Clinical validity of Midway PGT-A: a comparative study with traditional PGT-A and analysis of fertilization strategies.

Graphical abstractAbstractInfertile patients initially undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with fresh embryo transfer often lack baseline indications for preimplantation genetic testing for aneuploidy (PGT-A); however, after multiple failed transfers, they may become eligible for PGT-A, which can be performed on residual vitrified-thawed embryos (a strategy termed 'Midway PGT-A'), whose clinical value remains unconfirmed. This study aimed to assess the clinical utility of Midway PGT-A and whether fertilization methods (IVF vs ICSI) affect its chromosomal testing results and clinical outcomes. A 2020-2023 retrospective cohort study analyzed 463 PGT-A cycles, comprising 202 Midway PGT-A cycles (132 IVF and 70 ICSI subcycles) and 261 traditional PGT-A cycles, with comparisons made regarding blastocyst aneuploidy profiles and clinical pregnancy outcomes. The results showed that compared with traditional PGT-A, Midway PGT-A was associated with fewer biopsied blastocysts (P < 0.05), a higher rate of numerical chromosomal abnormalities (P < 0.05), and a lower rate of structural chromosomal abnormalities (P < 0.05). In the Midway PGT-A group, IVF and ICSI subcycles had similar euploidy and aneuploidy rates, but the IVF subcycle exhibited a significantly higher clinical pregnancy rate (P < 0.05) and implantation rate (P < 0.05). Multivariable logistic regression confirmed that ICSI was independently associated with a lower clinical pregnancy rate compared with IVF. In summary, Midway PGT-A delivers equivalent outcomes compared with traditional PGT-A. IVF does not alter the chromosomal detection results of Midway PGT-A and may further optimize clinical reproductive performance, validating the clinical value of Midway PGT-A for patients with post-transfer PGT-A eligibility.Lay summaryMany people undergoing fertility treatments do not need embryo genetic testing initially. However, after repeated failed pregnancies, miscarriages, or having a baby with birth defects, they may need this test later. We tested the genetic health of their leftover frozen embryos - a strategy we call 'Midway testing'. Our study of 463 cycles found that Midway testing worked as well as standard testing done earlier. The number of embryos tested was lower for Midway testing, but it found more whole-chromosome issues and fewer chromosome structure issues. Fertilization methods did not change test results, but one method led to higher pregnancy and implantation rates. This testing offers a valuable option for people who need genetic embryo checks after failed fertility cycles, helping them use existing frozen embryos effectively.