Mediastinal large B-cell lymphoma and pregnancy: difficulties in diagnosis and choice of rational medical tactics



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Abstract

A woman pregnant for the second time was admitted to the obstetric hospital at full-term gestational age with complaints of dyspnea at rest and dry cough, which had been bothering her for the past three months. During examination, signs of severe respiratory failure were noticeable. Based on the results of computed tomography of the chest organs, a volumetric formation measuring 200x150 mm with compression of the mediastinal organs and infiltrative changes in the lower lobe of the left lung was revealed. Given the life-threatening condition of the pregnant woman with a high risk of death, a decision was made to perform an emergency delivery with simultaneous biopsy of the space-occupying lesion. Based on the results of histological examination of the biopsy material, diffuse large B-cell lymphoma was detected. In the postoperative period, immunochemotherapy was started according to the RCHOP regimen, which resulted in a significant decrease in the size of the lesion, perifocal edema, and the degree of compression of adjacent organs. The safest diagnostic methods during pregnancy are ultrasound and magnetic resonance imaging (MRI). However, it should be remembered that if there is a threat to the mother's life, there are no absolute contraindications to various research methods, including radiation, at any stage of gestation. Modern scanning protocols, as well as protective equipment, help minimize perinatal risks.

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Mediastinal large B-cell lymphoma and pregnancy: difficulties in diagnosis and choice of rational medical tactics

RELEVANCE
Mediastinal large B-cell lymphoma (MLBCL) is a type of non-Hodgkin's lymphoma (NHL), refers to primary rapidly progressing extranodal tumors, affects mainly young women aged 20 to 40 years and is characterized by the expression of CD19, CD20, CD22 and CD79a receptors on the surface of B-lymphocytes [1, 2]. This type of lymphoma is associated with the presence of mutations in the genes that regulate the maturation and differentiation of B-lymphocytes of the thymus medulla, which determine the humoral immune response. Common subtypes of B-cell lymphomas include diffuse large cell lymphoma (DLBCL), caused by mutations in the MYC gene, and follicular lymphoma (FL), formed due to translocation of the BCL2 gene [3]. Mediastinal large B-cell lymphoma is usually characterized by local growth and is most often located in the anterior mediastinum with damage to the pericardium, lungs, pleura, heart muscle, and chest wall. Symptoms depend on the size of the tumor. The implementation of reproductive function in patients with MLCL is a significant medical and social problem due to the need to adapt diagnostic and treatment methods in order to minimize risks to the life and health of the mother and fetus [4, 5]. The features of the course of MLCL during pregnancy vary from virtually asymptomatic to quite aggressive. The clinical picture of MLCL is nonspecific and is typical for a large number of respiratory diseases, since its main symptoms include cough and shortness of breath. In addition, patients with MLBC are bothered by chest pain, enlarged lymph nodes and so-called B-symptoms - an increase in body temperature > 38°C lasting > 3 days without laboratory signs of an infectious and inflammatory process, profuse night sweats and weight loss of 10% of the initial body weight over the past 6 months [6, 7, 8]. The standard method of treating diffuse large B-cell lymphoma is chemotherapy. The literature describes the successful implementation of immunochemotherapy, including during pregnancy, starting from the second trimester. Currently, immunochemotherapy is most often carried out according to the RCHOP scheme, which includes the following drugs: cyclophosphamide, which has an alkylating, immunosuppressive, antitumor and cytostatic effect, doxorubicin hydrochloride - an antitumor antibiotic of the anthracycline series, vincristine sulfate - an antitumor agent of plant origin and prednisolone - a corticosteroid drug for systemic use, as well as a humanized monoclonal antibody anti-CD20 - rituximab. This treatment regimen leads to a significant increase in the life expectancy of patients and a marked decrease in the number of relapses [9, 10, 11]. Thus, Melisa Inquilla Coyla et al. (2022) described a clinical case of detection of primary mediastinal B-cell lymphoma at the 29th week of gestation in a 26-year-old patient who reported that she had been bothered by cough, shortness of breath, orthopnea and tachycardia for two months. According to the results of chest tomography, a space-occupying lesion measuring 10x12 cm was revealed, according to echocardiography - compression of the right heart. The histological diagnosis was established using percutaneous biopsy. The patient had an abnormal heart rhythm within the framework of sinus bradycardia and ectopic atrial bradycardia. Due to the rapid deterioration of the pregnant woman's condition, an early delivery was performed by cesarean section followed by chemotherapy, against the background of which cardiovascular complications regressed [12]. Buchholtz ML et al. (2018) also presented a clinical observation in which a 28-year-old patient in the third trimester of gestation had symptoms of mediastinal obstruction for several weeks - shortness of breath, cough, swelling of the face and upper extremities, which were mistakenly associated with the presence of a cold and edema of pregnancy. Due to the progression of signs of heart failure at the 34th week, an early delivery was performed by cesarean section. The diagnosis of primary mediastinal B-cell lymphoma was established after delivery based on the biopsy results. The authors emphasized the importance of timely examination of pregnant women with symptoms of mediastinal obstruction using transthoracic echography [13]. Hersey AE et al. (2020) described a clinical case of diffuse large B-cell lymphoma diagnosed in a patient in the third trimester. In this observation, labor induction was performed at 34 weeks of pregnancy, followed by a standard chemotherapy protocol after delivery. The patient breastfed her baby according to the temporary lactation protocol [5]. But Azin Alizadehasl et al. (2023) in their clinical observation presented a 25-year-old patient who complained of chronic cough with progressive dyspnea, as well as hypotension and tachycardia at the 25th week of pregnancy. Echocardiography revealed significant pericardial effusion with compression of the right heart and the development of signs of cardiac tamponade due to the presence of a large space-occupying lesion in the anterior mediastinum. Pericardiocentesis was performed urgently. Pathological and immunohistochemical analysis of the biopsy specimen of the space-occupying lesion revealed the presence of lymphoma with positive expression of CD3, CD20, CD30, CD45, PAX5 and negative expression of CD15. In the context of prolongation of pregnancy, three courses of chemotherapy according to the CHOP regimen were administered every three weeks with a satisfactory response and subsequent delivery by cesarean section at 37 weeks of gestation. No maternal and perinatal complications were identified [7]. Daiki Hattori et al. (2019) also described a case of primary B-cell lymphoma of the anterior mediastinum with tracheal compression in a 31-year-old patient at 11 weeks of gestation due to the appearance of complaints of shortness of breath. The patient underwent steroid pulse therapy followed by treatment with vincristine, cyclophosphamide, and prednisolone (VCP), against the background of which the complaints regressed. Then, at 13 weeks of pregnancy, 8 courses of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP) therapy were administered. At 35 weeks and 6 days of pregnancy, the patient was delivered. The condition of the newborn was assessed as satisfactory. Postpartum positron emission tomography showed that the lymphoma had achieved a complete metabolic response. This clinical observation shows that steroid pulse therapy followed by courses of VCP and R-CHOP is a safe and effective treatment method for pregnant patients with malignant lymphoma [10]. Yoshinori Hashimoto et al. (2019) also presented a clinical observation in which, at 15 weeks of pregnancy, the patient was diagnosed with primary mediastinal B-cell lymphoma due to the development of superior vena cava syndrome and then administered chemotherapy. Maternal and perinatal outcomes were described as favorable, based on which the authors also concluded that the use of treatment regimens similar to CHOP in the second and third trimesters of pregnancy is relatively safe [11]. Joshua Hagège et al. (2024) reported the results of expectant management of lymphoma during pregnancy using vinblastine monotherapy, which in terms of obstetric complications, response rate, and overall survival (100%) supports the idea that strategies that do not involve the use of combination therapy (including the use of ABVD-type polychemotherapy - adriamycin, bleomycin, vinblastine, and dacarbazine - associated with both obstetric complications and fetal toxicity) are possible and give good results [14]. Sandy On and Abraham Chang (2022) analyzed the medical records of 37 patients with high-grade NHL treated with rituximab and concomitant chemotherapy during pregnancy. Most patients were treated in the second and third trimesters with an average of four cycles of combination immunochemotherapy. In 14/17 (82%) cases, stable remission was achieved. Of the three patients treated in the first and second trimesters, two had spontaneous abortions and one had intrauterine fetal death. Of the 34 (91.9%) live births, 6 (16.2%) cases had respiratory and cardiovascular complications, and 5 (13.5%) had hematological complications. This review emphasizes the efficacy and safety of immunochemotherapy in the second and third trimesters of pregnancy [15]. The clinical case presented below highlights the clinical course of mediastinal large B-cell lymphoma during pregnancy and outlines the challenges associated with the examination and management of patients with this disease.

CASE DESCRIPTION
A 35-year-old woman pregnant for the second time was admitted to the obstetric hospital at 37-38 weeks of pregnancy with complaints of dyspnea at rest and a dry cough that worsened in the supine position.
Unproductive cough without fever had been bothering the patient for the past three months, for which she consulted her local therapist, but the recommended symptomatic therapy had no clinical effect.
Upon admission to the hospital, the general condition was assessed as severe, the patient was in a forced position - sitting or lying on the left side. Tachypnea was noted with a respiratory rate (RR) of 22 per minute, a decrease in blood oxygen saturation (SpO2) to 92% (with a norm of 95-100%), tachycardia with a heart rate (HR) of 118 beats / min, arterial hypertension with blood pressure (BP) of 145/87 mm Hg. Art. Body temperature was within physiological limits (36.60C). During auscultation of the lungs, breathing was harsh, weakened on the left in the lower sections. Ultrasound examination of the uterus and fetus, as well as Doppler study of hemodynamics in the mother-placenta-fetus system did not reveal any pathological changes. Laboratory examination of the patient using clinical blood test data revealed hypochromic microcytic anemia (hemoglobin 93 g/l with a norm of 105-115 g/l in the third trimester of pregnancy, MCH 24.2 pg with a norm of 26-33.5 pg, MCV 70 fl with a norm of 80-100 fl) against the background of decreased hematocrit (26.9% with a norm of 34.7-47.0%), as well as absolute (0.26x109/l with a norm of 1.26-3.20x109/l) and relative (4.2% with a norm of 19-45%) lymphopenia. Biochemical blood test results revealed hypoalbuminemia (32.7 U/l with a norm of 34-50 U/l). According to the echography of the pleural cavities on the left, separation of the pleural sheets was noted due to the presence of homogeneous anechoic contents. Given the increase in dyspnea, drainage of the left pleural cavity was performed - 500 ml of serous fluid was evacuated, the cytological analysis of which showed the presence of large blast cells of the lymphoid series. According to echocardiography (ECHO-CG), expansion of the cavities of the left and right atria, right ventricle, hypertrophy of the myocardium of the left ventricle, thickening of the aortic walls, separation of the pericardial sheets were detected. The results of computed tomography (CT) of the chest organs revealed the presence of a volumetric formation in the mediastinum measuring 200 x 150 mm with uneven, lumpy contours and signs of compression of the trachea and left main bronchus, infiltrative changes in the lower lobe of the left lung, signs of left-sided pleural and pericardial effusion, as well as the presence of a pleural formation on the right (Fig. 1).

Fig. 1. Chest computed tomography with visualization of a space-occupying lesion in the mediastinum with compression of the heart, aorta, trachea and main bronchi: a) coronal section in 3D mode, b) axial section in pulmonary mode.

Due to the presence of signs of respiratory failure, the patient was hospitalized in the intensive care unit. An interdisciplinary consultation was held, according to the conclusion of which, given the life-threatening condition of the patient due to the development of severe respiratory failure with a high risk of death, it was decided to deliver the multiparous woman urgently with a simultaneous biopsy of the space-occupying lesion in the mediastinum by transthoracic puncture to establish a histological diagnosis and determine further management tactics. Taking into account the severity of the patient's condition, cesarean section was chosen as the method of delivery. Due to the presence of severe respiratory failure, Joel-Cohen laparotomy and cesarean section in the lower uterine segment were performed in a forced position of the patient on the left side under combined endotracheal anesthesia and epidural analgesia. A live full-term baby was delivered in the cephalic presentation, the height and weight indicators of which corresponded to the physiological values ​​for the full-term pregnancy. The assessment of the newborn's condition according to the Apgar scale was 7 and 8 points at the 1st and 5th minutes of life, respectively. 10 minutes after the delivery of the baby and placenta, the patient developed bradycardia, however, as a result of timely therapeutic measures, the cardiac arrhythmia was eliminated. Tracheobronchoscopy was performed, revealing compression by a volumetric formation of the bifurcation part of the trachea and the mouths of both main bronchi, as well as ECHO-CG, revealing signs of pulmonary hypertension and hydropericardium - a pericardial puncture was performed and 240 ml of serous-hemorrhagic discharge was evacuated. According to the results of histological examination of the material obtained by intraoperative transthoracic puncture of the space-occupying lesion of the mediastinum, the morphological picture corresponded to a lymphoproliferative disease - diffuse large B-cell lymphoma. In the postoperative period, the patient's condition was assessed as extremely severe, due to the progression of signs of respiratory failure with the development and increase of heart failure, which required complex multicomponent therapy, including renal replacement therapy (RRT) to correct tissue hypoperfusion. Under conditions of ongoing artificial ventilation (ALV), pathogenetic therapy was started with prednisolone using mechanical circulatory support in the form of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). After the stabilization of the patient's condition, the mother was transferred to a hospital specialized in providing specialized medical care for the treatment of lymphoproliferative disease, where a course of combined immunochemotherapy (CT+R) according to the RCHOP scheme was started in the intensive care unit. A week later, stable positive dynamics were observed in terms of a significant decrease in the size of the space-occupying formation (Fig. 2), the patient's activation, and the resumption of independent nutrition and self-care. Subsequently, the mother was transferred to the hematology department with subsequent discharge from the hospital and recommendations for further monitoring and treatment of the underlying disease.

Fig. 2. Computed tomography of the chest organs with visualization of a space-occupying lesion in the mediastinum in the pulmonary mode, axial section: a) before immunochemotherapy, b) after the first course of immunochemotherapy.

Over the next three months, the patient received four courses of immunochemotherapy and is currently in satisfactory condition during the break between courses.

DISCUSSION
In analyzing the present clinical observation, it is necessary to point out the presence of the following difficulties in the diagnosis and management of diffuse large B-cell lymphoma during pregnancy. The first difficulty is in conducting an adequate diagnosis of diseases of the chest organs in pregnant women using such instrumental research methods that, on the one hand, are sufficiently informative, and on the other, are absolutely safe for the fetus, since the analysis of complaints and the implementation of physical examination methods (percussion, auscultation) cannot always help to correctly assess the situation. In this case, the clinical symptoms were nonspecific, and the effect of the empirically prescribed treatment was absent. Of course, the use of radiation research methods, such as plain radiography and computed tomography (CT), during pregnancy is highly discouraged, given the risk of their teratogenic effects on the fetus [16]. However, given the lack of regression of clinical symptoms and alertness regarding the presence of respiratory diseases, including those of specific etiology, such as, for example, pulmonary tuberculosis, coronavirus pneumonia, etc., it is still necessary to perform an instrumental examination of the chest organs for vital indications. As is known, the safest visualization methods during pregnancy are ultrasound (US) and magnetic resonance imaging (MRI), but, unfortunately, they do not always provide sufficient information for diagnosis. It should also be remembered that if there is a threat to the life of the mother, there are no absolute contraindications to the use of the necessary research methods at any stage of gestation, taking into account the principle that the potential benefit to the mother will exceed the possible risk to the fetus. In addition, there is evidence that intrauterine radiosensitivity directly depends on gestational age: ionizing radiation poses the greatest danger during the implantation period of the fertilized egg - the first 2-3 weeks from the moment of conception, as well as in the period from the 5th to the 8th week of pregnancy, when the main organs and systems are laid down and developed [17]. It should be taken into account that modern scanning protocols and protective equipment can minimize these risks. Thus, the radiation dose to the fetus during routine radiation examination of a pregnant woman (for example, CT of the chest organs) is about 0.03 mGy, while experimental data indicate that exposure to radiation doses < 50 mGy is not accompanied by an increased risk of fetal developmental abnormalities or pregnancy loss [18]. The maternity hospital absolutely correctly chose the tactics of pregnancy management – ​​emergency delivery, since the patient was in a state of severe respiratory failure, in which conditions further prolongation of pregnancy posed an immediate threat to the life of the mother and fetus. However, the second difficulty that doctors faced was the inevitable decompensation of the patient's condition against the background of delivery. It was caused by an increase in blood flow (venous return) to the right chambers of the heart as a result of the cessation of compression of the inferior vena cava, as well as an increase in the circulating blood volume (CBV) due to the redistribution of fluid into the bloodstream from the extravascular space due to a decrease in the size of the uterus and a decrease in intra-abdominal pressure after the extraction of the child and placenta [20]. Similar changes in hemodynamics are observed in all women after delivery, but in conditions of severe compression and displacement of the mediastinal organs by a volumetric formation, they were life-threatening.

CONCLUSION
Thus, the preferred diagnostic methods during pregnancy, including diseases of the chest organs, are ultrasound and MRI, but according to absolute indications, it is possible to use radiation diagnostic methods with the necessary protective equipment. It should be borne in mind that in the vast majority of cases, lymphoproliferative diseases are characterized by a rather aggressive course, therefore, if their presence is suspected, a histological diagnosis should be established and specific treatment should be started. Discussions regarding the safety of using drugs included in chemotherapy in conditions of prolongation of pregnancy continue to this day. Nevertheless, based on the literature, it can be concluded that if chemotherapy is not recommended in the first trimester, then its use in the second and third trimesters, even in conditions of prolongation of pregnancy to full-term (37 weeks or more), is recognized as relatively safe for the fetus and leads to similar results in the treatment of lymphoma in non-pregnant patients [10, 11, 14, 15, 19]. Of course, a rational choice of tactics for managing such patients becomes impossible without close cooperation of specialists of various profiles - obstetricians-gynecologists, resuscitators, hematologists, oncologists, and chemotherapists who have experience in treating lymphoproliferative diseases. Analyzing the features of the course and outcomes of pregnancy, we can confidently say that preserving the life of the mother and the birth of a healthy child in this clinical observation are an indisputable victory and an exceptional merit of high professionalism, clear continuity and impeccable work of the team of doctors.

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About the authors

Irina Vladimirovna Ignatko

Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)

Email: ignatko_i_v@staff.sechenov.ru
ORCID iD: 0000-0002-9945-3848
SPIN-code: 8073-1817
Scopus Author ID: 15118951800

член-корреспондент РАН, профессор, заведующий кафедрой акушерства, гинекологии и перинатологии Института клинической медицины имени Н.В. Склифосовского 

Russian Federation, 119991, Российская Федерация, г. Москва, ул. Трубецкая, дом 8, строение 2

Irina Mikhailovna Bogomazova

First Moscow State Medical University named after I.M. Sechenov of the Ministry of Health of the Russian Federation (Sechenov University)

Author for correspondence.
Email: bogomazova_i_m@staff.sechenov.ru
ORCID iD: 0000-0003-1156-7726
SPIN-code: 9414-1218
Scopus Author ID: 57191968287

Associate Professor, Associate Professor of the Department of Obstetrics, Gynecology and Perinatology of the N.V. Sklifosovsky Institute of Clinical Medicine

Russian Federation, 119991, Russian Federation, Moscow, Trubetskaya st., house 8, building 2

Vera Sergeevna Belousova

Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)

Email: belousova_v_s@staff.sechenov.ru
ORCID iD: 0000-0001-8332-7073
SPIN-code: 6026-9008
Scopus Author ID: 57193974992

доцент, профессор кафедры акушерства, гинекологии и перинатологии Института клинической медицины имени Н.В. Склифосовского 

Russian Federation, 119991, Российская Федерация, г. Москва, ул. Трубецкая, дом 8, строение 2

Elena Vladimirovna Timokhina

Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)

Email: timokhina_i_m@staff.sechenov.ru
ORCID iD: 0000-0001-6628-0023
SPIN-code: 4946-8849
Scopus Author ID: 25958373500

Профессор, профессор кафедры акушерства, гинекологии и перинатологии Института клинической медицины имени Н.В. Склифосовского

Russian Federation, 119991, г. Москва, Улица Трубецкая, дом 8, строение 2

Anastasia Alekseevna Churganova

Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)

Email: churganova_a_a@staff.sechenov.ru
ORCID iD: 0000-0001-9398-9900
SPIN-code: 3872-7167

доцент кафедры акушерства, гинекологии и перинатологии Института клинической медицины имени Н.В. Склифосовского

Russian Federation, 119991, г. Москва, улица Трубецкая, дом 8, строение 2

Svetlana Sergeevna Mirzakhamidova

Городская клиническая больница имени С.С. Юдина Департамента здравоохранения города Москвы

Email: rimatevs@mail.ru
ORCID iD: 0000-0002-5807-5027

заместитель главного врача по медицинской части Городской клинической больницы имени С.С. Юдина Департамента здравоохранения города Москвы

Russian Federation, 115446, г. Москва, Коломенский проезд, дом 4

Olga Viktorovna Ignatenko

Городская клиническая больница имени С.С. Юдина Департамента здравоохранения города Москвы;
Российская медицинская академия непрерывного постдипломного образования Министерства здравоохранения Российской Федерации

Email: ovignatenko@gmail.ru
ORCID iD: 0000-0002-6353-2552

заместитель главного врача по анестезиологии и реаниматологии Городской клинической больницы имени С.С. Юдина Департамента здравоохранения города Москвы;

доцент кафедры анестезиологии и реаниматологии имени профессора Е.А. Дамир 

Russian Federation, 115446, Российская Федерация, г. Москва, Коломенский проезд, дом 4; 125993, Российская Федерация, г. Москва, ул. Баррикадная, дом 2/1, строение 1

Elena Lvovna Muravina

Городская клиническая больница имени С.С. Юдина Департамента здравоохранения города Москвы

Email: ELENA.MURAVINA@MAIL.RU
ORCID iD: 0009-0004-3900-3898

врач акушер-гинеколог родильного дома

Russian Federation, 115446, Российская Федерация, г. Москва, Коломенский проезд, дом 4

Yulia Alekseevna Samoilova

Городская клиническая больница имени С.С. Юдина Департамента здравоохранения города Москвы;
Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)

Email: samoylova2005@yandex.ru
ORCID iD: 0000-0001-7448-515X

заведующий отделением патологии беременности №1 родильного дома;

ассистент кафедры акушерства, гинекологии и перинатологии Института клинической медицины имени Н.В. Склифосовского

Russian Federation, 115446, Российская Федерация, г. Москва, Коломенский проезд, дом 4; 119991, г. Москва, улица Трубецкая, дом 8, строение 2

Ksenia Igorevna Seurko

Городская клиническая больница имени С.С. Юдина Департамента здравоохранения города Москвы;
Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)

Email: kseurko@yandex.ru
ORCID iD: 0009-0001-3287-9254

врач акушер-гинеколог акушерско-физиологического отделения №1 родильного дома;

аспирант кафедры акушерства, гинекологии и перинатологии Института клинической медицины имени Н.В. Склифосовского

Russian Federation, 115446, Российская Федерация, г. Москва, Коломенский проезд, дом 4; 119991, г. Москва, улица Трубецкая, дом 8, строение 2

Sevda Fizuliyevna Askerova

Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)

Email: askerova_sevda12@mail.ru
ORCID iD: 0000-0002-4925-594X

ординатор кафедры акушерства, гинекологии и перинатологии Института клинической медицины имени Н.В. Склифосовского

Russian Federation, 119991, г. Москва, улица Трубецкая, дом 8, строение 2

Anastasia Alekseevna Kochnova

Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)

Email: nastakochetova11@mail.ru
ORCID iD: 0000-0002-1208-1480

ординатор кафедры акушерства, гинекологии и перинатологии Института клинической медицины имени Н.В. Склифосовского

Russian Federation, 119991, г. Москва, улица Трубецкая, дом 8, строение 2

Polina Eduardovna Temirbieva

Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)

Email: p.temirbieva@yandex.ru
ORCID iD: 0009-0009-8719-0479

ординатор кафедры акушерства, гинекологии и перинатологии Института клинической медицины имени Н.В. Склифосовского

Russian Federation, 119991, г. Москва, улица Трубецкая, дом 8, строение 2

Ludmila Gipppokratovna Leonova

Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)

Email: 9251404718@mail.ru
ORCID iD: 0000-0002-1196-0977

Студент

Russian Federation, 119991, г. Москва, улица Трубецкая, дом 8, строение 2

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