The role of prenatal diagnosis following preimplantation genetic testing for single‐gene conditions: A historical overview of evolving technologies and clinical practice

Abstract

Preimplantation genetic testing for monogenic conditions (PGT-M) has become a valued reproductive option for couples at risk of having a child with a single gene condition. In line with developments in molecular genetics, there has been an overall trend toward laboratory techniques with higher accuracy in comparison to earlier PGT-M techniques. The recommendation for confirmatory prenatal diagnostic testing has remained a standard component of PGT-M counseling, reflecting the inherent difficulties of testing the limited number of cells obtained from embryo biopsy, as well as recognition of the biological and human factors that may lead to misdiagnosis in a PGT-M cycle. Reported misdiagnosis rates are less than 1 in 200 pregnancies following PGT-M, although updated data regarding newer methods of PGT-M are required. There is limited evidence available regarding clinician and patient behavior in pregnancies resulting from PGT-M cycles. It remains essential that clinicians involved in the care of patients undergoing PGT-M provide appropriate counseling regarding the risks of misdiagnosis and the importance of confirmatory prenatal diagnosis. The nature of PGT-M test design lends itself to cell-free DNA-based noninvasive prenatal testing for monogenic conditions (NIPT-M), which is likely to become a popular method in the near future.

Preimplantation genetic testing and prenatal diagnosis in a family with pseudovaginal perineoscrotal hypospadias: A case report

“…[4,5] PGT-M prevents pregnancy termination and associated trauma by identifying affected embryos preimplantation. [5,11] With improving technology, PGT-M prevents genetic disease transmission and birth of affected children. [6]…”

Designing highly multiplex PCR primer sets with Simulated Annealing Design using Dimer Likelihood Estimation (SADDLE)

“…For example, in oncology tissue biopsies obtained through fine needle aspirates and core biopsies are frequently insufficient for standard NGS analysis, and cell-free DNA from peripheral blood plasma likewise are limited and impose sensitivity limitations to ligation-based approaches 32 . Furthermore, in reproductive medicine, samples from amniocentesis and preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD) are also very limited, and require rapid turnaround for molecular diagnostics due to the time-sensitivity of clinical decisions 33 .…”

Clinical outcomes of preimplantation genetic testing for hereditary cancer syndromes: A systematic review

“…Confirmatory prenatal diagnosis (PND) is a recommended component of PGT‐M and can provide evidence of false‐negatives or misdiagnoses 44,45 . A misdiagnosis may be technical (contamination of sample, failed amplification of DNA), biological (mosaicism, undetected crossover events), or human (sample mix‐up) in error 46 . In our review, only nine of the 18 studies included in the quantitative analysis discussed false‐negatives, but only four provided additional explanation regarding the way it was assessed (prenatal 22,33 vs. postnatal 17,19 testing).…”