In part 1 of this article, we discussed the immunological causes behind recurrent miscarriage. As this is a rather in-depth subject, here in part 2 we will be diving into the rest of them, as well as other treatments offered to those suffering from them.

Intralipid emulsions

Intralipid emulsions are a cheaper, synthetic alternative to IVIG infusions, and were initially suggested as a substitute immune therapy for women with recurrent miscarriage and failed IVF treatment cycles. Commonly referred to as ‘intravenous mayonnaise’ this intravenous nutrition contains lipids or fats in the form of a thick liquid emulsion. It has been said to decrease NK cell activation. However, there are side effects to this treatment such as enlargement of the liver and spleen, and there has also never been any scientific evidence that it improves pregnancy outcomes.

Corticosteroids

Corticosteroids are a synthetic type of hormonal or steroid drug that can suppress the body’s immune responses when taken at high doses. Over recent years, these types of steroids have become widespread in miscarriage and fertility clinics. However, it is important to note that there has never actually been any proven advantage of steroid use for women with a history of recurrent miscarriage, and they can trigger significant side effects such as diabetes, high blood pressure, and premature birth.

Anti-tumour necrosis factor blocking drugs

Tumour Necrosis Factor (TNF) is produced by the cells of the body’s immune systems such as NK cells. The TNF works by promoting an inflammatory response, allowing the immune system to attack the source of infection. TNF-alpha blocking agents are used to stop the inflammatory response - in turn reducing the effectiveness of the response altogether. Anti-TNF drugs have been used as an additional treatment for women with recurrent miscarriages, as they have NK cells in their uterine lining which can damage the embryo’s chance of implanting successfully by secreting TNF. However, many have warned that the TNF damages the DNA in the embryo, therefore resulting in it being unable to grow, divide and implant in the uterus.

Granulocyte colony-stimulating factor (GCSF)

Granulocyte colony-stimulating factor (GCSF) is another immunomodulatory option which has the potential to treat miscarriages and the repeated failure of an embryo being able to implant in the uterus. GCSF can be found in reproductive organs such as ovarian follicles and the endometrium. It works by stimulating neutrophilic Granulocyte (white blood cell) proliferation and differentiation. Although there are currently ongoing randomised control trials that are exploring the possibility that a synthetic form of GCSF may help women with unexplained recurrent miscarriages, the results of this are still awaited.

Decidual immunity and uterine NK cells

In more recent years, the medical field has discovered that the successful implantation of an embryo into the uterus requires the presence of specialised immune cells in the decidua. These cells have more recently become known as uterine natural killer cells (uNK cells). These NK cells ensure that the embryo is able to burrow into the decidual lining and gain a firm foothold during implantation. It has been said that high NK cell levels appear more in women with a history of recurrent miscarriage. However, other studies have indicated the opposite - that they are not harmful at all and play a crucial role in the development of pregnancy.

Inherited immune deficiencies

There has been evidence to suggest that inherited immune deficiencies may be at the root of some recurrent miscarriages. For example, it has been found that some couples who experience miscarriage have low levels of MBP in their blood, suggesting that these couples could potentially pass the MBP mutation to their growing fetus - causing an infection that could be overwhelming and fatal.

Autoimmune miscarriage

Autoimmunity describes immune reactions in the body caused by the production of antibodies which act against a human's own tissues. These are called ‘anti-self’ antibodies. These antibodies are in general, destructive, and can be passed from generation to generation. Women with autoimmune disorders such as lupus, for example, can experience various complications during pregnancy, and can be susceptible to a higher rate of miscarriage.

Chronic history Intervillositis (CHI)

This relatively rare autoimmune condition that can cause miscarriage is characterised by a huge infiltration of the placental intervillous space by massive numbers of white cells - lymphocytes, histiocytes, and monocytes. Experts have said that the presence of these cells indicates that an immune mechanism is responsible for any placental damage that can occur. Clinicians have agreed that offering the woman experiencing CHI treatment with a combination of aspirin and heparin during her next pregnancy is important. In some cases, steroids have also been suggested to be beneficial.

Blood group incompatibilities

Miscarriage can also be caused by blood group incompatibilities between mother and father, even if it is a very rare occurrence. An example of this is severe rhesus disease, which can happen when a thesis D negative mother and thesis D positive father have a thesis D positive fetus. If blood cells from the baby end up entering the mother’s bloodstream, she produces antibodies which travel back across the placenta, destroying the baby’s blood cells. This problem usually affects later pregnancies.

Anti-sperm antibodies

Some studies have suggested that men and women who develop antibodies to sperm in their blood have an increased risk of miscarriage. However, these reports have been based on small numbers of patients. These patients were all undergoing infertility investigations and treatments, and the apparent increase in the miscarriage rate is probably due to their infertility problems instead.

What are the immunological causes of recurrent miscarriage? (Part 2)

Unii tackles an upsetting subject for any parent-to-be.