Immunological Infertility Tests and Diagnosis

Broadening the issue from simply “autoimmune infertility”

Once again, please note that the question we are asking is not how to test for an autoimmune problem in the fertility context. Though we are testing for certain autoimmune abnormalities, like anti-nuclear antibodies and anti-phospholipid antibodies, the purpose is not to find a specific “culprit” that causes miscarriages or prevents implantation. We are checking for autoimmune abnormalities because they, among many others, are indicators of a hyperactive immune system that is the root cause of implantation failures, recurrent miscarriages and other fertility problems.

Using markers broadly to detect immune system hyperactivity

In other words, it does not matter much which “markers” are used to detect hyperactivity of the female immune system (see the table that demonstrates the markers CHR routinely uses). Because each, by itself, demonstrates that the immune system is not “at peace” but is fighting against “something.” If any one or more markers are positive, the affected patient will, likely induce tolerance only inadequately. Because her immune system is already “fighting,” it will have a harder time to welcome an embryo/a pregnancy by inducing new, appropriately functioning tolerance pathways. The table lists the markers CHR uses. Efficiency of recognizing immune system hyperactivity would, however, likely be very similar if other markers were to be used, which could include peripheral NK cells, cytokines, etc.

Testing for Immunological Infertility: Immune System Check List Routinely Used at CHR

CHR has over the years experimented with a large number of potential markers for a hyperactive immune system and found those listed below the as most effective in identifying patients who might benefit from immune-suppressive treatments.

  • Autoimmunity
    • Antinuclear antibody (ANA) panel
    • Antiphospholipid antibody panel
    • Thyroid autoantibody panel
  • Inflammation
    • C-reactive protein (CRP)
    • Interleukin-6 (IL-6)
  • General immune/allergy markers
    • CBC with differential
    • Immunoglobulins IgM, IgG, IgE and IgA

How many markers are positive, of course, also matters. That, and how positive those markers are, will help determine the interpretation of findings and, ultimately, impact treatment decisions (see also how to treat immunologic infertility). An ANA titer of 1:40, for example, has different meaning than a titer of 1:680; extremely low IgA is more typically associated with autoimmunity than a mildly or even significantly elevated IgA. Of course, a patients with a clinical level of autoimmunity (i.e., a defined autoimmune disease) will be considered to have a more significant problem than a woman with only some marginal laboratory findings.

Tests for immunological infertility need expert interpretation

What we are presenting here is not a cookbook but medical practice, where good clinical judgment still counts for something and where conclusions that cannot be reached from what is known within the infertility field, are borrowed from related relevant practice areas like, for example, transplantation medicine. We hope, with this detailed explanation, to have offered a better understanding of how CHR differs in the reproductive immunology field in understanding the importance of the female immune system for normal fertility and how we translate this unique understanding into clinical practice. There are good reasons why CHR physicians have been a leader in clinical reproductive immunology since inception of the field.

This is a part of the May 2019 CHR VOICE.

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.