The Influence of Maternal KIR Haplotype on the Reproductive Outcomes after Single Embryo Transfer in IVF Cycles in Patients with Recurrent Pregnancy Loss and Implantation Failure—A Single Center Experience

Maftei, Radu; Doroftei, Bogdan; Popa, Radu; Harabor, Valeriu; Adam, A. H.; Popa, Cristina; Harabor, Anamaria; Adam, Gigi; Nechita, Aurel; Vasilache, Ingrid-Andrada; Mihălceanu, Elena; Bivoleanu, Anca; Lunguleac, Gabriela; Cretu, Ana-Maria; Armeanu, Teodora; Diaconu, Roxana; Cianga, Petru

doi:10.3390/jcm12051905

Cited by 3 publications

(1 citation statement)

References 32 publications

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“…In this comprehensive Spanish case-control study encompassing women experiencing uRF and their respective partners, we delved into the genetic patterns of KIR and the combinations of KIR and HLA-C alleles within the couples. Our findings validated previous data on the significantly elevated frequency of the KIR AA haplotype among women with uRF compared to a reference population outlined by Cisneros and Maftei in RIF 31,36 . Upon categorizing patients into four distinct, non-overlapping groups, we identified a heightened prevalence of the KIR AA haplotype in the S-Group, RPL-Group, and RIF-Group, coupled with an increased susceptibility to encountering any of these complications in women possessing the KIR AA haplotype.…”

Section: Discussionsupporting

confidence: 91%

Centromeric AA motif in KIR as an optimal surrogate marker for precision definition of alloimmune reproductive failure

Gil Laborda,

de Frías,

Subhi-Issa

et al. 2024

Sci Rep

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Throughout pregnancy, the decidua is predominantly populated by NK lymphocytes expressing Killer immunoglobulin-like receptors (KIR) that recognize human leukocyte antigen-C (HLA-C) ligands from trophoblast cells. This study aims to investigate the association of KIR-HLA-C phenotypes in couples facing infertility, particularly recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), in comparison to a reference population and fertile controls. This observational, non-interventional retrospective case–control study included patients consecutively referred to our Reproductive Immunology Unit from 2015 to 2019. We analyzed the frequencies of KIR and HLA-C genes. As control groups, we analyzed a reference Spanish population for KIR analysis and 29 fertile controls and their male partners for KIR and HLA-C combinations. We studied 397 consecutively referred women with infertility and their male partners. Among women with unexplained RPL (133 women) and RIF (176 women), the centromeric (cen)AA KIR genotype was significantly more prevalent compared to the reference Spanish population (p = 0.001 and 0.02, respectively). Furthermore, cenAA was associated with a 1.51-fold risk of RPL and a 1.2-fold risk of RIF. Conversely, the presence of BB KIR showed a lower risk of reproductive failure compared to non-BB KIR (OR: 0.12, p < 0.001). Women and their partners with HLA-C1C1/C1C1 were significantly less common in the RPL-Group (p < 0.001) and RIF-Group (p = 0.002) compared to the control group. Moreover, the combination of cenAA/C1C1 in women with C1C1 partners was significantly higher in the control group than in the RPL (p = 0.009) and RIF (p = 0.04) groups, associated with a 5-fold increase in successful pregnancy outcomes. In our cohort, the cenAA KIR haplotype proved to be a more accurate biomarker than the classic AA KIR haplotype for assessing the risk of RPL and RIF, and might be particularly useful to identify women at increased risk among the heterogeneous KIR AB or Bx population. The classification of centromeric KIR haplotypes outperforms classical KIR haplotypes, making it a better indicator of potential maternal–fetal KIR-HLA-C mismatch in patients.

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Section: Discussionsupporting

confidence: 91%

Centromeric AA motif in KIR as an optimal surrogate marker for precision definition of alloimmune reproductive failure

Gil Laborda,

de Frías,

Subhi-Issa

et al. 2024

Sci Rep

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Immunomodulatory Treatment Impact on IVF Outcomes in KIR AA Genotype: Personalized Fertility Insights

Seles,

Zaha,

Luncan

et al. 2024

Medicina

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Background and Objectives: Recurrent implantation failure (RIF) affects 10% of couples undergoing in vitro fertilization (IVF), spurring exploration into tailored treatments to enhance implantation rates. Maternal immune tolerance towards embryos, particularly killer-cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells, is a focal point in RIF research. Materials and Methods: This retrospective cohort study, conducted at fertility clinic in Oradea, Romania, involved 65 infertile couples undergoing IVF treatment between January 2022 and December 2023. Couples were divided into two groups: KIR AA (Group A) and KIR Bx (Group B). Results: Factors such as age, type of infertility, oocytes retrieved, embryos produced, pregnancy rates in Group A without and with immunomodulatory treatment were documented. Group A, receiving immunomodulatory treatment, achieved a pregnancy rate of 47.8%, significantly higher than the 23.73% rate without treatment (p = 0.008). Group B had a higher mean patient age than Group A. However, miscarriage rates did not significantly differ between Group A with treatment and Group B (p = 0.2457), suggesting comparable outcomes with immunomodulation. Conclusions: The impact of immunological factors on recurrent implantation failure is being more and more emphasized and warrants the attention of specialists in human reproduction. Uterine natural killers and their function though KIR receptors deserve particular attention as immunomodulatory treatment may improve pregnancy rates in patients with KIR AA haplotype.

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Analysis of KIR genotyping results in women with recurrent implantation failure

Sosnina,

Zastavna,

Terpyliak

2023

Fakt. eksp. evol. org.

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Aim. To analyze the frequency and distribution of KIR genotypes in women with recurrent implantation failure after cycles of in vitro fertilization. Methods. DNA extraction and purification, PCR-SSP, agarose gel electrophoresis. Results. The spectrum of KIR genes and the frequency of KIR genotypes in women with recurrent implantation failure were determined. The study group was divided according to history, in particular, a group of 84 women whose diagnosis was outlined by the concept of "repeated failed implantations" was singled out. Statistical analysis of the obtained results using the Pearson test (χ2) indicates a significantly lower frequency of the KIR-AB genotype (χ2 = 9.7; p < 0.005) and a significantly higher frequency of the KIR-AA genotype (χ2 = 7.35; p < 0.01) in women with repeated failed implantations compared to the general group of women with reproductive failures. Conclusions. Taking into account the results of statistical data processing (OR = 2.05; CI 95 %: 1.21-3.45), we consider the KIR-AA genotype to be a significant risk factor for recurrent implantation failure after IVF. We define KIR genotyping as a genetic test to assess the risk of the embryo being rejected by the maternal immune system, and thus to direct medical interventions in order to achieve a successful pregnancy.

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The Influence of Maternal KIR Haplotype on the Reproductive Outcomes after Single Embryo Transfer in IVF Cycles in Patients with Recurrent Pregnancy Loss and Implantation Failure—A Single Center Experience

Cited by 3 publications

References 32 publications

Centromeric AA motif in KIR as an optimal surrogate marker for precision definition of alloimmune reproductive failure

Centromeric AA motif in KIR as an optimal surrogate marker for precision definition of alloimmune reproductive failure

Immunomodulatory Treatment Impact on IVF Outcomes in KIR AA Genotype: Personalized Fertility Insights

Analysis of KIR genotyping results in women with recurrent implantation failure

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