Clinical re-biopsy of segmental gains-the primary source of preimplantation genetic testing false positives

Purpose Does re-biopsy of blastocysts classified as abnormal (ABN) due to segmental aneuploidy (SA) have clinical utility? Methods The live birth (LB) outcomes of mosaic SAs, compared to other categories, were determined after transfer of 3084 PGT-A tested blastocysts. An initial 12-month trial thawed 111 blastocysts classified as ABN due to a SA for clinical re-biopsy, with an additional 58 from a subsequent 16-month revised protocol. Where re-biopsy failed to corroborate the original classification, blastocysts were reported as mosaic and suitable for clinical use. Results Segmental mosaics had a LB rate (54.1%) which was indistinguishable from that of euploid (53.7%). Numeric mosaics had statistically significant (P < 0.05) reduced LB rates compared to euploid, with high-level numerics (19.2%) also exhibiting a significant reduction compared to low level (42.3%). Of the initial 111 blastocysts with SAs, 85 could be re-biopsied. Segmental gains became suitable for re-biopsy at a high rate (90.9%), with 84.2% (16/19) of these reclassified as mosaic. Only 73.0% of deletions and complex changes were suitable for re-biopsy, of which 73.0% (46/63) were confirmed ABN. The subsequent 16-month period primarily focused on gains, confirming the high rate at which they can be reclassified as clinically useable. Conclusions Blastocysts harboring mosaic segmental duplications, rather than SAs in general, are the primary source of false-positive PGT-A results and represent a category with a LB rate similar to that of euploid. A high degree of confidence in the reliability of PGT-A results can be maintained by performing confirmatory clinical TE biopsies.

Automated summary

The study found that blastocysts with mosaic segmental duplications, rather than segmental aneuploidy as a whole, are the main cause of false-positive PGT-A results, and they have a similar live birth rate to euploid blastocysts. Performing confirmatory clinical TE biopsies can increase confidence in the reliability of PGT-A results.