Immunological Factors and Infertility

Currently, with few exceptions, practitioners of assisted reproduction tend to attribute “unexplained” and/or repeated IVF failure(s), almost exclusively to poor embryo quality, advocating adjusted protocols for ovarian stimulation and/or gamete and embryo preparation as a potential remedy. The idea that, having failed IVF, all it takes to ultimately succeed is to keep trying over and over using the same recipe is overly simplistic. There are numerous non-embryologic factors that can be responsible for failed IVF. This section addresses immunologic factors that cause implantation failure.

There are two types of immunologic reactions or immune factors involved in conception and infertility:

Autoimmune disorders are more common, implicated in >90% of immune-related infertility. Specifically, it means that woman’s immune cells are forming antibodies – small proteins that target and attach to cells and identify them for destruction – to tissue that is normal and part of their own body. This is an abnormal reaction that is associated with several non-pregnancy related diseases.

Alloimmune disorders, in contrast, involve the formation of antibodies against tissue associated with the male partner (e.g. paternal sperm proteins). Alloimmune problems are associated with less than 10% of implantation failure or recurrent pregnancy loss.

In order to understand how the immune system can cause infertility or recurrent pregnancy loss, let’s review what happens around the time of fertilization:

Implantation begins six or seven days after fertilization of the egg. At this time, specialized cells from the embryo (i.e. trophoblast), that later become the placenta, begin to create connections with the endometrial lining; encouraging growth up and around the developing embryo. The process is as much overgrowth of the embryo as it is invasion of the endometrium. At the site where the fetal and maternal tissue meet, the maternal immune cells in the lining, become involved in a “cross talk” with one another through mutual exchange of hormone-like substances called cytokines.

Because of this complex immunologic interplay, the uterus is able to foster the embryo’s successful growth without allowing bacteria and other abnormal cells to have a free pass. In other words, the immune cells aren’t shut down, they agree to host the embryo when all goes right. Thus the trophoblast establishes the very foundation for the nutritional, hormonal, and respiratory interchange between mother and baby. In this manner, the interactive process of implantation is not only central to survival in early pregnancy but also to the health of the baby after birth.

Problems occur when the maternal immune cells don’t cooperate. Typically when this occurs, it will lead to implantation failure or pregnancy loss thereafter. The risk factors that identify women most likely to have an immunologic fertility factor include:

  1. Family or personal history of autoimmune disease such as lupus erythematosis, hypothyroidism (Hashimoto’s disease), rheumatoid arthritis, etc.
  2. Unexplained or recurrent IVF failures
  3. Endometriosis
  4. Unexplained infertility
  5. Recurrent miscarriages