摘要目的：探讨以β地中海贫血基因检测结合人白细胞抗原（HLA）配型为目的的胚胎植入前遗传学诊断（PGD）技术的诊断效率及可行性。方法回顾性分析2010年10月至2015年10月于中山大学附属第一医院生殖医学中心接受以β地中海贫血基因检测结合HLA配型为目的的PGD的43个家庭的临床资料，每个家庭均至少有1例需求造血干细胞移植（HSCT）的先证者。经常规控制性促排卵、体外受精及胚胎培养后，进行胚胎活检，分为卵裂球活检及囊胚活检；对β地中海贫血的致病基因HBB基因及HLA基因进行检测，对检测结果进行分析以完成胚胎的遗传学诊断；并对已分娩患者的子代进行随访。结果43个β地中海贫血家庭共进行了84个促排卵周期，促排卵周期平均获卵数（14±7）个。活检周期共59个，其中卵裂球活检及囊胚活检分别为24和35个周期。卵裂球活检周期中，总活检胚胎数259个，活检成功率93.4%（242/259），遗传学诊断为配型相符的可用囊胚率为9.3%（24/259）。囊胚活检周期中，总活检胚胎数306个，活检成功率93.8%（287/306），配型相符的可用胚胎率14.4%（44/306）。囊胚活检周期中配型相符的可用胚胎率显著高于卵裂球活检（P<0.05）。43例女性携带者共完成了48个胚胎移植周期，其中新鲜胚胎移植3个周期，冻融胚胎移植45个周期。卵裂球活检周期中，有3个周期进行了新鲜胚胎移植，临床妊娠1例，并于孕36周分娩双活胎。囊胚活检后均为全胚冷冻。冻融胚胎移植共45个周期，总移植胚胎数54个，来自卵裂球活检和囊胚活检的胚胎分别为25和29个，其中配型相符的可用胚胎共42个；胚胎着床率为37%（20/54），临床妊娠率38%（17/45）。共分娩15例PGD出生儿，其中2例来自新鲜胚胎移植；冻融胚胎移植周期中，共出生13例新生儿。已分娩患者的产前诊断结果与PGD结果一致。4例新生儿已成功为先证者提供了HSCT。结论以β地中海贫血基因检测结合HLA配型为目的的PGD技术是1种有效的辅助生殖方法，可以帮助携带β地中海贫血基因的家庭在获得健康子代的同时，为先证者的HSCT治疗提供机会。

abstractsObjective 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,&nbsp;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.