Recurrent Miscarriage - Overview
Recurrent pregnancy loss can be defined as two or more failed clinical pregnancies. These are pregnancies where there is clear evidence that both by ultrasound and biochemistry of a pregnancy. This effectively means that a sack or collapse sac is seen on ultrasound and that there had been at least a positive pregnancy test.
A recurrent problem is when the period is late and has been bleeding and there is no evidence of pregnancy usually because a pregnancy test is not yet been performed. Often non-specialists will advise that they probably had been a pregnancy. In most cases this is not so. But even if this were to be the case extremely early pregnancy losses such as these are invariably due to chromosomal abnormality chromosomal abnormality would result in an abnormal baby. Your body is doing the right thing by rejecting back pregnancy.
It is estimated that fewer than 5% of women will experience two consecutive miscarriages and only 1-2% experience or more.
Factors that may affect recurrent pregnancy are our genetics, age, antiphospholipid syndrome, uterine abnormalities, thrombophilias, hormonal or metabolic disorders, infection, autoimmunity, sperm quality, and lifestyle issues such as smoking and weight.
Chromosome testing
Chromosome testing of both partners is an important investigation in recurrent miscarriage. This is to determine if there are recurrent causes of the till loss.
This is in contrast to the very high frequency of sporadic or random chromosomal abnormalities in products of conception. 60% of early pregnancy losses are is associated with random (non-recurrent) chromosomal abnormalities. Of those with a normal chromosome pattern structural abnormalities of the fetus has had been diagnosed in 18% of pregnancies.
The risk of miscarriage overall rises from about 10% in women under 35 to 50% in women older than 40.
The aim of chromosomal testing (karyotyping) is to identify patients that have a balanced reciprocal translocation. These are called Robertsonian translocations and are observed in 2 to 5% of couples with recurrent miscarriage. In these couples the risk of miscarriage is approximately 50% in each pregnancy. Continuing pregnancies will not have an increased risk of abnormality. They are not hereditary. Although these can be identified using pre-genetic diagnosis techniques. The net effect would be to reduce the fertility rate of these patients. Don't forget that we are talking about couples with a normal chance of fertility and conception. This is almost certainly higher than the chance of successful IVF.
Antiphospholipid syndrome
Antiphospholipid syndrome is associated with recurrent pregnancy loss. Between five and 20% of patients with recurrent pregnancy loss will test positive for antiphospholipid antibodies. The most widely accepted tests are for lupus anticoagulant, anticardiolipin antibody both IgG and IgM and anti-B2 glycoprotein one.
There are a number of other antiphospholipid antibodies by currently clinical assays for these are not standardised and the level of evidence does not warrant routine screening.
Miscarriage as a result of antiphospholipid syndrome usually occurs between the sixth and 12th week of pregnancy. Classically a fetal heart is seen at six weeks and miscarriage occurs after that. The standard treatment consists of low-dose aspirin and heparin. Most research suggests that this more than doubles the chance of the pregnancy continuing. It is important only to treat those patients that have an ongoing pregnancy i.e. that the fetal heart can be seen.
Administration of prednisone in Antiphospholipid syndrome does not improve pregnancy rates in this situation and may lead to pregnancy complications, such as high blood pressure and diabetes in pregnancy.
Female anatomy
Most congenital uterine abnormalities are associated with second trimester pregnancy loss. Abnormalities are present in 3 to 16% of women and most do not cause early pregnancy loss. The exception to this is those with a septum in the middle of the uterus and there is good evidence that correction of the set take defect may have a beneficial effect.
Patients with adhesions within the uterus and with uterine polyps or intrauterine fibroids may also benefit from surgery. This depends on the individual case.
There is interest in inflammation within the uterine cavity. Again this is a research area with possible advancement in the near future.
Inherited thrombophilia
An association between thrombophilia and the loss has been suggested but prospective studies have failed to confirm this. The American fertility Society does not recommend routine testing of women for inherited thrombophilia. Many women are heterozygote positive for a number of these and are not at risk. Unless their clotting is proved abnormal, there are obvious metabolites (ie raised homocysteine levels in Methylenetetrahydrofolate Reductase Mutations MTHFR) or they have a clear history of thrombosis they should not have treatment. Treatment is with aspirin 75-80mg daily.
Hormonal and metabolic factors
Uncontrolled diabetes is associated with increased pregnancy loss as is poorly managed thyroid disease. Correcting these reduces the risk substantially.
Administration progesterone to women with sporadic miscarriages is ineffective. In patients with three or more consecutive miscarriages impregnate the place of empiric progesterone is uncertain.
Patients with anti-thyroid antibodies may benefit from small doses of thyroxine, even if their thyroid function is normal.
Male factors
Currently there are contradictory data regarding the causal effect between pregnancy loss and fragmentation of sperm DNA in IVF cycles. Increased fragmentation may lead to increased miscarriage. The treatment is anti-oxidant supplementation which should begin 3 months before conception.
Infection
Infection is well known to cause sporadic miscarriage but as yet there appears no evidence that any infectious agent is related to recurrent early pregnancy loss. Intrauterine infection is more likely to affect implantation and prevent pregnancy altogether.
Psychological factors
Any pregnancy loss exacts an immense psychological pressure on affected couples. A number of studies have noticed that patients receiving regular ultrasound scans seem to miscarry less often than control groups. The data to support this is of limited quality but it seems sensible to offer support and close monitoring in these circumstances.
Immune factors
A number of studies looking for immunologic traits and factors have produced inconsistent data and we feel that they should be only provided in the context of a clinical trial. Treatment with intravenous immunoglobulin (IVIG) has been proposed but several trials have concluded that this is ineffective and so cannot be recommended.
The place of Natural Killer cells is still unclear; although natural killer cells have been implicated in recurrent miscarriage, peripheral blood natural killer cells do not reflect the natural killer cells present in the uterine cavity which are presumably those that are purported to cause a miscarriage. There is on-going research in this field and it may yet be an important causal factor. At present the methods of assessment of numbers of uterine NK cells is not standardised. If there is good evidence that these are causasl then steroids such as prednisolone should be considered.
Lifestyle
Both cigarette smoking and obesity have been shown to be associated with an increase in risk of miscarriage in women who conceive naturally. In the case of obesity less of these pregnancies appear to be chromosomally abnormal than normally weighted controls. This suggests that the uterine environment in obese women is more hostile. There is evidence that weight loss improves outcome in this circumstance.
As far as smoking goes the only advice is STOP.
Other lifestyle habits such as cocaine use, alcohol consumption and increased caffeine consumption have been associated with a risk of miscarriage.