Habitual spontaneous abortion

A habitual spontaneous abortion is a frequent 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 protection has focused on the early stages of pregnancy - the I trimester, since it is during this period that the fetoplacental system is formed, the laying of fetal tissues and organs, extraembryonic structures and provisional organs, which in most cases determines the further during pregnancy.

The habitual miscarriage of pregnancy (PNP) is still an actual problem of modern obstetrics, despite the successes achieved in recent years in the prevention and treatment of this pathology.

[1], [2], [3], [4], [5]

Epidemiology

Statistics of habitual spontaneous abortion

The frequency of spontaneous miscarriages remains quite high and stable, without showing a tendency to decrease. According to various authors, it ranges from 2 to 55%, reaching 50% in the first trimester, with some authors] saying that approximately 70% of pregnancies are interrupted, half of them spontaneous abortions occur very early, prior to the delay in menstruation, and are not diagnosed. According to other authors, only 31% of pregnancies are interrupted 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 menstruation) is 15%.

The usual spontaneous abortion is diagnosed with 2 or more spontaneous miscarriages in a row (in a number of countries - with 3 or more), i.e. 2-3 or more self-abortive pregnancy interruptions at terms up to 20 weeks. The prevalence of habitual spontaneous abortion is approximately 1 for 300 pregnancies. Tatiana Tatarchuk believes that a woman should be examined after two spontaneous abortions in a row, especially in those cases when the heartbeat of the fetus was determined by ultrasound before the abortion, the woman's age is more than 35 years and she was treated for infertility.

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

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

The absence of a decrease in the frequency of this pathology indicates difficulties in the management of women with such a diagnosis, the usual spontaneous abortion. On the one hand, they are due to the multifactority of the etiology and pathogenetic mechanisms of the disease, on the other - the imperfection of the diagnostic methods used and the lack of adequate monitoring of complications arising during pregnancy. This should be borne in mind when evaluating the effectiveness of different treatments for a habitual spontaneous miscarriage.

Causes Habitual spontaneous abortion

What causes a habitual spontaneous abortion?

Often the genesis of spontaneous miscarriage remains unsettled. In most women, examination and treatment have to be done during pregnancy, which does not always allow timely detection and elimination of existing disorders, despite the proven high effectiveness of pre-gravity training. In this regard, pregnant women with a habitual miscarriage in 51% of the cases observe a fetal outcome of pregnancy.

The desire to reduce these indicators in the case of miscarriage led to the search for the basic principles of early prevention, timely diagnosis and adequate therapy of habitual miscarriage /

The reason for the habitual termination of pregnancy is not yet fully understood, although several main reasons have been identified. Chromosomal abnormalities in partners are the only cause of doubt in the researchers cause of habitual spontaneous abortion. They are detected in 5% of pairs. Other causes include organic pathology of the genital organs (13%), endocrine diseases (17%), inflammatory diseases of the genital tract (5%) and immune diseases (50%). The remaining cases are due to other less frequent 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 a habitual abortion:

• genetic disorders (chromosomal and other anomalies) - 5%;
• organic pathology of the genital organs - 13%;
• congenital pathology (malformations): developmental defects of Mullerian ducts, mother's intake of diethylstilbestrol during pregnancy, abnormality of branching and branching of uterine arteries, ischemic-cervical insufficiency;
• acquired pathology: ischemic-cervical insufficiency, Asherman's syndrome, uterine myoma, endometriosis;
• endocrine diseases - 17%: deficiency of the yellow body, thyroid gland diseases, diabetes mellitus, violation of the secretion of androgens, violation of the secretion of prolactin;
• inflammatory diseases of the genital tract - 5%: bacterial; virus; parasitic; zoonoses; fungal;
• immune disorders - 50% humoral unit (antiphospholipid antibodies, antisperm antibodies, antibodies to trophoblast, deficiency of blocking antibodies);
• cell link (immune response to pregnancy-associated antigens mediated by T helper type 1, insufficiency of immune response mediated by T helper type 2, insufficiency of T suppressors, expression of certain HLA antibodies);
• other causes - 10%: adverse environmental factors; medicines; placenta, surrounded by a roller;
• internal diseases: cardiovascular diseases, kidney diseases, blood diseases, partner's pathology, inadequacy of the terms of ovulation and fertilization, sexual intercourse during pregnancy, physical activity during pregnancy.

TF Tatarchuk believes that all the reasons for the habitual spontaneous abortion can be conditionally divided into three groups: based on the results of controlled studies (proven); probable, ie, requiring more qualitative evidence; which are in the process of research.

We will try to consider in more detail all these causes of habitual spontaneous abortion

Genetic disorders

The most common chromosomal abnormality in spouses, leading to a habitual miscarriage, is a compensated translocation. Usually it leads to trisomy in the fetus. However, neither the family history data nor the information on the preceding births allow to exclude chromosomal abnormalities, and they can be detected only when the karyotype is determined. In addition to translocations, mosaicism, mutation of individual genes and inversion can lead to a habitual spontaneous miscarriage.

Orgpathology of the genital organs can be congenital and acquired (developmental defects of the Mullerian ducts, developmental defects of the cervix, leading to the development of ischemic-cervical insufficiency). With a septum in the uterus, the incidence of spontaneous abortions reaches 60%, with abortion occurring more often in the second trimester of pregnancy. The acquired pathology of the genital organs, which increases the risk of spontaneous abortion, is Asherman's syndrome, submucous uterine myoma, endometriosis. The pathogenesis of miscarriage in these conditions is not known, although some authors believe that this may be a blood flow disorder in uterine myomas and Ascherman's syndrome and immune disorders in endometriosis.

Endocrine disorders

Among the endocrine causes leading to a habitual miscarriage, it should be noted the lack of a yellow body, hypersecretion of luteinizing hormone, diabetes mellitus and thyroid gland diseases. The importance of luteal phase failure can be a consequence of a variety of 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 yellow body, 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 yellow body or resistance to it of the decidual shell and endometrium. In hypothyroidism, abortion is associated with impaired ovulation and malnutrition of the corpus luteum. Recently it has been proved that in women with habitual spontaneous abortion, the titers of antithyroid antibodies in serum are very often increased.

[6], [7], [8], [9], [10], [11], [12], [13], [14], [15]

Inflammatory diseases of the genitourinary system (VZMP)

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

It is believed that VWMP caused by bacteria, viruses and fungi, primarily Mycoplasma spp., Ureaplazma spp., Chlamidia trahomatis, etc., are believed to lead to miscarriage.

Immune disorders

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

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

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

The role of disturbances in the humoral link of immunity in the pathogenesis of habitual spontaneous abortion is more justified and elucidated. First of all, it is an antiphospholipid syndrome.

SI Zhuk believes that the causes of thrombophilic disorders in case of miscarriage are antiphospholipid syndrome, hyperhomocysteinemia and hereditary hemostasis defects.

Atypophospholipid syndrome is diagnosed in 3-5% of patients with a habitual spontaneous abortion. A habitual miscarriage with an antiphospholipid syndrome is due, apparently, to thrombosis of the vessels of the placenta, and they are caused by violations of both platelet and vascular links of the hemostasis.

Assumptions about the role of antisperm antibodies, antibodies to trophoblast and deficit of blocking antibodies in the pathogenesis of habitual miscarriage were not 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, inhalational anesthetics), smoking, drinking alcohol, ionizing radiation, chronic diseases of the genital area leading to disturbance of blood supply to the uterus.

An increase in the number of spontaneous abortions is observed with thrombocytosis (the number of platelets is more than 1 000 000 / μl) and hyperhomocysteinemia, which lead to the formation of subchorial hematomas and spontaneous termination of pregnancy in the early stages.

There is no connection between spontaneous miscarriage and work on the computer, staying near a microwave oven, living next to power lines.

Moderate coffee consumption (not more than 300 mg / day of caffeine), like moderate exercise, also does not affect the incidence of spontaneous abortions, but may increase the risk of intrauterine growth retardation.

The opinions of scientists about the role of sexual intercourse during early pregnancy in the pathogenesis of spontaneous abortion are contradictory.

Often in women with a habitual spontaneous abortion there are several mentioned reasons. In the early stages of pregnancy there are critical periods for which the various etiological factors of the development of a habitual miscarriage are characteristic.

Diagnostics Habitual spontaneous abortion

How to recognize a habitual spontaneous abortion?

Knowledge of these periods will allow a practical doctor with a fairly high probability of suspecting a pregnant woman of a particular pathology; abortion of pregnancy up to 5-6 weeks is most often caused by genetic and immunological disorders; interruption of pregnancy in terms of 7-9 weeks is mainly associated with hormonal disorders: insufficiency of the luteal phase of any genesis, hyperandrogenism (adrenal, ovarian, mixed), sensitization to own hormones (the presence of antibodies to hCG and endogenous progesterone); interruption of pregnancy in terms of 10-16 weeks is more often due to autoimmune disorders, including antiphospholipid syndrome, or thrombophilic disorders of another genesis (hereditary hemophilia, excess homocysteine, etc.); abortion after 16 weeks - pathological processes in the genitals: infectious diseases; isthmico-cervical insufficiency; thrombophilic disorders.

With the usual spontaneous termination of pregnancy, it is necessary to carefully collect the anamnesis from both partners before the onset of pregnancy and perform a gynecological and laboratory examination. Below is an approximate scheme of examination of a woman with a habitual spontaneous abortion.

Anamnesis: term, manifestations of previous spontaneous abortions; contact with toxic substances and taking medicines; VZMP; manifestations of antiphospholipid syndrome (including thromboses and false positive non-treponemal reactions); blood relationship between partners (genetic similarity); habitual spontaneous abortion in a family history; the results of previous laboratory studies; physical research; laboratory research; definition of karyotype of partners; Hysterosalpingography, hysteroscopy, laparoscopy; aspiration biopsy of the endometrium; a study of serum TSH and antitheroid antibodies; determination of antiphospholipid antibodies; determination of activated partial thromboplastin in time (APTT); general blood analysis; elimination of sexually transmitted infections.

Treatment Habitual spontaneous abortion

How is spontaneous abortion treated?

Treatment of habitual spontaneous abortion consists in restoration of normal anatomy of genital organs, treatment of endocrine disorders and VZMP, immunotherapy, in vitro fertilization of donor eggs and artificial insemination with donor sperm. Psychological support is also required. In a short time, a whole range of immunotherapeutic methods for the treatment of habitual spontaneous abortion (intravenous injection of plasma membranes of syncytiotrophoblast microvilli, a suppository with a liquid part of the donor sperm, was suggested, but the most promising in the treatment of habitual spontaneous abortion is subcutaneous administration of cryopreserved placenta tissue in early pregnancy. Academician of NAI of Ukraine V. I. Grishchenko and approved on the basis of the Specialized City Clinical Hospital about maternity hospital № 5 of Kharkov.The description of techniques can be studied in the publications of the staff of the Department of Obstetrics and Gynecology of KhNMU.

Patients with antiphospholipid syndrome in pregnancy are prescribed aspirin (80 mg / day inside) 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 with heparin. Weekly define ACT. To correct thrombophilic disorders, it is recommended to use folic acid 4-8 mg per day throughout the pregnancy, neurovitamin - 1 tablet 3 times a day, acetylsalicylic acid at a dose of 75 mg (except for the third trimester), dydrogesterone 10 mg 2 -3 times a day until 24-25 weeks.

Theoretically, with the usual spontaneous abortion, the administration of cyclosporine, pentoxifylline, nifedipine can be effective. However, their use is limited by serious side effects.

Immunosuppressive effect has progesterone in doses, providing its level in the serum of more than 10-2 μmol / l. Recently, instead of progesterone, dydrogesterone (dufastone) is often used at a dosage of 10 mg twice a day. Tatiana Tatarchuk studied women with a habitual spontaneous abortion and conducted pregravidual training, breaking them into 3 groups: in group I the patients received exceptionally anti-stress therapy, in group II - anti-stress therapy + dydrogesterone 10 mg × 2 times a day from the 16th on the 26th day of the cycle, the ІІ group 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 for the correction of hormonal and psychometric parameters were achieved in group II, but the most interesting was that the use of dyufastone contributed to the increase in the level of follicle-stimulating and luteinizing hormones in the first phase and the period of the period of the period.

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

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

The prognostic value of the determination of cytokines secreted by T-helper type I is shown. Prognostic value has also an ultrasound. So, if the fetal heart rate is determined at the 6th week of pregnancy, the probability of a favorable pregnancy outcome in a woman with two or more spontaneous abortions of an unknown etiology is 77% in the anamnesis.

Cand. Honey. Of Sciences VS LUPOYAD. Habitual spontaneous abortion // International Medical Journal, 2012, №4, pp. 53-57