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American Journal Of Biomedical Science & Pharmaceutical Innovation    
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ABSTRACT 

Vaginal agenesis is a congenital disorder commonly associated with Mayer-Rokitansky-Kuster-Hauser (MRKH) 

syndrome, which is characterized by failure to develop the Müllerian duct and vaginal agenesis. This syndrome occurs 

in approximately 1 case in 4000-10,000 births [1]. 

KEYWORDS 

Non-operative methods, the bladder, Vecchietti, Abbe-McIndoe and Davydov. 

INTRODUCTION

In adolescence, it is quite common for girls to complain 

of amenorrhea, and about 15% of them suffer from 

MRKH syndrome [5, 9, 10]. This syndrome is one of the 

main medical indications for neovaginoplasty. In 

addition, other indications for vaginal reconstruction 

include cloaca, intersex disorders, and cases where the 

vagina has been lost due to pelvic exenteration due to 

gynecologic cancer or postpartum necrosis. There are 

many surgical and conservative methods for vaginal 

restoration. Among non-operative methods, such as 

the Frank technique, serial dilatation is used to create 

a rudimentary vagina. The mucous membrane of the 

bladder, amnion and synthetic materials are also used 

to form the neovagina [9, 10, 11]. 

  Research Article 

 

CELLULAR RENEWAL OF THE INTESTINAL EPITHELIUM IN ARTIFICAL 

VAGINA IN WOMEN UNDERGOING VAGINOPLASTY 
 

Submission Date: May 20, 2024, Accepted Date:  May 25, 2024,  

Published Date: May 30, 2024  

Crossref doi: https://doi.org/10.37547/ajbspi/Volume04Issue05-06 

 

 

Khamidova Farida Muinovna 
Samarkand State Medical University, Uzbekistan 

 

Yakubov Munis Zakirovich 
Samarkand State Medical University, Uzbekistan 

Journal Website: 

https://theusajournals.

com/index.php/ajbspi 

Copyright: Original 

content from this work 

may be used under the 

terms of the creative 

commons attributes 

4.0 licence. 

 

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These approaches require prolonged dilatation and 

stenting to prevent closure of the canal. Research has 

shown that the use of isolated intestinal segments 

provides excellent results, bypassing the need for 

regular dilatation and providing natural lubrication [3, 

16, 17]. Numerous proposed treatment methods, which 

are even more diverse when taking into account their 

modifications, reflect the complexity of solving this 

problem. Nevertheless, the relevance of this problem 

remains, and for gynecologists it will always be an 

important issue to adequately solve it. Conservative 

and surgical treatment methods have been developed 

and used for a long time with possible modifications. 

Surgical methods can be divided into traction and 

transplantation. Methods such as Vecchietti, Abbe-

McIndoe and Davydov are considered among the most 

commonly used and recognized in the world.  

Intestinal vaginoplasty is a well-studied procedure that 

uses a pedunculated segment of the large or small 

intestine. This method is often used for vaginal 

agenesis, male-to-female sex reassignment surgery in 

cases of lack of phallic skin, and for revision after 

unsuccessful primary reconstruction. In our study, we 

describe the use of a pedunculated colon segment for 

vaginal reconstruction after serious complications of 

the initial surgery [8, 21, 22]. 

Currently, operations to reconstruct an artificial vagina 

are becoming increasingly common. However, 

histological analysis of the morphofunctional changes 

occurring in the functionally leading tissue of the 

formed bioprosthesis - the intestinal epithelium - 

remains insufficiently studied. Clinical specialists are 

naturally focused on the clinical and functional changes 

occurring both in the artificial vagina and in the patient 

as a whole. Thus, it is necessary to recognize that these 

changes are a consequence of reactive compensatory 

transformations in the mucous membrane, which 

interacts with an unusual microenvironment. Based on 

clinical biopsy material obtained from 15 to 40 months 

after surgery, two-phase changes in the epithelium 

were identified: first, a mosaic loss of microvilli by 

enterocytes was observed, and then the appearance of 

signs of transitional cellular metaplasia [18]. 

Additionally, some researchers, based on short-term 

observations of morphology, identify a period of three 

years during which the intestinal epithelium fully 

adapts to new conditions [12, 14]. However, such 

studies remain isolated, usually lacking theoretical 

justification and focused on solving specific clinical 

problems [13]. It was previously discovered that 

reactive compensatory processes in the mucous 

membrane of the urinary reservoirs, especially in the 

epithelium, develop in accordance with well-known 

classical patterns [4,20]. Traditionally, the reactive 

change process is thought to involve three main 

phases. The first of them is “emergency mobilization,” 

characterized by the activation of morphofunctional 

reserves in response to a sharp change in influencing 

factors. Then comes the “plateau” phase, when the 

system reaches relative stability at a new level of 

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(ISSN – 2771-2753) 
VOLUME 04 ISSUE 05 PAGES: 29-39 

SJIF IMPACT FACTOR (2022: 5. 705) (2023: 6.534) (2024: 7.7) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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functioning. With prolonged exposure to extreme 

factors, a phase of “failure” or decompensation may 

occur, characterized by a violation of the structural and 

functional organization. [15, 19]. It is clear that the 

duration of these phases depends not only on the 

characteristics of the influencing factor, but also on the 

histogenetic properties of the tissue on which it 

affects. Consequently, this also influences the choice 

of diagnostic and treatment strategies in the follow-up 

care of these patients after surgery. In addition, it is 

known that such an adaptation process covers all 

levels of the structural organization of matter, which 

are analyzed by a histologist, including subcellular, 

cellular, cellular-tissue and structural-functional units 

[4, 15].Transformations of the intestinal epithelium in 

the structure of the artificial vagina have not been fully 

considered from the point of view of the described 

general patterns of pathology. The epithelium of the 

intestinal type interacts with the connective tissue, 

forming the morphofunctional complex “crypt-villus” 

in the intestine. This complex is a self-regulating 

system characterized by constant renewal of 

enterocytes due to the proliferation of 

undifferentiated cells in the crypt [2]. In the lower part 

of the crypts there are intestinal epithelial stem cells 

that can differentiate into various cell types. This 

differentiation occurs in several directions, leading to 

the formation of prismatic enterocytes (villous 

epithelial cells), goblet exocrine cells, Paneth cells 

(with acidophilic granules) and enteroendocrine cells 

(gastrointestinal endocrinocytes) [6]. Under normal 

conditions, the cellular components that make up a 

particular tissue should maintain a standard ratio. This 

ratio ensures the full functioning of the tissue, 

including its ability for physiological regeneration and 

cell renewal [7]. It is assumed that under changed 

environmental conditions these ratios can change in 

order to maintain the initial state of the tissue, which 

indicates their adaptive nature [4]. Tissue reactivity is a 

term that is used to denote the individual ability of 

tissues to make compensatory-adaptive 

morphofunctional changes in response to various 

superphysiological influences [7]. 

The purpose of the study is to determine the patterns 

of changes in the cellular renewal of the intestinal 

epithelium in the vagina formed from the sigmoid 

colon.  

Materials and methods of research. The material was 

biopsy samples obtained during vaginoplasty after 

prolapse in women undergoing surgery to create an 

artificial vagina. At the same time, material obtained 

from different patients within a period of 6 months to 

10 years after reconstructive surgery was available for 

study. Biopsies were taken from several areas of the 

artificial vagina, usually from the anterior, left and right 

walls, as well as from the posterior wall. 

The obtained samples for histological examination 

were taken from 38 patients with congenital anomalies 

of the vagina. These specimens were fixed in 10% 

neutral formalin for 24–48 hours and subjected to 

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Volume 04 Issue 05-2024 32 

                 

 
 

   
  
 

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(ISSN – 2771-2753) 
VOLUME 04 ISSUE 05 PAGES: 29-39 

SJIF IMPACT FACTOR (2022: 5. 705) (2023: 6.534) (2024: 7.7) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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histological processing, including paraffin embedding 

and sectioning at 5–6 μm thickness. For morphological 

analysis of sections, hematoxylin and eosin staining 

methods, the Van Gieson method, and the Weigert 

method were used. 

Histochemical study. To identify the process of mucus 

formation, more precisely the formation of 

mucopolysaccharides in the goblet cells of the mucous 

membrane and glands of the submucosal layer, a 

histochemical study was performed using Alcian blue 

staining.  To identify glycol or aminohydroxyl groups 

that form dialdehyde, a PIR reaction (Schiff reagent 

staining) was performed. 

In addition, using the PAS reaction, it is possible to 

analyze the accumulation of mucin, glycogen, flu-like 

lesions, as well as lymphoproliferative processes in 

neovagina tissue. The results were assessed semi-

quantitatively (in points). 

A total of 76 blocks were processed, from which 208 

drugs were manufactured and studied. When studying 

micropreparations, histological and 

histomorphometric analyzes were performed. 

Histomorphometric analysis was carried out using a 

scanner on a NanoZoomer microscope (REF C13140-

21.S/N000198/HAMAMATSU PHOTONICS/431-

3196JAPAN), using the NDP.VIEV2.0.,QuPath.0.4.0.url 

program. 

To obtain statistically reliable results, at least 20 

objects were analyzed in several fields of view. A 

morphometric study was carried out with the 

calculation of the following parameters: average villi 

height (µm); average crypt depth (µm); average height 

of epithelial cells (µm); proportion of Paneth cells in 

relation to all crypt epithelial cells (%). 

Statistical data processing. Since a normal distribution 

of signs was not identified and taking into account the 

need to evaluate indicators before and after surgery, 

non-parametric methods were subsequently used to 

compare related groups based on quantitative 

characteristics. 

The statistical significance of the differences between 

each indicator before and after surgery at different 

times was assessed using the Wilcoxon test at P <0.05, 

the interpretation of the results was formalized with 

the exact p values.  

For comparison, the results obtained were compared 

with the data identified during the study of biopsy 

specimens of the native sigmoid colon. 

Results of our own research. It has been established 

that in the initial months of the functioning of the 

intestinal epithelium, reactive changes occur at all 

levels of its structural organization. This is especially 

true for the crypt-villus system and the cellular 

composition of the epithelial lining. Already in the first 

half of the year of exposure, significant structural 

changes are observed compared to the control. For 

example, after 6-12 months, a variety of sizes of 

intestinal villi is detected; their length varies even 

within one biopsy from 140 to 230 micrometers, while 

in a normal sigmoid colon this figure is approximately 

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Volume 04 Issue 05-2024 33 

                 

 
 

   
  
 

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(ISSN – 2771-2753) 
VOLUME 04 ISSUE 05 PAGES: 29-39 

SJIF IMPACT FACTOR (2022: 5. 705) (2023: 6.534) (2024: 7.7) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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357.5 ± 15.8 micrometers. Villi located close to each 

other differ in size, shape and structure, therefore the 

average values of villi height are arbitrary and not 

statistically significant. Most villi have a non-standard 

shape, with various bends and local thinning. The 

structure of the crypts remains constant and does not 

differ significantly from the normal mucosa; their 

depth ranges from 135.8 to 263.7 micrometers, while in 

normal intestine it is approximately 186 ± 4.0 

micrometers. These changes persist for 6-12 months. 

Further, an increase in the variety of shapes and sizes 

of villi is observed. They are located at unequal 

distances from each other, have different heights and 

shapes, with numerous bends between them. The villi 

themselves have an irregular, curved shape, and in 

some areas are absent for significant lengths. The 

crypts have a tortuous course, which leads to the 

presence of a large number of transverse and 

longitudinal sections of the crypts, and polymorphism 

is manifested in their different diameters. At 36 

months, extensive areas without villi were observed, 

and the crypts had a shallow depth of 170–220 

micrometers (Fig. 1). 

 

 

 

 

 

 

 

 

 

 

 

Fig. 1. Single-row cubic epithelium of the villi of the mucous membrane of the neovagina. Hematoxylin and eosin 

staining.  Increased 400.

These crypts were separated from each other and had 

some fibrotic structure, and were also infiltrated with 

lymphocytes and eosinophils. The remaining villi had an 

atypical shape with terminal extensions in the form of 

pins. At the level of cellular differentiation, a 

pronounced hyperplasia of cells that produce mucus 

was observed, and goblet cells became dominant 

among them. Under normal conditions of the sigmoid 

colon, the proportion of goblet cells among all 

epithelial cells usually does not exceed 12%, and they 

are found mainly in the upper third of the crypts. 

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Volume 04 Issue 05-2024 34 

                 

 
 

   
  
 

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(ISSN – 2771-2753) 
VOLUME 04 ISSUE 05 PAGES: 29-39 

SJIF IMPACT FACTOR (2022: 5. 705) (2023: 6.534) (2024: 7.7) 
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 However, already 6 months after 

reconstructive surgery, the proportion of goblet 

mucocytes sharply increases to 32.5%, and on the 

surface of the villus, half of all cells in which nuclei 

could be visualized are mucocytes. 

 Subsequently, changes in the proportion of 

goblet mucocytes were insignificant and remained 

stable until late follow-up, ranging from 18–30%, which 

is twice the usual values for the sigmoid colon. These 

cells were located deep in the crypts and in some cases 

could be found even at the 6–7 cell position. The 

dynamics of the proportion of Paneth cells showed 

significant fluctuations, however, the detected trends 

indicate that immediately after the onset of exposure 

to sexual contact - during the first 6-8 months - their 

proportion among all crypt cells increased sharply 

compared to the norm. Subsequently, this indicator 

stabilized at the level of 5-8%, which in most cases 

significantly exceeded the level in the sigmoid colon 

under normal conditions (3±0.14%). The synthetic 

activity of enterocytes remained at a typical level until 

18-26 months.  

The results of histological examination showed that 

the neovaginal mucosa was completely re-

epithelialized and began to produce glycogen within 

approximately 6 months in all cases. Vaginoscopic 

demonstrations using Schiller staining also confirmed 

this fact. They showed that the transformation of the 

single-layer epithelium of the sigmoid colon into a 

stratified epithelium secreting glycogen occurred due 

to the expansion of the initial epithelial beams 

originating from the entrance of the hymen upward to 

the apex of the vagina. 

 After 32-36 months, the mucous membrane 

showed significant disturbances in the architecture of 

the crypt-villus system. Typical villi were absent from 

the biopsies, replaced by widened and short stromal 

protrusions covered by single-layer intestinal 

epithelium. 

 In some cases, the initial sections of 

convoluted crypts were found inside these 

protrusions, infiltrated with lymphocytes. In the period 

from 36 to 48 months, single polymorphic villi were 

observed on the surface of the mucous membrane, 

some of which reached a significant length - from 160 

to 210 μm. In some areas, local polyp-like growths of 

the epithelium were also noted, which could be 

identified as anastomosing villi. Paneth cells were 

located at positions from 1 to 5 cells, exceeding their 

natural niche (1-3 cells). 48 months after the operation, 

subtotal villous atrophy and a decrease in the number 

of crypts are noted, in some cases their presence is 

reduced to single ones; the stroma becomes fibrotic. In 

a specimen obtained 76 months after surgery, villi of 

various lengths were found, with one long (150 µm) 

and 3-4 short (60-100 µm). The crypts become 

subatrophic, resembling intervillous folds, and can only 

be identified as crypts due to the presence of Paneth 

cells. 

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Volume 04 Issue 05-2024 35 

                 

 
 

   
  
 

American Journal Of Biomedical Science & Pharmaceutical Innovation    
(ISSN – 2771-2753) 
VOLUME 04 ISSUE 05 PAGES: 29-39 

SJIF IMPACT FACTOR (2022: 5. 705) (2023: 6.534) (2024: 7.7) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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 After 90 months, no villi are visible; there are 

only local elevations covered with polymorphic 

intestinal epithelium. Crypts become rare; Paneth cells 

are found only sporadically in them. The subepithelial 

layer of the stroma is sclerotic, and deeper there is the 

development of fibrous connective tissue with 

powerful collagen fibers. A similar picture persists after 

94 months. 

 At later stages, after 7-10 years, the proportion 

of goblet cells decreased, and in some cases they could 

no longer be identified morphologically. A statistically 

significant change in cell height was observed after 94 

months. Along with the elongation of the cells, they 

became significantly thinner, especially on the lateral 

surfaces of the villi or in the villous areas. 

 Consequently, by this moment there is a 

gradual increase in dysplastic processes, which 

indicates the beginning of the third phase of 

compensatory changes - decompensation. The most 

pronounced dysplasia was found in the biopsy 

specimen of a patient with a history of 8 years after 

surgery. Most epithelial cells were polymorphic spindle 

cells. When sections are stained with Alcian blue, 

different colors of goblet cells and submucosal gland 

cells are observed, from light and transparent to dark. 

Mucus formation persisted until late follow-up. 

Compared with the period of 1-3 years of observation, 

after 8-10 years of reconstructive surgery, a significant 

decrease in mucus formation was found in the mucous 

membrane of the neovagina. This is confirmed by the 

fact that at this stage dysplastic processes increased in 

favor of stratified squamous epithelium. 

 Single crypts turned out to be small, almost 

equal in depth to the height of epithelial cells and 

reached sizes of 90–95 µm. The underlying stroma 

consisted of compacted fibrous connective tissue with 

strong collagen fibers. The apical apparatus of 

enterocytes was characterized by sharply atrophied 

microvilli, which sometimes resembled membrane 

vesicles separated from the cell surface. The basal 

bodies were larger than the villi themselves. The 

differentiation of cells into different types of 

enterocytes was opaque, and in most cases the cells 

were filled with discrete vesicles with mucus-like 

contents. There were cells with a “mixed phenotype”, 

expressing characteristics of both bordered and goblet 

cells. The basolateral domain of cells was characterized 

by excessive tortuosity, and observation of the course 

of the basement membrane was difficult. 

 An unexpected finding was that binucleate 

enterocytes were clearly visible, which is considered a 

clear sign of intestinal epithelial dysplasia. In no case 

were there signs directly or indirectly indicating 

squamous metaplasia (Fig. 2), which probably 

corresponds to the determination of the epithelium of 

the endodermal type. 

 

 

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Volume 04 Issue 05-2024 36 

                 

 
 

   
  
 

American Journal Of Biomedical Science & Pharmaceutical Innovation    
(ISSN – 2771-2753) 
VOLUME 04 ISSUE 05 PAGES: 29-39 

SJIF IMPACT FACTOR (2022: 5. 705) (2023: 6.534) (2024: 7.7) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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Fig. 2. Hyperplasia of the basal cells of the stratified squamous non-keratinizing epithelium of the neovaginal 

mucosa. 8 years after surgery. Hematoxylin and eosin staining. Increased 400. 

 The conducted research allows us to conclude 

that there are significant structural and functional 

changes at the considered levels of organization: at the 

level of structural and functional units, the cellular 

differentiated level and their synthetic activity. 

However, changes do not occur at all these levels 

simultaneously. Regardless of the level of 

manifestation of reactive changes, they are all realized 

during a three-phase process, ending with dysplasia of 

the intestinal epithelium (Fig. 3). 

 

 

 

 

 

 

 

 

 

Fig. 3. Focal dysplasia of stratified squamous epithelium and moderate lymphocytic infiltration of the lamina 

propria. 10 years of observation. Hematoxylin and eosin staining.  Increased 400. 

 Such changes in the walls of the neovagina 

confirm the adaptive-transforming mechanisms of the 

artificial vagina and post-transplant accommodation of 

the sigmoid colon. This circumstance, despite the 

stability of the histogenetic type and the stable 

determination of the intestinal epithelium of the 

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Volume 04 Issue 05-2024 37 

                 

 
 

   
  
 

American Journal Of Biomedical Science & Pharmaceutical Innovation    
(ISSN – 2771-2753) 
VOLUME 04 ISSUE 05 PAGES: 29-39 

SJIF IMPACT FACTOR (2022: 5. 705) (2023: 6.534) (2024: 7.7) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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sigmoid colon, requires certain oncological attention in 

the later stages of the functioning of the artificial 

vagina. 

CONCLUSION 

Thus, this study indicates the success of surgery to 

create a neovagina in women with MRKH syndrome, as 

demonstrated by complete re-epithelialization of the 

mucous membrane and the onset of adaptive-

transforming processes 6-12 months after surgery. 

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Volume 04 Issue 05-2024 38 

                 

 
 

   
  
 

American Journal Of Biomedical Science & Pharmaceutical Innovation    
(ISSN – 2771-2753) 
VOLUME 04 ISSUE 05 PAGES: 29-39 

SJIF IMPACT FACTOR (2022: 5. 705) (2023: 6.534) (2024: 7.7) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Publisher: Oscar Publishing Services 

Servi 

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исследований. – 2023. – Т. 4. – №. 1. 

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реконструк¬ции отдела кишечника (обзор 

литературы) / В.В. 

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2008. – Т. 3, № 1. – С. 72–77. 

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особенности артифициального мочевого 

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В.С. Пауков, П.Ф. Литвицкий // В кн. 

Патология: руководство / Под ред. М.А. 

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ГЭОТАР Медицина, 2002. – С. 128–145. 

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//Gynecological Surgery. – 2020. – Т. 17. – №. 1. 

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Volume 04 Issue 05-2024 39 

                 

 
 

   
  
 

American Journal Of Biomedical Science & Pharmaceutical Innovation    
(ISSN – 2771-2753) 
VOLUME 04 ISSUE 05 PAGES: 29-39 

SJIF IMPACT FACTOR (2022: 5. 705) (2023: 6.534) (2024: 7.7) 
OCLC – 1121105677     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Publisher: Oscar Publishing Services 

Servi 

22. Miyake A. et al. Case Series of Mayer–

Rokitansky–Küster–Hauser Syndrome: 

Analysis of 17 Cases //Clinical and Experimental 

Obstetrics & Gynecology. – 2023. – Т. 50. – №. 

1. – С. 1. 

https://doi.org/10.37547/ajbspi/Volume03Issue03-01
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