Improved cycle outcomes using the HaploSeek comprehensive PGT-A and PGT-M combined analysis in monogenic-disease-affected couples

Research question: Is there a difference in clinical outcomes of IVF cycles using the HaploSeek method [preimplantation genetic testing for monogenic conditions (PGT-M) combined with preimplantation genetic testing for aneuploidy (PGT-A)] compared with clinical outcomes of IVF cycles using PGT-M alone? Design: This retrospective cohort study included patients aged ≤42 years undergoing IVF PGT-M with at least one blastocyst. The study group underwent HaploSeek, combining PGT-M and PGT-A. The control group underwent PGT-M alone, using short tandem repeat linkage. Analysis was performed following stratification into four groups: per woman, including the first retrieval and first transfer, with live birth rate (LBR) as the primary outcome; per retrieval, all retrievals, with the number of embryos available for transfer as the primary outcome; per embryo transfer, all transfers, with LBR as the primary outcome; and per informative retrieval, all retrievals in which the patient delivered or completed transfer of all embryos, calculating cumulative LBR (CLBR). Results: Seventy-three patients (mean ± SD age 33.5 ± 4.4 years) undergoing 128 retrievals were included in the study group. The control group consisted of 54 patients (mean ± SD age 33.4 ± 4.5 years; P = 0.57) undergoing 84 retrievals. The number of embryos available for biopsy per retrieval was similar between the study and control groups (mean ± SD 3.99 ± 3.1 versus 3.75 ± 4.14; P = 0.34), as was the number of transferable embryos per retrieval [mean ± SD 1.29 ± 1.52 (32.3%) versus 1.69 ± 2.37 (45.1%); P = 0.075]. LBR was higher per first retrieval per woman in the study group (35.6% versus 16.7%; P = 0.0181). A multivariable logistic regression for LBR in the first retrieval showed that HaploSeek and age were associated with higher probability of live birth. Per-transfer analysis revealed that LBR was significantly higher in the study group (P = 0.02). CLBR per informative retrieval was similar between groups. Conclusions: HaploSeek, evaluating both PGT-M and PGT-A, may significantly improve LBR per transfer without reducing CLBR in comparison with PGT-M alone in couples with monogenic diseases.