4.7 Article

We have reached a dead end for preimplantation genetic testing for aneuploidy

Journal

HUMAN REPRODUCTION
Volume 37, Issue 12, Pages 2730-2734

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/humrep/deac052

Keywords

assisted reproductive technique; human embryos; in vitro fertilization; mosaicism; preimplantation genetic testing for aneuploidy

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The hypothesis of preimplantation genetic testing for aneuploidy (PGT-A) was proposed 20 years ago, but recent studies have shown that its application does not have significant advantages and may even result in adverse outcomes when patient selection biases are reversed. Additionally, high embryo mosaicism leads to the unnecessary discarding of normal embryos, causing harm to patients. Therefore, it is recommended to restrict PGT-A to research protocols and to encourage professional societies to issue appropriate practice guidelines.
The hypothesis of preimplantation genetic testing for aneuploidy (PGT-A) was first proposed 20 years ago, suggesting that during IVF elimination of aneuploid embryos prior to transfer will improve implantation rates of remaining embryos and, therefore, increase pregnancy and live birth rates, while also reducing miscarriages. Subsequently, unvalidated and increasingly unrestricted clinical utilization of PGT-A called for at least one properly randomized controlled trial (RCT) to assess cumulative live birth rates following a single oocyte retrieval, utilizing all fresh and frozen embryos of an IVF cycle. Only recently two such RCTs were published, however both, when properly analysed, not only failed to demonstrate significant advantages from utilization of PGT-A, but actually demonstrated outcome deficits in comparison to non-use of PGT-A, when patient selection biases in favour of PGT-A were reversed. Moreover, because of high embryo mosaicism at the blastocyst stage and, therefore, high false-positive rates from trophectoderm biopsies, large numbers of chromosomal-normal embryos with normal pregnancy potential are unnecessarily left unused or discarded, indisputably causing harm to affected couples. We, therefore, strongly call for restricting PGT-A to only research protocols and, as of this point in time, encourage professional societies in the field to follow suit with appropriate practice guidelines.

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