Recurrent Miscarriage Specialists
Recurrent miscarriage and implantation failure are common fertility issues, but they can be particularly distressing for patients, when early hopes of a successful pregnancy are dashed. At CRGH, we adopt a personalised approach for women and couples experiencing recurrent pregnancy loss/miscarriage; understanding and compassion, coupled with leading edge investigations and support.
We have an established investigations service, including sperm DNA fragmentation testing, reproductive immunology, genetic testing, extensive evaluation of clotting disorders, endocrine testing, and a new range of tests focussing on endometrial health.
We introduced the UK’s first recurrent miscarriage clinic, combining a detailed medical assessment with ongoing support through early pregnancy.
Recurrent Miscarriage Clinic
This new service is led by our expert in recurrent pregnancy loss, Dr Srividya Seshadri. The clinic is open to new and existing patients, and for patients trying to conceive naturally as well as those having fertility treatment.
You will have an initial consultation with a specialist nurse to take your history and carry out initial investigations. You will then consult with Dr Seshadri for a personalised management plan. You will then have regular telephone contact (2-3 times per week) with our specialist nursing team. Recent studies have demonstrated that intensive clinical and emotional support can have a significant positive impact on reducing pregnancy loss.
If pregnancy loss occurs again, your management plan will include methods to more accurately diagnose causes, adjust the management plan, and provide further support. Our specialist team will be with you every step of the way.
Dr Seshadri is an expert in recurrent miscarriage/pregnancy loss, with an international reputation, and an active research programme. Publications include:
- The role of immunotherapy in in vitro fertilization and recurrent pregnancy loss: a systematic review and meta-analysis
- Natural killer cells in female infertility and recurrent pregnancy loss: a systematic review and meta-analysis
What is a Miscarriage?
A miscarriage is when you lose a pregnancy at some point during the first 23 weeks of gestation. When this happens three or more times it is called recurrent miscarriage.
Miscarriage is very common and can affects one in four pregnancies. Each woman’s feelings are different. Following a miscarriage, the recovery time varies from individual to individual.
Around one woman in every 100 will experience recurrent miscarriage. There are various causes of recurrent miscarriage which are detailed below. For others, however, no underlying problem can be identified; their repeated miscarriages may be due to chance alone. Most couples who have had recurrent miscarriages still have a good chance of a successful birth in the future.
What is the cause of a Recurrent Miscarriage?
There are a number of causes, outlined below, which may play a part in recurrent miscarriage.
For around three to five in every 100 women who have recurrent miscarriages, they or their partner have an abnormality on one of their chromosomes (the genetic structures within our cells that contain our DNA and the features we inherit from our parents). Although such abnormalities may cause no problem for you or your partner, they may sometimes cause problems if passed on to your baby. At CRGH, we offer chromosome analysis known as karyotype for couples. We can also offer “Products of Conception” testing for women who have experienced miscarriage so we can provide further investigative testing.
Abnormalities in the Embryo
An embryo is a fertilised egg. A chromosome abnormality in the embryo is the most common reason for single miscarriages. About half of all miscarriages happen because the chromosomes in the embryo are abnormal. This is not usually an inherited problem: it happens when the egg and sperm meet or soon after the egg is fertilised. The older you are the more likely this is to happen.
Antibodies are substances produced in our blood in order to fight off infections. Around 15 in every 100 women who have had recurrent miscarriages have particular antibodies, called antiphospholipid antibodies (aPL), in their blood; fewer than two in every 100 women with normal pregnancies have aPL antibodies. Some people produce antibodies that react against the body’s own tissues; this is known as an autoimmune response and it is what happens to women who have aPL antibodies. If you have aPL antibodies and a history of recurrent miscarriage, your chances of a successful pregnancy may be only one in ten.
Another type of antibody that is associated with miscarriages is the antinuclear antibody. The disease that we typically associate with antinuclear antibodies is Systemic Lupus Erythematosus (SLE). The miscarriage rate in SLE patients is much higher than that of the general population. Although most women who suffer recurrent miscarriages do not have clinical signs of SLE, many exhibit autoimmune phenomena which is similar to that seen in SLE patients. The placentas in these women are inflamed and weakened.
Thyroid antibodies were markers for “at-risk” pregnancies. The two antibodies studied, anti-thyroid peroxidase and anti-thyroglobulin antibodies, are collectively referred to as anti-thyroid antibodies (ATA).
It is not clear how far major irregularities in the structure of your womb can affect the risk of recurrent miscarriages. Estimates of the number of women with recurrent miscarriage who also have these irregularities range from two out of 100 to as many as 37 out of 100. Women who have serious anatomical abnormalities and do not have treatment for them seem to be more likely to miscarry or give birth early. Minor variations in the structure of your womb do not cause miscarriages.
In some women the entrance of the womb (the cervix) opens too early in the pregnancy and causes a miscarriage in the third to sixth month. This is known as having a weak (or ‘incompetent’) cervix. There is no reliable test to assess cervical competence outside of pregnancy.
If a serious infection gets into your bloodstream it may lead to a miscarriage. This includes toxoplasmosis, Rubella, listeria and genital infections. If you get a vaginal infection called bacterial vaginosis (BV) early in your pregnancy, it may increase the risk of having a miscarriage around the fourth to sixth month or of giving birth early. But it is not clear whether infection plays a role in recurrent miscarriage.
The inherited thrombophilias comprise a group of genetic disorders of the blood clotting pathways, leading to abnormal blood clot formation (thrombi). A common route involves resistance to a natural anticoagulant called activated protein C (APC). These diseases have been shown in several studies to cause vascular complications that lead to miscarriage, intrauterine fetal death, pre-eclampsia (toxaemia of pregnancy), and the HELLP syndrome which is a severe form of pre-eclampsia characterized by haemolysis (blood cells breaking up), elevated levels of liver enzymes, and thrombocytopenia (a low platelet count).
Women who carry the genes for inherited thrombophilias are more likely (2 to 14 times) to have a clotting problem leading to a miscarriage, compared with the normal population. The three major gene mutations that lead to inherited thrombophilias are:
- Factor V Leiden mutation
- Factor II (Prothrombin) G20210 gene mutation
- Methylene-tetrahydrofolate reductase (MTHFR) mutation, leading to hyperhomocytseinemia
The most common cause of APC resistance arises from the point (one DNA based-pair) mutation at the cleavage site of factor V, called factor V Leiden. It is the most common of the inherited thrombophilias, with a prevalence of 10% in the Caucasian population. The mutation has been discovered in 60% of patients who have clot formation during a pregnancy and is also a major cause of blood clots associated with oral contraceptive use.
The prothrombin (factor II) gene mutation has been shown to occur in 7.8% of women who experienced fetal loss due to a clotting disorder. Factor II is one of the major factors in the human clotting pathway.
Homocysteine is normally present in low levels in the bloodstream. It is derived from dietary methionine, an amino acid. A gene mutation for the enzyme methylene-tetrahydrofolate reductase (MTHFR), will lead to build up of homocysteine in the bloodstream. This condition, called hyperhomocytseinemia, results in blood clot formation and hardening of the arteries, even in childhood. Nutritional lack of vitamins B6, B12 and folic acid aggravate the problem. Women who have the homozygous form of the MTHFR gene mutation (both of her alleles having the mutation) are more than a two-fold increased risk for a miscarriage.
Recent studies have improved our understanding of the pathways that promote either the fertility permissive cells (Th2 and T regulatory) or the antagonistic cells (Th1, Th17 and natural killer cells (NKC)). Reducing abnormal pathways of immune activation and promoting those that encourage acceptance of the embryo/foetus may encourage the maintenance of the pregnancy from conception through to the delivery of a healthy baby.
If you have polycystic ovaries your ovaries are slightly larger than normal ovaries and produce more small follicles than normal. This may be linked to an imbalance of hormones. Just under half of women with recurrent early miscarriages have polycystic ovaries; this is about twice the number of women in the general population.
Having polycystic ovaries is not a direct cause of recurrent miscarriage and it does not mean that you are at any greater risk of further miscarriages. We are not sure what the link is.
Many women with polycystic ovaries and recurrent miscarriage have high levels of a hormone called luteinising hormone (LH) in their blood. Reducing the level of LH before pregnancy, however, does not improve your chances of a successful birth.
Diabetes and Thyroid Problems
Diabetes or thyroid disorders can be factors in single miscarriages. They do not cause recurrent miscarriage as long as they are treated and kept under control.
What can be done for Recurrent Miscarriage?
Supportive Antenatal Care
Women who have supportive care from the beginning of a pregnancy have a better chance of a successful birth. There is some evidence that attending an early pregnancy clinic can reduce the risk of further miscarriages.
Screening for Genetic Problems
As previously mentioned, you and your partner will be offered karyotype. If either or both of you turn out to have an abnormality you should be offered the chance to see a specialist called a clinical geneticist. They will tell you what your chances are for future pregnancies and will explain what your choices are. This is known as genetic counselling. It can help you decide what you want to do for the future.
If it seems likely that other members of your family could be affected by the same problem, they too may be offered genetic counselling.
We can also offer Carrier Match screening, Products of Conception testing and further investigations. Please speak with your nurse and consultant if you would like further information on these tests.
Screening for Abnormalities in the Embryo
If you have a history of recurrent miscarriage, your doctors may suggest checking for abnormalities in the embryo. They will do this by carrying out preimplantation genetic testing-aneuploidy (PGT-A).
PGT-A involves biopsy (removal of cells) from an embryo and screening for numerical chromosome abnormalities. If there is a suitable embryo, you will embark on a frozen embryo transfer. Your clinician will discuss PGT-A with you in detail at your consultation.
Treatment for aPL Antibodies
There is some evidence that if you have aPL antibodies and a history of recurrent miscarriages, treatment with low-dose aspirin tablets and low-dose heparin injections in the early part of your pregnancy may improve your chances of a live birth up to about seven in ten (compared to around four in ten if you take aspirin alone and just one in ten if you have no treatment).
Even with treatment, you will have a risk of extra problems during pregnancy (including pre-eclampsia, restriction in the baby’s growth and premature birth). You should be carefully monitored so that you can be offered appropriate treatment for any problems that arise.
Steroids (certain sorts of natural or synthetic hormones) have been used to treat aPL antibodies in recurrent miscarriage, but they do not seem to improve the chances of a successful delivery compared with aspirin and heparin.
Screening for Abnormalities in the Structure of your Womb
You should be offered a three-dimensional transvaginal pelvic ultrasound scan to check for and assess any abnormalities in the structure of your womb.
Tests and Treatment for a Weak Cervix
If you have a weak cervix, a vaginal ultrasound scan during your pregnancy may indicate whether you are likely to miscarry.
If you have a weak cervix, you may be offered an operation to put a stitch in your cervix, to make sure it stays closed.
Although having a cervical stitch after the third month of pregnancy slightly lowers your risk of giving birth early, it has not been proved to improve the chances of your baby surviving. Because all operations involve some risk, your obstetrician should only suggest it if you and your baby are likely to benefit. They should discuss the risks and benefits with you.
Screening for Vaginal Infection
If you have had miscarriages in the fourth to sixth month of pregnancy or if you have a history of going into labour prematurely, you may be offered tests (and treatment if necessary) for an infection known as bacterial vaginosis (BV).
If you have BV, treatment with antibiotics may help to reduce the risks of a miscarriage in the second trimester or of premature birth.
Treatment for Thrombophilia
A combination of low-dose aspirin plus low molecular weight heparin injections is used to treat the inherited thrombophilias. The therapy starts before pregnancy occurs, and continues four to six weeks after birth. Folic acid supplementation is given to patients with the MTHFR gene mutation.
Test and Treatment for Immune System Problem
Raised levels of uterine NK cells and/or in the blood may increase the risk of recurrent miscarriage. Please refer to the NK cell testing and immune therapy section of the CRGH website, which can be offered to reduce raised NK cell activity.
It has been suggested that taking progesterone hormones in early in pregnancy could help minimise the risk of a miscarriage.
What could it mean for me in future?
Your doctors will not be able to tell you for sure what will happen if you become pregnant again. However, even if they have not found a definite reason for your miscarriages, you still have a good chance of a healthy birth.
CRGH Miscarriage Management
At CRGH we have a designated team who are able to support you and offer surgical management of your miscarriage. If you wish to opt for conservative management i.e. waiting for the miscarriage to occur spontaneously or medical management, please contact your local early pregnancy unit.
We realise that you have had a distressing experience. Please do not hesitate to inform us should you wish to see our counsellors. Alternatively, you may contact the Miscarriage Association.
Please book a follow up appointment with your consultant once you have had a natural period after a miscarriage to discuss further investigations and your management.
If you would like to book an appointment with one of our doctors you can: