Adenomyosis (AM) is a prevalent and chronic condition affecting reproductive-aged women. Pathologically, it is similar to endometriosis and is characterized by the benignly infiltrate of endometrial glands and stroma into the underlying myometrium, leading to progressive uterine enlargement (1, 2). The most common clinical manifestations of AM are abnormal uterine bleeding associated with anemia, chronic pelvic pain (such as dysmenorrhea and dyspareunia), infertility, and an increased risk of adverse pregnancy outcomes, all of which seriously affect the quality of women’s lives in their reproductive age (3, 4).

In recent years, the incidence of AM has risen, with a notable trend of the younger women being affected, and an increasing number of AM patients are of childbearing age with seeking fertility needs. Alarmingly, 19.5% of AM patients experience infertility (5), with over 80% of infertile patients attributed to AM and more than 30% of these individuals having previously failed assisted reproductive technology (ART) treatments (6). Moreover, female infertility and subfertility present complex challenges, accompanied by substantial economic burden and profound psychosocial effects (7), including elevated levels of anxiety and depression (8). Therefore, understanding the mechanisms through which AM impacts fertility has garnered significant scholarly attention, elucidating these pathways is critical for developing accurately targeted treatment strategies.

Despite extensive research on AM-associated infertility, there remains a scarcity articles that offer preliminary insight into its pathogenesis. The exact pathogenesis underlying AM’s impact on fertility have yet to be fully elucidated, hindering the development of targeted therapies and presenting an enormous scientific challenge for researchers. Consequently, a comprehensive big data analysis of the pathogenesis, research progress, trends, and focal points concerning AM-associated infertility is essential. This effort not only to facilitates the generation of innovative research ideas but also fosters collaborative global initiatives aimed at overcoming the identified challenges (9).

Bibliometrics, a field that qualitatively and quantitatively analyzes academic publishing, employs mathematical and statistical method to assess published works within specific disciplines (10). Recently, scientometric analysis and data visualization have emerged as valuable methodologies, extensively applied across various biomedical sciences and public health disciplines (11, 12). Compared to the traditional literature reviews, scientometrics with its visual capabilities offers advantages in quickly identifying research hotspots, critical issues, and guiding future exploration within exciting fields (13–15). For instance, Jin et al. (16) employed bibliometrics techniques to reveal gaps, traditional focal points, and potential prospects in menopausal syndrome research, clarifying future research directions for investigators. Despite the emergence of several literature reviews and meta-analyses on AM-associated infertility in the last two decades, there has been a notable lacking in scientometric studies exploring the link between AM and infertility.

To fill the apparent gap in knowledge, our study conducted bibliometrics analysis for drawing scientific knowledge maps and generating data visualization to reveal the relationship between AM and infertility by using multiple software tools. The statistical results of the keyword analysis were analyzed and summarized, which included publication year, countries and regions, institutions, authors, journals, relevant references, timeline view, and keyword co-occurrence and citation burst analysis from 2000 to 2024. This study aims to elucidate research trends and core challenges in AM-associated infertility, ultimately providing new perspectives and ideas for future investigations and attracting increased attention from scientific community.

This study represents the first analysis of the global research landscape surrounding AM-associated infertility utilizing bibliometrics methodologies. Both AM and infertility are common gynecologic diseases that not only pose significant challenges for individuals but also impose substantial economic burdens on the national healthcare systems, society, and families (29, 30). The reported prevalence of AM can be as high as 70% (31), and it affects approximately 24.4% of infertile women (32). AM is widely recognized for its detrimental affects on fertility, contributing to infertility among women of childbearing age (33–35). Moreover, the incidence of AM associated with infertility is increasing annually, correlating with the tendency of delayed childbearing among women (5, 31). Cozzolino et al. (36) confirmed that women with AM have reduced live birth rates (LBR) (OR 0.59, 95% CI 0.37–0.92, p = 0.02), clinical pregnancy rate (OR 0.66, 95% CI 0.48–0.90), and ongoing pregnancy rate (OR 0.43, 95% CI 0.21–0.88), alongside an increased miscarriage rate (OR 2.11, 95% CI 1.33–3.33). Younes et al. (37) reported a 41% reduction in LBR among patients with AM. Vercellini et al. (38) elaborated a 28% decrease in the likelihood of clinical pregnancy via ART compared to women without AM. Additionally, Marvelous et al. (39) indicated a decline in clinical pregnancy among AM patients, ranging from 42.7% with an AM score of zero to 13% with a score of seven.

Consequently, a growing number of scholars are focusing on the relationship between AM and infertility, resulting in a large aggregation of articles and reviews exploring the complex mechanisms underlying this association. Despite this, a systematic method for analyzing and identifying key areas of interest in this research domain has been lacking. Bibliometric analysis, similar to epidemiological approaches, offers a robust means of highlighting potential future research directions by examining authorship, institutional contributions, journal impact, and keyword usage in existing literature. This approach provides valuable insights that can inform and deepen future investigations in the field (10, 40, 41).

In this study, we performed a scientometric analysis to grasp the current research hotspots, keywords, focal points, challenges, and trends pertaining to AM-associated infertility. Our analysis encompassed 456 articles and reviews published across 153 journals by 123 institutions in 51 countries/regions, yielding a total of 13,426 citations and 62 H-indexes. We established that AM remains a primary concern and a significant challenge within infertility research globally, with a continuous growth in the quantity of published articles since 2006. The significance of studying the association between AM and infertility is gradually gaining recognition within both academic and clinical circles. Major contributions were identified from China, the USA, Italy, France, and Japan, collectively ranking as the top five countries in terms of publications. This trend may be attributed to the high prevalence of AM and the relatively advanced status of infertility and biomedical study in these nations. We divided 190 keywords, which appeared more than five times, into eight clusters, mainly focused on pathogenesis, adverse factors affecting pregnancy, treatment methods, diagnostic modalities, disease progression, IVF management, infertility, and fertility management. These clusters indicate significant interest in AM-related infertility research over the past 24 years.

Additionally, by analyzing the citation burst of keywords, we discovered emerging research hotspots in the potential mechanisms of pathogenesis, diagnostic methods, and strategies for improving pregnancy success in AM-associated infertility. Recent investigations have increasingly aimed at decoding the intricate mechanism involved in the application of targeted therapies for AM patients with infertility. Although an unambiguous understanding of the pathogenesis is still pending, several hypotheses have gained traction. Altered endometrial function and receptivity in AM patients may give rise to a pro-inflammatory environment and heightened oxidative stress, negatively affecting embryo implantation and survival (42, 43). Other proposed mechanisms include abnormal uterotubal transport caused by adenomyomas with obstruction, which may block sperm transport by distorting the uterine cavity and disrupting normal myometrium structure and function (31, 33). Additionally, irregular uterine contractions during the follicular phase and disturbance in the uterine junctional zone have been implicated as potential contributors to AM-associated infertility (44–46). Recent findings show that increased amplitude and decreased contraction coordination in AM patients could significantly lead to infertility, particularly during the luteal phase when implantation occurs (47). The importance of uterine peristalsis during the peri-implantation phase is notably highlighted in the context of IVF implantation failures and adverse pregnancy outcomes in AM (48). These findings indicate quantifying abnormal patterns and measures of uterine contractility offers a potential new tool for explaining infertility associated with AM (47).

Moreover, evidence of AM with infertility, involving various biomarkers such as matrix metalloproteinases (MMP), interleukins (IL-6, IL-10), HOXA10, leukemia inhibitory factor (LIF), cytochrome P450, and RCAS1 (49). Previous studies suggest that the downregulation of HOXA10, NR4A receptor, and FOXO1A appears to impaired implantation in women with AM (50, 51), and dysregulation of LIF has a similar effect (52). Additionally, molecules like nitric oxide, which are expressed at abnormally high levels, adversely impact sperm transport, implantation, and decidualization, leading to AM-related infertility (53). Pro-oxidative and antioxidative cytokines, including copper (Cu), manganese superoxide dismutase (Mn-SOD), and zinc superoxide dismutase (Zn-SOD), are associated with increased inflammatory responses in the endometrium (54, 55). Consequently, prior research indicates significant opportunities for further investigations into the correlation between AM and infertility.

Although histopathological reports are considered the gold standard for diagnosing AM, they can lead to diagnostic delays of up to 12 years (56) and are not essential for treating patients with concurrent infertility. Instead, imaging techniques serve as the primary diagnostic tools (5, 29). Some studies utilize trans-vaginal ultrasound, while others employ MRI or a combination of both approaches, leading to potential inconsistencies in diagnostic effectiveness (57, 58). The incidence of infertility linked to AM appears to be classification-dependent (59). Moreover, underdiagnosis by less experienced practitioners cannot be discounted, as this may lead to the erroneous inclusion of women with AM in control group, thereby potentially underestimating the actual effect of AM on reproductive outcomes (34). Therefore, the accuracy of diagnosing AM in the context of infertility remains contentious. Further research is imperative to establish uniform diagnostic criteria that clarify the definitive connection between AM and infertility.

Regarding treatment options to improve pregnancy outcomes, there are currently no harmonized international guidelines for managing patients with AM who wish to preserve fertility (60, 61). Nonetheless, available evidence suggests that treatment can positively effect on fertility outcomes (33). For instance, surgical interventions have been shown to increase rates of natural conception (36). Additionally, the use of danazol-loaded devices yield a pregnancy rate of 41%, while GnRHa therapy results in a LBR of 36.2%. Uterine artery embolization has an even higher LBR of 83.3% (35). Other studies report pregnancy rates of 60.5% following complete excision and 46.9% after partial excision of AM (62). The odds ratio of clinical pregnancy post-surgery is reported as 6.22 (CI 2.34–16.54) (37). Furthermore, variations in AM types demonstrate different effects on fertility outcomes, focal AM is associated with a pregnancy rate of 49.1%, compared to 38.5% for the diffuse AM, and a miscarriage rate of 27.6% for focal AM versus 16.2% for the diffuse AM (63).

However, Mijatovic et al. (64), noted no significant increase in clinical pregnancy rates among infertile women with AM who had previously undergone GnRH treatment (36). The overall effectiveness of surgical treatment for AM affecting pregnancy rate remains inconclusive, with a reported risk of uterine rupture estimated at 6.0% (65). A systematic review further indicated that treatments involving oral contraceptives, antiprostaglandins, progestins, danazol, and GnRHa have not improved pregnancy rates for women with AM planning to conceive. However, high-intensity focused ultrasound and combination therapies before ART may benefit these patients (5). Although existing research confirms that pharmacological and surgical treatments for AM positively impact reproductive outcomes, including pregnancy rates and LBR, the comparative effectiveness of different treatments and the optimal timing for delaying pregnancy remain unclear. Additionally, limited evidence on the correlation between infertility and the severity and classification of AM may affect pregnancy rate statistics (66). Therefore, developing standardized protocols to address AM-related infertility is crucial, and the efficacy of these therapeutic options must be validated through prospective randomized controlled trials.

To the best of our knowledge, our study is the first in-depth scientometric analysis of AM-associated infertility. However, several limitations need attention. First, the data were sourced solely from the SCI-E database within the WoSCC, potentially omitting relevant literature and causing a bias in research conclusions. Second, the use of bibliometric software for author analysis does not currently allow for the differentiation of author name abbreviations, which may lead to inaccuracies. Additionally, bibliometric analysis based on machine algorithms does not permit an in-depth exploration of individual studies, possibly omitting some information. Moreover, as the review focuses exclusively on studies addressing infertility in AM, there may be a selection bias present. Finally, the lack of authoritative guidelines for bibliometric analyses in medical research is a significant challenge for academics who wish to gain a comprehensive and accessible understanding of bibliometric methods and their application in medical research.

However, the WoS is the most powerful search engine, and the WoSCC database contains extensive data on the theme of AM-associated infertility. In addition, the WoS is the premier research platform for biomedical and natural science, and the world’s most trusted publisher with an independent global citation database. Therefore, based on an adequate amount of data and the correct scientometrics methods, the outcomes of this study are convincing and may help accurately identify knowledge gaps, research hotspots, and development trends in AM-associated infertility. The perspectives presented here can guide the generation of novel ideas for further in-depth investigations into AM-associated infertility. Specifically, research on improving uterine receptivity during the peri-implantation period offers direction and encourages further exploration for focused collaboration between researchers and clinicians.

This study is the first to use bibliometric methods to detail global trends and the current status of AM-associated infertility over the past 20 years. The research highlights that international interest in this complex field remains strong. Key topics include pathogenesis, factors affecting pregnancy, treatment and diagnostic methods, disease progression, and IVF management. Although chronic disease management strategies, pharmacological treatments, and ART have improved fertility outcomes in AM patients, further collaboration between researchers and clinicians is crucial to facilitate translational clinical research. This study aids in identifying research hotspots and fostering regional collaboration for a deeper understanding of the AM-associated infertility landscape and its evolution.