Classification of recurrent miscarriage.

The outcome of miscarriage is usually the expulsion of the fetus (viable or not), less often the dead fetus remains in the uterus. A non-developing pregnancy in such cases is classified as a failed miscarriage or failed birth. In modern obstetrics, the following division of pregnancy loss according to the timing of the episode (according to the WHO classification) is accepted:

• Spontaneous abortion (miscarriage). Interruption of the gestation process up to 21 completed weeks. In Russia, early (up to 12 full weeks) miscarriage and late - from the thirteenth week are distinguished.

• Premature birth. Interruption from the 22nd to the full 37th week (with a fetal weight of 500 grams), including very early (at 22-27 weeks) and early (at 28-33 weeks) preterm birth. In Russia, pregnancy loss before the full 27th week does not apply to preterm birth, and perinatal mortality is counted from the 28th week.

Pathogenesis of recurrent miscarriage.

Habitual losses associated with the chromosomal factor are due to the abnormal initiation of the embryo and its initial non-viability. Other factors create an unfavorable background for implantation, the formation and normal functioning of the placenta, and the further development of the embryo. As a result of alloimmune disorders, the mother's immune system attacks the "foreign" antigens of the embryo received from the father, the mother's body rejects the fetal egg. Autoimmune reactions lead to damage to maternal tissues, which has an indirect adverse effect on the embryo.

A deficiency or imbalance of sex hormones provokes an inferior gravid transformation of the endometrium, a lack of progesterone leads to impaired immune restructuring. Latent infections potentiate an increase in the activity of local immunity. As a result of thrombophilia (including APS), the balance between the processes of fibrin formation and fibrinolysis during implantation is disturbed, thrombosis of the vascular bed occurs and uteroplacental blood flow is disturbed. All these changes become the causes of inferior trophoblast invasion, impaired placentogenesis and fetoplacental insufficiency.

Causes of habitual miscarriage.

Recurrent miscarriage is most often associated with long-term adverse endogenous effects. The etiological factors of this obstetric pathology are in many respects similar to those in infertility or sporadic interruption of gestation and differ only in lesser severity compared to infertility and a permanent nature, in contrast to the transient effect with spontaneous losses. The main causes of habitual miscarriage include:

• Autoimmune diseases. The proportion of immunological factors in the etiology of pregnancy loss is up to 80%. The most significant autoimmune disorders include antiphospholipid syndrome (APS), sensitization to human chorionic gonadotropin, thyroid hormones, and nuclear antigens. The risk group includes mothers suffering from autoimmune diseases, viral infections (hepatitis C, HIV).

• Alloimmune disorders. Among the alloimmune causes of miscarriage are high histocompatibility of spouses, the predominance of pro-inflammatory cytokines in the blood of the mother and endometrium, and a deficiency of the progesterone-induced blocking factor. The risk group includes women who are married to a blood relative, who have endocrine pathologies with progesterone deficiency.

• Congenital thrombophilia. In a third of pregnant women, recurrent miscarriage is provoked by mutations in factor V Leiden and the prothrombin gene, deficiency of antithrombin III, proteins C and S, and hyperhomocysteinemia. Risk factors: early (up to forty years) thromboembolism, recurrent thrombosis in a woman and her close relatives, thrombotic complications associated with gestation, childbirth and the use of hormonal contraceptives.

• Endocrine disorders. In 8-20% of patients, the cause of losses is luteal phase deficiency, increased secretion of luteinizing hormone, hyperandrogenism, hypothyroidism and decompensated diabetes mellitus. The risk group consists of women with obesity, signs of virilization, late menarche, sharp fluctuations in body weight, oligo- and amenorrhea, menstrual irregularities.

• Endometrial infections. In 87% of patients with miscarriage, persistence in the endometrium of several types of obligate anaerobic flora and viral agents (herpes simplex, cytomegalovirus, Coxsackie, enteroviruses) is noted. The likelihood of endometritis is increased in patients with chronic lower genital tract infection, bacterial vaginosis, induced abortions, and previous uterine surgery.

• Anatomical defects of the uterus. Congenital (duplication of the uterus, saddle-shaped, unicornuate uterus, intrauterine septum) and acquired (submucosal myomatous nodes, intrauterine adhesions) anatomical disorders are the cause of abortion in 10-16% of women. Risk factors for acquired pathologies: endometritis, artificial abortions, surgical interventions on the uterus.

• Pathology of the cervix. Isthmic-cervical insufficiency (ICI) can be anatomical or functional in nature and is involved in recurrent interruptions of gestation in 13-20% of cases. It often develops with hyperandrogenism of any genesis, cervicitis, after a difficult birth (accompanied by ruptures, the use of obstetric forceps), conization of the cervix, hyperovulation induction.

• Genetic abnormalities of the fetus. Usually these are chromosomal aberrations that lead to habitual miscarriage in 3-6% of cases. Among them, monosomy X0 (Shereshevsky-Turner syndrome), various trisomies, polyploidy. Risk factors: closely related marriage, hereditary diseases in the families of the patient and her spouse, the presence of children with congenital defects in a married couple, mental retardation.

General information about miscarriage.

According to the definition of the World Health Organization, recurrent miscarriage is a consecutive three-fold spontaneous interruption of gestation (including the cessation of development). However, according to many clinicians, the presence of two episodes of pregnancy loss should be considered as the criteria for recurrent miscarriage. The prevalence of pathology is 2-5%, a significant part of the habitual losses are recorded before the viability of the fetus (22 weeks). The probability of subsequent spontaneous interruption increases significantly with an increase in the number of previous episodes: if after the first loss the risk of the next one is 15%, then after two failures in a row this figure more than doubles - up to 36-38%.

What is recurrent miscarriage?

Recurrent miscarriage is a polyetiological reproductive pathology characterized by repeated consecutive episodes of spontaneous interruption of gestation up to the 38th (full 37) weeks. The main signs of a miscarriage include pelvic pain and spotting from the genital tract. Diagnosis includes history taking, physical examination, ultrasonography, coagulogram, bacteriological and PCR analysis for infections, spouse karyotyping, HLA II typing. Treatment is usually conservative; surgery may be required for anatomical abnormalities.

Forecast. Prevention of miscarriage.

Women with preterm labor, spontaneous miscarriages, missed pregnancies, as well as with threatened miscarriage and spotting during this pregnancy should be allocated to a high risk group for miscarriage for the timely administration of vaginal progesterone. Progesterone is prescribed from early pregnancy or from the moment of the threat of termination of pregnancy. The use of progesterone is also indicated to support the luteal phase after IVF. The route of administration of progesterone does not matter.

You can judge the favorable development of pregnancy by the indicators of hCG and progesterone. Until 6-7 weeks of pregnancy, the level of hCG should increase by 2 times every 1.5-2 days. If the hCG level is low or it goes down, then the pregnancy is not progressing.

With an ultrasound examination with a vaginal probe, the fetal egg should normally be visualized at a period of 4 weeks. The diameter of the ovum in this case is 3-5 mm, which corresponds to the hCG levels of 1500-2000 IU / l. In case of discrepancy with these criteria, the prognosis for the development of pregnancy is doubtful.

The level of progesterone can indirectly also be a predictor of pregnancy outcome:

• > 60 nmol/l - indicates the normal course of pregnancy;

• < 25 nmol / l - portends an unfavorable outcome of pregnancy.

Prevention of miscarriage includes:

• prevention of inflammatory diseases of the small pelvis, rehabilitation of foci of chronic inflammation;

• normalization of the biocenosis of the vagina;

• rejection of bad habits;

• healthy lifestyle;

• control of body weight;

• examination and treatment of general somatic pathology, correction of hormonal disorders;

• prevention of abortion;

• pregnancy planning;

• screening for sexually transmitted diseases and their timely treatment;

• diagnosis and treatment of TORCH infections, if any;

• avoidance of a large number of sexual partners.

Non-specific preconception preparation of the patient (preparation before pregnancy):

• psychological assistance to a patient who had an abortion;

• anti-stress therapy;

• normalization of the regime of work and rest, diet (it is recommended that 3 months before the intended conception, a woman should be given folic acid intake of 400 mcg per day);

• rejection of bad habits;

• medical genetic counseling for women with recurrent miscarriage.

If the cause of recurrent miscarriage is anatomical, surgical treatment is indicated: elimination of the intrauterine septum, synechia, myomatous nodes, endometrial polyps. After the elimination of the anatomical causes of miscarriage, the patient is prescribed a combined estrogen-gestagen preparation for a period of at least three months.

After the third miscarriage (recurrent miscarriage), with the exclusion of genetic and anatomical causes of miscarriage, a woman should be examined for possible coagulopathy (family history, determination of lupus anticoagulant and anticardiolipin antibodies, D-dimer, antithrombin 3, homocysteine, folic acid, antisperm antibodies).

Carrying out pathogenetically substantiated preconception preparation contributes to a significant reduction in gestational complications by 6-8 times, the overall frequency of adverse pregnancy outcomes by 4 times, spontaneous miscarriages by 4.5 times.

Treatment of miscarriage.

Termination threat therapy.

Pathogenetic therapy for miscarriage of endocrine genesis includes taking progesterone preparations for at least 12 weeks.

If hypothyroidism (insufficient functioning of the thyroid gland) was identified among the causes of miscarriage, then treatment is carried out in conjunction with an endocrinologist. In this case, it is necessary to take thyroid hormones throughout the pregnancy, such as L-Thyroxine, Euthyrox.

If the cause of miscarriage was an infection, then antibiotic therapy is carried out, taking into account the isolated flora.

In case of problems in the hemostasis system, anticoagulants are prescribed that inhibit the activity of the blood coagulation system (Fraxiparin, Kleksan) from the moment of conception to childbirth. Antiplatelet agents that prevent thrombosis ("Kurantil"), B vitamins, metafolin (the active form of folic acid).

With an immunological factor, some medical institutions use lymphocytotherapy (LIT) - the introduction of a partner's lymphocytes to a woman.

In a hospital, antispasmodics (No-shpa, drotaverine, papaverine), calcium channel blockers, magnesium solution intravenously are used to treat the threat of miscarriage.

With ICI, when the cervix is shortened by less than 25 mm and / or the cervical canal is opened by 10 mm, a suture is applied to the cervix up to 23 weeks, or an obstetric pessary is used for a period of more than 23 weeks. In parallel, bacteriological vaginal discharge is monitored, progesterone support is required.

If it is no longer possible to maintain a pregnancy in a medical institution, a therapeutic and diagnostic curettage of the uterine cavity and removal of the remnants of the fetal egg or placenta are performed.

In the future, the prophylactic use of antibiotics is mandatory. All Rh-negative women who do not have anti-Rh antibodies are given anti-D immunoglobulin.

To prevent miscarriage in case of a threat, it is necessary to take vitamins and trace elements. They improve the quality of oocytes (sex cells) involved in fertilization, contribute to the proper laying of organs in the embryo, in particular the formation of the neural tube, contribute to the harmonious development of the fetus and placenta, and are components for the synthesis of hormones that maintain pregnancy.

• Folate 3 months before pregnancy + the first 12 weeks - 400-800 mcg / day.

• Iodine preparations - 250 mcg / day 3 months before pregnancy + during the entire gestation period.

Desirable:

• Vitamin D: 3 months before pregnancy 600-800 IU/day and 800-1200 IU/day during pregnancy.

• PUFA - 200-300 mg / day (Omega-3 preparations).

An integrated approach in the management of severe patients is very important, since most of them require the participation of related specialists.

Diagnosis of miscarriage.

Examination stages:

1. Anamnesis - collection of information. Risk groups for preterm birth include:

• women with a history of preterm labor in the absence of symptoms;

• women who have a shortening of the cervix less than 25 mm are detected during transvaginal examination;

• women who have a history of premature birth, who have lost 2 or more pregnancies;

• pregnant women who had a threat of miscarriage, spotting and retrochorial hematoma in the early stages.

2. An objective examination - an examination is performed, weight, height are measured.

3. Gynecological examination, flora smear, cytology smear, colposcopy.

4. Ultrasound of the pelvic organs. During pregnancy, the threat of loss is evidenced by: shortening of the cervix to 25 mm or less according to transvaginal cervicometry in the period of 17-24 weeks. The length of the cervix is clearly correlated with the risk of preterm birth, this is one of the prognostic signs of preterm birth. Transvaginal ultrasound measurement of the length of the cervix is a necessary standard in risk groups for miscarriage.

5. Examination for infections (sexually transmitted diseases, TORCH infections, HIV, hepatitis B and C, syphilis).

6. Hormonal screening:

• on the 2nd-5th day of the menstrual cycle with a regular cycle or in the absence of menstruation any day in the morning on an empty stomach;

• Prolactin, FSH (follicle-stimulating hormone), LH (luteinizing hormone), TSH (thyroid-stimulating hormone), estradiol, free testosterone, DGA-sulfate, cortisol are determined.

7. Ultrasound of the mammary glands.

8. Ultrasound of the thyroid gland and adrenal glands.

According to indications: hysterosalpingography, hysteroscopy, laparoscopy, CT or MRI of the skull and sella turcica, spiral CT of the pelvis / MRI.

Examination of a man:

1. Consultation with an andrologist - a male doctor who specializes in diseases of the male genitourinary system. Often, miscarriage is associated with a male factor in the form of chronic inflammatory diseases of the genitourinary system of a man, the carriage of STDs, and abnormalities in the spermogram.

2. Spermogram + MAR test. The MAR test is a study aimed at detecting antisperm antibodies of the IgG and IgA classes for diagnosing the immunological causes of infertility in men. The MAR test shows the ratio (percentage) of normal, actively motile spermatozoa coated with antisperm antibodies to the total number of spermatozoa with the same characteristics. It also allows you to estimate the percentage of spermatozoa excluded from fertilization. A positive MAR test is a conditional criterion for immunological infertility in men (more than 50%). It is important to remember the rules for taking a spermogram: do not drink alcoholic beverages for 3-5 days, refrain from sexual intercourse, do not visit saunas and baths.

3. Infectious screening.

Complications of miscarriage.

Miscarriage is a rather severe multifactorial pathology. Therefore, it is not easy to predict the outcome of subsequent pregnancies. First of all, among the complications, one can note a pronounced depressive syndrome in a woman who has lost her desired pregnancy. Particularly severe psycho-emotional state in patients suffering from habitual miscarriage.

If an out-of-hospital spontaneous miscarriage occurs, and no follow-up and treatment is carried out, the woman may develop pelvic inflammatory disease, since the remnants of the ovum are an excellent breeding ground for microorganisms.

The formation of isthmic-cervical insufficiency (ICI) can also be considered a complication of an interrupted pregnancy. This is an anatomical or functional defect in the circular muscles of the cervix, which subsequently leads to the opening of the cervix, prolapse of the ovum (protrusion into the cervix) and habitual loss of pregnancy.

In the case of a frozen pregnancy, when the fetus dies and stays inside the uterus for a long time (over 4-6 weeks), especially in the 2nd trimester, bleeding may occur due to the development of DIC (disseminated intravascular coagulation) - a condition characterized by disorders in the blood coagulation system. In this case, depending on the stage of DIC, the formation of multiple blood clots in the vessels of various organs occurs, or bleeding occurs.

A pregnant woman with a history of miscarriage belongs to the high risk group for preterm birth.

A threat to a woman's life in case of miscarriage exists only in case of massive bleeding and hemorrhagic shock (a critical condition caused by acute rapid single blood loss) or in case of infectious complications. When the remains of the fetal egg are infected, inflammatory diseases of the pelvic organs may develop, such as endometritis (inflammation of the uterus), parametritis (inflammation of the periuterine tissue), peritonitis (inflammation of the peritoneum), complicated by blood poisoning (sepsis) and infectious toxic shock.

Classification and stages of development of miscarriage.

Classification according to ICD-10 (International Classification of Diseases 10th revision):

• O03 - Spontaneous abortion - spontaneous pathological termination of pregnancy.

• O02.1 - Miscarriage - a condition in which intrauterine fetal death occurs without expulsion of the fetal egg from the uterus.

• O20.0 - Threatened abortion is a threatened abortion, manifested by increased uterine tone and/or bloody discharge from the uterus before 22 weeks of gestation.

• N 96 - Habitual miscarriage - loss of pregnancy three times or more.

• O60 - Premature birth - delivery that occurred at a period of 22 to 37 completed weeks and with a fetal weight of more than 500 g.

The stages of the disease are:

• Threatening abortion - there are sensations of heaviness or slight pulling pains in the lower abdomen and in the sacrum. Bleeding is usually absent. The uterus is enlarged according to the delay in menstruation, there are no changes in the vaginal part of the cervix.

• Spontaneous miscarriage that has begun - the severity of the pain symptom increases, bloody discharge from the genital tract appears. The size of the uterus corresponds to the gestational age. The cervix is preserved, its canal is closed or slightly open.

• Abortion in progress - the appearance of cramping pain, increased bloody discharge. The cervix is shortened, the cervical canal is open. An abortion in progress may result in an incomplete abortion, when the fetal egg is partially expelled from the cavity. And in the uterus, the fetal membranes, chorionic tissue, placenta are retained.

• Failed spontaneous miscarriage (missed pregnancy) - after the death of the fetal egg, there is no contractile activity of the uterus, the dead fetal egg is not expelled from the uterus, but undergoes secondary changes (autolysis, mummification, resorption of amniotic fluid).

• With isthmic-cervical insufficiency (inability of the muscles of the cervix to hold the fetus and its membranes), abortion most often begins with premature rupture of amniotic fluid (due to infection and violation of the integrity of the membranes). A miscarriage occurs fairly quickly and painlessly.

• Premature birth - begins with an increase in the tone of the myometrium, dull pain in the lower abdomen, which then develop into cramping. The smoothing of the cervix and the opening of the uterine os progresses.

The disease does not always go through all stages. It can stop at one of them with timely treatment or when the factor that provoked the threat is not so strong.