P-589 Transfer outcomes of embryos with uniform whole chromosome and segmental aneuploidies diagnosed by NGS-based PGT-A: multicenter data from the International Registry of Mosaic Embryo Transfers(IRMET)

Abstract Study question What is the reproductive potential of uniformly aneuploid embryos with whole chromosome aneuploidy (WCA) and segmental chromosome aneuploidy (SCA) diagnosed by NGS based PGT-A? Summary answer Aneuploid WCA-embryos have limited developmental potential resulting in either no-implantation or miscarriage while SCA-embryos can result in euploid live-births in ∼20%. What is known already In humans, only a handful of WCA, such as trisomy(T) 21(Down syndrome), T18(Edwards syndrome), T13(Patau syndrome), and sex-chromosomal aneuploidies are viable, while the majority are incompatible with embryo and fetal development, leading to non-implantation or early miscarriage. Successful transfer of competent embryos is crucial for the success of IVF-treatment. Presently, PGT-A utilizing next-generation-sequencing(NGS) enables the selection and prioritization of euploid and mosaic embryos for personalized assisted reproductive technology (ART) treatments. Despite substantial evidence supporting the benefits of transferring euploid/mosaic embryos, there is limited data on the reproductive potential of embryos diagnosed as abnormal with WCA or SCA after NGS-based-PGT-A. Study design, size, duration This is a multicenter retrospective study of prospectively collected data, from 2016-2024 by IRMET on the transfer and pregnancy outcomes of 154 embryos diagnosed as aneuploid with WCA (n = 114) and SA (n = 41) by NGS-PGT-A. All embryos underwent PGT-A NGS testing on the Illumina platform with 20-80% thresholds for mosaicism. Primary outcomes were implantation rate (IR), miscarriage (MR) and live birth rate (LBR) after abnormal WCA and SA embryo transfer (ET). All patients received genetic counselling. Participants/materials, setting, methods Data on embryo-genetics,transfer/pregnancy outcomes, prenatal-follow-up testing and patient demographics were analyzed. 76%-WCA and 36%-SCA transfers were done without prior knowledge of embryo PGT-A-results, either because patients declined to know the PGT-A-results at the time of transfer or did fresh-transfer after embryo biopsy. Clinical outcomes were analyzed based on type of aneuploidy WCA and SA, (trisomy/monosomy/complex or segmental gain/loss/complex) and patient characteristics. Descriptive statistics and a two-tailed chi-square test were used to analyze the outcome measures. Main results and the role of chance In total, 154 aneuploid embryos were transferred to 101 patients (mean av age 40±4.3y) Of the 113 WCA abnormal embryos, 57 were single ET and the rest were as follows: 17-double ET, 3-triple ET, 2-quadriple ET and 1-quintal ET. Of the 41 SCA transferred, 31 were single-ET, and 5-double-ET. The implantation rate of WCA embryos was 22.8% (26/113) and for SCA embryos 48.8% (20/41). Of the implanted WCA embryos 8.8% (10/113) ended as biochemical pregnancy, 14.2% (16/113) had miscarriage. All WCA embryos that resulted in miscarriage 100% (n = 16) had trisomy (T21-1, T-20-1, T18-1, T16-2, T15-1, T14-1, T12-1, T11-1, T10-1, T9-1, TX-1, 2 with complex aneuploidy (3+ chromosomes) and one triploidy (69, XXX), while 60% (6/10) resulting in biochemical pregnancy had monosomic(M) chromosomes (M21-1, M15-1 and M11+M21), 30% had 2 aberrant chromosomes (M11+T22; T11T21; and T2+T16). and one had T17. Of the 20 SCA embryos that implanted 17% (7/41) resulted in biochemical pregnancy, 9.7% (4/41) resulted in miscarriage (3 first trimester and 1 second trimester) and 21.9% (9/41) resulted in healthy live birth. Two of the live births have normal amniocentesis-prenatal genetic testing and 2 have normal NIPT screening. Genetic testing was not performed, the rest delivered apparently healthy babies Limitations, reasons for caution The study’s retrospective design, despite prospective data entry, and the variability across IVF centers may limit generalizability. Potential errors in IVF and genetic testing labs, along with the possibility of natural conception, cannot be excluded. Ethical considerations and access to genetic counseling are essential prerequisites. Wider implications of the findings Our investigation offers further evidence that WCA embryos have limited potential for development. The use of PGT-A to exclude WCA-embryos can enhance the outcomes of ART by avoiding miscarriages, pregnancy terminations, and unsuccessful transfers. 20% of SCA embryos may result in live birth aiding in informed ET decision making. Trial registration number No

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