From Embryology

ILP2015 - Is there a role for Natural Killer cells in ectopic pregnancy?

Ectopic pregnancy (EP) is a life-threatening condition, in which a fertilised ovum abnormally implants outside the uterine cavity, most commonly in the fallopian tube (FT) (Parashi, Moukhah, & Ashrafi, 2014). Although EP is clinically well documented, much of its pathogenesis is still unknown. Because tubal (t)EP is associated with significant maternal mortality due to tubal rupture and intra-abdominal haemorrhage, greater understanding of this medical emergency is warranted (Kirk, Bottomley, & Bourne, 2014). Current literature on EP and research in the possible role of maternal Natural Killer (NK) cells in the FT interacting with the implanting embryo, aims to improve the potential of diagnostic markers, resulting in earlier EP management.

First do no harm: uterine natural killer (NK) cells in assisted reproduction

Hum Reprod. 2015 May 7. pii: dev098. [Epub ahead of print]

Moffett A1, Shreeve N2.


Natural killer (NK) cells are a type of lymphocyte circulating in peripheral blood named because of their effector functions in killing target cells. Immune cells that share similar phenotypic characteristics but are poor killers populate the uterine lining at implantation and during early pregnancy when the placenta is established. The functions of these uterine NK (uNK) cells are essentially unknown but available data point to a role in regulating placentation in concert with other elements of the decidua and invading trophoblast cells. Despite the lack of scientific rationale and advice from clinical governing bodies, such as the Human Fertilisation and Embryology Authority, an increasing range of tests and therapies are still offered to women undergoing IVF or attending recurrent miscarriage clinics based on the myth that uterine NK cells need suppressing to prevent damage to the embryo. New treatments can be introduced at whim with subsequent demands for expensive trials to prove/disprove their efficacy. The evidence that targeting uNK or peripheral blood NK cells assists women with recurrent pregnancy failure is lacking. Healthcare professionals and patients should very carefully evaluate the practice of immunomodulation to enhance pregnancy outcome. A discussion on how to move towards stricter regulation of immunotherapy in non-hospital settings is now needed because it is clear that the potential risks and costs of these therapies outweigh any benefits. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. KEYWORDS: assisted reproduction; embryo; immunotherapy; miscarriage; uterine natural killer cells

PMID 25954039

Uterine NK cells: active regulators at the maternal-fetal interface

J Clin Invest. 2014 May;124(5):1872-9. doi: 10.1172/JCI68107. Epub 2014 May 1.

Moffett A, Colucci F.


Pregnancy presents an immunological conundrum because two genetically different individuals coexist. The maternal lymphocytes at the uterine maternal-fetal interface that can recognize mismatched placental cells are T cells and abundant distinctive uterine NK (uNK) cells. Multiple mechanisms exist that avoid damaging T cell responses to the fetus, whereas activation of uNK cells is probably physiological. Indeed, genetic epidemiological data suggest that the variability of NK cell receptors and their MHC ligands define pregnancy success; however, exactly how uNK cells function in normal and pathological pregnancy is still unclear, and any therapies aimed at suppressing NK cells must be viewed with caution. Allorecognition of fetal placental cells by uNK cells is emerging as the key maternal-fetal immune mechanism that regulates placentation.

PMID 24789879

Links: Ectopic Implantation | Ectopic Implantation Research | Maternal Immune | Editing Basics