Table 1.

Basic research studies showing the associations between KIR and HLA and recurrent miscarriage

Reference	KIR (and HLA) implicated	Type of experiment/objective	Conclusions
[40]	Inhibitory KIRs (2DL1, 2DL2, and 2DL3)	26 childless couples with ≥ 2 abortions and 26 control couples. KIR genotyping	Some alloimmune abortions may occur when the MHC class I molecules on trophoblasts are recognized by decidual NK cells lacking appropriate inhibitory KIR receptors that would stop activating signals.
[41]	No association	51 women with unexplained recurrent spontaneous abortions consecutively referred/55 controls. KIR genotyping.	The data provide little evidence that KIR polymorphism plays a role in predisposition to recurrent spontaneous abortions.
[42]	Inhibitory KIRs (in particular 2DL2)	Cohort of 30 fertile couples (without previous abortions)/139 healthy controls/88 couples with ≥ 3 recurrent spontaneous abortions. KIR genotyping	The balance between inhibitory and activating receptors present in natural killer cells is inclined toward an activating state that may contribute to pregnancy loss.
[43]	Activating KIRs (in particular 2DS1). KIR2DS1 in the absence of KIR2DL1/HLA-C2.	73 pairs of childless couples with ≥ 3 abortions characterized as unexplained and 68 pairs of healthy control couples. KIR genotyping and HLA-C groups C1/C2 identification.	A decrease in the ligands for inhibitory KIRs could potentially lower the threshold for NK cell activation, mediated through activating receptors, thereby contributing to the pathogenesis of recurrent spontaneous abortion.
[44]	KIR2DS1	Male (n = 67) and female (n = 95) partners of couples with ≥ 3 spontaneous miscarriages/269 controls (women primiparae, no miscarriages, or ectopic pregnancies). KIR genotyping and HLA-C groups’ identification.	The findings support the idea that successful placentation depends on the correct balance of uNK cell inhibition and activation in response to trophoblasts.
[45]	Activating KIRs	68 patient couples with recurrent miscarriage and 68 control fertile couples. KIR genotyping	Recurrent miscarriage could be associated with NK cell activation mediated by a profile rich in activating KIR genes.
[46]	KIR2DL1/HLA-C2	177 couples with recurrent miscarriages (primary aborters, no live births) and 200 healthy couples (at least two live births and with no history of miscarriage, preeclampsia, ectopic pregnancy, or preterm delivery). Maternal KIR gene content and HLA-C genotypes to allele level in couples experiencing recurrent miscarriage and controls.	The activation spectrum of KIR-HLA-C compound genotype for NK cells may contribute to the immunological etiology of recurrent miscarriage.
	KIR2DS2/HLA-C1
[47]	Activating KIRs	40 women with unexplained recurrent miscarriage and 90 controls. KIR genotyping.	Shifted balance of KIRs toward an activating state in NK cells may contribute to recurrent miscarriage.
[48]	Inhibitory KIRs	Retrospective study that included 291 women, with recurrent miscarriages or recurrent implantation failure, who had a total of 1304 assisted reproductive cycles. KIR genotyping.	These new insights could have an impact on the selection of single embryo transfer in patients with miscarriages or recurrent implantation failure, and with a KIR AA haplotype.
[49]	KIR2DS1/HLA-C2	The frequencies of KIR and HLA-C1 and HLA-C2 genes were evaluated in 139 women with ≥ 2 consecutive spontaneous pregnancy losses.	KIR and HLA-C genotyping is important for predicting immune-related problems in women with recurrent pregnancy loss women.