Natural killer cells, miscarriage, and infertility

Introduction

Natural killer (NK) cells have an important role in the early responses to viral infections and have also been linked with failure of pregnancy. Recent reports in the media and the internet have exposed women to a baffling array of conflicting information about tests for NK cells and “cures” for infertility and miscarriage. These are based on the premise that malfunction of NK cells causes these conditions. Increasingly, clinics are offering blood tests to measure the number and activity of circulating NK cells. As a result of these investigations, many women are offered treatments such as steroids, intravenous immunoglobulins, and tumour necrosis factor α blocking agents. The scientific rationale for these tests and treatments, however, is not supported by our current knowledge of the function of uterine NK cells.

Uterine natural killer cells

Natural killer cells (identified by the surface marker CD56) are the dominant type of maternal immune cell populating the uterine mucosa during formation of the placenta.1 These uterine NK cells are also present in the endometrium of non-pregnant women, when they are under the control of ovarian hormones, cycling together with the glandular and stromal compartments. After ovulation, uterine NK cells proliferate vigorously so that by the late secretory phase they account for at least 30% of the endometrial stroma.

Uterine NK cells persist in the early decidua and accumulate in large numbers at the implantation site. Here they are in close contact with the invading placental trophoblast cells, which transform the spiral arteries into high conductance vessels. This transformation is essential to ensure a normal blood supply to the fetus and placenta throughout pregnancy. Of central importance is that uterine NK cells are phenotypically and functionally different …