title: Combination of uterine natural killer cell immunoglobulin receptor haplotype and trophoblastic HLA-C ligand influences the risk of pregnancy loss: a retrospective cohort analysis of direct embryo genotyping data from euploid transfers.
abstract: OBJECTIVE
  To compare maternal uterine natural killer cell immunoglobulin receptor (KIR) genotype and haplotype frequencies between patients whose euploid single-embryo transfer resulted in pregnancy loss and those that resulted in delivery and to determine if the risk of pregnancy loss was affected by the HLA-C genotype content in the embryo.
  
  
  METHODS
  Retrospective cohort.
  
  
  METHODS
  Academic research center.
  
  
  METHODS
  Autologous fresh IVF cycles resulting in positive serum β-hCG during 2009-2014.
  
  
  METHODS
  None.
  
  
  METHODS
  1) Relative risk of pregnancy loss according to maternal KIR genotypes and haplotypes. 2) Comparison of pregnancy loss rates within each KIR haplotype according to HLA-C ligand present in trophectoderm biopsy samples.
  
  
  RESULTS
  A total of 668 euploid single-embryo transfers with stored maternal DNA and available preamplification DNA from prior trophectoderm biopsy samples were studied. KIR2DS1, KIR3DS1, and KIR2DS5 were more common in patients who experienced pregnancy loss. Carriers of KIR A haplotype exhibited a decreased risk of pregnancy loss compared with KIR B haplotype carriers. However, among KIR A haplotype carriers, the risk of loss was significantly influenced by whether the transferred embryo carried a C1 allele versus no C1 alleles.
  
  
  CONCLUSIONS
  KIR A haplotype carriers experienced fewer pregnancy losses than KIR B haplotype carriers after euploid single-embryo transfer. However, this risk was modified by HLA-C alleles present in the embryo. High-risk combinations (KIR A/homozygous C2 and KIR B/homozygous C1) resulted in a 51% increased risk of loss over all other combinations.
authors.affiliation: Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: smorin@rmanj.com.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Morin
authors.affiliation: Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Treff
authors.affiliation: Foundation for Embryonic Competence, Basking Ridge, New Jersey.
authors.forename: Xin
authors.initials: X
authors.lastname: Tao
authors.affiliation: Foundation for Embryonic Competence, Basking Ridge, New Jersey.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Scott
authors.affiliation: Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Franasiak
authors.affiliation: Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Caroline R
authors.initials: CR
authors.lastname: Juneau
authors.affiliation: Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey.
authors.forename: Marcy
authors.initials: M
authors.lastname: Maguire
authors.affiliation: Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Scott
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D000328:Adult; D001706:Biopsy; D001755:Blastocyst / Q000276:immunology*; D004624:Embryo Transfer / Q000009:adverse effects*; D005260:Female; D005298:Fertility; D005307:Fertilization in Vitro / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000276:immunology*; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007246:Infertility / Q000235:genetics / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D008024:Ligands; D008875:Middle Aged; D011003:Ploidies; D011247:Pregnancy; D018873:Pregnancy Rate; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D014327:Trophoblasts / Q000276:immunology*; D014599:Uterus / Q000276:immunology* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D015236:HLA-C Antigens; D008024:Ligands; D054340:Receptors, KIR
keywords: Uterine natural killer cells; human leukocyte antigen; pregnancy loss