Record to update:
Adverse Occurrence type:
MPHO Type:
Estimates Frequency:
In 2010, 62 centres reported data for 5,780 cycles with oocyte retrieval; 1,071 oocyte retrievals were reported for chromosomal abnormalities, 108 for sexing for X-linked diseases, 1,574 for monogenic diseases, 2,979 for preimplantation genetic screening (PGS), 48 for social sexing. If we exclude cycles for social sexing, 2,914 of 5,732 were infertile couples. 851 couples of 2,914 underwent preimplantation genetic diagnoses (PGD), 2,063 preimplantation genetic screening (PGS). Only 3,994 cycles were completed with embryo transfer, and clinical pregnancies were 1,269 (22 % for oocyte retrievals, 32 % for embryo transfers). Deliveries were 997 (17% for oocytes retrievals, 25% for embryo transfers), miscarriages were 153 (13% of clinical pregnancies). Three misdiagnosis were reported in the data collection XIII. Thirty-one misdiagnosis were reported in the data collection I-XII. Including all cycles up to data XIII, misdiagnosis has been reported for only 13/9,317 PCR-based cycles (0,14%) and 21/34 855 FISH-based PGD cycles (0,06%).
Time to detection:
At time of prenatal testing or at birth
Alerting signals, symptoms, evidence of occurrence :
Three misdiagnosis were reported in the data collection XIII: in one case the cause was the transfer of the wrong embryo; the other two cases were two trisomies 21after PGS, one case was related to a lack of results from the second polar body, in the second misdiagnosis case, the single cell shown to be euploid after FISH, but may have been derived from a chromosomally mosaic euploid/aneuploid embryo. Moreover, two misdiagnosis were reported in HFEA of 2013: in one case a baby was born with a genetic condition following the transfer of a frozen PGD embryo, because of the type of testing that was used at the time the embryo was created; in the second case a misdiagnosis analysis led to a transfer of affected embryo. In this particular case, the investigation noted that the circumstances made diagnosis technically difficult. In HFEA reports of 2014, one misdiagnosis case was reported about a pregnancy affected by an unbalanced chromosome translocation afted PGD for a chromosomal translocation. This incident arose as a result of a recognised but rare failure of the testing technology.
Imputability grade:
3 Definite/Certain/Proven
Groups audience:
Suggest new keywords:
misdiagnosis
preimplantation genetic diagnosis
PGD
preimplantation genetic screening
PGS
FISH (fluorescence in situ hybridization)
Adverse occurrence description:
Misdiagnosis, Preimplantation Genetic Diagnosis (PGD)
Suggest references:
[4463] De Rycke, M.; Belva, F.; Goossens, V.; Moutou, C.; SenGupta, S.B.; Traeger-Synodinos, J.; Coonen, E.
ESHRE PGD Consortium data collection XIII: cycles from January to December 2010 with pregnancy follow-up to October 2011. Human reproduction (Oxford, England)//Hum Reprod 2015; 30 (8) :1763 - 89
HFEA Adverse incidents in fertility clinics lessons to learn 2013
HFEA Adverse incidents in fertility clinics lessons to learn 2014
Expert comments for publication:
Since 1999, the PGD Consortium has collected, analysed and published 12 data sets and an overview of the first 10 years of data collections. The 13th retrospective collection represents valuable data on PGD/PGS cycles, pregnancies and children: the main trend observed is the decrease in the routine implementation of PGS. In preceding years, the number of PGS cycles had increased annually but by 2010, a number of RCTs had clearly demonstrated that routine PGS using FISH at cleavage stage was not beneficial and a consensus was published by the ESHRE PGD Consortium stating that future studies with alternative biopsy timing and genetic testing were necessary to evaluate the clinical benefit of PGS. The causes of misdiagnosis include confusion of embryo and cell number, transfer of the wrong embryo, maternal or paternal contamination, allele dropout, use of incorrect and inappropriate probes or primers, probe or primer failure and chromosomal mosaicism. Unprotected sex has been mentioned as a cause of adverse outcome not related to technical and human errors. As many embryo transfers have no follow-up (no pregnancy or birth), and only a minority of centres perform audit through re-analysis of untransferred supernumerary embryos, the numbers reported in the data collections may not reflect the true misdiagnosis in PGD.