Clinical risk factors for infertility in reproductive-age patients with intramural uterine fibroids

封面

如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅存取

详细

Objective: To determine the clinical risk factors for infertility and develop a relative risk score for infertility in reproductive-aged patients with intramural uterine fibroids (UF).

Materials and methods: This was a single-center retrospective case-control study with multivariate logistic regression. The study included an analysis of the medical records of 200 reproductive-age patients with intramural UF measuring 3–5 cm (FIGO 3–6 type), who were examined and treated at the University Clinic "I am healthy!" (clinical base of the Department of Obstetrics and Gynecology with a perinatology course at the People’s Friendship University) from 2017 to 2021. The patients were divided into two groups: 100 infertile women with intramural UF ("case") and 100 fertile patients with UF ("control"). Factors, such as complaints and diseases with a duration exceeding 12 months, which could potentially affect fertility at the time of pregnancy planning, were assessed. The development of a relative risk score scale involved selecting parameters and combining them into a score scale. The binary logistic regression method was used to predict single-step (prognostic) conditions such as infertility.

Results: The relative risk score scale included anamnestic parameters such as long and heavy menstruation (lasting more than 12 months), chronic pelvic pain (lasting more than 12 months), insulin resistance, obesity (lasting more than 12 months), long-term iron deficiency anemia, history of endometrial hyperplastic processes, and phenotypic signs of undifferentiated connective tissue dysplasia (two or more signs). Mathematical calculations allowed us to determine the significance of each risk factor. The sum of these factors provides an estimate of the relative risk of infertility based on the obtained odds ratio value expressed in points. A score of >6 indicates an increased relative risk of infertility (p<0.001), while a score of >13 indicates a high relative risk of infertility with statistical significance (p<0.001). During the ROC analysis with recalculated point coefficients for each patient, we obtained a "cut off" value of 0.5035, above which the probability of infertility increased, reaching the maximum sensitivity and specificity.

Conclusion: The developed relative risk point scale, which includes clinical and phenotypic parameters, can be a valuable tool for assessing the risk of infertility (as well as the potential causes of failure in in vitro fertilization programs) in patients with intramural UF, including during the stages of pregnancy planning.

作者简介

Ekaterina Dubinskaya

Patrice Lumumba Peoples' Friendship University of Russia

编辑信件的主要联系方式.
Email: eka-dubinskaya@yandex.ru
ORCID iD: 0000-0002-8311-0381

Dr. Med. Sci., Professor at the Department of Obstetrics, Gynecology and Perinatology

俄罗斯联邦, Moscow

Svetlana Kolesnikova

Reaviz Moscow Medical University

Email: ksnmed@mail.ru
ORCID iD: 0000-0001-9575-0274

PhD, Associate Professor at the Department of Obstetrics, Gynecology and Pediatrics

俄罗斯联邦, Moscow

Elizaveta Alyoshkina

Patrice Lumumba Peoples' Friendship University of Russia

Email: alyoshkina.ev@yandex.ru
ORCID iD: 0000-0001-5339-1285

Teaching Assistant at the Department of Obstetrics, Gynecology and Reproductive Medicine

俄罗斯联邦, Moscow

Alexander Gasparov

Patrice Lumumba Peoples' Friendship University of Russia

Email: 13513520@mail.ru
ORCID iD: 0000-0001-6301-1880

Dr. Med. Sci., Professor, Professor at the Department of Obstetrics, Gynecology and Perinatology

俄罗斯联邦, Moscow

参考

  1. Министерство здравоохранения Российской Федерации. Миома матки. Клинические рекомендации. 2020. [Ministry of Health of the Russian Federation. Uterine fibroids. Clinical guidelines. 2020. (in Russian)].
  2. Дубинская Е.Д., Гаспаров А.С., Колесникова С.Н., Холбан И.В., Бабичева И.А. Эпигенетика в клинической гинекологии. Вопросы гинекологии, акушерства и перинатологии. 2021; 20(2): 110-6. [Dubinskaya E.D., Gasparov A.S., Kolesnikova S.N., Kholban I.V., Babicheva I.A. Epigenetics in Clinical Gynecology. Gynecology, Obstetrics and Perinatology. 2021; 20(2): 110-6. (in Russian)]. https://dx.doi.org/10.20953/1726-1678-2021-2-110-116.
  3. Дубинская Е.Д., Колесникова С.Н., Гаспаров А.С., Холбан И.В., Алешкина Е.В. Роль фетального программирования при миоме матки. Вопросы гинекологии, акушерства и перинатологии. 2022; 21(5): 27-35. [Dubinskaya E.D., Kolesnikova S.N., Gasparov A.S., Kholban I.V., Aleshkina E.V. Role of fetal programming in uterine fibroids. Gynecology, Obstetrics and Perinatology. 2022; 21(5): 27-35. (in Russian)]. https://dx.doi.org/10.20953/ 1726-1678-2022-5-27-35.
  4. Zhang L., Lu Q., Chang C. Epigenetics in health and disease. Adv. Exp. Med. Biol. 2020; 1253: 3-55. https://dx.doi.org/10.1007/978-981-15-3449-2_1.
  5. Protic O., Toti P., Islam M.S., Occhini R., Giannubilo S.R., Catherino W.H. et al. Possible involvement of inflammatory/reparative processes in the development of uterine fibroids. Cell. Tissue Res. 2016; 364(2): 415-27. https:// dx.doi.org/10.1007/s00441-015-2324-3.
  6. Elinav E., Nowarski R., Thaiss C., Hu B., Jin C., Flavell R. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat. Rev. Cancer. 2013; 13(11): 759-71. https://dx.doi.org/10.1038/nrc3611.
  7. Ma S., Xie N., Li W., Yuan B., Shi Y., Wang Y. Immunobiology of mesenchymal stem cells. Cell. Death Differ. 2014; 21(2): 216-25. https://dx.doi.org/10.1038/cdd.2013.158.
  8. Orciani M., Sorgentoni G., Torresetti M., Di Primio R., Di Benedetto G. MSCs and inflammation: new insights into the potential association between ALCL and breast implants. Breast Cancer Res. Treat. 2016; 156(1): 65-72. https:// dx.doi.org/10.1007/s10549-016-3745-8.
  9. Orciani M., Sorgentoni G., Olivieri F., Mattioli-Belmonte M., Benedetto G., Primio R. Inflammation by breast implants and adenocarcinoma: not always a bad company. Clin. Breast Cancer. 2017; 17(4): 286-92. https:// dx.doi.org/10.1016/j.clbc.2017.01.001.
  10. Islam M.S., Protic O., Stortoni P., Grechi G., Lamanna P., Petraglia F. et al. Complex networks of multiple factors in the pathogenesis of uterine leiomyoma. Fertil. Steril. 2013; 100(1): 178-93. https://dx.doi.org/10.1016/ j.fertnstert.2013.03.007.
  11. Jayes F., Liu B., Feng L., Aviles-Espinoza N., Leikin S., Leppert P. Evidence of biomechanical and collagen heterogeneity in uterine fibroids. PLoS One. 2019; 14(4): e0215646. https://dx.doi.org/10.1371/journal.pone.0215646.
  12. Goodwin N. Improving integrated care: can implementation science unlock the 'black box' of complexities? Int. J. Integr. Care. 2019; 19(3): 12. https:// dx.doi.org/10.5334/ijic.4724.
  13. Bonanni V., Reschini M., La Vecchia I., Castiglioni M., Muzii L., Vercellini P. et al. The impact of small and asymptomatic intramural and subserosal fibroids on female fertility: a case-control study. Hum. Reprod. Open. 2022; 2023(1): hoac056. https://dx.doi.org/10.1093/hropen/hoac056.
  14. Freytag D., Günther V., Maass N., Alkatout I. Uterine fibroids and infertility. Diagnostics (Basel). 2021; 11(8): 1455. https://dx.doi.org/10.3390/diagnostics11081455.
  15. Дубинская Е.Д., Колесникова С.Н., Алёшкина Е.В., Гаспаров А.С., Башкирова Е.С., Леффад М.Л. Дополнительные факторы инфертильности при интрамуральной миоме матки. Акушерство и гинекология. 2023; 5: 75-82. [Dubinskaya E.D., Kolesnikova S.N., Alyoshkina E.V., Gasparov A.S., Bashkirova E.S., Leffad M.L. Supplementary infertility factors in patients with intramural uterine fibroids. Obstetrics and Gynecology. 2023; (5): 75-82 (in Russian)]. https://dx.doi.org/10.18565/aig.2023.28.
  16. Дубинская Е.Д., Колесникова С.Н., Алёшкина Е.В., Гаспаров А.С. Клинические и фенотипические признаки недифференцированной дисплазии соединительной ткани при интрамуральной миоме матки как маркеры прогнозирования инфертильности. Вопросы гинекологии, акушерства и перинатологии. 2023; 22(4): 57-65. [Dubinskaya E.D., Kolesnikova S.N., Alyoshkina E.V., Gasparov A.S. Clinical and phenotypic signs of undifferentiated connective tissue dysplasia in intramural uterine leiomyoma as markers for predicting infertility. Gynecology, Obstetrics and Perinatology. 2023; 22(4): 57-65. (in Russian)]. https://dx.doi.org/10.20953/ 1726-1678-2023-4-57-65.
  17. Дубинская Е.Д., Колесникова С.Н., Гаспаров А.С., Алёшкина Е.В. Молекулярные паттерны, связанные с повреждением, при интрамуральной миоме матки и бесплодии. Акушерство и гинекология. 2024; 5: 108-17. [Dubinskaya E.D., Kolesnikova S.N., Gasparov A.S., Alyoshkina E.V. Damage-associated molecular patterns in patients with intramural uterine fibroids and infertility. Obstetrics and Gynecology. 2024; (5): 108-17. (in Russian)]. https://dx.doi.org/10.18565/aig.2024.48.
  18. Дубинская Е.Д., Колесникова С.Н., Алёшкина Е.В., Гаспаров А.С. Хроническое стерильное воспаление в патогенезе доброкачественных изменений миометрия. Вопросы гинекологии, акушерства и перинатологии. 2024; 23(1): 84-93. [Dubinskaya E.D., Kolesnikova S.N., Aleshkina E.V., Gasparov A.S. Chronic sterile inflammation in the pathogenesis of benign myometrial diseases. Gynecology, Obstetrics and Perinatology. 2024; 23(1): 84-93. (in Russian)]. https://dx.doi.org/10.20953/1726-1678- 2024-1-84-93.
  19. Российское научное медицинское общество терапевтов. Дисплазии соединительной ткани. Клинические рекомендации. 2017. [Russian Scientific Medical Society of Therapists. Connective tissue dysplasias. Clinical Guidelines. 2017. (in Russian)].
  20. Metwally M., Raybould G., Cheong Y.C., Horne A.W. Surgical treatment of fibroids for subfertility. Cochrane Database Syst. Rev. 2020; 1(1): CD003857. https://dx.doi.org/10.1002/14651858.CD003857.pub4.
  21. Karlsen K., Mogensen O., Humaidana P., Kesmodel U., Ravn P. Uterine fibroids increase time to pregnancy: a cohort study. Eur. J. Contracept. Reprod. Health Care. 2020; 25(1): 37-42. https://dx.doi.org/10.1080/ 13625187.2019.1699047.
  22. Stewart E., Cookson C., Gandolfo R., Schulze-Rath R. Epidemiology of uterine fibroids: a systematic review. BJOG. 2017; 124(10): 1501-12. https:// dx.doi.org/10.1111/1471-0528.14640.
  23. Don E., Mijatovic V., Huirne J. Infertility in patients with uterine fibroids: a debate about the hypothetical mechanisms. Hum. Reprod. 2023; 38(11): 2045-54. https://dx.doi.org/10.1093/humrep/dead194.
  24. Ojo O., Nwafor-Ezeh P., Rotimi D., Iyobhebhe M., Ogunlakin A., Ojo A. Apoptosis, inflammation, and oxidative stress in infertility: a mini review. Toxicol. Rep. 2023; 10: 448-62. https://dx.doi.org/10.1016/j.toxrep.2023.04.006.
  25. Hall J., Mouton A., da Silva A., Omoto A., Wang Z., Li X. et al. Obesity, kidney dysfunction, and inflammation: interactions in hypertension. Cardiovasc. Res. 2021; 117(8): 1859-76. https://dx.doi.org/10.1016/j.toxrep.2023.04.006.
  26. Bilsen J., Brink W., Hoek A., Dulos R., Caspers M., Kleemann R. et al. Mechanism-based biomarker prediction for low-grade inflammation in liver and adipose tissue. Front. Physiol. 2021; 12: 703370. https://dx.doi.org/10.3389/fphys.2021.703370.
  27. Lanser L., Fuchs D., Kurz K., Weiss G. Physiology and inflammation driven pathophysiology of iron homeostasis-mechanistic insights into anemia of inflammation and its treatment. Nutrients. 2021; 13(11): 3732. https:// dx.doi.org/10.3390/nu13113732.
  28. Bahrami A., Bahrami-Taghanaki H., Khorasanchi Z., Timar A., Jaberi N., Azaryan E. et al. Menstrual problems in adolescence: relationship to serum vitamins A and E, and systemic inflammation. Arch. Gynecol. Obstet. 2020; 301(1): 189-97. https://dx.doi.org/10.1007/ s00404-019-05343-1.
  29. O'Connor B., Pope B., Peters M., Ris-Stalpers C., Parker K. The role of extracellular matrix in normal and pathological pregnancy: Future applications of microphysiological systems in reproductive medicine. Exp. Biol. Med. (Maywood). 2020; 245(13): 1163-74. https://dx.doi.org/ 10.1177/1535370220938741.
  30. Afrin S., Islam M.S., Patzkowsky K., Malik M., Catherino W.H., Segars J.H. et al. Simvastatin ameliorates altered mechanotransduction in uterine leiomyoma cells. Am. J. Obstet. Gynecol. 2020; 223(5): 733.e1-733. https:// dx.doi.org/10.1016/j.ajog.2020.05.012.

补充文件

附件文件
动作
1. JATS XML
下载
2. Fig. 1. Study design

下载 (161KB)
索引源数据
3. Fig. 2. Results of the ROC-analysis

下载 (109KB)
索引源数据
##common.cookie##