To the content
Спецвыпуск . 2024

Pathogenesis of implantation failures in infertility associated with adenomyosis

Abstract

The aim of the study was to expand the understanding of the pathogenesis of implantation failure in infertility due to adenomyosis.

Design: an open, prospective, comparative clinical and morphologic study was conducted.

Material and methods. Fifty-seven women of reproductive age (mean age 36±4 years) with adenomyosis were included in the present study. During the study, the patients were divided into two groups: the main group (n=27) with adenomyosis and more than one unsuccessful attempt at embryo transfer in history and the comparison group (n=30), which consisted of fertile women of a similar age with adenomyosis. Endometrial biopsies were taken from all participants by Pipelle biopsy to perform a morphological and immunohisto-chemical examination of the endometrium using antibodies to MUC1 and pinopodia during the “implantation window” (days 19–22 of the menstrual cycle).

Results. During the study, in women suffering from infertility due to adenomyosis, significant morphofunctional changes were found in the eutopic endometrium: a significant (p<0.05) decrease in the implantation potential of the endometrium was noted against the background of desynchronization of the “implantation window”. In endometrial biopsies of participants with adenomyosis-associated infertility, a significant (p<0.01) decrease in the expression of pinopodia (30 vs 58%, p<0.01) on the apical surface of the endometrial glands was recorded, as well as a decrease in the expression of MUC1 (32 vs 52%, p<0.01).

Conclusion. Statistically significant low expression of pinopodia on the apical surface of endometrial glands (1.9 times, 30 vs 58%, p<0.01), as well as a decrease in MUC1 expression (1.6 times, 32 vs 52%, p<0.01) should be considered one of the key mechanisms of implantation failure in infertile women against the background of adenomyosis, which indicates asynchronous transformation and implantation failure of the endometrium.

Keywords:endometrial receptivity; adenomyosis; implantation failure

Funding. The study had no sponsor support.

Conflict of interest. The authors declare no conflict of interest.

Contribution. Selection of patients – Orazov M.R.; development of research design – Orazov M.R.; Mikhaleva L.M.; verification of critical content – Orazov M.R., Mikhaleva L.M.; development of the study design, conduct, analysis and interpretation of the results of morphological and immunohistochemical studies – Mikhaleva L.M.; text checking and editing – Radzinsky V.E., Barinova E.K.; review of publications on the topic of the article, collection of clinical material, processing, analysis and interpretation, statistical processing of data, writing the text of the manuscript – Barinova E.K.; approval of the manuscript for publication – Orazov M.R., Mikhaleva L.M., Radzinsky V.E., Khamoshina M.B., Barinova E.K.

For citation: Radzinskiy V.E., Orazov M.R., Mikhaleva L.M., Khamoshina M.B., Barinova E.K. Pathogenesis of implantation failures in infertility associated with adenomyosis. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie [Obstetrics and Gynecology: News, Opinions, Training]. 2024; 12. Supplement: 69–74. DOI: https://doi.org/10.33029/2303-9698-2024-12-suppl-69-74 (in Russian)

References

  1. Njagi P., Groot W., Arsenijevic , Dyer S., Mburu G., Kiarie J. Financial costs of assisted reproductive technology for patients in low- and middle-income countries: a systematic review. Hum Reprod Open. 2023; 2023 (2): hoad007.
  2. Infertility and endometriosis. Versions and contraversions. In: V.E. Radzinsky, M.R. Orazov (eds). Moscow: StatusPraesens, 2019: 208 p. (in Russian)
  3. Evans M.B., Decherney A.H. Fertility and endometriosis. Clin Obstet Gynecol. 2017; 60: 497–502.
  4. Khan K.N., Fujishita A., Mori T. Pathogenesis of human adenomyosis: current understanding and its association with infertility. J Clin Med. 2022; 11 (14): 4057. DOI: https://doi.org/10.3390/jcm11144057
  5. Bourdon M., Santulli P., Bordonne C., Millisher A.E., Maitrot-Mantelet L., Maignien C., et al. Presence of adenomyosis at MRI reduces live birth rates in ART cycles for endometriosis. Hum Reprod. 2022; 37 (7): 1470–9. DOI: https://doi.org/10.1093/humrep/deac083
  6. Gabidullina R.I., Kuptsova A.I., Koshel’nikova E.A., Nukh-bala F.R., Bagirli R.R., et al. Adenomyosis: clinical aspects, impact on fertility and pregnancy outcome. Ginekologiya [Gynecology]. 2020; 22 (4): 55–61. DOI: https://doi.org/10.26442/20795696.2020.4.200264 (in Russian)
  7. Zemlyanova V. Potential birth loss due to health-related problems in Russia. Sotsial’nye aspekty zdorov’ya naseleniya [Social Aspects of Public Health]. 2016; 48 (2): 4–15. (in Russian)
  8. Shmidt A.A., Zamyatnin S.A., Gonchar I.S., Korovin A.E., Gorodnyuk I.O., Kotsur A.V. Epidemiology of infertility in Russia and abroad. Klinicheskaya patofiziologiya [Clinical Pathophysiology]. 2019; 25 (1): 9–14. (in Russian)
  9. Bashmakova N.V., Melkozerova O.A., Khramtsova A.Yu., Grishkina A.A. Pathogenetic aspects of human embryo implantation disorders in ART programs. Lechenie i profilaktika [Disease Treatment and Prevention]. 2022; 12 (2): 92–8. (in Russian)
  10. Korsak V.S., Smirnova A.A., Shurygina O.V. ART Register of RAHR, 2017. Problemy reproduktsii [Problems of Reproduction]. 2019; 25 (6): 9–21. DOI: https://doi.org/10.17116/repro2019250619 (in Russian)
  11. Kozachenko F., Fayzullina N.M., Shchegolev A.I., Adamyan L.V. Endometrial receptivity in patients with benign uterine diseases and infertility before and after surgery. Akusherstvo i ginekologiya [Obstetrics and Gynecology]. 2020; (11): 147–58. DOI: https://doi.org/10.18565/aig.2020.11.147-158 (in Russian)
  12. Critchley H.O.D., Maybin J.A., Armstrong G.M., Williams A.R.W. Physiology of the endometrium and regulation of menstruation. Physiol Rev. 2020; 100 (3): 1149–79.
  13. Mikhaleva L.M., Orazov M.R., Volkova S.V., Khamoshina M.B., Khovanskaya T.N., Shustova V.B. Pathogenesis of implantation incompetence of endometrium in endometriosis-associated infertility. Doctor.Ru. 2021; 20 (6): 57–61. DOI: https://doi.org/10.31550/1727-2378-2021-20-6-57-61 (in Russian)
  14. Smirnova A.A. Estrogen supplementation in art (a review). Problemy reproduktsii [Problems of Reproduction]. 2015; 21 (4): 48–59. DOI: https://doi.org/10.17116/repro201521448-59 (in Russian)
  15. Radzinsky V.E., Mikhaleva L.M., Orazov M.R., Silant’eva E.S., Kamilova D.P., Midiber K.Yu., Orekhov R.E. Endometrium receptivity in patients with repeated implant failures. Doctor.Ru. 2022; 21 (1): 27–33. DOI: https://doi.org/10.31550/1727-2378-2022-21-1-27-33 (in Russian)
  16. Pirtea P., Cicinelli E., De Nola R., de Ziegler D., Ayoubi J.M. Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis. Fertil Steril. 2021; 115 (3): 546–60. DOI: https://doi.org/10.1016/j.fertnstert.2020.12.010 Epub 2021 Feb 11. PMID: 33581856.
  17. Munro G. Uterine polyps, adenomyosis, leiomyomas, and endometrial receptivity. Fertil Steril. 2019; 111 (4): 629–40. DOI: https://doi.org/10.1016/j.fertnstert.2019.02.008 PMID: 30929720
  18. Bulun S.E., Yildiz S., Adli M., Wei J.-J. Adenomyosis pathogenesis: insights from next-generation sequencing. Hum Reprod Update. 2021; 27 (6): 1086–97. DOI: https://doi.org/10.1093/humupd/dmab017
  19. Kazachkov E.L., Voropaeva E.E., Kazachkova E.A., Zatvornitskaya A.V., Dub A.A., Miroshnichenko L.E. Endometrial morphological characteristics in patients with hysteromyoma and chronic endometritis in infertility. Arkhiv patologii [Archive of Pathology]. 2019; 81 (6): 41–8. DOI: https://doi.org/10.17116/patol20198106141 PMID: 31851191. (in Russian)
  20. Wu F., Chen X., Liu Y., et al. Decreased MUC1 in endometrium is an independent receptivity marker in recurrent implantation failure during implantation window. Reprod Biol Endocrinol. 2018; 16 (1): 60. DOI: https://doi.org/10.1186/s12958-018-0379-1
  21. Hey A., Li T.C., Devine P.L., et al. MUC1 in secretory phase endometrium: expression in precisely dated biopsies and flushings from normal and recurrent miscarriage patients. Hum Reprod. 1995; 10 (10): 2655–62. DOI: https://doi.org/10.1093/oxfordjournals.humrep.a135762
  22. Jin X.Y., Zhao L.J. Luo D.H., et al. Pinopode score around the time of implantation is predictive of successful implantation following frozen embryo transfer in hormone replacement cycles. Hum Reprod. 2017; 32 (12): 2394–403. DOI: https://doi.org/10.1093/humrep/dex312
  23. Qiong Z., Jie H., Yonggang W., et al. Clinical validation of pinopode as a marker of endometrial receptivity: a randomized controlled trial. Fertil Steril. 2017; 108 (3): 513–7.e2. DOI: https://doi.org/10.1016/j.fertnstert.2017.07.006
  24. Margarit L., Taylor A., Roberts M.H., Hopkins L., Davies C., Brenton A.G., et al. MUC1 as a discriminator between endometrium from fertile and infertile patients with PCOS and endometriosis. J Clin Endocrinol Metab. 2010; 95 (12): 5320–9. DOI: https://doi.org/10.1210/jc.2010-0603 Epub 2010 Sep 8. PMID: 20826587.

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

CHIEF EDITORS
CHIEF EDITOR
Sukhikh Gennadii Tikhonovich
Academician of the Russian Academy of Medical Sciences, V.I. Kulakov Obstetrics, Gynecology and Perinatology National Medical Research Center of Ministry of Healthсаre of the Russian Federation, Moscow
CHIEF EDITOR
Kurtser Mark Arkadievich
Academician of the Russian Academy of Sciences, MD, Professor, Head of the Obstetrics and Gynecology Subdepartment of the Pediatric Department, N.I. Pirogov Russian National Scientific Research Medical University, Ministry of Health of the Russian Federation
CHIEF EDITOR
Radzinsky Viktor Evseevich
Corresponding Member of the Russian Academy of Sciences, MD, Professor, Head of the Subdepartment of Obstetrics and Gynecology with a Course of Perinatology of the Medical Department in the Russian People?s Friendship University
Journals of «GEOTAR-Media»