Results of concurrent preimplantation genetic testing for monogenic conditions (pgt-m), structural rearrangements (pgt-sr), and aneuploidy (pgt-a); setting patient expectations

To report the rate of unaffected and euploid embryo results for patients who underwent concurrent preimplantation genetic testing for monogenic conditions (PGT-M), structural rearrangements (PGT-SR), and aneuploidy (PGT-A). Retrospective analysis was conducted on trophectoderm (TE) biopsy results from in vitro fertilization (IVF) patients referred for PGT-M and PGT-SR with concurrent PGT-A between 2013 and 2023. TE biopsies were genotyped using Illumina Cyto12 SNP-based microarrays with informatics. 15 patients underwent concurrent PGT-M, PGT-SR, and PGT-A, 9 pursued more than one IVF cycle (mean maternal age 34.2 years; range 25-41 years). A total of 261 TE biopsy samples from 34 IVF cycles were tested (mean 7.7 embryos/cycle; range 1-12). 8 patients pursued PGT-M for an autosomal recessive (AR) condition, 4 for an X-linked (XL) condition, and 3 for an autosomal dominant (AD) condition. PGT-SR was performed for 10 maternal chromosome rearrangements and 5 paternal chromosome rearrangements including 13 reciprocal translocations, 1 Robertsonian translocation, and 1 inversion. Of 34 IVF cycles completed, 20 (58.8%) resulted in at least one euploid and unaffected embryo to transfer. Overall, 46/261 (17.6%) TE biopsy samples had euploid and unaffected results; 28 (60.9%) of these were tested for an AR condition, 3 (6.5%) for an XL condition, and 15 (32.6%) for an AD condition. 176/261 (67.4%) TE biopsy samples had aneuploid results; 87/176 (49.4%) had an inherited unbalanced chromosome rearrangement only, 66/176 (37.5%) had a sporadic aneuploidy only, and 23/176 (13.0%) had both an inherited and sporadic aneuploidy. Overall, 110/261 (42.1%) TE biopsy samples had an inherited unbalanced chromosome rearrangement. There were 7 (2.7%) TE biopsy samples with no results overall and 18 (6.9%) with no results for PGT-M only; 8 of these were from a single patient with a translocation involving the chromosome where the single gene variant is located. Excluding this patient, the rate of no results for PGT-M was 3.8% of TE biopsy samples. 6 patients were initially referred for PGT-M with concurrent PGT-A, and results were suspicious for a possible parental chromosome rearrangement that was subsequently confirmed by parental blood chromosome analysis. IVF with concurrent PGT-M, PGT-SR, and PGT-A is an option for patients who want to pursue testing for an inherited single gene condition and hereditary chromosome rearrangement simultaneously on a single TE biopsy sample. These data show that more than half of all IVF cycles resulted in at least one euploid and unaffected embryo to transfer and that this rate varies based on the inheritance pattern of the tested single gene condition. This information can be useful in counseling patients regarding IVF cycle outcome and the potential need for multiple IVF cycles to obtain an unaffected and euploid embryo to transfer.