Receptive status of the endometrium in patients of reproductive age with serous and mucinous ovarian cystadenoma before and after unilateral adnexectomy

Abstract

BACKGROUND: Currently, the incidence of benign ovarian tumors has increased, and numerous studies have reported its negative effect on women’s reproductive health. In modern literature, approximately 30% of patients with ovarian neoplasms have reproductive problems. In the presence of ovarian diseases, changes in the endometrium alter its receptivity, thereby reducing the chances of successful conception and gestation and gaining increasing attention. Patients seeking to preserve their reproductive function prefer organ-preserving surgical interventions; however, in clinical practice, adnexectomy is often necessary because of damaged ovarian tissue.

AIM: To analyze the morphofunctional state of the endometrium and its receptivity in patients with serous and mucinous ovarian cystadenomas before and after surgical treatment.

MATERIALS AND METHODS: The prospective study included patients of reproductive age with benign epithelial tumors (serous/mucinous cystadenomas) who had not received hormonal drugs for 6 months before surgical treatment. Group 1 included 32 patients with serous cystadenoma, and group 2 included 30 patients with mucinous cystadenoma. Before and 6–12 months after unilateral salpingo-oophorectomy, a pipelle biopsy of the endometrium was performed during the “implantation window.” The qualitative and quantitative parameters of pinopodes were examined, and the expression levels of estrogen (ER) and progesterone (PR) receptors in the glands and stroma of the endometrium were evaluated.

RESULTS: Preoperatively, the number of pinopodes decreased in patients with serous cystadenoma, and the expression level of ER in the stroma and those of PR in the stroma and glands was reduced. Postoperatively, the number of mature pinopodes increased, and the expression levels of ER in the stroma and PR in the stroma and glands was increasing. Preoperatively, in patients with mucinous cystadenomas, the expression levels of ER in the stroma and glands and PR in the stroma and glands decreased, and the number of pinopodes reduced. Postoperatively, compared with patients with serous cystadenomas in the glandular component of the endometrium, those with mucinous cystadenoma had lower expression levels of both ER and PR, lower PR expression level in the stromal component, and increased number of pinopodes.

CONCLUSIONS: The results of this study showed that benign ovarian tumors are accompanied by impaired morphofunctional state and receptivity of the endometrium, and timely surgical intervention positively affects these indicators and increases the reproductive potential of women.

Keywords

serous ovarian cystadenoma / mucinous ovarian cystadenoma / unilateral salpingo-oophorectomy / endometrial receptivity / estrogen receptors / progesterone receptors / pinopodes

References

[1] Mikhaleva LM, Solomatina AA, Kurtzer MA, et al. Immunohistochemical phenotype of recurrent ovarian endometriomas. Clinical and Experimental Morphology. 2017;(4):15–21. (In Russ).

[2] Михалева Л.М., Соломатина А.А., Курцер М.А., и др. Иммуногистохимический фенотип рецидивирующих эндометриоидных образований яичников // Клиническая и экспериментальная морфология. 2017. № 4. С. 15–1.

[3] Mikhaleva LM, Solomatina AA, Boltovskaya MN, et al. Clinical and morphological aspects of ovarian endometriosis depending on the severity of the disease. Clinical and Experimental Morphology. 2016;(3):15–21. (In Russ).

[4] Михалева Л.М., Соломатина А.А., Болтовская М.Н., и др. Клинико-морфологическая и иммуногистохимическая характеристика эндометриоза яичников в зависимости от тяжести заболевания // Клиническая и экспериментальная морфология. 2016. Т. 3, № С. 15–21.

[5] Ikromova ZM. Somatic and gynecological status of reproductive-age of women with benign tumors and tumor-like formations of the ovaries. Vestnik Avitsenny. 2017;19(1):7–11. (In Russ). doi: 10.25005/2074-0581-2017-19-1-7-11

[6] Икромова З.М. Соматический и гинекологический статус женщин репродуктивного возраста с доброкачественными опухолями и опухолевидными образованиями яичников // Вестник Авиценны. 2017. Т. 19, № 1. С. 7–11. doi: 10.25005/2074-0581-2017-19-1-7-11

[7] Mikhaleva LM, Milovanov AP, Khovanskaya TN, et al. Histomorphological and functional features of the eutopic endometrium in patients with ovarian endometriosis after surgery — a clinical study. Reproductive Sciences. 2021;28(8):2350–2358. doi: 10.1007/s43032-021-00508-3

[8] Mikhaleva L.M., Milovanov A.P., Khovanskaya T.N., et al. Histomorphological and functional features of the eutopic endometrium in patients with ovarian endometriosis after surgery — a clinical study // Reproductive Sciences. 2021. Vol. 28, N 8. P. 2350–2358. doi: 10.1007/s43032-021-00508-3

[9] Solopova AE, Dudina AN, Bychenko VG, Rubtsova NA. Ovarian malignancy risk stratification. The integration of mri into O-RADS. Obstetrics and Gynecology. 2020;(9):28–37. (In Russ). doi: 10.18565/aig.2020.9.28-37

[10] Солопова А.Е., Дудина А.Н., Быченко В.Г., Рубцова Н.А. Стратификация рисков злокачественности образований яичников. Интеграция МРТ в систему O-RADS // Акушерство и гинекология. 2020. № 9. С. 28–37. doi: 10.18565/aig.2020.9.28-37

[11] Orazov MR, Khamoshina MB, Abitova MZ, et al. Ovarian endometriosis associated infertility: a modern view to the problem. Gynecology. 2020;22(5):44–49. (In Russ). doi: 10.26442/20795696.2020.5.200405

[12] Оразов М.Р., Хамошина М.Б., Абитова М.З., и др. Бесплодие, ассоциированное с эндометриозом яичников: современный взгляд на проблему // Гинекология. 2020. Т. 22, № 5. С. 44–49. doi: 10.26442/20795696.2020.5.200405

[13] Protasova AE, Tsypurdeeva AA, Tsypurdeeva ND, Solntseva IA. Principles of diagnosis of ovarian neoplasms — minimization of errors. Journal of Obstetrics and Womans Diseases. 2019;68(4):71–82. (In Russ). doi: 10.17816/JOWD68471-82

[14] Протасова А.Э., Цыпурдеева А.А., Цыпурдеева Н.Д., Солнцева И.А. Принципы диагностики новообразований яичника: минимизация ошибок // Журнал акушерства и женских болезней. 2019. Т. 68, № 4. С. 71–82. doi: 10.17816/JOWD68471-82

[15] Chen YN, Ma F, Zhang YD, et al. Ultrasound features improve diagnostic performance of ovarian cancer pre dictors in distinguishing benign and malignant ovarian tumors. Curr Med Sci. 2020;40(1):184–191. doi: 10.1007/s11596-020-2163-7

[16] Chen Y.N., Ma F., Zhang Y.D., et al. Ultrasound features improve diagnostic performance of ovarian cancer pre dictors in distinguishing benign and malignant ovarian tumors // Curr Med Sci. 2020. Vol. 40, N 1. P. 184–191. doi: 10.1007/s11596-020-2163-7

[17] Chistyakova GN, Grishkina AA, Remizova II, et al. Immunohistochemical and morphometric analysis of thin endometrium. Kursk Scientific and Practical Bulletin “Man and His Health”. 2020;(1):37–42. (In Russ). doi: 10.21626/vestnik/2020-1/05

[18] Чистякова Г.Н., Гришкина А.А., Ремизова И.И., и др. Иммуногистохимическая и морфометрическая оценка тонкого эндометрия // Курский научно-практический вестник «Человек и его здоровье». 2020. № 1. С. 37–42. doi: 10.21626/vestnik/2020-1/05

[19] Szwarc MM, Hai L, Gibbons WE, et al. Early growth response 1 transcriptionally primes the human endometrial stromal cell for decidualization. J Steroid Biochem Mol Biol. 2019;189:283–290. doi: 10.1016/j.jsbmb.2019.01.021

[20] Szwarc M.M., Hai L., Gibbons W.E., et al. Early growth response 1 transcriptionally primes the human endometrial stromal cell for decidualization // J Steroid Biochem Mol Biol. 2019. Vol. 189. P. 283–290. doi: 10.1016/j.jsbmb.2019.01.021

[21] Aganezov SS, Ponomarenko KY, Morotskaya AV, Aganezova NV. Evaluation of expressiom of endometrial estrogens and progesterone receptors in women with a history of reproductive failures. East European Scientific Journal. 2018;2(30):65–69. (In Russ).

[22] Аганезов С.С., Пономаренко К.Ю., Мороцкая А.В., Аганезова Н.В. Оценка экспрессии рецепторов эстрогенов и прогестерона в эндометрии у женщин с нарушениями репродуктивной функции в анамнезе // Восточно-европейский научный журнал. 2018. Т. 2, № 30. С. 65–69.

[23] Tumasyan EA, Biryukov AE, Gracheva NA, et al. Receptive status of the endometrium in patients with benign ovarian tumors before and after organ-preserving operations. Arkhiv patologii. 2022;84(4):29–37. (In Russ). doi: 10.17116/patol20228404129

[24] Тумасян Е.А., Бирюков А.Е., Грачева Н.А., и др. Рецептивный статус эндометрия при доброкачественных опухолях яичников до и после органосохраняющих операций // Архив патологии. 2022. Т. 84, № 4. С. 29–37. doi: 10.17116/patol20228404129

[25] Solomatina AA, Breusenko LE, Khamzin IZ, et al. Three-dimensional ultrasound assessment of morphological and functional characteristics of the endometrium in patients after unilateral adnexectomy. Gynecology, Obstetrics and Perinatology. 2023;22(1):19–26. (In Russ). doi: 10.20953/1726-1678-2023-1-19-26

[26] Соломатина А.А., Бреусенко Л.Е., Хамзин И.З., и др. Трехмерная эхография в оценке морфофункционального состояния эндометрия у пациенток после односторонней аднексэктомии // Вопросы гинекологии, акушерства и перинатологии. 2023. Т. 22, № 1. С. 19–26. doi: 10.20953/1726-1678-2023-1-19-26

[27] Mikhaleva LM, Solomatina AA, Khovanskaya TN, et al. Morphological and functional state of the endometrium and its receptivity in patients with ovarian endometriosis. Russian Journal of Human Reproduction. 2020;26(3):68–75. (In Russ). doi: 10.17116/repro20202603168

[28] Михалева Л.М., Соломатина А.А., Хованская Т.Н., и др. Морфофункциональное состояние и рецептивность эндометрия у пациенток с эндометриозом яичников // Проблемы репродукции. 2020. Т. 26, № 3. С. 68–75. doi: 10.17116/repro20202603168

[29] Rudenko YuA, Kulagina EV, Kravtsova OA, et al. The readiness of the endometrium for extracorporeal fertilization: prognosis by the data of ultrasound and morphological study. Genes & cells. 2019;14(3):142–146. (In Russ). doi: 10.23868/201906025

[30] Руденко Ю.А., Кулагина Е.В., Кравцова О.А., и др. Готовность эндометрия к экстракорпоральному оплодотворению: прогноз по данным ультразвукового и морфологического исследования // Гены и клетки. 2019. Т. 14, № 3. С. 142–146. doi: 10.23868/201906025

[31] Krasnopol’skaja KV, Ershova IJu, Fedorova AA. Tonkii jendometrii. Lechenie besplodija u zhenshhin s gipoplaziei jendometrija. Moscow: GJeOTARMedia; 2020. (In Russ).

[32] Краснопольская К.В., Ершова И.Ю., Федорова А.А. Тонкий эндометрий. Лечение бесплодия у женщин с гипоплазией эндометрия. Москва : ГЭОТАР-Медиа, 2020.

[33] Kliman HJ, Frankfurter D. Clinical approach to recurrent im- plantation failure: evidence-based evaluation of the endometrium. Fertil Steril. 2019;111(4):618–628. doi: 10.1016/j.fertnstert.2019.02.011

[34] Kliman HJ, Frankfurter D. Clinical approach to recurrent im- plantation failure: evidence-based evaluation of the endometrium // Fertil Steril. 2019. Vol. 111, N 4. P. 618–628. doi: 10.1016/j.fertnstert.2019.02.011

[35] Makhmudova GM, Kibanov MV, Gokhberg YaA. In search for an ideal marker of endometrial receptivity from histology to comprehensive molecular genetics-based approaches. Almanac of Clinical Medicine. 2019;47(1):12–25. (In Russ). doi: 10.18786/2072-0505-2019-47-005

[36] Махмудова Г.М., Кибанов М.В., Гохберг Я.А. Поиск идеального маркера для оценки рецептивности эндометрия: от гистологии до современных молекулярно-генетических подходов // Альманах клинической медицины. 2019. Т. 47, № 1. С. 12–25. doi: 10.18786/2072-0505-2019-47-005

[37] Radzinsky VE, Mikhaleva LM, Orazov MR, et al. Endometrium receptivity in patients with repeated implant failures. Doctor.Ru. 2022;21(1):27–33. (In Russ). doi: 10.31550/1727-2378-2022-21-1-27-33

[38] Радзинский В.Е., Михалёва Л.М., Оразов М.Р., и др. Рецептивность эндометрия пациенток с повторными неудачами имплантации // Доктор.Ру. 2022. Т. 21, № 1. С. 27–33. doi: 10.31550/1727-2378-2022-21-1-27-33

[39] Craciunas L, Gallos I, Chu J, et al. Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis. Hum Reprod Update. 2019;25(2):202–223. doi: 10.1093/humupd/dmy044

[40] Craciunas L., Gallos I., Chu J., et al. Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis // Hum Reprod Update. 2019. Vol. 25, N 2. P. 202–223. doi: 10.1093/humupd/dmy044

[41] Coughlan C, Ledger W, Wang Q, et al. Recurrent implantation failure: definition and management. Reprod Biomed Online. 2014; 28(1):14–38. doi: 10.1016/j. rbmo.2013.08.011

[42] Coughlan C., Ledger W., Wang Q., et al. Recurrent implantation failure: definition and management // Reprod Biomed Online. 2014. Vol. 28, N 1. P. 14–38. doi: 10.1016/j.rbmo.2013.08.011

[43] Dorostghoal M, Ghaffari HO, Marmazi F, Keikhah N. Overexpression of endometrial estrogen receptor-alpha in the window of implantation in women with unexplained infertility. Int J Fertil Steril. 2018;12(1):37–42. doi: 10.22074/ijfs.2018.5118

[44] Dorostghoal M., Ghaffari H.O., Marmazi F., Keikhah N. Overexpression of endometrial estrogen receptor-alpha in the window of implantation in women with unexplained infertility // Int J Fertil Steril. 2018. Vol. 12, N 1. P. 37–42. doi: 10.22074/ijfs.2018.5118

[45] Kogan EA, Paramonova NB, Kolotovkina AV, Burmenskaya OV. The morphological and molecular biological signs of impaired endometrial receptivity in infertility in women suffering from external genital endometriosis. Arkhiv patologii. 2018;80(3):11–18. (In Russ). doi: 10.17116/patol201880311-18

[46] Коган Е.А., Парамонова Н.Б., Колотовкина А.В., Бурменская О.В. Морфологические и молекулярно-биологические признаки нарушения рецептивности эндометрия при бесплодии женщин, страдающих наружным генитальным эндометриозом // Архив патологии. 2018. Т. 80, № 3. С. 11–18. doi: 10.17116/patol201880311-18

[47] Karaoğlan Ö., Kuyucu Y., Ürünsak İ.F., et al. Morphological features of the secretory phase endometrium in women with unexplained infertility. Ultrastruct Pathol. 2021;45(3):243–256. doi: 10.1080/01913123.2021.1954117

[48] Karaoğlan Ö., Kuyucu Y., Ürünsak İ.F., et al. Morphological features of the secretory phase endometrium in women with unexplained infertility // Ultrastruct Pathol. 2021. Vol. 45, N 3. P. 243–256. doi: 10.1080/01913123.2021.1954117

[49] D’Ippolito S, Nicuolo F, Papi M, et al. Expression of pinopodes in the endometrium from recur- rent pregnancy loss women. Role of thrombomodulin and ezrin. J Clin Med. 2020;9(8):2634. doi: 10.3390/jcm9082634

[50] D’Ippolito S., Nicuolo F., Papi M., et al. Expression of pinopodes in the endometrium from recurrent pregnancy loss women. Role of thrombomodulin and ezrin // J Clin Med. 2020. Vol. 9, N 8. P. 2634. doi: 10.3390/jcm9082634

[51] Tolibova GH, Tral’ TG, Kogan IJu, Olina AA. Jendometrij. Atlas. Moscow: Mediabjuro Status prezens; 2022. 184 p. (In Russ).

[52] Толибова Г.Х., Траль Т.Г., Коган И.Ю., Олина А.А. Эндометрий. Атлас. Москва : Медиабюро Статус презенс, 2022. 184 с.

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Mikhaleva L., Solomatina A.A., Gashimova A.I., Biryukov A.E., Gracheva N.A., Mikhalev S.A., Tumasyan E.A., Ismaiilova P.J., Banin V.V.