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Preimplantation genetic testing with HLA matching: from counseling to birth and beyond

Journal of Human Genetics volume 65, pages 445–454 (2020)Cite this article

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Abstract

Preimplantation genetic testing-human leukocyte antigen ‘(PGT-HLA) only’ refers to the HLA typing of single or few cells biopsied from in vitro fertilized preimplantation embryos. The aim of the procedure is to establish a pregnancy, in which the fetus is HLA compatible with an affected sibling in need of a hematopoietic stem cell transplantation (HSCT). During PGT-M-HLA, the identification of a HLA-compatible embryo is combined with the detection of mutation(s) underlying immunodeficiencies and hemoglobinopathies. We report a combined retrospective and prospective cohort analysis of PGT-(M-)HLA procedures carried out from 1998 until 2017, with follow-up of transplantations to 2019. During the study period, 234 couples from 22 countries were invited for a multidisciplinary consultation. Two couples were rejected and 70 couples declined (various reasons), leaving 162 couples for which 414 clinical cycles were carried out. Cleavage stage biopsy followed by single-cell multiplex PCR for short tandem repeat-based haplotyping was applied in most cases (98.7%). The diagnostic efficiency was high (94.8%) but only 16.5% of the embryos was genetically suitable for transfer. Fresh and frozen-thawed embryo transfer resulted in 67 clinical pregnancies, 63 deliveries, and 74 live births, of which 60 children were HLA compatible. This yielded a live birth delivery rate of 30.3% per transfer. Information on neonatal characteristics of the matching PGT-(M-)HLA children showed reassuring outcomes. So far, HSCT was carried out successfully for 25 out of 26 cases. In conclusion, our data show that PGT-(M-)HLA is a valuable procedure: the high complexity and limited delivery rate are balanced by the successful HSCT outcome and the positive impact on families.

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Acknowledgements

We wish to thank the clinical, paramedical, and laboratory teams of the Center for Medical Genetics and the Center for Reproductive Medicine of the Universitair Ziekenhuis Brussel. We also would like to thank the clinicians for referring the couples and the couples who participated in the study.

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Author notes

  1. These authors contributed equally: M. De Rycke, A. De Vos

Authors and Affiliations

  1. Centre for Medical Genetics, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium

    M. De Rycke, F. Belva, V. Berckmoes, M. Bonduelle, A. Buysse, K. Keymolen, I. Liebaers, J. Nekkebroeck & P. Verdyck

  2. Vrije Universiteit Brussel (VUB), Reproduction and Genetics, Laarbeeklaan 101, 1090, Brussels, Belgium

    M. De Rycke

  3. Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium

    A. De Vos, J. Nekkebroeck & W. Verpoest

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  1. M. De Rycke
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De Rycke, M., De Vos, A., Belva, F. et al. Preimplantation genetic testing with HLA matching: from counseling to birth and beyond. J Hum Genet 65, 445–454 (2020). https://doi.org/10.1038/s10038-020-0732-z

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