Endometrial microbiome in women with and without a history of repeated failures of assisted reproductive technology: what are norm and pathology?


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Aim. To investigate the endometrial microbiome in healthy fertile women and patients with multiple unsuccessful assisted reproduction technology (ART) cycles. Materials and methods. The study included 20 women with infertility and multiple unsuccessful ART cycles (group 1) and 15 healthy fertile women with a history of at least one full-term childbirth (group 2). The endometrial microbiome was analyzed using next-generation sequencing of the 16S rRNA gene. Results. The endometrial microbiota of healthy fertile patients was dominated by Lactobacillus (29.4%), Comamonas (16.8%), and Mesorhizobium (6.0%). In infertile patients with multiple IVF failures, the most abundant were Lactobacillus (33.3%), Ralstonia (7.9%), and Pediococcus (4.8%). At the same time, the proportion of lactobacilli in patients of group 1 did not differ significantly from patients in group 2 (33.3% and 29.4%, respectively). Women with infertility and repeated unsuccessful IVF attempts had a significantly higher relative abundance of bacteria of the genera Brevundimonas and Ralstonia. At the same time, the fertile women in group 2 had a statistically significantly higher representation of Acidovorax, Brevibacillus, Caulobacter, Comamonas, Delftia, Distigma Pseudomonas, Schlegelella, Thermus. Conclusion. The study findings confirm the notion that the uterus may indeed be a non-sterile compartment and the existence of the uterine microbiome as a whole. Lactobacilli are dominant members of the uterine microbiome but not absolutely dominant, i.e.,> 90%. At the same time, the proportion of lactobacilli in fertile patients and patients with multiple ARTfailures did not differ significantly.

Full Text

Restricted Access

About the authors

Viktoriya V. Barinova

Rostov State Medical University, Ministry of Health of the Russian Federation; "Clinic of Professor Bushtyreva" LLC

Email: victoria-barinova@yandex.ru
PhD, Teaching Assistant at the Department of Obstetrics and Gynecology No. 1

Natalya B. Kuznetsova

Rostov State Medical University, Ministry of Health of the Russian Federation; "Clinic of Professor Bushtyreva" LLC

Email: lauranb@inbox.ru
Dr. Med. Sci., Professor at the Center for Simulation Training

Irina O. Bushtyreva

"Clinic of Professor Bushtyreva" LLC

Email: kio4@mail.ru
Dr. Med. Sci., Professor, Director

Oksana S. Oksenyuk

Rostov State Medical University, Ministry of Health of the Russian Federation

Email: oksenuk_o@bk.ru
PhD, Head of the Central Research Laboratory

Vasilisa V. Dudurich

Medical Genetics Center "Serbalab"

Email: vdudurich@cerbalab.ru
Biologist-Geneticist, Director for Development

Alexander E. Shatalov

Rostov State Medical University, Ministry of Health of the Russian Federation

Email: shatal321@mail.ru
6th year student at the Medical and Preventive Faculty

References

  1. Butler B. Value of endometrial cultures in sterility investigation. Fertil. Steril. 1958; 9(3): 269-73. https://dx.doi.org/10.1016/s0015-0282(16)33070-9.
  2. Bollinger C.C. Bacterial flora of the nonpregnant uterus: a new culture technic. Obstet. Gynecol. 1964; 23: 251-5.
  3. Drbohlav P., Hdlkovd E., Masata J., Rezdcovd J., Cerny V., Rossovd D. The effect of endometrial infection on embryo implantation in the IVF and ET program. Ceska Gynekol. 1998; 63(3): 181-5. https://dx.doi.org/10.1093/humrep/deu292.
  4. Cicinelli E., Matteo M., Tinelli R., Lepera A., Alfonso R., Indraccolo U. et al. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum. Reprod. 2015; 30(2): 323-30. https://dx.doi.org/10.1093/humrep/deu292.
  5. Cicinelli E., Matteo M., Tinelli R., Pinto V., Marinaccio M., Indraccolo U. et al. Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment. Reprod. Sci. 2014; 21(5): 640-7. https://dx.doi.org/10.1177/1933719113508817.
  6. Гусейнова Г.Э., Ходжаева З.С., Муравьева В.В. Роль микробиоты влагалища при досрочном преждевременном разрыве плодных оболочек. Акушерство и гинекология. 2020; 1: 20-5. https://dx.doi.org/10.18565/aig.2020.1.20-25.
  7. Ходжаева З.С., Горина К.А., Тимошина И.В., Припутневич Т.В. Программирование здоровья новорожденного - роль материнского микробиома. Акушерство и гинекология: новости, мнения, обучение. 2019; 7(4): 61-5. https://dx.doi.org/10.24411/2303-9698-2019-14004.
  8. Кузнецова Н.Б., Буштырева И.О., Дыбова В.С., Баринова В.В., Полев Д.Е., Асеев М.В., Дудурич В.В. Микробиом влагалища у беременных с преждевременным разрывом плодных оболочек в сроке от 22 до 28 недель беременности. Акушерство и гинекология. 2021; 1: 94-102. https://dx.doi.org/10.18565/aig.202U.94-102.
  9. Mitchell C.M., Haick A., Nkwopara E., Garcia R., Rendi M., Agnew K. et al. Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women. Am. J. Obstet. Gynecol. 2015; 212(5): 611.e1-9. https://dx.doi.org/10.1016/j.ajog.2014.11.043.
  10. Zervomanolakis I., Ott H.W., Hadziomerovic D., Mattie V., Seeber B.E., Virgolini I. et al. Physiology of upward transport in the human female genital tract. Ann. N. Y. Acad. Sci. 2007; 1101: 1-20. https://dx.doi.org/10.1196/annals.1389.032.
  11. Marchesi J.R., Ravel J. The vocabulary of microbiome research: a proposal. Microbiome. 2015; 3: 31. https://dx.doi.org/10.1186/s40168-015-0094-5.
  12. Fang R.L., Chen L.X., Shu W.S., Yao S.Z., Wang S.W., Chen Y.Q. Barcoded sequencing reveals diverse intrauterine microbiomes in patients suffering with endometrial polyps. Am. J. Transl. Res. 2016; 8(3): 1581-92.
  13. Franasiak J.M., Werner M.D., Juneau C.R., Tao X., Landis J., Zhan Y. et al. Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit. J. Assist. Reprod. Genet. 2016; 33(1): 129-36. https://dx.doi.org/10.1007/s10815-015-0614-z.
  14. Khan K.N., Fujishita A., Masumoto H., Muto H., Kitajima M., Masuzaki H., Kitawaki J. Molecular detection of intrauterine microbial colonization in women with endometriosis. Eur. J. Obstet. Gynecol. Reprod. Biol. 2016; 199: 69-75. https://dx.doi.org/10.1016/j.ejogrb.2016.01.040.
  15. Moreno I., Codoner F.M., Vilella F., Valbuena D., Martinez-Blanch J.F., Jimenez-Almazan J. et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am. J. Obstet. Gynecol. 2016; 215(6): 684-703. https://dx.doi.org/10.1016/j.ajog.2016.09.075.
  16. Verstraelen H., Vilchez-Vargas R., Desimpel F., Jauregui R., Vankeirsbilck N., Weyers S. et al. Characterization of the human uterine microbiome in non pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene. Peer J. 2016; 4: e1602. https://dx.doi.org/10.7717/peerj.
  17. Walther-Antonio M., Chen J., Multinu F., Hokenstad A., Distad T.J., Cheek E.H. et al. Potential contribution of the uterine microbiome in the development of endometrial cancer. Genome Med. 2016; 8(1): 122. https://dx.doi.org/10.1186/s13073-016-0368-y.
  18. Chen C., Song X., Wei W., Zhong H., Dai J., Lan Z. et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat. Commun. 2017; 8(1): 875. https://dx.doi.org/10.1038/s41467-017-00901-0.
  19. Miles S.M., Hardy B.L., Merrell D.S. Investigation of the microbiota of the reproductive tract in women undergoing a total hysterectomy and bilateral salpingo-oopherectomy. Fertil. Steril. 2017; 107(3): 813-20. https://dx.doi.org/10.1016/j.fertnstert.2016.11.028.
  20. Tao X., Franasiak J.M., Zhan Y., Scott R.T. III, Rajchel J., Bedard J. et al. Characterizing the endometrial microbiome by analyzing the ultra-low bacteria from embryo transfer catheter tips in IVF cycles: Next generation sequencing (NGS) analysis of the 16S ribosomal gene. Hum. Microbiome J. 2017; 3(1): 15-21. https://dx.doi.org/10.1016/j.humic.2017.01.004.
  21. Kyono K., Hashimoto T., Nagai Y., Sakuraba Y. Analysis of endometrial microbiota by 16S ribosomal RNA gene sequencing among infertile patients: a single-center pilot study. Reprod. Med. Biol. 2018; 17(3): 297-306. https://dx.doi.org/10.1002/rmb2.12105.
  22. Liu Y., Wong K.K., Ko E.Y., Chen X., Huang J., Tsui S.K. et al. Systematic comparison of bacterial colonization of endometrial tissue and fluid samples in recurrent miscarriage patients: implications for future endometrial microbiome studies. Clin. Chem. 2018; 64(12): 1743-52. https://dx.doi.org/10.1373/clinchem.2018.289306.
  23. Pelzer E.S., Willner D., Buttini M., Huygens F. A role for the endometrial microbiome in dysfunctional menstrual bleeding. Antonie Van Leeuwenhoek. 2018; 111(6): 933-43. https://dx.doi.org/10.1007/s10482-017-0992-6.
  24. Wee B.A., Thomas M., Sweeney E.L., Frentiu F.D., Samios M., Ravel J. et al. A retrospective pilot study to determine whether the reproductive tract microbiota differs between women with a history of infertility and fertile women. Aust. N. Z. J. Obstet. Gynaecol. 2018; 58(3): 341-8. https://dx.doi.org/10.1111/ajo.12754.
  25. Кебурия Л.К., Смольникова В.Ю., Припутневич Т.В., Муравьева В.В. Микробиота полости матки и ее влияние на репродуктивные исходы. Акушерство и г инекология. 2019; 2: 22-7. https://dx.doi.org/10.18565/aig.2019.2.22-27.
  26. Callahan B.J., McMurdie P.J., Rosen M.J., Han A.W., Johnson A.J., Holmes S.P. DADA2: High-resolution sample inference from Illumina amplicon data. Nat. Methods. 2016; 13(7): 581-3. https://dx.doi.org/10.1038/nmeth.3869.
  27. Wang Q., Garriy G.M., Tiedje J.M., Cole J.R. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl. Environ. Microbiol. 2007; 73(16): 5261-7. https://dx.doi.org/10.1128/ AEM.00062-07.
  28. Quast C., Pruesse E., Yilmaz P., Gerken J., Schweer T., Yarza P. et al. The SILVA ribosomal RNA.gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013; 41 (Database issue): D590-6. https://dx.doi.org/10.1093/nar/gks1219.
  29. Salter S.J., Cox M.J., Turek E.M., Calus S.T., Cookson W.O., Moffatt M.F. et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol. 2014; 12: 87. https://dx.doi.org/10.1186/s12915-014-0087-z.
  30. Winters A.D., Romero R., Gervasi M.T., Gomez-Lopez N., Tran M.R., Garcia-Flores V. Does the endometrial cavity have a molecular microbial signature? Sci. Rep. 2019; 9(1): 9905. https://doi.org/10.1038/s41598-019-46173-0.
  31. Khalki H., Deham H., Taghouti A., Yahyaoui G., Mahmoud M. Appendicite a comamonas testosteroni [Comamonas testosteroni appendicitis]. Med. Mal. Infect. 2016; 46(3): 168-70. https://dx.doi.org/10.1016/j.medmal.2015.12.009.
  32. Krishnan A., Raby E., Puttagunta H., Leung M., Thomas M. Mesorhizobium peritonitis: The first reported case. Nephrology. 2016; 22(1): 96. https://dx.doi.org/10.1111/nep.12716.
  33. Ryan M.P., Adley C.C. Ralstonia spp.: emerging global opportunistic pathogens. Eur. J. Clin. Microbiol. Infect. Dis. 2014; 33(3): 291-304. https://dx.doi.org/10.1007/s10096-013-1975-9.
  34. Porto M.C., Kuniyoshi T.M., Azevedo P.O., Vitolo M., Oliveira R.P. Pediococcus spp.: An important genus of lactic acid bacteria and pediocin producers. Biotechnol. Adv. 2017; 35(3): 361-74. https://dx.doi.org/10.1016/j.biotechadv.2017.03.004.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2021 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies