Endometriosis and Recurrent Pregnancy Loss
Maternal immunomodulation is an important step of early pregnancy. The immune system recognizes which cells belong to the mother, but occasionally targets the baby’s cells as foreign or different. During early pregnancy it is critical for the mother’s immune system to recognize and learn that the baby’s cells are not foreign cells and thus change and adjust the immune system. This learning process is called maternal immunomodulation. It requires the creation of pro-inflammatory cytokines during the implantation phase, and then a switch to anti-inflammatory cytokines.
The type of changes that occur in maternal immunomodulation are:
A shift from a pro-inflammatory to an anti-inflammatory state during implantation. This helps the mother's immune system accept the baby's cells and prevent rejection
A balance between pro-inflammatory and anti-inflammatory cytokines at different stages of pregnancy. This helps the mother's immune system fight infections and maintain a healthy environment for the baby.
A regulation of Toll-like receptor 4 (TLR4), a protein that recognizes bacteria and other foreign substances to prevent complications.
What do cytokines have to do with pregnancy loss and endometriosis?
The study by Vidali et al strengthened the known correlation between endometriosis and recurrent pregnancy loss. The cohort followed 29,563 women with endometriosis and 295,630 controls. The causes and consequences of both endometriosis and recurrent pregnancy loss (RPL) are both associated with immune dysregulation.
In order to have a successful implantation, a woman’s immune system has to have the perfect balance between pro-inflammatory cytokines (Th1 bias) followed by a swift anti-inflammatory state (Th2 profile). But recurrent pregnancy losses are associated with dysregulation in T cells and an imbalance in the response.
We know that chronic inflammation (in other words- endometriosis!) can negatively impact the expression of some of the cytokines. This is true with other auto-immune diseases too. In the case of pregnancy, chronic inflammation can affect a particular cytokine that affects implantation. It just doesn’t get made at the proper levels.
From a treatment perspective, there is limited evidence to suggest that surgery for endometriosis specifically prevents miscarriage. It’s important to remember that many people who suffer from RPL might not know they have endometriosis; but also many people who have successful pregnancies after losses might also be undiagnosed. Some immunological treatments might be effective, but because endometriosis is under established, more research is needed.
The study stated that there is minimal evidence to correlate endometriosis with recurrent second trimester losses nor stillbirth, which had been previously reported. But pregnancy loss, like infertility, is often kept silent among women. This is why advances in reproductive immunology require everyone to talk about their reproductive health.
Vidali A, Riccio LGC, Abrão MS, Endometriosis and recurrent pregnancy loss: Two manifestations of the same underlying dysfunction?, Fertility and Sterility (2023), doi: https:// doi.org/10.1016/j.fertnstert.2023.03.012.
