Global trends in fertility-preserving treatment for endometrial cancer: a bibliometric analysis, 2005-2024.

Between 2005 and 2024, the field of fertility-preserving treatment for endometrial cancer saw a substantial increase in publications, with 1106 publications total published, as depicted in Fig.  2 A. Analysis using linear regression demonstrated a robust positive association between the yearly publication output and time (R 2  = 0.85, p < 0.001), indicating an average annual growth of about 5.1 publications and a compound annual growth rate of 9.2%. Notably, from 2020 to 2024, 521 publications were published, marking a 106.7% surge compared to the preceding 5-year period (2015–2019), highlighting a significant intensification in research endeavors. Fig. 2 Trends in publication output ( A ) and citation impact ( B ) Trends in publication output ( A ) and citation impact ( B ) The literature from the same period has garnered 31,691 citations, averaging 29.7 citations per publication, indicating a consistent rise in academic influence (Fig.  2 B). The progression of average citations per publication unfolds in three stages: the formative phase (2005–2010) witnessed a climb from 0.4 to 18.5 citations; the expansion phase (2011–2015) maintained levels between 12.9 and 22.5 citations; and the explosive phase (2016–2024) soared to 29.9–41.9 citations, with both 2016 and 2024 surpassing 41 citations. Despite the recent publication dates, the average citations per paper (37.2) notably exceed the historical average, affirming the concurrent advancement in research productivity and academic impact in this domain. Research on fertility-preserving treatment for endometrial cancer over the last twenty years has engaged scholars from 61 countries. As shown in Table  1 , China and the United States have emerged as the most prolific contributors. Table 1 The top 10 countries according to total publications on endometrial cancer fertility-preserving treatment research during 2005–2024 Rank Country Publications Citations Average citations per publication Total link strength 1 China 256 3705 14.5 41 2 United States 222 7896 35.6 98 3 Italy 151 6841 45.3 119 4 Japan 107 2501 23.4 23 5 France 70 3936 56.2 99 6 United Kingdom 68 4418 65.0 114 7 South Korea 67 1773 26.5 18 8 Spain 45 2778 61.7 85 9 Canada 41 2946 71.9 75 10 Germany 41 1860 45.4 71 The top 10 countries according to total publications on endometrial cancer fertility-preserving treatment research during 2005–2024 The international collaboration network, depicted through VOSviewer software (Fig.  3 ), included 21 countries with ≥ 10 publications each. China, the United States, and Italy emerged as pivotal hubs within this collaborative framework. Italy and the United Kingdom demonstrated strong international cooperation, with total link strength values of 119 and 114. Despite China's lead in paper publications, its total link strength values and average citation rate (14.5) were comparatively modest. Conversely, Canada and the United Kingdom exhibited more substantial research influence, reflected in their higher average citation rates per paper (71.9 and 65.0, respectively). Fig. 3 Vosviewer visualization of international collaboration among 21 countries with a minimum of 10 publications. Node size represents the number of publications, while link size indicates the strength of collaboration Vosviewer visualization of international collaboration among 21 countries with a minimum of 10 publications. Node size represents the number of publications, while link size indicates the strength of collaboration This discrepancy may be attributed to several factors. First, the substantial volume of publications in China tends to diminish the average citation value. Second, there exists a phenomenon of "domestic citation circles," wherein research findings are predominantly circulated within the national academic community, resulting in limited international impact. Finally, this situation is compounded by the prevalence of studies published in journals with relatively low impact factors. In contrast, countries such as Canada and the United Kingdom exhibit higher average citations per paper, suggesting that their research findings have achieved greater resonance and influence within the international academic community. A total of 1515 research institutions have contributed publications in the field of endometrial cancer fertility-preserving treatment. The top 10 institutions in this field over the past 20 years are presented in Table  2 . Fudan University demonstrates the highest productivity, followed by the University of Naples Federico II and The University of Texas MD Anderson Cancer Center. These leading institutions are distributed across China (3), South Korea (3), Italy (2), and the United States (2). Noteworthy is South Korea's seventh position in national publication output, with three of its institutions ranking in the top 10, contributing to 92.5% of the country's total publications. The strong presence of these institutions, along with their high total link strength values, suggests a highly efficient and collaborative national research ecosystem in this field. Table 2 The top 10 most productive institutions on endometrial cancer fertility-preserving treatment research between 2005 and 2024 Rank Organization Publications Citations Total link strength Location 1 Fudan University 42 656 27 China 2 University of Naples Federico II 26 703 4 Italy 3 The University of Texas MD Anderson Cancer Center 26 685 10 United States 4 Seoul National University 23 677 37 South Korea 5 Memorial Sloan Kettering Cancer Center 21 891 7 United States 6 CHA University 21 760 26 South Korea 7 Università Cattolica del Sacro Cuore 19 406 4 Italy 8 Peking University 19 151 1 China 9 Shanghai Jiao Tong University 18 729 7 China 10 University of Ulsan 18 717 31 South Korea The top 10 most productive institutions on endometrial cancer fertility-preserving treatment research between 2005 and 2024 The institutional collaboration network (Fig.  4 ) includes 30 institutions, each with at least 10 publications. China, the United States, and South Korea demonstrate relatively robust domestic and international collaborations. In contrast, Italian institutions, specifically the University of Naples Federico II and Università Cattolica del Sacro Cuore, show limited international engagement despite their significant publication output. Fig. 4 Vosviewer visualization of institutional collaboration among 30 institutions with a minimum of 10 publications. Node size corresponds to the number of publications, and link size reflects the intensity of collaboration Vosviewer visualization of institutional collaboration among 30 institutions with a minimum of 10 publications. Node size corresponds to the number of publications, and link size reflects the intensity of collaboration Publications in this field have emerged in 282 distinct journals. Figure  5 illustrates the collaborative networks among 25 journals with at least 10 publications (Fig.  5 A) and 29 journals with co-citation frequencies of 300 or more (Fig.  5 B) related to endometrial cancer fertility-preserving treatment. Table 3 offers a comprehensive overview of the top 10 journals with the highest publication counts in this area. Gynecologic Oncology leads in publication volume with 85 articles, followed by the International Journal of Gynecological Cancer and Archives of Gynecology and Obstetrics. Table 4 lists the top 10 co-cited journals in this domain. The co-citation analysis indicates that Gynecologic Oncology exerts a dominant influence, with 5927 co-citations, significantly surpassing Fertility and Sterility and the International Journal of Gynecological Cancer. Notably, Gynecologic Oncology ranks first in both publication output and citation metrics, establishing it as the premier venue for researchers aiming to track advancements or publish their work in this specialty. Fig. 5 Graph illustrating collaboration among journals using VOSviewer. A Collaboration network between 25 journals with over 10 publications. B 29 journals with a co-citation frequency of at least 300. Node size indicates the number of publications, while link size indicates the degree of collaboration intensity Table 3 Top 10 prolific journals on endometrial cancer fertility-preserving treatment research from 2005 to 2024 Rank Journal Publications Citations IF* JCR Partitions 1 Gynecologic Cancer 85 3848 4.5 Q1 2 International Journal of Gynecological Cancer 64 2201 4.5 Q1 3 Archives of Gynecology and Obstetrics 37 643 2.1 Q2 4 Journal of Gynecologic Oncology 33 944 3.4 Q1 5 European Journal of Gynaecological Oncology 32 129 0.5 Q4 6 Cancers 26 343 4.5 Q1 7 Frontiers in Oncology 26 166 3.5 Q2 8 European Journal of Obstetrics & Gynecology and Reproductive Biology 23 616 2.1 Q2 9 Journal of Obstetrics and Gynaecology Research 22 229 1.6 Q3 10 Journal of Minimally Invasive Gynecology 21 691 4.3 Q1 *IF: Impact Factor Table 4 Top 10 co-cited journals on endometrial cancer fertility-preserving treatment research from 2005 to 2024 Rank Co-cited journal Co-citations IF* JCR Partitions 1 Gynecologic Oncology 5927 4.5 Q1 2 Fertility and Sterility 2393 6.6 Q1 3 International Journal of Gynecological Cancer 2336 4.5 Q1 4 Obstetrics and Gynecology 2133 5.8 Q1 5 Journal of Clinical Oncology 1532 42.1 Q1 6 American Journal of Obstetrics and Gynecology 1527 8.7 Q1 7 Human Reproduction 1377 6.0 Q1 8 Cancer 1356 6.1 Q1 9 Journal of Gynecologic Oncology 704 3.4 Q1 10 American Journal of Surgical Pathology 649 4.5 Q1 *IF: Impact Factor Graph illustrating collaboration among journals using VOSviewer. A Collaboration network between 25 journals with over 10 publications. B 29 journals with a co-citation frequency of at least 300. Node size indicates the number of publications, while link size indicates the degree of collaboration intensity Top 10 prolific journals on endometrial cancer fertility-preserving treatment research from 2005 to 2024 *IF: Impact Factor Top 10 co-cited journals on endometrial cancer fertility-preserving treatment research from 2005 to 2024 *IF: Impact Factor Over the past two decades, 5425 authors have contributed to publications concerning fertility-preserving treatment for endometrial cancer. As shown in Table  5 , the ten most productive and co-cited authors are recognized as key opinion leaders and potential collaborators in this domain. Xiaojun Chen ranks first in publication output, followed by Seok Tae Seong, Antonio Raffone, and Giovanni Scambia. In the co-citation analysis, Jong Yeob Park, Ioannis Gallos, and Philippe Morice emerged as the most frequently cited authors, indicating their significant academic influence. The collaboration network was visualized using VOSviewer, with Fig.  6 A illustrating author partnerships among 25 authors with more than 10 publications, while Fig.  6 B presents a co-citation network of 29 authors who achieved co-citation frequencies exceeding 100. These analyses highlight prominent research teams and influential scholarly works that are shaping the development of the field. Table 5 Top 10 prolific authors and co-cited authors on endometrial cancer fertility-preserving treatment research from 2005 to 2024 Rank Author Publications Citations Co-cited author Co-citations 1 Xiaojun Chen 26 354 Jong Yeob Park 444 2 Seok Tae Seong 18 697 Ioannis Gallos 296 3 Antonio Raffone 17 527 Philippe Morice 231 4 Giovanni Scambia 17 404 Martin Koskas 222 5 Martin Koskas 16 460 Kimio Ushijima 208 6 Weiwei Shan 15 200 Camilla C. Gunderson 191 7 Antonio Travaglino 15 511 Antonio Raffone 187 8 Jianliu Wang 14 111 Jacques Donnez 175 9 Yiqin Wang 14 88 Robert J. Kurman 163 10 Xuezhen Luo 13 219 Nicola Colombo 162 Fig. 6 Network diagram showcasing collaboration among 25 authors with more than 10 publications ( A ) and 29 coauthors achieved co-citation frequencies exceeding 100 ( B ) using VOSviewer. Node size represents the number of publications, and link size denotes the strength of collaboration Top 10 prolific authors and co-cited authors on endometrial cancer fertility-preserving treatment research from 2005 to 2024 Network diagram showcasing collaboration among 25 authors with more than 10 publications ( A ) and 29 coauthors achieved co-citation frequencies exceeding 100 ( B ) using VOSviewer. Node size represents the number of publications, and link size denotes the strength of collaboration Co-cited references denote commonly cited publications that highlight fundamental contributions to a research domain. A total of 28,698 co-cited references were identified, with Table  6 showcasing the top 11 most frequently cited works. Table 6 Top 11 co-cited reference according to total publications on endometrial cancer fertility-preserving treatment research from 2005 to 2024 Rank Co-citations Years Co-cited reference First authors 1 198 2007 Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women Ushijima K [ 10 ] 2 172 2012 Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis Gallos ID [ 11 ] 3 171 2012 Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review Gunderson CC [ 12 ] 4 125 2004 Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review Ramirez PT [ 13 ] 5 119 2013 Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002) Park JY [ 6 ] 6 117 2001 Conservative therapy for adenocarcinoma and atypical endometrial hyperplasia of the endometrium in young women: central pathologic review and treatment outcome Kaku T [ 14 ] 7 114 2003 Outcome of fertility-sparing treatment with progestins in young patients with endometrial cancer Gotlieb WH [ 15 ] 8 111 1997 Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40 Randall TC [ 16 ] 9 107 2014 Prognostic factors of oncologic and reproductive outcomes in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma: systematic review and meta-analysis Koskas M [ 17 ] 10 89 2001 Endometrial cancer in women 40 years old or younger Duska LR [ 18 ] 11 89 1985 The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients Kurman RJ [ 19 ] Top 11 co-cited reference according to total publications on endometrial cancer fertility-preserving treatment research from 2005 to 2024 The most co-cited publication was published in Journal of Clinical Oncology in 2007 [ 10 ], where researchers prospectively evaluated 45 patients treated with high-dose MPA and aspirin. Their findings demonstrated the efficacy of MPA-based fertility-preserving treatment, providing essential evidence for patient counseling and therapeutic decision-making, while also highlighting a noteworthy recurrence rate. Following this, a systematic review and meta-analysis published in the American Journal of Obstetrics and Gynecology [ 11 ] assessed regression, relapse, and live birth rates after fertility-preserving treatment for endometrial cancer and atypical complex endometrial hyperplasia. The third key study was a systematic review published in Gynecologic Oncology [ 12 ]. This comprehensive analysis synthesized data from 45 studies conducted between 2004 and 2011 to assess both the oncologic safety, including regression and recurrence, and reproductive outcomes, such as pregnancy and live birth, associated with progestin therapy in women diagnosed with endometrial hyperplasia and grade 1 endometrial adenocarcinoma. Among the other 8 highly cited articles, one was a review [ 13 ], one was a systematic evaluation and meta-analysis [ 17 ], and six were clinical studies [ 6 , 14 – 16 , 18 , 19 ]. The major studies have demonstrated the efficacy of fertility-preserving treatment in tumor management and assisted pregnancy. However, the high recurrence rate necessitates careful consideration in clinical decision-making. CiteSpace was utilized to analyze the dynamics of citation trends, revealing the most frequently cited articles in recent years (Fig.  7 ). Fig. 7 Top 25 References with the Strongest Citation Bursts Top 25 References with the Strongest Citation Bursts The first study assessed the efficacy of the levonorgestrel-releasing intrauterine device in treating low-risk endometrial cancer and atypical endometrial hyperplasia [ 20 ]. As a pivotal clinical investigation that provided direct evidence for a widely adopted fertility-preserving approach, it has become a cornerstone reference in both research and clinical guidelines. The second most cited article is the 2021 Management Guidelines for Endometrial Cancer Patients [ 21 ]. Its high citation frequency underscores its role as the most current and authoritative synthesis of evidence, serving as an essential framework for clinical decision-making and standards of care globally. The third notable publication is the 2020 Global Cancer Statistics [ 22 ], which indicated that corpus uteri malignancies accounted for 2.2% of all new cancer cases. This work is consistently highly cited as it establishes the critical epidemiological context, defining the disease burden and public health significance that underpins all subsequent research in the field. In summary, these three works constitute the foundational pillars of recent scholarly attention, collectively driving and shaping the current research agenda in fertility-preserving management for endometrial cancer. Using Citespace and VOSviewer, keywords reflecting the prominent research themes were identified. Among the 3437 keywords, 108 keywords appeared at least 15 times. After removing 15 words that were either directly related to or unrelated to the theme, a co-occurrence network was constructed for 93 keywords. Figure  8 shows the keyword collaboration network. Table 7 showed the top 20 most frequently occurring keywords. In the co-occurrence network, keywords were divided into three clusters: Cluster One includes “progestogen”, “medroxyprogesterone acetate”, “lng-ius”, primarily involving treatment modalities. Cluster Two includes “pregnancy outcome”, “recurrence”, “survival”, “quality of life”, focusing on reproductive, oncological, and survival outcomes in clinical studies, as well as other gynecological tumors like “cervical cancer”, “breast cancer”, “ovarian cancer”. Cluster Three includes “risk”, “age”, “obesity”, “lynch syndrome”, “mismatch repair” and “mutation”, mainly addressing risk factors for fertility-preserving treatment. It should be noted that “progestin therapy” and “hormonal therapy” were showed in the keywords. But when determining the retrieval words, we did not include these two words because they may be included in many studies related to advanced endometrial cancer that are not related to fertility-preserving treatment. Fig. 8 Visualization of keyword collaboration using VOSviewer. Node size corresponds to the number of occurrence, and link size reflects the intensity of collaboration. Node color represents distinct research clusters Table 7 Top 20 keywords on endometrial cancer fertility-preserving treatment research from 2005 to 2024 Rank Keyword Occurrences Total link strength 1 Young women 253 1120 2 Atypical endometrial hyperplasia 203 749 3 Endometrial hyperplasia 164 545 4 Medroxyprogesterone acetate 133 591 5 Risk 125 448 6 Ovarian cancer 98 337 7 Cervical cancer 95 365 8 Pregnancy 94 317 9 Outcome 92 323 10 Reproductive outcome 83 374 11 Breast cancer 80 285 12 Surgery 69 227 13 Endometriosis 67 157 14 Complex atypical hyperplasia 66 298 15 Recurrence 66 203 16 Hysteroscopy 64 255 17 Premenopausal women 64 301 18 Diagnosis 54 182 19 Chemotherapy 53 178 20 Gynecologic cancer 53 177 Visualization of keyword collaboration using VOSviewer. Node size corresponds to the number of occurrence, and link size reflects the intensity of collaboration. Node color represents distinct research clusters Top 20 keywords on endometrial cancer fertility-preserving treatment research from 2005 to 2024 Emerging keywords are those that have a high frequency of use in a short period, could reflect and predict research trends in the field. The keyword emergence chart (Fig.  9 ) shows changes in related keywords from 2005 to 2024 in the area of endometrial cancer fertility-preserving treatment. From 2005 to 2017, the emerging keywords mainly included “medroxyprogesterone acetate”, “young women”, “minimally invasive surgery”, “levonorgestrel-releasing intrauterine system”, “megestrol acetate”, “endometrial biopsy”, “progestin therapy”, which were mostly basic treatment regimens for fertility-preserving treatment. From 2017 to 2020, the emerging keywords included “aromatase inhibitor”, “gonadotropin-releasing hormone agonist”, “breast cancer”, and “endometrioid borderline ovarian tumor”. From 2020 to 2024, the keywords “molecular classification”, “quality of life”, “uterine cancer”, “MRI”, and “gynecological surgery” emerged prominently. Particularly, the emergence of molecular classification as a key research focus between 2021 and 2024 corresponds temporally with its prior endorsement for integration into standard clinical practice in 2020 [ 23 ]. Fig. 9 Top 25 Keywords with the Strongest Citation Bursts. The red segments indicate periods of high citation burst strength for a keyword Top 25 Keywords with the Strongest Citation Bursts. The red segments indicate periods of high citation burst strength for a keyword A cross-validation using PubMed demonstrated an almost identical temporal trend to the WOS data, with an exceptionally high Pearson correlation coefficient (r = 0.986, 2005–2024). This strong concordance supports the robustness of our bibliometric analysis and indicates that the use of WosCC alone did not introduce significant temporal bias in capturing the field's growth trajectory.

In this study, the Web of Science Core Collection (WoSCC) database was searched for relevant articles. All available citation indexes within WoSCC were searched. The search formula was set as follows: TS = (endometri*) AND TS = (cancer* OR carcinoma* OR neoplasms* OR adenocarcinoma OR tumor* OR tumour*) AND TS = ("fertility preserv*" OR fertility-preserv* OR "fertility sparing" OR fertility-sparing* OR conservative). The search was performed on 2025.3.25, and all documents were retrieved and collected within this day to mitigate the risk of time-related bias. The date of publication was limited to 2005–2024. This search only included original articles and review articles. Meeting abstracts, editorial materials, proceeding papers, letters, book chapters, retracted publications and retractions were excluded to ensure the quality and consistency of the dataset. The only language selected is English. Choose pertinent publications to export in the plain.txt format, ensuring full records and cited references are included. Through the above steps, we finally identified 1106 suitable studies. The bibliometric analysis and visualization of publications retrieved from WoSCC were conducted using VOSviewer and CiteSpace data analysis software. VOSviewer (version 1.6.20) was utilized to create, visualize and explore a collaborative network map of institutions, countries, authors, journals, and keywords. CiteSpace (version 6.3. R1) was used for keyword and reference literature prominence analysis. For a comprehensive understanding of the search strategy, refer to Fig.  1 . Fig. 1 Data collection and retrieval strategy Data collection and retrieval strategy Following the adjustment of the search strategy to include synonymous keywords and the application of consistent filters for date, publication type, and language, synchronized searches were performed on PubMed. The gathered records were subsequently analyzed using R bibliometrix to extract and assess annual publication trends. These findings were systematically compared with the initial dataset obtained from WoSCC.

This bibliometric analysis mapped global research on fertility-preserving treatment for endometrial cancer from 2005 to 2024 and showed that most studies focus on treatment modalities, clinical efficacy, and risk factors, while mechanistic and translational work remains relatively limited. In recent years, molecular classification has become a major hotspot, as it helps explain heterogeneity in progestin response and supports subtype-adapted fertility-sparing strategies, whereas immunotherapy is emerging as a potential option, particularly for MMR-d disease, with reproductive safety still to be clarified. Overall, the field is shifting from one-size-fits-all hormonal regimens toward biologically informed precision medicine, and future studies should generate subtype-specific prospective evidence and evaluate rational combination strategies to optimize both oncologic and fertility outcomes.

This study utilized bibliometric methods to systematically analyze the literature on fertility-preserving treatment for endometrial cancer published over the past two decades. The findings offer a comprehensive overview of the research landscape, highlighting key developments and providing insights to guide future investigations in this field. The analysis encompassed 1106 articles authored by 5415 researchers affiliated with 1515 institutions across 61 countries. The annual publication count exhibited significant growth in 2019, peaking in 2022, which reflects an increasing research interest in this area over the past 5 years. Geographically, China, the United States, and Italy emerged as the most productive countries. Fudan University (China), the University of Naples Federico II (Italy), and the University of Texas MD Anderson Cancer Center (United States) ranked as the top three contributing institutions. The collaboration network analysis revealed existing cooperative relationships among countries and institutions, albeit with varying degrees of connectivity. The most prolific contributions originated from the research team led by Xiaojun Chen at Fudan University. Their comprehensive investigations addressed multiple aspects of fertility-preserving treatment for endometrial cancer, including clinical efficacy evaluation [ 24 ], management strategies [ 25 ], and mechanistic studies of progesterone resistance [ 26 ]. Additionally, the team explored biological markers predictive of progesterone treatment response [ 27 ], examined the relationship between ovarian reserve function and treatment outcomes [ 28 ], and investigated differential treatment efficacy across molecular classifications [ 29 ]. The analysis of research hotspots and trends, incorporating both high-frequency and emergent keywords, indicates that current investigations predominantly emphasize clinical efficacy. Key areas of interest encompass treatment modalities, fertility outcomes, oncological outcomes, and associated risk factors. Notably, molecular classification has emerged as a significant focus of research in recent years, while mechanistic studies remain comparatively scarce. Our bibliometric analysis reveals a clear evolution in fertility-preserving treatment, shifting from broad use of systemic progestins to more selective agents and combined modalities. Early protocols relied predominantly on high-dose oral MPA and MA [ 30 ], which form the fundamental backbone of conservative therapy. Over time, the increasing prominence of the LNG-IUS reflects a critical transition toward targeted local delivery [ 31 ], aiming to preserve efficacy while reducing systemic adverse effects. In parallel, the growing emphasis on hysteroscopic resection underscores its role not merely as an alternative procedure but as a pivotal cytoreductive step that optimizes the endometrial environment for subsequent progestin therapy; meta-analytic data indicate that combined hysteroscopic resection plus progestin can achieve complete response rates of up to 95.3% [ 5 ]. Although gonadotropin-releasing hormone agonists (GnRH-a) are used in practice—particularly in regimens such as LNG-IUS + GnRH-a [ 32 ]—their relatively low frequency as keywords suggests that they have not yet emerged as a dominant independent research focus. Moreover, although immunotherapy holds promise in fertility preservation, its current under-representation in the published literature may account for its absence from the identified keyword clusters. Collectively, these developments illustrate a shift from one-size-fits-all hormonal therapy toward more refined, multimodal and mechanism-informed strategies. Our bibliometric analysis identifies a critical tripartite clinical paradigm in fertility-preserving treatment: achieving disease remission, mitigating recurrence, and realizing reproductive potential. The meta-analytic data reveal a notable trade-off: a promising complete remission rate of 76.3% is counterbalanced by a substantial recurrence rate of 30.7% [ 5 ]. This elevated recurrence risk transcends mere statistics, representing the central clinical dilemma of the fertility-preserving treatment. It emphasizes that effective management extends well beyond the initial treatment phase. The subsequent pregnancy and live birth rates of 26.8% and 20.5%, respectively [ 33 ], while demonstrating the feasibility of this approach, also underscore a significant "translational gap" between oncological success and reproductive achievement. A considerable proportion of patients who successfully overcome their cancer do not, or cannot, achieve a live birth. This gap may stem from factors such as disease recurrence, underlying infertility, or treatment-related effects on the endometrium. The necessity of comprehensive pre-treatment counseling is paramount. This discussion must clearly articulate the balance between risks and realistic outcomes. Additionally, the effectiveness of maintenance therapy in reducing recurrence [ 5 ] indicates a crucial shift in clinical strategy from a fixed treatment regimen to a dynamic, individualized management plan that extends from remission to conception. This approach should incorporate stringent patient selection based on evolving molecular classifiers, the immediate involvement of dedicated fertility specialists following remission, and long-term surveillance protocols that monitor for oncological recurrence while addressing barriers to conception. The success of fertility preservation is largely contingent upon individual patient characteristics, such as age, body mass index, and genetic background, which directly affect prognosis assessment and the selection of treatment plans. Younger patients not only serve as a demographic indicator but also suggest more favorable tumor biology. Specifically, patients under 40 exhibit a higher proportion of no specific molecular profile (NSMP) compared to those over 40, alongside a lower tumor mutation burden [ 27 ]. Patients under 35 years of age who undergo fertility-sparing therapy for endometrial cancer exhibit significantly higher clinical pregnancy rates and success rates [ 34 ]. A weight reduction exceeding 10% correlates with improved remission rates, decreased recurrence risk, and better pregnancy outcomes following fertility-preserving treatment [ 35 ]. Lynch syndrome affects approximately 1.8–2% of endometrial cancer patients [ 36 ]. These patients carry a lifetime cancer risk of 15–44% [ 37 – 39 ] and are diagnosed at an earlier age [ 40 ], which necessitates a careful evaluation of long-term oncological safety for any conservation strategy. Therefore, effective treatment for this population must extend beyond short-term remission goals, requiring long-term management strategies that encompass their reproductive years and beyond. Current advanced approaches, such as immune checkpoint inhibitor therapy proposed by Chen et al. [ 41 ], show promising potential; however, they are constrained by small sample sizes (n = 4) and short follow-up periods. This limitation highlights a critical research gap: our understanding of how these innovative therapies impact future fertility, pregnancy outcomes, and offspring health remains minimal. This highlights the pressing necessity for specialized prospective registry studies focused on this population. In conclusion, multidisciplinary evaluation and counseling have transitioned from recommendations to essential practices for patients with Lynch syndrome. This approach necessitates collaboration among specialists in gynecologic oncology, reproductive medicine, and genetic counseling to deliver a fully individualized decision based on genetic testing. Such testing must explicitly outline each patient's unique risk of recurrence, the potential benefits and uncertainties associated with emerging therapies, and a comprehensive, long-term follow-up plan. In our keyword burst analysis, “molecular classification” showed a marked citation burst between 2021 and 2024 (Fig.  9 ), indicating its emergence as a recent research hotspot. This trend is supported by co-citation clusters centered on the TCGA framework [ 42 , 43 ] and the ProMisE classifier [ 44 , 45 ], which together established and operationalized the four major molecular subtypes (POLE mutated, MMR-d, NSMP, p53abn). Thus, the bibliometric signal is closely aligned with the broader shift of endometrial cancer management toward precision medicine. Although current fertility-sparing guidelines still recommend hysteroscopic resection plus oral progestin as the preferred strategy irrespective of molecular subtype [ 46 ], accumulating evidence suggests that prognosis and treatment response differ substantially across these groups. NSMP and POLE-mutated tumors, which are common and generally hormone-sensitive, appear to be the most suitable candidates for conservative management [ 44 , 47 ]. In contrast, MMR-d tumors, characterized by distinct immune microenvironments and progesterone resistance [ 48 , 49 ], account for many treatment failures and naturally point to combination strategies such as “progestin + immunotherapy”. The consistent exclusion of p53abn tumors from fertility-sparing indications [ 46 ] further highlights the safety–critical role of molecular profiling. Going forward, the key challenge is to translate these subtype-based insights into pragmatic, biology-driven algorithms supported by prospective, subtype-specific data, thereby moving from a one-size-fits-all approach toward truly individualized fertility-preserving care. In 2023, the FIGO staging system officially integrated molecular subtypes into its guidelines [ 50 ], representing the highest level of acknowledgment of their prognostic significance. Nevertheless, existing guidelines continue to advocate for a standardized approach, thereby creating a notable disparity with the diverse prognoses indicated by molecular subtypes. Consequently, future research should advance beyond mere subtype identification to concentrate on the formulation of dynamic, biology-driven treatment algorithms. It is crucial to gather subtype-specific efficacy data through prospective studies, ultimately facilitating a comprehensive shift from "unified disease management" to "patient-specific cure" via a closed-loop approach. Immunotherapy is emerging as a transformative strategy to address the critical challenge of progesterone resistance in fertility-preserving treatment for endometrial cancer. The biological foundation of this approach is rooted in the capacity of immune checkpoint inhibitors to reactivate anti-tumor immune responses against hormone-resistant cancers. Although large-scale studies specifically assessing the efficacy of immunotherapy in fertility-preserving treatment are limited, Chen et al. [ 41 ] demonstrated its effectiveness in patients with Lynch syndrome, thereby providing foundational evidence for populations with MMR-d. Furthermore, the Phase III clinical trial NRG-GY018 revealed that the addition of pembrolizumab to chemotherapy significantly enhanced survival rates in patients with advanced or recurrent endometrial cancer, indicating potent systemic efficacy across various molecular subtypes [ 51 ]. This success in the most aggressive clinical scenarios naturally supports the exploration of immunotherapy at earlier stages within fertility-sparing treatment contexts, particularly for patients exhibiting high-risk characteristics or initial failure of progesterone therapy. Future clinical trial designs must prioritize molecular subtyping as a fundamental factor for enrollment and stratification. Although immunotherapy has not yet formed distinct clusters in current bibliometric analyses, its progression towards becoming a prominent research focus is evident due to its introduction of a new non-hormonal therapeutic pathway for addressing "progesterone resistance," particularly in hormone-insensitive subtypes such as MMR-d. This trend directs research towards two main avenues: firstly, investigating the synergistic effects of immune checkpoint inhibitors and progesterone to overcome resistance by stimulating the tumor immune microenvironment; secondly, conducting prospective studies to elucidate the effects of immune activation on ovarian function, endometrial receptivity, and the long-term safety of fertility—representing the most challenging yet crucial research objectives in this domain. In essence, the future of fertility-preserving treatment for endometrial cancer lies in an era of precision medicine guided by molecular subtyping and enhanced by innovative strategies like immunotherapy. Subsequent research will undoubtedly concentrate on deeply integrating these two trends to ultimately achieve optimal survival and fertility outcomes customized for each young patient. Recent multi-omics studies are uncovering distinctive biological features of early-onset endometrial cancer, with direct implications for fertility preservation. The CTNNB1 and SIGLEC10 hotspot mutations identified in young patients by Chen et al. [ 27 ] are particularly illuminating. CTNNB1 mutations, well-known drivers of the Wnt/β-catenin signaling pathway, are strongly linked to progesterone resistance, offering a mechanistic rationale for treatment failures in some young patients. The concurrent presence of SIGLEC10 mutations also indicates an immune evasion phenotype. This co-occurrence underscores the dual impact of proliferative signaling and microenvironmental regulation on tumor progression in this demographic. Ultimately, these discoveries advocate for a mechanism-driven approach, wherein molecular profiling informs personalized fertility preservation strategies that go beyond conventional histological methods. Although not prominently featured in our bibliometric analysis, the mTOR signaling pathway constitutes a vital area for future research due to its established role as a master regulator of cell growth, metabolism, and treatment resistance [ 52 ]. This positions mTOR as a crucial integrator of cellular metabolism and hormonal signaling. Building on this theoretical foundation, the inhibition of mTOR offers a rational strategy for enhancing tumor sensitivity to progesterone. Notably, a recent network meta-analysis has provided preliminary clinical evidence indicating that the addition of mTOR inhibitors to progesterone therapy can improve therapeutic outcomes [ 31 ]. Consequently, integrating mTOR's fundamental biological mechanisms with clinical research to advance biomarker-guided mTOR inhibition studies represents a logical next step in the development of personalized fertility protection strategies. A more profound comprehension of crucial carcinogenic signaling pathways provides novel perspectives on addressing progesterone resistance in the treatment of conservative endometrial cancer. The resistance mechanism may be intricately associated with cell proliferation and survival pathways. Research in endometrial cancer indicates that Dioscin, an active compound, can effectively hinder tumor cell migration and invasion by suppressing the MEK/ERK and JNK signaling pathways [ 53 ], underscoring the significant role of the MEK/ERK pathway in endometrial cancer advancement. Importantly, this mechanism is also presented in other cancer types. For example, in head and neck squamous cell carcinoma, nicotine-induced CHRNA5 activation fosters tumor recurrence and metastasis through the MEK/ERK pathway [ 54 ]. These inter-tumor discoveries collectively imply that the abnormal activation of the MEK/ERK pathway may function as a universal driver of tumor progression. Hence, we propose that progesterone resistance or insensitivity in specific subtypes of endometrial cancer, such as certain MMR-d variants, may result from excessive activation of alternative proliferative pathways, such as MEK/ERK. This suggests a promising avenue for forthcoming translational studies: investigating combined approaches that merge MEK/ERK pathway inhibitors with progesterone or immunotherapy. Such strategies have the potential to overcome resistance, broaden the scope of fertility-preserving treatment, and enhance their effectiveness. This study utilizes bibliometric analysis to unveil the dynamic evolution of fertility preservation in endometrial cancer. In comparison with a previous bibliometric study [ 55 ], we expanded the analysis data to 1106 documents through a more inclusive search strategy (such as "endometri*" and "conservative"), and further provided deeper and more novel insights in the following aspects: Firstly, regarding research hotspots and trends, we observed not only the overall growth of the field but also identified "molecular classification" (2021–2024) as the most prominent frontier through keyword emergence analysis. We integrated this with the clinical classification system and systematically elucidated the transformative role of molecular classification in patient selection, prognosis assessment, and treatment strategies. This indicates that the field is rapidly transitioning from a traditional pathology-oriented approach to one guided by precision medicine. Secondly, we have prospectively highlighted the potential of immunotherapy in specific subtypes such as MMR-d in terms of treatment development direction. This connection of molecular characteristics with emerging treatment approaches offers a clear roadmap for future exploration of combined strategies. Furthermore, our analysis of international cooperation and influence models transcends the mere ranking of published articles, uncovering deeper structural characteristics. While China excels in output quantity, its average citations per article and the strength of international connections remain comparatively constrained. In contrast, research from countries such as the UK and Canada demonstrates a greater influence on individual papers. Additionally, we have observed the distinct model of South Korea's effective domestic collaboration network, alongside Italy's institutions, which exhibit high productivity but relatively limited international engagement. These findings enhance our comprehension of the global research ecosystem. Finally, through the integration of literature up to 2024 and the utilization of advanced detection algorithms, we have accurately pinpointed significant recent developments, including the emergence of molecular typing and the investigation of immune checkpoint inhibitors. Consequently, we have delineated the shift from "standardized treatment" to "personalized precision medicine" as a substantiated and continuous evolutionary advancement. In conclusion, based on more comprehensive data, this study not only verified the growth trend of the field, but more importantly, clearly depicted the real-time trajectory of its transformation towards precision medicine driven by molecular typing, clarified the integration path for new directions such as immunotherapy, and revealed the differentiated roles of different countries and institutions in the global research network. This thus provides a more detailed basis for the future strategic layout of this field.

Endometrial cancer is the sixth most common malignancy among women worldwide, accounting for about 4.3% of all new cancer cases and ~ 97,000 deaths annually [ 1 ]. Its incidence is rising, and 3–5% of patients are younger than 40 years [ 2 , 3 ]. Against the backdrop of delayed childbearing, this epidemiologic pattern has led to a growing demand for fertility-preserving treatment. Fertility-sparing therapy is mainly offered to young women with early-stage, low-risk disease, typically with endometrioid histology, grade 1 differentiation, and minimal or absent myometrial invasion [ 4 ]. To meet this clinical need, treatment strategies have evolved from high-dose oral progestins, such as medroxyprogesterone acetate (MPA) and megestrol acetate (MA), to broader options including the levonorgestrel-releasing intrauterine system (LNG-IUS) and hysteroscopic resection. A meta-analysis reported a complete response rate of 76.3% for fertility-preserving treatment [ 5 ], and subsequent salvage surgery rarely leads to extra-uterine spread, supporting the oncologic safety of this approach [ 6 ]. However, important challenges remain. Patient selection still needs refinement, and integrating novel biomarkers—especially molecular classification—may help identify optimal candidates. Post-treatment surveillance protocols are not standardized, making it difficult to balance early detection of recurrence with follow-up burden. In addition, key elements of treatment standardization, such as the best combination regimens, treatment duration, and timing of assisted reproduction, require validation in high-quality studies. Bibliometrics offers a quantitative way to clarify these issues by mapping how research has developed over time. By analyzing citation networks, author collaborations, and keyword co-occurrence, bibliometric analysis can identify research trends, hotspots, and gaps, thereby informing strategic decision-making [ 7 ]. In this study, we systematically retrieved relevant publications from the Web of Science Core Collection and used VOSviewer [ 8 ] and CiteSpace [ 9 ] to perform quantitative analyses and visual mapping, in order to provide an integrated overview of the evolution and emerging directions in fertility-preserving treatment for endometrial cancer.

This study has several limitations. Firstly, we exclusively utilized literature from the WoSCC database. While WoSCC represents the established standard for bibliometric analysis due to its coverage of high-impact journals and data quality, the use of WoSCC introduces a known database bias. This results in the exclusion of certain research contributions cataloged by other databases, particularly leading to a "systematic underestimation" of scientific contributions from non-English speaking nations, while those from English-speaking countries like the United States and the United Kingdom, and countries active in WoSCC such as China, are relatively overestimated. Secondly, despite encompassing nearly two decades of literature, the presence of 21 articles from 2005 suggests that research in this domain commenced earlier. During the selection of search terms, to prevent the inclusion of literature on hormone therapy for advanced endometrial cancer, we omitted hormone therapy as a keyword, potentially leading to the oversight of some relevant studies. Nevertheless, given that our chosen keywords address the majority of discussions on fertility-preserving treatments, the exclusion of these studies is unlikely to impact the overall trend of the findings. Lastly, by focusing solely on English-language literature, there is a possibility of disregarding works by authors in other languages. However, our research conducted a comprehensive bibliometric analysis to delineate the current status and developmental trajectory of endometrial cancer conservation treatment research, thereby offering guidance for future investigations.