Recurrent Miscarriages

Although … of all recognized pregnancies end in miscarriage, this probability approaches 40% in women who have never had a live birth before and who have experienced 2 or more pregnancy losses. Although recurrent miscarriages are classically defined as 3 or more consecutive pregnancy losses, the loss of two pregnancies, especially after infertility treatment, is considered sufficient to initiate the necessary investigations. In general, 1% of women in the society face the problem of recurrent miscarriage. It has been suggested and researched that recurrent miscarriages may be caused by anatomical, genetic, hormonal, microbial and environmental factors or ‘defects in the immune system and coagulation system’.

It is known that congenital deformities in the uterus (such as septum, double uterus) as well as acquired diseases such as myomas and polyps, and especially intrauterine adhesions that can develop after curettage, can cause pregnancy loss by preventing the embryos from settling, developing or adequate bloodening.

It is possible to detect these problems with ultrasonography and hysteroscopy and to correct them with necessary surgical interventions. More than half of early pregnancy losses are caused by genetic problems. The majority of genetic problems are not transmitted either from the mother or father but occur in the foetus during pregnancy. However, 2-4% of recurrent miscarriages have inherited genetic defects.

Balanced translocations (structural chromosomal disorder) are the most common anomalies; followed by microdeletions, Robertsonian translocations and structural chromosome defects. Examination of miscarriage material and genetic examination of the family may be helpful in diagnosis. It can give information about the probability of recurrence.

Uncontrolled diabetes, thyroid diseases or other systemic diseases in women can cause pregnancy loss by disrupting egg development and endometrial development. Before a new pregnancy, the fact that necessary examinations are made according to the clinical condition of each woman and eliminating or controlling these problems before pregnancy can improve pregnancy outcomes.

To prevent the destruction of the pregnancy by recognizing the paternal antigens of the embryo as foreign by the mother’s immune system it is thought that some changes occur in the mother’s immune system during pregnancy.

Such as the failure of trophoblasts located in the uterus to produce MHC II antigens that stimulate the immune system, or the development of blocking antibodies that coat the paternal antigens and prevent contact with the mother’s immune system. During pregnancy, many substances are produced that make changes in the maternal immune system. While some of them show activity in favor of pregnancy (such as Th2, Il-3, Il-4, Il-5, Il-10, Il-13), some of them may be harmful for pregnancy (such as Th1, TNF-alpha, TNF-beta, gamma-interferon, Il-2). It is thought that especially Th1 cytokines can directly damage the placenta. Although it has been shown that the level of natural killer cells is high in the blood of women with reproductive problems, their role in pregnancy loss is still controversial. As a result, the state of the immune system in early pregnancy has not been fully clarified, as there is no effective treatment for possible problems here, and routine immune system tests are not available today.

Insemination with paternal or third-party leukocytes or intravenous gammaglobulin (IvIG) treatments have been tried for a long time, and  have not been shown any of its benefit in large-scale studies yet. For this reason, reproductive medicine associations in America and Europe follow their routine tests and treatments…

Coagulation and fibrinolysis (dissolution of clots formed) are simultaneous processes in the human body. The healthy balance between them prevents both excessive clotting (thrombosis) and bleeding. There are various congenital and acquired defects that disturb the balance in favor of coagulation. The tendency to clot during pregnancy can cause occlusion of placental vessels and cause miscarriage. Factor V Leiden mutation, prothrombin gene mutation and hyperhomocysteinemia are the most common congenital defects.

Less common ones are Protein C, protein S, and antithrombin III deficiencies. Another disease with an increased tendency to clot is Antiphospholipid syndrome, which can cause problems such as pregnancy loss, growth retardation during pregnancy, and premature birth. For these situations, following the necessary tests and diagnosis for these conditions, pregnancy results can be improved with blood thinners such as heparin during pregnancy.

The association of infectious agents with early pregnancy loss is quite weak, and they have not been shown to cause recurrent miscarriages. However, if a possible pregnancy continues, it can be taken into consideration that they should be screened and not treated when necessary due to the possible harms.

In addition to all these, being overweight or very low weight affects the course of pregnancy. It will do better if women with a body mass index outside of the range of 19 – 25 kg/m2 try to conceive after reaching normal body weight with a balanced diet including adequate folic acid. Since smoking, caffeine and alcohol use are associated with pregnancy loss, these substances should be avoided. The drugs used should be reviewed and the unsuitable ones should be changed.

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