Immunological therapies in infertility: the evidence
When implantation failures or miscarriages recur without an obvious cause, it is natural to search for an explanation — and the idea that “the immune system is to blame” is often proposed. Around this idea a host of tests and treatments has grown: measurements of “NK cells”, intralipid infusions, intravenous immunoglobulin, corticosteroids and others.
The question every couple should ask is whether these treatments actually increase the chance of having a baby. The answer from evidence-based medicine is, unfortunately, clearly negative for the vast majority of them.
Where does the idea of an “immune” cause come from?
Pregnancy is, from an immunological standpoint, a remarkable phenomenon: the mother’s body tolerates an embryo that also carries paternal genes. It is therefore reasonable to suppose that a “malfunction” of this tolerance could cause failures.
The hypothesis is attractive, but the step from theory to an effective treatment has not been achieved. Most of the “immune” tests on offer have not been shown to genuinely identify the women who would benefit.
Does testing “NK cells” make sense?
Testing natural killer (NK) cells in the blood or endometrium is often offered as an explanation for failures. However, the NK cells of the blood are different from those of the uterus, and the uterine cells have a normal, even beneficial role in establishing pregnancy.
There are no reliable, standardized normal ranges for these measurements, nor proof that a “high” value predicts outcome. NK-cell testing is therefore not recommended in clinical practice.
Do intralipids and immunoglobulin (IVIG) help?
Intralipids (a lipid emulsion given intravenously) and intravenous immunoglobulin (IVIG) are offered on the reasoning that they “regulate” the immune system. The ESHRE recommendations do not endorse them, as there are no reliable data that they increase the live-birth rate.
IVIG, moreover, is a blood product with possible side effects and high cost. Giving treatments without proven benefit burdens the couple financially and physically, with no corresponding gain.
What about corticosteroids or TNF inhibitors?
Corticosteroids (cortisone) and tumour-necrosis-factor inhibitors (TNF inhibitors), drugs that suppress the immune system, are sometimes used off-label in infertility. There is no evidence that they improve birth rates in women with recurrent failures or miscarriages.
On the contrary, these drugs are not harmless: they are associated with side effects for the mother and, some of them, with possible risks in pregnancy. The reasoning “it does no harm to try” does not apply here.
What about “lymphocyte immunotherapy”?
Lymphocyte immunotherapy (injecting the partner’s or a donor’s white blood cells into the woman) is an older approach that is not recommended. It has not been shown to increase births, while it carries risks of transmitting infections and of immune reactions.
In some countries this method has been banned or explicitly discouraged by regulators, precisely because of the absence of benefit and the presence of risks.
What is the right stance towards immunological therapies?
The right stance is not to reject all hope, but honesty: for the vast majority of “immune” tests and treatments there is no proof of benefit, while there are cost and possible risks. These interventions should be offered only within well-designed clinical trials.
For couples with recurrent failures, the more meaningful path is targeted testing for documented causes (such as antiphospholipid syndrome, anatomical or hormonal factors) and an individualized, realistic discussion of prognosis.
Summary
The idea that “the immune system is to blame” has spawned a host of tests and treatments — NK-cell testing, intralipids, IVIG, corticosteroids, TNF inhibitors, lymphocyte immunotherapy. For the vast majority there is no proof they increase births, while they carry cost and possible risks; ESHRE does not recommend them outside trials. The one documented immune cause that is genuinely treated is antiphospholipid syndrome. A couple’s best protection is honest, evidence-based information.
⚕ Medically reviewed by Prof. Stratis Kolibianakis · Thessaloniki Medical Association Reg. No. 16340
ARTICLE 27 · FERTILITY PRESERVATION
