Adenomyosis and infertility: Does immunology mapping help?

"Targeted immunotherapy" may be possible in adenomyosis-related infertility

Key Points

Highlights:

• The concept of “pregnancy as an immunity-related process” was put forward in 1950’ies. 
• Now, it has been realized that the immune system interacts with other mechanisms in adenomyosis-related fertility problems. 

Importance: 

• Local immune profiling, i.e. endometrial tissue analysis, of patients with adenomyosis-related pregnancy issues, may help in the clinical management yielding positive outcomes.

Outline:

• Following the briefing on the immunologic pathogenetic background of endometriosis and adenomyosis, Professor Küpfer presents their management methodology of infertility problems in adenomyosis patients following mid-luteal endometrial biopsy analysis, i.e. “immune mapping”.
• The immune system interactions with other mechanisms in adenomyosis-related fertility problems were described. 
• Different types of NK cells, which are a subset of lymphocytes, differ in their toxicity (80% of uterine NK cells have low toxicity, and high cytokine production, whereas peripheral NK cells yield high toxicity, and low cytokine production), and elevation of both cell types result in abortions, hypertension, preeclampsia besides fetal growth restriction.

Lay Summary

Professor Dr. Wolfgang Küpker (MD, PhD), Medical Director and CEO of IVF Baden Baden at the University of Schleswig Holstein in Lübeck delivered a conference at the  Annual International Medical Conference of the Endometriosis Foundation of America held in New York on April 1-2, 2023.

Adenomyosis was first described by Pathologist Rokitansky in the 19th century, nowadays it also has clinical implications in regard to pregnancy issues. It is now well known that endometriosis and adenomyosis both have activating mutations of KRAS and epigenetic abnormalities in stromal cells resulting in abnormal estrogen activation with deficient progesterone expression.

Natural killer (NK) lymphocytes are a crucial component of the innate immune response and they can rapidly eliminate tumors or infected cells without targeting normal cells. 80% of uterine NK cells have low toxicity but high cytokine production, whereas peripheral NK cells yield high toxicity with low cytokine production. An increase in the number of both cell types results in abortions, hypertension, and preeclampsia besides fetal growth restriction. CD8 T lymphocytes participate in immune tolerance, whereas CD4 T lymphocytes are important in inflammatory balance.

Adenomyosis especially shows elevations of proinflammatory molecules IL6, IL-1 beta, IFN alpha, and tumor necrosis factor-alpha. The immunoreactivity of the Progesterone receptor isoform B (PR-B) and IkBa, which is a protein known to inhibit NF-kB, were significantly reduced in ectopic as well as eutopic endometrium of adenomyosis patients.

With the delineation of the immunologic pathogenetic background of endometriosis and adenomyosis, Professor Küpfer presents their management of infertility problems in adenomyosis patients following endometrial immune analysis, i.e. “mapping” in mid-luteal endometrial biopsies. This evaluation of endometrial mid-luteal biopsy involves an endometrial receptivity map via analysis of the most important 48 genes of receptivity and immune cell analysis by flow cytometry. Genotyping of gametocytes is also made.

These results yield clinical management protocols involving corticosteroids, tacrolimus, hydroxychloroquine,e and TNF-alpha blockers. This clinical approach has resulted in a 51% success rate of immune-dysregulated adenomyosis fertility problems, told Dr. Küpker.

Research Source: Adenomyosis and infertility: Does immunology mapping help? - Wolfgang Küpker, MD, PhD