Mette Wulf Christensen

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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Jos Dreesen, Departments of Clinical Genetics and School for Oncology and Developmental Biology, GROW, Maastricht University Medical Centre, Maastricht, The Netherlands.
  • ,
  • Aspasia Destouni
  • ,
  • Georgia Kourlaba
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  • Birte Degn
  • ,
  • Mette Wulf Christensen
  • Filipa Carvalho
  • ,
  • Celine Moutou
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  • Sioban Sengupta
  • ,
  • Seema Dhanjal
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  • Pamela Renwick
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  • Steven Davies
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  • Emmanouel Kanavakis
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  • Gary Harton
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  • Joanne Traeger-Synodinos
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=0.001). Se was significantly higher when multiplex protocols versus singleplex protocols were applied (P=0.005), as well as for PGD applied on cells from good compared with poor morphology embryos (P=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.European Journal of Human Genetics advance online publication, 4 December 2013; doi:10.1038/ejhg.2013.277.
OriginalsprogEngelsk
TidsskriftEuropean Journal of Human Genetics
ISSN1018-4813
DOI
StatusUdgivet - 4 dec. 2013

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