What is meant by recurrent miscarriage?

Miscarriage is an emotionally challenging ordeal accompanied by all the feelings of bereavement. When it occurs more than once it may, understandably, be a devastating experience. Most experts suggest that investigations to detect the cause of recurring miscarriage should begin after three consecutive pregnancy losses. Regional centres have difficulty coping with referrals even for women who have miscarried three times. For those who have miscarried twice, this seems harsh. If we are pedantic, when something recurs it has happened more than once so the second miscarriage is obviously a recurrence. Some departments, have revised their criteria so that consultation and some investigations can commence after two consecutive miscarriages.

As the majority of pregnancies, even after three miscarriages, are likely to be successful, it is particularly difficult to scientifically prove that a particular treatment is effective. The one cause of early pregnancy loss that can be detected and for which there is effective treatment is increased levels of antiphospholipid antibodies. The blood tests are for lupus anticoagulant and anticardiolipin. If these prove to be positive, Aspirin (75mg daily) particularly in combination with heparin, significantly reduces the likelihood of early pregnancy loss.

The incidence of early pregnancy loss doubles from the age of 20 to 40 years and evidence from IVF with egg donation suggests that increased miscarriage problems in older women may be partly attributable to the state of the uterus. A recent study in Bologna, Italy compared implantation and pregnancy rates in an oocyte donation programme with women of different ages sharing oocytes from the same donor: clinical pregnancy rates and ongoing pregnancy rates were twice as likely in recipients of less than forty years old compared to older recipients.

Can miscarriage and recurrent miscarriage result in symptoms of anxiety and depression?

It is more than understandable that miscarriage is frequently associated with depression and anxiety for both the female and male partners. A miscarriage can be associated with all the symptoms associated with bereavement and reactive depression is a common feature. There may be anxiety that there may be difficulty achieving a family particularly if early pregnancy loss has occurred before.(20).


Pregnancy after Miscarriage.

If you are pregnant after a previous early pregnancy loss, the chances are that the pregnancy will be successful. Even after three miscarriages, your chance of a successful pregnancy is 55%.

Usually nature has detected some problem such as a chromosome abnormality (genes - chromosomes) and decides that it is in your interests to discontinue this pregnancy and give you an early chance to start a successful one. A blighted ovum (4), or an embryo with an abnormality would be reasons for spontaneous miscarriage. Occasionally there may be a different and perhaps remedial cause which would need consideration if you have three miscarriages.

What is the chance of a successful pregnancy after recurrent miscarriage?

This depends on the number of consecutive miscarriages that you have had (Table 12.2).

Table 12.2 The chance of subsequent miscarriage related to previous number of consecutive miscarriages.

Two 75
Three 55
Four 45
Five 42


Whilst this is to some extent reassuring, it means that the potential value of a new treatment is difficult to determine as a healthy baby could be as much due to chance as to the treatment. Large numbers of patients are required in controlled trials to demonstrate any true benef

Why do I keep miscarrying?

It is sad enough to lose one pregnancy but it is particularly devastating when this problem recurs; you will have the sympathies of all concerned.

Pregnancy may fail at any time from implantation to childbirth. The majority of unsuccessful pregnancies will fail in the first four months first trimester. About one pregnancy in five or six will result in a first trimester pregnancy loss about the same chance as rolling a 1 with a dice. When a miscarriage occurs the question to be answered is was this just chance?

. If you roll the dice once and get a 1 it seems reasonable to assume this is chance. A second 1 may still be chance but by the third consecutive 1 there is more than a suspicion that the dice is weighted. The investigation of recurrent miscarriage is really designed to check in the first instance whether the dice has been weighted and whether it is possible to get a new and fairer dice (6).

A successful pregnancy requires a healthy egg and a healthy sperm. The resulting embryo must be perfect and the womb capable of sustaining the pregnancy. There is a requirement for a series of appropriate changes in hormone production. When evaluating the potential value of the numerous tests that can be considered we need to determine how relevant the result may be to determining the likelihood of a further early pregnancy loss and particularly whether the result would influence treatment. During investigation, observations may be made that are incidental and not necessarily the cause of recurrent miscarriage (Q4.3). We are looking for a cause for which there is evidence based effective treatment (Q33.24).

Before considering the possible causes of recurrent miscarriage it should be emphasised at the outset that there is only one investigation that may identify a problem for which there is effective treatment, the antiphospholipid antibody tests (17). A diagnosis of polycystic ovary syndrome may lead to treatment with metformin which looks promising but it will take time before controlled trials have been undertaken to determine whether it is effective in reducing recurrent miscarriage.

The causation of a clinical problem may be reviewed under the headings identified in Q3.2. In Table 12.3 this grouping has been applied to recurrent miscarriage. Recurrent miscarriage is one of the most difficult clinical problems to identify the cause as it involves eggs, sperm, embryos, uterus and hormones.


Table 12. 3




Congenital uterine abnormality; Fetal abnormality


Cervical incompetence.


'TORCH' infections; Endometrial Infection; Syphilis.


Mineral deficiencyObesity


Hormone deficiency; LH excess (PCOS)


Antiphospholipid antibodies; Alloimmunity




Maternal age


Anxiety / depression



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 in Q3.3 . 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 early pregnancy losses 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 (IVF - egg donation) 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 (IVF - egg donation).

Preimplantation genetic diagnosis can be beneficial for three major subgroups of patients with recurrent pregnancy loss:

  • couples carrying chromosomal translocations
  • women more than 35 years of age
  • women of any age whose previous early pregnancy losses were due to fetal aneuploidy.

It is likely that the rate of early pregnancy loss will be further reduced with the new advances in methods of performing preimplantation genetic diagnosis for more chromosomes.0801

What traumatic conditions might be associated with miscarriages?

The cervix (neck of the womb) should remain closed through pregnancy but in labour it must stretch to allow the baby through. Cervical incompetence is characterised by weakness of the cervix allowing it to open without the typical labour pains, expelling the fetus during the middle weeks of pregnancy (mid-trimester miscarriage). For the cervix to be incompetent the internal os (top end of the cervix) must be weak. It is possible for the cervix to be weak from the outset particularly in association with congenital uterine abnormality. Cervical incompetence can result from outmoded traumatic obstetric delivery but we now resort to Caesarean section rather than difficult forceps delivery. Stretching the cervix beyond 10mm to terminate pregnancy may be a factor in cervical incompetence and every care is taken to avoid damage to the cervix during these procedures. Cone biopsy of the cervix (Q12.14) could theoretically damage the cervix but again care is taken to avoid the internal os and studies of the outcome of pregnancy following the modern loop cone procedures provide reassurance. 

The diagnosis of cervical incompetence is not easy. Painless miscarriage may occur when there was no apparent reason to predict that this would occur. Serial ultrasound assessment of the cervix looking for evidence of the internal os opening may be a reasonable approach. The treatment of cervical incompetence is a special stitch (cervical cerclage), which acts as a purse-string. No operation is without complication (surgery risks). Controlled studies (Q33.24) have not demonstrated that cervical cerclage is as beneficial as we originally believed. An interesting recently published concept is that the stitch may work by preventing bacteria ascending from the vagina into the uterus rather than as a mechanical barrier stopping the cervix from opening.

Can Infection Cause Recurrent Miscarriage?

Any acute infection in pregnancy can sometimes result in early pregnancy loss.

Listeriosis is caused by the Listeria bacterium which has the unusual ability to grow over a wide range of temperatures. Some miscarriages have been associated with this infection which can be acquired from undercooked foods and soft cheeses. Appropriate care with food preparation is particularly important during pregnancy.

The 'TORCH' infections (Toxoplasmosis, Rubella, Cytomegalovirus and Herpes may be associated with early pregnancy loss. Each of these infections, however, can occur on one occasion only as immunity is then acquired. It is, therefore, not possible for any one of these infections to be responsible for recurrent miscarriage. Toxoplasmosis is an infection acquired from the domestic cat. It has been shown that one woman in five in the UK has evidence of infection prior to pregnancy and this compares to 80% in France. The incidence of infection during pregnancy in the UK is low. Rubella is also known as German measles. Rubella infection can be prevented by immunisation. Cytomegalovirus can produce a flu-like illness. About 50% of women will have had this infection before pregnancy. Herpes infection is discussed in 3.

There has recently been increasing interest in the role of bacterial infection in relation to early pregnancy loss and premature labour. Bacterial vaginosis (Q 22.7) has been implicated in some studies but not all. The difficult question that remains to be answered is whether the bacteria that may be found in association with some miscarriages are the cause of the problem or whether they are opportunistic and proliferate as a result of the pregnancy loss.

Can a Metabolic condition cause recurrent miscarriage?

There has been a suggestion that deficiencies of minerals such as zinc may be a cause of early pregnancy loss but there are no controlled trials to demonstrate the efficacy of supplements.

Obesity has been shown to increase the risk of recurrent miscarriage but it is not known whether it is a direct effect or if PCOS underlies the obesity and recurrent miscarriage. Smoking increases the risk of early pregnancy loss but it is not known how the body chemistry is affected. One study in Italy found that the risk of early pregnancy loss is increased by 40% in smokers.

Can a hormonal problem cause recurrent miscarriage?

It is tempting to assume that administration of the pregnancy hormones HCG and progesterone would increase the chance of a successful outcome but there is no definite evidence to demonstrate that these treatments are effective. Some women have heard anecdotal stories of hormones being successful. Most IVF centres advocate hormone supplements in pregnancy and there is no evidence of any adverse effects. Gestone (progesterone) 100 mg injections, HCG 5000 units by injection, Crinone (progesterone) 4 or 8% on alternate days and Cyclogest pessaries 400mg each night until about 14 weeks are typical regimens.

An elevated FAI appears to be a prognostic factor for a subsequent early pregnancy loss in women with recurrent miscarriage and is a more significant predictor of subsequent miscarriage than an advanced maternal age (> or =40 years) or a high number (> or =6) of previous miscarriages in this study.0801

PCOS (Q7.2) and high levels of LH are thought to be associated with early pregnancy loss. It may be that metformin will prove to be effective, if there is evidence of such problems, but it will be some while before we have evidence.

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.

Lupus anticoagulant and anticardiolipin are two antiphospholipid antibodies that have been associated with early pregnancy loss. 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 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.