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Cited by 109Reproductive tract infections researchReproductive System and PregnancyGut microbiota and health

Does dysbiotic endometrium affect blastocyst implantation in IVF patients?

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Hashimoto, Tomoko, Kyono, Koichi·2019·Journal of Assisted Reproduction and Genetics
DOI 10.1007/s10815-019-01630-7PMC PMC6910901
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Abstract

Purpose: To analyze the pregnancy outcomes of IVF patients presenting eubiotic or dysbiotic endometrium at the time of embryo transfer and to analyze what bacterial profiles are suitable for embryo implantation. Methods: Ninety-nine IVF patients under 40 years old undergoing vitrified-warmed blastocyst transfer in HRT cycle had concurrent endometrial microbiome analysis. Samples from the endometrium were taken from the participants at the time of mock transfer; the bacterial profiles at genus level and percentage of lactobacilli in the endometrium of the patients were analyzed. Results: Thirty-one cases (31.3%) had dysbiotic endometrium. The background profiles, pregnancy rates per transfer (52.9% vs 54.8%), and miscarriage rates (11.1% vs 5.9%) were comparable between patients with eubiotic or dysbiotic endometrium. Major bacterial genera other than Lactobacillus detected in the dysbiotic endometrium were Atopobium , Gardnerella , and Streptococcus . Some patients achieved ongoing pregnancies with 0% Lactobacillus in the endometrium. The endometrial bacterial profiles of pregnant cases with dysbiotic endometrium were comparable with those of non-pregnant cases. Conclusion: Analyzing microbiota at the species-level resolution may be necessary for identifying the true pathogenic bacteria of the endometrium and avoiding over-intervention against non- Lactobacillus microbiota. Further studies are necessary for analyzing the mechanism of how the pathogenic bacteria affect embryo implantation.

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  • A shift in the population of Lactobacillus species has been implicated in diminished endometrial receptivity.

    “A shift in the population of Lactobacillus species, for instance, has been implicated in diminished endometrial receptivity [8, 9, 28, 29].”

    From Vaginal probiotics as therapeutic adjuncts for improving embryo transfer success rates: a systematic review and meta-analysis (2025) · cites this paper as [28]

    The Introduction reports that earlier studies associated lower endometrial Lactobacillus abundance with reduced implantation and pregnancy rates. However, the Discussion says this study found no effect of a non-Lactobacillus-dominated endometrium on implantation; it does not establish that a shift among Lactobacillus species diminishes endometrial receptivity. (LLM, conf=0.84)

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Research works printed but not linked: 29

  1. [1]Franasiak JM Werner MD Juneau CR Tao X Landis J Zhan Y Treff NR Scott RT Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit J Assist Reprod Genet 2016 33 1 129 136 10.1007/s10815-015-0614-z 26547201 PMC4717132 · DOI
  2. [2]Chen C Song X Wei W Zhong H Dai J Lan Z Li F Yu X Feng Q Wang Z Xie H Chen X Zeng C Wen B Zeng L du H Tang H Xu C Xia Y Xia H Yang H Wang J Wang J Madsen L Brix S Kristiansen K Xu X Li J Wu R Jia H The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases Nat Commun 2017 8 1 875 10.1038/s41467-017-00901-0 29042534 PMC5645390 · DOI
  3. [3]Moreno I Codoñer FM Vilella F Valbuena D Martinez-Blanch JF Jimenez-Almazán J Alonso R Alamá P Remohí J Pellicer A Ramon D Simon C Evidence that the endometrial microbiota has an effect on implantation success or failure Am J Obstet Gynecol 2016 215 6 684 703 10.1016/j.ajog.2016.09.075 27717732 · DOI
  4. [5]Ruiz-Alonso M Blesa D Díaz-Gimeno P Gomez E Fernandez-Sanchez M Carranza F The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure Fertil Steril 2013 100 818 824 10.1016/j.fertnstert.2013.05.004 23756099 · DOI
  5. [6]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 10.1002/rmb2.12105 30013432 PMC6046523 · DOI
  6. [7]Walters W, Hyde ER, Berg-Lyons D, Ackermann G, Humphrey G, Parada A et al., Improved bacterial 16S rRNA Gene (V4 and V4-5) and fungal internal transcribed spacer marker gene primers for microbial community surveys. mSystems. 2015; Dec 22; 1(1). PMC5069754 27822518
  7. [8]Rintala A Pietilä S Munukka E Eerola E Pursiheimo JP Laiho A Pekkala S Huovinen P Gut microbiota analysis results are highly dependent on the 16S rRNA gene target region, whereas the impact of DNA extraction is minor J Biomol Tech 2017 28 1 19 30 10.7171/jbt.17-2801-003 28260999 PMC5330390 · DOI · Paper page
  8. [9]Aronesty E Comparison of sequencing utility programs Open Bioinform J 2013 7 1 8 10.2174/1875036201307010001 · DOI
  9. [10]Edgar RC Haas BJ Clemente JC Quince C Knight R UCHIME improves sensitivity and speed of chimera detection Bioinformatics 2011 272 2194 2200 10.1093/bioinformatics/btr381 PMC3150044 21700674 · DOI · Paper page
  10. [11]Caporaso JG Kuczynski J Stombaugh J Bittinger K Bushman FD Costello EK Fierer N Peña AG Goodrich JK Gordon JI Huttley GA Kelley ST Knights D Koenig JE Ley RE Lozupone CA McDonald D Muegge BD Pirrung M Reeder J Sevinsky JR Turnbaugh PJ Walters WA Widmann J Yatsunenko T Zaneveld J Knight R QIIME allows analysis of high-throughput community sequencing data Nat Methods 2010 7 5 335 336 10.1038/nmeth.f.303 20383131 PMC3156573 · DOI · Paper page
  11. [12]Wang Q Garrity GM Tiedje JM Cole JR Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy Appl Environ Microbiol 2007 73 16 5261 5267 10.1128/AEM.00062-07 17586664 PMC1950982 · DOI
  12. [13]McDonald D Price MN Goodrich J Nawrocki EP DeSantis TZ Probst A Andersen GL Knight R Hugenholtz P An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea ISME J 2012 6 3 610 618 10.1038/ismej.2011.139 22134646 PMC3280142 · DOI
  13. [14]Salter SJ Cox MJ Turek EM Calus ST Cookson WO Moffatt MF Reagent and laboratory contamination can critically impact sequence-based microbiome analyses BMC Biol 2014 12 87 10.1186/s12915-014-0087-z 25387460 PMC4228153 · DOI · Paper page
  14. [16]Urushiyama D Suda W Ohnishi E Araki R Kiyoshima C Kurakazu M Sanui A Yotsumoto F Murata M Nabeshima K Yasunaga S Saito S Nomiyama M Hattori M Miyamoto S Hata K Microbiome profile of the amniotic fluid as a predictive biomarker of perinatal outcome Sci Rep 2017 7 1 12171 10.1038/s41598-017-11699-8 28939908 PMC5610236 · DOI
  15. [17]Gardner DK Schoolcraft WB Jansen R Mortimer D In vitro culture of human blastocyst Towards reproductive certainty: infertility and genetics beyond 1999 1999 Carnforth Parthenon Press 378 388
  16. [18]Wan CY Song C Diao LH Li GG Bao ZJ Hu XD Zhang HZ Zeng Y Laser-assisted hatching improves clinical outcomes of vitrified-warmed blastocysts developed from low-grade cleavage-stage embryos: a prospective randomized study Reprod BioMed Online 2014 28 5 582 589 10.1016/j.rbmo.2014.01.006 24631166 · DOI
  17. [19]Moreno I Cicinelli E Garcia-Grau I Gonzalez-Monfort M Bau D Vilella F The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology Am J Obstet Gynecol 2018 218 6 602.e1 602.e16 10.1016/j.ajog.2018.02.012 29477653 · DOI
  18. [20]Baker JM Chase DM Herbst-Kralovetz MM Uterine microbiota: residents, tourists, or invaders? Front Immunol 2018 9 208 10.3389/fimmu.2018.00208 29552006 PMC5840171 · DOI
  19. [21]Libby EK Pascal KE Mordechai E Adelson ME Trama JP Atopobium vaginae triggers an innate immune response in an in vitro model of bacterial vaginosis Microbes Infect 2008 10 4 439 446 10.1016/j.micinf.2008.01.004 18403235 · DOI
  20. [22]Freitas AC Hill JE Quantification, isolation and characterization of Bifidobacterium from the vaginal microbiomes of reproductive aged women Anaerobe 2017 47 145 156 10.1016/j.anaerobe.2017.05.012 28552417 · DOI
  21. [23]Kroon SJ Ravel J Huston WM Cervicovaginal microbiota, women’s health, and reproductive outcomes Fertil Steril 2018 110 3 327 336 10.1016/j.fertnstert.2018.06.036 30098679 · DOI
  22. [24]Tachedjian G O'Hanlon DE Ravel J The implausible “in vivo” role of hydrogen peroxide as an antimicrobial factor produced by vaginal microbiota Microbiome 2018 6 1 29 10.1186/s40168-018-0418-3 29409534 PMC5801833 · DOI
  23. [25]Witkin SS Mendes-Soares H Linhares IM Jayaram A Ledger WJ Forney LJ Influence of vaginal bacteria and D- and L-lactic acid isomers on vaginal extracellular matrix metalloproteinase inducer: implications for protection against upper genital tract infections MBio 2013 4 4 e00460 e00413 10.1128/mBio.00460-13 23919998 PMC3735189 · DOI
  24. [26]Nakagawa K, Kwak-Kim J, Kuroda K, Sugiyama R, Yamaguchi K. Immunosuppressive treatment using tacrolimus promotes pregnancy outcome in infertile women with repeated implantation failures. Am J Reprod Immunol. 2017;78(3). 10.1111/aji.12682. 28466977 · DOI
  25. [27]Campisciano G Zanotta N Licastro D De Seta F Comar M In vivo microbiome and associated immune markers: new insights into the pathogenesis of vaginal dysbiosis Sci Rep 2018 8 1 2307 10.1038/s41598-018-20649-x 29396486 PMC5797242 · DOI
  26. [28]van der Gaast MH Beier-Hellwig K Fauser BC Beier HM Macklon NS Endometrial secretion aspiration prior to embryo transfer does not reduce implantation rates Reprod BioMed Online 2003 7 1 105 109 10.1016/S1472-6483(10)61737-3 12930588 · DOI
  27. [29]Vilella F Ramirez L Berlanga O Martínez S Alamá P Meseguer M Pellicer A Simón C PGE2 and PGF2α concentrations in human endometrial fluid as biomarkers for embryonic implantation J Clin Endocrinol Metab 2013 98 10 4123 4132 10.1210/jc.2013-2205 23979956 · DOI
  28. [30]Liu Y Wong KK Ko EY Chen X Huang J Tsui SK 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 1752 10.1373/clinchem.2018.289306 30237148 · DOI
  29. [31]Muhleisen AL Herbst-Kralovetz MM Menopause and the vaginal microbiome Maturitas 2016 91 42 50 10.1016/j.maturitas.2016.05.015 27451320 · DOI

Cited by

Sorted by citations

Authors
Hashimoto, T., & Kyono, K.
Corresponding author
Hashimoto, Tomoko
ORCID
Venue
Journal of Assisted Reproduction and Genetics
Publisher
Springer Science and Business Media LLC
Published
2019-11-18
Volume
36
Issue
12
Pages
2471-2479
ISSN
  • 0740-7769 (ISSN-L)
  • 1058-0468
  • 1573-7330
DOI
10.1007/s10815-019-01630-7
PMC
PMC6910901
OpenAlex
W2983491158
Cited by
109
References
2
Citations by year
2026: 19 · 2025: 8 · 2024: 13 · 2023: 19 · 2022: 21 · 2021: 15 · 2020: 13 · 2018: 1
FWCI
9.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Assisted Reproduction and Genetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
endometrial microbiota, dysbiosis, embryo implantation, in vitro fertilization, pregnancy outcomes, Lactobacillus, Atopobium, Gardnerella, Streptococcus, embryo transfer, miscarriage
MeSH terms
Adult, Bacteria, Blastocyst, Embryo Transfer, Endometrium, Female, Fertilization in Vitro, Humans, Embryo Implantation, Pregnancy, Pregnancy Outcome, Pregnancy Rate, Vitrification, Microbiota, Dysbiosis

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