What are natural killer (NK) cells?
Natural killer cells (NK cells) are part of the body’s immune system. They help the body fight infection and cancer. Every organ has NK cells to protect it, including the womb (uterus). NK cells in the womb are known as uNK cells (uterine natural killer cells). Immune cells, and particularly uNK cells, play an important role in helping you become pregnant.
To get pregnant, an embryo needs to attach to the lining of your womb (implant). Your womb lining needs to be ready for this to happen when the embryo is ready to attach.
For the embryo to attach, your womb lining needs to inflame slightly. This inflammation needs to happen at the right time after ovulation.
After the embryo has attached, your womb lining needs to go through a really big change. It must change from tissue that breaks down every month or so, to tissue that is strong enough to support your pregnancy and placenta for 9 months.
In the past, it was thought that uNK cells attacked or rejected the embryo and that people with high levels of uNK cells were more likely to have a miscarriage.
Further research has shown that this is not true. In fact, uNK cells help make sure the right amount of inflammation happens at the right time to allow the embryo to attach. After the embryo has attached (implanted), uNK cells stop the inflammation by killing the cells that cause it. This is important to help the womb lining change again to support the ongoing pregnancy and not break down.
Can I get my level of uterine natural killer cells tested?
Some fertility clinics offer tests to check the level of uNK cells alone. These tests can’t give a clear picture and are no longer recommended.
Tommy’s researchers are working on a more detailed test called a digital Endometrial Function Test or dEFT, that can help measure the balance of different cells at different times in your cycle.
Unfortunately, the test it is not available on the NHS yet. It’s offered through a scheme called ‘self-funded NHS research’ which means that you only pay what the test actually costs. However, this is expensive at around £700. Researchers are working on making the test cheaper and we want to help make it available to everyone who needs it.
The dEFT is offered by the Implantation Clinic in the Centre for Reproductive Medicine in University Hospital Coventry and Warwickshire NHS Trust. You can find more information on their website.
Have you had 1 or more miscarriages?
If you have miscarried before, it's understandable to feel anxious about trying again.
The Tommy's Miscarriage Support Tool can give you a percentage chance of your next pregnancy being successful and gives personalised support and information.
Brighton, P et al (2017) Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. eLife https://elifesciences.org/articles/31274
Lucas, ES, Vrljicak, P., Muter, J et al (2020) Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window. Communications Biology 3, 37 (2020) https://www.nature.com/articles/s42003-020-0763-1
Royal College of Obstetricians & Gynaecologists (2016) The Role of Natural Killer Cells in Human Fertility https://www.rcog.org.uk/globalassets/documents/guidelines/scientific-impact-papers/sip_53.pdf
Muter, J. et al, (2021). ‘The Role of Decidual Subpopulations in Implantation, Menstruation and Miscarriage’. Frontiers in Reproductive Health 3 2021 DOI=10.3389/frph.2021.804921
Alecsandru, D., & García-Velasco, J. A. (2017). ‘Why natural killer cells are not enough: a further understanding of killer immunoglobulin-like receptor and human leukocyte antigen’. Fertility and sterility, 107(6), 1273–1278. https://doi.org/10.1016/j.fertnstert.2017.04.018
Díaz-Hernández I, Alecsandru D, García-Velasco JA, Domínguez F. Uterine natural killer cells: from foe to friend in reproduction. Hum Reprod Update. 2021 Jun 22;27(4):720-746. doi: 10.1093/humupd/dmaa062. PMID: 33528013.
SHRE Working Group on Recurrent Implantation Failure, D Cimadomo, M J de los Santos, G Griesinger, G Lainas, N Le Clef, D J McLernon, D Montjean, B Toth, N Vermeulen, N Macklon, ESHRE good practice recommendations on recurrent implantation failure, Human Reproduction Open, Volume 2023, Issue 3, 2023, hoad023, https://doi.org/10.1093/hropen/hoad023