Could A Congenital Abnormality Cause Recurrent Miscarriage?

It is now recognised that some inherited defects in the normal anticoagulant mechanism of the blood may be related to recurrent miscarriage. When tissues are cut they bleed and the blood should clot (coagulation) to stop the bleeding. There is a cascade of chemical changes in the blood that lead to this coagulation. The body also produces a set of chemicals that prevent the blood clotting inappropriately - these are anticoagulants. There is increasing interest in a number of inherited defects in these anticoagulants including activated protein C resistance, which is usually due to Factor V Leiden gene mutation, deficiencies of Protein C or S, antithrombin III, hyperhomocystinaemia, and prothrombin gene mutation. About 10% of women with recurrent miscarriages will prove to have inherited thrombophilia compared to 3% of controls. It is believed that anticoagulation treatment with aspirin 75 mg daily or injections of heparin may improve the prognosis but more research is required in this area.

Congenital structural abnormality may relate to the uterus or the fetus. Congenital uterine abnormalities are discussed inQ3.3 . It is not uncommon to find evidence of a congenital uterine abnormality during investigation of recurrent miscarriage. Many women with congenital uterine abnormality seem to have uneventful pregnancies. It is not certain whether there is an increased incidence of congenital uterine abnormality in association with recurrent miscarriage. There have been many women who have conceived whilst awaiting corrective uterine surgery and these pregnancies have proceeded uneventfully suggesting that the abnormality was not preventing a successful outcome. Controlled studies (placebo & controlled trials) are awaited to determine whether surgery reduces recurrent miscarriage.

Genetic evaluation of the embryo or placental tissue is only possible in about 60% of cases even in dedicated university departments. It would appear that in 50-60% of miscarriages there is evidence of chromosome defects. Recent developments in DNA analysis may indicate that an even higher proportion of miscarriages may be genetic. At this time there is no known treatment that would reduce the incidence of genetic disorders.

Parental chromosome abnormalities may be found in about 6% of couples with three miscarriages or more. These families require counselling from geneticists (doctors who specialise in gene disorders). Advice can be given on the chance of successful pregnancy and the risk of producing a child with a genetic disorder. On rare occasions, it may be appropriate to consider donated gametes, i.e. donor insemination (23) if the problem is with the male partner and IVF/ donated ova (27) if the problem is with the woman.

A woman of 30 was investigated for recurrent miscarriage and was found to have a balanced translocation between chromosomes 8 and 14 (genes - chromosomes). This causes no difficulties for the lady as she has all the required genetic material, albeit in an incorrect order. The problem is that her gametes (eggs) may contain an incorrect amount of chromosomes 8 and 14, which almost certainly accounts for recurrent miscarriage. A pregnancy could continue with a 5% risk of physical or intellectual problems for the baby. The options open to this couple were to continue trying for a pregnancy and in the event of success to accept CVS or amniocentesis (Q19.3) to check the baby's chromosomes. A second option would be IVF with donated eggs (27).

Preimplantation Genetic Testing included as part of an IVF program for couples with recurrent miscarriage does not seem to be advangateous.

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