Method of prevention and treatment of thread of abortion in women with uterus myoma in accordance with new conception of its etiopathogenesis

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to obstetrics and gynecology, and can be used for prevention and treatment of threat of abortion in women with uterus myoma. For this purpose patient is administered preventive wearing of Polish inserts "Piocal" for 8-15 hours per day. With beginning of pregnancy 5-7 hours per day. Simultaneously before pregnancy administered is "Dienay" in dose 1 capsule during 3 days. After that, 2 capsules 3 more days and on the following days in dose 2 capsules 2 times per day, course duration being 3 weeks. After 7-10 day break, administered is "Neurostrim" in dose 2 capsules in the morning and 1 capsule in the evening 30 minutes before meal with course 3-4 weeks. During pregnancy additionally administered is "Lohelan" - 20-30 minutes before meal, In dose one fourth of glass 2 times per day, with course of treatment 20 days, 2-3 courses during pregnancy, and "MIGI" - 1 tablespoon without dilution 3 times per day for 15 days, 1-2 courses for entire term of pregnancy.

EFFECT: application of invention makes it possible to eliminate chronic hypoxia of brain, normalise function of hypothalamic pituitary system, cure chronic inflammatory process of female genitalia, as well as improve utero-placental blood flow, thus creating favourable conditions for pregnancy prolongation.

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The invention relates to medicine, namely obstetrics and gynecology, and relates to an integrated method for the prevention and treatment of threatened abortion in women with uterine cancer, according to a new opinion on its etiopathogenesis.

The problem of miscarriage today is still relevant, despite significant advances in medical science and practice. It is acute social and medical significance. The frequency of miscarriage is according to different authors from 10 to 25% of all pregnancies. Such a high frequency of miscarriage due to the fact that miscarriages in the first trimester constitute 75-80% of all cases of abortion and are a kind of natural selection, by elimination often abnormally formed embryo. However, the death of the embryo or the threat of miscarriage in women with uterine myoma is different, except the simultaneous combination with abnormal development of the embryo.

According to the "Classification of the causes of miscarriage", received in our country's largest distribution, it is obvious that she is far from perfect, although it covers a variety of causes leading to abortion, in the first place are genetic causes. These reasons are dominiruyushie the character.

The second place is given neuroendocrine reasons (syndrome defective luteal phase, hyperandrogenism, polycystic ovary syndrome, thyroid disease) (Bazin M.I., Egorova A.T., Historical A.I. "Miscarriage". - Krasnoyarsk - 2004. - 43 C.). They recommend physical and sexual calm, psychotherapy, sedatives, antispasmodics (papaverine, no-Spa), hormones (utrogestan, progesterone), human chorionic gonadotropin.

According to our opinion these neuroendocrine factors are not the cause but the consequence of the main causes of chronic hypoxia brain against the background of increased intracranial pressure and circulatory disorders mild. Treatment should be focused first and foremost on the normalization of blood circulation and elimination of possible chronic hypoxia of the brain.

Most authors recognize the need for preventive treatment of couples or women only, depending on the identified causes. About pregravid prepare women for the prevention of miscarriage is reportedly in the works Kachesova O.V. et al. ("The efficacy of therapeutic plasma exchange and endovascular laser irradiation of blood in pregravid prepare women with a high risk Nevin is shivani pregnancy" // - The materials of the 9th all-Russian scientific forum "Mother and child", Moscow, 2007. with 112-113).

At the working group who "Drugs and pregnancy" in 1984 said about hormone therapy during pregnancy: "...the danger of drug use should always be borne in mind. Treatment only in those cases when it is extremely necessary."

About the physiological significance carolling rhythm of the hypothalamic - pituitary system to implement a complete emulatore - menstrual cycle shown in clinical studies Leyendecker G et al. (1980; 1983).

Of luteal insufficiency in 85% of women with habitual early pregnancy losses (based on tests of functional diagnostics) indicates Agadzhanova A.A. ("Modern methods of treatment of patients with habitual miscarriage" Russian journal of medicine, volume 11 (173), in 2003 - p.3-6).

In recent years, in practice the treatment of threatened abortion increasingly being introduced to Duphaston (Manukhin IB, Gevorgyan M.A., cold LB, Zakharova SO, manukhina H., Casenew EV Efficiency Duphaston in the treatment of the threat of termination of early pregnancy" // Materials of the 9th all-Russian scientific forum "Mother and child". - M, - 2007. with 156-157).

Published a special look, providing new insights into the cause arose the ovenia uterine fibroids (Reduty NR. A new look at the pathogenesis of uterine fibroids. // Materials of scientific-practical conference "Modern aspects of pathogenesis and treatment of uterine fibroids". - Tomsk - 2009. with 13-18), largely explains the reason for the frequent deviations in the course of pregnancy in women with fibroids, especially in the first trimester. Existing chronic hypoxia brain with easy blood circulation on the background of increased intracranial pressure, lasting in most cases, tens of years, leads to chronic shortages of basic supplies the brain with oxygen and nutrients with all the ensuing consequences. In particular, with the advent of menarche on the foreground there is dysfunction of the hypothalamic-pituitary-ovarian system. The extent of these violations will depend, of course, not only from the old process, but also on the severity of the changes in the brain.

It is known that the hypothalamus is an intermediate link between the nervous and endocrine system, bringing them together. On the one hand, he has to perceive and transmit nerve impulses, and on the other, to produce and allocate secrets (neurohormones). There are two types of hypothalamic secrets affecting gormonoobrazovanii function of the pituitary: growth hormone-releasing factors (to stimulate secretion of pituitary hormones) and inhibitor factors (depressing and and weaken their separation). The pituitary gland then releases the gonadotropic hormones FSH, LH, prolactin, acting on peripheral endocrine system.

Before puberty basal, or permanent, the secretion of gonadotropic hormones occurs without the participation of the hypothalamus. Normally, only when reaching sexual maturity hypothalamic secrets cause a sequence of (cyclic) increasing the production of gonadotropic hormones, which leads to growth and maturation of the follicle, ovulation, formation of the yellow body.

In the case of chronic hypoxia brain disorders in him circulatory mild, against the background of increased intracranial pressure, there are anatomical and functional changes, as in the hypothalamus and the pituitary gland, that is, there is dysfunction of the hypothalamic-pituitary system, and therefore cannot be complete and in sufficient quantity, as secret and hormones.

As a result of this dysfunction violation occurs not only in the hypothalamus-pituitary-ovaries, fails on many systems of the female body. For example, secreted by the pituitary gland thyroid-stimulating hormone may be insufficient both in quantity and in quality. If a woman lives in a region where there is a deficiency of iodine, then, of course, the function of the thyroid gland will suffer vdvoem is. Similar can be said about hormones such as ACTH, somatotropic.

Failure gonadotropic hormones (FSH, LH, prolactin) leads to the juvenile age more likely to persistence follicles, reducing the ovulatory peak of LH, premature induction of meiosis, vnutrimolekulyarnogo perezrevanie and degeneration of oocytes. These girls, and later women of childbearing age, dysfunction of the hypothalamic-pituitary system initially leads to DMK, follicular cysts, the cyst of a yellow body.

Hormonal correction, both the first and second phases of the menstrual cycle often helps to normalize them at some period of the menstrual cycle, and if necessary even to get pregnant. But the resulting yellow body is defective in anatomical and functional terms, that leads to the most frequent miscarriages in the first trimester of pregnancy, or clinic threatened abortion. Inferiority yellow body confirmed the effectiveness of the treatment of threatened abortion with gestagens (Duphaston, utrogestan).

Another factor contributing to the abortion or the threat of termination is decreased production by the pituitary gland prolactin in women with uterine myoma (nauryzbayeva USED, Kravtsova YEAR, Moseev A.M. Hormonal system mother - placenta - p of the od in pregnant women with fibroids // Materials of all-Russian scientific-practical conference with international participation - "The role of new perinatal technologies in reducing reproductive loss". - Ekaterinburg, 2001, s-218).

Of course, in no event it is impossible to dismiss the causes of miscarriages and factors such as genetic, anatomic, infectious, hormonal (hyperandrogenism), immunological. They can be related and the main factors, both threats and abortion.

Pregnancy, especially after the correction of menstrual cycle hormones, or other means, as a rule, is accompanied by the hospital, threatened abortion, and the next possible development of placental insufficiency, chronic hypoxia and fetal malnutrition. The severity of these changes, and hence the effectiveness of the treatment largely depends on the prescription of chronic hypoxia of the brain, its severity, the severity of the causes of intracranial hypertension, and, of course, from concomitant genital or extragenital pathology, if any.

Found that the available methods of treatment of threatened abortion in women with fibroids do not fully meet the etiopathogenesis of this disease.

The prototype of the invention is a method of treatment of miscarriage endocrine Genesis" (patent for invention №2063215). Treatment about what W ill result to pregnancy in the form of Central electroanalgesia, balneotherapy total hydrogen sulfide baths and vaginal irrigation. After pregnancy, control and treatment according to the usual method.

The task of the invention is to develop a method for the prevention and treatment of threatened abortion without the use of hormonal drugs in women with uterine myoma with the new look at the etiopathogenesis of its occurrence.

The technical result is the elimination of the chronic hypoxia of the brain, the normalization of microcirculation in the body (particularly the brain), the normalization of the function of the hypothalamic-pituitary-ovarian system, uteroplacental blood flow.

The proposed method for the prevention and treatment of threatened abortion without the use of hormonal drugs in women with uterine cancer on the basis of a new look on its etiopathogenesis is as follows.

1. For normalization of brain blood flow and improve the nutrition of brain cells recommend wearing liners "Piokal" before the pregnancy for 8-15 hours a day, and with the onset of pregnancy for 5-6 hours a day, every day, to improve uteroplacental blood flow and continue the normalization of blood flow in the brain. Treatment without medication! - technology treatment XX1 century, which is of no value DL is pregnant women.

2. In preparing women for pregnancy with history of infertility, miscarriage, chronic inflammation of the uterus and diseases of certain organs and systems of the body, designate parapharmaceutical - BAD "Diana" for a period of 3 weeks 1 capsule for the first 3 days, then 2 capsules 3 more days and in the coming days 2 capsules 2 times per day. "Diana" shown under such conditions as coronary heart disease, brain, varicose veins, thrombosis of different localization, anemia, chronic intoxication.

3. After an interval of 7-10 days to take in the subsequent Neurostim" - 2 capsules in the morning and 1 capsule in the evening for 30 minutes before a meal course of 3-4 weeks. A restorative effect on the brain due to the hydrolysate from the nervous tissue of squid. The drug improves cerebral circulation, removes obstacles to the flow. Normalizes metabolism and tissue respiration. Eliminates chronic depression, has anti-stress effect. Restores the function of the liver, lymph nodes.

4. To improve liver function, playing a key role in the synthesis and breakdown of hormones, enzymes, proteins, etc., recommend the acceptance of Lokelani" (extracts Russian Thistle, yarrow, burdock). Has a hepatoprotective effect, protivoyazvenno is, anti-inflammatory, antispasmodic and antioxidant action.

5. With prophylactic and therapeutic purposes, designate "MIGS" within 15 days and 1 tablespoon 2-3 times a day, in case of suspicion for the presence of purulent or viral infection, low content in the body women total protein and albumen fractions.

Characteristics of the drugs used

Liners "Pokal" made of a special material on the basis of foamed polyethylene. The invention patented in 53 countries around the world. They are treated in Japan, Canada, USA, Germany, France, Sweden, Israel. Liners make a braided, reflective and thermal effects on the receptors and the energy channels of the feet. To dilate the blood vessels, activates circulation, increases the activity of energy processes, accelerates the synthesis of ATP. Starts the process of self-regulation and redistribution produced by the body energy to maintain physiological processes at all levels: molecular, chemical, energy, cell. Good therapeutic effect is observed even when such diseases as cerebral palsy, cerebral stroke. And faster came therapeutic effect in people suffering from long ago (in women with chronic hypoxia brain disease duration occurs, ka is the rule, for decades). After the use of stimulants paralysis decreased or disappeared completely (as piotrowicz).

Jerzy Domansky sophisticated equipment proved the available improvement of the trophic function of brain cells when wearing liners "Pokal".

In preparing women for pregnancy with history of infertility, miscarriage, inflammatory processes and diseases of certain organs and systems of the body, appoint "Diana". This is the newest product developed and manufactured Siberian center of pharmacology and biotechnology, using electron-beam AXIS"-technologies that significantly improve the bioavailability of biomolecules, which are practically not absorbed in the intestine. Such substances include DNA, as well as bioflavonoids and quinoid compounds.

The active ingredient of the drug "Diana" is DNA extracted from eggs of the most ancient oceanic fish (salmon) and purified enzymes-proteases. Genetic memory, embedded in the DNA of sea creatures, having lived through many climatic disaster for hundreds of millions of years, put at the service of human health in the form of the latest bioregulator "Diana". It is known that the nucleic acid fragments that are included in Diani have a General restorative, tonic, healing, immunomodulatory effective the AMI. Extremely important, recently established by biologists and physicians the effect of the normalization of carbohydrate and lipid metabolism. Add in the power of fragments of the purified nucleic acid is accompanied by a drop in blood sugar and blood cholesterol, a significant increase mental and physical performance, improve memory. Already 5 days after the start of drug metabolism and tissue respiration compliance with the norms of people in early adolescence.

The elimination of the deficit nucleic acid restores balance to the nervous and immune systems, returns the health of the blood vessels, normalizes carbohydrate and fat metabolism.

Modern research has shown that the cause of many chronic and acute diseases lies in the chronic deficit of nucleic acids.

The composition of the drug: the fragmented DNA of salmon 9.5 mg, excipients (MCC, potato starch, sodium chloride). Due to the high bioavailability of the recommended intake provides the daily requirement of the body for DNA, and also eliminates the deficit oligonucleotides.

Contraindication is only stomach bleeding.

We studied the effects of the drug:

- immunomodulatory function through stimulation of the reticuloendothelial system;

- activate all sprouts bone marrow, because steam is the isolation of progenitor cells;

- strengthening and reparative anabolic functions of the body and, consequently, reducing blood sugar, cholesterol, lipoprotein and very low density;

- nutritive (nutrient): delivers high-ductility material for organs and tissues, bone marrow, muscle tissue and other Increases strength and endurance of muscles.

Shown in the following conditions:

1. Coronary heart disease, hypertension, preinfarction status and acute myocardial infarction.

2. Effects of ischemic strokes in the brain.

3. Peptic ulcer and duodenal ulcer.

4. Chronic diseases of lower extremities vessels (varicose veins, atherosclerosis).

5. Chronic inflammatory processes in gynecology.

6. Diseases of the musculoskeletal system (arthritis, osteochondrosis).

7. Diabetes 1 or type II.

8. Pneumonia and chronic bronchitis, re ARD.

9. Chronic diseases of the kidneys and urinary tract.

"Diana" is made on the background of basic therapy of the underlying disease. The first 3 days, 1 capsule a day 30 minutes before meals, the next 3 days, 1 capsule 2 times a day and then 2 capsules 2 times a day. The course is mainly determined individually (average 3 weeks). After an interval of 7-10 days, the drug can be repeated.

- Enhances therapeutic effect of antibi the ticks and painkillers;

- When taking the drug it is possible exacerbation of chronic diseases. In this case, the medication should be discontinued for 2-3 days and then start taking 1-2 capsules per day, with further good endurance gradually increase the dosage to 4 capsules per day;

- The drug is needed even healthy, especially during increased physical or mental stress, stress.

"Lachlan" (extracts Russian Thistle, yarrow, burdock) - has a hepatoprotective activity, anti-ulcer, anti-inflammatory, antispasmodic and antioxidant effects. Is Tomsk company "Biolit". For treatment 1 teaspoon (without top) dissolved in 1/2 Cup water (water temperature should be no higher than 38 degrees). Take 20-30 minutes before eating a quarter Cup 2 times a day. The treatment of 20 days, during pregnancy may 2-3 course.

The MIG - made from mussels grown on plantations in the Barents sea by acid hydrolysis. The advantage of hydrolysates before the feedstock is that when the hydrolysis synthesized new valuable ingredients with powerful properties, and are stored hydrolysates longer than the original raw materials. In 2002, biologically active additive "MIGS" was awarded a Gold medal to them. I.I. Mechnikov, Russian Academy of natural Sciences. Clinical trials who had a reduction in the incidence of suppurative complications and normalize the content of total protein and albumin in the blood plasma in the Department esophageal Oncology MINION them. Herzen. In the Moscow scientific research Institute of obstetrics and gynecology, said the increased resistance of the body of persons suffering from chronic inflammatory processes of female genital sphere. The action begins to occur by the end of 1-2 weeks.

"NEUROSTIM"-BAD - designed for biocorrection of the functions of the nervous system and vision. Neurostim a restorative effect on the brain due to the hydrolysate from the nervous tissue of squid. The drug improves cerebral circulation, removes obstacles to the flow. Normalizes metabolism and tissue respiration. Eliminates chronic depression, has anti-stress effect. Restores the function of the liver, lymph nodes.

Composition: "Diana" (high-purity proteolytic enzymes DNA salmon ROE fish, Tinactin" (dry hydrolyzed neurochanging squid)

Indications for use:

• traumatic brain injury or stroke;

• demyelinating diseases and faltering neuroinfections;

• prevention and bio-correction of Alzheimer's disease;

• recovery detoxification (liver, lymph nodes, the integrity of the intestinal wall);

• Cerebral palsy and attention deficit disorders;

• acute and chronic eye inflammation (conjunctivitis, keratitis);

• to increase learning, reaction speed, efficiency, mental labor is a;

• to overcome fatigue, chronic fatigue and depression, prevention and overcoming of intoxication.

How to use:

Assign inside 2 capsules in the morning and 1 capsule in the evening for 30 minutes before a meal. The course of treatment is 21 days. To repeat the course after a week's break.

It is recommended to repeat another course after six months.

Interaction with other drugs: heparin, dipyridamole, aspirin enhance the antithrombotic effect without increasing the risk of bleeding.

Inactivated preparations containing salts of calcium, magnesium and lithium, as well as with the antibiotic tetracycline.

We offer comprehensive method for the prevention and treatment of threatened abortion without the use of hormonal drugs in women with fibroids has several advantages over existing:

* First, is applicable to all women of childbearing age.

* Secondly, wearing liners "Pokal" leads to normalization of blood circulation and elimination of existing chronic hypoxia of the brain, in pregnancy to improve uteroplacental blood flow.

Normalization of brain blood flow helps to restore the normal function of the hypothalamic-pituitary-ovarian system.

* Thirdly, the purpose of the MIG leads to normalization of water-electr letnogo blood, because it contains all the macro - and micronutrients necessary female body (especially during pregnancy), restores the decreased levels of total protein and albumin. It can be used both before pregnancy and during pregnancy.

* Fourth, "Neurostim" restorative effect on the brain due to the hydrolysate from the nervous tissue of squid. The drug improves cerebral circulation, removes obstacles to the flow. Normalizes metabolism and tissue respiration. Eliminates chronic depression, has anti-stress effect. Restores the function of the liver, lymph nodes.

Interaction with other drugs: heparin, dipyridamole, aspirin enhance the antithrombotic effect without increasing the risk of bleeding. Inactivated preparations containing salts of calcium, magnesium and lithium, as well as with the antibiotic tetracycline.

* Fifth, the treatment is entirely possible on an outpatient basis.

- Sixthly, all applicable products domestic production (excluding liners "Pokal"), which is of no value.

* Seventh, "Diana", "Neurostim" is the latest drugs developed and manufactured Siberian center of pharmacology and biotechnology, using electron-beam AXIS"technology, which significantly increases the bioavailability of biomolecules which are practically not absorbed in the intestine.

The proposed method is illustrated by the following clinical example.

The patient And, 25 years old, came about infertility and aching pain in the lower abdomen. Sex life of 17 years, was guarded. Married 23 years, not protected, pregnancy does not occur. Was treated in the hospital with an inflammatory process of the genitals.

History: born to a mother with 3 childbirth. The duration of labour was within 3-4 hours, feature - was born with the umbilical cord entanglement around the neck, weight 2350, to Breastfeed the child was on the 4th day, she was discharged on the 10th day due to the severity of the child's condition. After 4 classes, Biking, fell and hit his head and shoulder on a log that lay along the fence. Had a broken collarbone.

Menarche age of 14, irregular to 18 years, the duration of 5-8 days. Considering burdened history assigned to the basal thermometry, pelvic ultrasound, REG, x-ray of the skull in lateral projection, a survey of the husband with the aim of eliminating the causes of infertility.

On the REG - obstruction of the venous outflow from the big hemispheres, more pronounced on the right.

On the radiograph of the skull in lateral projection is well expressed finger impressions, increased vascular pattern and hyperostoses.

Ultrasound uterine body size 68×53×48 mm, the uterine wall is non-uniform along the PE Edna the wall of the uterus myoma node to 27 mm, left in the field of vascular bundle and just above the two nodes size 14 and 22 mm Right ovary 32×26×20 mm, left - 38×32×29 mm with numerous follicular cysts (multifollicular), no larger than 9 mm

Gynecological examination detected an increase in the uterus up to 6-7 weeks of gestation, at the expense of myomatous nodes, in the field of appendages moderate pain, tictacti, is palpated on the left enlarged ovary, thick consistency.

Based on identified increased intracranial pressure, fibroids, primary infertility and previous inflammatory process in the uterus appointed:

* wearing liners " Pokal" for 10-15 hours per day;

* "Diana" 1 capsule for 3 days, then 2 capsules 3 more days and in the coming days 2 capsules 2 times a day, for 3 weeks;

* 7-10 days after receiving Diana" appointed "Neurostim" - 2 capsules in the morning and 1 in the evening 20 days;

* The MIG - 1 tbsp. spoon, not lemons, 3 times a day 30 minutes before meals with the first day of the menstrual cycle is 15 days. So for 3 cycles;

* "Lachlan" in the second half of the menstrual cycle according to the instructions;

* continue the measurement of basal body temperature and avoid pregnancy. Turnout in 3-4 months.

Re 4.5 months later with complaints of delay IU the yachnogo for 4 weeks. The house held the pregnancy test is positive. Pregnancy is very welcome, so come for further recommendations. Basal body temperature for the last 3 days decreased from 37.2 to 36,9.

On ultrasound in the uterus the embryo, the corresponding 6-week gestation period, marked hypertonicity of the front wall of the uterus. Diagnosis: the threat of miscarriage.

Offered hospitalization, which she declined for family reasons (sick mother).

Recommended to resume wearing liners for 5-7 hours a day (with the onset delay menstruation stopped wearing), to continue measuring the basal body temperature daily information to repeat a course "MIGS" and "Lokelani" according to the previous recommendations. Sexual peace. Bed rest as much as possible.

Through daily basal body temperature normalized (increased to 37,2-37,3), and one week after the start of treatment was stopped abdominal pain, marked improvement in overall health, improved sleep, appeared in my mind a feeling of "lightness". At 22-23 weeks of gestation on ultrasound myomatous nodes was not determined, deviations from the development of the fetus is not revealed.

Delivery vaginal delivery at 37-38 weeks of pregnancy, the fetus is female, weight 3140, with rating on a scale of Apgar scores 7 points.

Control ULTRASONIC ASCS shall adowanie 2.5 months after birth confirmed the absence of myomatous nodes.

Thus, the proposed method of treatment helps to normalize the menstrual cycle, effectively heal chronic inflammation in the uterus, uterine fibroids in women with chronic hypoxia of the brain and the blood circulation is mild on the background of increased intracranial pressure and to prevent the threat of interruption of pregnancy without the use of hormonal drugs. Treatment liners PICAL together with such drugs as "Diana" and "Neurostim", "MIGS" programs the woman's body for further improvement, normalization of brain blood flow and thereby eliminating chronic hypoxia of the brain. Improve the trophic brain cells helps normalize the function of the hypothalamic-pituitary-ovarian system.

The proposed method of treatment addresses the cause of recurrence of fibroids, and also improves the overall status of the patient, the health, increases efficiency, normalizes sleep, stops headaches, then there is a recovery of the female body in General.

Method for the prevention and treatment of threatened abortion in women with uterine cancer, wherein the patient is prescribed prophylactically wearing Polish liners "Pokal" for 8-15 hours a day, and with the onset of pregnancy for 5-7 h hedgehog is NEWNO, at the same time appointed to pregnancy "Diana" 1 capsule for 3 days, then 2 capsules 3 more days and in the coming days 2 capsules 2 times daily course of 3 weeks, then after a 7-10 day break "Neurostim" 2 capsules in the morning and 1 capsule in the evening for 30 minutes before a meal course of 3-4 weeks, during pregnancy appoint "Lochlan for 20-30 minutes before eating a quarter Cup 2 times a day, treatment of 20 days, during pregnancy 2-3 course, and the MIG - on 1 tablespoon of undiluted 3 times a day for 15 days, 1-2 rate for the entire term of pregnancy.