Multiple embryo manipulations in PGT-A cycles may result in inferior clinical outcomes

Research question: Do embryos that undergo a thaw, biopsy and re-vitrification (TBR) for pre-implantation genetic testing for aneuploidy (PGT-A) have different ploidy and transfer outcomes compared with fresh biopsied embryos? Design: Retrospective cohort study of all embryos that underwent the following procedures: fresh biopsy for PGT-A (fresh biopsy); embryos that were warmed, biopsied for PGT-A and re-vitrified (single biopsy TBR); embryos with a no signal result after initial biopsy that were subsequently warmed, biopsied and re-vitrified (double biopsy TBR). The patients who underwent transfers of those embryos at a single academic institution between March 2013 and December 2021 were also studied. Results: About 30% of embryos planned for TBR underwent attrition. Euploidy rates were similar after biopsy: fresh biopsy (42.7%); single biopsy TBR (47.5%) (adjusted RR: 0.99, 0.88 to 1.12); and double biopsy TBR 50.3% (adjusted RR: 0.99, 0.80 to 1.21). Ongoing pregnancy over 8 weeks was not statistically significant (double biopsy TBR: 6/19 [31.6%] versus fresh biopsy: 650/ 1062 [61.2%]) (adjusted RR 0.52, 95% CI 0.26 to 1.03). The miscarriage rate increased (double biopsy TBR: 4/19 [21.1%] versus fresh biopsy: 66/1062 [6.2%])(RR 3.39, 95% CI 1.38 to 8.31). Live birth rate was also lower per transfer for the double biopsy TBR group (double biopsy TBR [18.75%] versus fresh biopsy [53.75%]) (RR 0.35, 95% CI 0.12 to 0.98), though not after adjustment (adjusted RR 0.37, 95% CI 0.13 to 1.09). These differences were not seen when single biopsy TBR embryos were transferred. Conclusions: Embryos that undergo TBR have an equivalent euploidy rate to fresh biopsied embryos. Despite that, double biopsy TBR embryos may have impaired transfer outcomes.