O-051 Refreezing and rebiopsy – are these worth it?

Abstract

Abstract Preimplantation genetic testing of embryos offers the opportunity to avoid the transmission of hereditary disorders to the offspring by selecting out embryos affected by a single gene mutation or mutations (PGT-M), structural rearrangements of chromosomes (PGT-SR), aneuploidy (PGT-A) as well as polygenic risk (PGT-P). Over the last two decades, laboratory techniques have seen tremendous developments including extended embryo culture to blastocyst stage, trophectoderm biopsy and vitrification. The latter technique is highly efficient and allows multiple freezing and warming cycles when performed in proficient laboratories. At the same time whole genome analysis techniques provide the opportunity to analyse embryonic DNA in great detail for multiple indications simultaneously. The PGT process is sensitive to both biological and technical issues which sometimes lead to a failed PGT result. Failure of PGT diagnosis is reported to occur in between 2-12% of PGT cycles depending on the methodology used. The main causes of inconclusive diagnosis are DNA amplification failure and non-concurrent results. Independent variables that influence inconclusive results are day of embryo biopsy, number of cells taken at biopsy and the quality of the IVF laboratory. In order to seize every opportunity in reaching a diagnosis and optimize reproductive outcome for the patient, rebiopsy and retesting (double biopsy and double cryopreservation) can be performed. In situations where embryos need to be biopsied for PGT for reasons of newly found genetic indications or the clinical need for PGT-A, and after an initial cryopreservation, single biopsy and double cryopreservation may be performed with potential effect on subsequent reproductive outcome. A limited number of studies have addressed both the feasibility as well as the success rate of rebiopsy and refreezing. Most studies conclude that the technique is efficient in terms of diagnostic efficiency and reproductive outcome, when performed in expert laboratories. A few studies have addressed the health of the children after multiple biopsy and multiple freezing and have not shown increased risks. Larger studies are needed to establish the true clinical and health-economic value of rebiopsy and refreezing. The speaker will give an overview of existing evidence in literature and assess whether it is safe and worthwile to go the extra mile and consider refreezing and rebiopsy for PGT. Trial registration number XXXX