Can an autoimmune problem cause recurrent miscarriage?
An autoimmune disease is an illness that occurs when the body tissues are attacked by its own immune system. The immune system is a complex organization within the body that is designed normally to "seek and destroy" invaders of the body, including infectious agents. Patients with autoimmune diseases frequently have unusual antibodies circulating in their blood that target their own body tissues. Examples of autoimmune diseases include:-
- systemic lupus erythematosus,
- Sjogren syndrome,
- Hashimoto thyroiditis,
- rheumatoid arthritis,
- juvenile (type 1) diabetes,
- polymyositis,
- scleroderma,
- Addison disease,
- vitiligo,
- pernicious anemia,
- glomerulonephritis, and
- pulmonary fibrosis.
There are two issues to consider in the context of a possible autoimmune causation of recurrent pregnancy loss the antiphospholipid antibodies and alloimune pregnancy loss.
Treatment of Recurrent Miscarriage Associated with an autoimmune problem
Lupus anticoagulant and anticardiolipin are two antiphospholipid antibodies that have been associated with miscarriage. They increase the chance of the blood clotting (throbophilia - Q12-12) and this may damage the placenta . When they are present, and not treated, a live birth can only be expected in 25-50% of subsequent pregnancies. Scientifically controlled trials have demonstrated that low-dose aspirin in combination with heparin will increase the chance of a live birth in women with antiphospholipid antibodies. Many women have taken low dose aspirin in pregnancy apparently without problems. There is no evidence so far that low dose aspirin treatment will improve the outcome if there is no increased antiphospholipid antibodies although in one study involving IVF, low dose aspirin enhanced treatment outcome even in the absence of these antibodies.
In a 2009 study, heparin and aspirin did not confer incremental benefit compared to aspirin alone.2009 Regardless of treatment regimen, number of prior losses, or aPL positivity, almost 80% of women in our recurrnt pregnancy loss cohort had a successful pregnancy outcome. These findings contribute to a growing body of literature that contests the emerging standard of care comprising LMWH/ASA for this population.
In the era of blood transfusion and organ transplantation, we have all become aware of the importance of tissue typing and the problems of the immune response, which limits our choice of donors. In general, tissue typing is likely to show that a child could not donate an organ to its mother. In this context, it is remarkable that during pregnancy the baby is not rejected by the immune system even though the baby's blood comes into direct contact with maternal tissue in the placenta (afterbirth). The immune system is known to change in pregnancy and there must be some adaptation to allow the majority of pregnancies to continue. It has been suggested that some women who recurrently miscarry have a defect in this normal immune adaptation (alloimune pregnancy loss).
One method of treating women with recurrent miscarriage seeks to alter their immune response by immunising them with white blood cells obtained from their partners. It is still uncertain whether this treatment increases the live birth rate. One meta-analysis (Q33.23) suggests that there may be a 10% improvement. If it has a benefit it may be appropriate only for those who are deficient in the relevant antibody (APCA) and also those with a relatively high number of pregnancy losses.
- Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA Trial.(2009-01)
- Factor V Leiden mutation: a treatable etiology for sporadic and recurrent pregnancy loss.(2007-01)
- Association between adverse pregnancy outcomes and maternal factor V G1691A (Leiden) and prothrombin G20210A genotypes in women with a history of recurrent idiopathic miscarriages. (2005-01)
- Factor V leiden and acquired activated protein C resistance among 1000 women with recurrent miscarriage (2001-01)
- Factor XII but not protein C, protein S, antithrombin III, or factor XIII is a predictor of recurrent miscarriage (2001-02)
- Recurrent miscarriage - An aspirin a day? (2000-01)
- A population-based case-control teratologic study of acetylsalicylic acid treatments during pregnancy (2000-02)
- Primary habitual abortions are associated with high Frequency of Factor V Leiden mutation (2000-03)
- Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. (1999-01)
- The factor V Leiden mutation in Japanese couples with recurrent spontaneous abortion. (1999-02)
- Habitual abortions in 678 healthy patients: investigation and prevention. (1999-03)
- Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage. (1999-04)
- Antiphospholipid antibodies in infertile couples with two consecutive miscarriages after in-vitro fertilization and embryo transfer (1999-05)
- Lack of association between antiphospholipid antibodies and first- trimester spontaneous abortion: Prospective study of pregnancies detected within 21 days of conception (1998-01)
- Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospolipid antibodies (or antiphospholipid antibodies) (1997-01)
- Chromosome analysis of aborted conceptuses of recurrent aborters positive for anticardiolipin antibody (1997-02)
- Allogenic leukocyte immunization after five or more miscarriages (1997-03)
- Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: Effect on prostacyclin and thromboxane A2 production (1997-04)
- Adverse pregnancy outcome in the antiphospholipid syndrome: Focus for future research. (1997-05)
- Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. (1997-06)
- Intravenous immunoglobulin treatment of pregnant patients with unexplained recurrent abortions (1996-01)
- Antiphospholipid antibodies in women with habitual abortions. Treatment with prednisone and acetylsalicylic acid during pregnancy (1995-01)
- The prevalence of lupus anticoagulant and anticardiolipin antibodies in women with a history of first trimester miscarriages (1994-01)
- Immunotherapy and recurrent abortion: A randomized clinical trial (1994-02)
- The prevalence of lupus anticoagulant and anticardiolipin antibodies in women with a history of first trimester miscarriages (1994-03)
- Treatment of recurrent spontaneous abortion by immunization with paternal lymphocytes: Results of a controlled trial. (1993-01)
- Treatment of recurrent spontaneous abortion by immunization with paternal lymphocytes: Results of a controlled trial (1993-01)
- Lupus anticoagulant: Significance in habitual first-trimester abortion (1993-02)
- Antiphospholipid antibodies in pregnancy: Prevalence and clinical associations. (1993-03)
- 1 What is a miscarriage?
- 2 What are the different types of miscarriage?
- 3 How accurate are pregnancy tests?
- 4 What is a blighted ovum?
- 5 I have had a hydatidiform mole. What is this?
- 6 Why did I have a spontaneous miscarriage?
- 7 How frequently do miscarriages occur?
- 8 I am miscarrying. How should this be treated?
- 9 What is meant by recurrent miscarriage?
- 10 I have a problem with recurrent miscarriage. What is the chance of my next pregnancy being successful?
- Q 12.11 Recurrent Miscarriage I have miscarried again. Why does this keep happening?
- 12 What congenital problems might be associated with recurrent miscarriage and how could they be treated?
- 13 What traumatic conditions can cause recurrent miscarriage and how can they be treated?
- 14 Can infection cause recurrent miscarriage and would treatment help?
- 15 Could a metabolic disorder cause recurrent miscarriage?
- 16 Could a hormonal problem account for recurrent miscarriage and would hormone treatment help me?
- 17 Could an autoimmune problem cause recurrent miscarriage and how could this be treated?
- 18 Could a tumour cause recurrent miscarriage?
- 19 What degenerative processes may be associated with recurrent miscarriage?
- 20 After every miscarriage I become more depressed. Could this account for the problem?
- 21 Is it always possible to explain recurrent miscarriage?
- 22 I have a problem with recurrent miscarriage. What treatment is available to ensure that this does not happen again?
- 23 What is an ectopic pregnancy?
- 24 How frequently do ectopic pregnancies occur?
- 25 Why do ectopic pregnancies occur?
- 26 How can an ectopic pregnancy be diagnosed?
- 27 How can an ectopic pregnancy be treated?
- 28 Where can I obtain more information?
- 29 Support Groups.
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This is the personal website of David A Viniker MD FRCOG, Consultant Obstetrician and Gynaecologist at Whipps Cross University Hospital, London - Specialist Interests - Reproductive Medicine including Infertility, PCOS, PMS, Menopause and HRT.
I do hope that you find the answers to your women's health questions in the patient information and medical advice provided.
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