Influence of focused ultrasound ablation of uterine fibroids on endometrial receptivity in women of reproductive age

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OBJECTIVE

To study the effect of the energy of focused ultrasonic waves during FUS-MRI ablation of uterine fibroids on molecular markers of endometrial receptivity in women of reproductive age.

MATERIAL AND METHODS

A prospective comparative controlled study of 60 women of reproductive age was conducted. The main group consisted of 32 patients suffering from the symptomatic course of uterine fibroids who received treatment with FUS-MRI ablation of uterine fibroids. Depending on the localization of the treated node, the patients were divided into two subgroups: 17 women with localization of the node on the front wall of the uterus and the reflected action of ultrasonic waves on the endometrium and 15 women with localization of the node on the posterior wall of the uterus and direct penetrating effect of the waves. The control group consisted of 28 healthy fertile women. The endometrium obtained with pipelle biopsia on days 20—22 of the cycle was examined by immunohistochemistry before and three months after the treatment.

RESULTS

After FUS-MRI ablation of uterine fibroids in the endometrium, a statistically significant decrease in the stromal expression of natural uterine killers CD95^{+ bright} was observed to a level comparable to control values (from 70.22±9.77 to 48.81±5.47 c/s; in the control — 47.80±2.13 c/s; p<0.001). The ratio and expression level of steroid receptors, proliferation markers, p53-dependent apoptosis and its blockers, regulators and markers of angiogenesis, LIF and LIF-R signaling molecules in the stroma and endometrial glands did not change significantly after treatment (p>0.05 in treatment dynamics). It was found that focused ultrasound rays passing through the endometrium cause an increase in the level of expression of estradiol alpha recipes in the endometrial glands (118.07±14.01 points to 153.33±11.43 points; p=0.02) and a decrease in stromal p53 expression (30.80±21.61% to 14.66±3.74%; p=0.007). No dependence of the level of decrease in stromal expression of NK-cells of CD56^{+ bright} on the localization of the treated node was revealed. With the passage of ultrasonic waves through the endometrium, a significant increase in the expression of CD34⁺ in the stroma of the endometrium was noted to a level statistically comparable with control values (26.00±1.63 to 32.47±2.03 c/s; p=0.011, in the control 37.99±1.23 c/s).

CONCLUSIONS

The study did not reveal any significant negative effects of focused ultrasonic waves during FUS-MRI ablation of uterine fibroids on endometrial receptivity in women of reproductive age.

Keywords:

uterine fibroids

FUS-MRI ablation

receptivity

endometrium

Authors:

Melkozerova O.A.

Ural Research Institute for Maternity and Child Care, Ministry of Public Health of the Russian Federation

SPIN RSCI: 5782-7283
Scopus AuthorID: 56358107200
ORCID: 0000-0002-4090-0578

Shchedrina I.D.

Ural Research Institute for Maternity and Child Care, Ministry of Public Health of the Russian Federation

Bashmakova N.V.

Ural Research Institute for Maternal and Child Care

ORCID: 0000-0001-5746-316X

Chistyakova G.N.

Ural Research Institute for Maternity and Child Care, Ministry of Public Health of the Russian Federation

SPIN RSCI: 5436-8941
Scopus AuthorID: 56358317100
ORCID: 0000-0002-0852-6766

Grishkina A.A.

Ural Research Institute for Maternity and Child Care, Ministry of Public Health of the Russian Federation

Received:

02.03.2020

Accepted:

12.05.2020

List of references:

Martynova AE, Smolnikova VYu, Demura TA, Kogan EA. The effectiveness of the IVF program in women with uterine myoma taking into account endometrial receptivity markers — pinopodia, LIF, VEGF-A, claudin-5. Akusherstvo i ginekologiya. 2013;8(3):40-45. (In Russ.).
Horne AW, Critchley HO. The effect of uterine fibroids on embrio implantation. Seminars in Reproductive Medicine. 2007;25(6):483-489. https://doi.org/10.1055/s-2007-991046
Hasegawa E, Ito H, Hasegawa F, Hatano K, Kazuka M, Usuda S, Isaka K. Expression of leukemia inhibitory factor in the endometrium in abnormal uterine cavities during the implantation window. Fertility and Sterility. 2012;97(4):953-958. https://doi:10.1016/j.fertnstert.2012.01.113
Buyanova SN, Yudina NV, Gukasyan SA, Mgeliashvili MV. Modern aspects of the growth of uterine fibroids. Rossijskij vestnik akushera-ginekologa. 2012;12(4):42-48. (In Russ.).
Mioma matki, diagnostika, lechenie i reabilitaciya. Klinicheskie rekomendacii (protocol lecheniya). Pod red. Adamyan L.V., Andreevoy E.N. M. 2015. Accessed May 20, 2020. (In Russ.). https://stopmyoma.ru/wp-content/uploads/2017/09/2015.pdf
Fan H-J, Zhang Ch, Lei H-T, Cun J-P, Zhao W, Huang J-Q, Zhai Y. Ultrasound-guided high-intensity focused ultrasound in the treatment of uterine fibroids. Medicine. 2019;98(10):1-6. https://doi.org/10.1097/MD.0000000000014566
Dzhemlikhanova LKh, Niauri DA, Abdulkadyrova ZK. Uterine ibroids and the effectiveness of assisted reproductive technology programs. Zhurnal akusherstva i zhenskikh boleznei. 2016;65(6):79-87. (In Russ.). https://doi.org/10.17816/JOWD65679-87
Bernardi TS, Radosa MP, Weisheit A, Diebolder H, Schneider U, Schleussner E, Runnebaum IB. Laparoscopic myomectomy: a 6-year follow-up single-center cohort analysis of fertility and obstetric outcome measures. Archive Gynecology Obstetrics. 2014;290(1):87-91. https://doi.org/10.1007/s00404-014-3155-2
Olive DL. The surgical treatment of fibroids for infertility. Seminars in Reproductive Medicine. 2011;29(2):113-123. https://doi.org.10.1055/s-0031-1272473
Malartic C, Morel O, Akerman G, Tulpin L, Clément D, Barranger E. Laparoscopic myomectomy in 2007: state of the art. Journal de Gynécologie Obstétrique et Biologie de la Reproduction. 2013; 36(6):567-576. https://doi.org.10.1016/j.jgyn.2007.05.003
Adamyan LV, Filippov OS, Artymuk NV, Belokrinickaya NE, Shmakov RG, Baev OR, Tyutyunik VL, Pyregov AV, Filippovich GV, Strizhakov AN, Bashmakova NV, Malgina GB, Erofeev EN, Tskhai VB, Salov IA, Makarov OV, Tetruashvili NK, Klimenchenko NI, Drobinskaya AN. Kesarevo sechenie. Pokazaniya, metody obezbolivaniya, hirurgicheskaya tekhnika, antibiotikoprofilaktika, vedenie posleoperacionnogo perioda. Klinicheskie rekomendacii (protokol lecheniya). 2014. Accessed May 20, 2020. (In Russ.). https://prof.ncagp.ru/upload/files/conf/kesareva_cecheniya_2014.pdf
Kuznetsova IV, Evsyukova LV. Uterine fibroids and fertility. Ginekologiya. 2016; 18 (3): 23-29.
Fakhrutdinova EKh, Dukhin AO, Goldina AYa, Ermolova NP. Reproductive health of women after conservative myomectomy. Vestnik Rossijskogo universiteta druzhby narodov. Seriya: Medicina. 2002; 1:262-268. (In Russ.).
Kulinich SI, Burlakov OA. On the issue of restoration of reproductive function in young women after myomectomy. Sibirskij medicinskij zhurnal. 2010;97(6):84-86. (In Russ.).
Olive DL. The surgical treatment of fibroids for infertility. Seminars in Reproductive Medicine. 2011;29(2):113-123. https://doi.org/10.1055/s-0031-1272473
Fagherazzi S, Borgato S, Bertin M, Vitagliano A, Tommasi L, Conte L. Pregnancy outcome after laparoscopic myomectomy. Clinical and Experimental Obstetrics and Gynecology. 2014;41(4): 375-379. https://doi.org.10.12891/ceog19442014
Nazarenko GI, Krasnova TV, Tonkogorova IV, Bogdanova EG, Prilutskaya MA. Evaluation of the effectiveness and safety of high-intensity focused ultrasound ablation (HIFU-ablation) in the treatment of uterine fibroids depending on the location of the nodes. Ul’trazvukovaya i funkcional’naya diagnostika. 2016;1:29-39.
Karp HJA. Recurrent Pregnancy Loss: Causes, Controversies, and Treatment. Second Edition. H.J.A. Karp. C.R.S. Press: Taylor and Francis Group; 2017.
Karpanen T, Alitalo K. Molecular biology and pathology of lymphangiogenesis. Annual Review of Pathology. 2008;3:367-397. https://doi.org/10.1146/annurev.pathmechdis.3.121806.151515
Wilkens J, Male V, Ghazal P, Forster T, Gibson DA, Williams AR, Brito-Mutunayagam SL, Craigon M, Lourenco P, Cameron IT, Chwalisz K, Moffett A, Critchley HO. Uterine Natural Killer cells regulate endometrial bleeding in women and are suppressed by the progesterone receptor modulator asoprisnil. Journal Immunology. 2013;191(5):10-15. https://doi.org/10.4049/jimmunol.1300958
Robson A, Harris LK, Innes BA, Lash GE, Aljunaidy MM, Aplin JD, Baker PN, Robson SC, Bulmer JN. Uterine natural killer cells initiate spiral artery remodeling in human pregnancy. FASEB Journal. 2012;26(2):4876-4885. https://doi.org/10.1096/fj.12-210310
Cardozo ER, Clark AD, Banks NK, Henne MB, Stegmann BJ, Segars JH. The estimated annual cost of uterine leiomyomata in the United States. American Journal of Obstetrics and Gynecology. 2012;206:211-219. https://doi.org/10.1016/j.ajog.2011.12.002
Delage G, Moreau JF, Taupin Male V, Trundley A, Gardner L, Northfield J, Chang C, Apps R, Moffett A. Natural killer cells in human pregnancy. Methods in Molecular Biology. 2010;612:447-463.
Lai TH, Chang FW, Lin JJ, Ling Q.D. Gene expression of human endometrial L-selectin ligand in relation to the phases of the natural menstrual cycle. Science Repruduction. 2018;23:8(1):1443. https://doi.org/10.1038/s41598-018-19911-z
Manta L, Suciu N, Toader O, Purcărea R.M, Constantin A, Popa F. The etiopathogenesis of uterine fibromatosis. Journal of Medicine and Life. 2016;9(1):39-45.
Krylova YuM, Kvitnoy IM, Ailamazyan EK. Endometrial receptivity: molecular mechanisms for the regulation of implantation. Zhurnal akusherstva i zhenskih boleznej. 2013;2:63-74. (In Russ.)
Osnovnye pokazateli deyatel’nosti akushersko-ginekologicheskoj sluzhby v Rossijskoj Federacii v 2014, 2015 g. Pod red. Bajbarinoj E.N. M. 2015. (In Russ.). Accessed May 20, 2020. https://www.zdrav.ru/articles/4293655262-qqq-16-m12-11-12-2016-osnovnye-pokazateli-akushersko-ginekologicheskoy-slujby-v-rossii
Li ZL, Ueki K, Kumagai K. Regulation of bcl-2 transcription by estrogen receptor-alpha and C-Jun in human endometrium. Medicine Molecular Morphology. 2014;47(1):43-53. https://doi.org/10.1007/s00795-013-0043-y
Melkozerova OA, Shchedrina ID, Mikhelson AA, Zyryanov MN, Panacheva NM. The effectiveness of focused ultrasound ablation of uterine fibroids under the control of magnetic resonance imaging in patients of reproductive age with a symptomatic course of uterine fibroids. Rossijskij vestnik akushera-ginekologa. 2019;19(5):52-60. https://doi.org/10.17116/rosakush20191905152

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