinal and bulbar muscular atrophy . PGD . Frozen embryo transfer Capsule A description of a PGD cycle for the diagnosis of CCA and SBMA, resulting in the birth of a healthy boy.Linjun Chen and Zhenyu Diao contributed equally to this work.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The clinical application of preimplantation genetic diagnosis for the patient affected by congenital contractural arachnodactyly and spinal and bulbar muscular atrophy

Chen

Diao

et al. 2016

J Assist Reprod Genet

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“…PGS at day 3 of development counting 5 to 9 chromosomes with fluorescent in situ hybridization (FISH) in one biopsied cell knew a high flight in the nineties of last century, and the early years of this century [6] and was at some point more frequently performed than PGD. The practice of PGS was mainly supported by non-randomized studies with poor experimental design and inadequate control groups [7], and by 2010, 11 randomized controlled trials (RCTs) had been published that demonstrated that PGS did not increase, and in some cases even decreased, pregnancy rates [6]. With hindsight, that first version of PGS may not have worked because only a handful of chromosomes were counted, while all chromosomes seem to be affected in preimplantation embryos [8].…”

Section: Introductionmentioning

confidence: 99%

Preimplantation Genetic Screening

Sermon¹

2017

obm genet

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The main aim of PGS has always been to improve IVF outcome, especially in patient groups assumed to have higher rates of chromosomally abnormal embryos, such as patients of advanced maternal age. In that sense, PGS is quite different from other types of screening as discussed in other papers in this issue. Today it bears no doubt that blastocysts found to be uniformly aneuploid in a biopsy will fail to implant, or worse, will implant and lead to a pregnancy and birth carrying a major chromosomal abnormality, such as trisomy 21. However, it has been argued that a cohort of embryos cannot be improved, and that PGS is only a selection method for which efficiency has not been proven. PGS would never increase the live birth rate for that given cohort, even with a 100% efficiency rate of embryo cryopreservation. The current debate on whether PGS should be applied and to which patients it should be offered has shifted from the effect on live birth rates towards other outcomes such as the reduction of transfers and of miscarriages. Taking the undeniable higher cost of IVF into account when PGS is included, what is the benefit to the patient? The views on this question differ on whether PGS is an additional source of income for the IVF clinic and may or may not balance the extra cost for cryopreservation and embryo transfer for the patients, or whether society pays for IVF treatments and may decide not to want to invest in a medical act that does not improve the primary goal of IVF, i.e. having a healthy child. PGS is also often presented as diminishing patient anxiety and stress through decreasing unnecessary embryos transfers and miscarriages, although no data on this

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“…1,2 According to 10 years of data collection by the ESHRE PGD Consortium, PGD has been applied to over 190 different monogenic disorders. 3 Currently all methods for PGD to exclude monogenic diseases are based on the polymerase chain reaction (PCR), with or without prior whole-genome amplification. Genetic analysis may be performed at various stages post fertilization, including the oocyte/zygote biopsied on the first day postinsemination (polar body analysis), on 1-2 blastomeres from cleavage-stage embryos biopsied on the third day post-insemination (blastomere biopsy) or on 5-10 trophectoderm cells biopsied from blastocysts on the fifth day post-insemination (blastocyst biopsy).…”

Section: Introductionmentioning

confidence: 99%

“…During 10 years of data collection recording the outcome of over 4700 cycles for monogenic PGD, 12 adverse misdiagnoses were reported. 3,4 However, this is probably an underestimation, as many embryo transfers have no follow up (no pregnancy or birth). Furthermore, based on a survey done amongst ESHRE PGD consortium members in 2008 (unpublished results), only a minority of centres perform reanalysis of untransferred supernumerary embryos.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of PCR-based preimplantation genetic diagnosis applied to monogenic diseases: a collaborative ESHRE PGD consortium study

et al. 2013

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Preimplantation genetic diagnosis (PGD) for monogenic disorders currently involves polymerase chain reaction (PCR)-based methods, which must be robust, sensitive and highly accurate, precluding misdiagnosis. Twelve adverse misdiagnoses reported to the ESHRE PGD-Consortium are likely an underestimate. This retrospective study, involving six PGD centres, assessed the validity of PCR-based PGD through reanalysis of untransferred embryos from monogenic-PGD cycles. Data were collected on the genotype concordance at PGD and follow-up from 940 untransferred embryos, including details on the parameters of PGD cycles: category of monogenic disease, embryo morphology, embryo biopsy and genotype assay strategy. To determine the validity of PCR-based PGD, the sensitivity (Se), specificity (Sp) and diagnostic accuracy were calculated. Stratified analyses were also conducted to assess the influence of the parameters above on the validity of PCR-based PGD. The analysis of overall data showed that 93.7% of embryos had been correctly classified at the time of PGD, with Se of 99.2% and Sp of 80.9%. The stratified analyses found that diagnostic accuracy is statistically significantly higher when PGD is performed on two cells versus one cell (P ¼ 0.001). Se was significantly higher when multiplex protocols versus singleplex protocols were applied (P ¼ 0.005), as well as for PGD applied on cells from good compared with poor morphology embryos (P ¼ 0.032). Morphology, however, did not affect diagnostic accuracy. Multiplex PCR-based methods on one cell, are as robust as those on two cells regarding false negative rate, which is the most important criteria for clinical PGD applications. Overall, this study demonstrates the validity, robustness and high diagnostic value of PCR-based PGD.

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The ESHRE PGD Consortium: 10 years of data collection

Cited by 266 publications

References 45 publications

The clinical application of preimplantation genetic diagnosis for the patient affected by congenital contractural arachnodactyly and spinal and bulbar muscular atrophy

The clinical application of preimplantation genetic diagnosis for the patient affected by congenital contractural arachnodactyly and spinal and bulbar muscular atrophy

Preimplantation Genetic Screening

Evaluation of PCR-based preimplantation genetic diagnosis applied to monogenic diseases: a collaborative ESHRE PGD consortium study

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