In the Department of Miscarriage of the Center for Family Planning and Reproduction, patients with a history of spontaneous abortion (miscarriage) are examined and treated.
The reasons for miscarriage are numerous.
On the basis of TsPSiR it is possible to carry out complex diagnostics, including:
- Spouses karyotype.
- Spouses typing according to the HLA system.
- genetics consultation.
- Study of congenital defects of hemostasis.
- Diagnosis of antiphospholipid syndrome (antibodies to phospholipids and lupus anticoagulant).
- Expanded hemostasiogram with determination of markers of hypercoagulability.
- Identification of anatomical pathology leading to habitual miscarriage (malformations of the uterus, intrauterine synechia).
- Research on the immune system.
- Diagnosis of intrauterine infections, sexually transmitted diseases
- Comprehensive study of the endocrine system.
- Dynamic monitoring of the state of the cervix during pregnancy.
Preparing for pregnancy includes therapeutic and preventive measures aimed at normalizing the state of the reproductive system of the spouses. In the case of hormonal disorders, their elimination is necessary. In the presence of foci of infection, sanitation is carried out taking into account the sensitivity of the microflora to antibiotics. Identification of chronic hypercoagulation of various origins is an indication for prescribing drugs that eliminate it, etc.
Pregnancy is allowed only when all identified causes of miscarriage are eliminated.
Observation during pregnancy and treatment with the threat of its interruption is carried out taking into account the causes and timing of gestation. In all cases, monitoring of ultrasound, hormonal status and hemostasiogram is mandatory. In the second trimester of pregnancy, the state of the cervix is monitored for the timely detection of isthmic-cervical insufficiency. In the third trimester of pregnancy, cardiotocography is used to dynamically monitor its course.
With the threat of termination of pregnancy, the patient is hospitalized in specialized departments of the Center for Family Planning and Reproduction.
Algorithm for examining patients with recurrent miscarriage (loss of more than 2 pregnancies)
- Ultrasound of the pelvic organs:
- on the 5th-7th day of the menstrual cycle;
- on the 20-23rd day of the menstrual cycle (with dopplerometry of the uterine arteries)
- FSH, LH, estradiol, prolactin, cortisol;
- free testosterone index (testosterone, SHBG);
- 17-OH-progesterone, DEA sulfate;
- TSH; free T3, free T4.
- rubella, CMV, HSV I, II types, toxoplasmosis
- chlamydia, mycoplasma, ureaplasma, CMV, HSV
- prothrombin, annexin, beta 2 glycoprotein 1
Causes of the pathology of miscarriage
With the pathology of "miscarriage", treatment should be carried out under the close supervision of professional doctors who can identify the cause and prevent its development.
The clinic "Medicine and Beauty on Paveletskaya" has specially developed an extended pregnancy management program for miscarriage in history using innovative technologies, modern medical equipment and time-tested methods of its effective treatment.
Expanded program of examination for the management of pregnancy GP 6 in case of miscarriage in anamnesis
Obstetrician gynecologist applies appropriate examination methods that allow timely identification of the causes of miscarriage associated with disorders of the immune system, HLA compatibility, hemostasis, hormonal levels and inflammatory processes.
Program composition:
Experienced gynecologists of the clinic "Medicine and Beauty on Paveletskaya" management of pregnancy with a history of miscarriage, determine the causes, and also carry out a complex of diagnostic procedures in order to identify predispositions and pathologies in the early stages of pregnancy.
Medical Center "Medicine and Beauty on Paveletskaya": we will help you to know the joy of motherhood!
Miscarriage is a spontaneous termination of pregnancy in the period from conception to 37 weeks, counting from the first day of the last menstruation. Spontaneous termination of pregnancy up to 28 weeks is called spontaneous abortion, from 28 to 37 weeks - premature birth. In a number of countries, at the suggestion of WHO, termination of pregnancy between 22 and 28 weeks is considered early preterm birth and perinatal mortality is calculated from 22 weeks. Habitual N.b. or habitual miscarriage, is called the termination of pregnancy two or more times in a row. The frequency of miscarriage is 10-25% of the total number of pregnancies.
What are the causes of miscarriage?
Etiology N.b. varied. An important role is played by unfavorable socio-biological factors. Thus, premature termination of pregnancy is often observed in women whose work is related to physical activity, vibration, noise, chemicals(dyes, benzene, insecticides). At the frequency of N.b. factors such as the interval between pregnancies (less than 2 years), the amount of housework, the nature of relationships in the family, etc.
Genetically determined developmental disorders of the embryo (fetus), which may be hereditary or occur under the influence of various factors (infections, hormonal disorders, chemical, including some drugs, drugs, etc.) are the most common cause of miscarriage in the 1st trimester . In 2.4% of patients with habitual N.b. find significant structural abnormalities of the karyotype (10 times more often than in the population). Along with obvious anomalies of the chromosome set in women with habitual N.b. and their spouses, so-called chromosomal variants are often identified, which can cause a genetic imbalance in the fetus and lead to spontaneous abortion.
Early miscarriage
In the etiology of spontaneous abortion in the 1st trimester, hormonal disorders in a woman's body play an important role - most often, corpus luteum insufficiency and increased production of androgens of various origins. For N.b. usually characterized by erased forms of hormonal disorders, which appear only during pregnancy. Endocrine diseases(e.g. diabetes mellitus, dysfunction thyroid gland or adrenal cortex) complicate the course of pregnancy and often lead to its termination. In some cases, N.b. due to a violation of the receptor apparatus of the endometrium; most often it occurs in patients with malformations of the uterus, genital infantilism, chronic endometritis.
Among the reasons for N.b. one of the first places is occupied by infectious and inflammatory diseases of a pregnant woman, primarily hidden ones: pyelonephritis, infections caused by cytomegalovirus, herpes simplex virus, etc. Termination of pregnancy is often observed in acute infectious diseases: viral hepatitis, rubella, influenza, etc.
The significance of the immunological causes of N.b. is discussed in the literature. If, until recently, spontaneous abortion was assessed as a hyperimmune reaction of the maternal organism, at present, abortion is considered as an immunodeficiency state in which reduced immunological reactions of the maternal organism cannot provide the necessary level of immunosuppression to form the blocking properties of serum and protect the embryo (fetus) from immune mother's aggression. This condition may be due, on the one hand, to a violation of placentation processes and a decrease in the function of the trophoblast, on the other hand, the incompatibility of the organisms of the mother and fetus according to the antigens of the HLA system. The pathology of miscarriage can also be associated with autoimmune processes, for example, with the appearance of antinuclear antibodies, antibodies to cardiolipins.
Miscarriage in the second trimester
One of the most common causes of abortion in the second trimester is isthmic-cervical insufficiency due to structural and (or) functional changes in the isthmic part of the uterus. Structural changes are often the result of previous curettage of the mucous membrane of the cervical canal and body of the uterus, ruptures of the cervix, pathological childbirth; they are especially dangerous in women with malformations of the uterus, genital infantilism. Functional insufficiency of the cervix is a consequence of violations of the response of the structural elements of the cervix to neurohumoral stimuli. Common causes of abortion are the uterus, uterine malformations, intrauterine synechia (fusion). With extragenital diseases of the mother (primarily diseases of the cardiovascular system, chronic diseases of the kidneys, liver), premature birth often occurs.
Preterm labor in the third trimester
Termination of pregnancy in the II and III trimester is often caused by complications associated with pregnancy: toxicosis that occurs in the second half of pregnancy, anomalies of attachment and premature detachment of the placenta, abnormal position of the fetus, multiple pregnancy, polyhydramnios, etc.
Treatment of miscarriage
Treatment of N.b. effective under the condition of a thorough and comprehensive examination of the couple outside of pregnancy (because during pregnancy in almost half of the cases it is not possible to identify the cause of its interruption). The examination can be carried out in the antenatal clinic, the "Family and Marriage" consultation, in diagnostic centers. Examination outside of pregnancy is necessary to establish the cause of N.b., assess the state of the reproductive system of the spouses and conduct rehabilitation therapeutic and preventive measures in order to prepare for a subsequent pregnancy.
Prevention of miscarriage
Examination of a woman begins with an anamnesis, special attention is paid to information about previous diseases, the menstrual cycle, and childbearing function. Anamnesis, general examination data (body type, body hair) and the results of a gynecological examination help to suggest the causes of N.b. and outline a plan for further examination, which includes functional diagnostic tests (recording for three menstrual cycles); metrosalpingography on the 20-24th day of the menstrual cycle, which allows to exclude isthmic-cervical insufficiency, malformations of the uterus, intrauterine synechia; ultrasound examination with registration of the size of the uterus, ovaries and determination of the structure of the ovaries; bacteriological examination of the contents of the cervical canal; determination of excretion of 17-ketosteroids. It is mandatory to assess the state of health of the husband, incl. examination of his sperm.
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If, after the examination, the cause of N.b. not detected, it is necessary to determine the content of testosterone, lutropin, follitropin, prolactin and progesterone in the blood of a woman (on the 7-8th day and 21-23rd day of the menstrual cycle) to exclude hidden forms of hormonal deficiency. With an increase in the excretion of 17-ketosteroids, a dexamethasone test is indicated to determine the source of androgen hyperproduction. In cases of early termination of pregnancy, stillbirth, fetal malformations, medical genetic counseling is necessary. If an infectious genesis is suspected, N.b. conduct research aimed at identifying mycoplasmas, chlamydia, toxoplasma, viruses in the contents of the vagina, cervical canal and urethra.
The treatment of miscarriage is a complex and creative task for the doctor, especially when it comes to “recurrent miscarriage”. Treatment and preparation are carried out taking into account the data of the diagnostic examination and the factors that cause miscarriage.
The main therapeutic approaches can be found below.
- Treatment of miscarriage in an inferior luteal phase (NLF) of the cycle.
Cyclic hormone therapy may be used to prepare for pregnancy. The appointment of only gestagenic drugs in the II phase of the cycle is not enough, since the reduced level of progesterone is most often due to the low level of estrogens in the I phase of the cycle due to the formation of an inferior follicle.
Simultaneously with hormonal preparations, vitamins for pregnant women and folic acid are prescribed so that the total dose folic acid was 400 mcg.
With minor manifestations of NLF and alternating cycles with NLF with normal cycles, it is possible to prepare for pregnancy with estrogen-gestagen preparations according to the usual scheme for contraceptives. Treatment is carried out in 2 cycles. During this period, ovulation is inhibited, and when the drug is discontinued, a rebaum effect is observed, full ovulation and the development of the corpus luteum occurs, which ensures the secretory transformation of the endometrium and its preparation for implantation of the embryo. If it is not possible to normalize the second phase of the cycle by the above methods, in recent years, ovulation stimulation with Clostilbegit or Clomiphene citrate has been successfully used to prepare for pregnancy.
Good results have been obtained using electromagnetic field with a power of 0.1 mW / cm and a frequency of 57 GHz with an exposure of 30 minutes for 10 days of the first phase of the menstrual cycle. An increase in the level of progesterone, normalization of the antioxidant activity of plasma and the appearance of secretory transformation of the endometrium were noted. Good results have been obtained with the use of acupuncture.
- Treatment of miscarriage in patients with hyperandrogenism.
At the first stage, it is necessary to clarify the source of hyperandrogenism (an increase in the content of male sex hormones). Hyperandrogenism is adrenal, ovarian and mixed.
In this section, we will dwell in more detail on the most common form of hyperandrogenism, which requires correction in the treatment of miscarriage.
Mixed form of hyperandrogenism extremely similar to the ovarian form of hyperandrogenism, but with a hormonal study, it is determined:
- elevated levels of DHEA;
- moderate hyperprolactinemia;
- there is no significant increase in 17-hydroxyprogesterone;
- the level of 17KS is increased only in 51.3% of patients;
- elevated LH levels, decreased FSH levels;
- on ultrasound, 46.1% have a typical picture of polycystic ovaries, 69.2% have small cystic changes;
- at elevated level 17-KS marked hirsutism, excess body weight;
- in the dexamethasone test with hCG, there is a mixed source of hyperandrogenism, a tendency to an increase in 17KS, a significant increase in testosterone and 170P after stimulation of hCG against the background of suppression by dexamethasone.
In patients with a mixed form of hyperandrogenism, stressful situations, head injuries are quite common in anamnesis, changes in the bioelectric activity of the brain are often detected on encephalograms. These patients are characterized by hyperinsulinemia, lipid metabolism disorders, increased blood pressure. Hyperinsulinemia often leads to the development of type II diabetes (diabetus mellitus).
Preparation for pregnancy in women with mixed genesis of hyperandrogenism begins with weight loss, normalization of lipid and carbohydrate metabolism, diet, unloading days, exercise, the use of sedatives (peritol, difenin, rudotel). Useful sessions of acupuncture. At the time of this stage of preparation for pregnancy, it is advisable to prescribe oral contraceptives such as Diana-35, to treat hirsutism.
With a normal level of glucose, insulin, lipids, it is advisable to prescribe gestagens in the second phase of the cycle while taking 0.5 mg of dexamethasone, then stimulate ovulation with clostilbegid.
In preparation for pregnancy, regardless of the form of hyperandrogenism, it is recommended to prescribe complexes of metabolic therapy. This is necessary due to the fact that glucocorticoids, even in small doses, have an immunosuppressive effect, and most patients with recurrent miscarriage, regardless of its genesis, are virus carriers. To prevent exacerbation of a viral infection while taking dexamethasone, it is advisable to use metabolic therapy complexes, which, by removing tissue hypoxia, prevent viral replication.
- Tactics of managing patients in the treatment of miscarriage of infectious origin.
Habitual miscarriage is characterized by the presence of persistent forms of bacterial and viral infection in the mother's body.
The manifestations of an acute infection, or an exacerbation of a chronic infection, are always accompanied by changes in the hemostasis system, so the control of hemostasis and the normalization of all parameters are extremely important for the treatment of infection. Therapeutic and preventive measures in case of infection of a patient, or rather, a married couple, depend on the severity of the infectious process, the characteristics of the immune and interferon status, and the financial capabilities of patients.
Proteolytic enzymes are involved in virtually all immune processes:
- affect individual components of the immune system, immunocompetent cells, antibodies, complement, etc.;
- have an immunomodulatory effect on the normalization of all parameters of the immune system;
- have a direct stimulating effect on the processes of phagocytosis, the secretory activity of macrophages, natural killers. The immunomodulatory effect of enzymes is manifested in the achievement of the activity of various cells involved in immunological reactions. Enzymes, even at low concentrations, contribute to the breakdown and removal of circulating immune complexes (CIC), this is especially important when there is a combination of infection and autoimmune disorders.
An important property of enzymes is their effect on the hemostasis system and, first of all, their ability to dissolve fibrin deposits in the vessels, thereby restoring blood flow, facilitating the process of destruction of blood clots. This feature of enzymes is extremely useful, since in chronic inflammatory processes there is a depletion of its own fibrinolytic potential in the body.
- Treatment of isthmic-cervical insufficiency (ICN) outside of pregnancy (treatment of miscarriage).
When CI is detected, treatment should be etiological. So, with gross anatomical changes in the cervix due to old ruptures (if this is the only cause of miscarriage), surgical treatment is necessary outside of pregnancy (cervical plasty).
Before surgical treatment, a thorough bacteriological examination and prophylactic antibacterial treatment are necessary, since in most cases with CI, the uterine cavity is infected due to the absence of the obturator function of the isthmic cervical region.
With functional CI or with anatomical but not requiring reconstructive surgery, the first step in preparing for the next pregnancy is a thorough bacteriological examination and antibiotic therapy, taking into account the pathogen for 2 menstrual cycles in combination with physiotherapy. After that, immunological and hormonal control and pathogenetic therapy are necessary, taking into account the data obtained. Hormonal preparation is the final stage of treatment before pregnancy.
Surgery for isthmic-cervical insufficiency is also performed during pregnancy.
- Treatment of miscarriage in antiphospholipid syndrome.
If primary antiphospholipid syndrome (APS) is suspected according to the anamnesis: habitual miscarriage, episodes of thrombophilic complications preceding pregnancy with fetal growth retardation, with early onset of toxicosis in the second half of pregnancy, complications in the form of detachment of a normally located placenta, in early pregnancy with detachment chorion - a blood test is performed - a hemostasiogram and the determination of lupus anticoagulant (LA). When determining VA, a number of studies are indicated to confirm the immune or infectious nature of VA.
In the treatment of miscarriage with antiphospholipid syndrome, plasmapheresis is performed. Given the fact that almost all APS patients have a persistent viral infection, the first stage of preparation for pregnancy is antibacterial and antiviral therapy.
You should start with complexes of metabolic therapy, systemic enzyme therapy for at least a month. Interferon inducers, enterosorbents are used.
After plasmapheresis, hemostasis parameters are monitored and lupus anticoagulant is re-determined.
If after the treatment of miscarriage there are changes in the hemostasiogram, then antiplatelet agents and / or anticoagulants are used, and plasmapheresis may be repeated.
- Preparation for pregnancy of patients with sensitization to hCG.
The basis for determining autosensitization to hCG is habitual miscarriage, a history of induced abortion, the use of gonadotropic drugs to stimulate ovulation; infectious and allergic diseases and complications.
Preparation for pregnancy is carried out in the same way as it is carried out with sensitization to phospholipids. A distinctive feature is the need to correct the insufficiency of the luteal phase, which is observed more often with anti-CHG sensitization. It is recommended to conduct courses of systemic enzyme therapy. Violations in the hemostasis system in patients of this category outside of pregnancy are very rare, but if they are, it is advisable to prescribe antiplatelet agents and / or anticoagulants. Glucocorticoids (prednisolone, metipred) are prescribed in the second phase of the cycle after ovulation, determined by the rectal temperature chart. Dose selection is carried out individually. Usually 5 or 10 mg of prednisolone in the morning after breakfast.
Preparing for pregnancy allows you to reduce the percentage of complications in the first trimester: the threat of interruption, the development of a chronic form of DIC, the duration of antithrombotic therapy, and reduce the dose of glucocorticoids.
- Tactics of preparation for pregnancy (treatment of miscarriage) in patients with uterine malformations and intrauterine synechia.
Preparation of women with uterine malformations for pregnancy should be carried out taking into account the history and type of uterine malformation. Very often, a woman has a normal reproductive function and does not suspect that she has a malformation of the uterus.
In addition to the malformation of the uterus, patients with recurrent pregnancy loss have NLF, isthmic-cervical insufficiency, and chronic endometritis.
When preparing for pregnancy, it is necessary to exclude the presence of a bacterial and / or viral infection, hormonal disorders. If the tests of functional diagnostics do not correspond to hormonal parameters, exclude lesions of the receptor apparatus of the endometrium.
Preparation for pregnancy is based on the results of a full examination.
This may be antibacterial, antiviral, immunomodulatory therapy. Normalization of the II phase of the cycle through the use of cyclic hormonal therapy in combination with physiotherapy (Ci electrophoresis), moreflexotherapy.
In the event that conservative methods of preparing for pregnancy and managing pregnancy fail to complete the pregnancy safely, then surgical treatment of the malformation of the uterus can be recommended. Good results are observed when removing the intrauterine septum with hysteroresectoscopy.
With malformations in the form of a bicornuate uterus, in some cases, metroplasty according to the Strassmann method is recommended. The operation consists in dissection of the uterine horns, excision of the upper part of the uterine horns, formation of the uterus. After the operation, a spiral is inserted into the cavity for a period of 3 months to prevent the formation of synechia, and cyclic hormonal therapy is carried out. With favorable flow postoperative period after 3 months, the spiral is removed, a control hysterosalpingography or hysteroscopy is performed. After 6 months, the level of hormones is assessed. If all parameters are within the normal range, then after 3 months pregnancy is allowed.
Thus, the treatment of miscarriage is aimed at eliminating the underlying cause identified during a full examination.
In addition to the examination and consultation of related specialists (hematologists, geneticists, and a number of others), in some cases additional short-term preparation is indicated immediately before pregnancy planning. This is especially true in cases of genetic causes of miscarriage, as well as in the correction of factors associated with a violation of the blood coagulation system.
Pregnancy that occurred after the correction of miscarriage factors deserves special attention. Such patients should be observed in institutions whose specialists have the appropriate knowledge to properly manage such women and timely identify the threat of miscarriage.
Among the most important problems of practical obstetrics, one of the first places is miscarriage, the frequency of which is 20%, i.e., almost every 5th pregnancy is lost, and does not tend to decrease, despite the numerous and highly effective diagnostic and treatment methods developed in recent years. It is believed that the statistics do not include a large number of very early and subclinical miscarriages. Sporadic termination of pregnancy at short terms is considered by many researchers as a manifestation of natural selection with a high frequency (up to | 60%) of the abnormal karyotype of the embryo. Habitual pregnancy loss (childless marriage) occurs in 3-5% of couples.
With habitual pregnancy loss, the frequency of abnormal embryonic karyotype is much lower than with sporadic miscarriage. After two spontaneous miscarriages, the frequency of termination of a subsequent pregnancy is already 20-25%, after three - 30-45%. Most specialists dealing with the problem of miscarriage now come to the conclusion that two consecutive miscarriages are enough to classify a married couple as habitual pregnancy loss, followed by a mandatory examination and a set of measures to prepare for pregnancy.
Miscarriage- its spontaneous interruption in terms from conception to 37 weeks. In world practice, it is customary to distinguish between early pregnancy loss (from conception to 22 weeks) and premature birth (from 22 to 37 weeks). Premature births are divided into 3 groups, taking into account the gestational age from 22 to 27 weeks - very early preterm birth, from 28 to 33 weeks - early preterm birth and at 34-37 weeks of gestation - premature birth. This division is quite justified, since the causes of termination, treatment tactics and pregnancy outcomes for the newborn are different during these periods of pregnancy.
As for the first half of pregnancy, it is completely illogical to bring everything into one group (early pregnancy losses), since the causes of termination, management tactics, and therapeutic measures differ even more than with a gestational age after 22 weeks.
In our country, it is customary to single out early and late miscarriages, termination of pregnancy at 22-27 weeks and premature birth at 28-37 weeks. Early pregnancy losses up to 12 weeks make up almost 85% of all losses, and the shorter the gestational age, the more often the embryo dies at first, and then the symptoms of abortion appear.
The causes of abortion are extremely diverse, and often there is a combination of several etiological factors. Nevertheless, there are 2 main problems in terminating a pregnancy in the first trimester:
1st problem- the state of the embryo itself and chromosomal abnormalities arising de novo or inherited from parents. Hormonal diseases can lead to chromosomal disorders of the embryo, leading to disturbances in the processes of maturation of the follicle, the processes of meiosis, mitosis in the egg, in the sperm.
2nd problem- the state of the endometrium, i.e., a characteristic of the pathology due to many reasons: hormonal, thrombophilic, immunological disorders, the presence of chronic endometritis with persistence in the endometrium of viruses, microorganisms, high level pro-inflammatory cytokines, high content of activated immune cells.
However, both in the 1st and 2nd groups of problems, there is a violation of the processes of implantation and placentation, improper formation of the placenta, which subsequently leads either to termination of pregnancy, or when it progresses to placental insufficiency with delayed fetal development and the occurrence preeclampsia and other complications of pregnancy.
In this regard, there are 6 large groups of causes of habitual pregnancy loss. These include:
- genetic disorders (inherited from parents or arising de novo);
- endocrine disorders (insufficiency of the luteal phase, hyperandrogenism, diabetes, etc.);
- infectious causes;
- immunological (autoimmune and alloimmune) disorders;
- thrombophilic disorders (acquired, closely related to autoimmune disorders, congenital);
- pathology of the uterus (malformations, intrauterine synechia, isthmic-cervical insufficiency).
Each stage of pregnancy has its own pain points, which for most women are the leading causes of abortion.
When a pregnancy is terminated up to 5-6 weeks the leading reasons are:
- Features of the karyotype of parents (translocations and inversions of chromosomes). Genetic factors in the structure of the causes of recurrent miscarriage account for 3-6%. With early pregnancy losses, anomalies in the karyotype of the parents, according to our data, are observed in 8.8% of cases. The probability of having a child with unbalanced chromosomal abnormalities in the presence of balanced chromosomal rearrangements in the karyotype of one of the parents is 1 - 15%.
The difference in the data is related to the nature of the rearrangements, the size of the involved segments, the gender of the carrier, and family history. If a couple has a pathological karyotype even in one of the parents, prenatal diagnosis during pregnancy (chorionic biopsy or amniocentesis is recommended due to the high risk of chromosomal abnormalities in the fetus). - In recent years, much attention in the world has been paid to the role of the HLA system in reproduction, protection of the fetus from the mother's immune aggression, and in the formation of tolerance to pregnancy. The negative contribution of certain antigens, the carriers of which are men in married couples with miscarriage, has been established. early dates. These include HLA class I antigens - B35 (p< 0,05), II класса - аллель 0501 по локусу DQA, (р < 0,05). Выявлено, что подавляющее число анэмбрионий приходится на супружеские пары, в которых мужчина имеет аллели 0201 по локусу DQA, и/или DQB, имеется двукратное увеличение этого аллеля по сравнению с популяционными данными. Выявлено, что неблагоприятными генотипами являются 0501/0501 и 0102/0301 по локусу DQA, и 0301/0301 по локусу DQB. Частота обнаружения гомозигот по аллелям 0301/0301 составляет 0,138 по сравнению с популяционными данными - 0,06 (р < 0,05). Применение лимфоцитоиммунотерапии для подготовки к беременности и в I триместре позволяет доносить беременность более 90% женщин.
- It has been established that the immunological causes of early pregnancy losses are due to several disorders, in particular, a high level of pro-inflammatory cytokines, activated NK cells, macrophages in the endometrium, and the presence of antibodies to phospholipids. High levels of antibodies to phosphoserine, choline, glycerol, inositol lead to early pregnancy losses, while lupus anticoagulant and high levels of antibodies to cardiolipin are accompanied by intrauterine fetal death in later pregnancy due to thrombophilic disorders. A high level of pro-inflammatory cytokines has a direct embryotoxic effect on the embryo and leads to chorionic hypoplasia. Under these conditions, pregnancy cannot be maintained, and if pregnancy persists at lower levels of cytokines, then primary placental insufficiency is formed. CD56 endometrial large granular lymphocytes account for 80% of the total immune cell population in the endometrium at the time of embryo implantation. They play an important role in trophoblast invasion, change the mother's immune response with the development of pregnancy tolerance by releasing progesterone-induced blocking factor and activating Tp2 to produce blocking antibodies; provide the production of growth factors and pro-inflammatory cytokines, the balance of which is necessary for trophoblast invasion and placentation.
- In women with failures in the development of pregnancy, both in recurrent miscarriage and after IVF, the level of aggressive LNK cells, the so-called lymphokine-activated (CD56+l6+ CD56+16+3+), increases dramatically, which leads to an imbalance between regulatory and pro-inflammatory cytokines towards the predominance of the latter and to the development of local thrombophilic disorders and abortion. Very often, women with high levels of LNK in the endometrium have a thin endometrium with impaired blood flow in the vessels of the uterus.
With habitual abortion at 7-10 weeks The leading causes are hormonal disorders:
- insufficiency of the luteal phase of any genesis,
- hyperandrogenism due to impaired folliculogenesis,
- hypoestrogenism at the stage of choosing a dominant follicle,
- defective development or overmaturation of the egg,
- defective formation of the corpus luteum,
- defective secretory transformation of the endometrium.
- As a result of these disorders, defective invasion of the trophoblast and the formation of an inferior chorion occur. Pathology of the endometrium due to hormonal disorders, not
- always determined by the level of hormones in the blood. The receptor apparatus of the endometrium may be disturbed, there may be no activation of the genes of the receptor apparatus.
With habitual miscarriage over 10 weeks The leading causes of violations in the development of pregnancy are:
- autoimmune problems
- closely related thrombophilic, in particular antiphospholipid syndrome (APS). In APS without treatment, in 95% of pregnant women, the fetus dies due to thrombosis, placental infarction, placental abruption, development of placental insufficiency and early manifestations gestoses.
The thrombophilic conditions during pregnancy, leading to habitual miscarriage, include the following forms of genetically determined thrombophilia:
- antithrombin III deficiency,
- factor V mutation (Leidin mutation),
- protein C deficiency
- protein S deficiency,
- mutation of the prothrombin gene G20210A,
- hyperhomocysteinemia.
An examination for hereditary thrombophilia is carried out with:
- the presence of thromboembolism in relatives under the age of 40,
- unclear episodes of venous and / or arterial thrombosis under the age of 40 with recurrent thrombosis in the patient and close relatives,
- with thromboembolic complications during pregnancy, after childbirth (repeated pregnancy losses, stillbirths, delayed prenatal development fetus, placental abruption, early onset preeclampsia, HELLP syndrome),
- when using hormonal contraception.
Treatment is carried out with antiplatelet agents, anticoagulants, with hyperhomocysteinemia - the appointment of folic acid, vitamins of group B.
During pregnancy after 15-16 weeks the causes of miscarriage of infectious genesis (gestational pyelonephritis), isthmic-cervical insufficiency come to the fore. In connection with the local immunosuppression characteristic of pregnant women during these periods, candidiasis, bacterial vaginosis, and banal colpitis are often detected. Infection by the ascending route in the presence of isthmic-cervical insufficiency leads to premature rupture of amniotic fluid and the development of contractile activity of the uterus under the influence of the infectious process.
Even this by no means small list of reasons shows that it is impossible to solve these problems during pregnancy. It is possible to understand the causes and pathogenesis of interruption only on the basis of a thorough examination of a married couple before pregnancy. And for the examination, modern technologies are needed, i.e., highly informative research methods: genetic, immunological, hemostasiological, endocrinological, microbiological, etc.
It also requires a high professionalism of a doctor who can read and understand a hemostasiogram, draw conclusions from an immunogram, understand information about genetic markers of pathology, and, based on these data, select etiological and pathogenetic, and not symptomatic (ineffective) therapy.
Biggest Discussions cause problems that arise with a gestational age of 22-27 weeks. According to WHO recommendations, this period of pregnancy is referred to as premature birth. But children born at 22-23 weeks practically do not survive and in many countries births from 24 or 26 weeks are considered premature. As a result, the rate of preterm birth varies between different countries.
In addition, during these periods, possible fetal malformations are specified according to ultrasound data, according to the results of fetal karyotyping after amniocentesis, and abortion is performed for medical reasons. Can these cases be classified as preterm births and included in perinatal mortality rates?
Often, fetal weight at birth is taken as a marker of gestational age. If the fetus weighs less than 1000 g, it is considered an abortion. However, about 64% of babies up to 33 weeks' gestation have intrauterine growth retardation and birth weights that are not appropriate for their gestational age.
The gestational age more accurately determines the outcome of childbirth for a premature fetus than its weight. Analysis of pregnancy losses at 22-27 weeks of gestation at the Center showed that the main immediate causes of abortion are isthmicocervical insufficiency, infection, prolapse of the fetal bladder, premature rupture of water, multiple pregnancies with the same infectious complications and malformations.
Nursing children born during these terms of pregnancy is a very complex and expensive problem, requiring huge material costs and high professionalism of medical personnel. The experience of many countries, in which preterm births are counted from the above terms of pregnancy, indicates that with a decrease in perinatal mortality in these terms, disability from childhood increases by the same amount.
Pregnancy 28-33 weeks accounts for approximately 1/3 of all preterm births, the rest are preterm births at 34-37 weeks, the outcomes of which for the fetus are almost comparable to those in full-term pregnancy.
An analysis of the direct causes of abortion showed that up to 40% of preterm births are due to the presence of infection, 30% of births occur due to premature rupture of amniotic fluid, which is also often due to ascending infection.
Isthmic-cervical insufficiency is one of the etiological factors of preterm birth. The introduction into practice of assessing the state of the cervix by transvaginal ultrasound showed that the degree of competence of the cervix can be different and often isthmic-cervical insufficiency manifests itself in late pregnancy, which leads to prolapse of the fetal bladder, to infection and to the onset of labor.
Another significant cause of preterm birth is chronic fetal distress due to the development of placental insufficiency in preeclampsia, extragenital diseases, and thrombophilic disorders.
Overstretching of the uterus during multiple pregnancy is one of the causes of premature birth and extremely complicated pregnancy in women after the use of new reproductive technologies.
Without knowledge of the causes of preterm labor, there can be no successful treatment. Thus, tocolytic drugs with different mechanisms of action have been used in world practice for more than 40 years, but the frequency of preterm birth does not change.
In most perinatal centers in the world, only 40% of preterm births are spontaneous and pass through the natural birth canal. In other cases, abdominal delivery is performed. The outcome of childbirth for the fetus, the incidence of newborns during abortion by surgery may differ significantly from the outcomes of childbirth for a newborn with spontaneous preterm birth.
So, according to our data, in the analysis of 96 preterm births at a period of 28-33 weeks, of which 17 were spontaneous and 79 ended with a caesarean section, the outcome of childbirth for the fetus was different. The stillbirth rate for spontaneous delivery was 41%, for caesarean section - 1.9%. Early neonatal mortality was 30% and 7.9%, respectively.
Given the adverse outcomes of preterm birth for the child, it is necessary to pay more attention to the problem of preventing preterm birth at the level of the entire population of pregnant women. This program should include:
- examination outside of pregnancy of women at risk of miscarriage and perinatal losses and rational preparation of spouses for pregnancy;
- control of infectious complications during pregnancy: in world practice adopted
- screening for infections at first visit, followed by bacteriuria and Gram smear evaluation every month.
In addition, attempts are being made to determine the markers of early manifestations of intrauterine infection (fibronectin IL-6 in cervical mucus, TNFa IL-IB in the blood, etc.)
- timely diagnosis of isthmic-cervical insufficiency (ultrasound with a transvaginal sensor, manual assessment of the cervix up to 24 weeks, and with multiple pregnancy up to 26-27 weeks) and adequate therapy - antibacterial, immunotherapy;
- prevention of placental insufficiency from the first trimester in risk groups, control and therapy of thrombophilic disorders, rational therapy of extragenital pathology;
- prevention of preterm birth by improving the quality of management of pregnant women at the level of the entire population.
V. M. SIDELNIKOVA
MISSION OF PREGNANCY - A MODERN VIEW ON THE PROBLEM
Journal of Obstetrics and Gynecology, 2007, No. 5, 24-27.
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