Having a pregnancy loss can be heartbreaking. Having multiple miscarriages can be truly devastating. Each new pregnancy brings hope, but also great anxiety; each new miscarriage aggravates the feelings of loss, grief and sense of failure… 

It is natural to want answers. Knowing the reason of a pregnancy loss can help you make sense of what has happened. Furthermore, finding the cause of the problem will help prevent it from happening again, or at least reduce its risk. Things are not so simple though when it comes to recurrent miscarriage: most of the times, investigations don’t come out with a clear answer…

The purpose of this article is to help you understand recurrent pregnancy loss and to present the most recent scientific information regarding its cause, diagnosis and treatment. Due to the extensiveness of the subject, this first article will deal only with the known causes of repeated miscarriage; two other articles on testing and treatment will follow.

What is Recurrent Pregnancy Loss?

A pregnancy loss is the spontaneous loss of a pregnancy before 24 weeks of gestation. Recurrent Pregnancy Loss (RPL) is considered after the loss of two or more pregnancies; this includes pregnancies after spontaneous conception or after assisted reproduction (e.g. IUI and IVF/ICSI). Other pregnancy complications such as ectopic pregnancies and molar pregnancies are not included. 

• Primary RPL is a term used for women who have not had a baby before their pregnancy losses. 
• Secondary RPL means they have had at least one baby before their losses. 

It is estimated that RPL affects 1 to 2% of couples.

What causes RPL?

There are several factors that may be responsible for RPL. But you should know that in about half (50%) of the RPL cases, no cause is found. This is called unexplained RPL.

Here are some of the causes that are related to multiple miscarriages:

1) Age

The older you are, the greater your risk of having a miscarriage. If a woman is aged over 40, more than 50% of pregnancies end in a miscarriage. The same is true for RPL. Miscarriages may also be more common if the father is older, although it is not clear whether paternal age is related to repeated miscarriages.

2) Genetic problems

• Genetic defects resulting in an abnormal fetus can be a major cause of miscarriage. About half of all miscarriages in the first three months of pregnancy are due to chromosomal problems, although most of the times this is of random occurrence .
• In about 4 in 100 couples (4%) with recurrent miscarriage, one partner will have an abnormality on one of their chromosomes. Although this may not affect the parent, it may sometimes cause a miscarriage.

3) Thrombophilia

Thrombophilia is a condition in which your blood clots more than usual; it may be inherited (passed down genetically) or acquired (not inherited). Thrombophilia is not only related to RPL, but also to other pregnancy complications.

• Inherited thrombophilia is due to certain gene defects. According to the gene involved, it may be related to early or late repeated miscarriage.
• Antiphospholipid syndrome (APS) is an acquired thrombophilic condition. It is uncommon but strongly related to RPL.

4) Abnormal hormone levels

Miscarriage can occur when the uterine lining does not develop sufficiently, therefore the fertilized egg does not have the best environment for implantation and nourishment; this can be the result of abnormal hormone levels.

Women with thyroid problems and women with diabetes (or insulin problems) are usually at a higher risk for miscarriage due to hormonal imbalances. Women with polycystic ovaries syndrome, are also at risk. In addition, elevated prolactin levels can also disrupt normal uterine lining development.

5) Problems of the uterus

The shape of the uterus may cause miscarriage, usually by interfering with the implantation of the fertilized egg.

• A septum, that is a fibrous wall which divides the uterine cavity, can cause poor implantation and pregnancy loss.
• Uterine fibroids, polyps, adhesions may eventually cause pregnancy loss by blocking the opening of the fallopian tube(s) or if their position is affecting the normal functioning of the uterine lining. Their relationship though with RPL is less clear.
• Another probable cause of miscarriage is an incompetent cervix, meaning the cervical muscle is weak and cannot remain closed; as the developing fetus grows puts pressure on the cervix, it starts to shorten and open, resulting in miscarriage.

6) Immune Causes

It has been suggested that some women miscarry because their immune system does not respond to the baby in the usual way. This is known as an alloimmune reaction. Although numerous immunological factor have been investigated, there is no clear evidence to support this theory at present, and further research is needed.

7) Sperm defects

Sperm DNA is the most important part of the sperm, as it contains the genetic information that will be passed on to the baby. DNA can be damaged during sperm production and transport; this damage is known as DNA fragmentation. The recents years it has become evident that high levels of sperm DNA fragmentation seem to increase the likelihood of pregnancy loss.

Sperm DNA fragmentation can be provoked by stress, smoking, recreational drugs, obesity and other unhealthy lifestyle factors. 

8) Infections

Certain infections have been proposed as the cause of RPL, such as rubella, herpes simplex, ureaplasma, cytomegalovirus and chlamydia. However, the role of these infections in recurrent miscarriage is unclear and probably null. A persistent infection of the endometrium (chronic endometritis) may be related to RPL, but more research is needed to know this for sure.

9) Environmental Factors

Certain toxins you may be exposed to can also result in fetal damage or miscarriage, especially if you experience regular exposure. Toxins such as organochlorine pesticides, certain heavy metals (selenium, lead cadmium), organic solvents, anesthetic gases (occupational exposure), have all been blamed for causing RPL. Likewise, lack of certain micronutrients (zinc, copper, vitamin E) have been proposed as possible causes of RPL. 

Although exposure to possible hazardous substances should be avoided during pregnancy (this is true for all pregnant women), there are insufficient data to recommend protection against a certain occupational or environmental factor in women with RPL.

10) Lifestyle-related factors 

• Studies also indicate that the use of marijuana, tobacco, alcohol and excessive consumption of caffeine can all affect fetal development and result in miscarriage. Although their relationship with RPL is not clear, it is recommended that women limit or avoid their use during pregnancy.
• Being overweight or significantly underweight have been both associated with miscarriages, as well as with pregnancy and childbirth complications. While maternal obesity is a strong risk factor in RPL, the association with very low weight is less clear. Male overweight may also be a negative factor, since is responsible for DNA damage (see above). Striving for a healthy, normal weight is recommended, both for the female and male partner. 
• Intensive exercise or no exercise at all have been both blamed as a cause of RPL, but there is not clear scientific evidence and further research is needed. Moderate (leisure) physical activity seems to be safe, and beneficial for other pregnancy complications, such as diabetes and hypertension of pregnancy.
• Whether stress increases the chances of another pregnancy loss in the next pregnancy is a major concern for all couples with RPL. Studies to date indicate that there is an association between stress and pregnancy loss, but it is not whether the stress is a result or a causal factor in RPL.

 

Read the second part here: Understanding Recurrent Pregnancy Loss – Testing (coming soon)

 

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