The Immune System and Fertility

Because the immune system’s primary role is to defend against foreign cells, it must adapt to allow sperm and embryos to survive.

Background

The immune system is a complex network of cells, tissues, and organs that protects the body by distinguishing between what belongs (“self”) and what doesn’t (“foreign”). To maintain health, the system manages a delicate balance between immune surveillance (pro-inflammatory) and immune tolerance (anti-inflammatory). Depending on what it encounters, the immune system constantly shifts between these states to promote healing and prevent long-term damage.

Inflammation

Inflammation is part of the immune system’s surveillance and defense response, increasing its readiness to identify and respond to potential threats. In a heightened, pro-inflammatory state, this can make it more difficult for the immune system to tolerate an embryo. Even in the case of acute inflammation, where the inflammation is resolved once a threat is eliminated, the immune system is in a surveillance state and it can complicate fertility. In contrast, chronic inflammation (see list below) represents a state in which the immune system remains continuously in a pro-inflammatory state.  As highlighted on a study published in 2025, titled “The effect of chronic inflammation on female fertility”, chronic inflammation strongly affects female fertility at many levels and through several possible mechanisms.

“It is clear from existing data that chronic inflammation strongly affects female fertility at many levels and through several possible mechanisms.”

Chronic inflammation examples

• Autoimmune Disorders: Rheumatoid arthritis, lupus (systemic lupus erythematosus), multiple sclerosis, and Hashimoto’s thyroiditis.

• Cardiovascular Diseases: Atherosclerosis (plaque buildup in arteries), high blood pressure, and heart disease.

• Gastrointestinal Conditions: Inflammatory bowel disease (IBD), specifically Crohn's disease and ulcerative colitis.

• Metabolic Disorders: Type II diabetes and obesity-related metabolic dysfunction.

• Respiratory Diseases: Asthma and chronic obstructive pulmonary disease (COPD).

• Skin Disorders: Psoriasis and eczema.

• Neurodegenerative Diseases: Alzheimer’s disease and Parkinson’s.

• Other Conditions: Cancer, chronic kidney disease, and persistent infections

The important role of Uterine Natural Killer (uNK) cells

Uterine natural killer (uNK) cells are a specialized group of immune cells that increase significantly during the “window of implantation” and early pregnancy. They are the most abundant immune cells in the endometrium at this time, making up approximately 70–90% of decidual leukocytes.

Unlike other natural killer cells, uNK cells are not primarily designed to destroy cells. Instead, they support implantation by interacting with trophoblast cells (the outer layer of the blastocyst), promoting immune tolerance, placental development, and healthy fetal growth. When uNK cells are too few—or not functioning properly—implantation failure and recurrent pregnancy loss may occur.

However, balance is key. Inflammatory states, especially when chronic, can increase both the number and activity of uNK cells. This may lead to overactivation, shifting them toward a more cytotoxic (cell-damaging) role. Excessive activation has been associated with impaired placental development and increased risk of miscarriage.

Research supports this dual role. A 2025 study published in Cell Proliferation found that abnormal activation or dysfunction of uNK cells may contribute to placental insufficiency and immune-mediated pregnancy failure.

Additional evidence comes from a study in the Turkish Journal of Obstetrics and Gynecology, which compared women with recurrent implantation failure to those with successful pregnancies. The study found that lower uNK cell levels were associated with implantation failure, highlighting their importance in normal pregnancy progression.

Progesterone and uNK cells

Progesterone is the primary driver of uNK cell proliferation and maturation. Ensuring adequate progesterone levels is crucial for creating a fertile ground where uNK cells grow. In addition, progesterone promotes immune tolerance by inducing the production of Progesterone-Induced Blocking Factor (PIBF), which inhibits the cytotoxic activity of NK cells, preventing them from attacking the fetus.

Assessing inflammation

Because uterine natural killer (uNK) cells do not circulate in the bloodstream like peripheral NK cells, they cannot be measured with a standard blood test. Assessment typically requires an endometrial (uterine) biopsy. In contrast, systemic inflammation can be evaluated through blood markers such as C-reactive protein (CRP). Elevated CRP levels have been associated with reduced fertility, lower clinical pregnancy rates, and decreased live birth rates. A more sensitive measure, high-sensitivity CRP (hs-CRP), has also been linked to implantation failure, increased risk of pregnancy loss, and longer follicular phases—particularly when levels exceed 3 mg/L.

Acupuncture and immunity

Acupuncture is one of the most widely used forms of complementary and alternative medicine worldwide. With roots in China, it has been practiced for over 3,000 years and is supported by a growing body of clinical and theoretical research. Emerging evidence suggests that acupuncture may help regulate immune function and support the body’s response to certain pathological conditions.

A review published in 2023 by Frontiers in Immunology, incorporated and covered the immunomodulatory function and mechanism of acupuncture practice. The review, which makes reference to 124 papers, reviews and studies, concluded that in addition to dramatically regulating immune cells and molecules, including innate and adaptive immune responses, acupuncture can stimulate and support immunological responses that are anti-inflammatory and anti-infectious.

A literature review published by Frontiers in 2025, titled “Acupuncture as an adjunct therapy for enhancing endometrial receptivity in female infertility” reviewed multiple studies where acupuncture was used to improve endometrial receptivity in female infertility. Based on the conclusion of each of the studies, the review concluded that:

“These findings suggest that acupuncture could be a viable complementary therapy for improving pregnancy outcomes in women with compromised endometrial receptivity.”

Conclusion

The immune system’s ability to distinguish between foreign and self is critical for reproductive success. Immune tolerance in fertility involves the acceptance of a genetically different embryo by the mother’s immune system. Emerging research suggests that acupuncture may help regulate immune function. Because inflammation reflects a heightened immune surveillance state, excessive or persistent inflammation—whether from autoimmune conditions, diet, or injury—may reduce the immune system’s ability to tolerate an embryo.