Causes of recurrent pregnancy loss

There are several key causes for recurrent pregnancy loss that are identifiable and understood by medical science. Some are treatable. Some are not. And some are treatable only depending on the condition.  Conditions that may cause recurrent pregnancy loss are covered in more detail below.  However, it's also important to understand that there will always be some couples whose miscarriages remain unexplained. .

Uterine Abnormalities

Several abnormalities of the uterus are commonly linked to repeated pregnancy loss. Most of them can be treated with surgery. They include:

• Congenital abnormalities. These are defects present from birth. For instance, a woman may have a uterus that is divided into two sections by a wall of tissue (septate uterus).
• Uterine fibroids (leiomyomata). Uterine fibroids are benign growths (not cancer) made up of uterine muscle tissue.
• Incompetent cervix. An incompetent cervix is one that begins to widen and open too early, in the middle of pregnancy, without any sign of pain or labor. Incompetent cervix is not a cause for recurrent first trimester losses.

Blood clotting (thrombophilic) disorders

Although it has been known for a considerable time that a woman's blood becomes thicker in pregnancy, it has only recently been established that this process is more pronounced in some women compared with others. Blood clotting disorders (thrombophilias) can be inherited (genetic) or acquired. Antiphospholipid antibodies, the two most important of which are the lupus anticoagulant and the anticardiolipin antibodies, cause blood to clot more easily. Women with a history of recurrent pregnancy loss who have persistently positive tests for either lupus anticoagulant and/or anticardiolipin antibodies are said to have Antiphospholipid Syndrome.

Inherited thrombophilias include Factor V Leiden, prothrombin gene mutations in the gene that codes for MTHFR, an enzyme involved in folate metabolism. If blood clots occur in the blood vessels of the placenta, the blood flow to the baby is decreased and this can lead to either second trimester miscarriage or, if the pregnancy proceeds, to the birth of a baby that is smaller than he or she ought to be. Women with these disorders are also at risk of developing high blood pressure later in pregnancy.

For a long time, it was believed that thicker, "sticky" blood can cause first trimester miscarriages because it leads to blood clots in the developing placenta, preventing the embryo from getting the oxygen it needs. We now know that the first trimester placenta doesn't actually have any blood flowing through it- blood vessels are developing but they are plugged by placenta cells. In addition, our experience with embryos in IVF has taught us that oxygen is toxic to early embryos, so direct blood flow would be damaging.

It now appears that the antiphospholipid antibodies in acquired thrombophilias, or the proteins made by genes in inherited thrombophilias, prevent the placental cells from properly attaching to the mother's uterus. Without normal placenta development, the embryo cannot grow.

Chromosomal abnormalities

Chromosomes are tiny structures inside the centre of all cells that come in pairs, one from each parent. Each chromosome carries many genes and it is these genes that define all of a person's physical characteristics (such as sex, blood type, hair & eye colour... to mention just a very few). Having too much or too little of a chromosome causes an imbalance in gene activity.

One-off pregnancy losses can occur when the cells of the placenta and the fetus contain an abnormal number of chromosomes. Mostly the extra chromosome or the deficient chromosome is not present in the parents: instead the abnormality occurs as mature eggs or (less often) sperm cells are formed just before they are released

The miscarriage happens by chance. In most cases, there is nothing wrong with the mother or father's health and miscarriage is not likely to occur again in a later pregnancy.

There is, however, an important exception - balanced translocations

Balanced translocations

A person with a balanced translocation has the correct amount of each chromosome and so has no outward signs of genetic abnormality. However, their chromosomes are arranged incorrectly, which will cause problems when the chromosomes divide - as in the creation of sperm and eggs.

The diagram below shows the possible outcomes when the chromosomes of a person with a translocation divide.

If a translocation is suspected as the cause for recurrent pregnancy loss, both parents can be tested and, if possible, products of conception can be tested as well to confirm the finding.

Upon confirmation, there are several options. As can be seen from the diagram above, there is a 50% chance the embryo will have a normal balance of chromosomes - although there is a chance that it will carry a translocation itself. If the couple continue trying to get pregnant naturally, these odds determine their chance (other factors aside) of carrying a child to term and that child being healthy.

An alternative is preimplantation genetic diagnosis (PGD) . In this procedure, the couple undergo a course of IVF and the resulting embryos are tested as they develop in the laboratory. In this way, embryos with unbalanced chromosomes can be avoided.

Immune disorders

The immune system is designed to recognise and attack foreign substances within the body. Antibodies are formed to help the body fight off disease and heal itself in case of infection. Normally, the mother's body protects the "foreign" fetus from attack by her own antibodies. It is thought that this protection could be absent in the blood of some women who have had repeated pregnancy loss.  Other immune system problems are caused by differences between the mother and the fetus and even between the mother and the father.  For instance, the mother's immune system could produce antibodies to the cells of her body. This can cause pregnancy loss.  Tests can be done that may help find problems with the immune system.

Hormonal disorders

There are a number of hormonal disorders that are commonly associated with recurrent pregnancy loss. The four most common hormonal disorders are:

1. Progesterone

Low levels of progesterone hormone are frequently found in women whose pregnancies are miscarrying. However, low progesterone levels in early pregnancy reflect the fact that the pregnancy has not implanted successfully in the womb lining, rather than because the developing placenta is not producing enough progesterone to maintain the pregnancy. This is an important point - low progesterone is the effect not the cause of the miscarriage. This explains why giving women progesterone and/or hCG hormone injections in early pregnancy does not improve pregnancy outcome. The exception to this is when we take advantage of the immunosuppressant effects of progesterone in women who are found to have immune problems.

2. Follicle Stimulating Hormone

Follicle stimulating hormone (FSH) drives the ovary to start growing follicles. Unfortunately, some women with a history of pregnancy loss are also found to have high FSH levels because their ovaries have become prematurely menopausal. Although rare, this is obviously a very important problem to identify. If FSH levels are high, the appropriate next step is referral to a fertility specialist.

3. The uterine lining (the endometrium)

At the present time the only way of determining the response of the endometrium at the time of implantation is to sample it and look at the histological (microscopic) evidence of the state of the tissues. An endometrial biopsy can be performed towards the end of your cycle (approximately day 26). This biopsy is no more uncomfortable than undergoing a cervical smear test. However, in order to be able to obtain the most useful information from the biopsy, it is important to know exactly the time of ovulation.

4. Polycystic ovarian syndrome

A pelvic ultrasound scan shows that many women with recurrent miscarriage have polycystic ovaries (PCO). This is a common condition, found in 25% of all women, in which there are multiple small cysts within the ovary. These cysts are not dangerous and cannot be removed as they are within the ovary. Polycystic ovaries can sometimes be associated with a number of hormonal imbalances such as increased production of LH and testosterone. A number of carefully designed studies have shown that neither PCO nor high LH levels are a cause for recurrent miscarriages.

Infections

The role that vaginal infections may play in recurrent pregnancy loss is the subject of a new field of research. Infection may well play a role in causing late pregnancy losses (14 weeks gestation) in a small number of women but it is unlikely to be important in causing early miscarriages.

Environment and lifestyle factors

The risk of miscarriage may be increased in pregnant women who:

• Smoke
• Drink alcohol
• Use illegal drugs
• Are exposed to high levels of radiation or toxic agents

Avoid these things during pregnancy - it's not just sound medical sense, it's common sense.