Signs of Immunological Infertility

What are the signs of immunological infertility and immune-related pregnancy loss?

Diagnostic challenges of immune-related infertility

Please note that the question addressed here is _not _when to suspect an autoimmune problem or when to suspect any other immune system-related problems. This is on purpose because we, again and again, want to stress the point that it is not autoimmunity (or any other single factor) that, likely, causes implantation failure and miscarriages but inadequate development of tolerance, which subsequently is responsible for an allo-immune (not auto-immune) attack on the pregnancy.

Let us, therefore, answer the here posed question, which is actually a very difficult one to answer for most patients. There are many reasons for that: Since our understanding of how a woman’s immune system develops the necessary tolerance toward an implanting embryo and the growing pregnancy is at best incomplete, one currently still must accept that we can never be absolutely certain in diagnosing an immune problem as it relates to pregnancy. Specific tests to reach a diagnosis of immunological infertility do not yet exist, whether infertility is due to premature ovarian aging (POA), also called occult primary ovarian insufficiency (oPOI), an implantation problem, or repeat miscarriages. We know that all of these conditions (and some additional ones, like the recently reported hypo-androgenic-like PCOS), are all statistically associated with autoimmunity and, therefore, with a hyperactive immune system.

When to suspect immunological infertility

So, when then should one suspect that a female infertility patient may have a hyperactive immune system? The table summarizes the answers and demonstrates that a hyperactive female immune system should be suspected with patient or family history of autoimmunity, inflammation and/or hyper-allergenic responses and with specific patient diagnoses, such as unexplained infertility, POA/oPOI, POF/POI or H-PCOS-like phenotype. Though autoimmunity is, likely, the by far most frequent cause for a hyper-active immune system, it is not the only cause of immune system hyperactivity.

Signs of female hyperactive immune system resulting in fertility issues

At CHR, physicians stay vigilant for these signs of hyperactive immune system that may be resulting in immunological infertility or immune-related pregnancy loss

• History of autoimmune disease(s) in patient
• History of autoimmune findings on lab tests
• Family history of autoimmunity
• History of inflammatory condition(s) in patient
• History of positive inflammatory laboratory findings
• History of inflammatory diseases
• History of repeated pregnancy loss in patient or mother
• History of being hyper-allergenic (multiple severe allergies to foods, environmental factors, etc.)
• History of unexplained infertility in patient or mother
• Premature ovarian aging (POA)/occult primary ovarian insufficiency (oPOI) or premature ovarian failure (POF)/primary ovarian insufficiency (POI) in patient or mother
• Hypo-androgenic PCOS-like phenotype in patient or mother

This is why searching only for autoimmunity would be the wrong approach. It is the development of inadequate tolerance due to hyperactivity of the maternal immune system that is the cause of most immunological infertility because insufficient tolerance levels activate allogeneic immune responses against the pregnancy, at whatever stage it may be. And this is precisely why being on the lookout for signs of immune system hyperactivity is the first, crucial step in treating immunological infertility.

Norbert Gleicher, MD, FACOG, FACS

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, 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.

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