Liu X Y, Wang J, Zeng Y H, Ding C H, Shen X T, Zhou W, Li R, Zhou C Q, Xu Y W
Reproductive Medical Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Zhonghua Fu Chan Ke Za Zhi. 2016 Jul 25;51(7):491-7. doi: 10.3760/cma.j.issn.0529-567X.2016.07.003.
To investigate the efficacy and feasibility of preimplantation genetic diagnosis(PGD)with human leukocyte antigen(HLA)matching for beta-thalassemia.
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.
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.
PGD with HLA matching is an established method for conceiving a child who may donate hematopoietic stem cells to save an ill sibling.
探讨人类白细胞抗原（HLA）配型的植入前基因诊断（PGD）用于β地中海贫血的有效性和可行性。
2010年至2015年期间，共有43对转诊的β地中海贫血夫妇在中山大学附属第一医院接受了HLA配型的PGD，这些夫妇至少有一个孩子需要造血干细胞移植（HSCT）。对这些夫妇的PGD周期进行回顾性分析，并对15例PGD-HLA出生的婴儿进行随访。
共进行了84个取卵周期，每个周期平均获取14±7个卵母细胞。进行了59个胚胎活检周期，其中24个为卵裂期活检周期，35个为囊胚期活检周期。在卵裂期，共活检了259个胚胎，其中93.4%（242/259）获得了明确的分子诊断，未受影响胚胎（正常纯合子和杂合子）的比例为71.4%（185/259）。HLA配型的未受影响胚胎的比例为9.3%（24/259）。在囊胚期，共活检了306个胚胎，其中93.8%（287/306）获得了明确诊断，未受影响胚胎的比例为70.6%（216/306）。囊胚期活检中HLA配型的未受影响胚胎的比例为14.4%（44/306），高于卵裂期活检（P<0.05）。43名女性携带者进行了48个胚胎移植周期，包括3个新鲜胚胎移植周期和45个冻融胚胎移植周期。在卵裂期活检后进行了3个新鲜胚胎移植周期，产下了孕36周的健康双胞胎。所有胚胎在囊胚活检后均被冷冻。在45个冻融胚胎移植周期中共移植了54个冻融胚胎，其中25个来自卵裂期活检胚胎，29个来自囊胚期活检胚胎，其中42个HLA配型。冻融胚胎移植的临床妊娠率和每个周期的着床率分别为38%（17/45）和37%（20/54）。共出生15名婴儿，2名来自新鲜胚胎移植周期，13名来自冻融胚胎移植周期。分娩病例的产前诊断结果与PGD结果相符。4名患病儿童已通过这些HLA配型出生的同胞的HSCT治愈。
HLA配型的PGD是一种成熟的方法，可用于孕育一个能够捐献造血干细胞以挽救患病同胞的孩子。
