Sadly, many people have either experienced a miscarriage or know someone who has. 25% of women will unfortunately experience a miscarriage at some point in their lives^[1]”Tommy’s. Miscarriage statistics 2017. Available from: https://www.tommys.org/our-organisation/charity-research/pregnancy-statistics”.

It is for this reason that research into the causes of miscarriages is so important, in the hope that in the future fewer lives will be affected by this heartbreak. Often, unfortunately, the affected women do not understand the miscarriage causes. We have identified seven.

First & Second Trimester

The reasons behind miscarriages can be separated into those which normally happen in the first trimester of pregnancy (first three months) and those in the second trimester (between weeks 14- 26). Most miscarriages happen in the first trimester, and these are usually the result of problems in the unborn baby (called an embryo first then a fetus later in its development while it is still in the womb).

The most common problem affecting the embryo during the first trimester is genetic abnormalities. In the second trimester, other reasons for miscarriage are more prevalent such as chronic health conditions affecting the mother and infections^[2]. “NHS Choices. Miscarriage 2015. Available from: https://www.nhs.uk/conditions/miscarriage/“.

Easily Explained: First Trimester Miscarriage

Genetic abnormalities in the baby

Up to two thirds of early miscarriages are due to problems with the genetic information inside the developing baby, called the embryo^[3]”NHS Choices. Miscarriage 2015. Available from: https://www.nhs.uk/conditions/miscarriage/“. This information is stored in the form of chromosomes, and the number of chromosomes present in the embryo depends on a sequence of events happening in which a healthy sperm cell fertilises a healthy egg cell (oocyte).

The sperm and egg cells should each have the correct number of chromosomes and if this is not the case, the resulting embryo will have too many or too few chromosomes.

The consequences of this are miscarriage or a range of birth defects including Down’s syndrome. Unfortunately the risk of genetic abnormalities is particularly a problem in older women, and the risk of miscarriage increases with maternal age[4. “Andersen AMN, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ. 2000; 320(7251): 1708-1712. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC27416/“].

With more women delaying having children, maternal age as a risk factor affects a large proportion of pregnancies.

New Research

Research from Sarah Wignall and her team at Northwestern University has made exciting inroads into understanding the process responsible for these genetic errors with their work[5. “Science Daily. Northwestern University: New insights into leading cause of miscarriage, birth defects discovered 2017. Available from: https://www.sciencedaily.com/releases/2017/10/171002145008.htm“]. Their work focused on meiosis, which is the process that forms egg cells (or oocytes) and this is the time at which the number of chromosomes an egg cell will have is determined.

During this process of cell division, an elaborate structure called the spindle separates the chromosomes. In most cells, structures called centrosomes play an important role in organising the chromosomes so that they separate properly with the correct number ending up in each separate cell. Strangely, these centrosomes are not found in egg cells.

The fact that something unusual is happening in these cells is why research into this area is so important in order to find out why the process of egg cell division is so prone to errors.

Genetic Systems Change With Age

The team at Northwestern University researched this specialised method of cell division, and found that egg cells have their own mechanism for detecting and preventing errors in a different way to other cells of the body[5. “Davis-Roca MC, Muscat CC, Wignall SM. Caenorhabditis elegans oocytes detect meiotic errors in the absence of canonical end-on kinetochore attachments. JCB 2017; 216(5): 1243. Available from: https://jcb.rupress.org/content/216/5/1243“]. This mechanism allows the process of cell division to be delayed if needed, so that it does not progress through a part of the meiosis called anaphase during which the chromosomes move apart.

In other major research from Northwestern University, Wignall and her team showed the importance of two proteins called KLP-15 and KLP-16 in helping to assemble the intricate spindle which is responsible for separating the chromosomes correctly, without the centrosomes which would usually play a role in other cells ⁽⁶⁾.

When Wignall and her team examined the process of cell division in the absence of KLP-15 and KLP-16, they discovered that the genetic material became disorganised at first, as would be expected. But to their surprise it miraculously reassembled with the help of other proteins called SPD-1 and KLP-18.

This backup system allowed the cell to become somehow reorganised despite the important missing elements. This backup system should in theory be able to repair errors that occur in human egg cell division, but Wignall has a theory that some sort of change affects this backup protein as women become older[5. “Science Daily. Northwestern University: New insights into leading cause of miscarriage, birth defects discovered 2017. Available from: https://www.sciencedaily.com/releases/2017/10/171002145008.htm“].

This could explain the higher rate of miscarriages and birth defects in older women, however Wignall’s research uses C. elegans which is a type of worm commonly used in labs. Her findings are promising but these experiments will be done on other organisms to clarify the results, and to make sure that human cells react in the same way as shown in Wignall’s research.

.

Hormonal causes

There are many hormones which interact with each other and play important parts in having a healthy pregnancy. A hormone called progesterone is responsible for developing the lining of the uterus so that the embryo will be nourished enough allowing it to develop properly.

If the levels of progesterone are not high enough, this can unfortunately result in a miscarriage. Other hormones are also important and miscarriages can affect women with thyroid problems and poorly controlled diabetes[7. “Multiple Miscarriages 2017. Available from: https://resolve.org/infertility-101/medical-conditions/multiple-miscarriage/“].

Blood clotting disorders

Conditions such as systemic lupus erythematosus (SLE or lupus) and antiphospholipid syndrome can sadly result in more than one miscarriage. Women who have lost three or more pregnancies one after another are said to have had recurrent miscarriages.

In women with blood clotting disorders, the blood is too sticky to supply all the nutrients and oxygen needed and it can form clots in areas where it should not. The placenta links the mother’s blood supply to the developing baby, and clots can interfere with the placenta so that it does not function properly.

Blood tests can diagnose these conditions, and treatment involves thinning the blood with medications[8. “Tommy’s. Recurrent miscarriage 2017. Available from: https://www.acog.org/womens-health/faqs/repeated-miscarriages“].

Infections

There are a number of infections which can affect an embryo’s development and in the worst case scenario, they can increase the risk of having a miscarriage. These include: rubella (German measles), cytomegalovirus, bacterial vaginosis, HIV, chlamydia, gonorrhoea, syphilis and malaria[2. “NHS Choices. Miscarriage 2015. Available from: https://www.nhs.uk/conditions/miscarriage/“].

.

Cervical insufficiency / cervical incompetence

The cervix is the narrow passage between the uterus and the vagina. If the cervix is weak it may not be able to hold the pregnancy, which can result in the developing tissue being expelled from the body much earlier than it should be. This usually occurs in the second trimester, and it can be treated during the next pregnancy with a stitch in the cervix. This holds the cervix shut until the time of delivery[5. “Web MD. Pregnancy and Miscarriage 2017. Available from: https://www.webmd.com/baby/guide/pregnancy-miscarriage#1“].

Structural problems

When the egg is fertilised, it needs to be able to attach itself correctly in the uterus to be able to develop. Any structural problem which can block this from happening can result in a miscarriage. This includes fibroids, which are non-cancerous growths which can develop in the womb[9. “NHS Choices. Fibroids 2015. Available from: https://www.nhs.uk/conditions/fibroids/ “].

If a woman has an abnormally shaped womb, this can also prevent the healthy development of an embryo.

Other factors which increase the risk of miscarriage[7. “NHS Choices. Miscarriage 2015. Available from: https://www.nhs.uk/conditions/miscarriage/“]

Detailed lecture-style overview of causes of miscarriage

Bibliography