The immune system, as defined by the World Health Organisation, is the body’s natural ability to defend itself against pathogenic organisms (e.g. viruses or bacteria) and resist infection (1). It is in its weakest state that allergies, illness, fatigue and a long list of other symptoms that can occur when the immune system is not strong are rampant.
While an immune deficiency can affect many areas, it also leads to complications in reproductive health. Here, in commemoration of World Health Day, we look at how immune incompatibilities can seriously affect pregnancy and assisted reproduction.
Immunological incompatibility refers to the difference between the donor’s and recipient’s immune systems. In some cases, the recipient woman’s immune system may naturally mistake the sperm for foreign agents (2). This provokes a destructive reaction with the misleading aim of protection.
This adverse reaction may even attack the embryo in its early stages of life, resulting in high difficulty for implantation itself or, in the worst case, ending in gestational loss.
Why might the immune system reject pregnancy?
Sometimes, the maternal immune system does not recognise the arrival of the embryo, activating an inflammatory or cytotoxic response that causes damage to the correct implantation of the embryo, rejection of the pregnancy or failure of assisted reproduction treatments.
This natural reaction is due to the fact that the immune tolerance mechanisms recognise this “semi-allogenic graft” as dangerous for their own system.
Types of immunological incompatibility
There are different types of immunological incompatibility. These can be: sperm immunity, embryo rejection and alterations in NK cells (Natural Killers).
Sperm immunity
Sperm immunity occurs when the expectant mother’s immune system identifies sperm as a foreign agent, thereby generating anti-sperm antibodies (ASA) due to an allergic reaction to semen (3). These antibodies can affect sperm motility, survival and fertilisation ability, making natural conception difficult.
Embryo rejection:
It occurs when the mother’s immune system does not identify the embryo as her own. The response of the woman’s body is to cause implantation failure and/or repeated miscarriages in the first, second or even third trimester of pregnancy.
Antiphospholipid syndrome is particularly relevant here. This autoimmune disease causes all the complications mentioned above. In addition, it can also lead to a decrease in foetal growth and to the foetus being born prematurely with a low birth weight for its age. In other words, the foetus is born before 37 weeks (4):
Alterations in NK cells:
NK (natural killer) cells are a type of lymphocytes of the immune system that can cause recurrent miscarriages if they do not perform their function correctly. These alterations are due to a deficiency or excess of these cells (5).
It is in excess of these cells that there is a high risk of miscarriage. Although no real cure has yet been found, there are specific treatments to regulate and improve the number of natural killer cells.
How is an immune incompatibility diagnosed?
When a woman suffers repeated implantation failures or repeated miscarriages without apparent cause, diagnostic tests are sought. The purpose of these tests is to identify alterations in the immune system response, which may be preventing the embryo from implanting properly or the pregnancy from progressing.
What are the immunological tests in assisted reproduction?
The main immunological tests in the field of assisted reproduction are:
- H4 NK cell studies. These are used to measure the percentage of activation of these natural killer cells in peripheral blood or in the endometrium (6).
- Cytokine profile. Measure blood levels of proinflammatory and anti-inflammatory cytokines.
- Detection of FAS syndrome. They measure the presence of antibodies such as anticardiolipin, anti-β2-glycoprotein I and lupus anticoagulant (7).
- HLA (Human Leukocyte Antigen) study. They measure the degree of HLA compatibility between partners.
- Regulatory T-cell (Treg) study. These measure the levels and functionality of CD4+/CD25+ Treg cells. Treg cells are important because they promote the immune tolerance necessary for maternal acceptance of the embryo.
*Although not all assisted reproduction clinics perform these tests, Ovoclinic has the necessary tools and specialists to carry them out successfully.
What do treatments for immunological incompatibility in assisted reproduction include?
A good and accurate diagnosis by the specialist will indicate which treatment should be applied according to the results of the study carried out previously. These treatments may include the following:
- Immunotherapy: Use of corticosteroids to suppress overactive immune responses.
- Heparin and aspirin: Administered to improve uterine circulation and reduce the risk of thrombosis in cases of PBS.
- Intravenous immunoglobulins (IVIG): Therapy to modulate the immune response and increase implantation rates in the presence of elevated NK cells.
- Sperm washings and assisted reproductive techniques: Procedures such as intrauterine insemination (IUI) or in vitro fertilisation (IVF) may be effective in cases of ASA.
- Egg or sperm donation: Considered when there are significant genetic incompatibilities between the couple.
Several studies indicate that the combination of immunological therapies and assisted reproductive techniques improves pregnancy rates in couples with immunological incompatibilities. If after reading this you have identified a condition, do not hesitate to contact the professionals at Ovoclinic. They will guide you to a successful pregnancy with full guarantees.
Bibliography
- World Health Organization. (2021). Update 49: Immune response to SARS-CoV- https://www.who.int/docs/default-source/coronaviruse/risk-comms-updates/update49-immune-response-es.pdf?sfvrsn=7dfe5bb8_33
- Cumlaude Lab. (n.d.). Immune system and fertility: a close relationship. https://www.cumlaudelab.com/sistema-inmune-y-fertilidad-una-relacion-estrecha/
- WebMD. (n.d.). Anti-sperm antibodies and fertility. https://www-webmd-com.translate.goog/infertility-and-reproduction/fertility-antisperm-antibodies/?_x_tr_sl=en&_x_tr_tl=es&_x_tr_hl=es&_x_tr_pto=sge
- Inforeuma. (n.d.). Antiphospholipid syndrome (APS). https://inforeuma.com/enfermedades-reumaticas/sindrome-antifosfolipido-saf/
- Nicklaus Children’s Hospital. (n.d.). NK cell disorders. https://www.nicklauschildrens.org/condiciones/trastornos-de-las-celulas-nk
- Robertson, S.A. et al. (2018). The role of uterine natural killer cells in early pregnancy success. Human Reproduction Update, 24(5), 535-548.
- Mekinian, A. et al. (2017). Recommendations for the management of obstetric antiphospholipid syndrome. Autoimmunity Reviews, 16(9), 1040-1048.
DOI: 10.1016/j.autrev.2017.07.003
