Reproductive Immunology

Before and during implantation, immune cells participate in three essential processes: uterine vascular and tissue remodelling, regulating the inflammatory/anti-inflammatory balance, and foetal tolerance. Dysregulation in the adaptive changes of the endometrium’s immune system can cause pregnancy complications such as implantation failures or recurrent spontaneous abortion. In turn, incorrect immunosuppressive treatment can increase foetal risk and pregnant patients’ susceptibility to infection.

The Im Map® test identifies the different immune subpopulations in the endometrium so that alterations in their levels can be detected, offering patients a specific immunotherapy treatment that restores the immune balance in the endometrium and increases foetal tolerance, implantation, and the probability of successful pregnancy.

Tissue and vascular remodelling

Immune cells present in the endometrium are essential for the correct regulation of trophoblastic invasion, tissue remodelling, angiogenesis, and embryo growth. These processes are carried out through the specific secretion of factors stimulating fetal growth and tissue and vascular remodelling.

It has been shown that an alteration in the levels and activation of the immune subpopulations is related to an alteration in vascular and tissue remodelling causing implantation failure, spontaneous miscarriages, as well as pre-eclampsia, premature births, and fetal growth restriction^1,2 .

Pro-inflammatory/anti-inflammatory balance

Immune cells secrete small proteins called cytokines that regulate the inflammatory state of the endometrium. These can be categorised into pro-inflammatory cytokines that act as active agents in the induction of the immune response, and anti-inflammatory cytokines that regulate this response. The synthesis of both cytokines allows for the establishment of the pro-inflammatory/anti-inflammatory balance present in the endometrium during the implantation window.

The study of the pro-inflammatory/anti-inflammatory balance is essential, as, for successful implantation, the maternal endometrium must exhibit a specific inflammatory state that promotes this process. Indeed, deregulation of the pro-inflammatory/anti-inflammatory balance has been linked to pregnancy loss, preterm birth, or preeclampsia^3. Additionally, other studies have shown that women with recurrent miscarriages have increased levels of pro-inflammatory cytokine-producing cells compared to women who have successful pregnancies^4,5,6.

Foetal tolerance

The embryo expresses paternal components that can be recognised by the maternal immune system and that may lead to the rejection of the embryo during pregnancy. To ensure reproductive success, the endometrial maternal-foetal interface exhibits a distinctive immune profile that promotes immunosuppression and ensures foetal tolerance and survival 7.

Several studies have shown alterations in the immune subpopulations that play a role in regulating the immune response and, consequently, an alteration in tolerance, in patients who have experienced spontaneous miscarriages during the first trimester 8.

How do we perform the Im Map® tests?

ImMap® is carried out through an endometrial biopsy in the luteal phase for diagnosis.

The endometrial biopsy sample can be obtained concurrently with the biopsy for our endometrial receptivity analysis test, ER Map®, on LH+7 in a natural cycle, P+5.5 in a substituted cycle, and hCG+7 in a modified natural cycle.

The samples are analysed using multiparametric flow cytometry. Flow cytometry is a biophysical technology used to detect immunological markers and to conduct a count of cellular populations.

This technique allows for the simultaneous multiparametric analysis of the physical and chemical characteristics of millions of cells within minutes. In cases where abnormal levels of immune cells are detected, various immunotherapy options suitable for each patient may be offered.