Decoding uterine (dys)function in fibroids through multimodal assessment of functional determinants: a systematic review and meta-analysis

Abstract Study Question Is there a difference in uterine functional determinants between women with fibroids and women without myometrial pathology? Summary Answer Women with uterine fibroids consistently exhibit altered uterine functional determinants compared to controls, characterized by increased perfusion, elevated stiffness, and impaired contractility. What is Known Already The functional determinants of the non-pregnant uterus remain largely unexplored and underreported. Uterine fibroids, as a well-defined morphological myometrial pathology, offer a unique model for understanding uterine functionality. Study Design, Size, Duration This systematic review and meta-analysis included original articles published in English and indexed in PubMed, Embase, and Scopus databases up to 20 December 2024. The search strategy combined terms related to uterine fibroids with those describing uterine functional parameters (e.g. uterine vascularity, stiffness, and contractility), together with diagnostic methods (including Doppler ultrasound, elastography, and magnetic resonance imaging). Participants/Materials, Setting, Methods Observational studies evaluating quantitative uterine functional determinants in non-pregnant women with fibroids and controls without myometrial pathology were selected using predefined Population, Intervention (Investigated measure), Comparator, Outcome(s), Study type (PICOS) criteria. Outcomes included quantitative measures of uterine functionality such as vascularization (uterine artery Doppler indices), stiffness (elastography parameters), and contractility (peristalsis parameters). Study quality was evaluated using the Newcastle–Ottawa Scale. Pooled estimates for continuous outcomes were calculated using random-effects models, expressed as mean difference (MD) with 95% CIs. Subgroup analyses addressed potential confounders, including menopausal status, hormonal therapy use, and symptom severity. Main Results and the Role of Chance Fourteen studies met the inclusion criteria: seven on vascularization (n = 961), five on stiffness (n = 342), and two on contractility (n = 62). The uterine artery pulsatility index was significantly lower in women with fibroids compared to controls (MD −0.63, 95% CI −0.91 to −0.36; I2 = 91.98%), with greater reductions observed in premenopausal, non-hormonally treated, and symptomatic women. The resistance index also decreased (−0.09, 95% CI −0.15 to −0.03; I2 = 95.86%), showing similar patterns across subgroups. Time-averaged maximum velocity was higher in the fibroid group (+18.46, 95% CI +5.54 to +31.37; I2 = 93.64%), particularly in premenopausal and symptomatic cases. Elastography showed increased myometrial stiffness in uterine fibroids compared to controls, with a higher elastic modulus (+35.58 kPa, 95% CI +24.94 to +46.22; I2 = 0%) and shear wave velocity (+1.14 m/s, 95% CI +0.62 to +1.65; I2 = 0%). Limited evidence pointed to reduced peristaltic activity and altered contraction patterns in symptomatic fibroids. Limitations, Reasons for Caution The relatively small study population and high heterogeneity of estimates warrant cautious interpretation, although findings were consistent across multiple uterine functional determinants. Wider Implications of the Findings Women with uterine fibroids consistently exhibit altered uterine functional determinants compared to controls without myometrial pathology, highlighting how structural abnormalities parallel functional changes. Leveraging fibroids as a model, integrating structural imaging with functional assessment through advanced multimodal approaches may deepen our understanding of uterine diseases, ultimately enhancing treatment and patient care. Study Funding/Competing Interest(s) This study was partially funded by the Italian Ministry of Health—Current research IRCCS. The funding source had no role in the study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication. E.S. reports payments from Ferring, Theramex, and IBSA for research grants and honoraria from IBSA, Gedeon-Richter, and Sandoz for lectures. He serves as Editor-in-Chief of Human Reproduction Open. P.V. has received honoraria as Co-Editor in Chief of Journal of Endometriosis and Uterine Disorders. The remaining authors have no conflicts of interest to disclose. Registration Number PROSPERO ID: CRD42024619633—registered on 10 December 2024.

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