Immunological infertility
There are several treatment options available to patients with immunological infertility. Treatment options may include one of the following techniques: antibiotics, intrauterine insemination, drugs, IVF.
Antibiotics
Antibodies are sometimes produced by men with an infection of the prostate. Long term administration of antibiotics can sometimes result in a significant reduction of antibodies and some pregnancies have been achieved following treatment.
Intrauterine insemination
The intrauterine insemination technique involves washing the sperm free of antibodies and then introducing them into the uterus.
Drugs
Men may be given steroids to suppress the production of antisperm antibodies; they will need to take them for a few months and in high doses. There is a one in three chance of a natural conception. Most pregnancies occur 6-9 months after the treatment. The outcome of the treatment with steroids is unpredictable, as some men may not benefit from it. Treatment with steroids is associated with significant side effects.
IVF
The IVF technique involves washing the sperm and eggs prior to them mixed together.
Immunotherapy
- Antiphosphlipid antibodies syndrome or thrombophilia is treated with low molecular weight heparin (Heparin is anticoagulant) and low dose aspirin (Aspirin inhibits enzyme cyclo-oxygenase in the platelets, and prevent the production of thromboxane which cause constriction of the blood vessel and hence increase the blood supply). A meta analysis of 22 studies including 16,138 patient who took aspirin and 48,980 controls did not demonstrate an overall increase risk in congenital malformations. Heparin and aspirin start at the time of ovarian stimulation and continued through the pregnancy.
- HLA DK sharing is treated with lymphocyte immunization treatment (LIT) and Intravenous Immunoglobulin infusion (IVIG).
- Anti DNA and ANA etc is treated with steroids.
- Elevated NK cell activation markers and or high cytotoxicity levels. The rationale of the treatment is temporary suppression of NK cell activity. Treatment options include:
- High dose steroids (prednisolone) pills, it temporarily suppresses the immune system and inflammation. There are different regimens for administering steroids. For example, Prednisolone 25 mg daily after food in the morning starting on day 7 of gonadotrophin injection in a stimulated IVF cycle or day 10 in a frozen embryo transfer cycle and continued till 14 weeks if pregnant with a tailoring off the dose gradually over the two weeks. Like all other drugs there are side effects including high blood pressure, high blood sugar, increased susceptibility to infection etc. Very little of prednisolone cross the placenta. It is associated with an increase risk of cleft lip and palate in the new born (1: 150 compared to 1: 500 background risk).
- Intravenous Immunoglobulin G infusion (IVIG) this is prepared from pooled human blood donors, it contain highly purified immunoglobulin G. The dose depends on women weight, level of activation markers or cytotoxicity levels. The rationale of treatment is to down-regulate the peripheral NK cell and its activity. It also reduces antibodies production. The treatment usually starts from 1-7 days before egg collection. The infusion takes 3-6 hours and close monitoring during the infusion is essential. The NK cytotoxicity assay should be repeated 3 weeks after IVIg treatment and repeat infusions may be required. IVIg is costly about £1500 ($2500) per dose and is also not risk free. It is associated with anaphylactic reaction; hence patient should have her blood tested prior to IVIG to check the level of IgA. Other side effects include headache, a feeling of faintness, feeling unwell, fever, muscle pains. Furthermore, there is the risk of transmission of infections such as hepatitis and HIV. There is also a theoretical risk that the antibodies cross the placenta and may affect the fetus immune system.
- TNF alpha blocking agents. TNF alpha is a chemical product produced by immune cells such as NK cells, it promotes inflammation. It has a role in inducing endometrial cells apoptosis. Drugs such as Humira and Enbrel block the action of TNF alpha. In the UK, these drugs are not licensed for use in pregnancy.
Apart from treating antiphospholipids syndrome/ thrombophilia, to date there are no large randomised trials evaluating the benefits and risks of the other treatment modalities mentioned .Furthermore, neither the Royal College of Obstetricians Gynecologists nor the American College of Obstetricians & Gynecologists endorse such treatments. Moreover, these tests and subsequent treatments can be very expensive and as with all medical interventions, carry with them risks and potential side effects. There is a great need for large prospective randomized studies to provide robust answers to the safety and clinical effectiveness of immunological testings and treatment modalities.
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