Mr. Vikram Talaulikar is an associate specialist at the reproductive medicine unit in University College London Hospitals NHS Foundation Trust and Hon. Associate Professor in Women’s Health at University College London. He cares for women who have hormone related issues or couples who have difficulty conceiving.
In this article, Mr Talaulikar gives to answer some of the common questions on recurrent miscarriage.
Recurrent miscarriage (RM) is also known as recurrent pregnancy loss and is a distressing clinical condition. Women or couples affected by RM often have several questions: why did this happen to me? is there an underlying cause? and what could be done to avoid another miscarriage in future?
What is RM and how common is it?
A miscarriage or pregnancy loss is when you lose a pregnancy at some point in the first 23 weeks. When this happens three or more times it is called recurrent miscarriage. Around one woman in every 100 experiences recurrent miscarriage. This is about three times more than you would expect to happen just by chance. While for some women there are specific causes why this may happen, no underlying problems can be identified for others and repeated pregnancy loss may be, as mentioned, due to chance alone and nothing more. Most couples who have suffered from recurrent miscarriage still have a good chance of a successful birth in future, although the rate of pregnancy loss increases gradually with age.
What are the known causes?
In about 5 in every 100 women who have experienced recurrent miscarriage, they or their partner have an abnormality on one of their chromosomes which are the genetic structures within our cells that contain our DNA. Although such abnormalities may cause no problem for them or their partner, they may sometimes cause problems if passed on to the baby.
Abnormalities in the embryo
An embryo is a fertilised egg and an abnormality in the embryo is the most common reason for single pregnancy loss. The chances of such abnormalities increase with advancing age of the woman.
Suffering from a serious infection during pregnancy can lead to miscarriage. It is not entirely clear though, whether infections cause recurrent miscarriage.
Antibodies are substances produced in our blood to fight off infections. Some women produce antibodies that react against the body’s own tissues – this is known as an autoimmune response.
About 15 in every 100 women who have RM have antibodies called antiphospholipid antibodies in their blood and these can increase the chance of having further miscarriages. Another type of antibody that is associated with pregnancy loss is the antinuclear antibody. The condition that we typically associate with antinuclear antibodies is Systemic Lupus Erythematosus (SLE). The pregnancy loss rate in women with SLE patients is much higher than that of the general population.
Thyroid antibodies are also a marker for ‘at-risk’ pregnancies. The two antibodies studied, anti-thyroid peroxidase and anti-thyroglobulin antibodies, are collectively referred to as anti-thyroid antibodies.
In some women the neck of the womb, the cervix, may open, or give way, too early in pregnancy and cause miscarriage. This typically happens between 12-24 weeks of pregnancy. This condition is known as ‘cervical weakness’.
Women who have serious anatomical abnormalities of the shape and/or size of the womb cavity seem to be more likely to miscarry or give birth early. Minor variations in the structure or shape of your womb do not cause repeated pregnancy loss.
The inherited ‘thrombophilias’ are a group of genetic disorders of the blood-clotting pathway which cause abnormal or excessive blood clot formation (thrombosis). These conditions are associated with increased risk of pregnancy loss, intrauterine fetal death, and high blood pressure/pre-eclampsia during pregnancy.
Following are the major thrombophilias:
- Factor V Leiden mutation
- Factor II (Prothrombin) G20210 gene mutation
- Methylene-tetrahydrofolate reductase (MTHFR) mutation, leading to hyperhomocysteinemia
- Protein C deficiency
- Protein S deficiency
- Hormonal imbalance
Uncontrolled diabetes and thyroid abnormalities can cause repeated pregnancy loss. Also, Polycystic Ovary Syndrome (PCOS) causes an imbalance of hormones. Just under half of women with recurrent early pregnancy loss have polycystic ovaries; this is about twice the number of women in the general population. It is however unclear whether PCOS on its own can cause recurrent miscarriage and what the possible mechanism is.
What are the tests that can be done to rule out a cause for repeated pregnancy loss?
The tests include:
Blood parameters such as chromosomal analysis, hormone profiling, blood clotting/thrombophilia testing and autoimmune testing. Imaging tests include pelvic ultrasound scan/3D SIS ultrasound procedure for uterine cavity assessment and ovarian reserve assessment.
What are the treatment options following tests?
Screening and treatment for genetic problems
The test for chromosomal abnormalities is known as karyotyping. If either or both partners turn out to have an abnormality, they are offered the chance to see a specialist clinical geneticist. They will provide information about the risks for future pregnancies and will explain what the management choices are including IVF treatment with pre-implantation genetic diagnosis.
With history of recurrent pregnancy loss, doctors may also suggest checking for abnormalities in the embryo or the placenta following any future pregnancy losses. They will do this by checking the chromosomes of the embryo through karyotyping, although it may not always possible to get a result depending on the stage at which miscarriage happened. They may also request examination of the placenta through a microscope. The results of these tests will help identify any abnormalities and the appropriate next treatment steps.
Treatment for anti-phospholipid antibodies
There is evidence that if a woman has anti-phospholipid antibodies and a history of recurrent pregnancy loss, treatment with low-dose aspirin tablets and low-dose heparin injections in the early part of your pregnancy can improve chances of a live birth up to about seven in ten (compared to around four in ten if aspirin is taken alone and just one in ten without treatment).
Even with treatment, there is a slightly increased risk of some problems during pregnancy including pre-eclampsia, restriction in the baby’s growth and premature birth. There is a need for careful monitoring during pregnancy so that appropriate treatment for any problems that arise can be offered in a timely manner.
Screening and treatment for abnormalities in the structure of your womb
A pelvic ultrasound scan checks for and assesses any abnormalities in the structure of the womb or scarring inside the womb cavity, so that they can be surgically treated if necessary, using a technique called hysteroscopy.
Treatment for a weak cervix
If diagnosed with a weak cervix, a vaginal ultrasound scan to measure the shape and length of the neck of the womb during pregnancy may indicate whether one is likely to miscarry. In such situation, an operation can be offered to put a stitch in the cervix, to make sure it stays closed. It is usually done through the vagina, but occasionally it may be done through a ‘bikini line’ cut in your abdomen, just above the line of the pubic hair. Because all operations involve some risk, the doctors will only suggest this if the woman and baby are likely to benefit. They will discuss the risks and benefits of the procedure.
Screening and treatment for vaginal infections
If pregnancy loss happens in the fourth to sixth month of pregnancy or there is a history of starting labour prematurely, women may be offered tests, and treated if necessary, for an infection known as bacterial vaginosis (BV).
If BV is detected, treatment with antibiotics may help to reduce the risks of miscarriage or premature birth.
Treatment for thrombophilia/blood clotting problems
A combination of low-dose aspirin tablets plus low molecular weight heparin injections is used to treat the inherited thrombophilias. The therapy starts as soon as pregnancy occurs and continues four to six weeks after birth. High dose folic acid supplementation is recommended to patients with MTHFR gene mutations.
We certainly recommend empirical progesterone treatment in early pregnancy as
there is some evidence that it could help prevent a pregnancy loss. Although evidence is conflicting, metformin can be continued throughout the first trimester of pregnancy in women with PCOS who have experienced previous miscarriage. It is also very important that thyroid hormone levels are optimised during pregnancy. A small dose of thyroxine to reduce your risk of miscarriage may be offered throughout pregnancy based on your thyroid blood test results.
RM is a distressing condition which affects about 1% of couples trying to achieve a pregnancy. It can be challenging for both patients and clinicians as the cause remains unexplained in at least 50% of couples despite multiple investigations.
A systematic and evidence-based approach to testing and management is important to avoid tests or treatments which are unnecessary or of unproven benefit. Access to specialist recurrent miscarriage clinic services and psychological support form a key part of the management of couples with recurrent miscarriage.
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