P-567 Cycle outcomes using Haploseek combining PGT-M and PGT-A compared to PGT-M only in patients tested for monogenic diseases

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Abstract Study question Is there a difference in cycle outcomes when embryos are tested solely for monogenic diseases (PGT-M) or a combination of PGT-M and chromosomal abnormalities (PGT-A)? Summary answer The Haploseek combining PGT-M & PGT-A resulted in higher pregnancy rates per transfer with no difference in cumulative live birth rates (CLBR). What is known already The goal of PGT-M in patients with monogenic diseases is to avoid pregnancy with an affected embryo. Combining testing for chromosomal abnormalities (PGT-A) provides the chance to shorten time to pregnancy (TTP) and reduce miscarriage rates, while avoiding additional invasive procedures and added costs. However, concerns have been raised that healthy embryos may be excluded due to mis-diagnostic results thus affecting CLBR. The Haploseek is a low-cost, user-friendly, and accurate, next-generation sequencing-based, validated method, for single-cell gene variant detection combined with comprehensive chromosome screening in a 24-hour workflow protocol. Study design, size, duration A retrospective single-center cohort-study (2021-2023) including patients≤42 years, undergoing IVF for a single monogenic disease, having at least one available blastocyst for biopsy. The study group underwent Haploseek testing, combining PGT-A and PGT-M. Patients in the control group underwent PGT-M using Short Tandem Repeat linkage only. Genetics and clinical outcomes were calculated. Participants/materials, setting, methods Analysis was performed following stratification into three groups: 1. Per retrieval–all retrieval cycles, with a main outcome of number of embryos per transfer. 2. Per Embryo transfer–all transfers, with pregnancy and live birth rates included in the clinical outcomes. 3. Per informative retrieval–all retrievals in which either the patient became pregnant or completed transfer of all available embryos with a main outcome of CLBR. Main results and the role of chance Seventy-three patients (34.2±4.3 years) undergoing 128 retrieval cycles were included in the study group. 93 cycles had an AD (72.7%) and 35 AR mutation (27.3%). The control group consisted of 54 patients (33.4±4.5 years; p = 0.57) undergoing 84 retrievals, with 63 (75.0%) AD and 21 (25.0%) AR mutation. The number of embryos available for biopsy per retrieval was similar between the study and control groups (3.99±3.10 vs 3.75±4.14; p = 0.63) as were number of transferable embryos per retrieval (1.27±1.49 (31.9%) vs.1.69±2.37 (45.1%); p = 0.11). Analysis per transfer revealed significantly higher clinical pregnancy rate (45/73 (61.6%) vs. 24/61 (39.3%); p = 0.01), and LBR (41/73 (56.2%) vs. 22/61 (36.1%); p = 0.02) in the study group. There was no difference in early miscarriage rates (6/51 (11.8%) vs. 4/28 (14.3%); p = 0.73). Clinical and ongoing pregnancy rates per informative retrieval were similar between groups as was the CLBR (41/100 (41%) vs. 22/72 (30.6%); p = 0.19). TTP of patients with a live birth was 130.6 + 74.4 days in the study group compared to 141.0 + 93.1 days in the control group (p = 0.63). Limitations, reasons for caution A retrospective study with a relatively small sample size, limiting our ability to address potential differences in miscarriage rate and TTP. Wider implications of the findings The Haploseek is an accurate and rapid validated method of evaluating both PGT-M and PGT-A from the same biopsy, for women undergoing fertility treatment due to monogenic diseases. Implementing this method may result in higher LBR per transfer, without reducing CLBR. Trial registration number No

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