Clinical utility of combined preimplantation genetic testing methods in couples at risk of passing on beta thalassemia/hemoglobin E disease: A retrospective review from a single center

PLoS One. 2019 Nov 21;14(11):e0225457. doi: 10.1371/journal.pone.0225457. eCollection 2019.


Thalassemia and hemoglobinopathy is a group of hereditary blood disorder with diverse clinical manifestation inherited by autosomal recessive manner. The Beta thalassemia/Hemoglobin E disease (HbE/βthal) causes a variable degree of hemolysis and the most severe form of HbE/βthal disease develop a lifelong transfusion-dependent anemia. Preimplantation genetic testing (PGT) is an established procedure of embryo genetic analysis to avoid the risk of passing on this particular condition from the carrier parents to their offspring. Preimplantation genetic testing for chromosomal aneuploidy (PGT-A) also facilitates the selection of embryos without chromosomal aberration resulting in the successful embryo implantation rate. Herein, we study the clinical outcome of using combined PGT-M and PGT-A in couples at risk of passing on HbE/βthal disease. The study was performed from January 2016 to December 2017. PGT-M was developed using short tandem repeat linkage analysis around the beta globin gene cluster and direct mutation testing using primer extension-based mini-sequencing. Thereafter, we recruited 15 couples at risk of passing on HbE/βthal disease who underwent a combined total of 22 IVF cycles. PGT was performed in 106 embryos with a 3.89% allele drop-out rate. Using combined PGT-M and PGT-A methods, 80% of women obtained satisfactory genetic testing results and were able to undergo embryo transfer within the first two cycles. The successful implantation rate was 64.29%. PGT accuracy was evaluated by prenatal and postnatal genetic confirmation and 100% had a genetic status consistent with PGT results. The overall clinical outcome of successful live birth for couples at risk of producing offspring with HbE/βthal was 53.33%. Conclusively, combined PGT-M and PGT-A is a useful technology to prevent HbE/βthal disease in the offspring of recessive carriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Family Characteristics
  • Female
  • Fertilization in Vitro / statistics & numerical data
  • Genetic Testing / methods*
  • Hemoglobin E / genetics*
  • Humans
  • Male
  • Microsatellite Repeats
  • Mutation
  • Pregnancy
  • Preimplantation Diagnosis / methods*
  • Retrospective Studies
  • Sequence Analysis, DNA
  • beta-Globins / genetics*
  • beta-Thalassemia / genetics*


  • beta-Globins
  • Hemoglobin E

Grants and funding

The research was supported in grants to the sub-project ‘Search the molecular basis of rare genetic disorders as a model for disease prevention using preimplantation blastocyst technology’ (to O. Trachoo) and ‘Preimplantation genetic diagnosis for rare genetic disorders’ (to W. Choktanasiri) by the Thailand Research Fund. The grants for next-generation sequencing were partially supported by the Center for Medical Genomics in collaboration with the Faculty of Medicine, Ramathibodi Hospital, Mahidol University and the Thailand Center of Excellence for Life Science (TCELS), Ministry of Science, Thailand (to W. Chantratita).