Using affected embryos to establish linkage phase in preimplantation genetic testing for thalassemia

BACKGROUND: This study aimed to evaluate the ability of next-generation sequencing (NGS) to conduct preimplantation genetic testing (PGT) for thalassemia using affected embryos. METHODS: This study included data from 36 couples who underwent PGT for thalassemia without probands and relative pedigrees. NGS results were compared with prenatal diagnosis results. RESULTS: Thirty-six couples (29 α-thalassemia and 7 β-thalassemia) underwent 41 PGT cycles (31 α-thalassemia and 10 β-thalassemia). Analysis using NGS produced conclusive results for all biopsied blastocysts (100%, 217/217). One hundred and sixty (73.7%, 160/217) were unaffected by thalassemia. Preimplantation genetic testing for aneuploidy revealed that 112 (70.0%, 112/160) were euploid. Single blastocysts were transferred into the uteri of 34 women (53 frozen embryo transfer [FET] cycles). Thirty-two cycles resulted in clinical pregnancies, with a clinical pregnancy rate of 60.1% (32/53) per FET cycle. Twenty-two cycles (22 couples) resulted in 23 live births, with a live birth rate of 43.4% (23/53; 3 cycles were ongoing pregnancies). All 25 embryos’ prenatal diagnosis results and/or thalassemia gene analyses after delivery were concordant with the NGS-PGT results. Seven embryos (21.9%, 7/32) were miscarried before 12 weeks’ gestation, and the abortion villus in four showed a normal karyotype and thalassemia results consistent with the NGS-PGT results. Aborted fetus samples from 3 cycles were not available because the pregnancy lasted less than 5 weeks. CONCLUSION: NGS can be used to conduct PGT for thalassemia using affected embryos as a reference. TRIAL REGISTRATION: Retrospectively registered. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12958-022-00948-9.