Women facing recurrent miscarriage and unknown causes for their infertility should not be given a certain test that some clinics routinely perform, say British doctors at the University of Cambridge.
But other experts disagree, arguing that the points made by the British experts "do not represent the whole truth."
NK Cells: To Test or Not to Test?
In an editorial published in an issue of the British Medical Journal this past November,1 Dr. Ashley Moffett in the department of Pathology at the university and her colleagues claim tests to measure levels of natural killer (NK) cells in the blood have "no rational scientific basis", and thus, should not be offered to women who are "particularly vulnerable to financial exploitation."
"Until more is known about their role in normal pregnancy, there is no evidence of any benefit in offering NK cell testing to women with recurrent miscarriage and infertility," Moffett and her associates wrote.
The Role of NK Cells
Natural killer cells make up part of our body's immune system, and they play an important role in early attacks against viruses and other disease-causing organisms. NK cells can also be found in high numbers in the uterine lining before pregnancy. After ovulation, these cells increase in number rapidly in the uterus. They also tend to accumulate at the site of implantation, the Cambridge scientists maintain. In some ways, the cells may play roles in the early stages of implantation, but that is still being investigated, they stress.
However, testing for blood concentrations of these cells is useless, they state, explaining that NK cells found in the blood are completely different in form and function from those residing in the uterus.
"Examination of peripheral blood NK cells will not tell us what is happening in the uterus. This is akin to estimating the number and activity of black cabs in Trafalgar Square by analyzing red mini-cabs circulating on the M25 [a highway around London]," the scientists maintain.
'Conflicting Information' in the Media
The scientists claim while an increasing number of fertility clinics are offering NK cell tests, they are also making treatments like steroids and IV immunoglobulins available for women with high blood levels of NK cells. But the levels of NK cells in the blood are based on any number of variables, including a person's age, race, gender and stress level, they say. The treatments prescribed, as well, are not licensed for this use in reproductive medicine, and may be "harmful to both mother and fetus."
"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," wrote Moffett and her colleagues. "These are based on the premise that malfunction of NK cells causes these conditions."
While the role of NK cells in the uterus is "intriguing", Moffett and her team are quick to add that "the scientific rationale for these tests and treatments is not supported by our current knowledge of the function of uterine NK cells."
The scientists pointed to recent guidelines by Britain's Royal College of Obstetricians and Gynecologists, and two randomized studies that concluded that there is no evidence to prove these therapies are beneficial.
Contrasting Views
Not all experts agree, however. Siobhan Quenby, MD, in the department of Obstetrics and Gynecology at Liverpool Women's Hospital in Liverpool, England has published several studies on the topic.2,3
In responding to the Moffett editorial, Quenby wrote: "I agree that there is a lack of understanding of the biological mechanisms that link endometrial NK cells and miscarriage, but there is an undoubted link, demonstrated in three separate studies, including an uncited report by one of the review authors.4 Women with high numbers of endometrial NK cells, pre-pregnancy, are more likely to have recurring miscarriage."
However, Quenby is quick, to add that "there is no basis for recommending steroid treatment for women with high concentrations of endometrial NK cells unless a randomized trial shows this to be effective and safe."
Meanwhile, while most of the points made by Moffett and her colleagues are true, they don't tell the entire truth, says Benjamin Rivnay, PhD, vice-president of Research and Development at Repromedix, a Massachusetts-based infertility testing laboratory that evaluates NK tests among others.
Rivnay says while it's true that NK cells are found in high numbers in the uterus, a completely separate subset of NK cells thought to play a role in miscarriage is not found in the uterus except in rare cases, and predominately makes its presence known in the bloodstream. It is this subset that is responsible for inflammation in the uterus, and thus threats an early pregnancy, he says, contrary to the argument of the British experts.
The argument that NK cells found in blood aren't the same as those that populate the endometrium "does not eliminate or reduce their harmful nature," Rivnay said.
Finally, Rivnay points out, infertility testing is not a perfect science, and will improve as more becomes known. "The utility of testing NK [cells], as well as the utility of the associated therapies will improve when we understand the mechanism in more detail."
Infertility, he says, "is a multifactorial pathology. Scientists' progress is a never-ending story, and if we wait until all is clear, we will never test and never treat. Infertility patients cannot wait for that. They should and ought to be given the benefit of less-than-perfect studies, if it's helpful even for 1 in ten patients."
1. Moffett A, Regan L, Braude P. Natural killer cells, miscarriage, and infertility. BMJ 2004 Nov 27;329(7477):1283-5.
2. Quenby S, Bates M, Doig T et al. Pre-implantation endometrial leukocytes in women with recurrent miscarriage. Hum Reprod 1999 Sep;14(9):2386-91.
3. Quenby S, Farquharson R, Young M, Vince G. Successful pregnancy outcome following 19 consecutive miscarriages: case report. Hum Reprod 2003 Dec;18(12):2562-4.
4. Clifford K, Flanagan AM, Regan L. Endometrial CD56+ natural killer cells in women with recurrent miscarriage: a histomorphometric study. Hum Reprod 1999 Nov;14(11):2727-30.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
