Analysis of the impact of uterine fibroids of different locations and sizes on the perfusion and metabolic characteristics of the endometrium
- Authors: Polenov N.I.1, Yarmolinskaya M.I.1, Zakuraeva K.A.1, Krutikova V.Y.2, Potapova E.V.2, Kogan I.Y.3, Shengelia N.D.4
-
Affiliations:
- The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
- Orel State University named after I.S. Turgenev
- The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
- N.A. Semashko City Hospital No. 38
- Issue: Vol 72, No 2 (2023)
- Pages: 51-62
- Section: Original Research
- URL: https://journals.rcsi.science/jowd/article/view/131194
- DOI: https://doi.org/10.17816/JOWD120126
- ID: 131194
Cite item
Abstract
BACKGROUND: Uterine fibroids are the most common benign tumor of the female reproductive system. A number of factors affect endometrial receptivity in patients with uterine fibroids such as transcription factors HOXA10 and HOXA11, cytokines (growth factors and inflammatory markers), etc. The negative effect of myomatous nodes, which deform the uterine cavity, on endometrial receptivity has been well studied and is beyond doubt, while the influence of intramural and intramural-subserosal fibroids on the endometrium is debatable. An important point is to define clear criteria that justify myomectomy in patients without clinical symptoms of the disease who are planning pregnancy, in particular, with the help of assisted reproductive technology. This article presents the results of studies on the impact of uterine fibroids of different locations on the endometrium. The data were obtained from foreign literature sources and such electronic databases as PubMed, CyberLeninka, and Google Scholar in the period from 2000 to 2022. This survey also reflects the main aspects of federal clinical recommendations and demonstrates the results of our own research.
AIM: The aim of this study was to determine the effect of intramural and intramural-submucosal myomatous nodes nodes on the perfusion and metabolic characteristics of the endometrium.
MATERIALS AND METHODS: We conducted a comprehensive examination of 20 patients of reproductive age with uterine fibroids who underwent surgical treatment in Gynecological Department One with Operating Unit of the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott (Saint Petersburg, Russia) and the Gynecological Department of N.A. Semashko City Hospital No. 38 (Saint Petersburg, Russia). Two groups were formed: group I consisted of 10 patients with multiple uterine fibroids (FIGO types 2 and 3); group II included 10 patients with intramural and intramural-subserosal myomatous nodes (FIGO types 4 to 6). Studies of endometrial perfusion and metabolism were carried out using a fiber optic system that implements fluorescence spectroscopy and laser Doppler flowmetry, including the LAKK-M diagnostic complex (Lazma Ltd., Russia) and a laparoscopic fiber optic probe, followed by registration of optical signals.
RESULTS: In the group of patients with uterine fibroids that deform the uterine cavity, we revealed a statistically significant decrease in the microcirculation index in endometrial tissues and an increase in fluorescence signals at a wavelength of 365 nm. This may indicate hypoxic phenomena in endometrial tissues of patients with FIGO types 2 and 3 fibroids. These findings are some of the significant pathogenetic causes of implantation disorders and abnormalities in the physiological course of pregnancy in patients of this study group.
CONCLUSIONS: The data obtained substantiate the need to continue research in this direction in order to develop perfusion-metabolic criteria that allow for optimizing the choice of treatment strategies in patients with uterine fibroids.
Full Text
##article.viewOnOriginalSite##About the authors
Nikolay I. Polenov
The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
Email: polenovdoc@mail.ru
ORCID iD: 0000-0001-8575-7026
SPIN-code: 9387-1703
MD, Cand. Sci. (Med.)
Russian Federation, Saint PetersburgMaria I. Yarmolinskaya
The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
Email: m.yarmolinskaya@gmail.com
ORCID iD: 0000-0002-6551-4147
SPIN-code: 3686-3605
Scopus Author ID: 7801562649
ResearcherId: P-2183-2014
MD, Dr. Sci. (Med.), Professor, Professor of the Russian Academy of Sciences
Russian Federation, Saint PetersburgKarina A. Zakuraeva
The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
Email: kareen07kbr@gmail.com
ORCID iD: 0000-0002-8128-306X
SPIN-code: 5215-7869
Scopus Author ID: 57197793723
Russian Federation, Saint Petersburg
Valentina Yu. Krutikova
Orel State University named after I.S. Turgenev
Email: krutikowa@bk.ru
ORCID iD: 0000-0002-5680-1574
SPIN-code: 6862-5861
Scopus Author ID: 58190824100
Russian Federation, Orel
Elena V. Potapova
Orel State University named after I.S. Turgenev
Author for correspondence.
Email: potapova_ev_ogu@mail.ru
ORCID iD: 0000-0002-9227-6308
SPIN-code: 9315-8770
Scopus Author ID: 57194048862
Cand. Sci. (Tech.), Assistant Professor
Russian Federation, OrelIgor Yu. Kogan
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: ikogan@mail.ru
ORCID iD: 0000-0002-7351-6900
SPIN-code: 6572-6450
Scopus Author ID: 56895765600
ResearcherId: P-4357-2017
MD, Dr. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences
Russian Federation, Saint PetersburgNodari D. Shengelia
N.A. Semashko City Hospital No. 38
Email: nod802210@yandex.ru
ORCID iD: 0000-0003-0677-494X
SPIN-code: 7495-9480
Russian Federation, Saint Petersburg
References
- El-Balat A, DeWilde RL, Schmeil I, et al. Modern myoma treatment in the last 20 years: a review of the literature. Biomed Res Int. 2018;2018. doi: 10.1155/2018/4593875
- Giuliani E, As-Sanie S, Marsh EE. Epidemiology and management of uterine fibroids. Int J Gynaecol Obstet. 2020;149(1):3–9. doi: 10.1002/ijgo.13102
- Lewis TD, Malik M, Britten J, et al. A comprehensive review of the pharmacologic management of uterine leiomyoma. Biomed Res Int. 2018;2018. doi: 10.1155/2018/2414609
- Cardozo ER, Clark AD, Banks NK, et al. The estimated annual cost of uterine leiomyomata in the United States. Am J Obstet Gynecol. 2012;206(3):211.e1–211.e2119. doi: 10.1016/j.ajog.2011.12.002
- Segars JH, Parrott EC, Nagel JD, et al. Proceedings from the third national institutes of health international congress on advances in uterine leiomyoma research: comprehensive review, conference summary and future recommendations. Hum Reprod Update. 2014;20(3):309–333. doi: 10.1093/humupd/dmt058
- Yarmolinskaya MI, Polenov NI, Kunitsa VV. Uterine fibroids: the role of signaling pathways in the pathogenesis. A literature review. Journal of Obstetrics and Women’s Diseases. 2020;69(5):113–124. (In Russ.) doi: 10.17816/JOWD695113-124
- Rossiĭskoe obshchestvo akusherov-ginekologov. Mioma matki. Klinicheskie rekomendatsii 2020. (In Russ.) [cited 2023 Feb 12]. Available from: https://roag-portal.ru/recommendations_gynecology#pdfcontent_gin_2
- Tskhay VB, Badmaeva SZ, Narkevich AN, et al. A predictive model for calculating the likelihood of recurrent uterine fibroids after surgical intervention. Fundamental and Clinical Medicine. 2021;6(3):64–70. (In Russ.) doi: 10.23946/2500-0764-2021-6-3-64-70
- Paulson RJ. Introduction: endometrial receptivity: evaluation, induction and inhibition. Fertil Steril. 2019;111(4):609–610. doi: 10.1016/j.fertnstert.2019.02.029
- Dvořan M, Vodička J, Dostál J, et al. Implantation and diagnostics of endometrial receptivity. Implantace a diagnostika receptivity endometria. Ceska Gynekol. 2018;83(4):291–298.
- Fox C, Morin S, Jeong JW, et al. Local and systemic factors and implantation: what is the evidence? Fertil Steril. 2016;105(4):873–884. doi: 10.1016/j.fertnstert.2016.02.018
- Morotskaya AV. Molekulyarnye faktory retseptivnosti endometriya. Journal of Obstetrics and Women’s Diseases. 2017;66:128–129.
- Onogi S, Ezoe K, Nishihara S, et al. Endometrial thickness on the day of the LH surge: an effective predictor of pregnancy outcomes after modified natural cycle-frozen blastocyst transfer. Hum Reprod Open. 2020;2020(4). doi: 10.1093/hropen/hoaa060
- Bu Z, Hu L, Yang X, et al. Cumulative live birth rate in patients with thin endometrium: a real-world single-center experience. Front Endocrinol. 2020;11:469. doi: 10.3389/fendo.2020.00469
- Gautray JP. Uterine diseases of receptivity of central origin. C R Soc Fr Gyncol. 1959;29(1):46–53. (In Fr.)
- Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006;12(6):731–746. doi: 10.1093/humupd/dml004
- Pritts EA, Parker WH, Olive DL. Fibroids and infertility: an updated systematic review of the evidence. Fertil Steril. 2009;91(4):1215–1223. doi: 10.1016/j.fertnstert.2008.01.051
- Dey SK, Lim H, Das SK, et al. Molecular cues to implantation. Endocr Rev. 2004;25(3):341–373. doi: 10.1210/er.2003-0020
- Taylor HS. The role of HOX genes in human implantation. Hum Reprod Update. 2000;6(1):75–79. doi: 10.1093/humupd/6.1.75
- Taylor HS, Arici A, Olive D, et al. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J Clin Invest. 1998;101(7):1379–1384. doi: 10.1172/JCI1057
- Cakmak H, Taylor HS. Molecular mechanisms of treatment resistance in endometriosis: the role of progesterone-hox gene interactions. Semin Reprod Med. 2010;28(1):69–74. doi: 10.1055/s-0029-1242996
- Benson GV, Lim H, Paria BC, et al. Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression. Development. 1996;122(9):2687–2696. doi: 10.1242/dev.122.9.2687
- Das SK, Lim H, Paria BC, et al. Cyclin D3 in the mouse uterus is associated with the decidualization process during early pregnancy. J Mol Endocrinol. 1999;22(1):91–101. doi: 10.1677/jme.0.0220091
- Rackow BW, Taylor HS. Submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity. Fertil Steril. 2010;93(6):2027–2034. doi: 10.1016/j.fertnstert.2008.03.029
- Doherty LF, Taylor HS. Leiomyoma-derived transforming growth factor-β impairs bone morphogenetic protein-2-mediated endometrial receptivity. Fertil Steril. 2015;103(3):845–852. doi: 10.1016/j.fertnstert.2014.12.099
- Li Q, Kannan A, Das A, et al. WNT4 acts downstream of BMP2 and functions via β-catenin signaling pathway to regulate human endometrial stromal cell differentiation. Endocrinology. 2013;154(1):446–457. doi: 10.1210/en.2012-1585
- Paria BC, Ma W, Tan J, et al. Cellular and molecular responses of the uterus to embryo implantation can be elicited by locally applied growth factors. Proc Natl Acad Sci USA. 2001;98(3):1047–1052. doi: 10.1073/pnas.98.3.1047
- Li Q, Kannan A, Wang W, et al. Bone morphogenetic protein 2 functions via a conserved signaling pathway involving Wnt4 to regulate uterine decidualization in the mouse and the human. J Biol Chem. 2007;282(43):31725–31732. doi: 10.1074/jbc.M704723200
- Speroff L., Fritz M. A. Clinical gynecologic endocrinology and infertility. 8th ed. Lippincott: Williams Wilkins; 2005.
- Stewart CL, Kaspar P, Brunet LJ, et al. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature. 1992;359(6390):76–79. doi: 10.1038/359076a0
- Hasegawa E, Ito H, Hasegawa F, et al. Expression of leukemia inhibitory factor in the endometrium in abnormal uterine cavities during the implantation window. Fertil Steril. 2012;97(4):953–958. doi: 10.1016/j.fertnstert.2012.01.113
- Unlu C, Celik O, Celik N, et al. Expression of endometrial receptivity genes increase after myomectomy of intramural leiomyomas not distorting the endometrial cavity. Reprod Sci. 2016;23(1):31–41. doi: 10.1177/1933719115612929
- Dimitriadis E, Stoikos C, Baca M, al. Relaxin and prostaglandin E(2) regulate interleukin 11 during human endometrial stromal cell decidualization. J Clin Endocrinol Metab. 2005;90(6):3458–3465. doi: 10.1210/jc.2004-1014
- Karpovich N, Klemmt P, Hwang JH, et al. The production of interleukin-11 and decidualization are compromised in endometrial stromal cells derived from patients with infertility. J Clin Endocrinol Metab. 2005;90(3):1607–1612. doi: 10.1210/jc.2004-0868
- Gellersen B, Brosens JJ. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr Rev. 2014;35(6):851–905. doi: 10.1210/er.2014-1045
- Zenclussen AC, Hämmerling GJ. Cellular regulation of the uterine microenvironment that enables embryo implantation. Front Immunol. 2015;6:321. doi: 10.3389/fimmu.2015.00321
- Paiva P, Salamonsen LA, Manuelpillai U, et al. Interleukin 11 inhibits human trophoblast invasion indicating a likely role in the decidual restraint of trophoblast invasion during placentation. Biol Reprod. 2009;80(2):302–310. doi: 10.1095/biolreprod.108.071415
- Ernst M, Inglese M, Waring P, et al. Defective gp130-mediated signal transducer and activator of transcription (STAT) signaling results in degenerative joint disease, gastrointestinal ulceration, and failure of uterine implantation. J Exp Med. 2001;194(2):189–203. doi: 10.1084/jem.194.2.189
- Fabi F, Grenier K, Parent S, et al. Regulation of the PI3K/Akt pathway during decidualization of endometrial stromal cells. PLoS One. 2017;12(5). doi: 10.1371/journal.pone.0177387
- Avellaira C, Villavicencio A, Bacallao K, et al. Expression of molecules associated with tissue homeostasis in secretory endometria from untreated women with polycystic ovary syndrome. Hum Reprod. 2006;21(12):3116–3121. doi: 10.1093/humrep/del183
- Ujvari D, Hulchiy M, Calaby A, et al. Lifestyle intervention up-regulates gene and protein levels of molecules involved in insulin signaling in the endometrium of overweight/obese women with polycystic ovary syndrome. Hum Reprod. 2014;29(7):1526–1535. doi: 10.1093/humrep/deu114
- Zhang Y, Sun X, Sun X, et al. Molecular characterization of insulin resistance and glycolytic metabolism in the rat uterus. Sci Rep. 2016. Vol. 6. doi: 10.1038/srep30679
- Miura S, Khan KN, Kitajima M, et al. Differential infiltration of macrophages and prostaglandin production by different uterine leiomyomas. Hum Reprod. 2006;21(10):2545–2554. doi: 10.1093/humrep/del205
- Klatsky PC, Lane DE, Ryan IP, et al. The effect of fibroids without cavity involvement on ART outcomes independent of ovarian age. Hum Reprod. 2007;22(2):521–526. doi: 10.1093/humrep/del370
- Somigliana E, Vercellini P, Daguati R, et al. Fibroids and female reproduction: a critical analysis of the evidence. Hum Reprod Update. 2007;13(5):465–476. doi: 10.1093/humupd/dmm013
- Baranov VS, Osinovskaya NS, Yarmolinskaya MI. Pathogenomics of uterine fibroids development. Int J Mol Sci. 2019;20(24). doi: 10.3390/ijms20246151
- Sunkara SK, Khairy M, El-Toukhy T, et al. The effect of intramural fibroids without uterine cavity involvement on the outcome of IVF treatment: a systematic review and meta-analysis. Hum Reprod. 2010;25(2):418–429. doi: 10.1093/humrep/dep396
- Eldar-Geva T, Meagher S, Healy DL, et al. Effect of intramural, subserosal, and submucosal uterine fibroids on the outcome of assisted reproductive technology treatment. Fertil Steril. 1998;70(4):687–691. doi: 10.1016/s0015-0282(98)00265-9
- Christopoulos G, Vlismas A, Salim R, et al. Fibroids that do not distort the uterine cavity and IVF success rates: an observational study using extensive matching criteria. BJOG. 2017;124(4):615–621. doi: 10.1111/1471-0528.14362
- Healy DL. Impact of uterine fibroids on ART outcome. Environ Health Perspect. 2000;108:845–847. doi: 10.1289/ehp.00108s5845
- Hart R, Khalaf Y, Yeong CT, et al. A prospective controlled study of the effect of intramural uterine fibroids on the outcome of assisted conception. Hum Reprod. 2001;16(11):2411–2417. doi: 10.1093/humrep/16.11.2411
- Khalaf Y, Ross C, El-Toukhy T, et al. The effect of small intramural uterine fibroids on the cumulative outcome of assisted conception. Hum Reprod. 2006;21(10):2640–2644. doi: 10.1093/humrep/del218
- Guven S, Kart C, Unsal MA, et al. Intramural leoimyoma without endometrial cavity distortion may negatively affect the ICSI - ET outcome. Reprod Biol Endocrinol. 2013;11:102. doi: 10.1186/1477-7827-11-102
- Seoud MA, Patterson R, Muasher SJ, et al. Effects of myomas or prior myomectomy on in vitro fertilization (IVF) performance. J Assist Reprod Genet. 1992;9(3):217–221. doi: 10.1007/BF01203816
- Sagi-Dain L, Ojha K, Bider D, et al. Pregnancy outcomes in oocyte recipients with fibroids not impinging uterine cavity. Arch Gynecol Obstet. 2017;295(2):497–502. doi: 10.1007/s00404-016-4273-9
- Ng EH, Chan CC, Tang OS, et al. Endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound in patients with small intramural uterine fibroids during IVF treatment. Hum Reprod. 2005;20(2):501–506. doi: 10.1093/humrep/deh594
- Kandurova K, Dremin V, Zherebtsov E, et al. Fiber-optic system for intraoperative study of abdominal organs during minimally invasive surgical interventions. Applied Sciences. 2019;9(2):217. (In Russ.) doi: 10.3390/app9020217
- Kandurova KYu, Dremin VV, Zherebtsov EA, et al. Optical biopsy methods and their prospects of application for intraoperative analysis of tissue metabolism and blood microcirculation in minimally invasive surgery. Regional hemodynamics and microcirculation. 2018;17(3):71–79. (In Russ.) doi: 10.24884/1682-6655-2018-17-3-71-79
- Dunaev AV. Mul’timodal’naya opticheskaya diagnostika mikrotsirkulyatorno-tkanevykh sistem organizma cheloveka. Staryy Oskol: TNT; 2023. (In Russ.) [cited 2023 Feb 12]. Available from: https://www.tnt-ebook.ru/library/book/746
- Zherebtsov EA, Dremin VV, Zherebtsova AI, et al. Fluorestsentnaya diagnostika mitokhondrial’noy. Orel: OGU imeni I.S. Turgeneva, 2018. (In Russ.) [cited 2023 Feb 12]. Available from: https://bmecenter.ru/sites/default/files/publications/Monografia_Zherebtsov_2018.pdf
- Hickey M, Krikun G, Kodaman P, et al. Long-term progestin-only contraceptives result in reduced endometrial blood flow and oxidative stress. J Clin Endocrinol Metab. 2006;91(9):3633–3638. doi: 10.1210/jc.2006-0724
- Bungum L, Kullander S, Maltau JM. Laser Doppler flowmetry of human endometrial microvasculature. A preliminary communication. Acta Obstet Gynecol Scand. 1996;75(2):178–181. doi: 10.3109/00016349609033314
- Damirov MM, Murtuzalieva ZZ, Poletova TN, et al. The use of laser Doppler flowmetry to assess microcirculation in patients with hyperplastic processes of the endometrium. Voprosy ginekologii, akusherstva i perinatologii. 2006;5(5):40–44. (In Russ.)
- Aplin JD, Charlton AK, Ayad S. An immunohistochemical study of human endometrial extracellular matrix during the menstrual cycle and first trimester of pregnancy. Cell Tissue Res. 1988;253(1):231–240. doi: 10.1007/BF00221758
- Mayevsky A, Rogatsky GG. Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies. Am J Physiol Cell Physiol. 2007;292(2):C615–C640. doi: 10.1152/ajpcell.00249.2006