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What is Reproductive Immunology?


Have you heard the term reproductive immunology? It’s an intersection of reproductive health and immunology – a field of research full of unanswered questions. Although doctors disagree over the mechanisms and importance of reproductive immunology, it’s clear that the mom’s immune system has an crucial role in conception, as well as the maintenance of a healthy pregnancy. For some women, reproductive immunology is key to their success on the TTC journey. Let’s take a look at this fascinating field.


Immune system basics

A capable defender of our bodies, the immune system is a network of organs like spleen and bone marrow; various kinds of white blood cells like T cells, macrophages and natural killer cells; antibodies and chemicals. 

A healthy immune system can identify the organisms and substances that are foreign to your body, like a virus, fungus or bacteria. Once it picks up an invader, the immune system activates an elaborate defense system to attack, kill and remove the invading pathogens. Many symptoms of infections, such as inflammation, fever or swollen lymph nodes are signs that your immune system is working hard to fight off the infection.


What is reproductive immunology?

Reproductive immunology is a field of medicine that studies the role of the immune system within the reproductive health context. It goes beyond extending the immunological protection to the baby in utero, though that’s also quite important, as the baby doesn’t develop its own full immune system until 2-3 months after birth. For a pregnancy to happen and progress, the mom’s reproductive system and immune system must work together.


Mom's immune system during pregnancy

The central tenet of reproductive immunology is this: For a successful pregnancy, the mom’s immune system has to develop tolerance toward the baby. Why? It’s because the developing baby is only 50% mom, genetically speaking. The other half of the baby’s genetic material comes from the dad. In other words, the fetus developing in the uterus is foreign to the mom’s immune system. 

In every situation other than a pregnancy, the mom’s immune system would recognize the fetus as a foreign invader, just like a virus or bacteria. To defend the mom’s body from this external threat, her immune system would attack it. In a pregnancy, however, something amazing happens: The maternal immune system changes its response pattern to tolerate and even protect the baby.



How does the maternal immune system tolerate the fetus?

Scientists know that multiple factors and pathways are involved in this crucial immunological change. For example, estrogen and progesterone are both up-regulated during pregnancy. Both of these reproductive hormones have a role in modulating the mom’s immune response.

Placenta – the “interface” between the mom and the baby – also plays an important role in protecting the baby from the potential attack by the mom’s immune system. Especially in the early pregnancy, a type of immune cells called uterine natural killer cells (uNK cells) are one of the most abundant immune cells present. 

Like other NK cells, uNK cells are cytotoxic toward foreign invaders. However, in a healthy pregnancy, the number and types of receptors on the uNK cells change so that they don’t recognize the fetus as “foreign” and its cytotoxic functions don’t target the fetus. Uterine NK cells may even secrete a type of growth factor that acts as an immunosuppressant.

Some studies also suggest that even semen plays a role. For example, semen contains signaling agents that interact with the female reproductive tract to prepare the immune system for possible implantation of the embryo. This may explain why couples who have sex during their IVF cycles have a better chance of a pregnancy.


Reproductive immunology: What happens when it goes wrong

When this process malfunctions, the mom’s immune system can make it difficult for an embryo to implant in the uterus. Even when the embryo manages to implant, a failure to develop tolerance can lead to a miscarriage, which can also be recurring. Some doctors suspect immune issues when couples can’t get pregnant without a clear cause.

If you’ve experienced any of these conditions without a clear explanation (like a genetic abnormality of the embryo), it may be worth discussing reproductive immunology with your doctor. Women who have overactive immune system in general – like those with severe allergies or autoimmune conditions – may also want to watch out for problems with immunological tolerance around pregnancy.

If this rings a bell, seek out a doctor who specializes in reproductive immunology - or a reproductive endocrinologist (fertility doctor) with experience in this field. Not all doctors are up to date in reproductive immunology, and some women report being dismissed or not taken seriously by their doctors. Please reach out if we can answer any questions - we are with you.




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