Alecsandru D, Garrido N, Vicario J L, Barrio A, Aparicio P, Requena A, García-Velasco J A
Department of Immunology and Department of Reproductive Endocrinology and Infertility, Instituto Valenciano de Infertilidad-Madrid, Rey Juan Carlos University (IVI), Madrid, Spain
Andrology Department, Instituto Valenciano de Infertilidad, Guadassuar 1 Bajo, Valencia 46015, Spain.
Hum Reprod. 2014 Dec;29(12):2637-43. doi: 10.1093/humrep/deu251. Epub 2014 Oct 14.
In patients with recurrent miscarriages (RM) or recurrent implantation failure (RIF), does the maternal killer immunoglobulin-like receptor (KIR) haplotype have an impact on live birth rates per cycle after embryo transfer with the patient's own or donated oocytes?
After double embryo transfer (DET) in patients with the maternal KIR AA haplotype, a significantly increased early miscarriage rate was observed when the patient's own oocytes were used, and a significantly decreased live birth rate per cycle after embryo transfer was observed when donated oocytes were used.
Interactions between fetal HLA-C and maternal KIR influence placentation during human pregnancy. There is an increased risk of RM, pre-eclampsia or fetal growth restriction in mothers with the KIR AA haplotype when the fetus has more HLA-C2 genes than the mother.
STUDY DESIGN, SIZE AND DURATION: Between 2010 and 2014, we performed a retrospective study that included 291 women, with RM or RIF, who had a total of 1304 assisted reproductive cycles.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnancy, miscarriage and live birth rates per cycle after single or DET, categorized by the origin of the oocytes and the presence of maternal KIR haplotypes, were studied. KIR haplotype regions were defined by the presence of the following KIR genes: Cen-A/2DL3; Tel-A/3DL1 and 2DS4; Cen-B/2DL2 and 2DS2; as well as Tel-B/2DS1 and 3DS1.
Higher rates of early miscarriage per cycle after DET with the patient's own oocytes in mothers with the KIR AA haplotype (22.8%) followed by those with the KIR AB haplotype (16.7%) compared with mothers with the KIR BB haplotype (11.1%) were observed (P = 0.03). Significantly decreased live birth rates per cycle were observed after DET of donated oocytes in mothers with the KIR AA haplotype (7.5%) compared with those with the KIR AB (26.4%) and KIR BB (21.5%) haplotypes (P = 0.006). No statistically significant differences were observed for pregnancy, miscarriage and live birth rates per cycle among those with maternal KIR AA, AB and BB haplotypes after single embryo transfer (SET) with the patient's own or donated oocytes. The large number of cases studied strengthens the results and provides sufficient power to the statistical analysis.
LIMITATIONS, REASONS FOR CAUTION: During the IVF procedure, DET induces the expression of more than one paternal HLA-C and the oocyte-derived maternal HLA-C in the oocyte-donation cycles probably behaves like paternal HLA-C. Because this was a retrospective study, we did not have data about the HLA-C of the parent, donor, chorionic villi, or infant, which is a limitation because we cannot show differences according to paternal or oocyte donor HLA-C1 and HLA-C2.
These new insights could have an impact on the selection of SET in patients with RM or RIF, and a KIR AA haplotype. Also, it may help in oocyte and/or sperm donor selection by HLA-C in patients with RM or RIF and a KIR AA haplotype.
STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. The authors have no conflicts of interest to declare.
在复发性流产（RM）或反复种植失败（RIF）患者中，母体杀伤细胞免疫球蛋白样受体（KIR）单倍型对使用患者自身或捐赠卵母细胞进行胚胎移植后每个周期的活产率有影响吗？
在母体KIR AA单倍型患者进行双胚胎移植（DET）后，当使用患者自身卵母细胞时，观察到早期流产率显著增加；当使用捐赠卵母细胞时，观察到胚胎移植后每个周期的活产率显著降低。
胎儿HLA - C与母体KIR之间的相互作用会影响人类妊娠期间的胎盘形成。当胎儿比母亲拥有更多HLA - C2基因时，具有KIR AA单倍型的母亲发生RM、先兆子痫或胎儿生长受限的风险增加。
研究设计、规模和持续时间：2010年至2014年期间，我们进行了一项回顾性研究，纳入了291名患有RM或RIF的女性，她们总共进行了1304个辅助生殖周期。
参与者/材料、环境、方法：研究了按卵母细胞来源和母体KIR单倍型分类的单胚胎移植（SET）或DET后每个周期的妊娠、流产和活产率。KIR单倍型区域由以下KIR基因的存在来定义：着丝粒 - A/2DL3；端粒 - A/3DL1和2DS4；着丝粒 - B/2DL2和2DS2；以及端粒 - B/2DS1和3DS1。
与KIR BB单倍型母亲（11.1%）相比，KIR AA单倍型母亲（22.8%）在使用自身卵母细胞进行DET后每个周期的早期流产率更高，其次是KIR AB单倍型母亲（16.7%）（P = 0.03）。与KIR AB（26.4%）和KIR BB（21.5%）单倍型母亲相比，KIR AA单倍型母亲在使用捐赠卵母细胞进行DET后每个周期的活产率显著降低（7.5%）（P = 0.006）。在使用患者自身或捐赠卵母细胞进行单胚胎移植（SET）后，母体KIR AA、AB和BB单倍型患者每个周期的妊娠、流产和活产率之间未观察到统计学上的显著差异。大量的研究病例加强了结果，并为统计分析提供了足够的效力。
局限性、谨慎原因：在体外受精过程中，DET会诱导多个父本HLA - C的表达，并且在卵母细胞捐赠周期中卵母细胞来源的母体HLA - C可能表现得像父本HLA - C。由于这是一项回顾性研究，我们没有关于父母、供体、绒毛膜绒毛或婴儿的HLA - C的数据，这是一个局限性，因为我们无法根据父本或卵母细胞供体的HLA - C1和HLA - C2显示差异。
这些新见解可能会影响RM或RIF且具有KIR AA单倍型患者的SET选择。此外，它可能有助于RM或RIF且具有KIR AA单倍型患者通过HLA - C选择卵母细胞和/或精子供体。
研究资金/利益冲突：本研究未获得资金支持。作者声明无利益冲突。
