Pre-implantation Genetic Testing for Monogenic Disorders at Chiang Mai University : 20 Years Experience
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Abstract
Objectives: The prevention and control program for severe thalassemias in Thailand has been very successful. However, at present, some families at risk of having an offspring with severe thalassemias are looking for a better option other than termination of pregnancy. Pre-implantation genetic testing of monogenic disorders (PGT-M) or embryo selection would be the correct answer. This study presents the PGT-M with 20 years experience at Chiang Mai University.
Materials and Methods: The couples at risk of having the offspring with Hemoglobin Bart’s (Hb Bart’s) disease, beta-thalassemia major, and beta-thalassemia-Hb E disease came in for genetic counselling and PGT-M treatment. PGT-M protocols are based on multiplex fluorescent polymerase chain reaction (PCR) and mini-sequencing. PGT-M protocols for Hb Bart’s disease, beta-thalassemia major, and beta-thalassemia-Hb E disease have been developed, tested, and clinically applied.
Results: Since 2003, a total of 168 PGT-M cycles in 125 families have been performed, giving rise to a total of 75 pregnancies (85 healthy babies). A total of 132 clinical PGT-M cycles were performed for 111 couples at risk of having the offspring with Hb Bart’s disease, beta-thalassemia major, and beta-thalassemia-Hb E disease giving rise to 66 pregnancies with 76 babies. No misdiagnosis has been detected. Notably, three families were at risk of having the offspring with both Hb Bart’s disease and beta-thalassemia-Hb E disease. Two families had already had a affected child with beta-thalassemia-Hb E disease and came in for PGT-M of beta-thalassemia-Hb E disease and human leukocyte antigen (HLA) matching.
Conclusion: The pregnancy rates were 44.6%, however, some PGT-M cycles are still on-going and the embryos are kept frozen. More pregnancies should be obtained when the patients return for embryo transfer. In addition to severe thalassemias, PGT-M for other rare diseases have been done. During the past 20 years, over 20 PGT-M protocols have been developed, tested, and clinically applied. All protocols were novel and home grown.
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