Elucidating the PGT-A paradox: marginalising the detriment relegates the benefit.

Abstract

The hypothetical analysis presented offers insight into the effect of maternal age and protocol on the cost-effectiveness of PGT-A to reduce the risk of clinical miscarriage without materially jeopardising the chance of a first live birth when attempting to transfer every suitable embryo one at a time. Reflecting current practices, the diagnostic accuracy of PGT-A is sensitive to the prevalence of embryos with chromosome aneuploidy which increases with advancing maternal age, and the power of the test to discern a non-viable embryo is higher for older women and sensitive to protocol. PGT-A is effective to mitigate (reduce not eliminate) the risk of clinical miscarriage; however, excluding embryos with intermediate copy number results from transfer is detrimental to accomplishing a first live birth from a full cycle. Paradoxically, the number of blastocysts needed to marginalise the detriment is achieved only for some younger women (≤ 40years) who are less likely to benefit by avoiding pregnancy loss; this also makes PGT-A an expensive adjuvant. The paradox can be avoided by excluding from transfer only embryos with a 'uniform' aneuploid test result, which mitigates the risk of miscarriage for all women with the potential to be cost-effective for those > 40years.