Visualization in the domain of endometrial fluid (2000-2023): a bibliometric analysis

doi:10.21203/rs.3.rs-3620059/v1

Download PDF

Research Article

Visualization in the domain of endometrial fluid (2000-2023): a bibliometric analysis

https://doi.org/10.21203/rs.3.rs-3620059/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background: Endometrial fluid represents the condition of the endometrium and testing it brings less harm to patients. Thus, we overviewed the domain of endometrium fluid by bibliometric analysis, the results of which are comprehended by researchers more easily and rapidly.

Method: The publications were retrieved with the terms on endometrial fluid from the Web of Science Core Collection on October 30, 2023. Data were analyzed by VOSviwer, CiteSpace, and Excel.

Results: The analyzed data include 5024 articles and 769 reviews. Both the USA and Texas A&M Universityown the most publications, the quantity of which are 1508 and 68 respectively. Researchers published most often in Human Reproduction. The most productive author is Roberto Romero, who publishes 37 articles and owns a higher value of citations per document with 171. Besides, this article clustered keywords, analyzed them at the timeline level, and discovered the hotspot that will become the future development trend.

Conclusions: This research gives a new perspective to people who just stepped into the field and more intuitive and comprehensive choices for them and sophisticated persons to study in suitable institutions and to collaborate with appropriate authors, which will accelerate the advancement of the domain.

endometrial fluid

research hotspots

scientometric analysis

bibliometric analysis

Endometrial fluid is secreted by the endometrium and is considered a relatively non-invasive gynecology testing method. This research mapped the geographical map of publications and found the high-economy regions publish more articles, such as North America, Eastern Asia, and Europe. The USA and Texas A&M University were the most productive countries and institutions. Besides, Roberto Romero published the most articles in this domain and had a higher value of citations per document. Furthermore, the articles in the field were published more in journals with a higher impact factor, and keywords in analyzed publications were profiled to discover a hotspot that was extracellular vesicles.

Endometrial fluid is secreted by the endometrium, represents the condition of the endometrium, and has exclusive components such as microbiota and extracellular vesicles [1, 2]. Besides, for transformation from scientific research to clinical, it owns advantages of less harm to patients, such as infertility persons whose endometrial fluids were extracted transfer cycle and whose pregnancy outcomes were not worse [3, 4]. Therefore, it can be used in the diagnosis of disease and exploration of the mechanism of molecular, which parallels the trends that Non-invasive testing has been pursued in many medical disciplines because of fewer risks and more comfortable feelings [5].

The field of bibliography has emerged in recent years on account of the comprehensive comprehension of the county, author, institutions, and the prediction of the cut-edge hotspots [6]. In addition, the comprehension of the study field by reading bibliometric articles is more effective for researchers. For example, bibliometric research summarizes the distribution of countries and author in the field of infertility and come up with a suggestion for future research aspects [7].

The combination of endometrial fluid research and bibliography is the current study. We collected the publications from 2000 to 2023 in the field of endometrial fluid and analyzed the data by the software, CiteSpace and VOSviewer. Then, we elucidated and visualized the distribution of the from countries to persons and pointed out development trends in the domain of endometrial fluid. Cutting-edge profiles could be caught by researchers more quickly, comprehensively, and intuitively by this research.

Data

The literature was retrieved from the Web of Science Core Collection on October 30, 2023. The index words included “endometrial fluid”, “endometrium fluid”, “uterine fluid”, and “uterus fluid”. The document types were article and review. From 2000 to 2023, a total of 5793 records were gained.

Methods

The VOSviewer (Nees Jan van Eck and Ludo Waltman, https://www.vosviewer.com/) was used to cluster countries, institutions, authors, and keywords and explore their time variation of them [8]. The hotspot keywords were analyzed in detail by CiteSpace (Chaomei Chen, CiteSpace version 6.2.R4: https://citespace.podia.com/) in recent years [6]. The journals and publication years were counted in Excel. The method of generating a publication map was written here [9].

Timeline and geographic distribution of literature

This research generated 5024 articles and 769 reviews. In Figure.1a, the quantity of documents over the publication year is presented. The number of publications is approximately 180 from 2000 to 2005, increases steadily from 2008 and peaks in 2021. From 2018 through 2021, the velocity of the growth is sharp, which might indicate the domain at that period. Besides, the quantity of publications decreases dramatically in 2023. The geographic distribution of literature is presented in Figure.1b. Compared with fewer publications in Africa, both Western Europe and North America have more interest in the study of endometrial fluid. Besides, some regions also publish many publications in Eastern Asia.

Timeline analysis of countries and institutions

The USA publishes the most papers in the domain of endometrial fluid, followed by the People’s Republic of China and Japan (see Supplementary Table 1). Besides, the USA and Australia also have higher values of citations per document. Additionally, the United Arab Emirates, Iran, and Saudi Arabia, in recent years, have started researching this domain of endometrial fluid in Figure.2a. In productive countries, China and Brazil remain active, compared with others, such as the USA, Germany, and England. In general, the more publications the country publishes, the stronger the relationship between the country and others.

There are five institutions from the USA ranking in the top ten institutions in Supplementary Table 2. Furthermore, it’s noted that Wayne State University has a much higher value than the others in terms of citations per document. Compared with other institutions in the top ten list, there are two institutions, the University of São Paulo and the Fudan University, activating recently, which is shown in Fig. 2b. There are stronger relationships among the Wayne State University, the Seoul National University, the Michigan State University, the University of Michigan, and the Eunice Kennedy Shriver National Institute.

Journals

As is shown in Supplementary Table 3, Human Reproduction, with a 6.1 impact factor, publishes 171 papers which is the highest quantity in journals, followed by Theriogenology and Fertility and Sterility. The journal, Theriogenology, mainly focuses on animal research. Fertility and Sterility owns 152 publications and a 6.7 impact factor. The higher quantity and impact factor may implicate the possibility of optimizing diagnosis and treatment. Of the top ten journals, there are seven journals related to reproduction, five out of which have an impact factor greater than 3.0. Therefore, the domain of reproduction may attract more attention from researchers specializing in endometrial fluid.

Timeline analysis of authors

In Supplementary Table 4, Roberto Romero from Wayne State University, a productive institution, publishes the most literature and owns a very high value of citations per document. In the top ten list, two persons, Fuller W Bazer, and Guoyao Wu, come from the same institution, Texas A&M University which is the most productive institution. As before, both Naguib Salleh and Sekaran Muniandy come from the University of Malaya. In Fig. 3, there is no strong association between authors with high production. Moreover, productive authors were active in the early period, but the authors collaborated frequently with them and published in recent years. Some relatively productive authors who do research with fewer collaborators, such as Sergio Podgaec and Carlos Simon.

Keywords

As is shown in Supplementary Table 5, endometriosis has the highest quantity of occurrence, followed by pregnancy, and endometrium. Additionally, there are two terms with relevance to inflammation. According to Fig. 4a, keywords are mainly clustered into five parts, which are represented with different colors that are purple, green, red, blue, and yellow. Keywords with purple color are related to endometriosis. The green nodes are associated with infertility and cancer, such as ovarian cancer and endometrial cancer. Inflammation and testing techniques are the main domains of the red and blue regions respectively. The relation between the uterus and other species or anatomic sites is exhibited in yellow keywords. Besides, the blue keywords are distributed sporadically among other clusters and are considered as the pivot between different clusters.

The co-occurrence of keywords in the time dimension is shown in Fig. 4b. In 2011, keywords were about apoptosis, cervix, and parturition. The researchers, in 2014, paid more attention to the domains of endometriosis and infertility, such as pregnancy, implantation, embryo, and sperm. The field of extracellular vesicles and exosomes caught more researchers’ attention. Furthermore, CiteSpace was utilized to explore burst keywords from 2013 to the present. The burst detection of keywords is presented in Fig. 5. Nowadays researchers primarily focus on extracellular vesicles, which is correspondent with the results analyzed by VOSviwer.

Results of this research were analyzed from publications, containing 5024 articles and 769 reviews, related to the domain of endometrial fluid from 2000 to 2023. According to trends of literature, the quantity of publications, from 2000 to 2010, remained stable, which implies the domain had been studied at that time. Then, from 2011 to now, the rapid increase of publications on endometrial fluid suggests that the domain is taken seriously by researchers possibly due to the movement towards precision medicine in the whole medical field [10]. The quantity of papers published in 2023 decreases obviously on account of the absence of articles throughout the year. Based on the geographic map of publications, there is no denying that high-economy regions publish more literature, such as North America, China, Japan, Europe, and Australia.

Furthermore, at the aspect results of country, the collaboration between productive countries is fewer. The cooperation between them ought to be strengthened to push the advancement rapidly because a study pointed out that the influence of collaborative papers is higher than that of independent papers and the international cooperation publications are the most powerful papers [11]. For instance, both Brazil and China rank in the top ten countries and should collaborate more frequently on account of the less cooperation between them. Same as to countries mentioned above, the institutions are also supposed to cooperate more frequently due to obvious local aggregation in the co-occurrence network of institutions and a lower frequency of collaboration among the productive institutions.

As for the analysis of journals, both Human Reproduction and Fertility and Sterility own superior publications and impact factors, which indicates that research published from them might be more presentative and the freshman of this domain ought to read papers from them when they begin to dive into the field. About authors in this domain, Roberto Romero published the most literature and has the most value of citations per document. Therefore, knowledge generated from him might be cut-edge more probably. For instance, a case report of him, published in the American Journal of Obstetrics and Gynecology with an impact factor of 9.8, was cited 32 times and elaborated that there was higher bacterial diversity and lower Lactobacillus abundance in the endometrial fluid of a person with a healthy pregnancy, compared with that of spontaneous clinical miscarriage patients [12].

Profiling keywords was performed by two software, CiteSpace and VOSviewer. The keywords were primarily clustered into five parts. Based on the clusters of keywords in results formed by VOSviwer, the species of diseases and testing technology are the features that differentiate each other. Moreover, at the timeline level, the research trends changed from specific macroscopical diseases, such as endometriosis and chorioamnionitis, to the exploration of microscopical matters used for diagnosis and treatment. Furthermore, there are many studies analyzing the components in the endometrial fluid at the microscopical level to identify its application in infertility diagnosis, such as cytokine [13], microRNA [14], protein [15], extracellular vesicles [4], cells [16], and microbiota [17].

According to timeline analysis and burst detection of keywords, the domain of extracellular vesicles is an emerging aspect for researchers. Extracellular vesicles mainly consist of three subtypes, which are microvesicles, exosomes, and apoptotic bodies, which are differentiated by many features, such as size, content, and function [18], and have a tremendous treatment prospect in many disciplines [19]. Firstly, for the application of extracellular vesicles on endometrial fluid, a study confirmed that there was no significant composition difference in two endometrial fluid samples two days apart [4], which offers a piece of robust evidence that infertile women can test endometrial fluid, a relatively less harmful test method [3], when they are in embryo implantation cycle. For the best method of extracting extracellular vesicles for analyzing microRNAs, there isn’t a consistent conclusion in different research, which confirmed the best approach is ultracentrifugation [20], size exclusion chromatography using the qEV column [4], and polymer-based precipitation [21].

The correlation between extracellular vesicles and diseases in the field of endometrial fluid is utilized to elaborate the potentially pathologic mechanism and is considered as an alternative for diagnosis and treatment. For instance, in a study published by Fertility and Sterility, there is a statistical difference in twelve small non-coding RNAs between healthy and infertile women, which included eleven microRNAs and one piwi-interacting RNA [20], and that results in the analysis of two methods, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, show that the chosen microRNAs are associated with immune response, cell junction, extracellular matrix, and embryonic development. Another meta-analysis also generated a similar conclusion that the differences in pathway enrichment of RNA extracted from endometrial fluid between women with failure and successful pregnancy were primarily immune response and cell junction [2]. In addition, lectin galactoside-binding soluble three binding protein was deemed as a poor prognosis in patients with endometrial cancer due to its higher correlation with blood vessel density [22]. For the application for treatment, there is none in this domain, but the treatment using it has been studied in other fields, such as cardiovascular diseases [23], kidney diseases, and liver diseases [24], and it will finally step into the clinic [25]. In summary, the study on extracellular vesicles will hopefully help more patients in diagnosis and treatment.

This research visualized the geographic distribution of literature and timeline analysis of countries, institutions, authors, and keywords. Hotspots were discovered by two software, CiteSpace and VOSviewer. There was also a limitation because the database that we selected is only Web of Science Core Collection, but most bibliometric analysis uses that for analysis and it includes most publications on endometrial fluid. Besides, since 2023 is not over yet, the literature for 2023 is not complete, an advantage of which is the better competence of hotspot prediction.

This article concluded and visualized the overviews of the domain of endometrial fluid from 2000 to 2023, and pointed out cut-edge trends for researchers to explore in the future. Freshmen could intuitively know the overviews of the domain from different perspectives. It also helps them and sophisticated persons to choose institutions for continuing education, authors for collaboration, and research trends for carrying out simultaneously, which would push the advancement of the field of endometrial fluid.

IVF

In Vitro Fertilization

VEGF

Vascular Endothelial Growth Factor

Acknowledgements

We thank all potential reviewers for their comments and suggestions.

Funding

None.

Availability of data and materials

See Supplementary Dataset.

Authors’ contribution

FG conceived and designed the study. HG drafted the manuscript. FG and HG reviewed and revised the manuscript. HG and GL designed the data collection tool, collected the data, and performed the data analysis. HG and FG produced the charts. All authors approved the final submission of the manuscript and agreed to be responsible for all aspects of the work.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Ethics approval and consent to participate

Not applicable.

Moreno I, et al. Endometrial microbiota composition is associated with reproductive outcome in infertile patients. Microbiome. 2022;10(1):1.
Giacomini E, et al. Global transcriptomic changes occur in uterine fluid-derived extracellular vesicles during the endometrial window for embryo implantation. Hum Reprod. 2021;36(8):2249–74.
van der Gaast MH, et al. Endometrial secretion aspiration prior to embryo transfer does not reduce implantation rates. Reprod Biomed Online. 2003;7(1):105–9.
Saraee F, et al. Human uterine fluid lavage-derived extracellular vesicle isolation: a comparative study for minimally invasive endometrial receptivity assessment. Reprod Biomed Online. 2022;45(3):457–72.
Badeau M, et al. Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women. Cochrane Database Syst Rev. 2017;11(11):CD011767.
Sabe M, et al. Thirty years of research on negative symptoms of schizophrenia: A scientometric analysis of hotspots, bursts, and research trends. Neurosci Biobehav Rev. 2023;144:104979.
Chen P, et al. Brain-gut axis and psychiatric disorders: A perspective from bibliometric and visual analysis. Front Immunol. 2022;13:1047007.
van Eck NJ, Waltman L. Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics. 2010;84(2):523–38.
MapChart. [cited 2023; Available from: https://mapchart.net/world-advanced.html.
Konig IR et al. What is precision medicine? Eur Respir J, 2017. 50(4).
KATZ JS. How much is a collaboration worth? A calibrated bibliometric model. Scientometrics. 1997;40(3):541–54.
Moreno I, et al. The first glimpse of the endometrial microbiota in early pregnancy. Am J Obstet Gynecol. 2020;222(4):296–305.
Cermisoni GC, et al. Uterine fluid cytokine/chemokine levels of women undergoing ART with and without oral Vitamin D supplementation. Hum Reprod Open. 2022;2022(2):hoac017.
von Grothusen C, et al. Uterine fluid microRNAs are dysregulated in women with recurrent implantation failure. Hum Reprod. 2022;37(4):734–46.
Azkargorta M, et al. Differential proteomic analysis of endometrial fluid suggests increased inflammation and impaired glucose metabolism in non-implantative IVF cycles and pinpoints PYGB as a putative implantation marker. Hum Reprod. 2018;33(10):1898–906.
Herrera L, et al. Natural killer cell subsets in endometrial fluid: a pilot study of their association with the endometrial cycle and reproductive parameters. J Assist Reprod Genet. 2023;40(9):2241–50.
Reschini M, et al. Endometrial microbiome: sampling, assessment, and possible impact on embryo implantation. Sci Rep. 2022;12(1):8467.
Doyle LM, Wang MZ. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 2019. 8(7).
Elsharkasy OM, et al. Extracellular vesicles as drug delivery systems: Why and how? Adv Drug Deliv Rev. 2020;159:332–43.
Li T, et al. Cargo small non-coding RNAs of extracellular vesicles isolated from uterine fluid associate with endometrial receptivity and implantation success. Fertil Steril. 2021;115(5):1327–36.
Ibanez-Perez J, et al. microRNA-based signatures obtained from endometrial fluid identify implantative endometrium. Hum Reprod. 2022;37(10):2375–91.
Song Y, et al. Plasma exosomes from endometrial cancer patients contain LGALS3BP to promote endometrial cancer progression. Oncogene. 2021;40(3):633–46.
Sahoo S, et al. Therapeutic and Diagnostic Translation of Extracellular Vesicles in Cardiovascular Diseases: Roadmap to the Clinic. Circulation. 2021;143(14):1426–49.
Wu R, et al. Mesenchymal Stem Cell-Derived Extracellular Vesicles in Liver Immunity and Therapy. Front Immunol. 2022;13:833878.
Cully M. Exosome-based candidates move into the clinic. Nat Rev Drug Discov. 2021;20(1):6–7.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Visualization in the domain of endometrial fluid (2000-2023): a bibliometric analysis

Status:

Version 1

Abstract

Figures

Plain English Summary

Introduction

Materials and Methods

Data

Methods

Results

Timeline and geographic distribution of literature

Timeline analysis of countries and institutions

Journals

Timeline analysis of authors

Discussion

Strengths and limitations

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1