Amh 69 00004 v2
Amh 69 00004 v2
Amh 69 00004 v2
Microbiology Department, School of Medicine, Faculty of Health Science, Aristotle University of Thessaloniki,
54636 Thessaloniki, Greece; mexidari@auth.gr (M.E.); dihi@auth.gr (D.C.); ggioula@auth.gr (G.G.)
* Correspondence: pfoteinid@auth.gr
Abstract: The endometrial cavity was considered sterile until the second half of the 20th century.
Through modern technological advances and the sequencing of the bacterial 16S rRNA gene, it was
proven that the area possesses its own unique microbiome, which can be categorised into two types,
Lactobacillus-dominant (LD, with a Lactobacillus spp. abundance percentage greater than 90%) and non-
Lactobacillus-dominant (non-LD, with a Lactobacillus spp. abundance percentage smaller than 90%),
with other species like Bifidobacterium, Gardnerella, Prevotella, and Streptococcus also being prominent.
The aim of this study was to investigate the possible correlation of the endometrial microbiome
to female infertility, through the identification and appraisal of studies published in the databases
PubMed, Web of Science, and Scopus. Moreover, 12 studies met the research criteria, including the
analysis of endometrial fluid or tissue samples from infertile women through PCR, culturomics-based,
or NGS methods. According to most of these studies, a eubiotic LD-type microbiome seems to be
best for maximising endometrial receptivity and pregnancy chances, whereas a dysbiotic non-LD-
type microbiome, with increased α-diversity and a higher number of pathogens, has a harmful
effect. There were few studies that presented contradictory results without, however, a satisfactory
explanation. Thus, more time and a greater number of studies are required to clarify contradictions
and achieve more certain results.
[MeSH terms] OR infertil* [All fields] OR fertil* [All fields] OR steril* [All fields]). The
number of retrieved results was 177.
For the Scopus database, the search strategy was formed as follows: (endometrium OR
endometrial) (Title, Abstract, Keywords) AND (microbiot* OR microbiom*) (Title, Abstract,
Keywords) AND (infertil* OR fertil* OR steril*) (Title, Abstract, Keywords). The number of
retrieved results was 261.
Finally, for the Web of Science database, the search strategy was formed as follows:
(endometrium OR endometrial) (Topic) AND (microbiot* OR microbiom*) (Topic) AND
(infertil* OR fertil* OR steril*) (Topic). The number of retrieved results was 230.
3. Results
3.1. Search Results
The search strategy described previously retrieved a total of 668 results. After combin-
ing the results from all databases and deleting duplicates, there were 338 unique results
3. Results
3.1. Search Results
Acta Microbiol. Hell. 2024, 69 18
The search strategy described previously retrieved a total of 668 results. After com-
bining the results from all databases and deleting duplicates, there were 338 unique re-
sults
left,left,
whichwhich
werewere
thenthen screened
screened for for their
their relativity
relativity to the
to the search
search criteria.
criteria. Then,
Then, thethe
irrel-
irrelevant results were also removed, and the full texts of the 258
evant results were also removed, and the full texts of the 258 remaining articlesremaining articles were
were
retrieved,
retrieved, which
whichwere
werethen
then further assessed for
further assessed foreligibility
eligibilityaccording
according to the
to the criteria
criteria de-
described
scribed in Section 2.2. Finally, 12 studies’ articles were chosen to be included
in Section 2.2. Finally, 12 studies’ articles were chosen to be included in this review, which in this re-
view, which contained all the necessary data about the endometrial microbiome
contained all the necessary data about the endometrial microbiome analysis on infertile analysis
onwomen
infertileandwomen and its potential
its potential correlation
correlation to pregnancy
to pregnancy achievement
achievement or theoroutcome
the outcome
of IVF
of treatment,
IVF treatment, and all of the relevant data were extracted for further studying.
and all of the relevant data were extracted for further studying. The full selection The full
selection and retrieval process is shown
and retrieval process is shown in Figure 1. in Figure 1.
Figure 1. PRISMA
Figure flow
1. PRISMA diagram.
flow diagram.
3.2.3.2. Publication
Publication Characteristics
Characteristics
From
From 20202020 until
until October
October 2023,
2023, 12 12 studies
studies havehave been
been published
published about
about endometrial
endometrial mi-mi-
crobiomeanalysis
crobiome analysisonon infertile women
womenand anditsits
correlation
correlationto pregnancy
to pregnancyachievement and/or
achievement
the outcome
and/or of IVF
the outcome of treatment and and
IVF treatment werewere
therefore included
therefore includedin this review.
in this FiveFive
review. of them
of
(41.67%) were published in 2023, four (33.33%) in 2022, two (16.67%)
them (41.67%) were published in 2023, four (33.33%) in 2022, two (16.67%) in 2021, and in 2021, and only one
(98.33%) in 2020. With regard to the country where each study was
only one (98.33%) in 2020. With regard to the country where each study was conducted, conducted, three studies
eachstudies
three (25%) were conducted
each (25%) wereinconducted
Japan andin Italy,
Japan twoand
(16.67%)
Italy, intwo Spain, and one
(16.67%) each (8.33%)
in Spain, and
oneineach
Turkey, Russia,
(8.33%) China and
in Turkey, the U.S.A.
Russia, The the
China and main goal The
U.S.A. of these
mainstudies
goal ofwas thestudies
these analysis
wasand thestudy of the
analysis andendometrial
study of the microbiome,
endometrialeither exclusively
microbiome, or along
either with the
exclusively vaginal
or along
and/or cervical microbiome, in women with infertility, and mainly in cases with repeated
implantation failure (RIF). In some studies, a comparison to the microbiome of healthy
(fertile) women was performed, with the ultimate goal always being the investigation of
its microbial composition and its potential correlation to pregnancy achievement and the
Acta Microbiol. Hell. 2024, 69 19
outcome of IVF treatment or embryo implantation in cases where these were performed.
The basic publication characteristics of each study are shown in Table 1.
Reference
Author(s) Year Country Aim
Number
Shunsaku Fujii, Takaaki Evaluation of the correlation of age and
2023 Japan [25]
Oguchi microbiome to endometrial receptivity.
Identification of specific microbial
Takuhiko Ichiyama communities in the vaginal and endometrial
2021 Japan [23]
et al. microbiomes as potential biomarkers for
implantation failure.
Correlation of the disruption of the vaginal
Ozlem Sezer et al. 2022 Turkey and endometrial microbiome to unexplained [26]
infertility.
Comparison of the endometrial microbiome
Francisca Maria Lozano
2023 Spain between patients with and without RIF before [27]
et al.
undergoing IVF.
Comparison of the qualitative and
quantitative species abundance of bacteria,
Mark Jain et al. 2023 Russia [28]
viruses and fungi in vaginal, cervical and
endometrial fluid samples of infertile women.
Investigation of the effect of the balance
between Lactobacillus and other pathogens in
Maho Miyagi et al. 2022 Japan [29]
the vaginal and endometrial microbiome on
IVF outcomes of infertile patients.
Comparison of the vaginal and endometrial
microbiomes of women undergoing IVF, and
Marco Reschini et al. 2022 Italy [30]
correlation to the possibility of a successful
pregnancy.
Investigation of the possible effect of the
Immaculada Moreno
2022 U.S.A. composition of the endometrial microbiome [17]
et al.
on the reproductive result.
Use of culturomics-based methods for
Federica Cariati et al. 2023 Italy endometrial microbiome analysis, and [31]
correlation to pregnancy rates.
Description and comparison of the vaginal
and endometrial microbiomes between
Maria del Carmen
2021 Spain women with and without a successful [32]
Diaz-Martinez et al.
pregnancy after IVF, as well as between
women with and without RIF.
Investigation of structural differences
between the vaginal and endometrial
Lucia Riganelli et al. 2020 Italy [33]
microbiome to define potential biomarkers
related to implantation failure.
Recording of the endometrial microbiome
Yixuan Zou et al. 2023 China profiles of women with RIF, and investigation [34]
into the use of antibiotics on these patients.
cavity, underlying infections, etc. The age range of the patients was between 18 and
50 years, and no studies presented any further demographic data. In every study, the
12 consecutive months of natural efforts, or as infertile with RIF, meaning infertile with a
patients were characterised either as infertile, meaning unable to achieve clinical pregnancy
history of at least three failed IVF attempts and good-quality embryo transfers. Moreover,
after 12 consecutive months of natural efforts, or as infertile with RIF, meaning infertile with
the studies can also be split into those where IVF or embryo transfer was performed as
a history of at least three failed IVF attempts and good-quality embryo transfers. Moreover,
part of them and those that only included microbiome analysis. In total, five studies were
the studies can also be split into those where IVF or embryo transfer was performed as
conducted on infertile patients with a simultaneous IVF attempt, including 549 patients
part of them and those that only included microbiome analysis. In total, five studies were
and 26 controls,
conducted whilepatients
on infertile four studies
with awere conducted
simultaneous onattempt,
IVF patientsincluding
with RIF549with a simulta-
patients and
neous
26 IVF attempt,
controls, while fourincluding
studies387 patients
were and 18
conducted oncontrols.
patientsOne
withstudy was aconducted
RIF with simultaneouswith
a simultaneous
IVF IVF attempt
attempt, including on patients
387 patients andwith and without
18 controls. OneRIF. With
study wasregard to the studies
conducted with a
not including an IVF attempt, one of them was conducted on a total of 100 infertile
simultaneous IVF attempt on patients with and without RIF. With regard to the studies patients
not
and one on
including anaIVF
total of 145 patients
attempt, withwas
one of them RIF.conducted
The basic on
population
a total ofcharacteristics of each
100 infertile patients
study
and areonshown
one a totalinofTable 2.
145 patients with RIF. The basic population characteristics of each
study are shown in Table 2.
Table 2. Basic population data of the studies.
Table
Reference Number Patients 2. BasicControls
Total population dataAge
of the studies.
(Years) Patients’ Characterisation IVF Attempt
[25] 185 No 25–47 With RIF Yes
Reference Number Patients Total Controls Age (Years) Patients’ Characterisation IVF Attempt
[23] 145 21 N/A With RIF No
[25] 185 No 25–47 With RIF Yes
[26] 26 26 20–45 Infertile Yes
[23] 145 21 N/A With RIF No
[27]
[26] 2726 1826 <45
20–45 With RIF
Infertile Yes
Yes
[28]
[27] 10027 No18 N/A<45 Infertile
With RIF YesNo
[28]
[29] 100
35 NoNo N/A
N/A Infertile
Infertile NoYes
[29]
[30] 5335 NoNo N/A
N/A Infertile
Infertile Yes
Yes
[30] 53 No N/A Infertile Yes
[17]
[17] 342
342 NoNo <50
<50 Infertile
Infertile Yes
Yes
[31]
[31] 9393 NoNo 29–47
29–47 Infertile
Infertile Yes
Yes
[32]
[32] 4848 NoNo 18–50
18–50 With
With and withoutRIF
and without RIF Yes
Yes
[33]
[33] 3434 NoNo 22–43
22–43 With RIF
With RIF Yes
Yes
[34] 141 No <40 With RIF Yes
[34] 141 No <40 With RIF Yes
3.4.
3.4. Sample
Sample Types
TypesandandAnalysis
AnalysisMethods
Methods
The
The main
main type
type ofof sample
sample used
used for
for microbiome
microbiomeanalysis
analysiswaswas endometrial
endometrial fluid,
fluid, which
which
was used in eight studies (66.67%). In three studies (25%), an endometrial
was used in eight studies (66.67%). In three studies (25%), an endometrial tissue sample tissue sample
was
wastaken
takenafter
aftera abiopsy,
biopsy,and in in
and one study
one (8.33%),
study samples
(8.33%), from
samples bothboth
from endometrial fluidfluid
endometrial and
tissue were used. There were some studies that also used vaginal and/or cervical
and tissue were used. There were some studies that also used vaginal and/or cervical sam- samples
for
plesanalysis and and
for analysis comparison,
comparison,butbut
for for
thethe
purposes
purposes ofof
this
thisreview,
review,only
onlythe
theendometrial
endometrial
samples
samples were
were taken
taken into
into consideration.
consideration. A A graph
graph with
with the
the percentage
percentage distribution
distribution ofof the
the
sample types used in the included studies is shown in
sample types used in the included studies is shown in Figure 2. Figure 2.
Sample types
Figure2.
Figure 2. Sample
Sample types
types used
used in
inthe
thestudies.
studies.
Acta Microbiol. Hell. 2024, 69, FOR PEER REVIEW
Regarding the methods used for DNA analysis after its extraction, the majori
Regarding
studies, and the methods
more used for nine
specifically DNA of analysis
themafter its extraction,
(75%), used NGS the methods
majority offor
the sequen
studies, and more specifically nine of them (75%), used NGS methods for sequencing the
16S rRNA gene. Real-time PCR, wide-spectrum PCR, and MALDI-TOF (matrix-
16S rRNA gene. Real-time PCR, wide-spectrum PCR, and MALDI-TOF (matrix-assisted
laserdesorption/ionisation—time
laser desorption/ionisation—time ofmass
of flight) flight) mass spectrometry
spectrometry afterused
after culture were culture
in were
onestudy
one study each.
each. A graph
A graph with
with the the percentage
percentage distribution
distribution of the DNA of the DNA
analysis methodsanalysis m
used in the included studies is shown in Figure 3.
used in the included studies is shown in Figure 3.
NGS
Real-time PCR
Wide-spectrum PCR
Culture and MALDI-TOF mass spectomectry
Figure
Figure DNA
3. 3. analysis
DNA methods
analysis used inused
methods the studies.
in the studies.
3.5. Data and Results from the DNA Analysis
3.5. According
Data and Results from
to the data thethe
from DNA Analysis
analysis of the microbial DNA extracted from the
samples,According
a non-LD-typeto the data from
microbiome the analysis
was found of thewith
in most women microbial
infertility DNA extracted f
or RIF, with
low percentages of Lactobacillus and a higher abundance of
samples, a non-LD-type microbiome was found in most women with infertilitypathogenic bacterial genera,
primarily Prevotella, Gardnerella, Atopobium, Pseudomonas, Streptococcus and Staphylococcus.
with low percentages of Lactobacillus and a higher abundance of pathogenic bacte
In general, the main trend in patients with infertility problems seems to be the presence of
aera, primarily
dysbiotic Prevotella,
microbiome, Gardnerella,
with looser Atopobium,
and disorganised Pseudomonas,
connections Streptococcus
among microbial species and S
coccus.
in In general,
its communities, whilethe main
it also seemstrend in β-diversity,
that the patients with infertility
meaning problems
the composition of theseems t
microbial communities of the endometrium, plays a more important
presence of a dysbiotic microbiome, with looser and disorganised connections am role in endometrial
receptivity and pregnancy rates rather than the α-diversity, meaning the number of species
crobial species in its communities, while it also seems that the β-diversity, mea
in the communities, as the α-diversity did not significantly differ between infertile patients
composition
and the controls.of the microbial
Regarding communities
the outcome of the
of IVF attempts, in endometrium,
the studies where plays a more im
they were
role in endometrial
performed, in most cases, receptivity and pregnancy
there were successful ratesinrather
pregnancies womenthan with antheLD-type
α-diversity, m
microbiome,
the numberwith a higher in
of species Lactobacillus abundance as
the communities, andthelowα-diversity
percentages did of pathogens.
not significant
However,
between infertile patients and the controls. Regarding the outcome of IVFofattemp
this is not absolute because, in some cases, it was proven that the abundance
Lactobacillus was not as important for pregnancy achievement as it did not differ greatly
studies patients
between where who theygotwere performed,
pregnant and those in who
most didcases, there
not, but were
rather, the successful
presence of pregna
women with
pathogens was ofan LD-type
greater microbiome,
importance, which seems withtoadecrease
higher the
Lactobacillus
chances of aabundance
successful and
centages
IVF attemptofand
pathogens.
pregnancy.However,
Moreover,this it isisworth
not absolute
noting thatbecause, in some
in one study, the cases,
high it was
abundance of species other than Lactobacillus seemed beneficial,
that the abundance of Lactobacillus was not as important for pregnancy achievem as there were higher
pregnancy rates in women with this microbiome type, while another study presented a
did not differ greatly between patients who got pregnant and those who did not
higher number of pregnancies in women with a complete absence of Lactobacillus and a
ther, the
higher presence
IVF failure rate of pathogens
in women with anwas of greater
LD-type importance,
microbiome. The datawhichfrom theseems
DNA to decr
chancesand
analysis ofthe
a successful
basic results IVF attempt
of each study areand pregnancy.
shown in Table 3.Moreover, it is worth noting
one study, the high abundance of species other than Lactobacillus seemed bene
there were higher pregnancy rates in women with this microbiome type, while
study presented a higher number of pregnancies in women with a complete ab
Lactobacillus and a higher IVF failure rate in women with an LD-type microbio
data from the DNA analysis and the basic results of each study are shown in Tab
Reference
Analysis Data Results
Acta Microbiol. Hell. 2024, 69 22
Table 3. Cont.
4. Discussion
4.1. Population Characteristics and Demographics
With regards to the age of the patients recruited for the studies, it is only mentioned
in half of the studies. The patients cover almost the entire range of the reproductive
ages (18–50 years old), with the majority of them, however, being 25 to 40 years old. As
the studies investigate the correlation of the microbiome of the endometrium and, in some
cases, of other organs of the reproductive system to female infertility, we can safely deduce
that the rest of the patients whose age is not included in the studies, are also of reproductive
age. Other demographic data are also omitted, apart from the countries where the studies
were conducted, which also constitute the patients’ countries of origin. Regarding these,
half of the studies were conducted in Asian countries and the rest in European countries
(and more specifically, in countries of the European south), apart from one which was
conducted in the U.S.A. It is obvious that the number of countries is quite limited, which
could potentially lead to misleading results. For this reason, it is suggested that subsequent
studies on the subject include patients from a larger number of countries, especially African,
American and Oceanian countries, which have not so far been represented. This way, the
results can be more representative, and there can be further investigation on whether
Acta Microbiol. Hell. 2024, 69 24
the country of origin and the lifestyle and standard of living there plays a role in the
composition of the microbiome and infertility. Finally, the population sample sizes were
quite small, with the average being 103 patients per study and the median being 73 patients
per study, which is mainly due to the complexity of the process and the time required to
choose and recruit the appropriate patients and perform all the analyses. Nonetheless,
studies with a significantly larger sample size, to the extent that this is feasible, would
lead to safer and more complete results and would help us decipher if any unusual or
unexpected results are really statistically important or just the result of chance.
sequencing straight from the sample, even if only a small amount is available, produce a high
data volume in real time and only require a little amount of space.
From these, it becomes clear that modern molecular methods are the most advanta-
geous, defined by their high degree of sensitivity, specificity and reliability. However, the
endometrial cavity is a niche of the human body whose microbiome is only recently starting
to get more thoroughly explored. Thus, a universal protocol for sample analysis has not
yet been created, and therefore it is up to each researcher to choose the desired methods,
according to the available funds and materials and the specific needs and expected results
of each study.
differ between control patients and ones with RIF, with the successful pregnancy rates also
being similar between patients with a Lactobacillus percentage greater and smaller than
90% [23]. Finally, one study showed a higher α- diversity in the microbiome of pregnant
patients than non-pregnant ones, which led the researchers to assume that more diverse
microbiomes are more beneficial for endometrial receptivity than a non-LD-type one [30].
Therefore, it seems that in some cases, the absence of Lactobacillus and the presence of more
diverse microbiomes does not necessarily lead to dysbiosis, while higher Lactobacillus levels
could even prove to be detrimental to pregnancy chances. However, these studies are only
a small percentage of the total, and as none of them provide a satisfactory explanation, a
larger number of studies are required in order to prove if these results are indeed statistically
important or just the result of chance.
5. Conclusions
This review investigated the composition of the endometrial microbiome and its
potential correlation to female infertility and the outcome of IVF treatment based on the
most recent studies on the topic. The strength of this study is that it examines a very
interesting topic that only recently started getting more attention from researchers, and
since female infertility is a problem many people are struggling with, we feel that this
study would be valuable to researchers and practitioners working in the field of human
reproduction. According to the majority of the studies included in this systematic review,
as well as most of the earlier ones, a eubiotic LD-type microbiome seems to be best for
maximising endometrial receptivity and the chances of a successful pregnancy, whereas a
dysbiotic non-LD-type microbiome, with increased α- diversity and a higher number of
pathogens present, has a harmful effect. On the other hand, there were few studies that
presented contradictory results, without, however, a satisfactory explanation. Thus, also
taking into consideration the fact that studies on the endometrial microbiome are still in
the early stages, there is only a small number of them, from few countries and with small
population sizes, and it is clear that more time and a larger number of studies are needed
in order to decipher contradictions and produce more certain results.
Author Contributions: Conceptualization, P.F. and G.G.; methodology, G.G.; software, P.F.; validation,
P.F., M.E., D.C. and G.G.; formal analysis, P.F.; investigation, P.F. and G.G.; resources, P.F. and G.G.;
data curation, P.F.; writing- original draft preparation, P.F.; writing-review and editing, P.F., M.E.,
D.C. and G.G.; visualisation, P.F., M.E., D.C. and G.G.; supervision, M.E., D.C. and G.G.; project
administration, M.E., D.C. and G.G. All authors have read and agreed to the published version of
the manuscript.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflict of interest.
References
1. Lloyd-Price, J.; Abu-Ali, G.; Huttenhower, C. The healthy human microbiome. Genome Med. 2016, 8, 51. [CrossRef]
2. Ursell, L.K.; Metcalf, J.L.; Parfrey, L.W.; Knight, R. Defining the human microbiome. Nutr. Rev. 2012, 70, S38–S44. [CrossRef]
[PubMed]
3. Manos, J. The human microbiome in disease and pathology. APMIS 2022, 130, 690–705. [CrossRef] [PubMed]
4. Dickson, R.P.; Erb-Downward, J.R.; Martinez, F.J.; Huffnagle, G.B. The Microbiome and the Respiratory Tract. Annu. Rev. Physiol.
2016, 78, 481–504. [CrossRef] [PubMed]
5. Bessède, E.; Mégraud, F. Microbiota and gastric cancer. Semin. Cancer Biol. 2022, 86, 11–17. [CrossRef] [PubMed]
6. Amon, P.; Sanderson, I. What is the microbiome? Arch. Dis. Child. Educ. Pract. Ed. 2017, 102, 258–261. [CrossRef]
7. Davenport, E.R.; Sanders, J.G.; Song, S.J.; Amato, K.R.; Clark, A.G.; Knight, R. The human microbiome in evolution. BMC Biol.
2017, 15, 127. [CrossRef]
8. Iavarone, I.; Greco, P.F.; La Verde, M.; Morlando, M.; Torella, M.; de Franciscis, P.; Ronsini, C. Correlations between Gut Microbial
Composition, Pathophysiological and Surgical Aspects in Endometriosis: A Review of the Literature. Medicina 2023, 59, 347.
[CrossRef]
Acta Microbiol. Hell. 2024, 69 27
9. Zhang, M.; Hu, R.; Huang, Y.; Zhou, F.; Li, F.; Liu, Z.; Geng, Y.; Dong, H.; Ma, W.; Song, K.; et al. Present and Future: Crosstalks
Between Polycystic Ovary Syndrome and Gut Metabolites Relating to Gut Microbiota. Front. Endocrinol. 2022, 13, 933110.
[CrossRef]
10. Turnbaugh, P.J.; Ley, R.E.; Hamady, M.; Fraser-Liggett, C.M.; Knight, R.; Gordon, J.I. The Human Microbiome Project. Nature 2007,
449, 804–810. [CrossRef]
11. Clarridge, J.E. Impact of 16S rRNA gene sequence analysis for identification of bacteria on clinical microbiology and infectious
diseases. Clin. Microbiol. Rev. 2004, 17, 840–862. [CrossRef] [PubMed]
12. Cho, I.; Blaser, M.J. The human microbiome: At the interface of health and disease. Nat. Rev. Genet. 2012, 13, 260–270. [CrossRef]
[PubMed]
13. Franasiak, J.M.; Scott, R.T. Endometrial microbiome. Curr. Opin. Obstet. Gynecol. 2017, 29, 146–152. [CrossRef] [PubMed]
14. Toson, B.; Simon, C.; Moreno, I. The endometrial microbiome and its impact on human conception. Int. J. Mol. Sci. 2022, 23, 485.
[CrossRef]
15. Peric, A.; Weiss, J.; Vulliemoz, N.; Baud, D.; Stojanov, M. Bacterial colonization of the female upper genital tract. Int. J. Mol. Sci.
2019, 20, 3405. [CrossRef] [PubMed]
16. Canha-Gouveia, A.; Pérez-Prieto, I.; Rodríguez, C.M.; Escamez, T.; Leonés-Baños, I.; Salas-Espejo, E.; Prieto-Sánchez, M.T.;
Sánchez-Ferrer, M.L.; Coy, P.; Altmäe, S. The female upper reproductive tract harbors endogenous microbial profiles. Front.
Endocrinol. 2023, 14, 1096050. [CrossRef]
17. Moreno, I.; Garcia-Grau, I.; Perez-Villaroya, D.; Gonzalez-Monfort, M.; Bahçeci, M.; Barrionuevo, M.J.; Taguchi, S.; Puente, E.;
Dimattina, M.; Lim, M.W.; et al. Endometrial microbiota composition is associated with reproductive outcome in infertile patients.
Microbiome 2022, 10, 1. [CrossRef]
18. Medina-Bastidas, D.; Camacho-Arroyo, I.; García-Gómez, E. Current findings in endometrial microbiome: Impact on uterine
diseases. Reproduction 2022, 163, R81–R96. [CrossRef]
19. Punzón-Jiménez, P.; Labarta, E. The impact of the female genital tract microbiome in women health and reproduction: A review.
J. Assist. Reprod. Genet. 2021, 38, 2519–2541. [CrossRef] [PubMed]
20. Franasiak, J.M.; Werner, M.D.; Juneau, C.R.; Tao, X.; Landis, J.; Zhan, Y.; Treff, N.R.; Scott, R.T. Endometrial microbiome at the
time of embryo transfer: Next-generation sequencing of the 16S ribosomal subunit. J. Assist. Reprod. Genet. 2016, 33, 129–136.
[CrossRef] [PubMed]
21. Slatko, B.E.; Gardner, A.F.; Ausubel, F.M. Overview of Next-Generation Sequencing Technologies. Curr. Protoc. Mol. Biol. 2018,
122, e59. [CrossRef]
22. Kitaya, K.; Nagai, Y.; Arai, W.; Sakuraba, Y.; Ishikawa, T. Characterization of microbiota in endometrial fluid and vaginal
secretions in infertile women with repeated implantation failure. Mediat. Inflamm. 2019, 2019, 4893437. [CrossRef]
23. Ichiyama, T.; Kuroda, K.; Nagai, Y.; Urushiyama, D.; Ohno, M.; Yamaguchi, T.; Nagayoshi, M.; Sakuraba, Y.; Yamasaki, F.; Hata,
K.; et al. Analysis of vaginal and endometrial microbiota communities in infertile women with a history of repeated implantation
failure. Reprod. Med. Biol. 2021, 20, 334–344. [CrossRef]
24. Oberle, A.; Urban, L.; Falch-Leis, S.; Ennemoser, C.; Nagai, Y.; Ashikawa, K.; Ulm, P.A.; Hengstschläger, M.; Feichtinger, M. 16S
rRNA long-read nanopore sequencing is feasible and reliable for endometrial microbiome analysis. Reprod. Biomed. Online 2021,
42, 1097–1107. [CrossRef]
25. Fujii, S.; Oguchi, T. Age-and endometrial microbiota-related delay in development of endometrial receptivity. Reprod. Med. Biol.
2023, 22, e12523. [CrossRef]
26. Sezer, O.; Soyer Çalışkan, C.; Celik, S.; Kilic, S.S.; Kuruoglu, T.; Unluguzel Ustun, G.; Yurtcu, N. Assessment of vaginal and
endometrial microbiota by real-time PCR in women with unexplained infertility. J. Obstet. Gynaecol. Res. 2022, 48, 129–139.
[CrossRef] [PubMed]
27. Lozano, F.M.; Lledó, B.; Morales, R.; Cascales, A.; Hortal, M.; Bernabeu, A.; Bernabeu, R. Characterization of the Endometrial
Microbiome in Patients with Recurrent Implantation Failure. Microorganisms 2023, 11, 741. [CrossRef] [PubMed]
28. Jain, M.; Mladova, E.; Dobychina, A.; Kirillova, K.; Shichanina, A.; Anokhin, D.; Scherbakova, L.; Samokhodskaya, L.; Panina, O.
Comparison of microbial profiles and viral status along the vagina-cervix-endometrium continuum of infertile patients. Syst. Biol.
Reprod. Med. 2023, 69, 310–319. [CrossRef] [PubMed]
29. Miyagi, M.; Mekaru, K.; Tanaka, S.E.; Arai, W.; Ashikawa, K.; Sakuraba, Y.; Nakamura, R.; Oishi, S.; Akamine, K.; Aoki, Y.
Endometrial and vaginal microbiomes influence assisted reproductive technology outcomes. J. Bras. Reprod. Assist. 2023, 27,
267–281. [CrossRef] [PubMed]
30. Reschini, M.; Benaglia, L.; Ceriotti, F.; Borroni, R.; Ferrari, S.; Castiglioni, M.; Guarneri, D.; Porcaro, L.; Vigano’, P.; Somigliana, E.;
et al. Endometrial microbiome: Sampling, assessment, and possible impact on embryo implantation. Sci. Rep. 2022, 12, 8467.
[CrossRef] [PubMed]
31. Cariati, F.; Carotenuto, C.; Bagnulo, F.; Pacella, D.; Marrone, V.; Paolillo, R.; Catania, M.R.; Di Girolamo, R.; Conforti, A.; Strina, I.;
et al. Endometrial microbiota profile in in-vitro fertilization (IVF) patients by culturomics-based analysis. Front. Endocrinol. 2023,
14, 1204729. [CrossRef] [PubMed]
32. Diaz-martínez, M.D.C.; Bernabeu, A.; Lledó, B.; Carratalá-munuera, C.; Quesada, J.A.; Lozano, F.M.; Ruiz, V.; Morales, R.; Llácer,
J.; Ten, J.; et al. Impact of the vaginal and endometrial microbiome pattern on assisted reproduction outcomes. J. Clin. Med. 2021,
10, 4063. [CrossRef] [PubMed]
Acta Microbiol. Hell. 2024, 69 28
33. Riganelli, L.; Iebba, V.; Piccioni, M.; Illuminati, I.; Bonfiglio, G.; Neroni, B.; Calvo, L.; Gagliardi, A.; Levrero, M.; Merlino, L.; et al.
Structural Variations of Vaginal and Endometrial Microbiota: Hints on Female Infertility. Front. Cell. Infect. Microbiol. 2020, 10,
350. [CrossRef]
34. Zou, Y.; Liu, X.; Chen, P.; Wang, Y.; Li, W.; Huang, R. The endometrial microbiota profile influenced pregnancy outcomes in
patients with repeated implantation failure: A retrospective study. J. Reprod. Immunol. 2023, 155, 103782. [CrossRef] [PubMed]
35. Terzic, M.M.; Aimagambetova, G.; Terzic, S.; Norton, M.; Bapayeva, G.; Garzon, S. Current role of Pipelle endometrial sampling
in early diagnosis of endometrial cancer. Transl. Cancer Res. 2020, 9, 7716–7724. [CrossRef]
36. Vitale, S.G.; Ferrari, F.; Ciebiera, M.; Zgliczyńska, M.; Rapisarda, A.M.C.; Vecchio, G.M.; Pino, A.; Angelico, G.; Knafel, A.;
Riemma, G.; et al. The role of genital tract microbiome in fertility: A systematic review. Int. J. Mol. Sci. 2022, 23, 180. [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual
author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to
people or property resulting from any ideas, methods, instructions or products referred to in the content.
Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.
Alternative Proxies: