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PRE-COURSE TRAINING OF WOMEN WITH REPRODUCTIVE LOSS
OF FETUS IN ANAMNESIS
Khafizova Dilnoza Bahodirovna
https://doi.org/10.5281/zenodo.13141066
Introduction.
Due to the widespread prevalence of reproductive losses, this
problem is especially urgent today, remaining one of the leading in obstetrics.
According to some scientists, reproductive losses are more often observed in
young pregnant women - up to 20 years old or pregnant women over 30 years
old.
According to various experts, up to 23% of diagnosed pregnancies end in
spontaneous abortion. Thus, the problem of reproductive losses is not only a
medical, but also a social problem (a decrease in population growth, an increase
in the level of perinatal and child mortality, a negative impact on the
reproductive function of women).
One of the priority areas of modern medicine is the study of the effect of
extragenital diseases in women on the course of pregnancy and childbirth, on
the development of the fetus and newborn, its adaptive capabilities, morbidity
and mortality [2, 5, 10]. Violation of gestational restructuring of various systems
of the maternal div in early pregnancy has different consequences and can lead
to both the development of complications and reproductive losses in the
absence of optimal conditions for the progression of gestation [1, 3, 4].
One of the complications of pregnancy requiring early delivery is
reproductive loss of the fetus, which can manifest itself at different periods of
gestation. The frequency of reproductive losses is quite high and ranges from 10
to 20%, in England - 2.8%, in the USA - 15%, in the CIS countries - 15-25%, in
Uzbekistan - 16.4%. At the same time, the frequency of reproductive fetal loss in
the first trimester is 68.6%, in the second - 21.3%, in the third - 10.1% [4, 5, 13].
Despite the significant progress achieved in antenatal protection of the fetus, in
some cases, under the influence of various unfavorable factors, its intrauterine
death occurs at different periods of gestation, which dictates the need for early
delivery of a woman [14, 15, 17].
Reproductive loss in humans is about 50% in relation to the total number
of conceptions. The frequency of miscarriage remains high, despite the progress
achieved in the prevention and treatment of reproductive disorders in humans.
At present, various types of spontaneous abortion are considered as
multifactorial diseases [16, 18, 19], the development of which can be triggered
by a combination of several factors. The individual contribution of each factor
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may be insignificant, and only their sum leads to the development of the disease.
The causes of early embryonic loss are many and varied. Anomalies of the
karyotype of the fetus are detected when the development stops and with a
naturally occurring pregnancy, and with assisted reproductive technologies.
Purpose of the study
To study the outcome of pregnancy depending on
the performance of pre-gravid preparation in women with a history of
reproductive losses.
Materials and research methods.
The study included 65 women who
gave written informed consent to participate. The study was carried out
prospectively by complex laboratory and instrumental examinations at the stage
of pre-gravid preparation (Fig. 1) for pregnancy, which were divided into 2
groups.
Main group -
39 women, pregravid drug preparation was carried out for at
least 3 months for the purpose of contraception (Yarina plus, Jess plus) before
the onset of subsequent pregnancy, depending on the cause of reproductive loss
of the fetus. Also, all pregnant women of the main group underwent drug
prevention of placental insufficiency (PI) from early gestation.
Comparison group
- 26 pregnant women who did not receive pre-gravid
training.
Women of the main group at the pregravid stage and during gestation
underwent a comprehensive laboratory and instrumental examination. Pregnant
comparison groups underwent standard obstetric follow-up and examination at
the local polyclinic. Women in the control group at the pregravid stage and
during gestation underwent examination similar to the main groups.
For the effectiveness of pregravid preparation in women with a history of
reproductive loss of the fetus for the contraception of COCs with folates (Yarina
plus or Jess plus), despite etiological reasons, in order to prevent thrombotic
complications and in case of insufficiency of the fetoplacental system, women
were prescribed phlebotonics before and during pregnancy (Phlebodia 600mg)
and L-arginine (Tivortin 100 ml IV drip followed by syrup according to the
scheme).
Yarina plus, Jess plus is a low-dose monophasic combined estrogen-
gestagenic contraceptive drug with auxiliary vitamins containing calcium
levomefolate. The introduction of calcium levomefolate in the composition of an
oral contraceptive drug reduces the risk of developing a neural tube of the fetus,
fetal abnormalities, congenital malformations and, of course, the risk of anemia
and micronutrient deficiency in both the mother and the fetus.
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Phlebotonics (Phlebodia 600 mg) has a venotonic effect: it reduces the
elasticity of the veins, increases the tone of the veins, reduces venous
congestion, enhances the vasoconstrictor effect of adrenaline, norepinephrine.
One tablet contains 600 mg of diosmin, which is the optimal daily dose for the
venotonic effect. And also has - angioprotective effect: improves
microcirculation; increases capillary resistance; reduces their permeability. Acts
on the lymphatic system, i.e. improves lymphatic drainage, increases the tone
and frequency of contraction of lymphatic capillaries, increases their functional
density, reduces lymphatic pressure. In addition, it has a decongestant effect.
Reduces the symptoms of inflammation (dose-dependent effect) and, most
importantly, reduces the adhesion of leukocytes to the venous wall and their
migration to paravasal tissues; improves oxygen diffusion and tissue perfusion.
Blocks the production of free radicals, the synthesis of prostaglandins and
thromboxane.
L
Arginine is a conditionally essential amino acid; the average daily L-
arginine intake is 5.4 g.
TTable 4.1
... The role of L-arginine (Tivortin) in the functioning of various div systems
(Stepanov Yu.M. et al., 2004)
Functional systems of
the div
Physiological reactions
The cardiovascular system Relaxation of blood vessels of the brain, retina,
heart, lungs, kidneys, intestines, cavernous tissue,
heart muscles
Respiratory
system,
digestive and urogenital
tracts
Relaxation of smooth muscle tissue of the trachea,
stomach, intestines, urinary bladder, uterus
Central and peripheral
nervous systems
Neuromodulatory activity that determines long-
term potentiation, memory formation, pain
perception, visual analysis
Hemostasis system
Regulation of the interaction of leukocytes with
vascular walls. Regulation of platelet activity
The immune system
Antipathogenic reactions, nonspecific cytotoxicity,
antitumor protection, pathogenesis of toxemias,
transplant rejection
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The physiological need of tissues and organs of most mammals for
arginine is satisfied by its endogenous synthesis and / or intake with food,
however, for young individuals and adults under stress or illness, this amino
acid becomes essential (Table 4.1).
Arginine serves as a necessary precursor for the synthesis of proteins and
many biologically important molecules such as ornithine, proline, polyamines,
creatine and agmatine. However, the main role of arginine in the human div is
to be a substrate for the synthesis of nitric oxide (NO) (Visek WJ, 1986; Wu G.,
Morris SM Jr., 1998; Böger RH, 2007).
To assess the effectiveness of pregravid preparation in the system of
antenatal protection of the fetus, an analysis of the course of pregnancy in two
groups of patients was carried out.
Figure: 1. Algorithm for pregravid training for women with a history of
reproductive loss
Research results.
The average age of women in the main group was 27.7
± 4.8 years, in the comparison group - 28.4 ± 4.7 years, while 86% of women in
the studied groups were in the age category from 20 to 34 years.
Women with a history of reproductive loss of the fetus
If bacterial infections prevail
When detecting viral infections
Proteflozid 8-10 drops 3 times a day
for a month and vaginally
suppositories for 10 days. Elevit 1
tablet 1 time per day for 30 days (with
repeated courses) with anemia
(ferlatumfol 1 month)
Antibacterial therapy (Amoxiclav
1000) 1 tablet 2 times a day for 7 days
Elevit 1 tablet 1 time per day for 3
months, Inotir according to the
scheme.
In order to prevent thrombophilic complications, the use of LMWH (clexane 0.1 /
kg) and phlebotonics (phlebodia 600, 1 tablet 1 time per day for 3 months), L-
arginine (Tivortin 100 ml drip intravenously for 5 days, followed by syrup , for the
purpose of contraception (Yarina plus, Jess plus) 3 months
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Analysis of the course of pregnancy showed that the incidence of
complications at different periods of gestation, in particular, those that lead to
the development of FPI and pose a risk of antenatal fetal death (threat of
miscarriage, preeclampsia, chronic fetal hypoxia) was significantly higher in
patients of the comparison group (Fig. 2 ).
Fig. 2 Complications of pregnancy in observed patients
In the management of pregnant women in both groups, special attention
was paid to identifying early signs of FPI. For this, the most modern methods for
assessing the function of the placenta were used: namely, dopplerometry of the
uteroplacental-fetal complex.
To assess venous hemodynamics, we used ultrasound and Doppler methods
of investigation. To assess the uterine-fetal-placental blood flow, the Doppler
indices of the uterine artery blood flow rate (MA), umbilical cord artery (AP) and
middle cerebral artery artery (Table 2) of the fetus (CMA) were recorded. Doppler
study was included in the standard fetal ultrasound scan and was performed three
times or more (depending on the indications) during pregnancy.
Studies of hemodynamic parameters in the terminal branches of the
umbilical cord artery in pregnant women made it possible to determine an
increase in vascular resistance only at 38–40 weeks of gestation (P <0.01). A
comprehensive analysis of these parameters showed that the earliest signs of an
unfavorable course of pregnancy were changes in hemodynamics in the placenta
during Doppler measurements with three-dimensional image reconstruction.
Despite careful pregravid preparation and observation during pregnancy,
FPI was diagnosed in 5 (5.2%) patients: in 2 pregnant women with combined
hypertensive disorders of moderate severity; in one patient of hypertensive
disorders with a combination of grade II anemia, in 2 women with a burdened
8,2
6,2
5,2
2,1
34,9
16,1
19,8
12,4
0
5
10
15
20
25
30
35
40
The threat of non-
developing pregnancy
Preeclampsia
Placental insufficiency
(FPI)
IUGR
Main group
Control group
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obstetric history (a history of more than 3 medical abortions, spontaneous
abortions, missed pregnancies, repeated cases of antenal fetal death). This
dictates the need to allocate patients with repeated adverse pregnancy
outcomes in history into a separate group of dispensary observation for in-
depth diagnostic and therapeutic measures.
Table 2.
Doppler indices of uteroplacental-fetal hemodynamics in women of the
examined groups (M ± m)
Investigated parameter
Main group
n = 36
Comparison
group
n = 29
Systole-diastolic volume (LMS)
Uterine arteries
2.18 ± 0.02 ***
1.89 ± 0.05
Artery of the umbilical cord
2.65 ± 0.05 ***
3.21 ± 0.02
Middle cerebral artery
4.65 ± 0.02 ***
2.82 ± 0.02
Resistance index (IR)
Uterine arteries
0.39 ± 0.05 ***
0.61 ± 0.02
Artery of the umbilical cord
1.11 ± 0.02 ***
0.63 ± 0.01
Middle cerebral artery
0.74 ± 0.01 ***
0.91 ± 0.02
Ripple Index (PI)
Uterine arteries
0.56 ± 0.02 ***
0.93 ± 0.05
Artery of the umbilical cord
065 ± 0.05 ***
0.84 ± 0.08
Middle cerebral artery
1.39 ± 0.02 ***
1.89 ± 0.02
Note
* - differences relative to the data of the comparison
group are significant (***
- P <0.001)
Doppler analysis of various parts of the placenta in the 2nd and 3rd
trimesters showed that the vascularization index in healthy pregnant women in
the central zone is higher than in the paracentral and marginal regions (7.93 ±
0.08; 6.45 ± 0.06; 5.77 ± 0 , 06 respectively). This indicates that the central area
of the placenta is the most functionally important site of the placenta.
Depending on the index of vascularization and the blood flow index in
patients with reproductive losses, two variants of changes were revealed:
•
in 42.3% of cases - a decrease in indices within placental hemodynamics
by 1.5-2 times, which was regarded as hypovascularization of the placenta;
•
in 57.7% of cases - an increase in the vascularization index by more than
1.5-2 times, which was interpreted as hypervascularization of the placenta.
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The use of placental dopplerometry made it possible to detect minimal
hemodynamic disturbances in the chorion and in the placenta.
The course of labor in patients with a history of reproductive loss was
characterized by a rather high incidence of complications, which may be
associated with an initial impairment of their reproductive function. In women
in labor in the comparison group, significantly more often than in the main
group, there was a violation of the regulation of labor in the form of an
unsatisfactory labor process (21.9% and 9.3%) and weakness in labor (18.1%
and 7.3%, respectively). In addition, in patients without pregravid preparation,
acute fetal hypoxia during childbirth was 3.4 times more likely (10.5% and
3.1%, respectively). This led to a higher frequency of cesarean sections in the
comparison group (21.9% and 11.5%, respectively).
Caesarean section in the groups was performed mainly in a planned manner
(63.6% and 56.2%, respectively) according to the sum of relative indications. Of
course, in patients with antenatal losses in the anamnesis, there was an
expansion of indications for CS, taking into account the age of pregnant women,
burdened by obstetric history, fetal condition. Attention is drawn to the fact that
women in labor in the comparison group 2 times more often than in the main
group experienced acute fetal hypoxia (2.6% and 1.05%, respectively).
It is obvious that the outcome of pregnancy is largely determined by the
patient's pregravid state and the course of the entire gestational period. Studies
have shown that in women of group I who underwent preliminary examination
and treatment, in the vast majority of cases it was possible to identify and
eliminate the main etiopathogenic factors causing antenatal losses. As a result,
their pregnancy outcomes were significantly better than those of group II
patients who did not seek medical help before the onset of a real pregnancy
(Table 3).
The data presented in Table 3 are a convincing argument proving the
necessity and obvious effectiveness of pregravid training for women with a
history of reproductive losses. The overall incidence of adverse pregnancy
outcomes (spontaneous abortions, missed pregnancies, antenatal fetal death,
premature birth) in the study group was 2 times lower than in the comparison
group (5.6% and 9.8%, respectively). It should be especially noted that there
were no cases of antenatal fetal death in patients of the main group, and
termination of pregnancy in the first and second trimesters was almost 2.5 times
less frequent (2.8% and 6.8%, respectively).
Table 3
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Pregnancy outcome in women surveyed groups
Pregnancy outcome
Main group
(n = 36)
Comparison group
(n = 29)
Abs.
%
Abs.
%
Urgent labor
34
94.5 *
23
79.3
Premature birth
2
5.6 *
3
10.3
Spontaneous
miscarriage in the first
trimester
-
-
one
3.4
Spontaneous
miscarriage
in
the
second trimester
one
2.8
one
3.4
Non-developing
pregnancy
-
-
one
3.4
Antenatal fetal death
-
-
2
6.8
* Differences between the indicators of the compared groups are significant
(p <0.05).
Particularly significant is the fact that, despite the greater number of various
complications during gestation, including FPI, antenatal losses in the
prospective observation groups were minimal (6.8% in the comparison group),
and most of the patients reported pregnancy before term of 37-40 weeks (the
frequency of preterm birth was 5.6% and 10.3%, respectively).
Output.
Thus, pregnant women with reproductive loss of the fetus in a previous
pregnancy constitute a group of extremely high perinatal risk of reproductive
loss. Comprehensive pregravid examination of women with a history of
reproductive loss of the fetus reveals risk factors for recurrent adverse
outcomes of subsequent pregnancy: infectious, genetic, thrombophilic,
hemodynamic, structural. This allows for treatment to reduce their pathological
effects during implantation and placentation. Dynamic laboratory and
instrumental examination, drug prevention of placental insufficiency from early
pregnancy, development of individual obstetric tactics in pregnant women with
a history of reproductive loss of the fetus are the key to improving perinatal
outcomes and reducing perinatal morbidity.
Literature:
1.
Dustovа N.K., Babadjаnоva G.S., Ikhtiyаrova G.A. Pathogenetic rеаsоns fоr
thе dеvеlоpеnt оf vаricоse discounts in prеgnаnt wоmen .Centtrаlоdiаsiаn.No.2
(2) P 87-96
ACADEMIC RESEARCH IN MODERN SCIENCE
International scientific-online conference
74
2.
Gagnier J.J., Kienley G., Altman D.G., Moher D., Sox H., Riley D., et al. CARE
Recommendations: Developing guidelines for case management based on
consensus. GlobAdvHealthMed. 2013; 2: 38–43.
3.
Ikhtiyarova G.A., Dustova N.K., Babadjanova G.S. Pathogenetic reasons for
the development of varicose disease in pregnant women // Central Asian
journal of pediatrics. -2019.No.2 (2). - C.78- 85
4.
Ikhtiyarova G. et al. Criteria For Prediction Of Complications In Pregnant
Women With Antenatal Fetal Death //International Journal of Research. – 2019.
– Т. 6. – №. 01. – P. 694-704.
5.
Ikhtiyarova G.A., Dustova N.K., Qayumova G. Diagnostic characteristics of
pregnancy in women with antenatal fetal death// European Journal of Research.
- 2017. - №5(5). - Р. 3 - 15.
6.
Ikhtiyarova, G. A., Dustova, N. K., Khasanova M. A., Suleymanova G. S., &
Davlatov, S. S. (2021). Pathomorphological changes of the placenta in pregnant
women infected with coronavirus COVID-19. International Journal of
Pharmaceutical Research, 13(1), 1935-1942. doi: 10.31838/ijpr/2021.13.01.283
7.
Ikhtiyarova, G.A., Tosheva, I.I., Aslonova, M.J., Dustova, N.K. Prenatal
rupture of amnion membranes as A risk of development of obstetrics
pathologies // European Journal of Molecular and Clinical Medicine, 2020, 7(7),
стр. 530–535
8.
Inoyatov A.Sh., Ikhtiyarova G.A., Musaeva D.M., Karimova G.K. Assessment
of the status of pregnant women with diabetes mellitus infected with COVID-19
// New day in medicine, 2020, 2(30), P - 102
9.
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurogic mаnifestаtiоns оf
hоspitalizеd pаtiеnts with corоnаvirus disаse 2019 in Wuhan, China. JAMA
Neurol. 2020.
10.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical char- acteristics оf
138 hоspitalizеd publications with 2019 novel corоnаvirus-infectious
pneumonia in Wuhan, China. JAMA. 2020.
11.
Zhоu F, Yu T, Du R, Fаn G, Liu Y, Liu Z, еt аl. Clinicаl соurе аnd risk factors
fоr mоrtаlity оf аndult іnpatients with COVID-19 in Wuhan, China: а а
retrospectivе соhоrt study. LаncеtLоndЕngl. 2020; 395: 1054–62.
12.
Arzhanova O.N., Kosheleva N.G., Gromyko G.L. and other Placental
insufficiency: Diagnosis and treatment: // Textbook. allowance. - St. Petersburg.,
2017. –S. 32.
ACADEMIC RESEARCH IN MODERN SCIENCE
International scientific-online conference
75
13.
Brewer J., Owens M.Yu., Wallace K., Reeves AA, Morris R., Hahn M. et al.
Posterior reversible encephalopathy syndrome in 46 of 47 patients with
eclampsia. Am J ОbstеtGynеcоl. 2013; 208: 468.e1-6.
14.
General Assembly of the World Medical Association. Declaration of
Helsinki by the World Medical Association: Ethical Principles for Medical
Research with Human Participation. J АmCоllDеnt. 2014; 81: 14-8.
15.
Dobrokhotova Yu.E., Ikhtiyarova G.A., Dustova N.K. -Featurеs оf аcurrent
prеgnаncy аnd delivеryinprеgnаnt wоmen with varicоse // Eurasian Bulletin of
Pediatrics. 2020. No. 2 (5). -FROM.182.
16.
Dustova
N.K.
Hypertension
and
pregnancy
//
News
of
Dermatovenereology and Reproductive Health. 2014.Vol.2. P. 86.
17.
Dustova N.K. Features of the course of pregnancy and its outcome
depending on the severity of preeclampsia // Problems of Biology and Medicine,
2012.Vol. 1.P. 129.
18.
Ikhtiyarova G.A., Khaibullina Z.R., Suleimanova G.G. Study of the effects of
ultra-low doses of antioxidants on the lipid component of brain cells in
experimental perinatal hypoxia // News of Dermatovenereology and
Reproductive Health. - 2019. - No. 3 - 4. - C. 4 - 7.
19.
Ikhtiyarova G.A., Dobrokhotova Yu.E., Matrizaeva G.Zh., Aslonova M.Zh.-
Featurеs оf а current prеgnаncy аnd dеlivеry in prеgnаnt wоmen with vаricоse
//Tibbiyotda yangi kun. - 2020. -S. 474-481.
20.
Ikhtiyarova G.A., Khodzhaeva N.B., Kosimova N.I.Etiology of varicose veins
of the small pelvis during pregnancy // Problems of Biology and Medicine.
Samarkand. 2012 No. 1 (68) .- P.154-155
21.
Kirienko A.I., Bogachev V.Yu., Prokubovsky V.I.Varicose veins of the small
pelvis. Phlebology. // Ed. V.S. Saveliev. Moscow. Medicine 2015; - S. 246.
