A new perspective on the causes of reproductive failure in women with chronic endometritis

Zefirova T.P., Sadykova D.A., Dzamukov R.A., Tolibova G.Kh., Gusev V.I., Evsegneeva I.V.

1) Kazan State Medical Academy, branch of the Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia, Kazan, Russia; 2) Medical-Sanitary Unit of Kazan (Volga Region) Federal University, Kazan, Russia; 3) Archak Morphological Research Center LLC, Kazan, Russia; 4) D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction, St. Petersburg, Russia; 5) I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, St. Petersburg, Russia; 6) Brand-Pharm LLC, Moscow, Russia

Objective: To determine the incidence of human papillomavirus (HPV) infection of the endometrium in women with reproductive failure and to evaluate immune changes and expression of p16ink4a protein accompanying viral invasion of the endometrium.
Materials and methods: Thirty women with chronic endometritis and reproductive failures who met the criteria were included in a prospective study. The main methods were quantitative analysis of HPV DNA, immunohistochemical examination of endometrial biopsy specimens to identify viral antigens, inflammatory markers and expression of p16ink4a protein.
Results: Viral infection of the endometrium was detected in 100% of women. HPV was found in 70% of patients and it was often combined with type I and type II herpes virus. Proinflammatory markers, mainly cytotoxic T-lymphocytes (CD8+) and B-lymphocytes (CD20+), were elevated in most patients; their increase indicated a chronic course of the inflammatory process. The expression of p16ink4a protein which is involved in cell cycle regulation was observed in all endometrial samples, suggesting its possible role in impaired implantation and embryogenesis.
Conclusion: Impaired reproductive function in women with chronic endometritis may be associated with viral infection of the endometrium. The expression of p16ink4a protein may be involved in the development of reproductive failure as it affects cellular processes in the endometrium and embryo.

Authors’ contributions: Zefirova T.P. – development of study design, data analysis, literature review of the topic, text editing; Sadykova D.A. – collection of clinical data, development of study design, data analysis, writing the text; Dzamukov R.A. – undertaking histological and immunohistochemical studies; Tolibova G.Kh. – undertaking immunohistochemical study of p16ink4a protein expression, morphometric analysis; Gusev V.I. – clarifying the mechanism of action of "Allokin-alpha" and its pharmacological properties; Evsegneeva I.V. –development of study design, data analysis, literature review of the topic.
Conflicts of interest: Authors declare lack of the possible conflicts of interest.
Funding: The study was carried out without sponsorship.
Ethical Approval: The study was approved by the Ethics Committee of KGMA, branch of RMACPE, Ministry of Health of Russia dated September 14, 2023 (extract from protocol No. 9/09). 
Patient Consent for Publication: All the patients provided an informed consent for the publication of their data and associated images. 
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Zefirova T.P., Sadykova D.A., Dzamukov R.A., Tolibova G.Kh., Gusev V.I., Evsegneeva I.V. 
A new perspective on the causes of reproductive failure in women with chronic endometritis.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (9): 156-162 (in Russian)
https://dx.doi.org/10.18565/aig.2024.237

Keywords

chronic endometritis
reproductive failures
human papillomavirus
p16ink4a protein

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Received 19.09.2024

Accepted 25.09.2024

About the Authors

Tatyana P. Zefirova, Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology, Kazan State Medical Academy - branch of RMACPE, Ministry of Health
of Russia, 420012, Russia, Kazan, Mushtari str., 1, +7(987)290-45-99, tzefirova@gmail.com, https://orcid.org/0000-0001-6785-6063
Dina A. Sadykova, obstetrician-gynecologist at Womens’ clinic, Medical and Sanitary Unit of Kazan (Volga Region) Federal University of Kazan (Volga) Federal University, 420061, Russia, Kazan, Nikolai Ershov str., 2, +7(987)285-02-64, SDina98@mail.ru, https://orcid.org/0000-0002-0177-5137
Rodion A. Dzamukov, pathologist of the highest category, PhD, Center for Morphological Research “Archak”, 420141, Russia, Kazan, Gabisheva str., 38, +7(917)278-87-34, drodion@narod.ru, https://orcid.org/0009-0007-9211-4011
Gulrukhsor K. Tolibova, Dr. Med. Sci., Head of the Department of Pathomorphology, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology,
199034, Russia, St. Petersburg, Mendeleevskaya line, 3; Professor, Department of Obstetrics and Gynecology named after S.N. Davydov, I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, gulyatolibova@yandex.ru, https://orcid.org/0000-0002-6216-6220
Vladimir I. Gusev, Chief Specialist for Advanced Research, Brand-Farm LLC, 109316, Russia, Moscow, Ostapovsky proezd, 5/1, bldg. 2, +7(926)981-51-82,
skilledgoose@gmail.com
Irina V. Evsegneeva, Development Director, Brand-Farm LLC, +7(925)880-21-66, rise@brand-pharm.ru

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