The experience of 3 years of external quality assessment of preimplantation genetic diagnosis for cystic fibrosis

Abstract

Preimplantation genetic diagnosis (PGD) was first performed over 20 years ago and has become an accepted part of genetic testing and assisted reproduction worldwide. The techniques and protocols necessary to carry out genetic testing at the single-cell level can be difficult to master and have been developed independently by the laboratories worldwide offering preimplantation testing. These factors indicated the need for an external quality assessment (EQA) scheme for monogenic disease PGD. Toward this end, the European Society for Human Reproduction and Embryology came together with United Kingdom National External Quality Assessment Services for Molecular Genetics, to create a pilot EQA scheme followed by practical EQA schemes for all interested parties. Here, we detail the development of the pilot scheme as well as development and findings from the practical (clinical) schemes that have followed. Results were generally acceptable and there was marked improvement in results and laboratory scores for those labs that participated in multiple schemes. Data from the first three schemes indicate that the EQA scheme is working as planned and has helped laboratories improve their techniques and result reporting. The EQA scheme for monogenic PGD will continue to be developed to offer assessment for other monogenic disorders.

Figure 1

Example of a CF PGD EQA Case. EQA Clinical Case: Phillipe Morris and Katherine Morris requested PGD for CF. Their son, Simon Morris [deceased], was affected with CF and was a compound heterozygote for the c.1521_1523delCTT; p.Phe508del (deltaF508) mutation and the c.3717+10kbC>T (3849+10kbC>T) mutation. Phillipe was a carrier of the c.1521_1523delCTT; p.Phe508del (deltaF508) mutation and Katherine carried the c.3717+10kbC>T (3849+10kbC>T) mutation. Mutation nomenclature is given using NM_000492.3 with numbering starting at the A of the ATG initiation codon according to HGVS guidelines (www.hgvs.org). Traditional nomenclature is given in parentheses. All EQA names are fictional and any resemblance to any known individual is purely coincidental.