Immune and anti-coagulant therapy: does it have a role in fertility treatment?

Fertility clinics around the world may offer immune and anti-coagulant therapy, claiming it will increase the success rates of in vitro fertilisation (IVF) and that it may reduce the risk of miscarriage in women who have lost several pregnancies. The evidence that different types of immune and anti-coagulant therapies work varies from reasonable to non-existent. If one of these treatments is recommended to you by a fertility clinic abroad or at home, you need to find out exactly why, ask about the risks and decide whether you want to go ahead.

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Why might immune and anti-coagulant therapy be recommended?

Some fertility experts have proposed that IVF may fail or that women may have repeated miscarriages because their body produces antibodies to their fetus, or because their blood clots too easily, causing the placenta to fail. Some of these theories have some merit, but others are not well accepted and it is important to look at the evidence when considering immune and anti-coagulant therapy during fertility treatment or during pregnancy.

Anti-coagulant therapy is necessary in women with thrombophilia, a genetic disease that causes their blood to clot much more easily than normal. Women affected need life-long treatment with anti-coagulants and are able to become pregnant naturally, in which case their treatment continues. However, if they are taking the standard treatment of warfarin they must switch to low molecular weight heparin as this cannot cross the placenta and harm the growing fetus.

Some women who have repeated miscarriages might do so because of an undiagnosed thrombophilia. Starting anti-coagulant therapy is therefore then important for their general health, and may help them to carry a pregnancy to term, whether they conceive naturally or through a fertility treatment such as IVF.

Immune and anti-coagulant therapy and anti-phospholipid antibody syndrome (APS)

Another group of women who may need anti-coagulant therapy throughout life, as well as in pregnancy or during IVF treatment, are those with anti-phospholipid antibody syndrome (APS). This can also be called Hughes syndrome, APLS, APLA or simply sticky blood syndrome.

APS is an autoimmune condition that can occur in people with systemic lupus erythematosus, other known autoimmune diseases, or by itself. The body produces antibodies to phospholipids, the fatty molecules that make up the membranes of normal cells. The result is that the blood tends to clot a lot more easily, as it does in someone with thrombophilia. So, although the cause of the blood clotting is different in someone with APS, the anti-coagulant therapy necessary will be the same.

Around 15 % of women who have repeated miscarriages are found to have APS, and starting them on anti-coagulant therapy may make it possible for them to carry a baby for longer.

Could anti-coagulant therapy help every woman having IVF?

There is no evidence that the vast majority of women undergoing IVF, or trying to get pregnant naturally, can benefit from having anti-coagulant therapy, and taking any drugs of this type that cross the placenta could be dangerous for the growing baby. If you do not have an established blood clotting problem, be very wary of a fertility clinic that offers anti-coagulant therapy as a ‘booster’ to IVF success rates, even if it is only aspirin.

Immune therapy and fertility treatments: what are the theories?

Some fertility clinics propose that IVF will be more successful if the woman’s body is prevented from rejecting the embryo and later the fetus. They suggest that some women produce natural killer cells in the uterus, which prevent implantation and pregnancy, or that cause miscarriage.

There is very little evidence that this happens and the suggestion that you should have immune therapy during IVF treatment needs to be considered very cautiously. Natural killer cells do occur in the uterus but they may be necessary for the normal implantation and development process. This involves cell death as well as cell division.

Expert reviews have also questioned the relationship between the level of natural killer cells in the mother’s blood and the need for immune therapy. Natural killer cells do not cross the placenta.

The dangers of immune therapy in pregnancy

Many fertility experts are also concerned because of the types of immune therapies that are suggested to help boost IVF success rates. These include:

  • Steroids given at high doses: steroids are given by injection to people with autoimmune diseases such as rheumatoid arthritis, but doctors recommend that pregnant women stop their therapy because of the risk of harm to the baby, particularly during the first three months.
  • Intravenous treatment with immunoglobulin: this is made from antibodies collected from donated blood. Also used in autoimmune disease therapy, there is no evidence that this can help increase the chances of a successful pregnancy whether due to IVF or natural conception.
  • Drugs that block tumour necrosis factor alpha: this form of immune therapy is used in many autoimmune diseases, such as severe rheumatoid arthritis, but only when other treatments have failed. The effects of these drugs on an unborn baby are not clearly understood, but their use in pregnancy is not recommended.

The Human Fertilisation and Embryology Authority in the UK has collected the published evidence and notes that steroids, intravenous immunoglobulin and agents that block tumour necrosis factor alpha “are not licensed for use in reproductive medicine”.

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