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Parental human leukocyte antigen-C allotypes are predictive of live birth rate and risk of poor placentation in assisted reproductive treatment
Fertility and Sterility ( IF 6.6 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.fertnstert.2020.05.008
Diana Alecsandru 1 , Ana Barrio 2 , Nicolás Garrido 3 , Pilar Aparicio 4 , Antonio Pellicer 5 , Ashley Moffett 6 , Juan A García-Velasco 7
Affiliation  

OBJECTIVE To study the pregnancy, miscarriages, and live birth rates (LBRs) according to maternal killer cell immunoglobulin-like receptor (KIR) genes expressed by uterine natural killer cells and paternal or oocyte donor human leukocyte antigen-C (HLA-C) genes expressed by trophoblast cells in patients with recurrent reproductive failure. DESIGN Prospective observational cohort study. SETTING Private infertility center. PATIENT(S) Participants included 204 women with recurrent miscarriage or recurrent implantation failure. INTERVENTION(S) The KIR and HLA-C genotypes of all women and HLA-C of their partners, gamete donors, miscarriage tissue, and babies were analyzed. MAIN OUTCOME MEASURE(S) All clinical variables (pregnancy, miscarriage, and LBRs) were analyzed and categorized based on KIR, oocyte origin, and single embryo transfer (SET)/double embryo transfer (DET). RESULT(S) A higher miscarriage rate was observed after DETs in KIR AA mothers (47.8% egg donation and 37.5% in vitro fertilization [IVF]) compared with KIR AB (10.5% egg donation and 12.5% IVF) or KIR BB (6.7% egg donation and 0% IVF). A significantly decreased LBR was observed after DETs with oocyte donation in KIR AA patients (4.3%) compared with KIR AB (26.3%) or BB (46.7%). The LBR decreased significantly as the fetal HLA-C2 load increased in KIR AA women. CONCLUSION(S) Elective SET improves the reproductive outcomes compared with DET. An increased embryo HLA-C2 load has a negative impact on the LBR in KIR AA patients. The selection of HLA-C1 over HLA-C2 donors could have a positive impact on the LBR in KIR AA patients. CLINICAL TRIAL REGISTRATION NUMBER NCT04052438.

中文翻译:

亲本人类白细胞抗原-C 同种异型可预测活产率和辅助生殖治疗中胎盘不良的风险

目的根据子宫自然杀伤细胞表达的母体杀伤细胞免疫球蛋白样受体(KIR)基因和父方或卵母细胞供体人白细胞抗原-C(HLA-C)基因表达的妊娠、流产和活产率(LBR)进行研究由滋养层细胞在复发性生殖衰竭患者中表达。设计前瞻性观察队列研究。设置私人不孕不育中心。患者 参与者包括 204 名反复流产或反复植入失败的女性。干预措施 分析了所有女性的 KIR 和 HLA-C 基因型以及她们的伴侣、配子捐赠者、流产组织和婴儿的 HLA-C。主要结果测量 所有临床变量(妊娠、流产和 LBR)均根据 KIR、卵母细胞来源、和单胚胎移植(SET)/双胚胎移植(DET)。结果(S)与 KIR AB(10.5% 卵子捐赠和 12.5% IVF)或 KIR BB(6.7%)相比,在 KIR AA 母亲(47.8% 的卵子捐赠和 37.5% 的体外受精 [IVF])中观察到更高的流产率% 卵子捐赠和 0% 试管婴儿)。与 KIR AB (26.3%) 或 BB (46.7%) 相比,KIR AA 患者 (4.3%) 捐卵 DET 后观察到 LBR 显着降低。随着胎儿 HLA-C2 负荷在 KIR AA 妇女中增加,LBR 显着降低。结论(S)与 DET 相比,选择性 SET 改善了生殖结果。增加的胚胎 HLA-C2 负荷对 KIR AA 患者的 LBR 有负面影响。选择 HLA-C1 而非 HLA-C2 供体可能对 KIR AA 患者的 LBR 产生积极影响。临床试验注册号 NCT04052438。
更新日期:2020-10-01
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