Endo-Immune Test
Some reproductive failure are immunologically determined.
Overview about Endo-Immune Test
To analyses the immune competency of the endometrium, “Endo- Immune test” comprised of
immune cells and cytokines described as active participants (uNK cells, Plasma Cells, Th1,
Th17) in immunity-derived infertility. For implantation to occur, there must be a balance between
pro-inflammatory and anti-inflammatory cytokines. The endometrium with Immune dysfunction is
not ready for embryo attachment. The rejection of embryo occurs in such an environment. In
women with recurrent pregnancy losses (RPL) (multiple miscarriages), recurrent implantation
failure (RIF) and unexplained infertility, the immune balance is disturbed and leads to
implantation failure. “Endo-Immune Test” finds out whether the immune imbalance in the
endometrium is there or not, which hinders the implantation process. “Endo-Immune test” allows
the identification of implantation failure or recurrent miscarriage causes in the case where
embryonic factors have been previously ruled out / normal.
Pregnancy is a complex immunological
process for the mother. The maternal
immune system plays a critical role in
establishing, maintaining, and
completing a healthy pregnancy. Cells
and molecules of the maternal immune
system interact in such a way as to
prevent the rejection of the
semiallogenic fetus
and support its
growth and
development. Successful pregnancy is associated
with a balance between Th1 & Th2-type immunity
and Th17 & Treg cells. Th1-type immunity and Th17
responses are considered potentially dangerous
and detrimental for continuing pregnancy. The
increased number of uterine natural killer (uNK)
cells, imbalance of Th1, Th17 cytokines, and the
presence of plasma cells have been linked to
habitual spontaneous abortion, RPL, and
implantation failure. An Immune compromised
endometrium cannot carry potential implantation
and pregnancy to the term. The endometrium is
the maternal tissue that comes into direct contact
with the immunogenic embryo, so it is expected
that an immune dysregulation of the endometrium
may cause reproductive failure. A well-balanced
equilibrium of the innate and adaptive local
immune system is fundamental for successful
implantation and pregnancy.
To analyses the immune competency of the endometrium, we designed an "Endo- Immune test" comprised of
immune cells and cytokines described as active participants (uNK cells, Plasma Cells, Th1, Th17) in immunity-
derived infertility. "Endo- Immune test" allows the identification of implantation failure or recurrent
miscarriage causes in the case where embryonic factors have been previously ruled out / normal.
Indications
Women with a history of
- Recurrent Implantation Failure (RIF)
- Recurrent Pregnancy Loss (RPL)
- Miscarriage / abortion
- Endometrium > 7mm but failed ET.
- Endometriosis
- Irregular bleeding, pelvic pain, or dyspareunia
Pathophysiology
Uterine Natural killer (uNK) cells detect small cancerous cells and kill them before becoming tumors. If these cells are highly active, they may misinterpret the fetus as cancer and kill it. On the other hand, low activity of NK cells will lead to anomalies like infection and reduced angiogenesis. Hence, a moderate activity of NK cells is necessary to generate the balance required for successful implantation. The uNK cells, through the secretion of cytokines, also have extended mother self-tolerance to the fetus to avoid rejection.
Th1 pro-inflammatory cytokines affect trophoblast cell growth and function directly, or they may cause activation of macrophages which could attack the trophoblast. TNF-α is a Th1pro-inflammatory cytokine, if
produced excessively, can cause pathological changes and lead to tissue damage and chronic inflammation
through necrosis or apoptosis. Further, pregnancy destroying molecules (PDMs) or IL-17 (a Th17 pro-inflammatory cytokine) are involved in the pathogenesis of inflammation, autoimmune diseases, and
immunological rejection of non-self-tissue. An elevation in PDM results in the loss of self-tolerance of the fetus
via its detrimental effect on the quality and quantity of T regulatory cells resulting in fetal rejection. Therefore,
an imbalance between Th1:Th2 and Th17: Treg cells might lead to failure in implantation and other pregnancy problems.
Chronic endometritis (CE) or chronic inflammation of the endometrial lining induces high uterine innate and
adaptive immune cells at the fetal-maternal interface. Dysregulation of the uterine immune status due to CE
may affect maternofetal tolerance, alter the endometrial receptivity, and lead to recurrent reproductive
failure. CE is characterized by the infection-induced inflammation of the endometrium. Irregular bleeding,
pelvic pain, or dyspareunia can be symptoms of CE; however, in most cases, patients with a CE remain
asymptomatic. Chronic endometritis factor (CEF) or plasma cells are thought to cause CE that may lead to RIF, RM, and RPL. The reported prevalence of CE is 7%–56% in patients with RM, 10%–27% in RPL, and 7.7%–44% in RIF patients.
Treatment
Several local and systemic modifications have been suggested to protect the developing fetus from maternal immune system attack. The available immune therapies and antibiotic treatments can help to improve
reproductive outcomes, increasing the chance of embryo implantation.
The Endo-immune test-guided patient-specific treatment will enhance the chances of implantation more
effectively.
Mathodology
Biopsy of endometrial tissue @ P+6 – 8 LH + 7 - 9
Place tissue in the collection vials
Sample shipment @ room temperature
Analysis of molecular biomarkers
Result in 10 working days
Treatment Antibiotics / Immunotherapy
Reference
- Hirata, K., Kimura, F., Nakamura, A., Kitazawa, J., Morimune, A., Hanada, T., ... & Murakami, T. (2021). Histological diagnostic criterion for chronic endometritis based on the clinical outcome. BMC Women's Health, 21(1), 1-11.
- Kolanska, K., Bendifallah, S., Cohen, J., Placais, L., Selleret, L., Johanet, C., ... & Mekinian, A. (2021). Unexplained recurrent implantation failures: Predictive factors of pregnancy and therapeutic management from a French multicentre study. Journal of Reproductive Immunology, 145, 103313.
- Sehring, J., & Jeelani, R. (2021). Human implantation: The complex interplay between endometrial receptivity, inflammation, and the microbiome. Placenta.
- Vomstein, K., Feil, K., Strobel, L., Aulitzky, A., Hofer-Tollinger, S., Kuon, R. J., & Toth, B. (2021). Immunological Risk Factors in Recurrent Pregnancy Loss: Guidelines Versus Current State of the Art. Journal of Clinical Medicine, 10(4), 869.
- Li, Y., Yu, S., Huang, C., Lian, R., Chen, C., Liu, S., ... & Zeng, Y. (2020). Evaluation of peripheral and uterine immune status of chronic endometritis in patients with recurrent reproductive failure. Fertility and sterility, 113(1), 187-196.
- Freitag, N., Pour, S. J., Fehm, T. N., Toth, B., Markert, U. R., Weber, M., ... & Bielfeld, A. P. (2020). Are uterine natural killer and plasma cells in infertility patients associated with endometriosis, repeated implantation failure, or recurrent pregnancy loss?. Archives of Gynecology and Obstetrics, 302(6), 1487-1494.
- Ticconi, C., Pietropolli, A., Di Simone, N., Piccione, E., & Fazleabas, A. (2019). Endometrial immune dysfunction in recurrent pregnancy loss. International journal of molecular sciences, 20(21), 5332.
- Teirilä, L., Heikkinen-Eloranta, J., Kotimaa, J., Meri, S., & Lokki, A. I. (2019, October). Regulation of the complement system and immunological tolerance in pregnancy. In Seminars in immunology (Vol. 45, p. 101337). Academic Press.
- El Hachem, H., Crepaux, V., May-Panloup, P., Descamps, P., Legendre, G., & Bouet, P. E. (2017). Recurrent pregnancy loss: current perspectives. International journal of women's health, 9, 331.
- British society for Immunology. Reproductive immunology: immunology of pregnancy
