Habitual spontaneous abortion

Habitual spontaneous abortion is a common pathology of pregnancy, which has serious psychological consequences.

The etiology and pathogenesis of habitual spontaneous abortion, diagnosis, methods of modern treatment of these conditions and prevention of miscarriage are shown.

Key words: habitual spontaneous abortion, etiopathogenesis, diagnostics, treatment, prevention. In recent years, the scope of scientific interests in perinatal fetal care has focused on the early stages of pregnancy - the first trimester, since it is during this period that the fetoplacental system is formed, the tissues and organs of the fetus, extraembryonic structures and provisional organs are laid down, which in most cases determines the further course of pregnancy.

Recurrent pregnancy loss (RPL) remains a pressing problem in modern obstetrics, despite the advances made in recent years in the prevention and treatment of this pathology.

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Epidemiology

The frequency of spontaneous abortions remains quite high and stable, showing no tendency to decrease. According to various authors, it ranges from 2 to 55%, reaching 50% in the first trimester, and some authors believe that approximately 70% of pregnancies are terminated, of which half of spontaneous abortions occur very early, before the delay of menstruation, and are not diagnosed. According to other authors, only 31% of pregnancies are terminated after implantation.

The frequency of spontaneous termination of pregnancy from the moment of its diagnosis to 20 weeks (counting from the first day of the last menstrual period) is 15%.

The diagnosis of habitual spontaneous abortion is made after 2 or more spontaneous miscarriages in a row (in some countries - after 3 or more), i.e. after 2-3 or more spontaneous terminations of pregnancy before 20 weeks. The prevalence of habitual spontaneous abortion is approximately 1 in 300 pregnancies. T. F. Tatarczuk believes that examination of a woman should begin after two spontaneous abortions in a row, especially in cases where fetal heartbeat was detected by ultrasound before the abortion, the woman is over 35 years old and she has been treated for infertility.

It is believed that as the number of spontaneous abortions increases, the risk of miscarriage in subsequent pregnancies increases dramatically.

The authors note that after four spontaneous miscarriages, the risk of a fifth is 40–50%.

The lack of a decrease in the frequency of this pathology indicates the difficulties that arise in the management of women with such a diagnosis, habitual spontaneous abortion. On the one hand, they are due to the multifactorial nature of the etiology and pathogenetic mechanisms of the disease, on the other hand, the imperfection of the diagnostic methods used and the lack of adequate monitoring of complications that arise during pregnancy. This should be remembered when assessing the effectiveness of different methods of treating habitual spontaneous abortion.

Causes habitual spontaneous abortion

Often the genesis of spontaneous miscarriage remains unidentified. Most women have to undergo examination and treatment during pregnancy, which does not always allow for timely detection and elimination of existing disorders, despite the proven high efficiency of pre-gravid preparation. In this regard, in pregnant women with habitual miscarriage, an unfavorable pregnancy outcome for the fetus is noted in 51% of observations.

The desire to reduce these indicators in case of miscarriage served as a reason for searching for the basic principles of early prevention, timely diagnosis and adequate therapy of habitual miscarriage.

The cause of habitual abortion is not yet fully understood, although several main causes have been named. Chromosomal abnormalities in partners are the only cause of habitual spontaneous abortion that researchers do not doubt. They are found in 5% of couples. Other causes include organic pathology of the genitals (13%), endocrine diseases (17%), inflammatory diseases of the genital tract (5%), and immune diseases (50%). The remaining cases are due to other, rarer causes. Despite this, even with the most thorough examination, the etiology of habitual spontaneous abortion remains unclear in 60% of cases.

J. Hill compiled a list of the main etiological factors leading to habitual termination of pregnancy:

• genetic disorders (chromosomal and other anomalies) - 5%;
• organic pathology of the genital organs - 13%;
• congenital pathology (malformations): malformations of the derivatives of the Müllerian ducts, maternal intake of diethylstilbestrol during pregnancy, anomalies of the origin and branching of the uterine arteries, isthmic-cervical insufficiency;
• acquired pathology: isthmic-cervical insufficiency, Asherman's syndrome, uterine fibroids, endometriosis;
• endocrine diseases - 17%: corpus luteum insufficiency, thyroid disease, diabetes mellitus, androgen secretion disorder, prolactin secretion disorder;
• inflammatory diseases of the genital tract - 5%: bacterial; viral; parasitic; zoonoses; fungal;
• immune disorders - 50% humoral link (antiphospholipid antibodies, antisperm antibodies, trophoblast antibodies, deficiency of blocking antibodies);
• cellular link (immune response to antigens formed during pregnancy, mediated by T-helper type 1, deficiency of the immune response mediated by T-helper type 2, deficiency of T-suppressors, expression of certain HLA antibodies);
• other causes - 10%: adverse environmental factors; medications; placenta surrounded by a cushion;
• internal diseases: cardiovascular diseases, kidney diseases, blood diseases, pathology in the partner, discrepancy between the timing of ovulation and fertilization, sexual intercourse during pregnancy, physical activity during pregnancy.

T. F. Tatarczuk believes that all causes of habitual spontaneous abortion can be divided into three groups: those based on the results of controlled studies (proven); probable, i.e. requiring more high-quality evidence; those in the process of research.

Let's try to consider in more detail all these reasons for habitual spontaneous abortion.

Genetic disorders

The most common chromosomal abnormality in spouses that leads to habitual miscarriage is compensated translocation. It usually leads to trisomy in the fetus. However, neither family history nor information about previous births can exclude chromosomal abnormalities, and they can only be detected by determining the karyotype. In addition to translocations, habitual spontaneous miscarriage can be caused by mosaicism, mutations of individual genes, and inversions.

Orgpathology of the genital organs can be congenital and acquired (malformations of the derivatives of the Müllerian ducts, malformations of the cervix leading to the development of isthmic-cervical insufficiency). With a septum in the uterus, the frequency of spontaneous abortions reaches 60%, and most often abortion occurs in the second trimester of pregnancy. Acquired pathology of the genital organs that increases the risk of spontaneous termination of pregnancy is Asherman's syndrome, submucous uterine myoma, endometriosis. The pathogenesis of miscarriage in these conditions is unknown, although some authors believe that this may be a violation of the blood supply in uterine myoma and Asherman's syndrome and immune disorders in endometriosis.

Endocrine disorders

Among the endocrine causes leading to habitual miscarriage, it is necessary to note the insufficiency of the corpus luteum, hypersecretion of luteinizing hormone, diabetes mellitus and thyroid diseases. The significance of the luteal phase insufficiency can be a consequence of many different factors and their combinations - concomitant endocrine pathology. But today the main diagnostic criterion is the concentration of progesterone. In the early stages of pregnancy, it is produced by the corpus luteum, then mainly by the trophoblast. It is believed that miscarriage before the 10th week of pregnancy is associated with insufficient secretion of progesterone by the corpus luteum or resistance to it of the decidua and endometrium. In hypothyroidism, abortion is associated with ovulation disorders and insufficiency of the corpus luteum. It has recently been proven that women with habitual spontaneous abortion very often have elevated titers of antithyroid antibodies in the serum.

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Inflammatory diseases of the genitourinary system (IDG)

The role of infections in the development of habitual spontaneous miscarriage is the most controversial, although it has been studied quite well.

It is believed that miscarriage is caused by pelvic inflammatory diseases caused by bacteria, viruses and fungi, primarily Mycoplasma spp., Ureaplasma spp., [ 10 ] Chlamidia trahomatis, etc.

Immune disorders

Recognition of a foreign body and development of an immune response are regulated by HLA antibodies. The genes encoding them are localized on chromosome 6. HLA antigens are divided into 2 classes - HLA class I (antigens A, B, C) are necessary for recognition of transformed cells by cytotoxic T-lymphocytes, and HLA class II (antibodies DR, DP, DA) ensure interaction between macrophages and T-lymphocytes during the immune response.

Habitual spontaneous abortion is also associated with other disorders of the cellular link of immunity. Among them, the insufficiency of T-suppressors and macrophages is highlighted. Some authors suggest that the activation of cytotoxic T-lymphocytes, leading to spontaneous abortion, is facilitated by the expression of HLA class I antigens of the syncytiotrophoblast.

Other authors reject this pathogenetic mechanism, since HLA antigens are not detected in the elements of the fertilized egg.

The role of disturbances in the humoral link of immunity in the pathogenesis of habitual spontaneous abortion is more substantiated and clarified. First of all, we are talking about antiphospholipid syndrome.

S. I. Zhuk believes that the causes of thrombophilic disorders during miscarriage are antiphospholipid syndrome, hyperhomocysteinemia and hereditary hemostasis defects.

Antiphospholipid syndrome is diagnosed in 3-5% of patients with habitual spontaneous abortion. Habitual miscarriage in antiphospholipid syndrome is apparently explained by thrombosis of the placental vessels, which are caused by disturbances in both platelet and vascular hemostasis.

The hypothesis about the role of antisperm antibodies, trophoblast antibodies and deficiency of blocking antibodies in the pathogenesis of habitual miscarriage has not been confirmed.

Other causes of miscarriage and habitual spontaneous abortion include contact with toxic substances, especially heavy metals and organic solvents, the use of drugs (cytostatics, mifepristone, inhalation anesthetics), smoking, drinking alcohol, ionizing radiation, chronic diseases of the genital area, leading to disruption of the blood supply to the uterus.

An increase in the number of spontaneous abortions is observed with thrombocytosis (platelet count over 1,000,000/μl) and hyperhomocysteinemia, which lead to the formation of subchorionic hematomas and spontaneous termination of pregnancy in the early stages.

No link has been established between spontaneous miscarriage and working on a computer, being near a microwave oven, or living near power lines.

Moderate coffee consumption (no more than 300 mg/day of caffeine), as well as moderate physical activity, also does not affect the frequency of spontaneous abortions, but may increase the risk of intrauterine growth retardation of the fetus.

Scientists' opinions on the role of sexual intercourse during early pregnancy in the pathogenesis of spontaneous abortion are contradictory.

Often, women with habitual spontaneous abortion have several of the above reasons. In the early stages of pregnancy, there are critical periods characterized by various etiological factors in the development of habitual miscarriage.

Diagnostics habitual spontaneous abortion

Knowledge of these periods will allow a practicing physician to suspect with a fairly high degree of probability the presence of a particular pathology in a pregnant woman; termination of pregnancy before 5-6 weeks is most often due to genetic and immunological disorders; termination of pregnancy at 7-9 weeks is mainly associated with hormonal disorders: luteal phase insufficiency of any genesis, hyperandrogenism (adrenal, ovarian, mixed), sensitization to one's own hormones (the presence of antibodies to hCG and endogenous progesterone); termination of pregnancy at 10-16 weeks is more often caused by autoimmune disorders, including antiphospholipid syndrome, or thrombophilic disorders of another genesis (hereditary hemophilia, excess homocysteine, etc.); termination of pregnancy after 16 weeks - pathological processes in the genitourinary organs: infectious diseases; isthmic-cervical insufficiency; thrombophilic disorders.

In case of habitual spontaneous abortion, it is necessary to carefully collect anamnesis from both partners before pregnancy occurs and conduct gynecological and laboratory examination. Below is an approximate scheme of examination of a woman with habitual spontaneous abortion.

Anamnesis: period, manifestations of previous spontaneous abortions; contact with toxic substances and intake of drugs; IUD; manifestations of antiphospholipid syndrome (including thrombosis and false-positive nontreponemal reactions); consanguinity between partners (genetic similarity); habitual spontaneous abortion in family history; results of previous laboratory tests; physical examination; laboratory tests; determination of karyotype of partners; hysterosalpingography, hysteroscopy, laparoscopy; endometrial aspiration biopsy; study of serum TSH level and antithyroid antibody level; determination of antiphospholipid antibodies; determination of activated partial thromboplastin time (APTT); complete blood count; exclusion of sexually transmitted infections.

Treatment habitual spontaneous abortion

Treatment of habitual spontaneous abortion consists of restoring the normal anatomy of the genitals, treating endocrine disorders and VZMP, immunotherapy, in vitro fertilization of donor eggs and artificial insemination with donor sperm. Psychological support is also necessary. In a short time, a number of immunotherapeutic methods for the treatment of habitual spontaneous abortion have been proposed (intravenous administration of syncytiotrophoblast microvilli plasma membranes, suppositories with the liquid part of donor sperm, but the most promising in the treatment of habitual spontaneous abortion is the subcutaneous administration of cryopreserved placental tissue in the early stages of pregnancy. The method was proposed by Academician of the NAI of Ukraine V. I. Grishchenko and tested at the Specialized City Clinical Maternity Hospital No. 5 in Kharkov. Descriptions of the methods can be found in the publications of the employees of the Department of Obstetrics and Gynecology of the Kharkiv National Medical University.

Patients with antiphospholipid syndrome during pregnancy are prescribed aspirin (80 mg/day orally) and heparin (5000–10,000 units subcutaneously 2 times a day). Prednisolone is also used, but it has no advantage over the combination of aspirin and heparin. APTB is determined weekly. To correct thrombophilic disorders, it is recommended to use folic acid at 4–8 mg per day throughout pregnancy, Neurovitan - 1 tablet 3 times a day, acetylsalicylic acid at a dose of 75 mg (except for the 3rd trimester), dydrogesterone at 10 mg 2–3 times a day up to 24–25 weeks.

Theoretically, in case of habitual spontaneous abortion, the use of cyclosporine, pentoxifylline, and nifedipine may be effective. However, their use is limited by serious side effects.

Progesterone has an immunosuppressive effect in doses that ensure its level in the blood serum of more than 10–2 μmol/l. Recently, dydrogesterone (Duphaston) in a dosage of 10 mg 2 times a day is more often used instead of progesterone. T. F. Tatarczuk examined women with habitual spontaneous abortion and carried out pre-pregnancy preparation, dividing them into 3 groups: in group 1, the patients received only anti-stress therapy, in group 2 - anti-stress therapy + dydrogesterone 10 mg × 2 times a day from the 16th to the 26th day of the cycle, group 3 took dydrogesterone 10 mg from the 16th to the 26th day of the cycle at a dose of 10 mg × 2 times a day. The best results in terms of correction of hormonal and psychometric parameters were achieved in Group II, but the most interesting thing was that the use of Duphaston contributed to an increase in the level of follicle-stimulating and luteinizing hormones in the first phase and periovulatory period.

The outcome of pregnancy depends on the cause and number of spontaneous abortions in the anamnesis.

Even after four spontaneous miscarriages, the probability of a favorable outcome is 60%, with genetic disorders - 20-80%, after surgical treatment of pathology of the genital organs - 60-90%. After treatment of endocrine diseases, 90% of pregnancies proceed normally, after treatment of antiphospholipid syndrome - 70-90%.

The prognostic value of determining cytokines secreted by T-helpers type I has been demonstrated. Ultrasound examination also has prognostic value. Thus, if the fetal heartbeat is detected at 6 weeks of pregnancy, the probability of a favorable pregnancy outcome in a woman with two or more spontaneous abortions of unclear etiology in her history is 77%.

Sources

PhD V. S. LUPOYAD. Habitual spontaneous abortion // International Medical Journal, 2012, No. 4, pp. 53-57