Causes of Miscarriage - Women's Health
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Recurrent Miscarriage •
FAQ Recurrent Miscarriage •
Causes of Miscarriage In approximately 50% of couples, extensive investigations fail to establish a cause for RM. Although it may disappoint some couples that their problem remains unexplained, in fact the outlook for such couples is often better than for those in whom a cause is found! The known causes of RM can be classified as follows:
•Immunological
•Blood clotting disorders (thrombophilias)
•Hormonal
•Infection
•Anatomic
•Chromosomal
•Environmental
• Immunological causes of recurrent miscarriage
Historically, a pregnancy has been compared to a heart, kidney or liver transplant. This is because the fetus derives half of its genetic information from its father, who is unrelated to the mother. Everybody knows that for a transplant to "take" attempts are made to match the tissue type of the donor to that of the recipient, and even when a match is close, powerful drugs still have to be given to the recipient to suppress the immune system to prevent the transplant being "rejected". In human pregnancy, not only is there no physical match, but no drugs are given, yet the pregnancy thrives. For decades this apparent paradox has fascinated immunologist, who have sought the Holy Grail which has enabled the fetus to elude the mother's immune system. We now know that the comparison of the fetus to a transplant is wholly simplistic and in fact inappropriate, but there is strong evidence that in some instances, the immune system, whose prime function is to protect the body against infections, can be implicated in recurrent miscarriage. It is, however, important to recognize that much of our knowledge in this area remains rudimentary.
• Natural Killer (NK) cells
NK cells are part of the so-called innate immune system, which protects the body against viral and bacterial infection without the need for prior sensitization. A strong body of research has now shown that in normal pregnancy NK cells in the peripheral blood reduce both in number and in their capacity to kill. Further research has suggested that in women with recurrent miscarriage, and in those with implantation failure following Assisted Reproductive Technology treatment, there are increased numbers and activity of NK cells. Unfortunately studies have either confined themselves to the peripheral blood or to the lining of the womb, but usually not to both.
There are important subtle differences between those cells found in the womb and those in the peripheral blood, and further research is needed to clarify the role of NK cells in recurrent miscarriage. Treatments that cause suppression of the immune system such as steroids are promising, but have yet to be subjected to rigorousevaluation. We offer NK cell testing and are evaluating the role of abnormal findings in recurrent miscarriage, and the outcome following treatment with prednisolone, heparin and aspirin.
• Cytokines
Cytokines are small chemicals
• Immunologic disease - eg SLE
Immunological diseases, especially auto-immune conditions (where the body's immune system turns on itself and attacks its own organs and other systems causing disease) may compromise fertility and pregnancy. Systemic lupus erythematosus is the best example of a disease that compromises pregnancy: this includes recurrent miscarriage, poor fetal growth, intrauterine death and pregnancy complications such as pre-eclampsia.
Although it would be uncommon for a woman with SLE to present for the first time with recurrent miscarriage rather than with other features of the disease, the screening tests performed in the Recurrent Miscarriage Clinic would pick up the markers of SLE and suggest extended investigations to confirm the diagnosis. Treatment of active disease is usually with steroids, and if other markers such as the lupus anticoagulant or anticardiolipin antibody are also present, then heparin and aspirin may also be indicated. Patients with SLE and other connective tissue disorders require specialized care and so-operation between obstetricians, rheumatologists and sometimes renal physicians.
The Recurrent Miscarriage Clinic has direct links to a joint Connective Tissue Disorders Clinic run by an Obstetrician (Mr Isaac Manyonda) and a Rheumatologist (Dr John Axford).
• Blood clotting disorders (Thrombophilias)
Individuals with a thrombophilia are at increased risk of forming blood clots, leading to deep vein thrombosis (DVT) and /or pulmonary embolism (PE - clot on the lung) if the clot in the vein dislodges and is propelled in the blood stream to the lungs. This increased risk of clot formation is because the individual makes too much of a clot-promoting protein, or too little of a protein that promotes dissolution of clots. Pregnancy itself, even in women without a thrombophilia, increases the risk of clot formation 6-fold. So women with a thrombophilia are at significant risk of clot formation during pregnancy.
In recent years, research has shown that thrombophilias, some of which are acquired while others are inherited, are a significant contributor to recurrent miscarriage. While it is tempting to suppose that thrombophilias impair pregnancy by the formation of blood clots around the early after-birth, in reality the story is more complex. The good news is that once identified, there are effective therapeutic interventions for these disorders.
The Primary Antiphospholipid syndrome (PAPS) - this is an example of an acquired thrombophilia the most important markers of which are the lupus anticoagulant and the anticardiolipin antibodies. It is estimated that PAPS can be diagnosed in about 15% of women with recurrent miscarriage. Left untreated, women suffer a miscarriage rate of up to 90%. Earlier studies showed that treatment with a combination of low dose aspirin and low molecular weight heparin gave a 70% chance of successful pregnancy, while aspirin on its owngave a 40% chance of success. Intriguingly, more recent reports have suggested that aspirin on its own can in effect achieve the high results achieved by the combination with heparin!
Factor V Leiden (FVL) mutation- this is an example of an inherited thrombophilia which, in the absence of treatment, is associated with recurrent miscarriage. FVL is carried by 5% of Caucasians, but is rarely found among Blacks people. Again the current approach is to treat carriers of this mutation with a combination of heparin and low dose aspirin.
Other thrombophilias - these include Protein C deficiency, Protein S deficiency, Antithrombin III deficiency, G20210A prothrombin gene mutation, hyperhomocysteinemia etc. Theses disorders are in fact rare, and because of the small numbers no conclusive studies have been conducted to prove that they in fact cause recurrent miscarriage. However, the pragmatic approach is to assume that if they are the only finding in a woman presenting with recurrent miscarriage, they may well be contributory. Treatment is similarly with heparin and aspirin, and if this is not given to "cure" recurrent miscarriage, it will at least protect the woman against blood clot formation!
• Continue Reading » Page 2: Causes of Miscarriage
If you have any queries regarding the topics raised within this article please do not hesistate to contact the Women's Health Clinic via the email form at the bottom of the page or by calling our London clinic on 020 8947 9877.
