What causes recurrent miscarriage and how is it treated?

The sad stories of women who have suffered recurrent miscarriages have certain similarities. The recurrent miscarriages or spontaneous abortion occur one after another approximately at the same term. After several unsuccessful attempts to bear a child, a woman starts suffering from hopelessness, self-doubt, and sometimes a sense of guilt. Such a mental condition only worsens the situation and can be the reason for another miscarriage. Remember – there is always hope. What you need to do is undergo a thorough medical examination to find out and subsequently cure or manage the condition that influenced premature pregnancy termination. In this article, we review the most common causes of recurrent miscarriage and their treatment methods.

Key points about recurring miscarriage

What is recurrent miscarriage?

The diagnosis of recurrent miscarriage is made if a woman has two consecutive preterm terminations of pregnancy. If it terminates before 22 weeks of pregnancy, it is considered a miscarriage. If after, it is a premature birth in which a baby can survive.

The definition of the WHO says that miscarriage is a termination of pregnancy when the weight of the baby is less than 500 g (1.1 lbs).
The frequency of miscarriage is about 15-20% of the total number of all detected pregnancies. The major part of miscarriages, 80% of cases, occurs during the first 6-8 weeks of pregnancy. Later in pregnancy, the frequency of miscarriage lowers. Recurrent miscarriage occurs, on average, in 1 in 300 pregnancies.

Causes of recurrent miscarriages

Usually, miscarriage occurs as a result of not one but several reasons rendering its effect at the same time or successively. The main reasons for miscarriage including recurrent miscarriage include:

- Genetic factors;
- Sexually transmitted infections;
- Endocrine disorders;
- Immune factors;
- Congenital and acquired diseases,
- Changes in the uterus (fibroids, developmental abnormalities, etc.).

In 45-50% of women, it is impossible to establish the true cause of miscarriage. Preterm pregnancy termination is a multifactorial disease in which most women have a combination of several reasons, therefore, the examination of patients should be comprehensive and include all the necessary modern clinical, instrumental, and laboratory methods.

Let’s review all possible causes in detail:

- Genetic violations. These violations make up around 5% in the total cases of early pregnancy termination. The major part here is played by the chromosomal anomalies in both or one of the partners that can be detected only by special tests. Both parents must conduct a blood karyotype test to detect such chromosomal abnormalities. Worth noting that role of chromosomal anomalies starts to play an even more significant role with age – women older than 35 have a higher risk of miscarriage due to such anomalies than younger women. The latest research also shows that the risk is greater if a father is older than 40.
- Fetus infection. Miscarriage can occur as a result of penetration of the infectious agents from the mother’s body into the placenta. Mother can have no symptoms or show signs of inflammation. Some infectious diseases accompanied by fever and intoxication can increase the muscle tone of the uterus which can result in miscarriage. Besides, some pathogens can disrupt the structure of the fetal membranes, which causes premature rupture of amniotic fluid and termination of pregnancy. Worth noting, the impact of infection depends on the mother’s general health condition and pregnancy term. The major risk is present during the first trimester when the placental barrier is not fully formed. The most dangerous infections are the infections of the reproductive system. It is important to diagnose the disease early and undergo prescribed treatment. Note that you must not use any medications without consulting your doctor first.
- Endocrine factors causing recurrent miscarriage. These factors contribute to 17-25% cases of miscarriage. They include: insufficiency of the second (luteal) phase of the menstrual cycle; adrenal glands dysfunctions; thyroid disease; diabetes, etc. For the preparation of the uterus for pregnancy, sufficient levels of estrogens, progesterone, and their balance during the menstrual cycle are crucial especially during the second phase of the cycle. The insufficiency of the luteal phase is detected in 40% of women with recurrent miscarriage and 28% with infertility and regular menstrual cycle. This is especially relevant for women older than 35 years. Thus, it is recommended to undergo a thorough medical examination with the tests for the key pregnancy hormones in different phases of the menstrual cycle before conception. For the treatment of this pathology, progesterone medications are appointed, for instance, Duphaston is commonly used.

Hyperandrogenism, another type of endocrine disorder. It is a pathological state occurring as a result of increased levels of androgens occurring in certain diseases of ovaries and adrenal glands. Hyperandrogenism is the cause of spontaneous miscarriage in 20-40% of women. If the disorder is diagnosed before conception, a woman undergoes treatment with the medications aimed to lower the level of androgens. The medications and dosages are selected individually and the effectiveness of the treatment is controlled with monthly blood tests for androgens. Usually, the duration of the therapy is from 6 to 12 months. The need for drug use in pregnancy is determined by the doctor based on the characteristics of the clinical course of pregnancy, the presence of symptoms of the threat of miscarriage, as well as the dynamics of hormone levels. For women with thyroid dysfunction, it is recommended to eliminate the dysfunctions before the next conception. They also need to take the medications during pregnancy based on the doctor’s recommendations and control hormone levels during the whole pregnancy. Women with diabetes are advised to plan pregnancy after a thorough examination of an endocrinologist and the achievement of successful control over their disease.

- Immune factors. The frequency of recurrent miscarriages due to immune factors accounts for around 40-50% of all cases. There are two groups of disorders - in the humoral and cellular links of immunity. Disorders in the humoral link of immunity are associated with antiphospholipid syndrome. Antiphospholipid syndrome (APS) is an autoimmune dysfunction associated with miscarriage. APS can cause miscarriage in any trimester, placental thrombosis, and placental underdevelopment. Insufficient blood supply to the fetus due to thrombosis of the blood vessels of the placenta can cause pregnancy loss. The study of the mechanisms of miscarriage allows choosing a specific treatment. To identify this cause, the tests for the presence of APS are appointed to all women with recurrent miscarriage.
Alloimmune disorders are causing miscarriage due to the violation in the cellular level of the immunity. They cause miscarriage as a response of the mother’s body to the paternal antigens of the embryo. It is proven that the crucial role for the prevention of miscarriages at the early stages plays an impact on progesterone receptors.

Thus, progesterone, for instance, Duphaston, is commonly appointed when preparing for conception. It has an immune-modulating effect necessary for the maintenance of the normal function of the endometrium, stabilization of its functional state, and relaxation of the uterus muscles. It is assumed that these effects are due to the reducing the production of prostaglandins by endometrial cells, as well as blocking the release of cytokines and other mediators of inflammation. But this is an additional treatment method. The two main methods of treatment are:

- Immunocytotherapy with partner's (or donor's) lymphocytes;
- Intravenous administration of immunoglobulin.

- Pathology of the reproductive system. Organic pathology causing miscarriage can be either congenital or acquired. The frequency of miscarriages in women with uterine malformations is 30% higher than in women without it. At the same time, many women with certain disorders of the uterus can bear a child without any problems. The peculiarity of this cause of miscarriage is that it maintained during the whole term of pregnancy. The diagnosis of such disorders is made based on the clinical and gynecological examination, ultrasound, X-ray, and laparoscopy. Nowadays, the majority of organic pathologies can be treated with surgery. This can solve the problem of recurrent miscarriages and lower the risk to the normal minimum.

Cervical insufficiency. Cervical insufficiency frequently develops as a result of traumatic injuries of the cervix and after intrauterine interventions, abortion, and childbirth. The incidence of this pathology is from 7.5 to 13%. Usually, pregnancy in cervical insufficiency proceeds without symptoms of threatened termination. If a miscarriage occurs due to cervical insufficiency, it happens during the second or third trimester. Nowadays doctors observe the rise of incidence of cervical insufficiency in endocrine disorders (insufficiency of the luteal phase, hyperandrogenism). To correct cervical insufficiency, stitches to the cervix are made. The need of suturing the cervix is decided individually in each specific clinical situation.
- Other causes of miscarriage. Other, undiagnosed causes of miscarriage make up 10%. They include unfavorable environmental factors, including ecology, the effect of medicines, radiotherapy, bacterial and viral infections during pregnancy, partner diseases, including impaired spermatogenesis, sex life during pregnancy; heavy physical activity, stress, and others.

How to prevent miscarriage?

First of all, it is recommended to undergo a thorough examination before conception to detect all possibly dangerous factors and eliminate them. It is especially important for women who have already had a miscarriage before. Timely and reasonable treatment, dynamic complex monitoring during pregnancy can significantly reduce the risk of recurrent miscarriage.

Post by Karen Willson, gynecologist at Mother and Baby Centre, London, UK