WO2024063671A1 - Système d'analyse cytologique fonctionnel de pathologie du col de l'utérus - Google Patents

Système d'analyse cytologique fonctionnel de pathologie du col de l'utérus Download PDF

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Publication number
WO2024063671A1
WO2024063671A1 PCT/RU2023/050209 RU2023050209W WO2024063671A1 WO 2024063671 A1 WO2024063671 A1 WO 2024063671A1 RU 2023050209 W RU2023050209 W RU 2023050209W WO 2024063671 A1 WO2024063671 A1 WO 2024063671A1
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WO
WIPO (PCT)
Prior art keywords
cytochamber
camera
gynecologist
patient
processor
Prior art date
Application number
PCT/RU2023/050209
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English (en)
Russian (ru)
Inventor
Денис Алексеевич ИВАНОВ
Константин Анатольевич КОНСТАНТИНОВ
Ирина Владимировна ИВАНОВА
Игорь Алексеевич РЯЗАНОВ
Наталья Николаевна БАЯНДИНА
Елена Николаевна СЛАВНОВА
Original Assignee
Ооо "Хоспитекс Диагностикс"
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from RU2022124850A external-priority patent/RU2813628C1/ru
Application filed by Ооо "Хоспитекс Диагностикс" filed Critical Ооо "Хоспитекс Диагностикс"
Publication of WO2024063671A1 publication Critical patent/WO2024063671A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/002—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor having rod-lens arrangements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/303—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor for the vagina, i.e. vaginoscopes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31—Apparatus therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H10/00—ICT specially adapted for the handling or processing of patient-related medical or healthcare data
    • G16H10/40—ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis

Definitions

  • the present invention relates to the field of medicine and is intended to perform a microscopic examination of scrapings from the cervix (cervix) and cervical canal (CC) in real time (online).
  • Cervical cancer is the fourth most common cancer in women worldwide. Early treatment can prevent up to 80% of cases of cervical cancer. Over the last decade, there has been a noticeable “rejuvenation” of cervical cancer due to an increase in the number of affected women of reproductive age: up to 70%. The intensive increase in the incidence of cervical cancer is especially noticeable in the group of women under 29 years of age, where over the past 20 years the increase has been more than 200%. CC ranks first among all gynecological oncological diseases in the age group of women under 30 years old. In women aged 25-40 years, invasive forms of cervical cancer account for about 30%. One of the main causes of mortality at this age is cervical cancer, ranking second after breast cancer.
  • Diagnostic and screening examination of cervical pathology is a periodic comprehensive examination of women of a certain age group as part of a medical program to prevent and reduce morbidity and mortality from cervical cancer.
  • the closest technical solution can be considered the method of performing screening during a patient appointment, disclosed in the American patent application US 2022170951, in which a specialist takes a cytological analysis, loads the sample into a processor containing a rotor with a cytochamber, in which the sample is stained, including using various reagents, then the stained sample is placed in a scanner to obtain multiple images or videos, which can then be combined into a single whole, then the finished image is loaded into storage, after which another specialist analyzes the resulting sample and makes a diagnosis, while the resulting samples remain stored in patient's medical history.
  • This method is implemented using a set of stations (modules) installed on a support, while the stations are equipped with functionality, depending on the type of screening (diagnostics) performed, which ensures cost-effectiveness of screening, prompt receipt of results, and creation of a digital database with results.
  • the disadvantage of the prototype is the impossibility of obtaining a screening result in one visit to a gynecologist, as well as the significant price of the equipment, the complexity of its design, use and maintenance.
  • the technical problem to be solved by the proposed invention is to ensure the possibility of obtaining the result of a diagnostic and screening study of cervical pathology in one visit to a gynecologist.
  • the technical result achieved in this case is to reduce the loss of cellular material, to simplify the process of diagnostic and screening examination of cervical pathology and reduce its cost, including by reducing logistics costs, to significantly reduce the time to obtain the result of a diagnostic and screening examination of cervical pathology uterus, in the patient receiving timely treatment, as well as in increasing the number of patients received by the gynecologist.
  • a system for performing a diagnostic and screening study of cervical pathology during one patient visit, which contains: a processor installed in the gynecologist's office for preparing and staining microslides, containing a housing, a housing cover, a multiplexer, cartridges with solutions and dyes, a rotor with a cytochamber and a drain tank, while the multiplexer is made with the ability to load working fluids by installing removable cartridges containing dyes and solutions into it, the multiplexer filling hole is located above the cytochamber, the cytochamber is made with the ability placement of only one sample with a microslide, while the cytochamber contains a place for placing a glass slide, pressed by the lid of the cytochamber, in which there is a place for the tip of a cytobrush with biomaterial, and the cytochamber is configured to be attached to the rotor of the cytochamber, made with the possibility of clockwise and counter
  • the scanner camera will be capable of controlling and transmitting images and/or video with pre-installed software or will be capable of communicating with a personal computer , phone, tablet, as well as control and transmission of images and/or video via a personal computer, phone, tablet.
  • the tip of the cytobrush is placed directly into the apparatus and the cells are deposited on a glass slide (currently in the field of liquid-based cytology, the cytobrush is placed in a preservative liquid for transporting the biomaterial to the laboratory).
  • the proposed design of the scanner designed for sequential scanning of one slide with a smear of the current patient at an appointment, and not for simultaneous loading of several slides for scanning, as in laboratory devices, provides: - ease of manufacture;
  • FIG. 2 is a general view of the processor with the cover of the processor housing open and the drain container removed;
  • - Fig.4 is a sectional view of the multiplexer (the position of the liquid channel purging);
  • - Fig. 5 is a sectional view of the multiplexer (the liquid channel is connected to a removable cartridge);
  • - Fig.7 is a general view of the cytochamber with the lid closed
  • - Fig. 8 is a general view of the cytochamber with the lid open;
  • - Fig. 16 motorized object table, top view
  • - Fig. 17 sectional view of a motorized object table
  • a Papanicolaou sample staining processor (processor) - a completely new device, with unique components and operating principles, and a scanner for scanning samples and sending them to a cytologist online for diagnosis in real time.
  • the processor for preparing and staining microslides is designed to be installed directly in a doctor’s office to perform microscopic examination of scrapings with cervical tissue and blood clots online.
  • the processor 1 includes a housing 2 and a housing cover 3, which may be made of plastic or other materials known in the art.
  • a multiplexer 4 - a device for dispensing liquid by switching (rotating) the output channel from one liquid to another. Liquid dosing occurs over time.
  • the multiplexer is made with the ability to load working fluids by installing removable cartridges 5 containing dyes, solutions and other liquids into it.
  • the filling hole 6 of the multiplexer 4 is located above the cytochamber 7, however, intermediate positions are also provided when liquid does not flow through it; in this state, air is blown through the through holes in the body of the multiplexer to remove excess liquid in the channel.
  • Liquids are supplied from multiplexer 4 and cellular biomaterial is deposited onto glass and then stained using Papanicolaou staining. After the processor has finished operating, cytochamber 7 can be pulled out, opened, and a glass slide with the finished microspecimen can be taken away.
  • the multiplexer rotor is a disk 11, in the center of which there is a metal core 12 for pressing the disk against the sealing rubber bands (pressing is carried out by a magnet 13 installed in the multiplexer housing).
  • a disk 14 made of fluoroplastic is installed with one hole at the level of channels 15 for liquid in the body of the multiplexer (thus the main friction pair in the multiplexer is fluoroplastic-rubber).
  • the output channel smoothly transitions to the axis of rotation of the rotor. All liquids flow in turn through the outlet channel, so there are intermediate positions of the rotor in which the outlet channel is located opposite the high-pressure zone formed by fan 16.
  • the distribution rotor is attached to the multiplexer by a magnet installed in the multiplexer mounting plate and a steel shaft in the rotor.
  • the rotor is rotated by a stepper motor 8 using a gear 17. All other components are connected by screw connections.
  • the multiplexer is capable of dispensing various liquids with an accuracy of +-150 ⁇ l.
  • the amount of liquid dispensed is from 0.3 ml to 20 ml. Dosing is done according to time. It is possible to use aggressive media (alcohols, hydrocarbons, acids, solvents).
  • the second main node of the processor 1 is the cytochamber 7, which is designed to accommodate only one sample with analysis.
  • the cytochamber 7 consists of a body, a sealing rubber in the center of the top cover 18 and a latch 19.
  • the cytochamber body 7, the top cover 18 and the latch 19 can be made of plastic or other known materials used in the art. Sealing rubber - an elastic band that is resistant to all liquids and solutions used is needed to seal between the hole in the top cover and the slide. It prevents cellular material and solutions from spreading throughout the glass beyond the opening, and keeps everything within a certain area.
  • a glass slide 20 is placed on the bottom of the cytochamber 7, then the lid 18 of the cytochamber 7 is closed with a latch 19, fixing the glass slide 20.
  • the clamping place is a circle-shaped place raised above the surface of the cytochamber 7 bottom for better sealing of the rubber band and the slide 20.
  • Contact of the slide 20 with the bottom of cytochamber 7 occurs only at the point of pressure, and not along the entire bottom. Contact at a small point on the surface minimizes any surface irregularities and prevents the slide from breaking.
  • cytobrush tip the working part of the cytobrush
  • cells with biomaterial
  • the tip of the cytobrush is not fixed on the cover 18 of the cytochamber 7, and lies freely in the place allocated for it, after which the rotor of the cytochamber turns and dumps it into the drain container along with the liquids.
  • the cytochamber 7 is attached to the cytochamber rotor 22, which is designed to rotate clockwise and counterclockwise.
  • the rotor 22 of the cytochamber is a unit for discharging liquid from the cytochamber 7 using centrifugal acceleration during its rotation.
  • Rotor 22 is equipped with position sensors.
  • the zero position of the rotor 22 is the position from which painting should begin. If the sensor is triggered, this means that rotor 2 needs to take the zero position to start the apparatus cycle.
  • the position sensor determines what position the rotor is currently in.
  • a waste container 23 which can be made of plastic or other materials known in the art.
  • Drain container 23 is a container for all waste liquids and cytobrush tips. It is removable, you can take it out, wash it and use it in the next cycle.
  • the drain container 23 is designed to cover the rotor 22 with the cytochamber 7 during operation of the processor and has a container for collecting liquid, a drain channel, a handle 24 and a viewing window 25, designed to provide control over the processes of operation of the processor 1. Through the viewing window 25 you can see the operation rotor and painting process.
  • the handle 24 can be made of any convenient shape, which is not important, since the handle 24 is designed for ease of manipulation of the drain container 23.
  • liquid is supplied from the cartridges to the multiplexer and, using the filling spout, the liquid enters the cytochamber.
  • the rotor of the cytochamber moves to the exposure position and keeps the liquid on the sample for a certain time for a given solution.
  • the cytochamber rotor then assumes the droplet discharging position and rotates counterclockwise until all liquid is drained into the drainage container. The cycle is repeated until the entire process is completed.
  • staining a beep sounds
  • the drain container is opened by pulling it out by the handle and emptied through the drain channel.
  • the cytochamber is removed from the cytochamber rotor by lifting the latch hook, and the slide with the finished sample is removed.
  • the cytochamber can be reused - a new slide is loaded, a new cytobrush tip with a sample is loaded, the cytochamber is attached to the rotor, the drain container is installed in place and the cycle starts again after pressing the power button.
  • the slide is installed in the cytochamber of the processor (staining apparatus).
  • the gynecologist takes a smear from the patient with a cytobrush.
  • the brush tip is detached and placed on top of the cytochamber.
  • the cytochamber is attached to the rotor, after which it is closed with a drain container.
  • the processor starts by pressing the start button 26.
  • Screen 27 shows what stage the sample is currently at.
  • Fluids are dispensed from the multiplexer and the cellular material is deposited onto a glass slide and then stained with Papanicolaou staining.
  • cytochamber 7 can be pulled out, opened, and the finished glass slide with the stained sample material can be taken away.
  • Points 6-12 use of substances for classical staining of a cell sample using the Papanicolaou method. This is a public method. It uses specific dyes and their sequence. Hematoxylin stains cell nuclei; water is needed to bluish hematoxylin and changes the color of cell nuclei. Next, the dye is applied OG-6, it will eventually stain dead cells and rough epithelium. Next comes the EA dye, which colors the cytoplasm of the cell pink and blue-green depending on the maturity of the cell.
  • the second independent autonomous device designed to implement the proposed system is scanner 28, which allows you to scan images of samples, record video, stitch them into a single whole, send them for storage to the sample database (to the cloud) and to the cytologist’s workplace for making a diagnosis in real time .
  • the scanner 28 contains a motorized stage 29, designed to accommodate only one slide 20.
  • the movement of the slide 20 with the prepared (stained) cell sample (biomaterial) on the stage 29 is carried out using drivers 30, 31 and eccentric cams 32, 33, driven by stepper motors 34, 35.
  • the cam mechanism ensures the movement of the glass slide 20 along a certain trajectory.
  • the trajectory is determined by the rotation of cams 32, 33, their special shape, as well as with the help of drivers 30, 31.
  • the drivers 30, 31 move by transferring pressure from the glass slide 20.
  • the cams 32, 33 move the glass slide 20, the drivers 30, 31 give it the opportunity to move along the “X” axis and along the “Y” axis, or vice versa, they press it in the opposite direction.
  • the drivers 30, 31 are attached to the X-axis linear movement unit 36 and to the Y-axis linear movement unit 37, respectively, by means of a screw connection. They provide linear movement of the glass slide 20 when the opposite cam presses on the glass slide.
  • the drivers 30, 31 are spring-loaded towards the X-axis cam 32 and the Y-axis cam 33, respectively.
  • Units 36, 37 of linear movement of the “X” and “Y” axes are an assembly of linear rail bearings (guides and carriages).
  • the X-axis stepper motor 34 and the Y-axis stepper motor 35 drive the X- and Y-axis eccentric cams 32, 33, respectively.
  • the X-axis stepper motor 34 is coupled to and rotates the X-axis drive cam 32.
  • the "X" axis cam 32 presses on the glass slide 20 towards the "X” axis.
  • the driver 30 moves along the axis "X”.
  • the pressure from the cam on the slide and, therefore, on the driver disappears (the cam rotates)
  • the driver returns to its previous position, pushing the slide back.
  • the body of the object stage 29 houses its main control elements:
  • condenser 38 an optical system consisting of lenses that collects rays from a light source and directs them to the object being examined or projected;
  • a camera holder 41 designed to accommodate a camera 42 configured to capture images and/or video, with the ability to combine the resulting images and/or video into one continuous one. Merging occurs using software on the camera itself, if it is a phone or tablet, or using software after transferring images to a computer, phone or tablet.
  • Camera 42 is configured to transfer the obtained results to a data storage and to a third-party computer, phone or tablet.
  • the camera 42 can be a mobile phone, or a smartphone, or a tablet, or a photo camera, or a video camera.
  • Photo and video cameras or other shooting devices can be controlled using a computer, phone or tablet, or using pre-installed programs.
  • Uploading an image and/or video to cloud storage can be done:
  • a magnifying lens 43 is placed above the scanner slide 20.
  • a microscope lens can be used as a magnifying lens, which provides magnified images for detailing individual cells.
  • the eyepiece 44 is the device where the camera is directed.
  • the camera 42 looks into the eyepiece 44, like a human eye into the eyepiece of a microscope.
  • the eyepiece 44 is optically connected to the lens 43.
  • the finished glass with the colored sample is removed from the processor and placed in the scanner on an automatic motorized stage.
  • the glass moves along a certain path under the lens.
  • a cytologist remotely looks at the sample and makes a diagnosis. Or he gathers a council of other cytologists, if the case is complex and requires the opinion of several doctors. While viewing the smear, the cytologist can make notes on the images.
  • the program for viewing digital smears can be equipped with a function with Artificial Intelligence to recognize normal and pathological cells. This function will help the cytologist pay attention to certain areas in the microslide or determine the norm.
  • the cytologist gives a conclusion and passes it back to the gynecologist. All tagged images are uploaded back to the cloud along with the conclusion.
  • the sample itself is stored in a cloud archive.
  • the gynecologist reviews the cytologist’s report using a computer, tablet, phone or other device with a screen and Internet access, diagnoses the patient and prescribes treatment and/or other procedures if necessary.
  • the gynecologist takes a smear from the patient and immediately immerses the tip of the cytobrush into the processor. After 10-15 minutes, he takes the finished glass slide out of the apparatus and loads it into the scanner. After 2-5 minutes, the scanned smear is uploaded to the cloud database, and the cytologist begins analysis. If the smear is adequate, then the cytologist will need up to 2 minutes to make a diagnosis and issue the result. If the smear is inadequate, a second smear is taken at the same appointment and the above steps are carried out.
  • the cytologist examining the digital smear, has the opportunity to clarify the medical history with the gynecologist during the patient’s appointment online, as well as minimize subjective errors through the use of a medical decision support system (AI) and/or a collegial opinion, which increases the sensitivity of the test. After 20-25 minutes, the patient knows the results of the tests and does not need to come for a second appointment with the gynecologist.
  • AI medical decision support system

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Pathology (AREA)
  • Surgery (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medical Informatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Analytical Chemistry (AREA)
  • Radiology & Medical Imaging (AREA)
  • Optics & Photonics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Veterinary Medicine (AREA)
  • General Physics & Mathematics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biochemistry (AREA)
  • Gynecology & Obstetrics (AREA)
  • Reproductive Health (AREA)
  • Epidemiology (AREA)
  • Primary Health Care (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L'invention se rapporte au domaine de la médecine et a pour but de mener des études microscopiques de grattages du col de l'utérus et du canal cervical en temps réel. Ce système d'analyse cytologique fonctionnel de pathologie du col de l'utérus en un prélèvement du gynécologue pour des études diagnostiques et de criblage, comprend, dans le cabinet du gynécologue, un processeur pour préparer et colorer des micro-préparations et un scanner capable de transmettre en ligne et à distance les images obtenues, ce qui permet d'obtenir un résultat de recherche diagnostique et de criblage de pathologie du col de l'utérus en un prélèvement du gynécologue et, dans le cas où le frottis est inadéquat, de faire un nouveau frottis et établir un diagnostic. Le résultat technique consiste en une diminution des pertes de matériau cellulaire, une simplification du processus de recherche diagnostique et de criblage de pathologie du col de l'utérus et une diminution de ses coûts intrinsèques, l'obtention par le patient d'un traitement en temps voulu, ainsi que la réduction du temps d'obtention du résultat de recherche diagnostique et de criblage de pathologie du col de l'utérus.
PCT/RU2023/050209 2022-09-21 2023-09-06 Système d'analyse cytologique fonctionnel de pathologie du col de l'utérus WO2024063671A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RU2022124850A RU2813628C1 (ru) 2022-09-21 Способ оперативного цитологического анализа патологии шейки матки в рамках одного приема гинеколога для диагностических и скрининговых исследований и устройства для осуществления способа
RU2022124850 2022-09-21

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WO2024063671A1 true WO2024063671A1 (fr) 2024-03-28

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7830598B2 (en) * 2005-10-13 2010-11-09 Tokai Hit Co., Ltd. Microscope stage and microscope observing unit
US20120283574A1 (en) * 2011-05-06 2012-11-08 Park Sun Young Diagnosis Support System Providing Guidance to a User by Automated Retrieval of Similar Cancer Images with User Feedback
US9567651B2 (en) * 2011-09-13 2017-02-14 Koninklijke Philips N.V. System and method for the detection of abnormalities in a biological sample
US20180136451A1 (en) * 2000-05-03 2018-05-17 Leica Biosystems Imaging, Inc. Fully automatic rapid microscope slide scanner
US20220276268A1 (en) * 2019-07-09 2022-09-01 The Regents Of The University Of California Automated rapid on-site evaluation machine and stain

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180136451A1 (en) * 2000-05-03 2018-05-17 Leica Biosystems Imaging, Inc. Fully automatic rapid microscope slide scanner
US7830598B2 (en) * 2005-10-13 2010-11-09 Tokai Hit Co., Ltd. Microscope stage and microscope observing unit
US20120283574A1 (en) * 2011-05-06 2012-11-08 Park Sun Young Diagnosis Support System Providing Guidance to a User by Automated Retrieval of Similar Cancer Images with User Feedback
US9567651B2 (en) * 2011-09-13 2017-02-14 Koninklijke Philips N.V. System and method for the detection of abnormalities in a biological sample
US20220276268A1 (en) * 2019-07-09 2022-09-01 The Regents Of The University Of California Automated rapid on-site evaluation machine and stain

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MINKINA T.N.: "TSitologicheskii skrining raka sheiki matki: ot traditsionnykh PAP-testa k kompiuternym tekhnologiiam [CYTOLOGICAL SCREENING OF THE CERVICAL CANCER: FROM THE TRADITIONAL PAP-TEST TO COMPUTER TECHNOLOGIES]", AKUSHERSTVO, GINEKOLOGIIA I REPRODUKTSIIA, vol. 11, no. 1, 1 January 2017 (2017-01-01), pages 56 - 63, XP009553676, ISSN: 2313-7347, DOI: 10.17749/2313-7347.2017.11.1.056-063 *

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