Head of
"Oncogenetics"

Zhusina
Julia Gennadievna

Graduated from the Pediatric Faculty of the Voronezh State Medical University. N.N. Burdenko in 2014.

2015 - internship in therapy on the basis of the Department of Faculty Therapy of the Voronezh State Medical University. N.N. Burdenko.

2015 - certification course in the specialty "Hematology" on the basis of the Hematological Research Center in Moscow.

2015-2016 – therapist of the VGKBSMP No. 1.

2016 - the topic of the dissertation for the degree of candidate of medical sciences "study of the clinical course of the disease and prognosis in patients with chronic obstructive pulmonary disease with anemic syndrome" was approved. Co-author of more than 10 publications. Participant of scientific and practical conferences on genetics and oncology.

2017 - advanced training course on the topic: "interpretation of the results of genetic studies in patients with hereditary diseases."

Since 2017 residency in the specialty "Genetics" on the basis of RMANPE.

Head of
"Genetics"

Kanivets
Ilya Vyacheslavovich

Kanivets Ilya Vyacheslavovich, geneticist, candidate of medical sciences, head of the genetics department of the medical genetic center Genomed. Assistant of the Department of Medical Genetics of the Russian Medical Academy of Continuous Professional Education.

He graduated from the Faculty of Medicine of the Moscow State University of Medicine and Dentistry in 2009, and in 2011 he completed residency in the specialty "Genetics" at the Department of Medical Genetics of the same university. In 2017, he defended his thesis for the degree of candidate of medical sciences on the topic: Molecular diagnostics of copy number variations of DNA segments (CNVs) in children with congenital malformations, phenotype anomalies and/or mental retardation using high-density SNP oligonucleotide microarrays»

From 2011-2017 he worked as a geneticist at the Children's Clinical Hospital. N.F. Filatov, scientific advisory department of the Federal State Budgetary Scientific Institution "Medical Genetic Research Center". From 2014 to the present, he has been in charge of the genetics department of the MHC Genomed.

Main activities: diagnosis and management of patients with hereditary diseases and congenital malformations, epilepsy, medical genetic counseling of families in which a child was born with a hereditary pathology or malformations, prenatal diagnostics. During the consultation, an analysis of clinical data and genealogy is carried out to determine the clinical hypothesis and the required amount of genetic testing. Based on the results of the survey, the data are interpreted and the information received is explained to the consultants.

He is one of the founders of the School of Genetics project. Regularly makes presentations at conferences. He lectures for geneticists, neurologists and obstetricians-gynecologists, as well as for parents of patients with hereditary diseases. He is the author and co-author of more than 20 articles and reviews in Russian and foreign journals.

The area of ​​professional interests is the introduction of modern genome-wide studies into clinical practice, the interpretation of their results.

Reception time: Wed, Fri 16-19

Head of
"Neurology"

Sharkov
Artem Alekseevich

Sharkov Artyom Alekseevich– neurologist, epileptologist

In 2012, he studied under the international program “Oriental medicine” at Daegu Haanu University in South Korea.

Since 2012 - participation in the organization of the database and algorithm for the interpretation of xGenCloud genetic tests (http://www.xgencloud.com/, Project Manager - Igor Ugarov)

In 2013 he graduated from the Pediatric Faculty of the Russian National Research Medical University named after N.I. Pirogov.

From 2013 to 2015, he studied in clinical residency in neurology at the Federal State Budgetary Scientific Institution "Scientific Center of Neurology".

Since 2015, he has been working as a neurologist, researcher at the Scientific Research Clinical Institute of Pediatrics named after Academician Yu.E. Veltishchev GBOU VPO RNIMU them. N.I. Pirogov. He also works as a neurologist and a doctor in the laboratory of video-EEG monitoring in the clinics of the Center for Epileptology and Neurology named after A.I. A.A. Ghazaryan” and “Epilepsy Center”.

In 2015, he studied in Italy at the school "2nd International Residential Course on Drug Resistant Epilepsies, ILAE, 2015".

In 2015, advanced training - "Clinical and molecular genetics for practicing physicians", RCCH, RUSNANO.

In 2016, advanced training - "Fundamentals of Molecular Genetics" under the guidance of bioinformatics, Ph.D. Konovalova F.A.

Since 2016 - the head of the neurological direction of the laboratory "Genomed".

In 2016, he studied in Italy at the school "San Servolo international advanced course: Brain Exploration and Epilepsy Surger, ILAE, 2016".

In 2016, advanced training - "Innovative genetic technologies for doctors", "Institute of Laboratory Medicine".

In 2017 - the school "NGS in Medical Genetics 2017", Moscow State Scientific Center

Currently, he is conducting scientific research in the field of epilepsy genetics under the guidance of Professor, MD. Belousova E.D. and professor, d.m.s. Dadali E.L.

The topic of the dissertation for the degree of Candidate of Medical Sciences "Clinical and genetic characteristics of monogenic variants of early epileptic encephalopathies" was approved.

The main areas of activity are the diagnosis and treatment of epilepsy in children and adults. Narrow specialization - surgical treatment of epilepsy, genetics of epilepsy. Neurogenetics.

Scientific publications

Sharkov A., Sharkova I., Golovteev A., Ugarov I. "Optimization of differential diagnostics and interpretation of results of genetic testing by the XGenCloud expert system in some forms of epilepsy". Medical Genetics, No. 4, 2015, p. 41.
*
Sharkov A.A., Vorobyov A.N., Troitsky A.A., Savkina I.S., Dorofeeva M.Yu., Melikyan A.G., Golovteev A.L. "Surgery for epilepsy in multifocal brain lesions in children with tuberous sclerosis." Abstracts of the XIV Russian Congress "INNOVATIVE TECHNOLOGIES IN PEDIATRICS AND PEDIATRIC SURGERY". Russian Bulletin of Perinatology and Pediatrics, 4, 2015. - p.226-227.
*
Dadali E.L., Belousova E.D., Sharkov A.A. "Molecular genetic approaches to the diagnosis of monogenic idiopathic and symptomatic epilepsy". Abstract of the XIV Russian Congress "INNOVATIVE TECHNOLOGIES IN PEDIATRICS AND PEDIATRIC SURGERY". Russian Bulletin of Perinatology and Pediatrics, 4, 2015. - p.221.
*
Sharkov A.A., Dadali E.L., Sharkova I.V. "A rare variant of type 2 early epileptic encephalopathy caused by mutations in the CDKL5 gene in a male patient." Conference "Epileptology in the system of neurosciences". Collection of conference materials: / Edited by: prof. Neznanova N.G., prof. Mikhailova V.A. St. Petersburg: 2015. - p. 210-212.
*
Dadali E.L., Sharkov A.A., Kanivets I.V., Gundorova P., Fominykh V.V., Sharkova I.V. Troitsky A.A., Golovteev A.L., Polyakov A.V. A new allelic variant of type 3 myoclonus epilepsy caused by mutations in the KCTD7 gene // Medical genetics.-2015.- v.14.-№9.- p.44-47
*
Dadali E.L., Sharkova I.V., Sharkov A.A., Akimova I.A. "Clinical and genetic features and modern methods of diagnosing hereditary epilepsy". Collection of materials "Molecular biological technologies in medical practice" / Ed. corresponding member RANEN A.B. Maslennikova.- Issue. 24.- Novosibirsk: Academizdat, 2016.- 262: p. 52-63
*
Belousova E.D., Dorofeeva M.Yu., Sharkov A.A. Epilepsy in tuberous sclerosis. In "Brain Diseases, Medical and Social Aspects" edited by Gusev E.I., Gekht A.B., Moscow; 2016; pp.391-399
*
Dadali E.L., Sharkov A.A., Sharkova I.V., Kanivets I.V., Konovalov F.A., Akimova I.A. Hereditary diseases and syndromes accompanied by febrile convulsions: clinical and genetic characteristics and diagnostic methods. //Russian Journal of Children's Neurology.- T. 11.- No. 2, p. 33-41. doi: 10.17650/ 2073-8803-2016-11-2-33-41
*
Sharkov A.A., Konovalov F.A., Sharkova I.V., Belousova E.D., Dadali E.L. Molecular genetic approaches to the diagnosis of epileptic encephalopathies. Collection of abstracts "VI BALTIC CONGRESS ON CHILDREN'S NEUROLOGY" / Edited by Professor Guzeva V.I. St. Petersburg, 2016, p. 391
*
Hemispherotomy in drug-resistant epilepsy in children with bilateral brain damage Zubkova N.S., Altunina G.E., Zemlyansky M.Yu., Troitsky A.A., Sharkov A.A., Golovteev A.L. Collection of abstracts "VI BALTIC CONGRESS ON CHILDREN'S NEUROLOGY" / Edited by Professor Guzeva V.I. St. Petersburg, 2016, p. 157.
*
*
Article: Genetics and differentiated treatment of early epileptic encephalopathies. A.A. Sharkov*, I.V. Sharkova, E.D. Belousova, E.L. Dadali. Journal of Neurology and Psychiatry, 9, 2016; Issue. 2doi:10.17116/jnevro20161169267-73
*
Golovteev A.L., Sharkov A.A., Troitsky A.A., Altunina G.E., Zemlyansky M.Yu., Kopachev D.N., Dorofeeva M.Yu. "Surgical treatment of epilepsy in tuberous sclerosis" edited by Dorofeeva M.Yu., Moscow; 2017; p.274
*
New international classifications of epilepsy and epileptic seizures of the International League against epilepsy. Journal of Neurology and Psychiatry. C.C. Korsakov. 2017. V. 117. No. 7. S. 99-106

Head of
"Prenatal Diagnosis"

Kyiv
Yulia Kirillovna

In 2011 she graduated from the Moscow State Medical and Dental University. A.I. Evdokimova with a degree in General Medicine Studied in residency at the Department of Medical Genetics of the same university with a degree in Genetics

In 2015, she completed an internship in Obstetrics and Gynecology at the Medical Institute for Postgraduate Medical Education of the Federal State Budgetary Educational Institution of Higher Professional Education "MGUPP"

Since 2013, he has been conducting a consultative appointment at the Center for Family Planning and Reproduction, DZM

Since 2017, he has been the head of the "Prenatal Diagnostics" department of the Genomed laboratory

Regularly makes presentations at conferences and seminars. Reads lectures for doctors of various specialties in the field of reproduction and prenatal diagnostics

Conducts medical genetic counseling for pregnant women on prenatal diagnostics in order to prevent the birth of children with congenital malformations, as well as families with presumably hereditary or congenital pathologies. Conducts interpretation of the obtained results of DNA diagnostics.

SPECIALISTS

Latypov
Artur Shamilevich

Latypov Artur Shamilevich – doctor geneticist of the highest qualification category.

After graduating from the medical faculty of the Kazan State Medical Institute in 1976, for many years he worked first as a doctor in the office of medical genetics, then as head of the medical genetic center of the Republican Hospital of Tatarstan, chief specialist of the Ministry of Health of the Republic of Tatarstan, teacher at the departments of Kazan Medical University.

Author of more than 20 scientific papers on the problems of reproductive and biochemical genetics, participant in many domestic and international congresses and conferences on the problems of medical genetics. He introduced methods of mass screening of pregnant women and newborns for hereditary diseases into the practical work of the center, performed thousands of invasive procedures for suspected hereditary diseases of the fetus at different stages of pregnancy.

Since 2012, she has been working at the Department of Medical Genetics with a course in prenatal diagnostics at the Russian Academy of Postgraduate Education.

Research interests – metabolic diseases in children, prenatal diagnostics.

Reception time: Wed 12-15, Sat 10-14

Doctors are admitted by appointment.

Geneticist

Gabelko
Denis Igorevich

In 2009 he graduated from the medical faculty of KSMU named after. S. V. Kurashova (specialty "Medicine").

Internship at the St. Petersburg Medical Academy of Postgraduate Education of the Federal Agency for Health and Social Development (specialty "Genetics").

Internship in Therapy. Primary retraining in the specialty "Ultrasound diagnostics". Since 2016, he has been an employee of the Department of the Department of Fundamental Foundations of Clinical Medicine of the Institute of Fundamental Medicine and Biology.

Area of ​​professional interests: prenatal diagnosis, the use of modern screening and diagnostic methods to identify the genetic pathology of the fetus. Determining the risk of recurrence of hereditary diseases in the family.

Participant of scientific and practical conferences on genetics and obstetrics and gynecology.

Work experience 5 years.

Consultation by appointment

Doctors are admitted by appointment.

Geneticist

Grishina
Christina Alexandrovna

In 2015 she graduated from the Moscow State Medical and Dental University with a degree in General Medicine. In the same year, she entered residency in the specialty 30.08.30 "Genetics" at the Federal State Budgetary Scientific Institution "Medical Genetic Research Center".
She was hired in the Laboratory of Molecular Genetics of Complexly Inherited Diseases (Head - Doctor of Biological Sciences Karpukhin A.V.) in March 2015 as a research laboratory assistant. Since September 2015, she has been transferred to the position of a researcher. He is the author and co-author of more than 10 articles and abstracts on clinical genetics, oncogenetics and molecular oncology in Russian and foreign journals. Regular participant of conferences on medical genetics.

Area of ​​scientific and practical interests: medical genetic counseling of patients with hereditary syndromic and multifactorial pathology.

Consultation with a geneticist allows you to answer the following questions:

Are the child's symptoms signs of a hereditary disease? what research is needed to identify the cause determining an accurate forecast recommendations for conducting and evaluating the results of prenatal diagnosis everything you need to know about family planning IVF planning consultation field and online consultations

took part in the scientific-practical school "Innovative genetic technologies for doctors: application in clinical practice", the conference of the European Society of Human Genetics (ESHG) and other conferences dedicated to human genetics.

Conducts medical genetic counseling for families with presumably hereditary or congenital pathologies, including monogenic diseases and chromosomal abnormalities, determines the indications for laboratory genetic studies, interprets the results of DNA diagnostics. Advises pregnant women on prenatal diagnostics in order to prevent the birth of children with congenital malformations.

Geneticist, obstetrician-gynecologist, candidate of medical sciences

Kudryavtseva
Elena Vladimirovna

Geneticist, obstetrician-gynecologist, candidate of medical sciences.

Specialist in the field of reproductive counseling and hereditary pathology.

Graduated from the Ural State Medical Academy in 2005.

Residency in Obstetrics and Gynecology

Internship in the specialty "Genetics"

Professional retraining in the specialty "Ultrasound diagnostics"

Activities:

• Infertility and miscarriage
Vasilisa Yurievna



She is a graduate of the Nizhny Novgorod State Medical Academy, Faculty of Medicine (specialty "Medicine"). She graduated from the clinical internship of the FBGNU "MGNTS" with a degree in "Genetics". In 2014, she completed an internship at the clinic of motherhood and childhood (IRCCS materno infantile Burlo Garofolo, Trieste, Italy).

Since 2016, she has been working as a consultant doctor at Genomed LLC.

Regularly participates in scientific and practical conferences on genetics.

Main activities: Consulting on clinical and laboratory diagnostics of genetic diseases and interpretation of results. Management of patients and their families with suspected hereditary pathology. Consulting when planning a pregnancy, as well as during pregnancy on prenatal diagnostics in order to prevent the birth of children with congenital pathology.

Associate Professor of the Department of Obstetrics and
Gynecology VolgGMU, Ph.D.
E.P. Shevtsova
Volgograd

REPRODUCTIVE LOSS (2009)
ABORTIONS
1 161 690
↓
51045 ectopic
pregnancy
SPONTANEOUS
INTERRUPTS
176 405
BIRTH
17 245 523
↓
1/5 - habitual
miscarriage
↓
premature
new births

DYNAMICS OF SPONTANEOUS ABORTIONS IN RUSSIA.% OF TOTAL NUMBER OF ABORTIONS

16
14
12
10
8
abs. value
6
4
2
0
1995 1997 1999 2001 2003 2005 2007 2009

Miscarriage and prematurity
- more than 25% of all pregnancies.
Spontaneous miscarriages
I trimester are
instrument of natural
selection, because in 60%-80% of abortions
find chromosomal abnormalities.

Habitual miscarriage

is a history of interruption 3 and
more pregnancies
up to 22 consecutive weeks.
Frequency 25%

Miscarriage -
spontaneous interruption
from conception to 37 weeks.
Early pregnancy loss
up to 22 weeks. 2 groups:
- Up to 12 weeks
- From 13 to 22 weeks.

preterm birth

1 gr. 22-27 weeks - very early
premature birth.
2 gr. 28-33 weeks – early
premature birth.
3 gr. 34-37 weeks -
premature birth.

Loss of pregnancy up to 12 weeks.
correspond to 80% of all losses.
The shorter the gestation period
the more often the embryo at the beginning
dies and then reappears
interruption symptoms.

The result is defective
trophoblast invasion and
formation of inferior
chorion.
Endometrial pathology is not always
correlates with hormone levels
blood. More often impaired reception
endometrium.

Problems of the habitual
miscarriage cannot be resolved in
the process of pregnancy. To
preservation treatment
pregnancy was
effective, you need to know
causes of violations leading to
termination of pregnancy.

Reasons for termination of pregnancy in the first trimester.

I - the state of the embryo itself and chromosomal
anomalies arising de novo or
inherited from parents (8.8% - 15%),
hormonal disorders.
II - the state of the endometrium, due to many
reasons:
1) Hormonal
2) Thrombophilic
3) Immunological
4) Chronic metritis with a high level
pro-inflammatory cytokines
5) Violation of the sensitivity of receptors
endometrium to ovarian hormones.

Genetic anomalies

Anomalies in the development of the uterus

In risk groups for ICI from 14 weeks.
1 time in 10 days: transvaginal
Ultrasound combined with manual
examination of the state of the cervix
uterus

Ultrasound data for ICI

The length of the closed part of the cervical
channel less than 2.5 cm.
V and U - figurative shape of the area
internal os and proximal
part of the cervical canal
Diameter of the internal pharynx more than 5 mm
Tactics - stitches on the cervix or
unloading obstetric pessary.

Cerclage (Shirodkar method)

Indications for suture removal

The gestation period is 37 weeks;
Leakage or rupture of amniotic fluid
waters;
Bloody discharge from the uterus;
Cutting seams (forming
fistula)
Start of regular labor
at any time.

Pessary (Meyer ring)

luteal phase deficiency

Menogram

Chronic endometritis

Antiphospholipid Syndrome

Termination of pregnancy up to 5-6 weeks. -
features of the karyotype of the parents or
chromosomal abnormalities
7-10 weeks
1. NLF
2. Hyperandrogenism
3. Hypoestrogenism at the stage of selection
dominant follicle
4. Defective secretory
endometrial transformation

More than 10 weeks
1. APS
2. Genetically determined thrombophilias
(hyperhomocysteinemia, Leiden mutation
and etc.)
15-16 weeks
1. Infectious (gestational
pyelonephritis)
2. Isthmic - cervical
failure.

In 20-50% of pregnant women in the first
weeks of pregnancy
spotting of blood,
caused by invasion
cytotrophoblast into the vanishing
(decidual) membrane of the cavity
uterus. These secretions stop
independently and do not require treatment.
THIS IS THE NORMAL OPTION!

definition

Spontaneous interruption
pregnancy until the fetus
viable gestational age.
WHO - spontaneous expulsion or
extraction of an embryo or fetus up to 500g,
which corresponds to a gestational age of less than 22
weeks.

Classification by clinical manifestations

Threatened abortion
Started abortion
Abortion in progress (complete and incomplete)
Non-developing pregnancy

Threatened abortion clinic

Bloody discharge from the genital tract
Pain in the lower abdomen and lower back
delayed menstruation
Increasing the tone of the uterus
The body of the uterus corresponds to the term
pregnancy
Internal os of the cervical canal
closed
Ultrasound records fetal heart rate

Abortion clinic

More severe pain and bleeding
allocation
The cervical canal is ajar

Incomplete Abortion Clinic

Delay in the uterine cavity elements
gestational sac
No full reduction
uterus
Bleeding
Uterus is smaller than expected
gestational age
Ultrasound: in the uterine cavity are determined
the remains of the fetal egg, in the II trimester -
remnants of placental tissue.

Complete Abortion Clinic

The cervical canal may be closed
Ultrasound - closed uterine cavity
The size of the uterus is less than the gestational age
Small spotting

What not to do with threatened abortion.

1. Threatened abortion does not require hospitalization.
2. Do not prescribe treatment until the threat is clarified
interruptions other than sedatives
(valerian, motherwort) and folic acid preparations
acid 0.4 mg daily until 16 weeks.
3. After clarifying the reasons, use the treatment,
correcting the identified violations.
4. Do not prescribe drugs with unproven
action in the treatment of threatened abortion
(magne B6, vitamin E, glucocorticoids, etc.)

Indications for hospitalization in a round-the-clock hospital.

1. For surgical treatment with
abortion in progress and incomplete abortion,
non-developing pregnancy.
2. Infected miscarriage.

What to do with threatened abortion.

1. Conduct an examination in the residential complex:
A) determination of B - subunit of hCG
B) Ultrasound to exclude ectopic
pregnancy and developmental disorders
fertilized egg.
C) with normal development of the fetal egg
– day hospital, sedation
therapy.

Non-developing (missed pregnancy)

Complex of pathological symptoms
(subjective signs disappear
pregnancy, no movement
fetus, menstruation is restored).
Intrauterine fetal death
pathological inertia of the myometrium
Violation of the hemostasis system

Signs of impaired development of the fetal egg.

1. Absence of the heartbeat of an embryo with a coccygeal size of 5 mm or more.
2. The absence of an embryo with the size of the fetal
eggs 25 mm or more with abdominal
scanning and 18 mm or more at
transvaginal.
3. Abnormal yolk sac (more
gestational age, irregular shape,
displaced to the periphery or calcified)

4. Heart rate
less than 100 embryos per minute
gestational age 5-7 weeks.
5. Large sizes
retrochorial hematoma (more
25% of the surface of the fetal egg)

Non-developing pregnancy by type of embryo death

Algorithm of actions of an obstetrician-gynecologist with a threatened abortion

ultrasound
Violation
development
fertilized egg and
embryo
Finding out
reasons for the threat
Management in outpatient
conditions
Hospitalization in a hospital
for surgical treatment
if possible with
karyotype determination
Absence
risk
prolongation
pregnancy
Fetal development
eggs and embryos
norm
Ultrasound, PAPP-A-test, HCG subunit,
consultation with a geneticist
12 weeks
Treatment in
According to
identified
reasons
Risk
chromosomal
anomalies
Biopsy
chorion

This tactic when threatened
termination of pregnancy before
12 weeks will significantly reduce
number of pregnant women
unjustified hospitalization in
round-the-clock hospital
unnecessary medicinal
purpose, often harmful
short-term impact
pregnancy.

Local increase in tone
uterus on ultrasound
is a sign of danger
interrupt is not
reason for any therapy. This is a property
pregnant uterus!

Surgical methods of abortion

Cannula Karman
Vacuum aspiration

Curettage (curettage of the uterine cavity)

Therapeutic methods of abortion

mifepristone preparations (mifolian, pencrofton, mifegin) and
misoprostol (mirolute).
Mifepristone blocks progesterone receptors
causing the endometrium to lose its ability to support growth
embryo, softening of the cervix occurs and increases
sensitivity of the uterus to contracting substances. Misoprostol
- prostaglandin - causes uterine contraction and expulsion
contents of the uterine cavity.
The effectiveness of medical abortion is 95-98% for
early pregnancy (42 days from the first day of the last
menstruation or 6 weeks of pregnancy).
uterine pregnancy up to 6 weeks

Catad_tema Pathology of pregnancy - articles

Actual problems of miscarriage

V.M. Sidelnikova, G.T. Dry

Guide for practitioners

Moscow 2009

Introduction
	Physiology of the reproductive system
	Formation and functioning of the mother-placenta-fetus system
	2.1. Fertilization and the processes of implantation and placentation
	2.2. Formation of the placenta
	2.3. Hormones of the placenta, decidua and fetal membranes
	2.4. Embryo and fetus development.
	2.5. Features of steroidogenesis in the mother-placenta-fetus system.
	2.6. Adaptive changes in the mother's body during pregnancy.
	Epidemiology of miscarriage
	Genetic causes of miscarriage
	Endocrine aspects of miscarriage
	5.1. Defective luteal phase
	5.2. Hyperandrogenism and pregnancy
	5.3. Thyroid and pregnancy
	5.4. diabetes and pregnancy
	5.5. Hyperprolactinemia and pregnancy
	5.6. Sensitization to human chorionic gonadotropin as a cause of recurrent pregnancy loss.
	5 .7. Progesterone sensitization in patients with recurrent pregnancy loss.
	Thrombophilic disorders and recurrent pregnancy loss
	6.1. Physiology of the hemostasis system and methods for its assessment
	6.2. The main methods for diagnosing disorders in the hemostasis system
	6.3. Features of the hemostasis system in uncomplicated pregnancy
	6.4. Antiphospholipid Syndrome
	6.4.1. Features of the hemostasis system in pregnant women with APS
	6.4.2. Tactics of preparation for pregnancy in patients with APS
	6.4.3. Management of pregnancy in patients with APS
	6.4.4. Catastrophic APS
	6.5. Hereditary thrombophilia in obstetric practice
	6.6. Disseminated intravascular coagulation syndrome (DIC)
	6.7. coagulopathy disorders. Bleeding during pregnancy (causes, tactics, management)
	6.7.1. Detachment of the chorion.
	6.7.2. Premature placental abruption in the II and III trimesters
	6.7.3. Branched chorion presentation
	6.7.4. Retention of the embryo / fetus in the uterus after death
	Alloimmune mechanisms of repeated pregnancy losses
	7.1. The HLA system and its role in human reproduction
	7.2. Role of HLA-G in recurrent miscarriage
	7.3. The role of blocking anti-paternal antibodies in miscarriage
	7.4. Features of the immune status in patients with recurrent miscarriage
	7.5. Treatment methods for alloimmune disorders
	Infectious aspects of miscarriage
	8.1. Tactics of preparation for pregnancy and its management
	8.2. Cytomegalovirus infection in patients with recurrent miscarriage
	8.3. Herpes simplex virus infection
	8.4. coxsackievirus infection
	8.5. bacterial infection
	8.6. Tactics of preparation for pregnancy in patients with miscarriage of infectious genesis
	8.7. Immunomodulatory therapy for recurrent miscarriage
	8.8. Pregnancy management tactics in patients with infectious genesis of recurrent miscarriage
	Pathology of the uterus - as a cause of miscarriage
	9.1. Malformations of the uterus
	9.2. Genius infantilism
	9.3. uterine fibroids
	9.4. Intrauterine synechia
	9.5. Isthmic-cervical insufficiency
	Paternal causes of miscarriage
	Examination of patients with recurrent miscarriage
	Clinical options for abortion. Tactics of conducting
	preterm birth
	13.1. The role of infection in the development of preterm labor
	13.2. Premature rupture of amniotic fluid in preterm pregnancy
	13.3. The role of isthmic-cervical insufficiency in preterm labor
	13.4. Stimulating role of corticotropin-releasing hormone in the development of preterm labor
	13.5. Multiple pregnancy - risk of preterm birth
	13.6. Diagnosis of threatening preterm birth
	13.7. Management and treatment of threatened preterm labor
	13.8. Prevention of respiratory distress syndrome (RDS)
	13.9. Features of the course and management of spontaneous preterm labor
	13.10. Management of preterm labor
	13.11. Prevention of preterm birth
	Premature rupture of amniotic fluid in preterm pregnancy
Literature

Introduction

The problem of protecting the health of mother and child is considered as the most important component of health care, which is of paramount importance for the formation of a healthy generation of people from the earliest period of their life. Among the most important problems of practical obstetrics, one of the first places is the problem of miscarriage.

Miscarriage - spontaneous abortion in the period from conception to 37 weeks, counting from the first day of the last menstruation. Termination of pregnancy between conception and 22 weeks is called spontaneous abortion (miscarriage). Termination of pregnancy between 28 weeks and 37 weeks is called preterm birth. A gestation period of 22 weeks to 28 weeks, according to the WHO nomenclature, is referred to as very early preterm birth, and in most developed countries, perinatal mortality is calculated from this gestation period. In our country, it is planned to switch to the WHO nomenclature in the near future.

Spontaneous abortion is one of the main types of obstetric pathology. The frequency of spontaneous miscarriages is from 15 to 20% of all desired pregnancies. It is believed that the statistics do not include a large number of very early and subclinical miscarriages.

Many researchers believe that spontaneous first trimester miscarriages are a tool of natural selection, since 60 to 80% of embryos with chromosomal abnormalities are found in the study of abortuses.

The causes of sporadic spontaneous abortion are extremely varied and not always clearly defined. These include a number of social factors: bad habits, harmful production factors, unsettled family life, hard physical labor, stressful situations, etc. Medical factors: genetic damage to the karyotype of parents, the embryo, endocrine disorders, malformations of the uterus, infectious diseases, previous abortions and etc.

Habitual miscarriage (miscarriage) – spontaneous abortion two or more times in a row.

In a number of countries, 3 or more spontaneous abortions are considered a habitual miscarriage, but a survey to identify the causes of abortion is recommended after 2 interruptions. The frequency of habitual miscarriage in the population ranges from 2% to 5% of the number of pregnancies. In the structure of miscarriage, the frequency of habitual miscarriage ranges from 5 to 20%.

Recurrent miscarriage is a polyetiological complication of pregnancy, which is based on dysfunction of the reproductive system. The most common causes of recurrent miscarriage are endocrine disorders of the reproductive system, erased forms of adrenal dysfunction, damage to the endometrial receptor apparatus, clinically manifested as an inferior luteal phase (LFP); chronic endometritis with persistence of conditionally pathogenic microorganisms and/or viruses; isthmic-cervical insufficiency, uterine malformations, intrauterine synechia, antiphospholipid syndrome and other autoimmune disorders. Chromosomal pathology for patients with recurrent miscarriage is less significant than with sporadic abortions, however, in spouses with recurrent miscarriage, structural karyotype anomalies occur 10 times more often than in the population and account for 2.4%.

The reasons for sporadic abortion and recurrent miscarriage may be identical, but at the same time, a couple with recurrent miscarriage always has a pathology of the reproductive system that is more pronounced than with sporadic interruption. When managing patients with recurrent pregnancy loss, it is necessary to examine the state of the reproductive system of a married couple outside of pregnancy.

The problem of recurrent miscarriage cannot be solved during pregnancy. In order for pregnancy maintenance treatment to be effective, it is necessary to know the causes and better understand the pathogenesis of those disorders that lead to abortion.

This can only be found out with a thorough examination outside of pregnancy, for rehabilitation therapy and more rational management of pregnancy. Only such an approach, individual in each case, can ensure the successful course of pregnancy and the birth of a healthy child.

Preterm birth is one of the most important issues of this problem, as it determines the level of perinatal morbidity and mortality. Premature babies account for up to 70% of early neonatal mortality and 65-75% of infant mortality. Stillbirth in preterm birth is 8-13 times more likely than in timely birth.

According to B. Guyer et al. (1995), in the United States, prematurity and its complications are the main cause of death in fetuses and newborns without developmental anomalies and account for 70% of total perinatal mortality. Long-term consequences of prematurity: psychomotor development disorders, blindness, deafness, chronic lung diseases, cerebral palsy, etc. - are well known. According to M. Hack et al. (1994), children born weighing less than 1500 g are 200 times more likely to die in newborns and, if they survive, 10 times more likely to have neurological and somatic complications than children born weighing more than 2500 g. And even if the neonatal period passes without complications , most of these children have problems during their school years. Over the past 30 years, great success has been achieved in the world in nursing premature babies, as a result of which infant mortality, immediate and long-term morbidity have been significantly reduced, but the frequency of preterm birth has not decreased in recent years, but, on the contrary, has increased, especially in developed countries.

According to K. Damus (2000), in the United States over the past 10 years, the frequency of preterm birth has increased from 10% to 11.5%, and this is due to an increase in the number of multiple pregnancies after IVF programs and other methods of ovulation stimulation, as well as a wider distribution of harmful habits (tobacco, drugs, alcohol).

The problem of premature birth has a psychosocial aspect, since the birth of a premature baby, his illness and death are severe mental trauma. Women who have lost a child feel fear for the outcome of a subsequent pregnancy, a sense of their own guilt, which ultimately leads to a noticeable decrease in their vital activity, conflicts in the family, and often to the rejection of a subsequent pregnancy. In this regard, the problem of preterm birth is not only medical, but also of great social importance.

The problem of premature birth is of great social importance, given the high cost of nursing premature babies. According to A. Antsaklis (2008), the cost of medical care for premature newborns is $16.9 billion - $33,200 per premature baby. According to J. Rogowski (2000), the average cost of nursing a child weighing 500 g is more than 150,000 US dollars, and only 44% of them survive. With a child weighing 1251-1500 g, the average cost of nursing is approximately 30,000 US dollars and the survival rate is 97%. But there is no data on the non-medical cost of maintaining these children for the family and society as a whole (Bernstein P., 2000).

Apparently, the solution to the problems of a premature baby, both medically and socially, lies in the problem of preventing preterm birth. This is not a simple problem, and many attempts have been made to develop such programs in the world (Papiernik E., 1984), but, unfortunately, N.Eastmen's statement, made back in 1947, remains valid: “Only when the factors underlying basis of prematurity are fully understood and attempts can be made to prevent them.”

In recent years, many causes of preterm birth and mechanisms of their development have become clear, and this inspires certain hopes.

Premature birth is not just a birth that is not on time, it is a birth to a sick mother, a sick child.

In this regard, most of the book is devoted to modern aspects of the etiology of miscarriage, as well as the principles of examination and treatment outside of pregnancy of a married couple suffering from recurrent pregnancy loss.

The book also discusses the modern basic principles of hormonal, immune relationships in the mother-placenta-fetus system, the role of genetic disorders in abortion.

A large section is devoted to the prevention and treatment of infection in patients with recurrent miscarriage. The book focuses on thrombophilic complications in obstetric practice, in particular, antiphospholipid syndrome, sensitization to human chorionic gonadotropin. Much attention is paid to the problem of preterm birth, tactics of their management and prevention.

The book presents literature data of recent years, the authors' own observations, the results of the work of teams from the Department of Therapy and Prevention of Miscarriage and the Laboratory of Immunology, who are currently working and left to work in other teams after defending their dissertations.

The book uses materials obtained in joint research with E.M. Demidova, L.E. Murashko, S.I. Sleptsova, S.F. Ilovaiskaya, L.P. Zatsepina, A.A. Khodjaeva, P.A. Kiryushchenkov, O.K. Petukhova, A.A. Zemlyanaya, N.F. Loginova, I.A. Stadnik, T.I. Shubina. Former graduate students and doctoral students of the department: V.N. Moshin, V.Bernat, N.M.Mamedaliyeva, A.T.Raisova, R.I.Chen, E.Kulikova, M.Rasulova, A.S.Kidralieva, T.V.Khodareva, N.B.Kramarskaya, N.Karibayeva, Zh.Z.Ballyyeva, N.V.Khachapuridze, L.G.Dadalyan, R.Skurnik, O.V.Rogachevsky, A.V.Borisova, N.K.Tetruashvili, N.V.Tupikina, R.G. Shmakov, V.V. Gnipova, K.A. Gladkova, T.B. Ionanidze, Y. Shakhgyulyan, S.Yu.

For many years we have been conducting clinical and scientific work in close cooperation with other laboratories of the Center and all clinical departments of the Center. This book reflects the results of joint research. The authors are deeply grateful to these teams for their constant assistance in scientific and clinical work and hope that this monograph will be useful to obstetricians and gynecologists in their practical work and will gratefully accept all comments.

We are especially grateful to Borisova O.S. for technical assistance in the preparation of the book.

LECTURE 15

MISSIONPREGNANCY

Definition of post-term pregnancy.

Diagnostics.

obstetric tactics.

Indications for CS surgery in post-term pregnancy.

Miscarriage consider spontaneous interruption of it at various times from conception to 37 weeks, counting from the 1st day of the last menstruation.

habitual miscarriage(synonymous with "habitual loss of pregnancy") - spontaneous abortion in a row 2 or more times.

Prematurity - spontaneous abortion in terms of 28 to 37 weeks (less than 259 days).

Termination of pregnancy before 22 weeks is called spontaneous abortion (miscarriage), and from 22 to 36 weeks - premature birth.

The frequency of miscarriage is 10-30% (spontaneous miscarriages 10-20%) of all pregnancies and does not tend to decrease. The urgency of the problem of miscarriage lies in high perinatal losses.

perinatal period begins at 28 weeks of gestation, includes the period of childbirth and ends after 7 completed days of the newborn's life. The death of a fetus or newborn during these periods of pregnancy and the neonatal period constitutes perinatal mortality. According to WHO recommendations, perinatal mortality is taken into account from 22 weeks of pregnancy with a fetus weighing 500 g or more.

perinatal mortality is calculated by the number of cases of stillbirth and death of a newborn in the first 7 days of life. This indicator is calculated per 1000 births. In preterm birth, this figure is 10 times higher. This is the urgency of the problem of premature birth.

Premature babies die due to the deep immaturity of organs and systems, intrauterine infection, birth trauma, as premature babies are unstable to birth trauma. The lower the weight of the newborn, the more often premature babies die.

Newborns born weighing up to 2500 g are considered low birth weight, up to 1500 g - very low birth weight, up to 1000 g - extremely low birth weight. Most often, children of the last two groups die in the neonatal period.

Etiology of miscarriage It is diverse, and the cause of miscarriage can be various factors or even combinations of them.

I trimester be belts:

chromosomal abnormalities of the embryo;

insufficiency of the hormonal function of the ovaries of a pregnant woman;

hyperandrogenism in a pregnant woman;

hypoplasia of the uterus and / or anomalies in the development of the uterus;

diabetes;

hypo- and hyperthyroidism;

acute viral hepatitis;

glomerulonephritis.

Etiology of miscarriage in II trimester pregnancy:

placental insufficiency;

isthmic-cervical insufficiency (ICN);

antiphospholipid syndrome;

somatic pathology of the mother (hypertension, bronchial asthma, diseases of the urinary tract, diseases of the nervous system).

Etiology of miscarriage in III trimester pregnancy:

• anomalies in the location of the placenta;

premature detachment of a normally located placenta (PONRP);

polyhydramnios and / or multiple pregnancy;

incorrect position of the fetus;

rupture of membranes and chorioamnionitis.

Pregnancy can end at anyperiod due to the following reasons:

genital infection;

anomalies in the development of the uterus and uterine fibroids;

diabetes;

• occupational hazards;

  immunological disorders;

  any cause leading to fetal hypoxia.

The pathogenesis of miscarriage

I. Impact of damaging factors ® hormonal and immune disorders in the trophoblast (placenta) ® cytotoxic effect on the trophoblast ® placental abruption.

II. Activation of local factors (prostaglandins, cytokines, fibrinolysis system) ® increased excitability and contractile activity of the uterus.

On the 7th-10th day after fertilization, the blastocyst nidates into the endometrium, due to the release of the dividing egg of chorionic gonadotropin (CG) by the primary chorion. The immersion process lasts 48 hours. CG maintains the function of the corpus luteum and puts it into a new mode of operation, like the corpus luteum of pregnancy (WTB).

The corpus luteum of pregnancy functions up to 16 weeks, releasing progesterone and estradiol, reducing the production of FSH and luteinizing hormone, and supports the functions of the trophoblast. After the formation of the trophoblast (placenta), it takes over (from 10 weeks of pregnancy) the function of the VTB and the entire endocrine function, controlling the homeostasis of the pregnant woman. The level of hormones in a woman's body rises sharply.

If the placenta is not formed intensively enough, such pregnancies have a complicated course, and, above all, in the early stages (up to 12 weeks). They are complicated by the threat of interruption. Consequently, one of the main mechanisms for the development of the threat of abortion is the insufficient development of the chorion.

In connection with the increase in hormone levels, intensive synthesis of pregnancy proteins begins. At the same time, the mother's immune system is inhibited (the production of antibodies to foreign proteins). As a result, the risk of infectious diseases increases, chronic infections become aggravated.

Mechanismthreat of interruption pregnancy at a later date is as follows: in each organ, only 30% of the vessels function, the rest are switched on only under load, these are reserve vessels. The uterus has a huge number of reserve vessels. Blood flow during pregnancy increases 17 times. If the blood flow is reduced by half (trophic deficiency), the child experiences hypoxia. In the urine of the fetus, incompletely oxidized products of hemoglobin metabolism - myoglobin appear. The latter, getting into the amniotic fluid of the fetus, is a powerful stimulator of prostaglandin synthesis. Labor activity at any stage of pregnancy is triggered by prostaglandins, they are produced by the decidual and aqueous membranes of the fetal egg. Any cause leading to fetal hypoxia can trigger the development of labor. During childbirth, uteroplacental blood flow decreases as a result of a powerful contraction of the uterine muscle, and myoglobin synthesis increases with an increase in labor activity.

It is impossible to stop the labor activity that has started. Pain during contractions due to ischemia of the uterine muscle. Therefore, the therapy of the threat of abortion should be aimed at mobilizing reserve vessels (bed rest, antispasmodics, drugs that relieve uterine contractions).

Terminology and classification

Termination of pregnancy in the period of the first 28 weeks is called an abortion or miscarriage, but if a born child weighs from 500.0 to 999.0 grams and has lived for more than 168 hours (7 days), then it is subject to registration in registry office as a newborn. In these cases, miscarriage is transferred to the category of early premature birth.

By the nature of the occurrence, abortion can be spontaneous and artificial. Artificial abortions, in turn, are divided into medical and criminal (produced outside the medical institution).

According to the terms of termination of pregnancy, abortions are divided into: early - up to 12 weeks and late - after 12 to 28 weeks.

According to the clinical course, there are:

Threatened abortion. The threat of interruption is indicated by: a history of miscarriages, a feeling of heaviness in the lower abdomen or slight pulling pains in the absence of bleeding, the size of the uterus corresponds to the gestational age, the external pharynx is closed. Ultrasound showed hypertonicity of the uterine muscles.

Initiated abortion. It is characterized by cramping pains in the lower abdomen and small spotting (associated with detachment of the fetal egg from the walls of the uterus). The size of the uterus corresponds to the gestational age. The cervix may be ajar.

The prognosis for carrying a pregnancy with an abortion that has begun is worse than with a threatening one, but pregnancy can be maintained.

Abortion is on the way. The fetal egg, exfoliated from the walls of the uterus, is pushed out through the dilated cervical canal, which is accompanied by significant bleeding. Preservation of pregnancy is impossible. The fertilized egg is removed with a curette as a matter of urgency.

incomplete abortion characterized by a delay in the uterine cavity of parts of the fetal egg, accompanied by bleeding, which can be moderate or profuse. The cervical canal is ajar, the size of the uterus is less than the expected gestational age.

Infected(feverish) abortion. In case of spontaneous abortion (beginning, beginning or incomplete), microflora can penetrate into the uterus and infect the membranes of the fetal egg (amnionitis, chorioamnionitis), the uterus itself (endometrium). Especially often, infection occurs during artificial termination of pregnancy outside a medical institution (criminal abortion).

An infected miscarriage can cause generalized septic complications. Depending on the degree of spread of infection, there are: uncomplicated febrile miscarriage (infection is localized in the uterus), complicated febrile miscarriage (the infection has gone beyond the uterus, but the process is limited to the pelvic area), septic miscarriage (the infection has become generalized).

delayed(missed) abortion. With a failed abortion, the death of the embryo occurs. At the same time, there may be no complaints and subjective sensations of "loss of pregnancy", there is no clinic of threatening or incipient miscarriage. In an ultrasound study: either the absence of an embryo (anembryony), or the visualization of an embryo with the absence of registration of its cardiac activity (embryo size, CTE - often less than the normative values ​​\u200b\u200bfor the expected gestational age).

Medical tactics - instrumental removal of the fetal egg.

Examination of women with miscarriage

The success of the prevention and treatment of miscarriage depends on the ability, ability and perseverance of the doctor to identify the causes of miscarriage. Examination is advisable to conduct outside of pregnancy, at the planning stage and during pregnancy.

Examination before pregnancy planning:

Expert reviews:

obstetrician-gynecologist;

therapist;

immunologist;

andrologist - urologist;

psychotherapist;

genetics (with habitual miscarriage).

At this stage, it is necessary to carry out the following activities:

Careful collection of anamnesis with clarification of the nature of past diseases, especially during the formation of menstrual function; the presence of extragenital and genital diseases.

The study of menstrual function (menarche, cyclicity, duration, pain of menstruation).

The study of childbearing function - the time interval from the onset of sexual activity to the onset of pregnancy is specified. The nature of all previous pregnancies and childbirth is assessed. In case of termination of pregnancy in the past - features of the clinical course (bleeding, pain, contractions, fever).

General examination: pay attention to height and weight, body type, severity of secondary sexual characteristics, the presence and nature of obesity, hirsutism. An examination of the mammary glands is mandatory (a well-protruding erectile nipple indicates normal hormonal ovarian function).

Gynecological examination: assessment of the vaginal part of the cervix, the presence of ruptures, deformities. The nature of cervical mucus and its amount, taking into account the day of the menstrual cycle. Dimensions, shape, consistency, position and mobility of the uterus, the ratio of the length of the body of the uterus to the length of the cervix. The size of the ovaries, mobility, sensitivity, the presence of adhesions.

Hysterosalpingography is performed to exclude CCI and malformations of the uterus.

Ultrasound of the genitals should be performed on days 5-7, 9-14 and 21 of the menstrual cycle.

It is advisable to conduct tests of functional diagnostics: (colpocytology, basal temperature, pupil symptom, fern symptom), the study of blood hormones (depending on the phase of the menstrual cycle - FSH, LH, prolactin are determined on day 5 of the cycle; on day 12, estradiol, FSH, LH; progesterone on day 21) and urinalysis for 17-ketosteroids in daily urine to rule out hyperandrogenism.

To exclude antiphospholipid syndrome, a hemostasiogram + antibodies to chorionic gonadotropin and lupus antigen are examined.

To exclude the infectious factor of miscarriage, a bacteriological examination of the contents of the cervical canal and vagina, a virological examination and examination for transplacental infections (toxoplasma, treponema, listeria, rubella, cytomegaly, herpes, measles), and an assessment of the immune status are carried out.

Examination during pregnancy:

Ultrasound at 10-12, 22, 32 weeks. One of the early signs of a threatened abortion is a local thickening of the myometrium on one of the walls of the uterus and an increase in the diameter of the internal os.

Hemostasiogram 1 time per month in case of autoimmune miscarriage.

Tank. sowing contents from the cervical canal in the 1st, 2nd, 3rd trimester.

Virological study in the 1st, 2nd, 3rd trimester.

Assessment of the state of the cervix from 12 to 24 weeks to exclude CI. Pregnant women at risk of developing ICI have vaginal examinations from the end of the first trimester once every 10 days. Particular attention is paid to the softening and shortening of the neck, the gaping of the cervical canal. These changes are clinical manifestations of CI.

Fetal CTG.

Dopplerometry from 16 weeks of pregnancy.

Determination of the content of hormones of the fetoplacental complex.

placental hormones:

Progesterone. Biosynthesis is carried out from maternal blood cholesterol and is concentrated in the corpus luteum at the beginning of pregnancy, and from the 10th week of pregnancy it passes entirely into the placenta, where it is formed in the trophoblast syncytium. Progesterone is the basis for the synthesis of other steroid hormones: corgicosteroids, estrogens, androgens. The content of progesterone in the blood serum during pregnancy is characterized by a gradual increase and reaches a maximum at 37-38 weeks. The aging of the placenta is accompanied by a decrease in its concentration.

Chorionic gonadotropin (CG) appears in the body of a woman only during pregnancy. The diagnosis of pregnancy is based on its definition. Its synthesis in the placenta begins from the moment of implantation on the 8-10th day. Its level rises rapidly, reaching a maximum by 7 weeks of gestation, after which it rapidly decreases and remains at a low level throughout the remainder of the pregnancy. Disappears from the body in the first week after childbirth. Reduces the release of gonadotropins by the pituitary gland of the mother, stimulates the formation of progesterone by the corpus luteum. Early or late appearance of the peak of hCG indicates a violation of the function of the trophoblast and the corpus luteum - this is an early indicator of the threat of termination of pregnancy.

Placental lactogen (PL) produced throughout pregnancy. In the blood serum, it is determined from 5-6 weeks, the maximum level is at 36-37 weeks of pregnancy, then its content is kept at the same level until 39 weeks and falls from 40-41 weeks in accordance with the beginning of the aging of the placenta. It has lactotropic, somatotropic and luteotropic activity. After childbirth, it quickly disappears from the blood of a woman.

Fetal hormones:

Estriol (E). It is synthesized by the placenta-fetus complex from maternal cholesterol metabolites. With the normal development of pregnancy, estriol production increases in accordance with the increase in its duration. A rapid decrease in the concentration of estriol in the blood serum by more than 40% of the norm is the earliest diagnostic sign of fetal development disorders. This gives the doctor time to carry out therapeutic measures.

Alpha-fetoprotein (AFP) - it is a glycoprotein, a fetal protein, that makes up about 30% of fetal plasma proteins. It has a high protein binding capacity for steroid hormones, mainly maternal estrogen. Synthesis of AFP in the fetus begins at 5 weeks of gestation in the yolk sac, liver, and gastrointestinal tract. It enters the blood of pregnant women through the placenta. The content of AFP in the blood of a pregnant woman begins to increase from 10 weeks of pregnancy, the maximum is determined at 32-34 weeks, after which its content decreases. A high concentration of AFP in the mother's blood serum is observed in: malformations of the brain, gastrointestinal tract, intrauterine fetal death, chromosomal diseases, multiple pregnancy. Low concentration - with fetal hypotrophy, non-developing pregnancy, Down syndrome.

9. Functional diagnostic tests are used to diagnose abortion in the first trimester.

Cytology of vaginal smears indicates the saturation of the body with estrogen. Karyopyknotic index - the ratio of cells with pyknotic nuclei to the total number of surface cells. KPI in the first trimester - no more than 10%; in the II trimester - 5%, in the III trimester - 3%. With the threat of abortion, the KPI increases to 20 - 50%.

Basal temperature with an uncomplicated course of pregnancy, it is 37.2 - 37.4 ° C. With the threat of termination of pregnancy, a decrease in basal temperature to 37 ° C indicates a lack of progesterone.

pupil symptom. In uncomplicated pregnancy, the content of mucus in the cervical canal is minimal.

With the threat of termination of pregnancy, a pronounced "symptom of the pupil" appears.

Treatment of miscarriage

Treatment of patients with miscarriage should be pathogenetically substantiated and widely combined with symptomatic therapy. A prerequisite for conducting conservation therapy should be the consent of the mother, the exclusion of fetal malformations and extragenital pathology, which is a contraindication for carrying a pregnancy.

Contraindications for pregnancy:

diabetes insulin-dependent mellitus with ketoacidosis;

diabetes mellitus + tuberculosis;

hypertension II, III;

heart defects with circulatory disorders;

epilepsy with personality degradation;

severe blood diseases.

Treatment of threatened miscarriage inItrimester:

Bed rest.

Sedatives (motherwort, trioxazine, nozepam, seduxen, diphenhydramine), psychotherapy.

Antispasmodics (papaverine, no-shpa).

hormone therapy.

Prevention of FPI

metabolic therapy.

hormone therapy.In the absence of a corpus luteumin the ovary which can be confirmed by the data of hormonal examination and echography, gestagens should be prescribed (replacing the lack of endogenous progesterone).

a) duphaston: threatening abortion - 40 mg at once, then 10 mg every 8 hours until the symptoms disappear; habitual abortion - 10 mg twice a day until 20 weeks of pregnancy.

b) utrogestan: threatening abortion or in order to prevent habitual abortions that occur against the background of progesterone deficiency: 2-4 capsules daily in two divided doses up to 12 weeks of pregnancy (vaginally).

If there is a corpus luteum in the ovary - chorionic gonadotropin (stimulation of the synthesis of endogenous progesterone by the corpus luteum and trophoblast, direct stimulating effect of hCG on the process of implantation of the ovum)

a) pregnyl: Initial dose - 10,000 IU - once (no later than 8 weeks of pregnancy), then 5,000 IU twice a week until 14 weeks of pregnancy.

Treatment of threatened miscarriageIIAndIIItrimesters:

Bed rest and psycho-emotional rest.

Appointment of b-agonists (tocolytics), which cause relaxation of the smooth muscles of the uterus (partusisten, ginipral, ritodrine). Treatment begins with an intravenous drip of 0.5 mg of partusisten diluted in 400 ml of NaCI 0.9%, starting with 6-8 drops per minute, but not more than 20 drops. The dose is increased until the cessation of contractile activity of the uterus. Before the end of the infusion, oral administration of the drug is started at 0.5 mg every 6-8 hours.

Calcium channel blockers: verapamil 0.04 3 times a day; isoptin 0.04 3 times a day.

Hormonal support: 17-OPC (hydroxyprogesterone capronate) 125 mg once a week until 28 weeks of pregnancy.

Magnesia therapy: magnesium sulfate 25% 10 ml per 200 ml NaCI 0.9% for 5-7 days; MagneV 6 2 tablets 2 times a day for 10-15 days; electrophoresis with 2% magnesium on the uterus 10 procedures.

Inhibitors of prostaglandin synthesis: indomethacin in tablets or suppositories, the total dose per course is not more than 1000 mg, the duration of the course is 5-9 days.

Prevention of fetal hypoxia.

Prevention of placental insufficiency.

With the threat of premature birth at 28-33 weeks, prevention of respiratory distress syndrome in newborns is carried out by prescribing pregnant women glucocorticoid drugs (dexamethasone) 8-12 mg per course or lazolvan, ambroxol, ambrobene 800-1000 mg per day for 5 days in / in drip.

Antispasmodics.

Sedative drugs.

With hyperandrogenism termination of pregnancy is due to the antiestrogenic action of androgens. Treatment for threatened interruption is with corticosteroids. It is based on the suppression of ACTH secretion, which leads, according to the feedback principle, to a decrease in the biosynthesis of androgens by the adrenal glands. Treatment is prescribed with a persistent increase in 17-CS with dexamethasone in an individually selected dose until the normalization of 17-CS. Hormonal treatment should be discontinued at 32-33 weeks of gestation so as not to suppress fetal adrenal function.

With antiphospholipid syndrome therapy is carried out with prednisolone 5 mg / day. VA control - in two weeks. If VA is detected again, the dose of prednisolone is doubled. If the result is negative, the dose should be considered adequate. A repeated study of VA, after selecting an adequate dose, is carried out once a month during the entire pregnancy for a possible dose adjustment of the drug. Plasmapheresis should be included in the complex of therapy.

In case of miscarriage against the background of immunoconflict bere changes according to erythrocyte antigens (the formation of erythrocyte antigens begins from 5 weeks of pregnancy) to all women with O (I) blood group with A (II) or B (III) blood group of the husband, as well as with Rh negative blood belonging to the pregnant woman, check the blood for group and Rh antibodies. Treatment is with allogeneic lymphocytes.

Isthmic-cervical insufficiency (ICN). ICI is characterized by inferiority of the circular muscles in the area of ​​the internal uterine os, which contributes to the development of insufficiency of the isthmus and cervix. The frequency of ICI is 7-13%. There are organic and functional ICI.

Organic ICI develops as a result of traumatic injuries of the isthmic cervical region during induced abortion, childbirth with a large fetus, surgical delivery (obstetric forceps).

Functional ICI is due to hormonal deficiency, usually develops during pregnancy and is observed more often than organic.

Diagnosis of ICI:

There are no complaints, the uterus is in a normal tone.

When examining in the mirrors: a gaping external pharynx with flaccid edges, prolapse of the fetal bladder.

3. During vaginal examination: shortening of the cervix, the cervical canal passes a finger beyond the area of ​​​​the internal pharynx.

4. Ultrasound of the internal os: the length of the cervix is ​​less than 2 cm - an absolute ultrasound sign of CCI and an indication for suturing the cervix.

The optimal time for suturing the cervix is ​​14-16 weeks, up to a maximum of 22-24 weeks. The suture is removed at 37 weeks, or at any time when labor occurs.

Management of early preterm labor depends on the severity of the clinical picture of this complication, the integrity of the amniotic fluid, the duration of pregnancy.

Management of preterm labor with whole fetusbubble:

Pregnancy term 22 - 27 weeks (fetal weight 500-1000g): you should try to remove labor activity by prescribing b-adrenergic agonists in the absence of contraindications to pregnancy. In the presence of ICI - suture the neck. Conduct courses of metabolic therapy. If possible, identify the cause of miscarriage and correct therapy based on the survey data obtained.

Pregnancy 28- 33 weeks (fetal weight 1000-1800 g): the therapy is the same, except for suturing the cervix. Against the background of the prevention of fetal RDS, control the degree of maturity of his lungs. The outcome for the fetus is more favorable than in the previous group.

Pregnancy 34- 37 weeks (fetal weight 1900-2500 g or more): due to the fact that the lungs of the fetus are almost mature, prolongation of pregnancy is not required.

Management of preterm labor in antenatal effusionti amniotic fluid:

Tactics depends on the presence of infection and the duration of pregnancy.

Expectant management is preferable, since with the lengthening of the anhydrous period, there is an accelerated maturation of the surfactant of the fetal lungs and, accordingly, a decrease in the incidence of hyaline membrane disease in the newborn.

Refusal of expectant tactics and labor induction are carried out in the following cases:

if there are signs of infection: temperature above 37.5 °, tachycardia (pulse 100 and more beats / min), leukocytosis with a shift to the left in the blood test, more than 20 leukocytes in the analysis of the vaginal smear in the field of view. In such situations, against the background of antibiotic therapy, labor induction should be started.

High risk of infection (diabetes mellitus, pyelonephritis, respiratory infection and other diseases in the mother).

Recurrent miscarriage: a modern look at an old problem

V.S. Lupoyad, I.S. Borodai, O.N. Aralov, I.N. Shcherbina

It is shown that the study of the state of the fetoplacental complex based on the results of a Doppler-metric study of blood flow in the yolk sac, intervillous space, umbilical cord artery in case of habitual miscarriage makes it possible to determine a threatening abortion at the preclinical stages and take appropriate measures in a timely manner to eliminate the causes leading to habitual miscarriage.

Currently, more and more attention is being paid to the issues of the birth of full-fledged offspring, with the main emphasis being placed on protecting the fetus in the first trimester of pregnancy, when all organs and systems are laid down.

It should be noted that the protection of the fetus becomes of great importance in case of such a complication of pregnancy as miscarriage, especially since the frequency of this pathology does not tend to decrease and continues to remain at the level of about 20% of all pregnancies.

Due to the high frequency of complications, it is one of the main causes of perinatal morbidity and mortality in most countries of the world, accounting for the number of births in a ratio of 2:10 and causing 75% of newborn deaths.

Among the causes of general mortality of the population, perinatal pathology ranks fourth and depends on the functional state of the "mother - placenta - fetus" system. Of particular note is the termination of pregnancy in the first trimester (up to 12 weeks).

This is due, firstly, to the high incidence of cases (up to 50% of the total number of miscarriages), and secondly, to the fact that the so-called “critical periods” occur in the first trimester of pregnancy, when the embryo and fetus are most sensitive to the action of various adverse factors. external and internal environment.

As a result, there are deficiencies in the development and death of embryos, which is the main cause of miscarriages in the early stages, perinatal and later child morbidity and mortality.

The causative factors and pathogenesis of preterm birth have not been fully elucidated, although there has been some progress in this direction. In particular, an important role of the infectious factor in initiating preterm labor and premature rupture of the fetal bladder has been established.

There is increasing evidence that the processes that occur in the reproductive system during the initiation of both urgent and preterm labor are in the nature of an inflammatory reaction and are accompanied by leukocyte infiltration of the cervix, the release of inflammatory cytokines and matrix metalloproteinases, an increase in the synthesis of contractile eicosanoids and corticotropin-releasing hormone.

Of great importance in the genesis of miscarriage is the ratio of progesterone and estrogens. Progesterone causes decidual changes in the endometrium and prepares it for the implantation of a fertilized egg, promotes the development and growth of the myometrium and its vascularization, reduces the excitability of the uterus by neutralizing the action of oxytocin, stimulates the growth and development of the mammary glands, reduces tissue immunological reactions.

Progesterone has immunosuppressive properties - it suppresses the embryotoxic effect of T-helpers. Estrogens during pregnancy cause vascular proliferation in the endometrium, increase oxygen uptake by tissues, energy metabolism, enzyme activity and nucleic acid synthesis, increase the sensitivity of the uterus to oxytocin, and affect the biochemical processes in the uterus.

Based on these ideas, in recent years, diagnostic systems for predicting preterm labor have been proposed, which are based on the determination of inflammatory cytokines, components of the extracellular matrix and have already shown certain advantages over traditional diagnostic methods.

However, in general, the problem of diagnosing the threat of abortion and predicting the term of preterm birth has not been finally resolved. Economic issues are not clear either. The high cost of many diagnostic tests makes them inaccessible to the majority of the population of our country.

Therefore, an in-depth study of risk factors for preterm birth, biochemical and immunological disorders that occur in a woman's body, and the development of effective and affordable diagnostic tests and treatment methods on this basis, continues to be one of the most pressing issues in obstetrics.

The functional system "mother - placenta - fetus" is a single complex with a complex hierarchy of interactions and adaptive reactions. The human placenta is a unique organ that performs extremely diverse functions: from the synthesis and deposition of substances necessary for the normal growth of the fetus, the immunological protection of the fetal alograft during gestation, participation in the maternal-fetal circulation to the inducing and regulating influence on the birth act.

Any disease of the mother (gestational or extragenital pathology) can cause changes in the homeostasis of the functional system "mother - placenta - fetus".

By the beginning of the XXI century. the transition from the desire to reduce perinatal mortality to the main goal of improving the health of the fetus and newborn was completed. Clinical and experimental studies have made it possible to develop the basic principles for the diagnosis and treatment of pregnancy complications.

Significant progress in recent decades has been made in the development of a system of antenatal fetal protection, which involves the early diagnosis of placental insufficiency (PI) and intrauterine fetal hypoxia, its correction, optimization of the timing and methods of delivery.

However, therapeutic measures taken in late pregnancy and postnatally are often ineffective, and children have some or other pathological abnormalities that are irreversible.

In recent years, the scope of scientific interests in the perinatal protection of the fetus has shifted to the early stages of pregnancy - to the first trimester, since it is during this period that the formation of the fetoplacental system occurs, the laying of organs and tissues of the fetus, extraembryonic structures and provisional organs, which in most cases determines the further course pregnancy.

In addition, in the later stages of pregnancy, in the event of complications and the presence of extragenital pathology in a woman, the issues of diagnosing the state of the fetoplacental system and the fetus, as well as obstetric tactics, become more complicated.

Thanks to the introduction of highly informative research methods, it became possible to comprehensively diagnose fetal disorders from the earliest stages, determine their severity and pathogenetic features of the development of clinical manifestations of PI.

One of the main reasons for the formation of chronic fetal suffering are

threatening and incipient abortion, most commonly seen in women with recurrent miscarriage (RPL).

The medical and social significance of the problem of miscarriage, its impact on perinatal morbidity and mortality and women's reproductive health puts scientific research in this area among the most important tasks of modern fundamental and clinical medicine.

Miscarriage - spontaneous termination of pregnancy in the period from conception to 37 weeks, counting from the first day of the last menstruation with a regular menstrual cycle. Termination of pregnancy in terms from conception to 22 weeks is called spontaneous abortion (miscarriage), in terms of 22 to 37 weeks of gestation - premature birth.

Babies born prematurely are considered preterm. The gestation period of 22-28 weeks according to the WHO nomenclature is referred to as very early preterm birth, and in most countries perinatal losses are calculated from the indicated gestational age.

In the event of the death of a newborn, a post-mortem examination is carried out, and if the child lived 7 days after birth, this death is referred to as indicators of perinatal mortality.

Spontaneous abortion is one of the main types of obstetric pathology. The frequency of spontaneous miscarriages is 15-20% of all desired pregnancies.

However, the statistics do not include a large number of very early pregnancy terminations (including subclinical spontaneous miscarriages). In addition, there is the term "fetal loss syndrome", the clinical criteria of which are: one or more spontaneous miscarriages for a period of 10 weeks or more; neonatal death of a morphologically normal newborn as a complication of preterm birth due to severe preeclampsia or PI; stillbirth; three or more spontaneous miscarriages at the pre-implantation or early embryonic stages in observations when anatomical, genetic and hormonal causes of miscarriage are excluded.

However, this term implies not only miscarriage and prematurity, but also perinatal losses at full term, so it is not similar to RPL. It should be noted that it is most often used for the clinical characterization of antiphospholipid syndrome (APS).

RNP is a polyetiological complication of the gestational process, which is based on dysfunction of the reproductive system. The most common causes of RPL are: endocrine disorders of the reproductive system; erased forms of adrenal dysfunction; lesions of the receptor apparatus of the endometrium, clinically manifested as luteal phase insufficiency (NLF); chronic endometritis with persistence of conditionally pathogenic microorganisms and/or viruses; isthmic-cervical insufficiency (ICN); malformations of the uterus, intrauterine synechia; APS and other autoimmune disorders.

Chromosomal pathology for patients with pregnancy loss syndrome is less significant than for sporadic abortions, however, in women with RPL, structural abnormalities of the abortus karyotype are detected in 2.4%.

The causes of sporadic abortion and RPL may be identical, but at the same time, a married couple with RPL always has a more pronounced degree of pathology of the reproductive system and a greater risk of complications of the gestational process.

Timely assessment of the development of the feto-placental system, starting from the earliest stages of gestation, can achieve a significant reduction in perinatal morbidity and mortality. The use of high-tech methods for studying the state of the embryo/fetus, provisional organs, extraembryonic structures makes it possible to assess the formation of the "mother - placenta - fetus" system, identify the features of its development for various causes of RPL, develop individual tactics for managing pregnancy, justify the need for certain preventive measures, and assess the effectiveness of drug therapy.

The above measures, based on a deep understanding of the processes occurring in the body of a woman and the fetus, make it possible to achieve a successful outcome of pregnancy - to enable a married couple to have a live, full-term and healthy newborn.

The desire to reduce the rates of perinatal morbidity and mortality in RPL was the reason for the search for the basic principles of early prevention, timely diagnosis and adequate treatment of pregnancy complications, including FPI, arising against the background of this pathology.

To date, as a result of clinical and experimental studies, fundamental data have been obtained regarding the etiology, pathogenesis, early diagnosis and correction of FPI and intrauterine fetal hypoxia.

Thanks to numerous works, risk factors for development and the main criteria for fetal disorders in the II and III trimesters of pregnancy are clearly defined. However, despite this, the effectiveness of therapeutic measures remains low, since the treatment is carried out against the background of an already clinically pronounced deviation from the normal course of pregnancy.

At the same time, it is extremely important to take into account the fact that violations can begin very early and manifest themselves already from 4 weeks of gestation. In this regard, early prenatal diagnosis of possible complications starting from the first trimester of gestation is of great importance in case of miscarriage.

Thus, it has been proven that hypoxia delays the maturation of the brainstem structures in the embryo already from 6-11 weeks of development, causes the occurrence of vascular dysplasia, slows down the maturation of the blood-brain barrier, the imperfection of which and increased permeability, in turn, are key in the occurrence of organic pathology of the CNS.

Therefore, early diagnosis of fetal development disorders in RPL, according to most scientists, would allow timely development of optimal tactics for further pregnancy management and decide on adequate therapy.

A detailed study of the structures of the fetal egg became possible due to the introduction of the transvaginal echography method into clinical practice, which made it possible to accurately assess the anatomical features of the development of both the embryo and extraembryonic structures.

To date, according to most researchers, the most important ultrasound criterion confirming the pathological course of pregnancy is the untimely detection of an embryo in the uterine cavity.

Thus, the absence of an embryo in the cavity of the fetal egg with a diameter of 16 mm or more after 6 weeks of gestation predetermines an unfavorable outcome of pregnancy in 62% of cases. According to E. Yu. Bugerenko (2001), in every fourth observation, which subsequently ended in a non-developing pregnancy and spontaneous abortion, there is a late primary visualization of the embryo.

However, the practical use of this marker is significantly limited by a small time interval during which it has a diagnostic and prognostic value [cit. according to 26].

Confirmation of the vital activity of the embryo is also of no small importance for predicting the further course of pregnancy in high-risk patients. According to M. Hickey et al. (2004), registration of normal cardiac activity at 8-12 weeks in 93-97% of cases indicates a favorable outcome of pregnancy.

Similarly, the absence of heart contractions in an embryo with a CTE of 5–8 mm (6 weeks) is considered as a sign of a pathological course of pregnancy with possible early death of the fetus [cit. according to 26].

Along with this, fetal bradycardia (less than 85 bpm) in the 8th week significantly increases the risk of miscarriage. So, according to E. Yu. Bugerenko, bradycardia was noted in 80% of cases that ended in spontaneous abortion [cit. according to 26]. K. Scroggins (2000) notes that with a pronounced violation of the fetal heartbeat, only 7% of women can continue the progression of pregnancy and the birth of a healthy child.

Along with the decrease, fetal heart palpitations in the first trimester are also anemia - 21.6%, acute infectious diseases - 23%. Primary PN is more likely to develop in women with a history of gynecological diseases, spontaneous miscarriages, non-developing pregnancy, and induced abortions.

At the same time, as V. M. Sidelnikova (2002) showed, for primary PI, which complicates the course of pregnancy in the presence of miscarriage in the anamnesis of a woman, low implantation of the fetal egg, a lag in its size from the gestational age, fuzzy visualization in the early stages of pregnancy, the presence of areas detachment and placentation on the anterior wall of the uterus.

At the same time, the causes of premature termination of pregnancy, accompanied by PI, are attachment anomalies and premature detachment of the placenta. Choosing the right obstetric tactics and adequate management of the neonatal period can reduce the incidence of adverse outcomes and improve long-term prognosis.

However, therapeutic measures traditionally carried out in the second trimester of pregnancy, when the period of placentation and the formation of cotyledons have already been completed, are not always effective, therefore, the relevance of early diagnosis and prognosis of this complication increases.

In this regard, the work of 0. B. Panina et al. is of great interest. (2002), who examined 152 pregnant women in dynamics from 10 to 38 weeks. gestation with the study of the formation of arterial and venous blood flow of the fetus and the determination of the possibility of predicting the development of PI and pregnancy outcomes in violations in various parts of hemodynamics.

Analysis of the results of the study showed that with a favorable outcome of pregnancy, normal blood flow in all parts of the uterine-placental-fetal bed in the early stages was observed in 65%, while with the development of PI and sdfd - only in 13% of cases.

It is important to note that in all these pregnant women, hypotrophy of the newborn, confirmed at birth, was I degree, the weight-height index was 0.57-0.59%. At the same time, the percentage of pathological blood flow at the end of the first trimester of gestation was significantly higher in women who gave birth to children with malnutrition (87%) than in the normal outcome of pregnancy (35%) [cit. according to 26].

Qualitative assessment of pathological blood flow in the early stages of pregnancy found that with sdfd, combined hemodynamic disorders (in fetal CM and SpA) were much more common - in 31% of women. With a favorable outcome of pregnancy, the incidence of combined disorders was 7%.

In addition, circulatory disorders isolated in the fetal CM were observed twice as often with sdfd as with uncomplicated pregnancy. Hence, the determination of the features of uteroplacental-fetal hemodynamics in the early stages is necessary as part of ultrasound screening at 11-14 weeks of gestation.

Identification of isolated circulatory disorders in the CM serves as an indication for re-examination at 18-20 weeks. Combined disorders (VP ​​and SpA) should serve as a basis for carrying out preventive therapeutic measures from early pregnancy.

Thus, a detailed study of the echographic features of the development of the fetal egg and Doppler indicators of uterine, fetal and intraplacental blood flow in the early stages seems to be especially relevant in the management of women with RPL.

In addition, it is extremely important to continue research based on modern technologies using non-invasive and relatively safe methods of functional assessment of the fetal condition, aimed at early diagnosis and prevention of PI in women with a history of RPL in the first and second trimesters, allowing the development of optimal management tactics and treatment.

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