Research Progress on Acupuncture Therapy in Infertility: A Bibliometric Analysis from 2000 to 2021 ()
1. Introduction
Infertility is characterized by the inability to establish a clinical pregnancy after 12 months of regular and unprotected sexual intercourse. It is estimated that 8% - 12% of couples of childbearing age suffer from infertility, which not only exerts a serious impact on the psychosocial health of couples and their families [1] [2] , but also induces potential adverse consequences on the health of future generations [3] .
The global census shows that infertility is still a persistent reproductive problem. In China, the prevalence rate of infertility in couples of childbearing age is 25%, and almost half of infertile couples do not seek medical assistance [4] [5] . However, accurate and effective treatment is still urgently required and common diagnosis and treatment decisions are lacking [6] . Reactive oxygen species (ROS) have been shown to be efficacious in the treatment of infertility [7] , whereas high levels of ROS can lead to inactivation of enzymes and protein oxidation in spermatozoa, resulting in infertility. Hormone therapy can correct gonadal dysfunction, but multiple pregnancy is still an important complication [8] .
Acupuncture has been proven to have potential efficacy for infertility. A survey of the websites of assisted reproductive clinics in the U.S. found that 111 of 456 clinics recommended the use of acupuncture with a high degree of recognition [9] . At present, accumulated studies have shown the beneficial effects of acupuncture, including increasing the pregnancy rate of patients with polycystic ovary syndrome (PCOS) infertility [10] , increasing the maximum follicular diameter [11] , elevating ovulation rate and endometrial thickness [12] , and mitigating anxiety [13] . Clinical randomized controlled trials (RCT) show that acupuncture can improve body mass index (BMI), decrease luteinizing hormone (LH) level and increase ovulation response in patients with PCOS infertility. The efficacy of acupuncture for infertility may ascribe to the changes in the activity of the autonomic nervous system and stimulation of neuropeptides or neurotransmitters related to the pathogenesis of infertility [14] , which is a potentially effective treatment of infertility.
Bibliometric analysis has been widely utilized to analyze published scientific literature. In recent years, bibliometric analysis has been increasingly conducted regarding the research progress and trend of global acupuncture treatment of depression [15] , tumor [16] , obesity [17] and knee osteoarthritis [18] . However, bibliometric analysis of acupuncture in the treatment of infertility has not been carried out. Therefore, this study was designed to evaluate the research trend of acupuncture and moxibustion for infertility through bibliometric analysis by using CiteSpace and VOSviewer based on the co-occurrence network of countries, institutions, authors, journals, references, keywords, the highest frequency of acupoints and acupuncture methods from 2000 to 2021.
2. Materials and Methods
2.1. Literature Review
All data were obtained from the Web of Science core database and PubMed on February 11, 2022. The search words were “infertility” and “acupuncture” (Table 1). The search period was from January 1, 2000 to December 31, 2021 not limited to categories, languages or document types. The search results were analyzed by CiteSpace and VOSviewer.
2.2. CiteSpace Bibliometric Analysis
CiteSpace (Version 5.6.R4) constructs a visual knowledge map to represent references, institutions, authors and countries [19] [20] . The links between map nodes represent cooperation or collaborative relationship, the colors of nodes and lines represent different years, and purple circles represent centrality. The parameters of CiteSpace are set as follows: 1) Time span (2000-2021), years per slice; 2) one node type is selected at a time; 3) selection criteria top 50 objects; 4) pathfinder and pruning sliced networks; 5) look back years (LBY = 8), 6) ink retaining factor (LRF = 2), 7) percentage of nodes to label (PNL = 5%), 8) maximum links per node (MLPN = 10), 9) e for top N (e = 2).
2.3. VOSviewer Bibliometric Analysis
VOSviewer (Version 1.6.14) is employed to analyze the co-occurrence knowledge graph of citation networks of countries, institutions, periodicals and documents [21] [22] . A node represents an element, such as countries, institutions, authors, journals, references and keywords. To ensure unity, the top 50 objects are selected for each element. The greater the link width between nodes is, the closer the cooperation relationship is, and the size of nodes indicates the number of elements represented. The node with high centrality represents the turning point or pivot point related to this field, which is represented by purple.
Two authors independently searched the references and screened these articles. Any differences were resolved by discussing or seeking the help of the third author. A total of 329 articles were identified (Table 1). Literature and result analyses indicated that there was no repetition of the literature.
3. Results
3.1. Annual Publications and Trends
From 2000 to 2021, although there were some fluctuations in the number of publications on acupuncture and moxibustion treatment of infertility in the Web of Science, the overall number showed an increasing trend (Figure 1). It is predicted that publication output will continue to expand in the future.
3.2. Literature Type Analysis
A total of 329 articles were derived from WOS and reused with Citespace. Finally, 316 articles (Table 2) were obtained, and 7 literature types were found. Article (n = 211) was the most frequent literature type, accounting for 66.77%, followed by Review Article (n = 85, 26.89%). “Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy [23] ” was the most frequently-cited article, with a total of 67 citations. The most frequently cited review was “A systematic review and meta-analysis of acupuncture in in-vitro fertilisation [24] ” published by El-Toukhy, T., which is cited 68 times.
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Table 1. Literature searching queries.
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Table 2. Literature types related to acupuncture for infertility.
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Figure 1. The annual number of publications and citations related to acupuncture for infertility.
3.3. Analysis of Countries
CiteSpace was adopted to analyze the co-occurrence of countries and regions. The combined network consisted of 34 nodes and 56 links, indicating that 34 countries conducted studies of acupuncture treatment of infertility (Figure 2(a)). From the perspective of national centrality, China ranked first, followed by U.S., Italy and U.K. In addition, VOSviewer was utilized to build country citation, density, and overlay visualization (Figures 2(b)-(d)). Among the top five countries, China (n = 126) had the largest number of publications, followed by the U.S. (n = 64), South Korea (n = 32), Australia (n = 31) and the U.K. (n = 27), respectively. The most frequently cited articles were from China (n = 1530), followed by U.S. (n = 1466), U.K. (n = 1385), Sweden (n = 675) and Australia (n = 632), as shown in Table 3. Japan, Indonesia and Singapore articles had been cited more frequently in recent years.
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Table 3. Top 10 countries in publications, centrality and citations related to acupuncture for infertility.
3.4. Analysis of Institutions
Among the 345 nodes and 557 links, Heilongjiang University Chinese Med (n = 16) ranked first in publication volume, followed by Korea Institute Oriental Med (n = 14) and Huangzhong University of Science & Technology (n = 12). In terms of centrality, the top three institutions were Beijing University Chinese Med (0.09), Karolinska Institute (0.06) and Heilongjiang University Chinese Med (0.05) (Figure 3(a), Table 4). Visual analysis (Figure 3(b), Figure 3(d)) was performed by VOSviewer. Karolinska Institute was the most cited institution (n = 372), followed by Heilongjiang University Chinese Med (n = 300) and University Adelaide (n = 292). In the knowledge map analyzed by the co-authors, red clustering showed that there was a close cooperative relationship among Yale University, Karolinska Institute, Gossberg University, Heilongjiang University of Chinese Medicine and University of Hong Kong. Blue clustering revealed cooperation among Shanghai University of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Xuzhou Medical University and Nanjing Medical University, while green clustering illustrated the cooperative relationship among Beijing University of Traditional Chinese Medicine, West Sydney University and University of New South Wales. Purple clustering showed cooperation among Kyunghee University and Korea Institute of Oriental. Yellow clustering indicated cooperation among Zhejiang University of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine and Peking University. (Figure 3(c)). West Sydney University, Heilongjiang University of Chinese Medicine, Nanjing University of Traditional Chinese Medicine and Zhejiang University were the core members of the cooperative network, promoting extensive cooperation among many institutions.
3.5. Analysis of Authors
461 authors who have published articles of acupuncture and moxibustion in the treatment of infertility were searched and analyzed. CiteSpace was used to analyze the author’s collaboration network and centrality (Figure 4(a)), and VOSviewer
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Table 4. Top 10 institutions in publications, centrality and citations related to acupuncture for infertility.
was utilized to analyze the author’s overlay visualization and collaboration network (Figures 4(b)-(d)). The top three authors of cited frequency were Stener-Victorin E (n = 493), Norman Robert J (n = 235), Sterzik, K (n = 178). Stener-Victorin E published the highest number of articles (n = 13, Table 5). Among the co-cited authors, Stener-Victorin E (n = 287) ranked first, followed by Caroline A. Smith (n = 157) and Manheimer E (96). The top three authors of centrality were Stener-Victorin E (0.15), Bae CS (0.11) and Caroline A. Smith (0.11), as shown in Table 6.
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Table 5. Top 10 authors in publications and centrality related to acupuncture for infertility.
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Table 6. Top 10 co-cited authors in citation and centrality related to acupuncture for infertility.
3.6. Analysis of Journals
VOSviewer analysis showed that Fertility and Sterility published 22 articles, citing 991 times, accounting for 6.9% of the total number of articles. It was the most effective journal, followed by Cochrane Database of Systematic Reviews (n = 465), Human Reproduction Update (n = 246) (Table 7, Figure 5(c), Figure 5(d)). VOSviewer was used to determine the total citation. In terms of co-cited frequency, Fertility and Sterility ranked first (n = 1252), followed by Hum Reprod (n = 716), and Cochrane Database of Systematic Reviews (n = 253) (Table 8, Figure 5(b)). The number of articles was not correlated with the amount of citations in academic journals. In terms of centrality, Acta Obstetricia et Gynecologica Scandinavica ranked first (0.16), followed by Acta Anaesthesiologica Scandinavica (0.13) and Acupuncture Electro (0.12), as illustrated in Table 8 (Figure 5(a)).
3.7. Analysis of References
CiteSpace was used to analyze literature centrality and clustering. In terms of centrality, Rashidi BH (2013) ranks first (0.12), and this article also had the highest citation frequency. The research results of Wu XK (2017) and Agarwal A(2015) attracted significant attention. Clustering was obtained from the cited literature by using keywords to analyze the research methods and frontier topics from 2000 to 2021. “Systematic review” was the largest cluster, with 61 members and a silhouette value of 0.85. The most active article under this cluster was “Somatosensory stimulation and assisted reproduction [25] ”. The first three clusters were “systematic review”, “polycystic ovary syndrome” and “vitro fertilization”, respectively. “Polycystic ovary syndrome” was the earlier cluster, while “acupuncture pretreatment” was the cluster in recent years (Table 9, Figure 6(a), Figure 6(b)).
VOSviewer was adopted to analyze the citation and co-citation of literature. In 2002, the article entitled “Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy [23] ” published by Paulus, W.E had the highest frequency of citation and co-citation (n = 141, n = 67). The articles published by Jedel (2011) and Dieterle, S (2006) also had higher cited frequency (Figure 6(c), Figure 6(d)). Acupuncture could increase the clinical pregnancy rate by reducing androgen levels [26] [27] . Wu, X.K (2017) [28] received more attention in recent years, which was published in JAMA Internal Medicine. The first 10 references were demonstrated in Table 10.
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Table 7. Top 10 journals in publications and citations related to acupuncture for infertility.
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Table 8. Top 10 co-cited journals related to acupuncture for infertility.
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Table 9. Top 10 cited references related to acupuncture for infertility in terms of centrality.
3.8. Analysis of Keywords and Burst Keywords
“Acupuncture” was the most frequent keyword, which was closely related to “infertility” and “in vitro fertilization” (Figure 7(a), Figure 7(d)). In terms of centrality, “complementary medicine” had the highest centrality (0.35), as shown in Table 11. Cluster analysis showed that the top three clusters were “vitro fertilization”, “complementary medical therapies” and “polycystic ovary syndrome” (Figure 7(b), Figure 8(a)). In recent years, increasing attention has been paid to the study of acupuncture treatment of infertility. The keyword of “systematic review” had the highest outbreak intensity. In the last five years, the most concerned keywords in this field were “polycystic ovary syndrome”, “quality”, “traditional Chinese medicine” and “outcome” (Figure 7(c), Figure 8(b)).
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Table 10. Top 10 co-cited references related to acupuncture for infertility.
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Table 11. Top 10 keywords related to acupuncture for infertility.
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Figure 8. (a) The cluster timeline view network of keywords related to acupuncture for infertility. (b) The top 15 keywords with the strongest citation bursts related to acupuncture for infertility. The color represents different frequent keywords (red: frequent; green: infrequent).
3.9. Analysis of Acupoints and Acupuncture Methods
To understand the common acupoints and acupuncture methods in the treatment of infertility, the centrality and correlation intensity of acupoints and acupuncture adjuvant therapy were calculated by SATI 4.0 and IBM SPSS Modeler 18.0. In terms of centrality, GV20 (Baihui), KI3 (Taixi), BL23 (Shenshu), ST36 (Zusanli), SP6 (Sanyinjiao), SP10 (Xuehai), PC6 (Neiguan), LR3 (Taichong), ST29 (Guiai), LI4 (Hegu) had the highest centrality among 91 acupoints (Figure 9(a)), of which SP6 (Sanyinjiao) had the highest neutrality (0.79), as shown in Table 12. Regarding acupuncture methods, “Manual acupuncture” had the highest centrality (0.79), and “Eletroacupuncture” “Chinese herbal medicine” “traditional Korean medicine” also had higher centrality (Figure 9(b)). In terms of correlation intensity, SP6 (Sanyinjiao), KI3 (Taixi), LR3 (Taichong), ST29 (Guilai) and ST36 (Zusanli) had the strongest correlation. In addition, LR3 (Taichong), GV20 (Baihui) and SP10 (Xuehai) also had a higher frequency of combined use (Figure 10(a), Table 12). In terms of treatment, Manual Acupuncture was the most common treatment, followed by Electroacupuncture. “Traditional Korean medicine” and “Chinese herbal medicine” were mainly used as adjuvant therapy for acupuncture treatment of infertility (Figure 10(b)).
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Figure 9. (a) The centrality of acupoints related to acupuncture for infertility. (b) The centrality of therapies related to acupuncture for infertility.
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Figure 10. (a) The correlation map of acupoints related to acupuncture for infertility. (b) The correlation map of therapies related to acupuncture for infertility.
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Table 12. Top 10 acupoints in correlation strength and centrality related to acupuncture for infertility.
4. Discussion and Conclusion
A growing number of publications show that the application of acupuncture in the treatment of infertility is gaining increasing attention [13] [28] [42] . It is expected that the number of publications will increase significantly in the coming years. As one of the most common complementary and alternative therapy for infertility, acupuncture is widely adopted in the treatment of infertility [43] [44] worldwide. China, the U.S., Germany, the U.K. and Australia have made tremendous contributions to the research on acupuncture treatment of infertility. In addition, China, the U.S., Australia and Switzerland maintain a high degree of cooperation with other countries. In this study, China was found to play a key role in this area, taking into account the number of publications, centrality and citations. In addition, in the past few years, China, South Korea, Türkiye, the U.K. and other countries have played an important role in the research on acupuncture treatment of infertility. In terms of centrality, the cooperation among countries, authors and institutions shows the characteristics of regional cooperation and intra-professional cooperation, while interdisciplinary international cooperation is not sufficiently conducted. Therefore, researchers from different research fields and institutions should strengthen cooperation to carry out high-quality research.
Using CiteSpace to generate institutional maps, 335 nodes and 347 links were generated. 958 publications were distributed among 335 research institutions. Heilongjiang University Chinese Med published the largest number of articles, the number of citations was 372 and the centrality was 0.06, indicating that the institution has made significant contribution to the research of acupuncture and moxibustion treatment of infertility. Wu, X.K from Heilongjiang University Chinese Med is an important scholar in acupuncture research. RCT on acupuncture in the treatment of infertility was published in JAMA Internal Medicine with an IF: 56.272. It is worth noting that in this article, Wu, X.K et al. found that in Chinese women with PCOS, acupuncture combined with or without clomiphene did not increase the live birth rate compared with acupuncture and placebo [24] . Interestingly, another article published by this scholar on the treatment of oligoasthenozoospermia with acupuncture pointed out that acupuncture can significantly increase the serum level of testosterone (T), reduce the concentration of follicle stimulating hormone (FSH), LH and estradiol (E2), and increase the pregnancy rate [45] . Beijing University of Traditional Chinese Medicine has published 13 articles with 267 citations and 0.05 centrality, indicating that it also plays an important role in this field. In addition, superimposed visualization shows that Huangzhong University of Science & Technology, Korea Oriental Medical College, Western Sydney University and Xuzhou Medical University have made significant contributions in this field in recent years.
Based on the network analysis of published articles, co-authors and co-cited authors, influential authors related to acupuncture and moxibustion treatment of infertility, such as Stener-Victorin E, Caroline A. Smith, Junyoung Jo and Fan QU, are important authors of acupuncture-moxibustion treatment of infertility. Stener-Victorin E, the principal researcher of Karolinska Institute, has devoted himself to the study of acupuncture in the treatment of PCOS in the past few years. He has published 17 articles and obtained the highest number of common citations. Among them, a study published by Adam H Balen, published in Human Reproduction Update (IF: 15.6), believes that there is no clear evidence that acupuncture exerts a therapeutic effect on women with PCOS [46] . In addition, Jie Cheng, Myeong Soo Lee, Choi Tae-Young and Ang Lin are prominent authors in the field of acupuncture and moxibustion for infertility in the past three years.
In this study, a large number of journals show that the efficacy of acupuncture in the treatment of infertility is receiving widespread attention. The average impact factor of the top ten journals is 4.2665. The top ten journals have published 129 articles, accounting for 39.21% of the total. Fertility and Sterility (IF: 7.329) focuses on the field of reproductive medicine. It is worth noting that Fertility and Sterility ranks first in terms of publication, citation and co-citation, indicating that the journal plays a key role in this field. In addition, three of the top 10 journals belong to complementary and alternative medicine, namely Journal of Alternative and Complementary Medicine, Evidence Based Complementary and Alternative Medicine and BMC Complementary and Alternative Medicine. A total of 32 articles have been published, accounting for 24.8% of the total number of articles published in the top 10 journals, indicating that more and more attention has been paid to the efficacy of complementary and alternative medicine in the treatment of infertility from 2000 to 2021. In the cooperative network, Fertility and Sterility and Human Reproduction Update have the highest correlation, indicating that there is a close cooperative relationship between these two journals in the research on acupuncture treatment of infertility.
Acupuncture is the keyword with the highest co-occurrence frequency, which appeared in 2002, with a citation intensity of 1.58, indicating that acupuncture has received extensive attention in the treatment of infertility from 2000 to 2021. In the previously published articles, some studies have shown that acupuncture is a valuable treatment, which exerts a significant effect on improving clinical pregnancy rate and alleviating anxiety [13] [27] . In contrast, alternative studies believe that the efficacy of acupuncture in the treatment of infertility lacks of supporting evidence [46] [47] , indicating that the efficacy of acupuncture in the treatment of infertility is not accurate and needs further research. In addition, in vitro fertilization also has high centrality and frequency, and the adjuvant effect of acupuncture in in vitro fertilization has been widely concerned. Some literature has shown that acupuncture can reduce the pressure of embryo transfer, improve endometrial thickness and improve patient satisfaction [13] [48] . The keyword cluster analysis suggests that “in vitro fertilization” is the largest cluster, with 66 members, and the most active reference in this cluster is “Acupuncture in improving endometrial receptivity: a systematic review and meta-analysis [49] ” published by Zhong Y, et al. In 2019, among the first 15 clusters, five are complementary and alternative medicine represented by Chinese traditional medicine (“Chinese herbal medicine” “acupuncture” “electroacupuncture” “moxa treatment”), indicating that complementary and alternative medicine is receiving increasing attention in the treatment of infertility. Combined with cluster analysis and outbreak keyword analysis, it can be found that infertility with PCOS and traditional Chinese medicine including acupuncture is one of the research directions for the treatment of infertility.
In terms of acupoint selection, GV20 (Baihui), KI3 (Taixi), BL23 (Shenshu), ST36 (Zusanli), SP6 (Sanyinjiao), SP10 (Xuehai), PC6 (Neiguan), LR3 (Taichong), ST29 (Guiai), LI4 (Hegu) are the most commonly used acupoints for acupuncture treatment of infertility. Most of these acupoints belong to The Liver Meridian, The Kidney Meridian, The Stomach Meridian and The Heart Meridian. These meridians are closely related to the “qi” and “blood” that regulate human body. Therefore, the occurrence of infertility may be related to the imbalance of “qi” and “blood”. In terms of acupuncture methods, manual acupuncture is the most common acupuncture method. Eletroacupuncture is also widely applied in acupuncture treatment of infertility. Chinese herbal medicine and traditional Korean medicine are mainly used as adjuvant interventions for acupuncture treatment of infertility. Interestingly, some studies have also combined acupuncture with Tai chi, Qi gong, Yoga and other oriental traditional medicine to treat male infertility [50] , which is considered to improve the sperm parameters and motility, mitigate genital inflammatory conditions, as well as immune system disorders, sexual dysfunction, and varicocele, etc.
Meta-analysis and systematic review have been widely employed to evaluate the efficacy of acupuncture in the treatment of infertility. At present, the evaluation of the efficacy of acupuncture remains to be elucidated. Taken together, the findings in this study provide a research hotspot for potential collaborators and institutions, offer a new perspective on the development trend of acupuncture for infertility, and assist researchers to explore new research directions in this field. The database included in this study is not comprehensive, and the software analysis may have some biases and limitations, which need to be further improved.
Acknowledgements
This work was supported by Weifang Nursing Vocational College and Weifang Weien Hospital. Thanks a lot for the help of CiteSpace, VOSviewer, SATI and IBM SPSS Modeler.