For an embryo to implant successfully, it must be accepted by the maternal immune system. This process requires a complex balance between immune tolerance and placental development. In this context, maternal KIR receptors and their interaction with the embryo’s HLA-C antigens have increasingly become a focus of research into certain cases of infertility, recurrent miscarriage, and recurrent implantation failure . However, current scientific evidence suggests that their clinical relevance is limited and may only be significant in very specific situations.
What are KIR receptors?
KIR receptors are proteins found on the surface of certain immune system cells known as uterine NK cells. In the uterus, NK cells interact with embryonic cells and play a role in implantation and early placental development. Depending on the haplotype, KIR receptors may have either activating or inhibitory effects:
- KIR type A: with predominantly inhibitory activity.
- KIR type B: with a stronger activating effect.
What are HLA-C antigens?
HLA-C antigens are molecules found on embryonic cells. They can be divided into two types: HLA-C1 and HLA-C2. These antigens are inherited from the genetic parents, meaning the embryo may present one of three possible combinations:
- HLA-C1C1
- HLA-C2C2
- HLA-C1C2
In theory, the maternal immune system may show lower tolerance when the embryo carries HLA-C types that differ from the mother’s own, regardless of whether they originate from the father or from an egg donor.
KIR/HLA-C combinations and pregnancy outcome
Certain combinations of maternal KIR receptors and embryonic HLA-C types may be associated with an increased risk of placental disorders and pregnancy loss. In particular, researchers have studied the potential risk in women with a type A KIR haplotype with predominantly inhibitory activity when the embryo carries an HLA-C2 type not inherited from the mother.
However, published studies suggest that this potential risk may mainly be relevant in situations where multiple embryos are transferred simultaneously, since exposure to embryonic HLA-C2 may be greater in these cases.
Does this have clinical value in assisted reproduction?
Although it was initially believed that KIR/HLA-C testing might help explain certain cases of infertility or miscarriage, published studies have not demonstrated significant clinical value for most patients. Current scientific evidence suggests that these immunological combinations may only have clinical implications in very specific situations.
In addition, two fundamental factors must be considered:
- There is currently no treatment proven to improve reproductive outcomes according to a patient’s KIR profile.
- The potential risk described appears to occur mainly when multiple embryos are transferred at the same time.
The Importance of Single Embryo Transfer (SET)
Therefore, the clinical relevance of these findings is considerably lower in centres where single embryo transfer is preferred. Transferring a single embryo significantly reduces the antigenic load, minimizing the impact of this immunological interaction.
When might KIR/HLA-C testing be considered?
KIR/HLA-C testing may be considered in selected situations, such as recurrent miscarriage or recurrent implantation failure. However, it should always be individualised and interpreted within the broader clinical context. In single embryo transfer cycles, the usefulness of these tests is very limited, and they cannot by themselves explain a negative treatment outcome, even in egg donation cases.
At Barcelona IVF , every case is assessed individually, and only tests with scientifically supported clinical value and the potential to provide meaningful information for treatment planning are considered in an honest and effective manner.
