Evaluating Treatment Options for Symptomatic Uterine Fibroids: A Systematic Review and Meta-analysis of Effectiveness, Recovery, and Long-Term Outcomes (MARIE WP1)

Evaluating Treatment Options for Symptomatic Uterine Fibroids: A Systematic Review and Meta-analysis of Effectiveness, Recovery, and Long-Term Outcomes (MARIE WP1) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Evaluating Treatment Options for Symptomatic Uterine Fibroids: A Systematic Review and Meta-analysis of Effectiveness, Recovery, and Long-Term Outcomes (MARIE WP1) Elena Bedggood, Sun Jie, Snehal Ghosh, Vindya Pathiraja, Tharanga Mudalige, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6073815/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Uterine fibroids can significantly impair the quality of life of women. While most fibroids remain asymptomatic, 25% of women diagnosed with uterine fibroids require medical intervention. Methods: A systematic review and meta-analysis protocol was developed and published in PROSPERO (CRD42022346251) to explore surgical treatment outcomes linked to uterine fibroids. Data was gathered using PubMed, Web of Science and ScienceDirect. The pooled data was analysed using the meta-package (version 8.0-1 and version 4.6-0) in R software (version 4.4.2). Results: Five studies met the eligibility criteria, and were further analysed to report quality of life, symptom severity and complications linked to surgery. Three studies (n=520) assessed HRQoL via UFS-QoL pre- and post-uterine artery embolisation and myomectomy. The pooled mean difference was -6.99 (95% CI: [-16.49, 2.51]; I²=71.9%; P=0.03), indicating no significant difference in quality of life impact between procedures. However, the pooled mean difference for UFS-QoL symptom severity was 4.85 (95% CI: [0.50, 9.21]; I²=0.0%; P=0.52), suggesting myomectomy significantly reduces symptom severity compared to uterine artery embolisation. Most studies did not report race and ethnicity, and the study sample was not representative of the global female populous. Conclusion: Uterine artery embolisation and myomectomy result in comparable improvements in health-related quality of life although myomectomy appears to offer a greater reduction in symptom severity compared to uterine artery embolisation. These findings can assist clinicians and patients make improved shared decisions when selecting the most appropriate treatment for uterine fibroids. Improved research study designs and representation in sample need to be considered when conducting future research. Women's studies Womens health Uterine Fibroids Symptom Severity Embolisation Myomectomy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 Figure 21 Introduction Uterine fibroids (UF), also known as uterine leiomyomas, are common benign tumours of the uterus that disproportionately affect women of reproductive age. While non-malignant, fibroids can significantly impair quality of life, causing symptoms such as heavy menstrual bleeding, pelvic pain, and infertility. The prevalence of UF increases with age, affecting approximately 40% of premenopausal women and nearly 50% of women by the age of 50 years( 1 ). While most fibroids are asymptomatic, around 25% of women who develop fibroids experience symptoms severe enough to require treatment( 2 ). These symptoms, including menorrhagia, pelvic pressure, and iron deficiency anaemia, can significantly impact physical and emotional well-being( 3 , 4 ). The prevalence of uterine fibroids is particularly high among women of African descent, with studies indicating that 60–80% of African American women will develop fibroids by age 50, compared to 30–40% of White women( 5 ). Black women also face a greater risk of requiring surgical intervention, with a 2.4-fold increased likelihood of undergoing a hysterectomy and a 6.8-fold higher chance of requiring multiple myomectomies( 6 ). These racial disparities reflect both biological factors and disparities in healthcare access, as women in lower-income regions or with limited access to care face greater challenges in managing the condition( 4 ). In high-income countries, fibroid treatment benefits from advanced healthcare systems, where access to diagnostic tools such as high-resolution ultrasound and magnetic resonance imaging (MRI) enables early detection and personalized care. Treatment options range from pharmacological therapies, such as hormonal treatments (gonadotropin-releasing hormone (GnRH) agonists, oral contraceptives, and progesterone-releasing intrauterine devices (IUDs), to minimally invasive procedures like uterine artery embolization ( 7 ), MRI-guided focused ultrasound, and robotic-assisted myomectomy( 5 , 8 ). For definitive management, hysterectomy remains a common option, with robotic and laparoscopic approaches offering quicker recovery times and fewer complications. These treatments are supported by comprehensive insurance coverage and a well-developed specialist workforce, ensuring women have access to timely and effective care( 9 – 11 ). However, in low- and middle-income countries (LMICs), fibroids management is constrained by limited healthcare resources, systemic challenges, and geographical disparities. Diagnostic capabilities are often limited to basic ultrasound, with advanced imaging modalities largely unavailable in rural or underserved regions. Medical treatments, including hormonal therapies, are hindered by inconsistent access to affordable medications and poor pharmaceutical supply chains. Advanced treatments like UAE and minimally invasive surgery are mostly confined to urban centres or private healthcare facilities, leaving many women with limited access to these options ( 4 , 6 ). In such settings, surgical interventions often include open myomectomy or hysterectomy, which may carry higher risks due to inadequate perioperative care( 11 , 12 ). Cultural factors and financial constraints in LMICs can also lead women to seek traditional remedies or community-based care. While these approaches may be culturally significant, they often lack the evidence base and effectiveness of modern medical treatments( 13 ). This reliance on traditional practices further highlights the healthcare disparities between resource-rich and resource-constrained settings, where access to optimal care for fibroids remains limited( 14 , 15 ). The global management of fibroids reflects stark disparities between developed countries and LMICs. In high-income nations, women have access to a range of advanced diagnostic and treatment options, ensuring timely and effective management. In contrast, women in LMICs often face significant barriers to care, with fewer treatment options and limited access to healthcare infrastructure. This article compares the impact of uterine artery embolisation, myomectomy, and hysterectomy on women’s quality of life, assess changes in symptom severity, and examine the occurrence of complications such as haemorrhage, urinary retention, infection, and vaginal discharge following each treatment of uterine fibroids. The study also examines the prevalence and treatment landscape of fibroids worldwide, highlighting the significant disparities in access to care, and proposes strategies to bridge these gaps. By fostering equitable healthcare solutions and increasing access to uterine-preserving treatments, we can improve outcomes for women with fibroids, regardless of their geographic location. Methods A systematic methodology was developed and published in PROSPERO (CRD42022346251) to explore outcomes based on surgical treatments among patients with uterine fibroids. Search strategy and Screening A search was conducted using PubMed, Web of Science and Science Direct. The key terms used were uterine fibroids, Eligibility criteria and study selection All studies that were included into the study sample comprised of quantifiable measures and outcomes linked to uterine fibroids. All randomised clinical trials, non-randomised clinical trials, mixed-methods, and epidemiology studies that reported on uterine fibroids that were peer reviewed and published in English from the 30 th of April 1980 to the 30 th of September 2024 were included to the data sample. Data extraction and analysis The data extraction process is demonstrated in the PRISMA diagram (Figure 1). All quantifiable measures of mean, median, mode, standard deviation, were extracted from all the studies. The data was refined using an independent reviewer and pooled using Endnote and Microsoft Excel by 2 reviewers (EB and JS). Finally, 42 articles were assessed for eligibility (Table 01). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were reported. Statistical analysis The meta-analysis combined myomectomy and hysterectomy into one group for comparison with the UAE group. All meta-analyses used either random-effects models or fixed-effects models based on the heterogeneity between studies. Statistical heterogeneity among studies was assessed using the Cochrane Q test and the I² statistic. Potential publication bias was evaluated using funnel plots and Egger's test. Data analysis was performed using the meta package (version 8.0-1) and the metafor package (version 4.6-0) in R software (version 4.4.2). Risk of bias The systematically identified sample was critically appraised by 1 independent reviewer and assessed for methodological quality and rigor using the Newcastle-Ottawa Scale (NOS). Studies were rated as good, fair, or poor based on the allocation of stars in the following domains: Good quality: 3–4 stars in selection, 1–2 stars in comparability, and 2–3 stars in outcomes. Fair quality: 2 stars in selection, 1–2 stars in comparability, and 2–3 stars in outcomes. Poor quality: 0–1 star(s) in selection, 0 stars in comparability, and 0–1 star(s) in outcomes. Results Quality of life Uterine fibroids can significantly impair quality of life. For women who do not respond to medical treatment, there are typically three treatment options: uterine artery embolization, myomectomy, and hysterectomy. We will conduct a meta-analysis to compare the impact of uterine artery embolization with myomectomy and hysterectomy on women’s quality of life. The Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) The Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) is a scale specifically designed to assess the quality of life in patients with uterine fibroids. This scale is divided into two main sections: health-related quality of life and symptom severity. In the following analysis, we will compare the changes in patients’ quality of life before and after undergoing uterine artery embolization and myomectomy. UFS-QOL health-related quality-of-life A total of three studies involving 520 patients reported changes in health-related quality of life (HRQoL) as measured by the UFS-QoL scale before and after undergoing uterine artery embolization and myomectomy. The pooled mean difference was -6.99 (95% CI = [-16.49, 2.51], heterogeneity I² = 71.9%, P = 0.03; Figure 2)(7, 16, 17). According to the 95% confidence interval, there is no statistically significant difference in the impact on patients’ quality of life between uterine artery embolization and myomectomy UFS-QOL symptom severity The pooled mean difference for the UFS-QoL symptom severity was 4.85 (95% CI = [0.50, 9.21], heterogeneity I² = 0.0%, P = 0.52; Figure 3)(7, 16, 17). This indicates that while there is no difference between the two procedures in improving patients’ quality of life, myomectomy significantly reduces symptom severity compared to uterine artery embolization. European Quality of Life 5 Dimensions 3 Level Version(EQ-5D-3L) Some studies have also used the EQ-5D-3L scale to measure patients’ quality of life. The following analysis compares the changes in EQ-5D-3L quality of life scores before and after treatment in patients undergoing uterine artery embolization versus those undergoing myomectomy or hysterectomy. According to reports from two studies involving a total of 353 patients, the pooled mean difference was -7.36 (95% CI = [-10.72, -4.00], heterogeneity I² = 0.0%, P = 0.78; Figure 4)(16, 18). This indicates that, when using the EQ-5D-3L scale to measure quality of life, the myomectomy or hysterectomy group showed a statistically significant improvement in quality of life compared to the uterine artery embolization (7) group. The 36-Item Short Form Health Survey (SF-36) Some studies have used the SF-36 scale to compare the mental and physical health status of patients before and after undergoing uterine artery embolization versus myomectomy or hysterectomy. According to reports from two studies involving a total of 313 patients, the pooled mean difference for mental health was -1.58 (95% CI = [-2.29, 0.86], heterogeneity I² = 0.0%, P =0.38; Figure 4), and the pooled mean difference for physical health was –1.45 (95% CI = [-4.20, 1.30], heterogeneity I² = 92.8%, P <0.005; Figure 5)(12, 16, 18). These results indicate that the ability of the uterine artery embolization group to improve patients’ mental health is significantly lower than that of the myomectomy or hysterectomy group. However, there is no difference in the impact on patients’ physical health between the two groups. Complications Patients undergoing uterine artery embolization, myomectomy, and hysterectomy may experience different complications, such as postembolization syndrome, haemorrhage, urinary retention, infection, and vaginal discharge. Post-embolization syndrome Postembolization syndrome is a common complication following uterine artery embolization (7). We analysed the incidence of postembolization syndrome in 431 patients across four studies(7, 16-18). The pooled incidence rate was 7% (95% CI = [2%, 21%], heterogeneity I² = 90.7%, P < 0.005; Figure 7). Haemorrhage Haemorrhage is common following UAE, myomectomy, and hysterectomy. We compared the risk of postoperative bleeding between the UAE group and the group undergoing hysterectomy or myomectomy. The pooled odds ratio (OR) was 0.16 (95% CI = [5%, 51%], heterogeneity I² = 0%, P = 0.39; Figure 8), indicating that UAE is 84% less likely to result in haemorrhage compared to hysterectomy or myomectomy(7, 16, 18). Urinary retention Urinary retention is a complication following hysterectomy and myomectomy. In two studies involving 111 patients who underwent hysterectomy or myomectomy, the pooled incidence rate of urinary retention was 2% (95% CI = [0%, 7%], heterogeneity I² = 0%, P = 0.91; Figure 9)(7, 18). While the absence of heterogeneity (I² = 0%) and a P-value of 0.91 demonstrate consistency between the two studies, the low statistical power stemming from the limited number of included studies may obscure true variability. Additionally, the P-value primarily confirms statistical consistency rather than providing clinically meaningful insights. Infection Patients undergoing hysterectomy and myomectomy may experience infections. Based on reports from four studies involving 311 patients, the pooled incidence rate of infections was 9% (95% CI = [6%, 13%], heterogeneity I² = 34.8%, P = 0.20; Figure 10)(7, 16-18). Vaginal discharge Changes in vaginal discharge are common after UAE. Results from two studies involving 255 patients showed a pooled incidence rate of vaginal discharge of 4% (95% CI = [1%, 20%], heterogeneity I² = 83%, P = 0.02; Figure 11)(7, 18). Publication bias The following funnel plots illustrate the publication bias for all outcomes. The funnel plots for UFS-QoL health-related quality-of-life score (Egger's test p-value = 0.3202, Figure 12), UFS-QoL symptom severity score (Egger's test p-value = 0.9254, Figure 13), Haemorrhage (Egger's test p-value = 0.1285, Figure 18), and Infection (Egger's test p-value = 0.3967, Figure 20) are symmetrical, indicating no publication bias. However, the funnel plot for Post-embolization syndrome (Egger's test p-value < 0.001, Figure 17, 18, 19, 20 and 21) is asymmetrical, indicating the presence of publication bias. Discussion The motivation for this systematic review is to provide a comprehensive comparison of the available treatment options for symptomatic uterine fibroids—specifically uterine artery embolization ( 7 ), myomectomy, and hysterectomy—in terms of their impact on women’s quality of life, symptom relief, and associated complications. Given the significant impact of uterine fibroids on women’s well-being, this review aims to guide clinicians in making informed treatment decisions by evaluating the effectiveness, recovery, and risks of each intervention. The study utilised several tools, including the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QoL), European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L), and SF-36 scale, to measure health-related QoL and symptom severity before and after the treatments. The principal findings of the study showed no statistically significant difference in the improvement of health-related QoL between UAE and myomectomy, as measured by the UFS-QoL scale. However, UAE was associated with a significant reduction in symptom severity compared to myomectomy. In contrast, when using the EQ-5D-3L scale, both myomectomy and hysterectomy led to significant improvements in QoL compared to UAE. The SF-36 scale revealed that while UAE was less effective in improving mental health, it did not differ significantly from myomectomy or hysterectomy in terms of physical health improvement. Regarding complications, UAE showed a significantly lower risk of haemorrhage, with a reduced likelihood of postembolisation syndrome, but it had a higher incidence of vaginal discharge compared to the other treatments. Myomectomy and hysterectomy were associated with risks of urinary retention and infection, although these complications were less frequent. The results from this study highlight the need for careful consideration when evaluating and reflecting on current treatment options for UF, as well as the diverse outcomes and complications associated with each approach. Uterine fibroids treatments are linked to a range of complications that vary depending on the intervention type, and these must be carefully balanced against the benefits of symptom relief and treatment efficacy. UAE was found to be associated with adverse events such as menstrual irregularities, menopausal symptoms, vaginal discharge and the potential need for additional interventions to manage persistent symptoms( 7 , 16 – 18 ). The aetiology is predominantly linked to tissue necrosis resulting from the embolization-induced ischemia, leading to expulsion of necrotic material through the vaginal canal. However, other factors, such as inflammatory responses and secondary infections, have also been implicated in some cases. The variability in reported incidence rates and lack of consensus on standardized diagnostic criteria for pathological discharge post-UAE underscore the need for further high-quality research. Longitudinal studies evaluating the risk factors, preventive strategies, and outcomes of different management approaches are particularly warranted to enhance the evidence base. While UAE provides a minimally invasive option that preserves the uterus, it does not offer a definitive solution, as fibroids may recur or remain symptomatic( 19 ). Hysterectomies, while offering a permanent resolution by completely removing fibroid-affected tissue, comes with a longer recovery period and increased risks related to surgery and anaesthesia. Myomectomy offers the benefit of preserving the uterus, making it a favourable option for women desiring fertility preservation( 20 ). However, it carries its own set of complications, including postoperative pain and the potential for reintervention if fibroids recur, as seen in the results where UAE showed a reduced ability to address severe symptoms in comparison to myomectomy( 21 , 22 ). The data indicates that UAE is less likely to result in postoperative haemorrhage compared to hysterectomy or myomectomy. However, the lack of statistical significance and the relatively wide confidence interval highlight the need for caution in drawing definitive conclusions. Pharmacological treatments, such as gonadotropin-releasing hormone (GnRH) analogues, provide symptom relief and can reduce fibroid size prior to surgery( 23 , 24 ). However, their long-term use is associated with menopausal symptoms, including hot flashes, mood swings, vaginal dryness, and an increased risk of osteoporosis. These medications induce a hypoestrogenic or hypoandrogenic state, which may negatively affect a woman's quality of life( 25 , 26 ). To mitigate these effects, hormone replacement therapy ( 27 ) is often prescribed in conjunction with GnRH analogues, but this introduces additional considerations and potential risks. Long-term use of GnRH analogues requires careful monitoring due to risks such as bone density reduction and cardiovascular issues. The prohibitive cost of these therapies presents a significant barrier in low- and middle-income countries (LMICs), where financial constraints may limit access to treatment. This disparity highlights the inequities in global healthcare, as patients in LMICs may be unable to afford these medications, leading to missed opportunities for symptom management and treatment. Preventing fibroids recurrence remains challenging due to the genetic and hormonal influences on fibroid growth. While complete prevention is not possible, several strategies may help reduce recurrence. Lifestyle and dietary adjustments, such as consuming diets rich in fruits, vegetables, and whole grains, may support hormonal balance and reduce the risk of recurrence. Avoiding high-fat, processed foods, especially red meats, is recommended due to their association with increased fibroid risk. Regular physical activity can help with weight management, potentially contributing to hormonal equilibrium. Additionally, hormonal therapies like low-dose oral contraceptives or GnRH analogues can be used to manage oestrogen levels post-treatment, but their use requires careful monitoring due to potential side effects( 28 ). Emerging treatments such as selective progesterone receptor modulators like ulipristal acetate and supplements like vitamin D or anti-inflammatory agents, such as curcumin, show promise, though further research is needed to confirm their effectiveness( 29 ). Clinical Implications: This review has a number of clinical implications. First, the findings of this systematic review shows the importance of considering treatment options based on individual patient factors. For women with severe symptoms of uterine fibroids who do not respond to medical therapy, UAE offers a less invasive approach with fewer risks of haemorrhage and quicker recovery. However, myomectomy and hysterectomy may offer better overall improvements in quality of life, especially mental health, and are more effective in reducing symptoms in the long term. Second, healthcare providers should discuss the potential benefits and risks of each treatment option with patients, particularly considering the long-term implications for mental health and symptom management. Thirdly, clinicians should be aware of specific complications linked to each treatment, such as postembolisation syndrome following UAE, and monitor patients accordingly. Research Implications: Regarding research implications of the present review, the analysis indicated a potential publication bias in studies on postembolisation syndrome, suggesting that more research is needed to explore this complication and its long-term effects. The study emphasises the need for further research focusing on long-term outcomes of each treatment modality for uterine fibroids, particularly in terms of sustained symptom relief and QoL improvements over several years. Additionally, the variation in tools used to assess QoL (UFS-QoL, EQ-5D-3L, SF-36) calls for more standardised metrics to improve comparability between studies and provide clearer clinical guidelines. Strengths and Limitations The study sample primarily consisted of research from high-income countries (HICs), which limits the applicability of the findings to women in LMICs, where healthcare access and treatment options are more limited. This imbalance in global health research reflects systemic inequities in healthcare funding, infrastructure, and access to innovative treatments, which disproportionately impact women's health in LMICs. Patients in these regions may rely on alternative or more invasive treatments due to a lack of access to advanced medical interventions, further exacerbating health disparities. This gap in research also underscores the need for more region-specific studies to develop culturally sensitive and effective treatments tailored to the unique needs of women in LMICs. Conclusion Although UAE, myomectomy, and hysterectomy each have their advantages and risks, myomectomy and hysterectomy tend to offer better long-term improvements in quality of life. However, UAE can be a good alternative for women seeking less invasive options with fewer risks of haemorrhage. Clinicians should offer a personalised treatment plan, considering patient preferences, symptom severity, and the potential risks and benefits of each procedure. There is a need for further large-scale studies to compare the long-term outcomes of these treatments, including the effects on fertility, recurrence of fibroids, and mental health. Research should also focus on minimising complications, particularly postembolisation syndrome and vaginal discharge in UAE patients. The lack of representation in global fibroids research from LMICs limits healthcare professionals' ability to make evidence-based decisions and implement effective interventions. It is crucial to foster global collaboration in research to ensure equitable representation and address the unmet needs of women worldwide. Such efforts can help bridge the gap between developed and developing nations, ensuring that all women, regardless of their geographic location, have access to the most effective and appropriate treatments for uterine fibroids. By prioritising these areas, healthcare systems can improve outcomes and ensure that women across all income settings have access to the care they need. Declarations Conflicts of interest: All authors report no conflict of interest. The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health and Social Care or the Academic institutions. Ethics approval: Not applicable Consent to participate: No participants were involved within this paper Consent for publication: All authors consented to publish this manuscript Funding: Not funded Author contributions: GD developed the ELEMI program and embedded the MARIE project. EB and GD conceptualised the methodology. First draft was written by EB, ES and GD and furthered by all other authors. EB completed data collection. JS, JQS, SE, EB and GD conducted the analysis. VP and TM completed quality and bias checks. All authors critically appraised, reviewed and commented on all versions of the manuscript. All authors read and approved the final manuscript. Acknowledgements: Associate Professor Linda Lefievre Availability of data and material: The data shared within this manuscript is publicly available. Code availability: Not applicable References Don EE, Mijatovic V, van Eekelen R, Huirne JAF. The effect of myomectomy on reproductive outcomes in patients with uterine fibroids: A retrospective cohort study. Reprod Biomed Online. 2022;45(5):970-8. Stewart EA, Lukes AS, Venturella R, Li Y, Hunsche E, Wagman RB, et al. Quality of life with relugolix combination therapy for uterine fibroids: LIBERTY randomized trials. Am J Obstet Gynecol. 2023;228(3):320.e1-.e11. 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Int J Gynaecol Obstet. 2011;112(2):126-30. Donnez J, Tatarchuk TF, Bouchard P, Puscasiu L, Zakharenko NF, Ivanova T, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012;366(5):409-20. Table Table 1 is available in the Supplementary Files section. Additional Declarations The authors declare no competing interests. Supplementary Files RoBofUterineFibroidsManagement.docx Table1.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6073815","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":418693285,"identity":"3e9fc67b-08c7-4ed7-8e5b-6261eeed7951","order_by":0,"name":"Elena Bedggood","email":"","orcid":"","institution":"University of Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Bedggood","suffix":""},{"id":418693286,"identity":"f101e240-e0b0-40c7-9662-da1d11748b3c","order_by":1,"name":"Sun Jie","email":"","orcid":"","institution":"Southern University of Science and 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10:25:22","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":60158,"visible":true,"origin":"","legend":"","description":"","filename":"RoBofUterineFibroidsManagement.docx","url":"https://assets-eu.researchsquare.com/files/rs-6073815/v1/ba14eb42d5af3fd89fcfffa5.docx"},{"id":77313422,"identity":"2bdf6a38-9656-4040-8e48-0cab72f02282","added_by":"auto","created_at":"2025-02-27 10:17:22","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":27990,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6073815/v1/c05b0d48522a91b4022fb09b.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eEvaluating Treatment Options for Symptomatic Uterine Fibroids: A Systematic Review and Meta-analysis of Effectiveness, Recovery, and Long-Term Outcomes (MARIE WP1)\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eUterine fibroids (UF), also known as uterine leiomyomas, are common benign tumours of the uterus that disproportionately affect women of reproductive age. While non-malignant, fibroids can significantly impair quality of life, causing symptoms such as heavy menstrual bleeding, pelvic pain, and infertility. The prevalence of UF increases with age, affecting approximately 40% of premenopausal women and nearly 50% of women by the age of 50 years(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). While most fibroids are asymptomatic, around 25% of women who develop fibroids experience symptoms severe enough to require treatment(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). These symptoms, including menorrhagia, pelvic pressure, and iron deficiency anaemia, can significantly impact physical and emotional well-being(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe prevalence of uterine fibroids is particularly high among women of African descent, with studies indicating that 60\u0026ndash;80% of African American women will develop fibroids by age 50, compared to 30\u0026ndash;40% of White women(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Black women also face a greater risk of requiring surgical intervention, with a 2.4-fold increased likelihood of undergoing a hysterectomy and a 6.8-fold higher chance of requiring multiple myomectomies(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). These racial disparities reflect both biological factors and disparities in healthcare access, as women in lower-income regions or with limited access to care face greater challenges in managing the condition(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn high-income countries, fibroid treatment benefits from advanced healthcare systems, where access to diagnostic tools such as high-resolution ultrasound and magnetic resonance imaging (MRI) enables early detection and personalized care. Treatment options range from pharmacological therapies, such as hormonal treatments (gonadotropin-releasing hormone (GnRH) agonists, oral contraceptives, and progesterone-releasing intrauterine devices (IUDs), to minimally invasive procedures like uterine artery embolization (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), MRI-guided focused ultrasound, and robotic-assisted myomectomy(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). For definitive management, hysterectomy remains a common option, with robotic and laparoscopic approaches offering quicker recovery times and fewer complications. These treatments are supported by comprehensive insurance coverage and a well-developed specialist workforce, ensuring women have access to timely and effective care(\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, in low- and middle-income countries (LMICs), fibroids management is constrained by limited healthcare resources, systemic challenges, and geographical disparities. Diagnostic capabilities are often limited to basic ultrasound, with advanced imaging modalities largely unavailable in rural or underserved regions. Medical treatments, including hormonal therapies, are hindered by inconsistent access to affordable medications and poor pharmaceutical supply chains. Advanced treatments like UAE and minimally invasive surgery are mostly confined to urban centres or private healthcare facilities, leaving many women with limited access to these options (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In such settings, surgical interventions often include open myomectomy or hysterectomy, which may carry higher risks due to inadequate perioperative care(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCultural factors and financial constraints in LMICs can also lead women to seek traditional remedies or community-based care. While these approaches may be culturally significant, they often lack the evidence base and effectiveness of modern medical treatments(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This reliance on traditional practices further highlights the healthcare disparities between resource-rich and resource-constrained settings, where access to optimal care for fibroids remains limited(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe global management of fibroids reflects stark disparities between developed countries and LMICs. In high-income nations, women have access to a range of advanced diagnostic and treatment options, ensuring timely and effective management. In contrast, women in LMICs often face significant barriers to care, with fewer treatment options and limited access to healthcare infrastructure. This article compares the impact of uterine artery embolisation, myomectomy, and hysterectomy on women\u0026rsquo;s quality of life, assess changes in symptom severity, and examine the occurrence of complications such as haemorrhage, urinary retention, infection, and vaginal discharge following each treatment of uterine fibroids. The study also examines the prevalence and treatment landscape of fibroids worldwide, highlighting the significant disparities in access to care, and proposes strategies to bridge these gaps. By fostering equitable healthcare solutions and increasing access to uterine-preserving treatments, we can improve outcomes for women with fibroids, regardless of their geographic location.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA systematic methodology was developed and published in PROSPERO (CRD42022346251) to explore outcomes based on surgical treatments among patients with uterine fibroids.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eSearch strategy and Screening\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA search was conducted using PubMed, Web of Science and Science Direct. The key terms used were \u003cem\u003euterine fibroids,\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eEligibility criteria and study selection\u0026nbsp;\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll studies that were included into the study sample comprised of quantifiable measures and outcomes linked to uterine fibroids. All randomised clinical trials, non-randomised clinical trials, mixed-methods, and epidemiology studies that reported on uterine fibroids that were peer reviewed and published in English from the 30\u003csup\u003eth\u003c/sup\u003e of April 1980 to the 30\u003csup\u003eth\u003c/sup\u003e of September 2024 were included to the data sample.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eData extraction and analysis\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe data extraction process is demonstrated in the PRISMA diagram (Figure 1). All quantifiable measures of mean, median, mode, standard deviation, were extracted from all the studies. The data was refined using an independent reviewer and pooled using Endnote and Microsoft Excel by 2 reviewers (EB and JS). Finally, 42 articles were assessed for eligibility (Table 01). \u0026nbsp;Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were reported.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eStatistical analysis\u0026nbsp;\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe meta-analysis combined myomectomy and hysterectomy into one group for comparison with the UAE group. All meta-analyses used either random-effects models or fixed-effects models based on the heterogeneity between studies. Statistical heterogeneity among studies was assessed using the Cochrane Q test and the I\u0026sup2; statistic. Potential publication bias was evaluated using funnel plots and Egger\u0026apos;s test. Data analysis was performed using the meta package (version 8.0-1) and the metafor package (version 4.6-0) in R software (version 4.4.2).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eRisk of bias\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe systematically identified sample was critically appraised by 1 independent reviewer and assessed for methodological quality and rigor using the Newcastle-Ottawa Scale (NOS). Studies were rated as good, fair, or poor based on the allocation of stars in the following domains:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eGood quality: 3\u0026ndash;4 stars in selection, 1\u0026ndash;2 stars in comparability, and 2\u0026ndash;3 stars in outcomes.\u003c/li\u003e\n \u003cli\u003eFair quality: 2 stars in selection, 1\u0026ndash;2 stars in comparability, and 2\u0026ndash;3 stars in outcomes.\u003c/li\u003e\n \u003cli\u003ePoor quality: 0\u0026ndash;1 star(s) in selection, 0 stars in comparability, and 0\u0026ndash;1 star(s) in outcomes.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eQuality of life\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eUterine fibroids can significantly impair quality of life. For women who do not respond to medical treatment, there are typically three treatment options: uterine artery embolization, myomectomy, and hysterectomy. We will conduct a meta-analysis to compare the impact of uterine artery embolization with myomectomy and hysterectomy on women\u0026rsquo;s quality of life.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eThe Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL)\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) is a scale specifically designed to assess the quality of life in patients with uterine fibroids. This scale is divided into two main sections: health-related quality of life and symptom severity. In the following analysis, we will compare the changes in patients\u0026rsquo; quality of life before and after undergoing uterine artery embolization and myomectomy.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eUFS-QOL health-related quality-of-life\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA total of three studies involving 520 patients reported changes in health-related quality of life (HRQoL) as measured by the UFS-QoL scale before and after undergoing uterine artery embolization and myomectomy. The pooled mean difference was -6.99 (95% CI = [-16.49, 2.51], heterogeneity I\u0026sup2; = 71.9%, P = 0.03; Figure 2)(7, 16, 17). According to the 95% confidence interval, there is no statistically significant difference in the impact on patients\u0026rsquo; quality of life between uterine artery embolization and myomectomy\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eUFS-QOL symptom severity\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe pooled mean difference for the UFS-QoL symptom severity was 4.85 (95% CI = [0.50, 9.21], heterogeneity I\u0026sup2; = 0.0%, P = 0.52; Figure 3)(7, 16, 17). This indicates that while there is no difference between the two procedures in improving patients\u0026rsquo; quality of life, myomectomy significantly reduces symptom severity compared to uterine artery embolization.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eEuropean Quality of Life 5 Dimensions 3 Level Version(EQ-5D-3L)\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSome studies have also used the EQ-5D-3L scale to measure patients\u0026rsquo; quality of life. The following analysis compares the changes in EQ-5D-3L quality of life scores before and after treatment in patients undergoing uterine artery embolization versus those undergoing myomectomy or hysterectomy. According to reports from two studies involving a total of 353 patients, the pooled mean difference was -7.36 (95% CI = [-10.72, -4.00], heterogeneity I\u0026sup2; = 0.0%, P = 0.78; Figure 4)(16, 18). This indicates that, when using the EQ-5D-3L scale to measure quality of life, the myomectomy or hysterectomy group showed a statistically significant improvement in quality of life compared to the uterine artery embolization (7) group.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eThe 36-Item Short Form Health Survey (SF-36)\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSome studies have used the SF-36 scale to compare the mental and physical health status of patients before and after undergoing uterine artery embolization versus myomectomy or hysterectomy. According to reports from two studies involving a total of 313 patients, the pooled mean difference for mental health was -1.58 (95% CI = [-2.29, 0.86], heterogeneity I\u0026sup2; = 0.0%, P =0.38; Figure 4), and the pooled mean difference for physical health was \u0026ndash;1.45 (95% CI = [-4.20, 1.30], heterogeneity I\u0026sup2; = 92.8%, P \u0026lt;0.005; Figure 5)(12, 16, 18). These results indicate that the ability of the uterine artery embolization group to improve patients\u0026rsquo; mental health is significantly lower than that of the myomectomy or hysterectomy group. However, there is no difference in the impact on patients\u0026rsquo; physical health between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eComplications\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePatients undergoing uterine artery embolization, myomectomy, and hysterectomy may experience different complications, such as postembolization syndrome, haemorrhage, urinary retention, infection, and vaginal discharge.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003ePost-embolization syndrome\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePostembolization syndrome is a common complication following uterine artery embolization (7). We analysed the incidence of postembolization syndrome in 431 patients across four studies(7, 16-18). The pooled incidence rate was 7% (95% CI = [2%, 21%], heterogeneity I\u0026sup2; = 90.7%, P \u0026lt; 0.005; Figure 7).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eHaemorrhage\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHaemorrhage is common following UAE, myomectomy, and hysterectomy. We compared the risk of postoperative bleeding between the UAE group and the group undergoing hysterectomy or myomectomy. The pooled odds ratio (OR) was 0.16 (95% CI = [5%, 51%], heterogeneity I\u0026sup2; = 0%, P = 0.39; Figure 8), indicating that UAE is 84% less likely to result in haemorrhage compared to hysterectomy or myomectomy(7, 16, 18).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eUrinary retention\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eUrinary retention is a complication following hysterectomy and myomectomy. In two studies involving 111 patients who underwent hysterectomy or myomectomy, the pooled incidence rate of urinary retention was 2% (95% CI = [0%, 7%], heterogeneity I\u0026sup2; = 0%, P = 0.91; Figure 9)(7, 18). While the absence of heterogeneity (I\u0026sup2; = 0%) and a P-value of 0.91 demonstrate consistency between the two studies, the low statistical power stemming from the limited number of included studies may obscure true variability. Additionally, the P-value primarily confirms statistical consistency rather than providing clinically meaningful insights.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eInfection\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePatients undergoing hysterectomy and myomectomy may experience infections. Based on reports from four studies involving 311 patients, the pooled incidence rate of infections was 9% (95% CI = [6%, 13%], heterogeneity I\u0026sup2; = 34.8%, P = 0.20; Figure 10)(7, 16-18).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eVaginal discharge\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eChanges in vaginal discharge are common after UAE. Results from two studies involving 255 patients showed a pooled incidence rate of vaginal discharge of 4% (95% CI = [1%, 20%], heterogeneity I\u0026sup2; = 83%, P = 0.02; Figure 11)(7, 18).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003ePublication\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e\u003cstrong\u003e\u0026nbsp;bias\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe following funnel plots illustrate the publication bias for all outcomes. The funnel plots for UFS-QoL health-related quality-of-life score (Egger\u0026apos;s test p-value = 0.3202, Figure 12), UFS-QoL symptom severity score (Egger\u0026apos;s test p-value = 0.9254, Figure 13), Haemorrhage (Egger\u0026apos;s test p-value = 0.1285, Figure 18), and Infection (Egger\u0026apos;s test p-value = 0.3967, Figure 20) are symmetrical, indicating no publication bias. However, the funnel plot for Post-embolization syndrome (Egger\u0026apos;s test p-value \u0026lt; 0.001, Figure 17, 18, 19, 20 and 21) is asymmetrical, indicating the presence of publication bias.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe motivation for this systematic review is to provide a comprehensive comparison of the available treatment options for symptomatic uterine fibroids\u0026mdash;specifically uterine artery embolization (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), myomectomy, and hysterectomy\u0026mdash;in terms of their impact on women\u0026rsquo;s quality of life, symptom relief, and associated complications. Given the significant impact of uterine fibroids on women\u0026rsquo;s well-being, this review aims to guide clinicians in making informed treatment decisions by evaluating the effectiveness, recovery, and risks of each intervention. The study utilised several tools, including the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QoL), European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L), and SF-36 scale, to measure health-related QoL and symptom severity before and after the treatments. The principal findings of the study showed no statistically significant difference in the improvement of health-related QoL between UAE and myomectomy, as measured by the UFS-QoL scale. However, UAE was associated with a significant reduction in symptom severity compared to myomectomy. In contrast, when using the EQ-5D-3L scale, both myomectomy and hysterectomy led to significant improvements in QoL compared to UAE. The SF-36 scale revealed that while UAE was less effective in improving mental health, it did not differ significantly from myomectomy or hysterectomy in terms of physical health improvement. Regarding complications, UAE showed a significantly lower risk of haemorrhage, with a reduced likelihood of postembolisation syndrome, but it had a higher incidence of vaginal discharge compared to the other treatments. Myomectomy and hysterectomy were associated with risks of urinary retention and infection, although these complications were less frequent.\u003c/p\u003e \u003cp\u003eThe results from this study highlight the need for careful consideration when evaluating and reflecting on current treatment options for UF, as well as the diverse outcomes and complications associated with each approach. Uterine fibroids treatments are linked to a range of complications that vary depending on the intervention type, and these must be carefully balanced against the benefits of symptom relief and treatment efficacy. UAE was found to be associated with adverse events such as menstrual irregularities, menopausal symptoms, vaginal discharge and the potential need for additional interventions to manage persistent symptoms(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The aetiology is predominantly linked to tissue necrosis resulting from the embolization-induced ischemia, leading to expulsion of necrotic material through the vaginal canal. However, other factors, such as inflammatory responses and secondary infections, have also been implicated in some cases. The variability in reported incidence rates and lack of consensus on standardized diagnostic criteria for pathological discharge post-UAE underscore the need for further high-quality research. Longitudinal studies evaluating the risk factors, preventive strategies, and outcomes of different management approaches are particularly warranted to enhance the evidence base. While UAE provides a minimally invasive option that preserves the uterus, it does not offer a definitive solution, as fibroids may recur or remain symptomatic(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHysterectomies, while offering a permanent resolution by completely removing fibroid-affected tissue, comes with a longer recovery period and increased risks related to surgery and anaesthesia. Myomectomy offers the benefit of preserving the uterus, making it a favourable option for women desiring fertility preservation(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). However, it carries its own set of complications, including postoperative pain and the potential for reintervention if fibroids recur, as seen in the results where UAE showed a reduced ability to address severe symptoms in comparison to myomectomy(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). The data indicates that UAE is less likely to result in postoperative haemorrhage compared to hysterectomy or myomectomy. However, the lack of statistical significance and the relatively wide confidence interval highlight the need for caution in drawing definitive conclusions.\u003c/p\u003e \u003cp\u003ePharmacological treatments, such as gonadotropin-releasing hormone (GnRH) analogues, provide symptom relief and can reduce fibroid size prior to surgery(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). However, their long-term use is associated with menopausal symptoms, including hot flashes, mood swings, vaginal dryness, and an increased risk of osteoporosis. These medications induce a hypoestrogenic or hypoandrogenic state, which may negatively affect a woman's quality of life(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). To mitigate these effects, hormone replacement therapy (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) is often prescribed in conjunction with GnRH analogues, but this introduces additional considerations and potential risks. Long-term use of GnRH analogues requires careful monitoring due to risks such as bone density reduction and cardiovascular issues. The prohibitive cost of these therapies presents a significant barrier in low- and middle-income countries (LMICs), where financial constraints may limit access to treatment. This disparity highlights the inequities in global healthcare, as patients in LMICs may be unable to afford these medications, leading to missed opportunities for symptom management and treatment.\u003c/p\u003e \u003cp\u003ePreventing fibroids recurrence remains challenging due to the genetic and hormonal influences on fibroid growth. While complete prevention is not possible, several strategies may help reduce recurrence. Lifestyle and dietary adjustments, such as consuming diets rich in fruits, vegetables, and whole grains, may support hormonal balance and reduce the risk of recurrence. Avoiding high-fat, processed foods, especially red meats, is recommended due to their association with increased fibroid risk. Regular physical activity can help with weight management, potentially contributing to hormonal equilibrium. Additionally, hormonal therapies like low-dose oral contraceptives or GnRH analogues can be used to manage oestrogen levels post-treatment, but their use requires careful monitoring due to potential side effects(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Emerging treatments such as selective progesterone receptor modulators like ulipristal acetate and supplements like vitamin D or anti-inflammatory agents, such as curcumin, show promise, though further research is needed to confirm their effectiveness(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section2\"\u003e \u003ch2\u003eClinical Implications:\u003c/h2\u003e \u003cp\u003eThis review has a number of clinical implications. First, the findings of this systematic review shows the importance of considering treatment options based on individual patient factors. For women with severe symptoms of uterine fibroids who do not respond to medical therapy, UAE offers a less invasive approach with fewer risks of haemorrhage and quicker recovery. However, myomectomy and hysterectomy may offer better overall improvements in quality of life, especially mental health, and are more effective in reducing symptoms in the long term. Second, healthcare providers should discuss the potential benefits and risks of each treatment option with patients, particularly considering the long-term implications for mental health and symptom management. Thirdly, clinicians should be aware of specific complications linked to each treatment, such as postembolisation syndrome following UAE, and monitor patients accordingly.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eResearch Implications:\u003c/h2\u003e \u003cp\u003eRegarding research implications of the present review, the analysis indicated a potential publication bias in studies on postembolisation syndrome, suggesting that more research is needed to explore this complication and its long-term effects. The study emphasises the need for further research focusing on long-term outcomes of each treatment modality for uterine fibroids, particularly in terms of sustained symptom relief and QoL improvements over several years. Additionally, the variation in tools used to assess QoL (UFS-QoL, EQ-5D-3L, SF-36) calls for more standardised metrics to improve comparability between studies and provide clearer clinical guidelines.\u003c/p\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003eStrengths and Limitations\u003c/h2\u003e \u003cp\u003eThe study sample primarily consisted of research from high-income countries (HICs), which limits the applicability of the findings to women in LMICs, where healthcare access and treatment options are more limited. This imbalance in global health research reflects systemic inequities in healthcare funding, infrastructure, and access to innovative treatments, which disproportionately impact women's health in LMICs. Patients in these regions may rely on alternative or more invasive treatments due to a lack of access to advanced medical interventions, further exacerbating health disparities. This gap in research also underscores the need for more region-specific studies to develop culturally sensitive and effective treatments tailored to the unique needs of women in LMICs.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAlthough UAE, myomectomy, and hysterectomy each have their advantages and risks, myomectomy and hysterectomy tend to offer better long-term improvements in quality of life. However, UAE can be a good alternative for women seeking less invasive options with fewer risks of haemorrhage. Clinicians should offer a personalised treatment plan, considering patient preferences, symptom severity, and the potential risks and benefits of each procedure. There is a need for further large-scale studies to compare the long-term outcomes of these treatments, including the effects on fertility, recurrence of fibroids, and mental health. Research should also focus on minimising complications, particularly postembolisation syndrome and vaginal discharge in UAE patients. The lack of representation in global fibroids research from LMICs limits healthcare professionals' ability to make evidence-based decisions and implement effective interventions. It is crucial to foster global collaboration in research to ensure equitable representation and address the unmet needs of women worldwide. Such efforts can help bridge the gap between developed and developing nations, ensuring that all women, regardless of their geographic location, have access to the most effective and appropriate treatments for uterine fibroids. By prioritising these areas, healthcare systems can improve outcomes and ensure that women across all income settings have access to the care they need.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflicts of interest:\u003c/h2\u003e\n\u003cp\u003eAll authors report no conflict of interest. The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health and Social Care or the Academic institutions.\u003c/p\u003e\n\u003ch2\u003eEthics approval:\u003c/h2\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch2\u003eConsent to participate:\u003c/h2\u003e\n\u003cp\u003eNo participants were involved within this paper\u003c/p\u003e\n\u003ch2\u003eConsent for publication:\u003c/h2\u003e\n\u003cp\u003eAll authors consented to publish this manuscript\u003c/p\u003e\n\u003ch2\u003eFunding:\u003c/h2\u003e\n\u003cp\u003eNot funded\u003c/p\u003e\n\u003ch2\u003eAuthor contributions:\u003c/h2\u003e\n\u003cp\u003eGD developed the ELEMI program and embedded the MARIE project. EB and GD conceptualised the methodology. First draft was written by EB, ES and GD and furthered by all other authors. EB completed data collection. JS, JQS, SE, EB and GD conducted the analysis. VP and TM completed quality and bias checks. All authors critically appraised, reviewed and commented on all versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements:\u003c/h2\u003e\n\u003cp\u003eAssociate Professor Linda Lefievre\u003c/p\u003e\n\u003ch2\u003eAvailability of data and material:\u003c/h2\u003e\n\u003cp\u003eThe data shared within this manuscript is publicly available.\u003c/p\u003e\n\u003ch2\u003eCode availability:\u003c/h2\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDon EE, Mijatovic V, van Eekelen R, Huirne JAF. The effect of myomectomy on reproductive outcomes in patients with uterine fibroids: A retrospective cohort study. Reprod Biomed Online. 2022;45(5):970-8.\u003c/li\u003e\n\u003cli\u003eStewart EA, Lukes AS, Venturella R, Li Y, Hunsche E, Wagman RB, et al. Quality of life with relugolix combination therapy for uterine fibroids: LIBERTY randomized trials. Am J Obstet Gynecol. 2023;228(3):320.e1-.e11.\u003c/li\u003e\n\u003cli\u003eRuuskanen A, Hippel\u0026auml;inen M, Sipola P, Manninen H. Uterine artery embolisation versus hysterectomy for leiomyomas: primary and 2-year follow-up results of a randomised prospective clinical trial. Eur Radiol. 2010;20(10):2524-32.\u003c/li\u003e\n\u003cli\u003eStewart EA, Al-Hendy A, Lukes AS, Madueke-Laveaux OS, Zhu E, Proehl S, et al. Relugolix combination therapy in Black/African American women with symptomatic uterine fibroids: LIBERTY Long-Term Extension study. Am J Obstet Gynecol. 2024;230(2):237.e1-.e11.\u003c/li\u003e\n\u003cli\u003eBhave Chittawar P, Franik S, Pouwer AW, Farquhar C. Minimally invasive surgical techniques versus open myomectomy for uterine fibroids. Cochrane Database Syst Rev. 2014;2014(10):CD004638.\u003c/li\u003e\n\u003cli\u003eBerman JM, Bradley L, Hawkins SM, Levy B. Uterine Fibroids in Black Women: A Race-Stratified Subgroup Analysis of Treatment Outcomes After Laparoscopic Radiofrequency Ablation. J Womens Health (Larchmt). 2022;31(4):593-9.\u003c/li\u003e\n\u003cli\u003eGoodwin SC, Bradley LD, Lipman JC, Stewart EA, Nosher JL, Sterling KM, et al. Uterine artery embolization versus myomectomy: a multicenter comparative study. Fertil Steril. 2006;85(1):14-21.\u003c/li\u003e\n\u003cli\u003eMaleux G, Michielsen K, Timmerman D, Poppe W, Heye S, Vaninbroukx J, et al. 2D versus 3D roadmap for uterine artery catheterization: impact on several angiographic parameters. Acta Radiol. 2014;55(1):62-70.\u003c/li\u003e\n\u003cli\u003eJun F, Yamin L, Xinli X, Zhe L, Min Z, Bo Z, et al. Uterine artery embolization versus surgery for symptomatic uterine fibroids: a randomized controlled trial and a meta-analysis of the literature. Arch Gynecol Obstet. 2012;285(5):1407-13.\u003c/li\u003e\n\u003cli\u003eLaughlin-Tommaso S, Barnard EP, AbdElmagied AM, Vaughan LE, Weaver AL, Hesley GK, et al. FIRSTT study: randomized controlled trial of uterine artery embolization vs focused ultrasound surgery. Am J Obstet Gynecol. 2019;220(2):174.e1-.e13.\u003c/li\u003e\n\u003cli\u003eHuyck KL, Panhuysen CI, Cuenco KT, Zhang J, Goldhammer H, Jones ES, et al. The impact of race as a risk factor for symptom severity and age at diagnosis of uterine leiomyomata among affected sisters. Am J Obstet Gynecol. 2008;198(2):168.e1-9.\u003c/li\u003e\n\u003cli\u003ede Bruijn AM, Ankum WM, Reekers JA, Birnie E, van der Kooij SM, Volkers NA, et al. Uterine artery embolization vs hysterectomy in the treatment of symptomatic uterine fibroids: 10-year outcomes from the randomized EMMY trial. Am J Obstet Gynecol. 2016;215(6):745.e1-.e12.\u003c/li\u003e\n\u003cli\u003eHehenkamp WJ, Volkers NA, Bartholomeus W, de Blok S, Birnie E, Reekers JA, et al. Sexuality and body image after uterine artery embolization and hysterectomy in the treatment of uterine fibroids: a randomized comparison. Cardiovasc Intervent Radiol. 2007;30(5):866-75.\u003c/li\u003e\n\u003cli\u003eShen TC, Yang CY, Huang YJ, Lin CL, Sung FC. Risk of depression in patients with uterine leiomyoma: A nationwide population-based cohort study. J Affect Disord. 2017;213:126-30.\u003c/li\u003e\n\u003cli\u003eSchlaff WD, Ackerman RT, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, et al. Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids. N Engl J Med. 2020;382(4):328-40.\u003c/li\u003e\n\u003cli\u003eManyonda I, Belli AM, Lumsden MA, Moss J, McKinnon W, Middleton LJ, et al. Uterine-Artery Embolization or Myomectomy for Uterine Fibroids. N Engl J Med. 2020;383(5):440-51.\u003c/li\u003e\n\u003cli\u003eManyonda IT, Bratby M, Horst JS, Banu N, Gorti M, Belli AM. Uterine artery embolization versus myomectomy: impact on quality of life--results of the FUME (Fibroids of the Uterus: Myomectomy versus Embolization) Trial. Cardiovasc Intervent Radiol. 2012;35(3):530-6.\u003c/li\u003e\n\u003cli\u003eEdwards RD, Moss JG, Lumsden MA, Wu O, Murray LS, Twaddle S, et al. Uterine-artery embolization versus surgery for symptomatic uterine fibroids. N Engl J Med. 2007;356(4):360-70.\u003c/li\u003e\n\u003cli\u003eDaniels J, Middleton LJ, Cheed V, McKinnon W, Rana D, Sirkeci F, et al. Uterine artery embolisation versus myomectomy for premenopausal women with uterine fibroids wishing to avoid hysterectomy: the FEMME RCT. Health Technol Assess. 2022;26(22):1-74.\u003c/li\u003e\n\u003cli\u003ePanagiotopoulou N, Nethra S, Karavolos S, Ahmad G, Karabis A, Burls A. Uterine-sparing minimally invasive interventions in women with uterine fibroids: a systematic review and indirect treatment comparison meta-analysis. Acta Obstet Gynecol Scand. 2014;93(9):858-67.\u003c/li\u003e\n\u003cli\u003eMoss JG, Cooper KG, Khaund A, Murray LS, Murray GD, Wu O, et al. Randomised comparison of uterine artery embolisation (UAE) with surgical treatment in patients with symptomatic uterine fibroids (REST trial): 5-year results. BJOG. 2011;118(8):936-44.\u003c/li\u003e\n\u003cli\u003eAbdElmagied AM, Vaughan LE, Weaver AL, Laughlin-Tommaso SK, Hesley GK, Woodrum DA, et al. Fibroid interventions: reducing symptoms today and tomorrow: extending generalizability by using a comprehensive cohort design with a randomized controlled trial. Am J Obstet Gynecol. 2016;215(3):338.e1-.e18.\u003c/li\u003e\n\u003cli\u003eLethaby A, Vollenhoven B, Sowter M. Efficacy of pre-operative gonadotrophin hormone releasing analogues for women with uterine fibroids undergoing hysterectomy or myomectomy: a systematic review. BJOG. 2002;109(10):1097-108.\u003c/li\u003e\n\u003cli\u003eMara M, Fucikova Z, Maskova J, Kuzel D, Haakova L. Uterine fibroid embolization versus myomectomy in women wishing to preserve fertility: preliminary results of a randomized controlled trial. Eur J Obstet Gynecol Reprod Biol. 2006;126(2):226-33.\u003c/li\u003e\n\u003cli\u003eAl-Hendy A, Lukes AS, Poindexter AN, Venturella R, Villarroel C, Critchley HOD, et al. Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy. N Engl J Med. 2021;384(7):630-42.\u003c/li\u003e\n\u003cli\u003ePritts EA, Parker WH, Olive DL. Fibroids and infertility: an updated systematic review of the evidence. Fertil Steril. 2009;91(4):1215-23.\u003c/li\u003e\n\u003cli\u003eMarlatt KL, Pitynski‐Miller DR, Gavin KM, Moreau KL, Melanson EL, Santoro N, et al. Body composition and cardiometabolic health across the menopause transition. Obesity. 2022;30(1):14-27.\u003c/li\u003e\n\u003cli\u003eSayed GH, Zakherah MS, El-Nashar SA, Shaaban MM. A randomized clinical trial of a levonorgestrel-releasing intrauterine system and a low-dose combined oral contraceptive for fibroid-related menorrhagia. Int J Gynaecol Obstet. 2011;112(2):126-30.\u003c/li\u003e\n\u003cli\u003eDonnez J, Tatarchuk TF, Bouchard P, Puscasiu L, Zakharenko NF, Ivanova T, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012;366(5):409-20.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Hampshire and Isle of Wight Healthcare NHS Foundation Trust","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Womens health, Uterine Fibroids, Symptom Severity, Embolisation, Myomectomy","lastPublishedDoi":"10.21203/rs.3.rs-6073815/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6073815/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eUterine fibroids can significantly impair the quality of life of women. While most fibroids remain asymptomatic, 25% of women diagnosed with uterine fibroids require medical intervention.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA systematic review and meta-analysis protocol was developed and published in PROSPERO (CRD42022346251) to explore surgical treatment outcomes linked to uterine fibroids. Data was gathered using PubMed, Web of Science and ScienceDirect. The pooled data was analysed using the meta-package (version 8.0-1 and version 4.6-0) in R software (version 4.4.2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFive studies met the eligibility criteria, and were further analysed to report quality of life, symptom severity and complications linked to surgery. Three studies (n=520) assessed HRQoL via UFS-QoL pre- and post-uterine artery embolisation and myomectomy. The pooled mean difference was -6.99 (95% CI: [-16.49, 2.51]; I²=71.9%; P=0.03), indicating no significant difference in quality of life impact between procedures. However, the pooled mean difference for UFS-QoL symptom severity was 4.85 (95% CI: [0.50, 9.21]; I²=0.0%; P=0.52), suggesting myomectomy significantly reduces symptom severity compared to uterine artery embolisation. Most studies did not report race and ethnicity, and the study sample was not representative of the global female populous.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUterine artery embolisation and myomectomy result in comparable improvements in health-related quality of life although myomectomy appears to offer a greater reduction in symptom severity compared to uterine artery embolisation. These findings can assist clinicians and patients make improved shared decisions when selecting the most appropriate treatment for uterine fibroids. Improved research study designs and representation in sample need to be considered when conducting future research.\u003c/p\u003e","manuscriptTitle":"Evaluating Treatment Options for Symptomatic Uterine Fibroids: A Systematic Review and Meta-analysis of Effectiveness, Recovery, and Long-Term Outcomes (MARIE WP1)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-27 10:17:16","doi":"10.21203/rs.3.rs-6073815/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2dfb9641-a5b4-436a-a94f-4459d06dc6e4","owner":[],"postedDate":"February 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":44643682,"name":"Women's studies"}],"tags":[],"updatedAt":"2025-02-27T10:17:17+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-27 10:17:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6073815","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6073815","identity":"rs-6073815","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}