Effectiveness and Clinical Outcomes of PGT-M Using Karyomapping for Successful Pregnancy and Birth in Various Types...

Background: Charcot-Marie-Tooth disease (CMT) is a genetically and clinically heterogeneous group of progressive peripheral neuropathies. Preimplantation genetic testing for monogenic disorders (PGT-M), a well-established assisted reproductive technology used to detect specific genetic mutations in embryos before implantation, has been used in common CMT subtypes (e.g., CMT1A); however, data on its application across rarer subtypes and in de novo cases remain limited. In this study, we aimed to evaluate the effectiveness of PGT-M using karyomapping in achieving clinical pregnancies and healthy births in families affected by various CMT types, including the previously unreported subtypes CMT1B and CMT2. Methods: We analyzed 31 PGT-M cycles from 13 families with genetically confirmed CMT, including cases of previously unreported subtypes CMT1B and CMT2. A total of 150 embryos were biopsied. Through 19 embryo transfer cycles, 21 embryos were transferred. In one de novo case, karyomapping was performed using amniotic fluid from an affected fetus as a reference. Results: Of the 19 embryo transfers, 15 resulted in clinical pregnancies. Prenatal diagnosis confirmed that all fetuses were unaffected, and all pregnancies resulted in healthy live births. Successful phasing using amniotic fluid from an affected fetus enabled accurate embryo selection and led to the birth of healthy twins. Conclusions: PGT-M using karyomapping is a rapid and reliable method for achieving successful pregnancies in families affected by diverse CMT subtypes, including de novo cases, and supports broader applicability to other monogenic disorders.