title: Maternal KIR haplotype influences live birth rate after double embryo transfer in IVF cycles in patients with recurrent miscarriages and implantation failure.
abstract: OBJECTIVE
  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?
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  No funding was received for this study. The authors have no conflicts of interest to declare.
authors.affiliation: Department of Immunology and Department of Reproductive Endocrinology and Infertility, Instituto Valenciano de Infertilidad-Madrid, Rey Juan Carlos University (IVI), Madrid, Spain diana.alecsandru@ivi.es.
authors.forename: D
authors.initials: D
authors.lastname: Alecsandru
authors.affiliation: Andrology Department, Instituto Valenciano de Infertilidad, Guadassuar 1 Bajo, Valencia 46015, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Garrido
authors.affiliation: Histocompatibility Department, Centro de Transfusión de Madrid, Av. de la Democracia s/n, Madrid 28032, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Vicario
authors.affiliation: Department of Immunology and Department of Reproductive Endocrinology and Infertility, Instituto Valenciano de Infertilidad-Madrid, Rey Juan Carlos University (IVI), Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Barrio
authors.affiliation: Department of Immunology and Department of Reproductive Endocrinology and Infertility, Instituto Valenciano de Infertilidad-Madrid, Rey Juan Carlos University (IVI), Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Aparicio
authors.affiliation: Department of Immunology and Department of Reproductive Endocrinology and Infertility, Instituto Valenciano de Infertilidad-Madrid, Rey Juan Carlos University (IVI), Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Requena
authors.affiliation: Department of Immunology and Department of Reproductive Endocrinology and Infertility, Instituto Valenciano de Infertilidad-Madrid, Rey Juan Carlos University (IVI), Madrid, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: García-Velasco
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D001723:Birth Rate; D010064:Embryo Implantation / Q000235:genetics; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D015236:HLA-C Antigens / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D015236:HLA-C Antigens; D054340:Receptors, KIR
keywords: Maternal KIR; embryo transfer; live birth rate; miscarriage rate; paternal HLA-C