[Clinical analysis of preimplantation genetic diagnosis with HLA matching for beta-thalassemia].

OBJECTIVE

To investigate the efficacy and feasibility of preimplantation genetic diagnosis(PGD)with human leukocyte antigen(HLA)matching for beta-thalassemia.

METHODS

A total of 43 referred beta-thalassemia couples, with at least on child in need of hematopoietic stem cell transplantation(HSCT), underwent PGD for HLA matching at the First Affiliated Hospital of Sun Yat-sen University from 2010 to 2015. PGD cycles of these couples were retrospectively analyzed, and 15 infants born from PGD-HLA were followed up.

RESULTS

A total of 84 oocyte retrieval cycles were performed, providing 14±7 oocytes per cycle. Fifty nine embryos biopsied cycles were done, including 24 cleavage stage and 35 blastocyst stage biopsy cycles. In cleavage stage, 259 embryos were biopsied, 93.4%(242/259)of them with conclusive molecular diagnosis, and the percentage of unaffected embryos(normo-homozygote and heterozygote)was 71.4%(185/259). The percentage of HLA matched unaffected embryos was 9.3%(24/259). In blastocyst stage, 306 embryos were biopsied, while 93.8%(287/306)of them were conclusive, and the percentage of unaffected embryos was 70.6%(216/306). The percentage of HLA matched unaffected embryos in blastocyst stage biopsy was 14.4%(44/306), which was higher than in cleavage stage biopsy(P< 0.05). Forty three female carriers underwent 48 embryo transfer cycles including 3 fresh and 45 frozen-thawed embryo transfer cycles. Three fresh embryo transfer cycles were done after cleavage stage biopsy, resulted in a birth of healthy twins born at 36 weeks' gestation. All the embryos were frozen after blastocyst biopsied. Totally, 54 frozen-thawed embryos that were transferred in 45 frozen-thawed embryo transfer cycles included 25 embryo from cleavage stage biopsy and 29 embryo from blastocyst stage biopsy, and 42 of them were HLA matched. Clinical pregnancy rate and implantation rate per cycle in frozen-thawed embryo transfer were 38%(17/45)and 37%(20/54)respectively. A total of 15 infants were born, 2 were from a fresh embryo transfer cycle, and 13 were from frozen-thawed embryo transfer cycles. RESULTS of prenatal diagnosis from delivered cases were matched to that of PGD. Four sick children have been cured by HSCT from these HLA matched born siblings.

CONCLUSION

PGD with HLA matching is an established method for conceiving a child who may donate hematopoietic stem cells to save an ill sibling.