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Scovazzi U, Xholli A, Schiaffino MG, Molinari F, Perugi I, Primizia E, Cagnacci A, Londero AP. Pilot Clinical and Radiomic Analysis of Deep Infiltrating Endometriosis of the Parametrium Using Shannon Entropy: A Retrospective Cohort Study. ULTRASOUND IN MEDICINE & BIOLOGY 2025; 51:1078-1083. [PMID: 40221222 DOI: 10.1016/j.ultrasmedbio.2025.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 02/28/2025] [Accepted: 03/12/2025] [Indexed: 04/14/2025]
Abstract
OBJECTIVE Ultrasound techniques for diagnosing deep infiltrating endometriosis (DIE) currently lack a quantitative method to assess microstructural heterogeneity in relation to diagnosis and clinical symptoms. This study evaluates Shannon entropy-based radiomics for differentiating DIE lesions from adjacent tissue and correlating these features with pain severity. METHODS In this retrospective cohort study (2020-2024), fertile women with histologically confirmed parametrial endometriosis and high-quality ultrasound images were evaluated. Pain was measured using a 10-cm visual analog scale. Two 25 mm² regions of interest (ROIs) were defined: one within the DIE nodule and one in the adjacent perilesional tissue. Each ROI was analyzed with the Shannon entropy algorithm to assess tissue heterogeneity. RESULTS In this study, 148/663 women (22.3%) were diagnosed with parametrial DIE, of whom 52 underwent surgery and were included in the study. DIE was localized in 92.3% in the posterior, in 5.8% in both posterior and anterior, and in 2% in the anterior parametrium. Primary symptoms were menstrual pain (88%) and pain at intercourse (63%). ROI entropy of DIE lesion was lower than that of the perilesional ROI (p = 0.05). The area-under-the-curve (AUC) of Shannon entropy for endometriotic vs. adjacent tissue was 91.36% (95% CI: 84.5%-98.21%). The ROI entropy of the DIE lesion exhibited an inverse correlation with menstrual pain (rho -0.46, CI 95% -0.74/-0.12, p = 0.025), and that of perilesional tissue with chronic pelvic pain (rho -0.41, 95% CI -0.73/- 0.04; p = 0.072). CONCLUSION Entropy analysis distinguishes DIE lesion from perilesional tissue and significantly correlates with menstrual pain.
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Affiliation(s)
- Umberto Scovazzi
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy; Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy
| | - Anjeza Xholli
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy.
| | - Maria Giulia Schiaffino
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy; Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy
| | - Filippo Molinari
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy; Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy
| | - Isabella Perugi
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy; Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy
| | - Elvira Primizia
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy; Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy
| | - Angelo Cagnacci
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy; Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy
| | - Ambrogio Pietro Londero
- Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy; Obstetrics and Gynaecology Unit, IRCCS Ospedale Pediatrico Giannina Gaslini, Genoa, Italy
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Matot R, Blickstein O, Leibner G, Bar‐Peled U, Borovich A, Geron Y, Gilboa Y, Krissi H, Perlman S. Differences in the Sonographic Features of Adenomyosis and Concurrent Endometriosis Compared to Isolated Adenomyosis: A MUSA Criteria Analysis. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2025; 44:1077-1084. [PMID: 39968848 PMCID: PMC12067169 DOI: 10.1002/jum.16667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 02/09/2025] [Accepted: 02/10/2025] [Indexed: 02/20/2025]
Abstract
OBJECTIVE To examine whether the co-occurrence of endometriosis affects the sonographic features of adenomyosis based on the revised Morphological Uterus Sonographic Assessment (MUSA) criteria. METHODS This prospective cohort study utilized data from a tertiary referral center collected between 2010 and 2022. Non-pregnant women aged 20-53 years who presented with symptoms potentially related to adenomyosis and underwent pelvic ultrasound scans were included. Diagnoses were based on the revised MUSA criteria, which distinguish between direct features (endometrial cysts, hyperechogenic islands, echogenic sub-endometrial lines, and buds) and indirect features (globular shape of the uterus, asymmetrical uterine wall thickening, irregular junctional zone, fan-shaped shadowing, translesional vascularity, and interrupted junctional zone). Patients were categorized into 2 groups: 1) concurrent adenomyosis and endometriosis and 2) isolated adenomyosis. Demographic and clinical characteristics were retrospectively collected. RESULTS Ninety-four patients were diagnosed with adenomyosis. Of these, 24 (27%) had concurrent endometriosis, while 70 had isolated adenomyosis. The most frequent sonographic features were globular uterine configuration (52%), myometrial cysts (44%), and asymmetrical myometrial thickening (33%). The isolated adenomyosis group had a higher proportion of direct features (29%) and both direct and indirect features (33%) compared to the concurrent group, which predominantly exhibited indirect features (71%) (P < .05). Direct features of myometrial cysts were significantly more frequent in the isolated adenomyosis group (51%) compared to the concurrent group (21%, P = .01). CONCLUSIONS Utilizing the revised MUSA criteria revealed significant differences in the sonographic features of adenomyosis in symptomatic patients with concurrent endometriosis compared to isolated adenomyosis. This highlights the necessity for standardized diagnostic methods and enhances understanding of the complex relationship between adenomyosis and endometriosis, underscoring the importance of accurate diagnosis in clinical practice.
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Affiliation(s)
- Ran Matot
- Helen Schneider Hospital for WomenRabin Medical CenterPetach TikvaIsrael
- The Sackler Faculty of MedicineTel‐Aviv UniversityTel‐AvivIsrael
| | - Ophir Blickstein
- Helen Schneider Hospital for WomenRabin Medical CenterPetach TikvaIsrael
- The Sackler Faculty of MedicineTel‐Aviv UniversityTel‐AvivIsrael
| | - Gideon Leibner
- The Faculty of MedicineHebrew University of JerusalemJerusalemIsrael
| | - Uval Bar‐Peled
- The Sackler Faculty of MedicineTel‐Aviv UniversityTel‐AvivIsrael
| | - Adi Borovich
- Helen Schneider Hospital for WomenRabin Medical CenterPetach TikvaIsrael
- The Sackler Faculty of MedicineTel‐Aviv UniversityTel‐AvivIsrael
- Obstetrics and GynecologyMaimonides Medical CenterBrooklynNYUSA
| | - Yossi Geron
- Helen Schneider Hospital for WomenRabin Medical CenterPetach TikvaIsrael
| | - Yinon Gilboa
- Helen Schneider Hospital for WomenRabin Medical CenterPetach TikvaIsrael
- The Sackler Faculty of MedicineTel‐Aviv UniversityTel‐AvivIsrael
| | - Haim Krissi
- Helen Schneider Hospital for WomenRabin Medical CenterPetach TikvaIsrael
- The Sackler Faculty of MedicineTel‐Aviv UniversityTel‐AvivIsrael
| | - Sharon Perlman
- Helen Schneider Hospital for WomenRabin Medical CenterPetach TikvaIsrael
- The Sackler Faculty of MedicineTel‐Aviv UniversityTel‐AvivIsrael
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Chen X, Lang J, Li L. Adenomyosis Patterns on Transvaginal Sonography Could Predict the Obstetrical Outcomes of Fertility-Sparing Surgeries: A Retrospective Cohort Study. J Minim Invasive Gynecol 2025; 32:540-549. [PMID: 39805535 DOI: 10.1016/j.jmig.2025.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 01/03/2025] [Accepted: 01/03/2025] [Indexed: 01/16/2025]
Abstract
STUDY OBJECTIVE To explore the associations between adenomyosis patterns on transvaginal sonography (TVS) and surgical outcomes. DESIGN A retrospective cohort study. SETTING Peking Union Medical College Hospital, Beijing, China. PATIENTS The medical records of 322 patients diagnosed with adenomyosis who underwent open or laparoscopic fertility-sparing surgeries from March 1 to December 31, 2018, were reviewed. Patients were divided into localized (221 patients) and diffuse (101 patients) adenomyosis groups on the basis of TVS findings. INTERVENTIONS Detailed epidemiological information, imaging evaluations, surgical reports, and pathological findings were retrospectively collected. MEASUREMENTS AND MAIN RESULTS The median postsurgical follow-up period was 52.8 months (range 6-88 months), with 24 patients (7.4%) lost to follow-up by July 1, 2019. The localized and diffuse adenomyosis groups had similar symptom relief and recurrent uterine lesions. Among the 104 patients who attempted pregnancy, 75 patients (72.1%) conceived, with 35 miscarriages (46.7%) and 59 live births (78.7%). For the whole cohort and the localized adenomyosis and diffuse adenomyosis groups, the cumulative 5-year conception rates were 75%, 83% and 60%, respectively; the cumulative 5-year live birth rates were 63%, 79% and 37%, respectively. The adenomyosis patterns found during sonography were the only independent risk factors related to clinical pregnancy and live birth in the Cox regression model. Patients with diffuse adenomyosis had significantly lower rates of conception (HR 0.5, 95% CI 0.3-1.0) and live birth (HR 0.4, 95% CI 0.2-0.8). CONCLUSION Adenomyosis patterns (localized versus diffuse) in pretreatment TVS could predict obstetrical outcomes, irrespective of surgical type and uterine size. CLINICAL REGISTRY The clinical trial registry name is the Cooperative Adenomyosis Network (CAN); the registration number is NCT03230994 (https://clinicaltrials.gov). This study started on June 30, 2017, and was completed on December 30, 2020.
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Affiliation(s)
- Xiaojing Chen
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (Chen, Lang and Li), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Chen, Lang and Li), Beijing, China; State Key Laboratory for Complex, Severe and Rare Diseases, Peking Union Medical College Hospital (Chen, Lang and Li), Beijing, China
| | - Jinghe Lang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (Chen, Lang and Li), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Chen, Lang and Li), Beijing, China; State Key Laboratory for Complex, Severe and Rare Diseases, Peking Union Medical College Hospital (Chen, Lang and Li), Beijing, China
| | - Lei Li
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (Chen, Lang and Li), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Chen, Lang and Li), Beijing, China; State Key Laboratory for Complex, Severe and Rare Diseases, Peking Union Medical College Hospital (Chen, Lang and Li), Beijing, China.
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Streuli I, Ramyead L, Silvestrini N, Petignat P, Dubuisson J. Impact of definitive uterine artery occlusion on ovarian reserve markers in laparoscopic myomectomy: a randomized controlled trial with 2-year follow-up. Hum Reprod 2025:deaf070. [PMID: 40420404 DOI: 10.1093/humrep/deaf070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 02/07/2025] [Indexed: 05/28/2025] Open
Abstract
STUDY QUESTION Does definitive occlusion of uterine arteries have a short- or long-term impact on ovarian reserve markers in reproductive-age women undergoing laparoscopic myomectomy? SUMMARY ANSWER Preventive definitive uterine artery occlusion (UAO) during laparoscopic myomectomy reduces intraoperative blood loss but does not impact serum AMH levels after short- and long-term follow-up in reproductive-age women. WHAT IS KNOWN ALREADY Uterine leiomyomas are the most common benign tumours in women of reproductive age. For symptomatic women willing to retain their uterus, especially for a future pregnancy, the current gold standard is surgical myomectomy for subserous/intramural leiomyoma. Temporary or definitive occlusion of uterine arteries can be performed to control bleeding during surgery but its impact on ovarian reserve markers is still unclear. A single randomized trial with a 1-year follow-up demonstrated that temporary bilateral UAO during laparoscopic myomectomy slightly decreased AMH levels at postoperative day 2 but has no significant impact at 3, 6, and 12 months after surgery. STUDY DESIGN, SIZE, DURATION We conducted a randomized controlled trial with a 2-year follow-up evaluating the effect of definitive occlusion of uterine arteries on ovarian reserve markers via sequential measures of AMH levels and AFC by ultrasound assessment. The study included 58 women with symptomatic leiomyoma type FIGO 3 to 6 scheduled for laparoscopic myomectomy between July 2015 and October 2021. Patient allocation was disclosed to the surgeon just before starting the procedure; women were blinded to group allocation throughout the study. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were randomized in two groups: the UAO group (laparoscopic myomectomy with preventive occlusion of uterine arteries) (n = 29 women) and the no-UAO group (laparoscopic myomectomy without occlusion of uterine arteries but with intra-myometrial injection of vasoconstrictive agents) (N = 29 women). Serum AMH levels and AFC were evaluated at baseline (T0) and followed at 1 month (T1), 3 months (T3), 6 months (T6), 12 months (T12), and 24 months (T24) after surgery. Intraoperative blood loss, evolution of uterine bleeding and pain symptoms, and leiomyoma recurrence were also evaluated as secondary outcomes. Pregnancies and live births were monitored. MAIN RESULTS AND THE ROLE OF CHANCE Women in both groups did not differ in their baseline characteristics in terms of age, body mass index, ethnicity, parity, wish to become pregnant, hormonal treatment, leiomyoma number and size, baseline haemoglobin levels, uterine bleeding symptoms, baseline serum AMH levels, and AFC. The mean operative time was similar between both groups. Mean blood loss during surgery was on average 138 (±104) ml in the UAO group versus 436 (±498) ml in controls (P < 0.001). In the UAO group, 0% had an intraoperative blood loss >500 ml versus 32.1% in the no-UAO group (P < 0.01). Regarding clinical symptoms, most patients in both groups had decreased menstrual flow at the last follow-up visit (24 months) compared to baseline and improvement of dysmenorrhea followed the same trend with a reduction in pain levels in both groups. The risk of leiomyoma recurrence was similar between both groups. Serum AMH levels did not differ between the groups at any time (T1, T3, T6, T12, and T24) and non-inferiority of preventive occlusion was demonstrated with a non-inferiority margin of [-3.5 pmol/l]. Differences between means and 95% CI (in parentheses) were as follows: at T1 -0.11 (-2.14 to 2.40), at T3 -0.25 (-2.36 to 2.21), at T6 0.81 (-2.69 to 3.84), at T12 -0.95 (-3.15 to 1.33), and at T24 1.18 (-1.95 to 3.82). AFC did not differ between the groups at any time, however, non-inferiority of preventive occlusion could not be demonstrated, presumably due to a large variability in this measurement. LIMITATIONS, REASONS FOR CAUTION Our sample size was calculated to detect a clinically relevant difference of at least two-thirds of the SD in serum AMH levels, but we cannot exclude that a larger sample size might have revealed a smaller impact on serum AMH. WIDER IMPLICATIONS OF THE FINDINGS Preventive UAO during laparoscopic myomectomy does not compromise ovarian reserve markers and can be used safely to improve perioperative bleeding control in women of reproductive age. Incorporating UAO as a preventive measure during laparoscopic myomectomy may enhance the safety of the procedure. STUDY FUNDING/COMPETING INTEREST(S) Funded by the Department of Paediatrics, Gynecology and Obstetrics of the Geneva University Hospitals. There are no competing interests to declare. TRIAL REGISTRATION NUMBER NCT02563392. TRIAL REGISTRATION DATE 9 July 2015. DATE OF FIRST PATIENT’S ENROLMENT July 2015.
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Affiliation(s)
- I Streuli
- Department of Paediatrics, Gynaecology and Obstetrics, Geneva University Hospitals and University of Geneva, Geneva, Switzerland
| | - L Ramyead
- Department of Paediatrics, Gynaecology and Obstetrics, Geneva University Hospitals and University of Geneva, Geneva, Switzerland
| | - N Silvestrini
- Department of Paediatrics, Gynaecology and Obstetrics, Geneva University Hospitals and University of Geneva, Geneva, Switzerland
| | - P Petignat
- Department of Paediatrics, Gynaecology and Obstetrics, Geneva University Hospitals and University of Geneva, Geneva, Switzerland
| | - J Dubuisson
- Department of Paediatrics, Gynaecology and Obstetrics, Geneva University Hospitals and University of Geneva, Geneva, Switzerland
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Smith D, Bolton G. Diagnosing adenomyosis using transvaginal ultrasound in current practice: A scoping review and service evaluation. ULTRASOUND (LEEDS, ENGLAND) 2025:1742271X251338147. [PMID: 40357226 PMCID: PMC12065711 DOI: 10.1177/1742271x251338147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 04/14/2025] [Indexed: 05/15/2025]
Abstract
Background A departmental audit identified a case of adenomyosis which had not been reported, highlighting the need to assess whether the current service provision is adequate in identifying patients with (possible) adenomyosis and how improvements in this part of the service could be made. Aim To assess whether sonographers are effectively identifying and reporting adenomyosis on transvaginal ultrasound. Methodology A scoping review and retrospective service evaluation was undertaken which included (n = 79) adult female premenopausal patients with symptoms of adenomyosis who had undergone a transvaginal ultrasound scan during the first quarter of 2023. Patients were identified using the CRIS statistic module according to pre-defined inclusion and exclusion criteria. All data were anonymised and collated to include the patient age, referral information (symptoms), scan report and sonographer. The scan report and archived images were evaluated using the sonographic signs identified by the Morphological Uterus Sonographic Assessment group (Harmsen et al., 2022) and then compared to the original report. Results In total, 21.5% (n = 17) of patients had signs of adenomyosis on image review, but only 23.5% (n = 4) of these were reported as such. The majority (n = 8) of unidentified cases were reported as having a 'heterogeneous myometrium'. Inter-rater agreement ranged from 50% to 100%. Conclusion Most ultrasonic diagnoses of adenomyosis were not identified in our service which is likely due to a lack of internationally agreed criteria for ultrasound diagnosis of adenomyosis preventing adequate reporting.
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Affiliation(s)
- Dawn Smith
- Southport and Ormskirk Hospitals, Mersey and West Lancashire NHS Teaching Hospitals, Ormskirk, UK
| | - Gareth Bolton
- Medical Sciences, Institute of Health, University of Cumbria, Carlisle, UK
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Arezzo F, Fanizzi A, Mancari R, Cocco E, Bove S, Comes MC, Gianciotta M, Lanza G, Lopez S, Cazzato G, Silvestris E, Vitale E, Vizza E, Cormio G, Massafra R, Loizzi V. A Radiomic-based model to predict the depth of myometrial invasion in endometrial cancer on ultrasound images. Sci Rep 2025; 15:15901. [PMID: 40335530 PMCID: PMC12058973 DOI: 10.1038/s41598-025-00906-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 05/02/2025] [Indexed: 05/09/2025] Open
Abstract
In Europe, endometrial carcinoma was found to be the fourth most common tumor in the female population in 2022. The depth of myometrial invasion is a well-established and crucial prognostic risk factor in endometrial cancer patients and is important for choosing the most appropriate management for the patient. However, while the preoperative assessment of tumor invasion carried out using radiological imaging is very important, it is a subjective examination and its accuracy is based on the experience of the operator. In this scenario we proposed a radiomic-based model to predict myometrial invasion for ultrasound images. We collected clinical data and qualitative ultrasound indicators of 77 consecutive patients affected by endometrial carcinoma. After a pre-processing phase of ultrasound images, a pre-trained Inception-V3 convolutional neural network (CNN) was used as features extractor. Then, a binary classification model and a multiclass model were trained, after a double step of feature selection; the first selection stage performed feature filtering based on a nonparametric test, the second stage selected features by evaluating not only the relationship with the outcome of interest, but also the relationship with other predictive features. For the multiclass prediction model, a cascade approach has been developed. The two proposed models were validated in 100 ten-fold cross-validation rounds. In addition, to assess the effect of the potential added value of using this tool in clinical practice, we compared the operator's performance with and without the developed automated support. The binary and multiclass model reached optimal classification performances with a mean AUC value equals to 90.76 (88.63-92.89 IC95%). When the operator was assisted by the radiomic-based decision-making system increased by 10% points in terms of precision. The multiclass model showed the per-classes recall were 93.33%, 71.88% and 90.00%, for focal infiltration, infiltration less than 50%, and infiltration greater than 50% class, respectively. The performances of the operator when assisted by the radiomic-based decision-making system were statistically superior both in terms of overall accuracy and per-class recall of intermediate class (rising to 82.82% and 71.88% compared to 71.88% and 56.25%, respectively). The proposed models have the potential to standardize examinations that rely on subjective evaluations, such as ultrasound. They can represent a valid support tool for the clinicians for an accurate estimate of the deep myometrial infiltration already in the diagnosis phase with an easily accessible, low-cost examination that causes no discomfort for the patient such as ultrasound.
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Affiliation(s)
- Francesca Arezzo
- Clinicalized Gynecological Oncology Unit , IRCCS Istituto Tumori 'Giovanni Paolo II' , Viale Orazio Flacco 65, 70124, Bari, Italy
| | - Annarita Fanizzi
- Biostatistics and Bioinformatics Laboratory, IRCCS Istituto Tumori 'Giovanni Paolo II', Viale Orazio Flacco 65, Bari, 70124, Italy
| | - Rosanna Mancari
- Gynecologic Oncology Unit, IRCCS Regina Elena National Cancer Institute, Rome, 00144, Italy
| | - Emiliano Cocco
- Sylvester Comprehensive Cancer Center, Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Samantha Bove
- Biostatistics and Bioinformatics Laboratory, IRCCS Istituto Tumori 'Giovanni Paolo II', Viale Orazio Flacco 65, Bari, 70124, Italy.
| | - Maria Colomba Comes
- Biostatistics and Bioinformatics Laboratory, IRCCS Istituto Tumori 'Giovanni Paolo II', Viale Orazio Flacco 65, Bari, 70124, Italy.
| | - Mariangela Gianciotta
- Obstetrics and Gynecology Unit, Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Giorgia Lanza
- Obstetrics and Gynecology Unit, Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Salvatore Lopez
- Clinicalized Gynecological Oncology Unit , IRCCS Istituto Tumori 'Giovanni Paolo II' , Viale Orazio Flacco 65, 70124, Bari, Italy
| | - Gerardo Cazzato
- Department of Emergency and Organ Transplantation, Pathology Section, University of Bari "Aldo Moro", Bari, Italy
| | - Erica Silvestris
- Clinicalized Gynecological Oncology Unit , IRCCS Istituto Tumori 'Giovanni Paolo II' , Viale Orazio Flacco 65, 70124, Bari, Italy
| | - Elsa Vitale
- Biostatistics and Bioinformatics Laboratory, IRCCS Istituto Tumori 'Giovanni Paolo II', Viale Orazio Flacco 65, Bari, 70124, Italy
| | - Enrico Vizza
- Gynecologic Oncology Unit, IRCCS Regina Elena National Cancer Institute, Rome, 00144, Italy
| | - Gennaro Cormio
- Clinicalized Gynecological Oncology Unit , IRCCS Istituto Tumori 'Giovanni Paolo II' , Viale Orazio Flacco 65, 70124, Bari, Italy
- Department of Interdisciplinary Medicine (DIM), University of Bari "Aldo Moro", Bari, Italy
| | - Raffaella Massafra
- Biostatistics and Bioinformatics Laboratory, IRCCS Istituto Tumori 'Giovanni Paolo II', Viale Orazio Flacco 65, Bari, 70124, Italy
| | - Vera Loizzi
- Clinicalized Gynecological Oncology Unit , IRCCS Istituto Tumori 'Giovanni Paolo II' , Viale Orazio Flacco 65, 70124, Bari, Italy
- Department of Translational Biomedicine and Neuroscience, University of Bari, Bari, Italy
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Catherino WH, Al-Hendy A, Zaim S, Bouzegaou N, Venturella R, Stewart EA, Wu R, Vannuccini S, Perry JS, Rakov VG, Munro MG. Efficacy and safety of relugolix combination therapy in women with uterine fibroids and adenomyosis: subgroup analysis of LIBERTY 1 and LIBERTY 2. Fertil Steril 2025:S0015-0282(25)00251-1. [PMID: 40320117 DOI: 10.1016/j.fertnstert.2025.04.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 04/24/2025] [Accepted: 04/24/2025] [Indexed: 05/24/2025]
Abstract
OBJECTIVE To assess the effects of relugolix combination therapy in women with uterine fibroids (UFs) and concomitant ultrasound-diagnosed adenomyosis. DESIGN This post hoc analysis used pooled data from completers of the pivotal LIBERTY studies. The subgroup of women with adenomyosis and UFs was compared with the overall study population on selected efficacy and safety endpoints. SUBJECTS Premenopausal women (aged 18-50 years) with diagnosed UFs (confirmed by ultrasonography) and heavy menstrual bleeding (assessed by the alkaline hematin method). INTERVENTION Once-daily relugolix combination therapy (40 mg relugolix, 1 mg estradiol, and 0.5 mg of norethindrone acetate) or placebo for 24 weeks, or delayed relugolix combination therapy (40 mg of relugolix monotherapy for 12 weeks, followed by relugolix combination therapy for 12 weeks). MAIN OUTCOME MEASURES Endpoints included the percentage of women with concomitant adenomyosis, the proportion of treatment responders (achieved or maintained a menstrual blood loss <80 mL and ≥50% reduction in menstrual blood loss volume from baseline over the last 35 days of treatment), the proportion of women achieving or maintaining amenorrhea over the last 35 days of treatment, and the change from baseline to week 24 in uterine volume and adverse events. RESULTS A total of 111 women (18.2%) had a baseline diagnosis of concomitant adenomyosis (37 in the relugolix combination therapy group, 45 in the delayed relugolix combination therapy group, 29 in the placebo group) and were included in this analysis. Of women with adenomyosis, 83.8% in the relugolix combination therapy group were treatment responders compared with 27.6% in the placebo group. Amenorrhea was achieved in 64.9% of women with adenomyosis treated with relugolix combination therapy and in 6.9% of women treated with placebo. The least square mean uterine volume of women with adenomyosis decreased by 22.2% and 5.8% in the relugolix combination therapy and placebo groups, respectively. Results for the above outcomes in the relugolix combination therapy population were similar to the delayed relugolix combination therapy group. CONCLUSION Efficacy outcomes in women with adenomyosis and UFs were comparable with those in women from the overall LIBERTY study population.
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Affiliation(s)
- William H Catherino
- Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of Health Sciences, Bethesda, Maryland.
| | - Ayman Al-Hendy
- Department of Medical Sciences, Khalifa University, Abu Dhabi, United Arab Emirates; Department of Obstetrics and Gynecology, University of Chicago, Chicago, Illinois
| | | | | | - Roberta Venturella
- Department of Clinical and Experimental Medicine, Unit of Obstetrics and Gynecology, Magna Graecia University of Catanzaro, Catanzaro, Italy
| | - Elizabeth A Stewart
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Mayo Clinic and Mayo Clinic Alix School of Medicine, Rochester, Minnesota
| | - Rui Wu
- Sumitomo Pharma America, Marlborough, Massachusetts
| | - Silvia Vannuccini
- Department of Experimental, Clinical and Biomedical Sciences "Mario Serio", University of Florence, Careggi University Hospital, Florence, Italy
| | | | | | - Malcolm G Munro
- Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California - Los Angeles, University of California, Los Angeles, California
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Trinchant R, Cruz M, Requena A, García-Velasco JA. Adenomyosis, especially in its focal nature, hampers implantation and live birth rate after single euploid embryo transfer. Int J Gynaecol Obstet 2025; 169:759-765. [PMID: 39673296 DOI: 10.1002/ijgo.16082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 11/26/2024] [Accepted: 11/30/2024] [Indexed: 12/16/2024]
Abstract
OBJECTIVE The primary objective of this study was to assess if uterine adenomyosis impacts live birth rate per euploid embryo transfer. The secondary objectives included addressing obstetric and perinatal outcomes in the study group. METHODS This was a multicenter and retrospective cohort study in which 228 patients diagnosed with adenomyosis undergoing single euploid embryo transfer between 2016 and June 2023 were included and matched on 1:1 ratio to control patients without ultrasonographic diagnostic criteria for adenomyosis. RESULTS A significant higher live birth rate per embryo transfer was observed in controls compared to women with adenomyosis: 107/228 (46.9%) versus 56/228 (24.6%), respectively (odds ratio (OR) = 2.71, 95% confidence interval [CI]: 1.73-4.13, p < 0.001). When dividing adenomyotic patients regarding the nature of the disease, a higher live birth rate per transfer was described in diffuse adenomyosis compared to focal adenomyosis: 47/166 (28.3%) versus 9/62 (15%), respectively (OR = 2.32, 95% CI: 1.03-5.78, p = 0.034). Described differences were constant even when correcting for multiple variables. There was no statistically significant difference in childbirth delivery method (vaginal vs. cesarean section) between the adenomyosis and control groups. Mean gestational age at the time of delivery, newborn size and weight, and incidences of low birth weight, preterm birth, and admission to the neonatal intensive care unit did not differ between the two groups. In addition, in vitro fertilization (IVF) and perinatal outcomes were similar in patients with diffuse compared with focal adenomyosis. CONCLUSION Adenomyosis, especially focal adenomyosis, affects clinical but may not affect perinatal outcomes after single euploid embryo transfer.
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Affiliation(s)
- Rafael Trinchant
- IVIRMA Global Research Alliance, IVIRMA Mallorca, Mallorca, Spain
- Escuela Internacional de Doctorado, Universidad Rey Juan Carlos, Madrid, Spain
| | - María Cruz
- IVIRMA Global Research Alliance, IVIRMA Madrid, Madrid, Spain
- IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
| | - Antonio Requena
- IVIRMA Global Research Alliance, IVIRMA Madrid, Madrid, Spain
- IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
| | - Juan Antonio García-Velasco
- IVIRMA Global Research Alliance, IVIRMA Madrid, Madrid, Spain
- IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
- Universidad Rey Juan Carlos, Madrid, Spain
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Nguyen XL, Huynh QH, Nguyen PN. Assessing the Clinical Characteristics and the Role of Imaging Modalities in Uterine Sarcoma: A Single-Center Retrospective Study From Vietnam. JOURNAL OF CLINICAL ULTRASOUND : JCU 2025. [PMID: 40312923 DOI: 10.1002/jcu.24046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 02/10/2025] [Accepted: 03/31/2025] [Indexed: 05/03/2025]
Abstract
BACKGROUND This study aims to describe the clinical and imaging characteristics of uterine sarcomas and the role of imaging modalities in assessing them. MATERIALS AND METHODS This retrospective study enrolled all patients diagnosed with uterine sarcoma at Tu Du Hospital, Vietnam between January 2020 and December 2023. The findings of ultrasound (US) and magnetic resonance imaging (MRI) were compared to histology as the reference. RESULTS Among 78 patients, 46.2% of cases were menopause. Abnormal vaginal bleeding was the most common symptom. Three common types of uterine sarcoma were leiomyosarcoma (50.0%), low-grade endometrial stromal sarcoma (23.1%), and carcinosarcoma (19.2%). Some imaging features of uterine sarcomas were found including nontypical lesion of fibroid (89.7%), solitary mass (84.6%), inhomogeneous structure (76.9%), invisible endometrium (67.9%), moderate-rich vascularization on Doppler signal (57.7%), irregular border of tumor (48.7%), classification of FIGO 0 (44.9%), cystic area within tumor (42.3%), acoustic shadowing (34.6%), "cooked" appearance (9.0%), and calcification image in tumor (6.4%). The sensitivity of standard US, consultant US, and MRI was 56.4%, 88.4%, and 87.5%, respectively. CONCLUSIONS Besides clinical presentations, uterine sarcomas present some specific features on US. Consultant US and MRI could be added to standard US to increase the accuracy and help in surgical decision making where applicable.
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Affiliation(s)
- Xuan Lan Nguyen
- Department of Imaging Diagnosis, Tu Du Hospital, Ho Chi Minh City, Vietnam
| | - Quang Huy Huynh
- Department of Radiology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
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Shats M, Zajicek M, Siedhoff MT, Meyer R. Updates on adenomyosis and fertility. Curr Opin Obstet Gynecol 2025:00001703-990000000-00190. [PMID: 40304236 DOI: 10.1097/gco.0000000000001039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2025]
Abstract
PURPOSE OF REVIEW Adenomyosis, characterized by ectopic endometrial tissue within the myometrium, causes chronic pelvic pain, heavy bleeding, and reduced fertility. Nowadays, diagnosis relies heavily on imaging, primarily transvaginal ultrasound, supplemented by MRI. While hysterectomy remains a definitive treatment, the rise in younger patients desiring fertility necessitates uterine-sparing approaches. This review aimed to evaluate these approaches in relation to their impact on fertility and obstetrical outcomes. RECENT FINDINGS Research highlights the association between adenomyosis and increased risk for pregnancy loss, preterm birth, and pre-eclampsia. Minimally invasive thermal ablation therapies and hysteroscopic techniques, including adenomyomectomy, offer promising fertility-sparing options, although long-term data on fertility outcomes and potential complications like uterine rupture remain limited. Advances in laparoscopic and laparotomy-based cytoreductive surgeries are also explored, but large-scale studies comparing efficacy and safety are lacking. SUMMARY This review examines recent advancements in understanding and managing adenomyosis, focusing on fertility-sparing interventions. Studies show varying success rates for these interventions, highlighting the need for larger, well-designed trials with standardized diagnostic criteria, to assess long-term fertility outcomes, and refine patient selection for optimal results. A consistent challenge across all approaches is the potential for uterine rupture and placenta accreta spectrum, demanding careful patient selection and close monitoring.
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Affiliation(s)
- Maya Shats
- Department of Obstetrics and Gynecology, Sheba Medical Center, Ramat-Gan
| | - Michal Zajicek
- Department of Obstetrics and Gynecology, Sheba Medical Center, Ramat-Gan
| | - Matthew T Siedhoff
- Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Raanan Meyer
- Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA
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11
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Santulli P, Vannuccini S, Bourdon M, Chapron C, Petraglia F. Adenomyosis: the missed disease. Reprod Biomed Online 2025; 50:104837. [PMID: 40287215 DOI: 10.1016/j.rbmo.2025.104837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 01/07/2025] [Accepted: 01/16/2025] [Indexed: 04/29/2025]
Abstract
Adenomyosis, a menstruation-related uterine disorder, refers to the presence of endometrial stroma and glands within the myometrium and is typically observed in reproductive-age women. The pathogenesis explaining the migration, persistence, proliferation and differentiation of ectopic endometrial cells includes a genetic and epigenetic background, an oestrogen/progesterone receptor imbalance and an inflammatory reaction driven by local immune dysfunction, along with fibrosis and neuroangiogenesis within the myometrium. In the past, it was thought that adenomyosis almost exclusively affected multiparous women after 40 years of age and the diagnosis was generally confirmed upon hysterectomy. Nowadays, using imaging techniques such as transvaginal ultrasonography and magnetic resonance imaging, adenomyosis is increasingly identified in young women with dysmenorrhoea, dyspareunia, abnormal uterine bleeding and heavy menstrual bleeding, and also in infertile patients. Furthermore, adenomyosis often coexists with other gynaecological conditions, such as endometriosis and uterine fibroids. Despite the improvement of non-invasive diagnostic tools, the awareness of the condition is still poor and the diagnosis is often missed, due also to a heterogeneity in clinical presentation and imaging criteria. In addition, medical and surgical management do not follow shared recommendations, even though adenomyosis requires a lifelong management plan, including pain and bleeding control, fertility preservation and pregnancy complications.
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Affiliation(s)
- Pietro Santulli
- Faculté de Santé, Faculté de Médicine Paris Centre, Université Paris-Cité, Paris, France.; Department of Gynecology Obstetrics II and Reproductive Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Paris, France.; Department of Development, Reproduction and Cancer, Institut Cochin, INSERM U1016, Paris, France
| | - Silvia Vannuccini
- Department of Experimental, Clinical and Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy.; Department of Maternal and Child Health, Careggi University Hospital, Florence, Italy
| | - Mathilde Bourdon
- Faculté de Santé, Faculté de Médicine Paris Centre, Université Paris-Cité, Paris, France.; Department of Gynecology Obstetrics II and Reproductive Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Paris, France.; Department of Development, Reproduction and Cancer, Institut Cochin, INSERM U1016, Paris, France
| | - Charles Chapron
- Faculté de Santé, Faculté de Médicine Paris Centre, Université Paris-Cité, Paris, France.; Department of Gynecology Obstetrics II and Reproductive Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Paris, France.; Department of Development, Reproduction and Cancer, Institut Cochin, INSERM U1016, Paris, France
| | - Felice Petraglia
- Department of Experimental, Clinical and Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy.; Department of Maternal and Child Health, Careggi University Hospital, Florence, Italy..
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12
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Afzali N, Hafizi L, Abdollahi S. Risk factors for uterine adenomyosis diagnosed by MRI in women of reproductive age. Ann Med Surg (Lond) 2025; 87:1941-1946. [PMID: 40212136 PMCID: PMC11981308 DOI: 10.1097/ms9.0000000000003175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 03/05/2025] [Indexed: 04/13/2025] Open
Abstract
Background Adenomyosis is a condition characterized by the presence of endometrial glands and stroma within the myometrium. It can manifest as either focal or diffuse. While histopathological examination of the uterus following hysterectomy remains the gold standard for definitive diagnosis, non-invasive imaging techniques, particularly magnetic resonance imaging (MRI), are crucial for diagnosis. This study aimed to investigate the risk factors and associated pathologies in women with MRI-confirmed adenomyosis. Methods In this case-control study, 50 women of reproductive age with MRI-confirmed adenomyosis were recruited as the case group, and fifty other women who underwent pelvic MRI due to various indications that were not diagnosed as adenomyosis were included as the control group. Pelvic MRI with and without intravenous contrast was done for all patients. Factors such as age, smoking, number of pregnancies, history of uterine surgery, endometriosis, ovarian cyst, and coexisting leiomyoma were searched and recorded in both groups, and their relationship with uterine adenomyosis was statistically analyzed. The software used was IBM-SPSS v.26. A Significance level of less than 5% was considered. Results No significant difference was found in terms of age (P = 0.891), smoking (P = 0.999), coexisting leiomyoma (P = 0.687), and ovarian cysts (P = 1.00) between case and control groups. The prevalence of endometriosis (P < 0.0001), history of uterine surgery (P = 0.002), and number of pregnancies (P = 0.012) were significantly higher in the case group. Conclusion The study findings suggest significant associations between endometriosis, number of pregnancies, and history of uterine surgery with adenomyosis. Therefore, managing these risk factors appropriately can substantially reduce the occurrence of adenomyosis.
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Affiliation(s)
- Narges Afzali
- Department of Radiology, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran
| | - Leili Hafizi
- Department of Obstetrics and Gynecology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Shamim Abdollahi
- Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran
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13
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Torres PC, Tàssies D, Castillo H, Gracia M, Feixas G, Reverter JC, Carmona F, Martínez-Zamora MA. Long-term follow-up of the effect of oral dienogest and dienogest/ethinylestradiol treatment on cell-free DNA levels in patients with deep endometriosis. Eur J Med Res 2025; 30:193. [PMID: 40114274 PMCID: PMC11927308 DOI: 10.1186/s40001-025-02429-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 03/04/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Endometriosis is currently considered a systemic inflammatory disease and different non-invasive inflammatory markers, such as cell-free DNA (cfDNA), have recently been evaluated. Hormonal treatments are frequently prescribed as first-line treatments to improve symptoms, reduce lesions and improve the quality of life of patients with endometriosis. The most frequently used hormonal treatments are estroprogestins and progestins due to their effectiveness and well-tolerated clinical profile. However, the impact these hormonal treatments may have on these markers has yet to be determined. The aim of this study was to assess whether cfDNA levels are modified under the two main first-line hormonal treatments in patients with deep endometriosis (DE). METHODS Ninety patients diagnosed with DE were analyzed in this prospective, observational study. Forty-five received daily oral treatment with dienogest 2 mg, and 45 with 2 mg dienogest/30 μg ethinylestradiol. Plasma cfDNA levels were evaluated by fluorescent assay prior to initiation of treatment and at 6 and 12 months of treatment. RESULTS An increase in cfDNA levels was observed during the follow-up at 6 and 12 months. However, these higher levels were only statistically significant at 12 months of treatment. The increase of cfDNA levels was similar with both treatments. CONCLUSION Higher cfDNA levels were observed in DE patients at 12 months of oral hormonal treatment showing similar results with dienogest or dienogest/ethinylestradiol. This increase could be explained by apoptosis of the endometriosis foci due to the treatment.
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Affiliation(s)
- P Carrillo Torres
- Gynaecology Department. Clinic Institute of Gynaecology, Obstetrics and Neonatology (ICGON), Hospital Clinic of Barcelona, Universitat de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain
| | - D Tàssies
- Hemotherapy and Hemostasis Department, Clinic Institute of Hemato-Oncological Disease (ICMHO), Hospital Clínic of Barcelona, Universitat de Barcelona, Barcelona, Spain
| | - H Castillo
- Gynaecology Department. Clinic Institute of Gynaecology, Obstetrics and Neonatology (ICGON), Hospital Clinic of Barcelona, Universitat de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain
| | - M Gracia
- Gynaecology Department. Clinic Institute of Gynaecology, Obstetrics and Neonatology (ICGON), Hospital Clinic of Barcelona, Universitat de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain
| | - G Feixas
- Gynaecology Department. Clinic Institute of Gynaecology, Obstetrics and Neonatology (ICGON), Hospital Clinic of Barcelona, Universitat de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain
| | - J C Reverter
- Hemotherapy and Hemostasis Department, Clinic Institute of Hemato-Oncological Disease (ICMHO), Hospital Clínic of Barcelona, Universitat de Barcelona, Barcelona, Spain
| | - F Carmona
- Gynaecology Department. Clinic Institute of Gynaecology, Obstetrics and Neonatology (ICGON), Hospital Clinic of Barcelona, Universitat de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain
| | - M A Martínez-Zamora
- Gynaecology Department. Clinic Institute of Gynaecology, Obstetrics and Neonatology (ICGON), Hospital Clinic of Barcelona, Universitat de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain.
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14
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Etrusco A, Agrifoglio V, D’Amato A, Chiantera V, Laganà AS, Haydamous J, Cobellis L, De Franciscis P, Vannuccini S, Krentel H, Naem A, Riemma G. Efficacy and safety of hormone therapies for treating adenomyosis-associated pelvic pain: a systematic review and network meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne) 2025; 16:1571727. [PMID: 40166680 PMCID: PMC11955467 DOI: 10.3389/fendo.2025.1571727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 02/17/2025] [Indexed: 04/02/2025] Open
Abstract
Background To date, there are no clear guidelines available on the treatment of adenomyosis-associated pelvic pain (AAPP); however, numerous hormonal treatments (HTs) are currently being used off-label. We conducted a systematic review and network metanalysis with the aim of assessing the efficacy and safety of HTs to reduce AAPP and ranking the available options. Methods MEDLINE, LILACS, EMBASE, Scielo.br, PROSPERO, Cochrane Library, conference proceedings, and international registries were searched with no time, region, or language restrictions. Randomized controlled trials that analyzed AAPP in women undergoing HTs were deemed suitable. Results Six studies (563 women affected by adenomyosis) were included. At 3 months, women who received a placebo or a levonorgestrel-based intrauterine system (LNG-IUS) experienced more AAPP than those who received dienogest [mean difference of visual analog scale (VAS) pain scores (MD) 4.10 (95% CI 0.49 to 7.71); high evidence; MD 3.05 (95% CI 0.45 to 5.65); high evidence]. At 6 months, women who received dienogest experienced significantly less AAPP compared to those who received combined oral contraceptives [MD -2.85 (95% CI -5.30 to -0.39); moderate evidence], while the prevalence of AAPP was higher among those who received a LNG-IUS than those who received dienogest [MD 1.79 (95% CI 0.06 to 3.53); low evidence]. Conclusion Dienogest seems to be the most effective HT for AAPP. However, although rare, it is also related to more adverse effects compared to other HTs. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier CRD42024535472.
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Affiliation(s)
- Andrea Etrusco
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
- Unit of Obstetrics and Gynecology, “Paolo Giaccone” Hospital, Palermo, Italy
| | - Vittorio Agrifoglio
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
- Unit of Obstetrics and Gynecology, “Paolo Giaccone” Hospital, Palermo, Italy
| | - Antonio D’Amato
- Department of Interdisciplinary Medicine (DIM), Unit of Obstetrics and Gynecology, University of Bari “Aldo Moro”, Policlinico of Bari, Bari, Italy
| | - Vito Chiantera
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
- Unit of Gynecologic Oncology, National Cancer Institute - IRCCS - Fondazione “G. Pascale”, Naples, Italy
| | - Antonio Simone Laganà
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
- Unit of Obstetrics and Gynecology, “Paolo Giaccone” Hospital, Palermo, Italy
| | - Joe Haydamous
- Department of Obstetrics Gynecology and Reproductive Sciences, McGovern Medical School at The University of Texas Health Science Center at Houston (UT Health), Houston, TX, United States
| | - Luigi Cobellis
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Pasquale De Franciscis
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Silvia Vannuccini
- Department of Experimental, Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
- Department of Maternal and Child Health, Careggi University Hospital, Florence, Italy
| | - Harald Krentel
- Department of Obstetrics, Gynecology, Gynecologic Oncology and Senology, Bethesda Hospital Duisburg, Duisburg, Germany
| | - Antoine Naem
- Faculty of Mathematics and Computer Science, University of Bremen, Bremen, Germany
| | - Gaetano Riemma
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
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15
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Moïse A, Dzeitova M, de Landsheere L, Nisolle M, Brichant G. Endometriosis and Infertility: Gynecological Examination Practical Guide. J Clin Med 2025; 14:1904. [PMID: 40142712 PMCID: PMC11943251 DOI: 10.3390/jcm14061904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Revised: 03/06/2025] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
Endometriosis, a prevalent gynecological condition affecting 10-15% of reproductive-age women, involves the growth of endometrial-like tissue outside the uterine cavity. This chronic inflammatory disease can significantly impact fertility by disrupting ovulation, tubal transport, and implantation. Clinical manifestations vary widely, ranging from asymptomatic cases to severe pelvic pain, dysmenorrhea, and dyspareunia. Accurate diagnosis remains challenging, often requiring a combination of patient history, clinical examination, and imaging studies. This paper will discuss the clinical approach to endometriosis during a first-line gynecological appointment, focusing on patient history, including detailed assessment of menstrual, pelvic, and bowel symptoms, and clinical examination; thorough gynecological examination, including abdominal and pelvic palpation, speculum examination, and bimanual examination; imaging evaluation (particularly of the role of ultrasound in identifying and characterizing endometriotic lesions, including the use of the #ENZIAN classification for deep infiltrating endometriosis and evaluation of fertility impact); and discussion of the Endometriosis Fertility Index (EFI) as a tool for assessing fertility potential. This comprehensive approach aims to guide clinicians in identifying and managing endometriosis effectively, improving patient outcomes and optimizing fertility management strategies. Methods: A literature search for suitable articles published from January 1974 to 2024 in the English language was performed using PubMed. Results: Endometriosis is associated with infertility rates ranging from 20% to 68%, with mechanisms including pelvic adhesions, chronic inflammation, and immune dysregulation. The revised American Society for Reproductive Medicine (rASRM) classification and #ENZIAN classification were identified as essential tools for staging and characterizing the disease. Transvaginal ultrasound (TVS) demonstrated high diagnostic accuracy for deep infiltrating endometriosis, with a sensitivity of up to 96% and specificity of 99%. EFI emerged as a valuable predictor of natural conception post-surgery. Additionally, the review underscores the frequent co-occurrence of adenomyosis in women with endometriosis, which may further compromise fertility. Despite advancements in imaging techniques and classification systems, the variability in symptom presentation and disease progression continues to challenge early diagnosis and effective management. Conclusions: Endometriosis is a prevalent gynecological condition affecting women of reproductive age and is associated with infertility. This paper describes the diagnostic approach to endometriosis during a first-line gynecological appointment, focusing on clinical history, physical examination, and the role of imaging, particularly ultrasound, in identifying and characterizing endometriosis lesions. The adoption of standardized classification systems such as #ENZIAN and EFI enhances disease staging and fertility prognosis, allowing for tailored treatment strategies. Despite improvements in non-invasive diagnostic methods, challenges persist in correlating symptom severity with disease extent, necessitating continued research into biomarkers and novel imaging techniques. Additionally, the frequent coexistence of adenomyosis further complicates fertility outcomes, underscoring the need for comprehensive management strategies. Further research is needed to enhance early detection strategies and optimize fertility preservation techniques for affected women.
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Affiliation(s)
- Alice Moïse
- Department of Obstetrics and Gynecology, Hopital de La Citadelle, University of Liège, 4000 Liège, Belgium; (L.d.L.); (M.N.); (G.B.)
| | | | - Laurent de Landsheere
- Department of Obstetrics and Gynecology, Hopital de La Citadelle, University of Liège, 4000 Liège, Belgium; (L.d.L.); (M.N.); (G.B.)
| | - Michelle Nisolle
- Department of Obstetrics and Gynecology, Hopital de La Citadelle, University of Liège, 4000 Liège, Belgium; (L.d.L.); (M.N.); (G.B.)
| | - Géraldine Brichant
- Department of Obstetrics and Gynecology, Hopital de La Citadelle, University of Liège, 4000 Liège, Belgium; (L.d.L.); (M.N.); (G.B.)
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Chen CH, Lin YH, Lee CY, Shen H, Hsu YT, Wu PC. Long-term clinical outcomes of dienogest for perimenopausal women with symptomatic adenomyosis. Sci Rep 2025; 15:8174. [PMID: 40059225 PMCID: PMC11891300 DOI: 10.1038/s41598-025-93156-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Accepted: 03/05/2025] [Indexed: 05/13/2025] Open
Abstract
We aimed to evaluate the successful long-term use of dienogest for the management of pelvic pain and bleeding control in perimenopausal women with symptomatic adenomyosis using real-world data. All women aged ≥ 40 years with adenomyosis who complained of dysmenorrhea and/or menorrhagia and received dienogest between September 2018 and December 2021 were retrospectively recruited. The primary outcome was successful long-term use of dienogest for pelvic pain and/or bleeding control. A total of 87 women were analyzed. Overall, forty-nine (56%) patients had excellent pain control, but 17 (20%) eventually underwent hysterectomy, while 21 (24%) received dienogest for over 24 months (mean 33.5 ± 8.5 months). According to subgroup analysis by age (≥ 45 vs. <45), older women easily discontinued dienogest due to side effects (51% vs. 30%, p = 0.047) but less frequently changed to surgery (11% vs. 30%, p = 0.012) than younger women. Older age, higher CA-125 value, and larger uterine size before treatment were linked to poorer long-term responses to dienogest. As risk factor, uterine volume > 352.7 cm3 reflects easier treatment failure (sensitivity = 65.4%, specificity = 66.7%, area = 0.68, p = 0.032). In perimenopausal women with symptomatic adenomyosis, nearly half of the treated patients benefitted from dienogest. Our informative findings can assist clinicians in pre-treatment counseling and identifying factors correlated with treatment effectiveness.
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Affiliation(s)
- Chi-Hau Chen
- Department of Obstetrics and Gynecology, National Taiwan University College of Medicine and Hospital, No. 8, Zhongshan S. Rd., Zhongzheng Dist, 100225, Taipei City, Taiwan (R.O.C.)
| | - Yi-Heng Lin
- Department of Obstetrics and Gynecology, National Taiwan University College of Medicine and Hospital, No. 8, Zhongshan S. Rd., Zhongzheng Dist, 100225, Taipei City, Taiwan (R.O.C.)
| | - Chia-Yi Lee
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Hsin-Chu Branch, No. 25, Ln. 442, Sec. 1, Jingguo Rd., North Dist, 300195, Hsinchu City, Taiwan (R.O.C.)
| | - Hung Shen
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Hsin-Chu Branch, No. 25, Ln. 442, Sec. 1, Jingguo Rd., North Dist, 300195, Hsinchu City, Taiwan (R.O.C.)
| | - Ya-Ting Hsu
- Department of Obstetrics and Gynecology, National Taiwan University College of Medicine and Hospital, No. 8, Zhongshan S. Rd., Zhongzheng Dist, 100225, Taipei City, Taiwan (R.O.C.)
| | - Pei-Chi Wu
- Department of Obstetrics and Gynecology, National Taiwan University College of Medicine and Hospital, No. 8, Zhongshan S. Rd., Zhongzheng Dist, 100225, Taipei City, Taiwan (R.O.C.).
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Hsin-Chu Branch, No. 25, Ln. 442, Sec. 1, Jingguo Rd., North Dist, 300195, Hsinchu City, Taiwan (R.O.C.).
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Xholli A, Perugi I, Cremonini F, Londero AP, Cagnacci A. Evaluation of Long-COVID Syndrome in a Cohort of Patients with Endometriosis or Adenomyosis. J Clin Med 2025; 14:1835. [PMID: 40142642 PMCID: PMC11943416 DOI: 10.3390/jcm14061835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 03/04/2025] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
Background: Long-COVID is characterized by the persistency of COVID-19 symptoms beyond 12 weeks, and it is probably consequent to immune dysregulation induced by SARS-CoV-2 infection. Immune dysregulation is associated with and probably involved in the pathogenesis of chronic gynecological conditions like endometriosis and adenomyosis. This study evaluated whether the presence of endometriosis or adenomyosis increases the risk of long-COVID, i.e., the persistence of COVID-19 symptoms beyond 12 weeks since infection. Methods: This retrospective observational study was performed at the outpatient service for endometriosis and chronic pelvic pain, at a university hospital. The diagnosis of endometriosis/adenomyosis was primarily based on clinical symptoms and ultrasonography assessment. Data regarding infection, vaccination, symptoms associated with SARS-CoV-2 infection, and their persistence for a minimum of 12 weeks were collected. Results: This study included 247 women, 149 controls without and 98 cases with endometriosis/adenomyosis. Among these, 194 (116 controls and 78 cases) had suffered from SARS-CoV-2 infection. Rates of infection and vaccination were similar in the two groups. The distribution of the SARS-CoV-2 vaccine was uniform across the two cohorts. COVID-19 patients with endometriosis or adenomyosis exhibited a higher prevalence (p < 0.001) of dyspnea and chest pain. The prevalence of long-COVID beyond 12 weeks was higher in cases than controls (42% vs. 12%; p < 0.001) with chest pain (p < 0.001) and ageusia (p < 0.05), forming the most representative symptoms. Conclusions: Symptoms of long-COVID are more frequent in women with than without endometriosis/adenomyosis.
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Affiliation(s)
- Anjeza Xholli
- Academic Unit of Obstetrics and Gynaecology, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy; (A.X.)
| | - Isabella Perugi
- Academic Unit of Obstetrics and Gynaecology, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy; (A.X.)
- Department of Neurology, Rehabilitation, Opthalmology, Genetics, Maternal and Infant Health (DINOGMI), 16132 Genova, Italy
| | - Francesca Cremonini
- Academic Unit of Obstetrics and Gynaecology, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy; (A.X.)
- Department of Neurology, Rehabilitation, Opthalmology, Genetics, Maternal and Infant Health (DINOGMI), 16132 Genova, Italy
| | - Ambrogio Pietro Londero
- Department of Neurology, Rehabilitation, Opthalmology, Genetics, Maternal and Infant Health (DINOGMI), 16132 Genova, Italy
- Obstetrics and Gynecology Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
| | - Angelo Cagnacci
- Academic Unit of Obstetrics and Gynaecology, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy; (A.X.)
- Department of Neurology, Rehabilitation, Opthalmology, Genetics, Maternal and Infant Health (DINOGMI), 16132 Genova, Italy
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18
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Devalla A, Mangla M, Ramavath K, Prabhala S, Kumar N, Jarathi A. Diffuse cystic adenomyosis simulating invasive uterine neoplasm on imaging: A postmenopausal diagnostic perplexity! Oncoscience 2025; 12:21-25. [PMID: 39931074 PMCID: PMC11810126 DOI: 10.18632/oncoscience.615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 02/04/2025] [Indexed: 02/13/2025] Open
Abstract
Postmenopausal bleeding (PMB) with a diffusely enlarged uterus necessitates Magnetic Resonance Imaging (MRI) to reach an accurate diagnosis. Adenomyosis, especially extensive glandular variant, is an extremely rare cause reported in a postmenopausal woman. We present a challenging case of an 81-year-old woman with PMB where preoperative MRI suggested possible invasive endometrial neoplasm. However, final histopathological evidence of the hysterectomy specimen suggested Adenomyosis with extensive glandular proliferation. The patient was a multiparous lady with controlled diabetes and hypertension (controlled on medications) and a Body Mass Index of 36 kg/m2. Bimanual examination suggested a diffusely enlarged uterus corresponding to 8-10 weeks gestation. Transvaginal ultrasound (TVUS) and Contrast Enhanced (CE) MRI were performed that reported multiple cystic areas with myometrial thinning at the fundal region- suspected infiltrating endometrial neoplasm. A hysteroscopic guided endometrial biopsy was suggestive of endometrial hyperplasia. In view of concerning MRI findings, a total abdominal hysterectomy and bilateral Salpingo-oophorectomy was performed. Histopathological examination revealed Adenomyosis with extensive glandular proliferation co-existing with endometrial hyperplasia and no atypia. This case highlights an important variant of Adenomyosis that potentially mimics an invasive uterine neoplasm. There is a dearth of uniform reporting standards for Adenomyosis and rarity of this condition in postmenopausal woman posing a significant preoperative diagnostic challenge.
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Affiliation(s)
- Anusha Devalla
- Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Bibinagar, Hyderabad 508126, India
| | - Mishu Mangla
- Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Bibinagar, Hyderabad 508126, India
| | - Krishna Ramavath
- Department of General Surgery, All India Institute of Medical Sciences, Bibinagar, Hyderabad 508126, India
| | - Shailaja Prabhala
- Department of Pathology, All India Institute of Medical Sciences, Bibinagar, Hyderabad 508126, India
| | - Naina Kumar
- Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Bibinagar, Hyderabad 508126, India
| | - Aparna Jarathi
- Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Bibinagar, Hyderabad 508126, India
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19
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Dantzler MD, Miller TA, Dougherty MW, Quevedo A. The Microbiome Landscape of Adenomyosis: A Systematic Review. Reprod Sci 2025; 32:251-260. [PMID: 39707139 DOI: 10.1007/s43032-024-01766-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 12/09/2024] [Indexed: 12/23/2024]
Abstract
Alterations in the microbiome composition have been identified in common gynecologic pathologies such as endometriosis carving a new frontier in diagnosis and treatment. We aimed to examine the existing literature on perturbations in the reproductive tract microbiome of individuals with adenomyosis informing future therapeutic targets. To examine the association between the reproductive tract microbiome composition among individuals with adenomyosis when compared to controls that can lead to new research evaluating novel mechanisms of action and treatment modalities. A systematic literature search identified studies that compared differences in microbiome composition using culture-independent microbiome analysis between individuals with adenomyosis when compared to controls. Five observational cross-sectional studies characterizing the lower and upper reproductive tract in humans were included. The diagnostic criteria of adenomyosis included surgical and imaging-based criteria. All studies used a 16S rRNA sequencing method. All individuals were recruited from either China or Thailand. An association between adenomyosis and alterations in the microbiome composition included relative deficiencies in Lactobacillus and relative enrichment of anaerobic and gram-negative bacteria when compared to control participants. Comparative studies suggest that there are significant perturbations in the microbiota composition of individuals with adenomyosis when compared with controls. Limiting conclusions include relative small sample sizes, a homogeneous population, and scant clinical phenotypic data. This systematic review identified significant alterations in the bacterial composition of adenomyosis cases that can be leveraged to design mechanistic studies and future innovative approaches to diagnose and manage this pathology. Trial registration: PROSPERO (CRD42023494563). Registered December 28, 2023.
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Affiliation(s)
| | - Tiffani-Amber Miller
- Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, FL, USA
| | - Michael W Dougherty
- Department of Gastroenterology, University of Florida College of Medicine, Gainesville, FL, USA
| | - Amira Quevedo
- Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, FL, USA.
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20
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Galati G, Olivieri C, Cosentino M, Azenkoud I, Cugini S, Sorrenti G, Rizzo G, Muzii L. Medical treatment before in-vitro fertilization in patients with adenomyosis: a systematic review and meta-analysis. J Assist Reprod Genet 2025; 42:381-388. [PMID: 39666211 PMCID: PMC11871277 DOI: 10.1007/s10815-024-03323-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 11/11/2024] [Indexed: 12/13/2024] Open
Abstract
The objective of this study is to evaluate if medical treatment before assisted reproductive technology (ART) improves the results in infertile patients with adenomyosis. A literature search was performed with EMBASE, PubMed, and Cochrane. The primary outcome was clinical pregnancy rate (CPR). Secondary outcomes were live birth rate (LBR) per cycle and miscarriage rate (MR) after ART with or without medical pretreatment. Additionally, a comparison was made between women undergoing medical pretreatment before frozen embryo transfer (FET) and those who underwent FET alone, including any type of endometrial preparation. Ten studies were included. The present meta-analysis supports the use of long-term GnRH agonist therapy in patients with adenomyosis, which enhances the CPR (odds ratio (OR) 1.49, 95% CI 1.15 to 1.92) in IVF/ICSI with fresh ET, while the comparison in women undergoing FET cycles did not reach statistical significance (OR 1.34 95% CI 0.70-2.55). Pretreatment with GnRH agonist did not demonstrate a benefit on the LBR and MR per cycle in IVF/ICSI with fresh ET in comparison to standard ovarian stimulation protocols. Similar results were observed in the setting of FET, failing to indicate a superiority of GnRH agonist pretreatment over standard FET protocols for LBR and MR. In conclusion, GnRH agonist pretreatment before ART carries a potential benefit in improving outcomes in terms of higher CPR, but there is no significant impact on LBR and MR. Pretreatment with GnRH agonists could be adopted as a possible alternative ART protocol in selected patients with adenomyosis and infertility.
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Affiliation(s)
- Giulia Galati
- Department of Maternal and Child Health and Urology, Sapienza University, Viale Regina Elena, 324 - 00161, Rome, Italy.
| | - Carlotta Olivieri
- Department of Maternal and Child Health and Urology, Sapienza University, Viale Regina Elena, 324 - 00161, Rome, Italy
| | - Martina Cosentino
- Department of Maternal and Child Health and Urology, Sapienza University, Viale Regina Elena, 324 - 00161, Rome, Italy
| | - Ilham Azenkoud
- Department of Maternal and Child Health and Urology, Sapienza University, Viale Regina Elena, 324 - 00161, Rome, Italy
| | - Sara Cugini
- Department of Medical and Surgical Sciences, Institute of Obstetrics and Gynecology, University of Foggia, Foggia, Italy
| | | | - Giuseppe Rizzo
- Department of Maternal and Child Health and Urology, Sapienza University, Viale Regina Elena, 324 - 00161, Rome, Italy
| | - Ludovico Muzii
- Department of Maternal and Child Health and Urology, Sapienza University, Viale Regina Elena, 324 - 00161, Rome, Italy
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21
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Kadam N, Khalid S, Jayaprakasan K. How Reproducible Are the Ultrasound Features of Adenomyosis Defined by the Revised MUSA Consensus? J Clin Med 2025; 14:456. [PMID: 39860462 PMCID: PMC11765981 DOI: 10.3390/jcm14020456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 01/05/2025] [Accepted: 01/08/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: The aim of this study is to assess the inter- and intra-observer reproducibility of the identification of direct and indirect ultrasonographic features of adenomyosis as defined by the revised Morphological Uterus Sonographic Assessment (MUSA) consensus (2022). Methods: A cohort of 74 women, aged 18 to 45, were recruited from the recurrent miscarriage and general gynaecology clinic at a university-based fertility centre. All the participants underwent 2D and 3D transvaginal Ultrasound scan (TVS) examination in the late follicular and early luteal phase. Conventional grey scale and power Doppler image volumes were acquired and stored. Subsequently, the stored 3D ultrasound images were independently re-evaluated offline by the two observers for the direct and indirect features of adenomyosis as outlined by the revised MUSA group. The intra- and the inter-observer reproducibility was estimated using Cohen's Kappa coefficient. Results: The intra- and interobserver reproducibility (K -0.27, 95% CI 0.06-0.48 and K 0.13, 95% CI -0.10-0.37, respectively) for at least one direct feature of adenomyosis was only modest. Amongst the individual direct features, the interobserver variability of identifying myometrial cysts was fair (K 0.21, 95% CI -0.00-0.42), whereas the intra-observer variability was moderate (K 0.44, 95% CI 0.26-0.63). While hyperechogenic islands identification achieved a fair level of intra- (K 0.31, 95% CI 0.09-0.53) and interobserver (K 0.24, 95% CI 0.01-0.47) agreement, the reproducibility of reporting sub-endometrial lines/buds was fair for the intra-observer (K 0.22, 95% CI -0.02 0.47) and poor for the interobserver (K 0.00, 95% CI -0.20-0.19). The interobserver agreement for indirect features varied from poor to moderate, while the intra-observer agreement ranged between poor to good. Conclusions: The reporting of adenomyosis using direct features suggested by the revised MUSA group consensus showed only modest interobserver and intra-observer agreement. The definitions of ultrasound features for adenomyosis need further refining to enhance the reliability of diagnosis criteria of adenomyosis.
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Affiliation(s)
- Nikit Kadam
- Derby Fertility Unit, Royal Derby Hospital, University Hospital of Derby and Burton, Derby DE22 3NE, UK
- Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, UK
| | - Somia Khalid
- Derby Fertility Unit, Royal Derby Hospital, University Hospital of Derby and Burton, Derby DE22 3NE, UK
| | - Kanna Jayaprakasan
- Derby Fertility Unit, Royal Derby Hospital, University Hospital of Derby and Burton, Derby DE22 3NE, UK
- Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, UK
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22
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Matot R, Bar-Peled U, Geron Y, Danieli-Gruber S, Gilboa Y, Drukker L, Krissi H, Borovich A, Perlman S. Effect of adenomyosis on placenta-related obstetric complications. Reprod Biomed Online 2025; 50:104414. [PMID: 39504845 DOI: 10.1016/j.rbmo.2024.104414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Revised: 07/29/2024] [Accepted: 08/09/2024] [Indexed: 11/08/2024]
Abstract
RESEARCH QUESTION What is the relationship between sonographic diagnosis of isolated adenomyosis and placenta-associated obstetric outcomes? DESIGN In this 12-year retrospective cohort study (2010-2022), patients presenting with adenomyosis-related symptoms were assessed via ultrasound. The study included 59 women diagnosed with adenomyosis and 62 controls, leading to 203 births (90 in the adenomyosis group and 113 in the control group). Patients with endometriosis, uterine fibroids and anomalies, and those using assisted reproductive technology were excluded. The primary outcome focused on a composite of placenta-associated adverse outcomes, including preterm birth, small-for-gestational-age fetuses, hypertensive disorders of pregnancy, placental abruption and post-partum haemorrhage. RESULTS No clinically significant differences in demographic characteristics were noted between the two groups. However, the adenomyosis group showed a significantly higher rate of adverse placental function outcomes (27%) compared with the control group (11%, P = 0.005). Adjusted analyses for maternal age, parity and aspirin usage revealed increased risk of hypertensive disorders (adjusted OR 5.91, 95% CI 1.50-30.0; P = 0.017) and adverse placental function outcomes (adjusted OR 3.44, 95% CI 1.53-8.09; P = 0.003) in the adenomyosis group. CONCLUSION Adenomyosis is significantly associated with increased risk of adverse placental function outcomes and hypertensive disorders of pregnancy. These findings suggest that adenomyosis may have a distinct impact on pregnancy, underscoring the need for further research to elucidate specific sonographic characteristics of adenomyosis and their effects on placental function.
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Affiliation(s)
- Ran Matot
- Obstetrics and Gynaecology, Helen Schneider Hospital for Women, Rabin Medical Centre, Petach Tikva, Israel; Tel Aviv University School of Medicine, Tel Aviv, Israel.
| | - Uval Bar-Peled
- Obstetrics and Gynaecology, Helen Schneider Hospital for Women, Rabin Medical Centre, Petach Tikva, Israel
| | - Yossi Geron
- Obstetrics and Gynaecology, Helen Schneider Hospital for Women, Rabin Medical Centre, Petach Tikva, Israel; Tel Aviv University School of Medicine, Tel Aviv, Israel
| | - Shir Danieli-Gruber
- Obstetrics and Gynaecology, Helen Schneider Hospital for Women, Rabin Medical Centre, Petach Tikva, Israel; Tel Aviv University School of Medicine, Tel Aviv, Israel
| | - Yinon Gilboa
- Obstetrics and Gynaecology, Helen Schneider Hospital for Women, Rabin Medical Centre, Petach Tikva, Israel; Tel Aviv University School of Medicine, Tel Aviv, Israel
| | - Lior Drukker
- Obstetrics and Gynaecology, Helen Schneider Hospital for Women, Rabin Medical Centre, Petach Tikva, Israel; Tel Aviv University School of Medicine, Tel Aviv, Israel
| | - Haim Krissi
- Obstetrics and Gynaecology, Helen Schneider Hospital for Women, Rabin Medical Centre, Petach Tikva, Israel; Tel Aviv University School of Medicine, Tel Aviv, Israel
| | - Adi Borovich
- Obstetrics and Gynaecology, Maimonides Medical Center, Brooklyn, NY, USA
| | - Sharon Perlman
- Obstetrics and Gynaecology, Helen Schneider Hospital for Women, Rabin Medical Centre, Petach Tikva, Israel; Tel Aviv University School of Medicine, Tel Aviv, Israel
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23
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Min N, van Keizerswaard J, Visser RH, Burger NB, Rake JWT, Aarts JWM, Van den Bosch T, Leonardi M, Huirne JAF, de Leeuw RA. Prediction of vesicouterine adhesions by transvaginal sonographic sliding sign technique: validation study. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2025; 65:114-121. [PMID: 39587459 DOI: 10.1002/uog.29128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 09/13/2024] [Accepted: 10/09/2024] [Indexed: 11/27/2024]
Abstract
OBJECTIVE Adhesions between the uterus, bladder and anterior abdominal wall are associated with clinical sequelae, including chronic pelvic pain and dyspareunia, and can also yield complications during surgery. The transvaginal sonographic (TVS) sliding bladder sign is a minimally invasive diagnostic tool to evaluate the presence of vesicouterine adhesions. This study aimed to determine the predictive value and intra- and interobserver variation of the TVS sliding bladder sign in the assessment of vesicouterine adhesions. METHODS This was a prospective observational double-blind diagnostic accuracy study conducted at the Amsterdam University Medical Center. Patients scheduled for gynecological laparoscopic surgery for a benign disorder between January 2020 and December 2022 were included consecutively. All patients underwent preoperative TVS, including a dynamic sliding bladder sign examination in our outpatient clinic. Videoclips of the TVS scans were stored for offline assessment and used as an index test. The recordings of both TVS and laparoscopy were evaluated for diagnostic characteristics of vesicouterine adhesions by independent assessors, who were blinded to the clinical situation in addition to the laparoscopic findings when assessing recordings of TVS and vice versa. The presence of adhesions on laparoscopy was used as the reference standard. The positive predictive value (PPV), negative predictive value (NPV), specificity and sensitivity of the sliding bladder sign were calculated. In addition, inter- and intraobserver variability of the sliding bladder sign on TVS were assessed. RESULTS Of 116 included women, 57 had a negative sliding bladder sign on TVS, while on laparoscopy, 51 women had mild and 28 had severe vesicouterine adhesions. A negative sliding bladder sign had a PPV of 94.7% (95% CI, 88.9-100%) for the presence of any vesicouterine adhesions, and a positive sliding bladder sign had a specificity of 91.9% (95% CI, 83.1-100%). For severe adhesions, the negative sliding bladder sign had a sensitivity of 89.3% (95% CI, 77.8-100%) and a positive sliding bladder sign had a NPV of 94.9% (95% CI, 89.3-100%). When using Cohen's kappa coefficient, inter- and intraobserver agreement between assessors was good. CONCLUSIONS Sliding bladder sign evaluation using TVS is a reliable diagnostic tool for the prediction of vesicouterine adhesions on laparoscopy. A negative sliding bladder sign indicates the presence of vesicouterine adhesions, while a positive sliding bladder sign makes the presence of severe adhesions unlikely. Establishing vesicouterine adhesions by TVS may optimize preoperative planning, and can be used for future studies to evaluate the relationship between symptomatology and vesicouterine adhesions and, subsequently, the effect of adhesion-prevention interventions. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Affiliation(s)
- N Min
- Amsterdam University Medical Center, location Vrije Universiteit Amsterdam, Department of Obstetrics & Gynecology, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development, Amsterdam, The Netherlands
| | - J van Keizerswaard
- Amsterdam University Medical Center, location Amsterdam Medical Center, Department of Obstetrics & Gynecology, Amsterdam, The Netherlands
| | - R H Visser
- Amsterdam University Medical Center, location Amsterdam Medical Center, Department of Obstetrics & Gynecology, Amsterdam, The Netherlands
| | - N B Burger
- Amsterdam University Medical Center, location Amsterdam Medical Center, Department of Obstetrics & Gynecology, Amsterdam, The Netherlands
| | - J W T Rake
- Amsterdam University Medical Center, location Amsterdam Medical Center, Department of Obstetrics & Gynecology, Amsterdam, The Netherlands
| | - J W M Aarts
- Amsterdam University Medical Center, location Amsterdam Medical Center, Department of Obstetrics & Gynecology, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Treatment and Quality of Life, Amsterdam, The Netherlands
| | - T Van den Bosch
- Department of Obstetrics and Gynecology, University Hospital KU Leuven, Leuven, Belgium
- Department of Development and Regeneration, KU Leuven, Leuven, Belgium
| | - M Leonardi
- Department of Obstetrics and Gynaecology, McMaster University, Hamilton, ON, Canada
| | - J A F Huirne
- Amsterdam University Medical Center, location Vrije Universiteit Amsterdam, Department of Obstetrics & Gynecology, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development, Amsterdam, The Netherlands
| | - R A de Leeuw
- Amsterdam University Medical Center, location Vrije Universiteit Amsterdam, Department of Obstetrics & Gynecology, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development, Amsterdam, The Netherlands
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24
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Bulut Aydemir HM, Kahyaoğlu S, Halilzade İ, Moraloğlu-Tekin Ö. Value of serum muscular creatinine phosphokinase levels in patients with adenomyosis as a non-invasive diagnostic marker. Int J Gynaecol Obstet 2025; 168:314-319. [PMID: 39081170 DOI: 10.1002/ijgo.15824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/05/2024] [Accepted: 07/13/2024] [Indexed: 12/18/2024]
Abstract
OBJECTIVE In the present study, we aimed to compare serum CK-MM levels in patients with and without adenomyosis and to investigate whether CK-MM level can be a non-invasive marker for myometrial damage due to adenomyosis. MATERIALS AND METHODS Our study was a prospective case-control study in a tertiary center and consisted of 40 patients with a clinical/ultrasonographic diagnosis of adenomyosis and 40 patients without a clinical/ultrasonographic diagnosis of adenomyosis as the control group based on recently published morphological uterus sonographic assessment (MUSA) criteria. Individuals of similar age who signed a voluntary consent form were included in our study. Demographic, clinical, and laboratory findings of the patients in both groups were recorded. Blood serum samples were used for the determination of serum CK-MM levels of the participants in our study. The samples were analyzed by using the human CK-MM enzyme-linked immunosorbent assay (ELISA) kit. RESULTS In our study, the mean serum CK-MM level was 16.2 ± 21.7 (ng/dL) in patients with adenomyosis and 2.6 ± 2.2 (ng/dL) in patients without adenomyosis. Serum CK-MM level was statistically significantly higher in the patient group with adenomyosis than in the control group (p < 0.001). The CK-MM threshold value of 3.43 ng/mL, with a sensitivity of 82.5% and specificity of 85%, has been found to be a valuable distinguishing level in patients with and without adenomyosis. CONCLUSION In this study, we demonstrated that serum CK-MM can be used as a non-invasive diagnostic method in patients with adenomyosis. As the number of studies around this subject in the literature is insufficient, larger studies are needed to use CK-MM as a diagnostic marker in adenomyosis.
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Affiliation(s)
| | - Serkan Kahyaoğlu
- Gynecology and Obstetrics Department, University of Health Sciences Ankara City Hospital, Ankara, Turkey
| | - İnci Halilzade
- Gynecology and Obstetrics Department, University of Health Sciences Ankara City Hospital, Ankara, Turkey
| | - Özlem Moraloğlu-Tekin
- Gynecology and Obstetrics Department, University of Health Sciences Ankara City Hospital, Ankara, Turkey
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25
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Cozzolino M, Bulun S, De Ziegler D, Exacoustos C, Fatemi H, Garcia-Velasco JA, Horne A, Petraglia F, Santulli P, Somigliana E, Soorin K, Van den Bosch T, Viganò P, Humaidan P. The First Lugano Workshop on the role of adenomyosis in ART. Reprod Biomed Online 2025; 50:104444. [PMID: 39672080 DOI: 10.1016/j.rbmo.2024.104444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/28/2024] [Accepted: 09/02/2024] [Indexed: 12/15/2024]
Abstract
Adenomyosis is an important clinical condition with uncertain prevalence, and clinical focus on adenomyosis in patients undergoing assisted reproductive technology (ART) has increased during recent years. Recognizing the limited clinical knowledge on the impact of adenomyosis on ART outcomes, the First Lugano Adenomyosis Workshop was a symposium involving experts in the field of adenomyosis, covering basic research, imaging, surgery and infertility to highlight current advances and future research areas over a wide range of topics related to adenomyosis. Adenomyosis is characterized by altered oestrogen and progesterone signalling pathways. Although the criteria of the Morphological Uterus Sonographic Assessment (MUSA) Consortium apply to patients with infertility, the presence of direct signs and localization in the different myometrial layers, particularly the inner myometrium, need more focus. In addition to the MUSA criteria, clinical symptoms and the magnitude of uterine enlargement should also be considered. Whilst pre-treatment with gonadotrophin-releasing hormone agonist with or without an aromatase inhibitor in frozen embryo transfer cycles seems promising, many issues related to therapy remain unanswered. During the Workshop, therapeutic progress over the past decades as well as novel insights were presented and discussed. The role of this opinion paper is to stimulate discussion and spark further interest in adenomyosis and the role of adenomyosis in infertility.
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Affiliation(s)
- Mauro Cozzolino
- IVIRMA Global Research Alliance, IVI Roma, Rome, Italy; IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
| | - Serdar Bulun
- Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL, USA
| | - Dominique De Ziegler
- Department of Obstetrics, Gynaecology and Reproductive Medicine, Hopital Foch - Université de Paris Ouest, Paris, France
| | - Caterina Exacoustos
- Department of Surgical Sciences, Obstetrics and Gynaecology Clinic, University of Rome 'Tor Vergata', Rome, Italy
| | | | | | - Andrew Horne
- MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
| | - Felice Petraglia
- Obstetrics and Gynaecology, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Careggi University Hospital, Florence, Italy
| | - Pietro Santulli
- Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; Assistance Publique - Hôpitaux de Paris, Hôpital Universitaire Paris Centre, Centre Hospitalier Universitaire Cochin, Department of Gynaecology Obstetrics II and Reproductive Medicine, Paris, France
| | - Edgardo Somigliana
- ART Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Kim Soorin
- IVIRMA Global Research Alliance, RMA Basking Ridge, NJ, USA
| | - Thierry Van den Bosch
- Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium
| | - Paola Viganò
- ART Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Peter Humaidan
- The Fertility Clinic, Skive Regional Hospital, Skive, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Lin CW, Ou HT, Wu MH, Yen CF, Taiwan Endometriosis Society Adenomyosis Consensus Group. Expert Consensus on the Management of Adenomyosis: A Modified Delphi Method Approach by the Taiwan Endometriosis Society. Gynecol Minim Invasive Ther 2025; 14:24-32. [PMID: 40143988 PMCID: PMC11936390 DOI: 10.4103/gmit.gmit-d-24-00055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 12/02/2024] [Accepted: 12/11/2024] [Indexed: 03/28/2025] Open
Abstract
Objectives To establish the expert opinions and consensus recommendations from the Taiwanese Endometriosis Society on managing adenomyosis. Materials and Methods This study employed a two-round modified Delphi method incorporating a national panel of expert gynecologists to form the consensus on managing adenomyosis. The first round of the Delphi procedure involved an expert panel from the board members to evaluate the relevance of each item. In the subsequent round of votes, gynecologists affiliated with the Taiwan Endometriosis Society participated and used a 5-point Likert scale to cast votes and approve each statement. The rating scales for each item of the key recommendations were analyzed for the distribution of degrees of agreement. Results The consensus for managing adenomyosis was developed, encompassing various aspects including imaging diagnosis, hormonal treatment, surgical treatment, noninvasive/minimally invasive treatment, infertility concerns, and obstetric considerations. In the first round of voting, all 25 recommendations received approval from the board members, advancing them to the second round. During the second round of voting, the majority of recommendations received either a "strongly agree" or "agree" response. There was divergence regarding the similarity of effectiveness in alleviating adenomyosis-related pain by either laparotomic or laparoscopic approaches (55% strongly agree or agree vs. 21% disagree or strongly disagree). Conclusion The Taiwan Endometriosis Society expert panel has established a set of consensus guidelines for the management of adenomyosis. There are diverging opinions among experts regarding the optimal surgical approaches for resection of adenomyosis.
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Affiliation(s)
- Chih-Wei Lin
- Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Huang-Tz Ou
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Meng-Hsing Wu
- Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chih-Feng Yen
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou, Taiwan
- Department of Obstetrics and Gynecology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- School of Medicine, National Tsing Hua University, Hsinchu, Taiwan
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Ciccarone F, Biscione A, Robba E, Pasciuto T, Giannarelli D, Gui B, Manfredi R, Ferrandina G, Romualdi D, Moro F, Zannoni GF, Lorusso D, Scambia G, Testa AC. A clinical ultrasound algorithm to identify uterine sarcoma and smooth muscle tumors of uncertain malignant potential in patients with myometrial lesions: the MYometrial Lesion UltrasouNd And mRi study. Am J Obstet Gynecol 2025; 232:108.e1-108.e22. [PMID: 39084498 DOI: 10.1016/j.ajog.2024.07.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 07/22/2024] [Accepted: 07/23/2024] [Indexed: 08/02/2024]
Abstract
BACKGROUND Differential diagnosis between benign uterine smooth muscle tumors and malignant counterpart is challenging. OBJECTIVE To evaluate the accuracy of a clinical and ultrasound based algorithm in predicting mesenchymal uterine malignancies, including smooth muscle tumors of uncertain malignant potential. STUDY DESIGN We report the 12-month follow-up of an observational, prospective, single-center study that included women with at least 1 myometrial lesion ≥3 cm on ultrasound examination. These patients were classified according to a 3-class diagnostic algorithm, using symptoms and ultrasound features. "White" patients underwent annual telephone follow-up for 2 years, "Green" patients underwent a clinical and ultrasound follow-up at 6, 12, and 24 months and "Orange" patients underwent surgery. We further developed a risk class system to stratify the malignancy risk. RESULTS Two thousand two hundred sixty-eight women were included and target lesion was classified as benign in 2158 (95.1%), as other malignancies in 58 (2.6%) an as mesenchymal uterine malignancies in 52 (2.3%) patients. At multivariable analysis, age (odds ratio 1.05 [95% confidence interval 1.03-1.07]), tumor diameter >8 cm (odds ratio 5.92 [95% confidence interval 2.87-12.24]), irregular margins (odds ratio 2.34 [95% confidence interval 1.09-4.98]), color score=4 (odds ratio 2.73 [95% confidence interval 1.28-5.82]), were identified as independent risk factors for malignancies, whereas acoustic shadow resulted in an independent protective factor (odds ratio 0.39 [95% confidence interval 0.19-0.82[). The model, which included age as a continuous variable and lesion diameter as a dichotomized variable (cut-off 81 mm), provided the best area under the curve (0.87 [95% confidence interval 0.82-0.91]). A risk class system was developed, and patients were classified as low-risk (predictive model value <0.39%: 0/606 malignancies, risk 0%), intermediate risk (predictive model value 0.40%-2.2%: 9/1093 malignancies, risk 0.8%), high risk (predictive model value ≥2.3%: 43/566 malignancies, risk 7.6%). CONCLUSION The preoperative 3-class diagnostic algorithm and risk class system can stratify women according to risk of malignancy. Our findings, if confirmed in a multicenter study, will permit differentiation between benign and mesenchymal uterine malignancies allowing a personalized clinical approach.
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Affiliation(s)
- Francesca Ciccarone
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy.
| | - Antonella Biscione
- Ovarian Cancer Center, Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy
| | - Eleonora Robba
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy
| | - Tina Pasciuto
- Data Collection G-STeP Research Core Facility, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy; Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Diana Giannarelli
- Epidemiology and Biostatistics Facility, G-STeP Generator, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Benedetta Gui
- Department of Diagnostic Imaging, Radiation Oncology and Hematology, Fondazione Policlinico "A. Gemelli" IRCCS, Rome, Italy; Catholic University of the Sacred Hearth, Rome, Italy
| | - Riccardo Manfredi
- Department of Diagnostic Imaging, Radiation Oncology and Hematology, Fondazione Policlinico "A. Gemelli" IRCCS, Rome, Italy; Catholic University of the Sacred Hearth, Rome, Italy; University Department of Radiological and Hematological Sciences, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Gabriella Ferrandina
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy; Section of Obstetrics and Gynecology, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Daniela Romualdi
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy
| | - Francesca Moro
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy
| | - Gian Franco Zannoni
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy; Section of Pathology, Department of Woman and Child Health and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Domenica Lorusso
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy; Section of Obstetrics and Gynecology, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Giovanni Scambia
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy; Section of Obstetrics and Gynecology, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Antonia Carla Testa
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy; Section of Obstetrics and Gynecology, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy
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Salmeri N, Di Stefano G, Viganò P, Stratton P, Somigliana E, Vercellini P. Functional determinants of uterine contractility in endometriosis and adenomyosis: a systematic review and meta-analysis. Fertil Steril 2024; 122:1063-1078. [PMID: 39067674 PMCID: PMC11624067 DOI: 10.1016/j.fertnstert.2024.07.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 07/22/2024] [Accepted: 07/22/2024] [Indexed: 07/30/2024]
Abstract
IMPORTANCE Evidence suggests that aberrant uterine contractility in nonpregnant women with endometriosis and adenomyosis contributes to symptoms and potentially heralds their pathogenesis. However, uterine peristalsis remains understudied, inconsistently measured, and poorly understood. OBJECTIVE To summarize evidence on uterine contractility across the menstrual cycle phases in women with endometriosis and adenomyosis. DATA SOURCES PubMed/MEDLINE, Embase, and Scopus databases searched up to May 2, 2024. STUDY SELECTION AND SYNTHESIS Observational studies compared quantitative measures of uterine contractility using magnetic resonance imaging, ultrasound, electrophysiology, or direct intrauterine pressure recording across different menstrual cycle phases between women with endometriosis/adenomyosis and controls on the basis of predefined problem/population, intervention, comparison, and outcome criteria. Study quality was assessed using the Newcastle-Ottawa Scale. Pooled estimates for primary (risk ratios with 95% confidence intervals [CIs]) and secondary (mean difference [MD] with 95% CIs) outcomes were calculated using random-effects models. MAIN OUTCOMES Pooled risk of retrograde menstruation uterine contraction pattern in cases vs. controls; pooled MD in continuous measures of uterine contractility (frequency, amplitude, and velocity of contractions) across all the menstrual cycle phases in cases vs. controls. RESULTS Nine studies met the inclusion criteria; most were studies that evaluated women with endometriosis. An increased risk of retrograde uterine contractions during menstruation was observed in women with endometriosis compared with that in controls (risk ratio, 8.63; 95% CI, 3.24-22.95; I2, 0). The pooled MDs in contraction frequency between cases and controls were 0.82 (95% CI, 0.13-1.52; I2, 18.61%) in the menstrual phase and 0.52 (95% CI, 0.22-0.83; I2, 27.18%) in the luteal phase. Results for the follicular and periovulatory phases were more heterogeneous. Higher contraction amplitudes in women with endometriosis or adenomyosis were reported across all menstrual cycle phases. Because of the paucity of data, especially for adenomyosis, evidence certainty was graded as low for most comparisons. CONCLUSION AND RELEVANCE The approximately ninefold increased risk of retrograde pattern during menstruation in endometriosis supports the potential role of retrograde menstruation in its etiopathogenesis. Abnormal uterine contractility, likely not limited to the menstrual phase, may be a mechanical factor contributing to development of endometriosis and related symptoms, including menstrual pain and infertility, with limited, mostly concordant evidence for adenomyosis. REGISTRATION NUMBER PROSPERO ID CRD42024512273-accepted on February 23, 2024.
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Affiliation(s)
- Noemi Salmeri
- Department of Obstetrics and Gynaecology, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Rehabilitation Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.
| | - Giorgia Di Stefano
- Academic Center for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Università degli Studi, Milano, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Paola Viganò
- Academic Center for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Università degli Studi, Milano, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Pamela Stratton
- Office of the Clinical Director, Intramural Research Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
| | - Edgardo Somigliana
- Academic Center for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Università degli Studi, Milano, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Paolo Vercellini
- Academic Center for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Università degli Studi, Milano, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
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De Bruyn C, Taliento C, Van Rompuy AS, Timmerman D, Coosemans A, Van den Bosch T. Central necrosis in uterine sarcoma. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2024; 64:716-720. [PMID: 38669593 DOI: 10.1002/uog.27669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 04/09/2024] [Accepted: 04/15/2024] [Indexed: 04/28/2024]
Affiliation(s)
- C De Bruyn
- Department of Development and Regeneration Woman and Child, KU Leuven, Leuven, Belgium
- Department of Obstetrics and Gynecology, University Hospital Antwerp, Edegem, Belgium
| | - C Taliento
- Department of Development and Regeneration Woman and Child, KU Leuven, Leuven, Belgium
- Department of Obstetrics and Gynecology, University Hospital 'Sant'Anna', Ferrara, Italy
| | - A-S Van Rompuy
- Department of Pathology, University Hospital Leuven, Leuven, Belgium
- Laboratory of Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, University of Leuven, Leuven, Belgium
| | - D Timmerman
- Department of Development and Regeneration Woman and Child, KU Leuven, Leuven, Belgium
- Department of Obstetrics and Gynecology, University Hospital Leuven, Leuven, Belgium
| | - A Coosemans
- Department of Oncology, Leuven Cancer Institute, Laboratory of Tumor Immunology and Immunotherapy, KU Leuven, Leuven, Belgium
| | - T Van den Bosch
- Department of Development and Regeneration Woman and Child, KU Leuven, Leuven, Belgium
- Department of Obstetrics and Gynecology, University Hospital Leuven, Leuven, Belgium
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Li Q, Dai Y, Li X, Wu Y, Gu Z, Zhang C, Yan H, Lyu S, Zhang B, Shi J, Leng J. Biological characteristics related to treatment effects of the levonorgestrel-releasing intrauterine system on adenomyosis-associated dysmenorrhoea. Reprod Biomed Online 2024; 49:104393. [PMID: 39413578 DOI: 10.1016/j.rbmo.2024.104393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 07/21/2024] [Accepted: 07/22/2024] [Indexed: 10/18/2024]
Abstract
RESEARCH QUESTION Are there correlations between the biological expression of steroid receptors and the extent of fibrosis in adenomyotic lesions, and the treatment effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) on alleviation of adenomyosis-associated dysmenorrhoea. DESIGN In this retrospective cohort study, 125 women with adenomyosis who underwent hysterectomy were screened. Tissue samples were collected from 41 patients who had undergone LNG-IUS treatment prior to surgery, and these patients were further categorized into the treatment effective group (n = 18) and the treatment failure group (n = 23) according to their self-reported relief from dysmenorrhoea after 6 months of treatment. Oestrogen receptor-α (ER-α) and progesterone receptor expression, and the extent of fibrosis in the adenomyotic lesions were measured using immunohistochemistry and Masson's trichrome staining, respectively. RESULTS Patients in the treatment failure group demonstrated lower expression of ER-α and progesterone receptors, and more pronounced fibrosis in the stroma of adenomyotic lesions compared with patients in the treatment effective group. In the glandular epithelium of lesions, ER-α expression was reduced significantly in the treatment failure group, whereas no notable difference in the expression of progesterone receptors was observed. Notably, the staining intensity of ER-α in the stroma of lesions was found to have the strongest positive correlation with the degree of symptom alleviation for dysmenorrhoea (r = 0.703, P < 0.001), with an area under the curve of 0.894 for prediction. CONCLUSIONS The reduced expression of steroid receptors in adenomyotic lesions, especially ER-α in the stroma, was associated with increased likelihood of treatment failure of LNG-IUS for alleviation of dysmenorrhoea.
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Affiliation(s)
- Qiutong Li
- Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China; National Clinical Research Centre for Obstetric and Gynaecologic Diseases, Beijing, China
| | - Yi Dai
- Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China; National Clinical Research Centre for Obstetric and Gynaecologic Diseases, Beijing, China
| | - Xiaoyan Li
- Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China; National Clinical Research Centre for Obstetric and Gynaecologic Diseases, Beijing, China
| | - Yushi Wu
- Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China; National Clinical Research Centre for Obstetric and Gynaecologic Diseases, Beijing, China
| | - Zhiyue Gu
- Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China; National Clinical Research Centre for Obstetric and Gynaecologic Diseases, Beijing, China
| | - Chenyu Zhang
- Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China; National Clinical Research Centre for Obstetric and Gynaecologic Diseases, Beijing, China
| | - Hailan Yan
- Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China; National Clinical Research Centre for Obstetric and Gynaecologic Diseases, Beijing, China
| | - Shiqing Lyu
- Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China; National Clinical Research Centre for Obstetric and Gynaecologic Diseases, Beijing, China
| | - Biyun Zhang
- Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China; National Clinical Research Centre for Obstetric and Gynaecologic Diseases, Beijing, China
| | - Jinghua Shi
- Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
| | - Jinhua Leng
- Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
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Lin Y, Sun H, Ming Y, Wang X, Jiao X, Pan Z, Ren Q, Yan S, Li D, Wang G. Efficacy and uterine bleeding patterns in initiating goserelin therapy during different menstrual phases in patients with adenomyosis: a prospective cohort study. Gynecol Endocrinol 2024; 40:2409918. [PMID: 39373327 DOI: 10.1080/09513590.2024.2409918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 07/17/2024] [Accepted: 09/23/2024] [Indexed: 10/08/2024] Open
Abstract
OBJECTIVE We carried out this study to explore the possibility of initiating goserelin therapy during the non-menstrual period in patients diagnosed with adenomyosis. METHODS 115 premenopausal adenomyosis patients were enrolled and divided into three groups based on their menstrual cycle phase during the initial outpatient visit: menstrual, follicular, and luteal. Each received a 3.6 mg subcutaneous dose of goserelin monthly for three months. The endpoints encompassed alterations in uterine volume, dysmenorrhea Numerical Rating Scale (NRS) score, CA125 level, hemoglobin (HGB) after a 12-week treatment course, and the occurrence and duration of uterine hemorrhage during the first treatment cycle. RESULTS Analysis revealed that the timing of goserelin therapy initiation in the menstrual cycle did not significantly impact its effectiveness in reducing uterine size, alleviating pain, lowering CA125 levels, or improving hemoglobin concentrations. However, patients starting treatment during the luteal phase experienced increased uterine bleeding (reference: menstrual period, OR = 4.33, 95% CI 1.23-15.25, p = .023). CONCLUSIONS The results suggested non-inferiority of goserelin therapy initiated during the non-menstrual period, but the uterine bleeding rate was higher in the luteal phase group. Therefore, goserelin treatment for outpatient adenomyosis patients should not be limited to starting during the menstrual period; it can also be initiated outside the menstrual period, providing more convenience for patients as most consultations occur outside the menstrual period. However, the use of goserelin during the luteal phase should be avoided to reduce the risk of exacerbated bleeding, especially in anemic patients with heavy menstrual bleeding. This study highlights the importance of individualizing treatment initiation based on the patient's health profile to optimize therapeutic outcomes and minimize adverse effects. TRIAL REGISTRATION ChiCTR2200059548.
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Affiliation(s)
- Ying Lin
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, China
- Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jinan Key Laboratory of Diagnosis and Treatment of Major Gynecological Disease, Jinan, China
- Gynecology Laboratory, Shandong Provincial Hospital, Jinan, China
- Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Hao Sun
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, China
- Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jinan Key Laboratory of Diagnosis and Treatment of Major Gynecological Disease, Jinan, China
- Gynecology Laboratory, Shandong Provincial Hospital, Jinan, China
- Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Yuan Ming
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, China
- Jinan Key Laboratory of Diagnosis and Treatment of Major Gynecological Disease, Jinan, China
- Gynecology Laboratory, Shandong Provincial Hospital, Jinan, China
- Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Xinyu Wang
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, China
- Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jinan Key Laboratory of Diagnosis and Treatment of Major Gynecological Disease, Jinan, China
- Gynecology Laboratory, Shandong Provincial Hospital, Jinan, China
- Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Xue Jiao
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, China
- Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jinan Key Laboratory of Diagnosis and Treatment of Major Gynecological Disease, Jinan, China
- Gynecology Laboratory, Shandong Provincial Hospital, Jinan, China
- Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Zangyu Pan
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, China
- Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jinan Key Laboratory of Diagnosis and Treatment of Major Gynecological Disease, Jinan, China
- Gynecology Laboratory, Shandong Provincial Hospital, Jinan, China
- Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Qianhui Ren
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, China
- Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jinan Key Laboratory of Diagnosis and Treatment of Major Gynecological Disease, Jinan, China
- Gynecology Laboratory, Shandong Provincial Hospital, Jinan, China
- Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Shumin Yan
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, China
- Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jinan Key Laboratory of Diagnosis and Treatment of Major Gynecological Disease, Jinan, China
- Gynecology Laboratory, Shandong Provincial Hospital, Jinan, China
- Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Dong Li
- Qilu Hospital of Shandong University, Jinan, China
| | - Guoyun Wang
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, China
- Jinan Key Laboratory of Diagnosis and Treatment of Major Gynecological Disease, Jinan, China
- Gynecology Laboratory, Shandong Provincial Hospital, Jinan, China
- Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
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Jiang Z, Jia S, Zhang J, Liu C, Luo X, Tang Y, Zhang G, Zhu Y. Preoperative identification from occult leiomyosarcomas in laparoscopic hysterectomy and laparoscopic myomectomy: accuracy of the ultrasound scoring system (PRESS-US). LA RADIOLOGIA MEDICA 2024; 129:1864-1875. [PMID: 39476275 DOI: 10.1007/s11547-024-01903-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 10/15/2024] [Indexed: 12/17/2024]
Abstract
PURPOSE To assess the diagnostic performance and inter-observer agreement of a PREoperative sarcoma scoring based on ultrasound (PRESS-US) in differentiating uterine leiomyosarcoma (uLMS) from leiomyoma (LM). METHODS We conducted a retrospective evaluation of patients who underwent surgery and received standardized ultrasound examinations due to the presence of uterine myoma-like masses. Histological diagnosis was used as the reference standard. The masses were analyzed using morphological uterus sonographic assessment criteria, and the diagnostic accuracy of PRESS-US was evaluated using ROC curve analysis. Kappa (κ) statistics were used to assess the inter-observer agreement between a less experienced and an expert radiologist. RESULTS Among the 646 patients, 632 (97.8%) were diagnosed with LM, and 14 (2.2%) had uLMS. The malignancy rates for low-risk and high-risk patients were 0.35% and 13.48%, respectively. The optimal PRESS-US cutoff was 17.5, resulting in an AUC of 89.7% (95% CI, 0.79-1.00), with a sensitivity of 85.7% and a specificity of 87.8%. The inter-observer agreement between a less experienced and an expert radiologist was excellent (κ = 0.811, P < 0.001). CONCLUSIONS PRESS-US provides effective risk stratification for uLMS for radiologists with different levels of experience, with high reliability. Subgrouping high-risk patients helps in better risk stratification.
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Affiliation(s)
- Zhuolin Jiang
- Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (UESTC), NO. 55, Section 4, Renmin South Road, Chengdu, 610041, China
| | - Shijun Jia
- Department of Pathology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (UESTC), Chengdu, 610041, China
| | - Jie Zhang
- Department Gynecologic Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (UESTC), NO. 55, Section 4, Renmin South Road, Chengdu, 610041, China
| | - Chun Liu
- Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (UESTC), NO. 55, Section 4, Renmin South Road, Chengdu, 610041, China
| | - Xinyi Luo
- Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (UESTC), NO. 55, Section 4, Renmin South Road, Chengdu, 610041, China
| | - Yixin Tang
- Department of Ultrasound, Suining Central Hospital, Suining, 629000, China
| | - Guonan Zhang
- Department Gynecologic Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (UESTC), NO. 55, Section 4, Renmin South Road, Chengdu, 610041, China.
| | - Yi Zhu
- Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (UESTC), NO. 55, Section 4, Renmin South Road, Chengdu, 610041, China.
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Russo C, Palumbo M, Reppuccia S, Iorio GG, Nocita E, Monaco G, Iacobini F, Soreca G, Exacoustos C. Evaluation of menstrual blood loss (MBL) by self-perception and pictorial methods and correlation to uterine myometrial pathology. Arch Gynecol Obstet 2024; 310:3121-3129. [PMID: 39614907 DOI: 10.1007/s00404-024-07729-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 09/06/2024] [Indexed: 12/18/2024]
Abstract
PURPOSE Evaluating menstrual blood loss (MBL) in primary healthcare is challenging. Our study aimed to assess MBL using two methods: self-perception and pictograms (Pictorial Blood Assessment Chart-PBAC and Menstrual Pictogram superabsorbent polymer-c version-MP) in women undergoing transvaginal ultrasound (TVS). METHODS We enrolled 221 premenopausal women with spontaneous menstruation, no hormonal therapy, and no ongoing pregnancy. They were divided into four age groups (12-20, 21-30, 31-40, and 41-55 years). Women self-reported normal (NMB) or heavy menstrual bleeding (HMB) and filled out PBAC and MP. A PBAC score ≥ 150 and MP score ≥ 80 ml indicated HMB. TVS was conducted on all patients, recording any pelvic pathologies. We compared self-perception with pictograms across the cohort, age groups, and ultrasound findings. RESULTS Of the cohort, 50.2% reported normal periods and 49.8% heavy periods. No significant differences were found between self-perception and pictograms in identifying NMB and HMB across all groups. However, significant differences were observed between PBAC and MP scores for NMB (56.1% vs 41.2%, p = 0.001) and HMB (43.9% vs 58.8%, p = 0.001), particularly in the 31-40 age group. Significant differences in PBAC and MP scores were noted between age groups 12-20 and 41-55, and 31-40 and 41-55. No significant differences were found between self-perception and pictograms regarding ultrasound findings like adenomyosis, fibroids, endometrial pathology, and uterine congenital malformations. CONCLUSION Self-perception could be a reliable method for describing MBL across all age groups and ultrasound findings. Given the complexity and potential errors in using pictograms, clinicians should consider relying on self-perception for assessing menstrual cycle quantity.
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Affiliation(s)
- Consuelo Russo
- Department of Surgical Sciences, Gynecological Unit, University of Rome "Tor Vergata", Viale Oxford, 81, 00133, Rome, Italy
- Dipartimento della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Mario Palumbo
- Department of Public Health, Gynecological Unit, University of Naples Federico II, 80138, Naples, Italy
| | - Sabrina Reppuccia
- Department of Public Health, Gynecological Unit, University of Naples Federico II, 80138, Naples, Italy
| | - Giuseppe Gabriele Iorio
- Department of Public Health, Gynecological Unit, University of Naples Federico II, 80138, Naples, Italy
| | - Elvira Nocita
- Department of Surgical Sciences, Gynecological Unit, University of Rome "Tor Vergata", Viale Oxford, 81, 00133, Rome, Italy
| | - Giulia Monaco
- Department of Surgical Sciences, Gynecological Unit, University of Rome "Tor Vergata", Viale Oxford, 81, 00133, Rome, Italy
| | - Federica Iacobini
- Department of Surgical Sciences, Gynecological Unit, University of Rome "Tor Vergata", Viale Oxford, 81, 00133, Rome, Italy
| | - Giorgia Soreca
- Department of Surgical Sciences, Gynecological Unit, University of Rome "Tor Vergata", Viale Oxford, 81, 00133, Rome, Italy
| | - Caterina Exacoustos
- Department of Surgical Sciences, Gynecological Unit, University of Rome "Tor Vergata", Viale Oxford, 81, 00133, Rome, Italy.
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Fiorillo M, Neri B, Mancone R, Russo C, Iacobini F, Schiavone SC, De Cristofaro E, Migliozzi S, Exacoustos C, Biancone L. Inflammatory Bowel Disease and Endometriosis: Diagnosis and Clinical Characteristics. Biomedicines 2024; 12:2521. [PMID: 39595086 PMCID: PMC11592220 DOI: 10.3390/biomedicines12112521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/25/2024] [Accepted: 10/28/2024] [Indexed: 11/28/2024] Open
Abstract
Background/Objectives: Endometriosis and inflammatory bowel disease (IBD) share some epidemiological, clinical and pathogenetic features. A differential diagnosis between pelvic endometriosis and IBD may be challenging, even for expert clinicians. In the present review, we aimed to summarize the currently available data regarding the relationship between endometriosis and IBD and their possible association. Methods: The PubMed and Scopus database were considered, by searching the following terms: "Crohn's Disease", "Ulcerative Colitis", "Endometriosis", "Adenomyosis", and "Inflammatory Bowel Disease", individually or combined. Full-text papers published in English with no date restriction were considered. Results: Few studies have researched the possible association between endometriosis and IBD. Both conditions are characterized by chronic recurrent symptoms, which may be shared (abdominal pain, fatigue, infertility, menstrual irregularities, diarrhea, constipation). Deep infiltrating endometriosis (DIE) can cause bowel symptoms. In a large Danish study, a 50% increased risk of IBD was observed in women with endometriosis. A missed diagnosis of endometriosis and an increased risk of endometriosis has been reported in IBD. Current evidence does not support an association between endometriosis and IBD characteristics. However, IBD may be associated with DIE, characterized by pelvic symptoms (dyschezia, dyspareunia). Preliminary observations suggest an increased IBD risk in patients with endometriosis treated with hormonal therapy. Conclusions: Current findings suggest that a careful search is needed for concomitant endometriosis in subgroups of patients with IBD showing compatible symptoms and vice versa. A multidisciplinary approach including dedicated gastroenterologists and gynecologists is required for a proper search for IBD and endometriosis in subgroups of patients. This approach may avoid diagnostic delays or overtreatments for these conditions.
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Affiliation(s)
- Mariasofia Fiorillo
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
| | - Benedetto Neri
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
- Therapeutic GI Endoscopy Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | - Roberto Mancone
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
| | - Consuelo Russo
- Obstetrics and Gynecological Unit, Department of Surgical Sciences, University “Tor Vergata” of Rome, 00133 Rome, Italy; (C.R.); (F.I.); (C.E.)
- Department of Women, Children, and Public Health Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Federica Iacobini
- Obstetrics and Gynecological Unit, Department of Surgical Sciences, University “Tor Vergata” of Rome, 00133 Rome, Italy; (C.R.); (F.I.); (C.E.)
| | - Sara Concetta Schiavone
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
| | - Elena De Cristofaro
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
| | - Stefano Migliozzi
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
| | - Caterina Exacoustos
- Obstetrics and Gynecological Unit, Department of Surgical Sciences, University “Tor Vergata” of Rome, 00133 Rome, Italy; (C.R.); (F.I.); (C.E.)
| | - Livia Biancone
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
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Khaladkar SM, Dhande A, Shah RN, KirdatPatil PP. Application of the Morphological Uterine Scoring Assessment in Ultrasound for Abnormal Uterine Bleeding. Cureus 2024; 16:e74709. [PMID: 39735030 PMCID: PMC11682851 DOI: 10.7759/cureus.74709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 11/26/2024] [Indexed: 12/31/2024] Open
Abstract
Abnormal uterine bleeding (AUB) is a common gynecological condition that disrupts women's health due to irregularities in menstrual frequency, duration, and volume, often resulting in a significant impact on daily life and productivity. Accurate diagnosis of AUB is critical but complicated by its varied etiologies and presentations. Recent advancements in imaging techniques, particularly the Morphological Uterus Sonographic Assessment (MUSA), have enhanced the diagnostic precision of uterine pathologies such as fibroids and adenomyosis. MUSA combines gray-scale sonography, color Doppler, and three-dimensional ultrasound to evaluate uterine abnormalities with standardized terminology, ensuring diagnostic consistency. This study aimed to assess the efficacy of MUSA in diagnosing and managing AUB. A descriptive observational study was conducted on 50 patients at Dr. D. Y. Patil Medical College and Hospital, focusing on pre- and post-menopausal women with clinically symptomatic AUB. Patients underwent detailed ultrasonography, including both transabdominal and transvaginal scans, to evaluate uterine structures and correlate findings with histopathology. Results showed that 62% of patients had adenomyosis, while 38% had fibroids. MUSA effectively differentiated between the two conditions based on key ultrasound characteristics such as serosal contour, junctional zone, myometrial wall symmetry, and echogenicity. Adenomyosis cases showed significantly higher rates of heterogeneous echogenicity and asymmetrical myometrial walls compared to fibroids. Statistical analyses revealed high diagnostic sensitivity and specificity for both conditions, with an overall accuracy of 88.9% for adenomyosis and 94.1% for fibroids. The findings confirm the utility of MUSA in improving diagnostic accuracy and informing management strategies for AUB, particularly in complex cases. The study highlights MUSA as an indispensable tool for clinicians, facilitating enhanced patient outcomes through precise evaluation and treatment of uterine pathologies.
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Affiliation(s)
- Sanjay M Khaladkar
- Radiodiagnosis, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Aryaman Dhande
- Radiodiagnosis, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Rohan N Shah
- Radiodiagnosis, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Prajakta P KirdatPatil
- Radiodiagnosis, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, IND
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Wang R, Luo H, Cao W. Clinical and ultrasound features of uterine perivascular epithelioid cell tumors: case series and literature review. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2024; 64:687-695. [PMID: 39395194 DOI: 10.1002/uog.29116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 08/25/2024] [Accepted: 09/03/2024] [Indexed: 10/14/2024]
Abstract
OBJECTIVE To describe the clinical and ultrasonographic features of uterine perivascular epithelioid cell tumor (PEComa) using standardized terminology. METHODS This was a retrospective analysis of patients with uterine PEComa diagnosed and confirmed by pathology and immunohistochemistry at West China Second University Hospital, Sichuan University, Sichuan, China, between January 2010 and September 2023. The Morphological Uterus Sonographic Assessment (MUSA) consensus and the International Endometrial Tumor Analysis (IETA) consensus were utilized for the standardized description of the sonographic characteristics of uterine PEComa. We summarized the clinical and ultrasound features of uterine PEComa in cases from our center and those found in a review of the literature conducted using PubMed from 1 January 2013 to 30 September 2023 (inclusive). RESULTS Five patients, aged 33-57 (median, 52) years, with a total of six uterine PEComa lesions were included in our cohort. All cases had complete ultrasonographic and pathological images. None of the patients had a history of tuberous sclerosis complex. Two patients had malignant PEComa (one patient had two lesions) and three had benign PEComa, originating from the cervix, myometrium or uterine cavity. Patients presented with symptoms including increased vaginal discharge, vaginal bleeding and pelvic or abdominal pain. The three patients with benign PEComa underwent total hysterectomy and bilateral adnexectomy, tumor excision and conservative management, respectively, while both malignant cases underwent total hysterectomy and bilateral adnexectomy followed by chemotherapy. Regular follow-up (from 6 to 24 months) revealed recurrence in one case. Two lesions were misdiagnosed as uterine fibroids, two as cervical cancer, one as metastatic cervical cancer (with myometrial invasion) and one was indeterminate. Ultrasound examination showed that most lesions displayed regular round or ovoid shape (66.7%), uniform echoes (66.7%) and hypoechogenicity (66.7%), with one (16.7%) malignant PEComa showing cystic areas and one (16.7%) benign PEComa showing punctate calcifications. All lesions lacked shadowing and the majority showed moderate to abundant vascularity (color score of 3-4, 83.3%). The color score was 2-4 in the periphery in 100% of cases and internally in 83.3% of cases. The three benign PEComas showed similar characteristics in vascular distribution, with scattered internal vessels and peripheral vessels exhibiting a circular pattern. The literature search identified 11 articles describing the ultrasonographic appearance of 18 cases of uterine PEComa, with similar characteristics to those in our cohort. CONCLUSIONS The sonographic features of uterine PEComa include a uniform or non-uniform hypoechogenic mass, typically round or ovoid with regular margins, occasionally containing cystic areas or calcifications, lacking shadowing and often showing moderate to abundant vascularity. Although the preoperative ultrasound diagnosis of uterine PEComa remains challenging, particularly given the non-specific nature of the sonographic characteristics described here, dispersed intratumoral vessels and a peripheral circular vascular distribution may serve as diagnostic clues for uterine PEComa, but more cases are needed for confirmation. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
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Affiliation(s)
- R Wang
- Department of Ultrasonic Medicine, West China Second Hospital of Sichuan University, Chengdu, Sichuan, China
| | - H Luo
- Department of Ultrasonic Medicine, West China Second Hospital of Sichuan University, Chengdu, Sichuan, China
| | - W Cao
- Department of Ultrasonic Medicine, West China Second Hospital of Sichuan University, Chengdu, Sichuan, China
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Xholli A, Molinari F, Scovazzi U, Londero AP, Perugi I, Kratochwila C, Cremonini F, Cagnacci A. Relationship between endometriosis and uterine cervical elasticity assessed using ultrasound strain elastography. Ultrasonography 2024; 43:490-498. [PMID: 39370860 PMCID: PMC11532525 DOI: 10.14366/usg.24117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 07/23/2024] [Accepted: 09/02/2024] [Indexed: 10/08/2024] Open
Abstract
PURPOSE Internal cervical os (ICO) stiffness is related to menstrual pain, a key symptom of endometriosis. The study evaluated whether women with endometriosis have a stiffer ICO than unaffected women. METHODS A retrospective cross-sectional analysis was conducted using prospectively collected data from women with and without endometriosis, spanning from June 2020 to September 2022. Endometriosis was diagnosed through clinical and ultrasound evaluations, with histological confirmation in a subset of participants. Strain elastography (SE) was employed to measure tissue elasticity in four cervical regions of interest: the ICO and the anterior, posterior, and middle cervical compartments (ACC, PCC, and MCC, respectively). Tissue elasticity was quantified using a color-based scoring system ranging from 0.1 (blue, indicating less elasticity) to 3.0 (red, indicating greater elasticity). RESULTS Overall, 287 women were included, with 157 diagnosed with endometriosis and 130 controls. On SE, women with endometriosis exhibited a lower color score (mean±standard deviation), indicating lower elasticity, for the ICO (0.56±0.28 vs. 0.70±0.26, P=0.001) and PCC (0.69±0.30 vs. 0.80±0.27, P=0.002). Additionally, they had a lower ICO/MCC ratio (0.45±0.28 vs. 0.60±0.32, P=0.001) and ICO/ACC ratio (0.68±0.42 vs. 0.85±0.39, P=0.001). Multiple logistic regression analysis revealed that endometriosis was associated with the ICO color score (odds ratio, 0.053; 95% confidence interval, 0.014 to 0.202; R2=0.358; P=0.001), even after adjusting for confounding factors like the presence of myomas (P=0.040) and the use of hormonal therapy (P=0.001). The results were corroborated in women with histologically confirmed endometriosis (n=71). CONCLUSION The findings suggest a potential relationship between a stiffer ICO and endometriosis.
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Affiliation(s)
- Anjeza Xholli
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy
| | - Filippo Molinari
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy
- Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy
| | - Umberto Scovazzi
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy
- Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy
| | | | - Isabella Perugi
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy
- Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy
| | - Chiara Kratochwila
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy
- Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy
| | - Francesca Cremonini
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy
- Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy
| | - Angelo Cagnacci
- Academic Unit of Obstetrics and Gynecology, IRCCS San Martino Hospital, Genoa, Italy
- Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal, and Infant Health (DiNOGMI), IRCCS San Martino Hospital, Genoa, Italy
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Frijlingh M, Stoelinga B, de Leeuw RA, Hehenkamp WJK, Twisk JWR, van den Bosch T, Juffermans LJM, Huirne JAF. Microvascular flow imaging of fibroids: A prospective pilot study. Acta Obstet Gynecol Scand 2024; 103:2193-2202. [PMID: 39263938 PMCID: PMC11502429 DOI: 10.1111/aogs.14914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 05/17/2024] [Accepted: 06/24/2024] [Indexed: 09/13/2024]
Abstract
INTRODUCTION Imaging fibroid vascularity may predict fibroid growth and aid to determine most appropriate therapy. Microvascular (MV) flow imaging is relatively new and is able to detect slow flow in small vessels. Data on feasibility, reproducibility, and reliability of MV-flow imaging in fibroids is lacking. The purpose of our study was to determine the reproducibility of MV-flow imaging and to explore this technique for clinical practice for assessing blood flow in fibroids. MATERIAL AND METHODS Thirty patients with one or multiple fibroids (diameter 1.5-12.0 cm) were prospectively included. Transvaginal ultrasound scanning was performed in B-mode, 2D MV-Flow™, 2D and 3D power Doppler mode (HERA W10, Samsung) by two experienced gynecologists at a tertiary care clinic from February to December 2021. The primary outcome was intra- and interobserver agreement of the vascular index (VI) and color score (CS). The following parameters: '2D MV-flow VI', '3DPD VI', '2D MV-flow CS' and '2DPD CS' were measured offline in the center, pseudocapsule, and entire fibroid. Secondary offline outcomes for exploring 2D MV-flow for clinical practice, included (1) ability to discern vascular structures, (2) assessing the degree of vascularity via CS and calculating a VI, and (3) determining penetration depth of the ultrasound signal in both power Doppler and MV-flow imaging. RESULTS All scans of the 30 included patients were of sufficient quality to analyze. Inter- and intra-observer correlations of all studied parameters were good to excellent, both for 2D MV-flow and 2D power Doppler (intercorrelation coefficient 0.992-0.996). Using 2D MV-flow different vascular structures were visible in detail, in contrary to using 2D and 3D power Doppler. In significantly more fibroids central flow could be visualized using 2D MV-flow (63%) than with 2D power Doppler (13%, p = 0.001). Finally, penetration of the ultrasound signal was deeper using 2D MV-flow (3.92 cm) than with 2D power Doppler (2.95 cm, p = 0.001). CONCLUSIONS Using 2D MV-flow imaging for determining vascularity is highly reproducible. It has potential added value for clinical practice as it depicts detailed vascular structures and the degree of vascularity, especially in the center of the fibroid.
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Affiliation(s)
- Marissa Frijlingh
- Department of Obstetrics and GynecologyAmsterdam UMC, location AMCAmsterdamThe Netherlands
- Amsterdam Reproduction and Development Research InstituteAmsterdamThe Netherlands
| | - Barbara Stoelinga
- Department of Obstetrics and GynecologyAmsterdam UMC, location AMCAmsterdamThe Netherlands
- Amsterdam Reproduction and Development Research InstituteAmsterdamThe Netherlands
| | - Robert A. de Leeuw
- Department of Obstetrics and GynecologyAmsterdam UMC, location AMCAmsterdamThe Netherlands
- Amsterdam Reproduction and Development Research InstituteAmsterdamThe Netherlands
| | - Wouter J. K. Hehenkamp
- Department of Obstetrics and GynecologyAmsterdam UMC, location AMCAmsterdamThe Netherlands
- Amsterdam Reproduction and Development Research InstituteAmsterdamThe Netherlands
| | - Jos W. R. Twisk
- Department of Epidemiology and BiostatisticsAmsterdam UMC, location VUmcAmsterdamThe Netherlands
| | | | - Lynda J. M. Juffermans
- Department of Obstetrics and GynecologyAmsterdam UMC, location AMCAmsterdamThe Netherlands
- Amsterdam Reproduction and Development Research InstituteAmsterdamThe Netherlands
| | - Judith A. F. Huirne
- Department of Obstetrics and GynecologyAmsterdam UMC, location AMCAmsterdamThe Netherlands
- Amsterdam Reproduction and Development Research InstituteAmsterdamThe Netherlands
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Martire FG, d’Abate C, Schettini G, Cimino G, Ginetti A, Colombi I, Cannoni A, Centini G, Zupi E, Lazzeri L. Adenomyosis and Adolescence: A Challenging Diagnosis and Complex Management. Diagnostics (Basel) 2024; 14:2344. [PMID: 39518312 PMCID: PMC11544982 DOI: 10.3390/diagnostics14212344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 10/18/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024] Open
Abstract
Adenomyosis is a chronic, hormone-related disease characterized by the presence of the endometrial glands and stroma within the myometrium. This condition can manifest in various features, focal or diffuse adenomyosis or as an adenomyoma, and it may involve different uterine walls (posterior, anterior, and/or lateral walls). The disease can also be classified into different degrees, as mild, moderate and severe, which can be associated with more intense symptoms, although this correlation is not always directly proportional. In fact, adenomyosis can be asymptomatic in about a third of cases or it can significantly impact patients' quality of life through painful symptoms, such as dysmenorrhea and dyspareunia, abnormal uterine bleeding-particularly heavy menstrual bleeding-and potential effects on fertility. Historically, adenomyosis has been considered a disease primarily affecting premenopausal women over the age of 40, often multiparous, because the diagnosis was traditionally based on surgical reports from hysterectomies performed after the completion of reproductive desire. Data on the presence of adenomyosis in adolescent patients remain limited. However, in recent years, advancements in noninvasive diagnostic tools and increased awareness of this pathology have enabled earlier diagnoses. The disease appears to have an early onset during adolescence, with a tendency to progress in terms of extent and severity over time. Adenomyosis often coexists with endometriosis, which also has an early onset. Therefore, it is important, when diagnosing adenomyosis, to also screen for concomitant endometriosis, especially deep endometriosis in the posterior compartment. The aim of this narrative review is to investigate the prevalence of different types and degrees of adenomyosis in younger patients, assess the associated symptoms, and describe the most appropriate diagnostic procedures for effective therapeutic management and follow-up, with the goal of improving the quality of life for these young women.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Errico Zupi
- Department of Molecular and Developmental Medicine, Obstetrics and Gynecological Clinic, University of Siena, Strada delle Scotte 14, 53100 Siena, Italy; (F.G.M.); (C.d.); (G.S.); (G.C.); (A.G.); (I.C.); (A.C.); (G.C.); (L.L.)
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Alson S, Henic E, Hansson SR, Sladkevicius P. Correlation of adenomyosis features to live birth rates after the first IVF/ICSI treatment, when using the revised Morphological Uterus Sonographic Assessment group definitions. Acta Obstet Gynecol Scand 2024. [PMID: 39382305 DOI: 10.1111/aogs.14986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 08/21/2024] [Accepted: 09/25/2024] [Indexed: 10/10/2024]
Abstract
INTRODUCTION Data regarding the impact of adenomyosis on the outcomes after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment are conflicting. Standardized diagnostic criteria are prerequisites for studying a potential association between adenomyosis and IVF/ICSI treatment outcomes. This study aims to examine the cumulative live birth rate (CLBR) after the first IVF/ICSI treatment in women with or without direct or indirect features of adenomyosis, using the revised Morphological Uterus Sonographic Assessment (MUSA) group definitions. MATERIAL AND METHODS This was a prospective cohort study of 1037 women aged 25-≤39 years, undergoing their first IVF/ICSI treatment between January 2019 and October 2022. The presence of MUSA features of adenomyosis was assessed prior to treatment start. RESULTS The CLBR after the first IVF/ICSI treatment was 424/1037 (40.9%, 95% CI, 37.9-43.8) in the total cohort. Women with direct features of adenomyosis had lower CLBR, 25/102 (24.5%; 95% CI, 17.5-31.5) than women without, 399/935 (42.7%; 95% CI, 39.5-45.8), p < 0.001. The adjusted relative risk (aRR) for live birth for women with direct features of adenomyosis compared to women without was 0.62 (95% CI, 0.43-0.88), p = 0.007. Direct features were associated with a higher risk of miscarriage after frozen embryo transfer, aRR 2.88 (95% CI, 1.49-5.57), p = 0.002. Women with indirect features had a lower CLBR [50/188 (26.6%, 95% CI, 20.3-32.9)] than women without [399/935, (42.7%, 95% CI, 39.5-45.8)], aRR 0.58 (95% CI, 0.45-0.75), p < 0.001. For features located in the inner myometrium, the aRR for live birth was 0.29 (95% CI 0.11-0.74), p = 0.010 and for the outer myometrium 2.61 (95% CI 1.42-4.8), p = 0.002. An interrupted junctional zone was the single feature that impacted CLBR the most. CONCLUSIONS The presence of direct or indirect MUSA features of adenomyosis correlates to reduced live birth rates in women undergoing their first IVF/ICSI treatment. Features located in the inner myometrium, particularly an interrupted junctional zone, reduced the chance of live birth the most, whereas location in the outer myometrium was associated with higher chances of live birth. Systematic ultrasound examinations should be considered for women scheduled for IVF/ICSI treatment, for adequate counseling on the chances of successful treatment.
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Affiliation(s)
- Sara Alson
- Department of Clinical Sciences, Obstetric, Gynecological and Prenatal Ultrasound Research, Lund University, Malmö, Sweden
- Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö, Sweden
- Reproductive Medicine Center, Skåne University Hospital, Malmö, Sweden
| | - Emir Henic
- Reproductive Medicine Center, Skåne University Hospital, Malmö, Sweden
- Department of Translational Medicine, Lund University, Malmö, Sweden
| | - Stefan R Hansson
- Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences, Unit for Translational Obstetric Research, Lund University, Sweden
| | - Povilas Sladkevicius
- Department of Clinical Sciences, Obstetric, Gynecological and Prenatal Ultrasound Research, Lund University, Malmö, Sweden
- Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö, Sweden
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Ray-Coquard I, Casali PG, Croce S, Fennessy FM, Fischerova D, Jones R, Sanfilippo R, Zapardiel I, Amant F, Blay JY, Martἰn-Broto J, Casado A, Chiang S, Dei Tos AP, Haas R, Hensley ML, Hohenberger P, Kim JW, Kim SI, Meydanli MM, Pautier P, Abdul Razak AR, Sehouli J, van Houdt W, Planchamp F, Friedlander M. ESGO/EURACAN/GCIG guidelines for the management of patients with uterine sarcomas. Int J Gynecol Cancer 2024; 34:1499-1521. [PMID: 39322612 DOI: 10.1136/ijgc-2024-005823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/27/2024] Open
Affiliation(s)
- Isabelle Ray-Coquard
- Department of Medical Oncology, Centre Leon Berard, Lyon, France
- Hesper Laboratory, Université Claude Bernard Lyon 1, Villeurbanne, France
| | - Paolo Giovanni Casali
- Medical Oncology Unit 2, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
- Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy
| | - Sabrina Croce
- Department of Biopathology, Institut Bergonié, Bordeaux, France
| | - Fiona M Fennessy
- Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Daniela Fischerova
- Department of Gynecology, Obstetrics and Neonatology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 2, Czech Republic
| | - Robin Jones
- Royal Marsden Hospital NHS Trust, London, UK
| | - Roberta Sanfilippo
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Ignacio Zapardiel
- Gynecologic Oncology Unit, La Paz University Hospital, Madrid, Spain
| | - Frédéric Amant
- Department of Oncology, KU Leuven, Leuven, Flanders, Belgium
- Department of Gynecology, Antoni van Leeuwenhoek Nederlands Kanker Instituut afdeling Gynaecologie, Amsterdam, Netherlands
| | - Jean-Yves Blay
- Department of Medical Oncology, Centre Leon Berard, Lyon, France
| | - Javier Martἰn-Broto
- Department of Medical Oncology, Fundación Jimenez Diaz University Hospital, Madrid, Spain
- University Hospital General de Villalba, Madrid, Spain
| | - Antonio Casado
- Department of Medical Oncology, University Hospital San Carlos, Madrid, Spain
| | - Sarah Chiang
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Angelo Paolo Dei Tos
- Department of Integrated Diagnostics, Azienda Ospedale-Università Padova, Padua, Italy
- Department of Medicine, University of Padua, Padua, Italy
| | - Rick Haas
- Department of Radiotherapy, Netherlands Cancer Institute, Amsterdam, Netherlands
- Department of Radiotherapy, Leiden University Medical Center, Leiden, Netherlands
| | - Martee L Hensley
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Department of Medicine, Weill Cornell Medical College, New York, New York, USA
| | - Peter Hohenberger
- Division of Surgical Oncology and Thoracic Surgery, Mannheim University Medical Centre, University of Heidelberg, Mannheim, Germany
| | - Jae-Weon Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
| | - Se Ik Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
| | | | - Patricia Pautier
- Department of Medical Oncology, Institut Gustave-Roussy, Villejuif, Île-de-France, France
| | - Albiruni R Abdul Razak
- Division of Medical Oncology and Hematology, Princess Margaret Hospital Cancer Centre Gynecologic Site Group, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Jalid Sehouli
- Department of Gynecology with Center for Oncological Surgery, Charite Universitatsmedizin Berlin, Berlin, Germany
| | - Winan van Houdt
- Department of Surgery, Netherlands Cancer Institute, Amsterdam, Netherlands
| | | | - Michael Friedlander
- Department of Medical Oncology, School of Clinical Medicine, Faculty of Medicine and Health, Sydney, New South Wales, Australia
- Department of Medical Oncology, Prince of Wales and Royal Hospital for Women, Randwick, New South Wales, Australia
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Zhao Q, Yang T, Xu C, Hu J, Shuai Y, Zou H, Hu W. Automatic diagnosis for adenomyosis in ultrasound images by deep neural networks. Eur J Obstet Gynecol Reprod Biol 2024; 301:128-134. [PMID: 39121648 DOI: 10.1016/j.ejogrb.2024.07.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 07/08/2024] [Accepted: 07/22/2024] [Indexed: 08/12/2024]
Abstract
OBJECTIVE To present a new noninvasive technique for automatic diagnosis of adenomyosis, using a novel end-to-end unified network framework based on transformer networks. STUDY DESIGN This is a prospective descriptive study conducted at a university hospital.1654 patients were recruited to the study according to adenomyosis diagnosed by transvaginal ultrasound (TVS). For adenomyosis characteristics and ultrasound images, automatic identification of adenomyosis were performed based on deep learning methods. We called this unique technique A2DNet: Adenomyosis Auto Diagnosis Network. RESULTS The A2DNet exhibits excellent performance in diagnosis of adenomyosis, achieving an accuracy of 92.33%, a precision of 96.06%, a recall of 91.71% and an F1 score of 93.80% in the test group. The confusion matrix of experimental results show that the A2DNet can achieve a correct diagnosis rate of 92% or more for both normal and adenomyosis samples, which demonstrate the superiority of the A2DNet comparing with the state-of-the-arts. CONCLUSION The A2DNet is a safe and effective technique to aid in automatic diagnosis of adenomyosis. The technique which is nondestructive and non-invasive, is new and unique due to the advantages of artificial intelligence.
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Affiliation(s)
- Qinghong Zhao
- Department of Ultrasound in Medicine, Renmin Hospital of Wuhan University, China
| | - Tongyu Yang
- School of Cyber Science and Engineering, Wuhan University, China
| | - Changyong Xu
- IT Department, China Southern Airlines Hubei Branch, Wuhan, China
| | - Jiaqi Hu
- Department of Ultrasound in Medicine, Renmin Hospital of Wuhan University, China
| | - Yu Shuai
- Department of Ultrasound in Medicine, Renmin Hospital of Wuhan University, China
| | - Hua Zou
- School of Computer Science, Wuhan University, China.
| | - Wei Hu
- Department of Ultrasound in Medicine, Renmin Hospital of Wuhan University, China.
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Bean EMR, Knez J, Thanatsis N, De Braud L, Taki F, Hirsch M, David A, Jurkovic D. Obstetric outcomes in women with pelvic endometriosis: a prospective cohort study. Fertil Steril 2024; 122:696-705. [PMID: 38838806 DOI: 10.1016/j.fertnstert.2024.05.162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 05/27/2024] [Accepted: 05/28/2024] [Indexed: 06/07/2024]
Abstract
OBJECTIVE To determine whether obstetric outcomes differ between women with endometriosis and those without, where all women undergo first-trimester screening for endometriosis. DESIGN A prospective observational cohort study. SETTING The Early Pregnancy Unit at University College London Hospital, United Kingdom. PATIENTS Women with a live pregnancy progressing beyond 12 weeks' gestation and concurrent endometriosis (n = 110) or no endometriosis (n = 393). INTERVENTION All women underwent a pelvic ultrasound examination in early pregnancy to examine for the presence of endometriosis and uterine abnormalities. MAIN OUTCOME MEASURES The primary outcome of interest was preterm birth, defined as delivery before 37 completed weeks' gestation. Secondary outcomes included late miscarriage, antepartum hemorrhage, placental site disorders, gestational diabetes, hypertensive disorders of pregnancy, neonates small for gestational age, mode of delivery, intrapartum sepsis, postpartum hemorrhage, and admission to the neonatal unit. RESULTS Women with a diagnosis of endometriosis did not have statistically significantly higher odds of preterm delivery (adjusted odds ratio [aOR] 1.85 [95% confidence interval {CI} 0.50-6.90]), but they did have higher odds of postpartum hemorrhage during cesarean section (aOR 3.64 [95% CI 2.07-6.35]) and admission of their newborn infant to the neonatal unit (aOR 3.24 [95% CI 1.08-9.73]). Women with persistent or recurrent deep endometriosis after surgery also had higher odds of placental site disorders (aOR 8.65 [95% CI 1.17-63.71]) and intrapartum sepsis (aOR 3.47 [95% CI 1.02-11.75]). CONCLUSION We observed that women with endometriosis do not have higher odds of preterm delivery, irrespective of their disease subtype. However, they do have higher odds of postpartum hemorrhage during the cesarean section and newborn admission to the neonatal unit.
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Affiliation(s)
- Elisabeth M R Bean
- Elizabeth Garrett Anderson Institute for Women's Health, Faculty of Population Health Sciences, University College London (UCL), London, United Kingdom.
| | - Jure Knez
- Clinic for Gynecology, University Medical Centre Maribor, Maribor, Slovenia
| | - Nikolaos Thanatsis
- Elizabeth Garrett Anderson Institute for Women's Health, Faculty of Population Health Sciences, University College London (UCL), London, United Kingdom
| | - Lucrezia De Braud
- Elizabeth Garrett Anderson Institute for Women's Health, Faculty of Population Health Sciences, University College London (UCL), London, United Kingdom
| | - Fatima Taki
- Elizabeth Garrett Anderson Institute for Women's Health, Faculty of Population Health Sciences, University College London (UCL), London, United Kingdom
| | - Martin Hirsch
- Nuffield Department of Women's and Reproductive Health, Oxford Endometriosis CaRe Centre, University of Oxford, Oxford, United Kingdom
| | - Anna David
- Elizabeth Garrett Anderson Institute for Women's Health, Faculty of Population Health Sciences, University College London (UCL), London, United Kingdom
| | - Davor Jurkovic
- Elizabeth Garrett Anderson Institute for Women's Health, Faculty of Population Health Sciences, University College London (UCL), London, United Kingdom
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Garg M, Rajanbabu A, Nair IR. Smooth muscle tumors of uncertain malignant potential or atypical leiomyomas: A long-term evaluation of surgical outcomes and clinicopathological features. Eur J Obstet Gynecol Reprod Biol 2024; 301:201-205. [PMID: 39154515 DOI: 10.1016/j.ejogrb.2024.07.062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 07/26/2024] [Accepted: 07/29/2024] [Indexed: 08/20/2024]
Abstract
OBJECTIVE The Primary Objective of this study was to analyse reproductive outcomes in patients with STUMP (Smooth Muscle Tumour of Uncertain Potential) or ALM (Atypical Leiomyoma) who underwent fertility-preserving surgeries. Secondary Objectives were to analyse long-term prognosis for these patients and to study the basic demographic and pathological characteristics of patients with STUMP or ALM. STUDY DESIGN This retrospective study was conducted at Amrita Institute of Medical Sciences. Cases of STUMP and ALM were retrieved from the hospital medical database between June 2014 and December 2022. Demographic parameters, clinical presentations, pathological features and clinical outcomes were analysed. Categorical variables were expressed in numbers and percentages. Normal distribution data were presented as mean while non-normal distribution was expressed as median and range. RESULTS Thirty-eight patients were included in the study with a diagnosis of STUMP or ALM in postoperative histology. Seven patients (18.4%) were nulliparous. Myomectomy was performed in 9 (23.6%), while hysterectomy was done in 29 patients (76.3%). Fertility-preserving surgeries were performed on six patients (15.7%). Of these six patients, 4(66.6%) conceived spontaneously and had successful pregnancies. Recurrences were found in 3 patients (7.8%) out of which one had undergone fertility-sparing surgery. All the patients with recurrences had previous history of myomectomies. Morcellation was reportedly done in 2 of these three patients. CONCLUSION Good reproductive outcomes have been demonstrated in patients diagnosed with STUMP or ALM and desiring fertility. However, these patients should be kept under follow-up care as they are prone for recurrences. Patients who have undergone morcellation mayhave an increased chance of recurrence.
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Affiliation(s)
- Monal Garg
- Department of Gynaecological Oncology, Amrita Institute of Medical Sciences, Ponekkara Rd, Edappally, Kochi, Ernakulam, Kerala 682041, India
| | - Anupama Rajanbabu
- Department of Gynaecological Oncology, Amrita Institute of Medical Sciences, Ponekkara Rd, Edappally, Kochi, Ernakulam, Kerala 682041, India; Department of Gynaecological Oncology, James Cook University Hospital, Marton Rd, Middlesbrough TS4 3BW, UK.
| | - Indu R Nair
- Department of Pathology, Amrita Institute of Medical Sciences, Ponekkara Rd, Edappally, Kochi, Ernakulam, Kerala 682041, India.
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Ferrari S, Salmeri N, He X, Schimberni M, Sangiorgi V, Bartiromo L, Tandoi I, Pagliardini L, Papaleo E, Candiani M. Thinking in context: Fibroids-to-uterine volume ratio in pre-surgical fertility evaluation for intramural fibroids. Eur J Obstet Gynecol Reprod Biol 2024; 301:194-200. [PMID: 39154514 DOI: 10.1016/j.ejogrb.2024.08.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 08/05/2024] [Accepted: 08/12/2024] [Indexed: 08/20/2024]
Abstract
OBJECTIVE To explore the utility of the total fibroids-to-uterine volume (FTUV) ratio as a simple, preoperative tool to assist in counseling patients seeking pregnancy who are undergoing myomectomy for intramural (IM) fibroids. STUDY DESIGN This is an historical cohort study on reproductive-aged patients seeking pregnancy who underwent laparotomic myomectomy for intramural fibroids from January 2017 to December 2021. Only G3 to G5 fibroids, according to the 2011 International Federation of Gynecology and Obstetrics (FIGO) classification, were included. Pre-operative transvaginal ultrasound (TVUS) was performed to measure the volume of intramural myomas (diameter1*diameter2*diameter3*0.52) and to calculate their total volume. The total fibroids-to-uterine volume (FTUV) ratio was calculated as the proportion of the uterine volume occupied by the sum of IM fibroids volumes. RESULTS A total of 166 women with pre-surgical TVUS evaluation of IM fibroids were included, with a mean age of 36.22 ± 5.15 years. The FTUV ratio was identified as a positive predictor of clinical pregnancy after surgery (adjOR, 1.04; 95 % CI, 1.02-1.06; p = 0.0001), whereas age showed a negative association (adjOR, 0.90; 95 % CI, 0.83-0.98; p = 0.012). Endometrial cavity distortion prior to surgery was also positively associated with pregnancy post-surgery (adjOR, 3.50; 95 % CI, 1.51-8.08; p = 0.003). Consistent results were found for live births, with the FTUV ratio being a significant positive predictor of live birth after surgery (adjOR, 1.03; 95 % CI, 1.01-1.05; p = 0.001) and age showing a negative association (adjOR, 0.88; 95 % CI, 0.80-0.96; p = 0.004). Parity prior to surgery also positively impacted live birth post-surgery (adjOR, 2.65; 95 % CI, 1.30-5.40; p = 0.007). An FTUV ratio threshold of 53.39 % accurately predicted clinical pregnancy in 68.46 % of cases (sensitivity of 71.70 % and specificity of 66.67 %). For live births, a higher FTUV ratio threshold of 59.21 % predicted outcomes accurately in 69.13 % of cases (sensitivity of 65.85 % and specificity of 70.37 %). CONCLUSION The use of the FTUV ratio in pre-operative ultrasound evaluation of IM fibroids may improve counseling for patients desiring to conceive after myomectomy. By providing a personalized assessment of the amount of myometrial volume occupied by fibroids, the FTUV ratio can help predict fertility outcomes after surgery, enabling better-informed decisions and treatment planning.
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Affiliation(s)
- Stefano Ferrari
- Gynecology and Obstetrics Unit, IRCCS San Raffaele Institute, 20132 Milan, Italy
| | - Noemi Salmeri
- Gynecology and Obstetrics Unit, IRCCS San Raffaele Institute, 20132 Milan, Italy.
| | - Xuemin He
- Gynecology and Obstetrics Unit, IRCCS San Raffaele Institute, 20132 Milan, Italy
| | - Matteo Schimberni
- Gynecology and Obstetrics Unit, IRCCS San Raffaele Institute, 20132 Milan, Italy
| | - Virginia Sangiorgi
- Gynecology and Obstetrics Unit, IRCCS San Raffaele Institute, 20132 Milan, Italy
| | - Ludovica Bartiromo
- Gynecology and Obstetrics Unit, IRCCS San Raffaele Institute, 20132 Milan, Italy
| | - Iacopo Tandoi
- Gynecology and Obstetrics Unit, IRCCS San Raffaele Institute, 20132 Milan, Italy
| | - Luca Pagliardini
- Gynecology and Obstetrics Unit, IRCCS San Raffaele Institute, 20132 Milan, Italy
| | - Enrico Papaleo
- Gynecology and Obstetrics Unit, IRCCS San Raffaele Institute, 20132 Milan, Italy
| | - Massimo Candiani
- Gynecology and Obstetrics Unit, IRCCS San Raffaele Institute, 20132 Milan, Italy
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Latif S, Kastora S, Al Wattar BH, Yasmin E, Saridogan E, Mavrelos D. The effectiveness of prolonged downregulation with gonadotrophin-releasing hormone analogue (GnRHa) treatment in women with adenomyosis undergoing IVF/ICSI: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2024; 301:87-94. [PMID: 39116480 DOI: 10.1016/j.ejogrb.2024.07.063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 06/14/2024] [Accepted: 07/30/2024] [Indexed: 08/10/2024]
Abstract
IMPORTANCE Adenomyosis can reduce the chance of clinical pregnancy in women undergoing assisted conception. Treatment with prolonged gonadotrophin-releasing hormone analogue (GnRHa) downregulation prior to IVF/ICSI has been postulated to improve pregnancy outcomes. OBJECTIVE We aimed to evaluate the effectiveness and safety of prolonged GnRHa treatment (minimum one month) versus no pre-treatment in women with adenomyosis undergoing IVF/ICSI using a systematic review and meta-analysis. DATA SOURCES We searched electronic databases: Embase (OVID), MEDLINE® (OVID), APA PsycInfo (OVID), Maternity & Infant Care Database (MIDIRS (OVID), HMIC Health Management Information Consortium (OVID) and ClinicalTrials.gov from inception until 27th of March 2023. STUDY SELECTION AND SYNTHESIS We included studies that reported on women with adenomyosis receiving GnRHa to down-regulate the hypothalamic-pituitary-ovarian axis for one to six months before IVF/ICSI. We pooled data using the Haensel-Mantel method and reported using Odds Ratio (OR) with 95 % confidence intervals (CI). We assessed the quality of included studies using the Newcastle-Ottowa Scale and confidence in evidence using the GRADE criteria. Bias analysis was conducted via the Cochrane recommended tool (RevMan Web, Academic License). MAIN OUTCOMES AND RESULTS We screened 365 citations and eight retrospective studies were included in the meta-analysis (n = 2422 women). The median age was 34 years [IQR 31.95-35.05], median BMI 21.30 kg/m2 [IQR 21.05-23.55] and median duration of GnRHa downregulation was 2.5 months [Range 1-4; IQR 1.37-3]. Women with adenomyosis receiving prolonged GnRHa treatment had a higher implantation rate 1/OR 1.69 [95 % CI 1.09, 2.56], I2 = 81 %, (P = 0.02) and clinical pregnancy rate 1/OR 1.42 [95 % CI 1.03, 2.0], I2 70 %, P = 0.03. There was no overall difference in live birth rate 1/OR 1.12 [95 % CI 0.70, 1.79], I2 = 78 %, p = 0.63), miscarriage rate 1/OR 0.92 [95 % CI 0.63, 1.28, P = 0.61, I2 0 % or mean number of oocytes retrieved (10 oocytes [IQR 8.95; 11.15] vs. 9.28 [IQR 8; 10.20], p = 0.22) between groups. CONCLUSIONS AND RELEVANCE The benefit of prolonged GnRHa treatment in women with adenomyosis undergoing assisted conception treatment is uncertain based on existing retrospective studies. Implantation and clinical pregnancy rates were higher following prolonged downregulation in this population, though there was no statistically significant difference in live birth and miscarriage rates. Given the limited, low-quality existing data, there is a need for a well-designed, prospective randomised controlled trial to precisely evaluate the effectiveness of prolonged GnRHa treatment in this population.
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Affiliation(s)
- Sania Latif
- Reproductive Medicine Unit, University College London Hospital, London, United Kingdom; Institute for Women's Health, University College London, London, United Kingdom.
| | - Stavroula Kastora
- Reproductive Medicine Unit, University College London Hospital, London, United Kingdom; Institute for Women's Health, University College London, London, United Kingdom
| | - Bassel H Al Wattar
- Beginnings Assisted Conception Unit, Epsom and St Helier University Hospitals, London, United Kingdom; Comprehensive Clinical Trials Unit, Institute for Clinical Trials and Methodology, University College London, London, United Kingdom
| | - Ephia Yasmin
- Reproductive Medicine Unit, University College London Hospital, London, United Kingdom; Institute for Women's Health, University College London, London, United Kingdom
| | - Ertan Saridogan
- Reproductive Medicine Unit, University College London Hospital, London, United Kingdom; Institute for Women's Health, University College London, London, United Kingdom
| | - Dimitrios Mavrelos
- Reproductive Medicine Unit, University College London Hospital, London, United Kingdom; Institute for Women's Health, University College London, London, United Kingdom
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Vercellini P, Piccini M, Caprara F, Cetera GE, Viganò P, Somigliana E. Potential anatomical determinants of retrograde menstruation: a comprehensive narrative review. Reprod Biomed Online 2024; 49:104345. [PMID: 39137508 DOI: 10.1016/j.rbmo.2024.104345] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 05/30/2024] [Accepted: 06/17/2024] [Indexed: 08/15/2024]
Abstract
A century ago, Sampson identified three uterine anatomical structures that may determine the amount of retrograde menstruation and the likelihood of the development of endometriosis: the cervix, the intramural portion of the fallopian tubes, and the myometrium. Critical appraisal was undertaken of data published over the last 40 years on the potential effect of the characteristics of these three anatomical variables on the risk of endometriosis. There is some evidence to support the pathogenic role of the diameter of the cervical canal, stenosis of internal or external orifices, and stiffness of cervical tissue. One study showed a significant association between the morphology of the intramural tubal tract and the frequency of endometriosis. A large body of evidence points to abnormalities of the myometrial structure as the anatomical aberration most consistently associated with endometriosis. These abnormalities have largely been interpreted as signs of early-onset adenomyosis, which may precede endometriosis and even lead to its development by increasing the amount of retrograde menstruation. Future research should aim to verify whether a positive relationship exists between the substantially increased number of ovulatory menses occurring in the decade following menarche, the development of anatomical myometrial abnormalities, changes in the amount of retrograde menstruation over time, and the risk of endometriosis.
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Affiliation(s)
- Paolo Vercellini
- Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Martina Piccini
- Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy
| | - Francesca Caprara
- Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy
| | - Giulia Emily Cetera
- Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Paola Viganò
- Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Edgardo Somigliana
- Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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48
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Della Corte L, D'Angelo G, Ascione M, Granata M, Giampaolino P, Di Spiezio Sardo A, Bifulco G. A comparative retrospective analysis on robot-assisted laparoscopic surgery compared to conventional laparoscopy in case of myomectomy: experience in a third-level hospital of Southern Italy. Updates Surg 2024; 76:2371-2378. [PMID: 38689199 PMCID: PMC11541250 DOI: 10.1007/s13304-024-01863-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 04/19/2024] [Indexed: 05/02/2024]
Abstract
Uterine myomas are the most common gynecological disease in reproductive-aged women, present several symptoms, and require effective medical and/or surgical strategies. This study aimed to compare robotic-assisted laparoscopic myomectomy (RALM) with laparoscopic myomectomy (LM) in terms of operative times, intraoperative estimated blood loss, pre- and post-hemoglobin levels drop, and length of hospital stay. Data from 50 clinical records (25 RALM in Group A and 25 LM in Group B) of patients with uterine fibroids were collected from December 2022 to December 2023 at Gynecological Unit of DAI Materno-Infantile Federico II in Naples, Italy. Patients aged 30-49 years with symptomatic fibroids were included. Data on peri-operative outcomes, including operative time for myomectomy (OTM), overall operative time (OOT), intraoperative estimated blood loss (EBL), pre- and post-operative hemoglobin levels, and length of hospital stay were analyzed. The OTM in the presence of > 5 myomas was 59 [52-65] vs 69 min [61-96] (p < 0.001) for RALM and LM groups, respectively. Moreover, also in presence of ≤ 5 myomas, a difference was observed in the RALM group 48[43-55] compared to the LM group 53[50-61] min (p = 0.07). The OOT was also statistically significant for Group A compared to Group B (83[65-93] vs 72[56-110] min, p < 0.001). There were no significant differences between the two groups in terms of pre- and post-operative hemoglobin levels and EBL (p = 0.178). Group A demonstrated a notably shorter hospital stay 1.2 [1-2] days compared to Group B 2.9[3-3.75] days (p = 0.007). Our study suggests potential advantages of RALM over LM in terms of reduced operative times and shorter hospital stays. The standardized approach and extensive surgical experience likely contributed to the favorable outcomes of RALM.
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Affiliation(s)
- Luigi Della Corte
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
| | - Giuseppe D'Angelo
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Via Sergio Pansini 5, 80131, Naples, Italy.
- Department of Public Health, University of Naples Federico II, Naples, Italy.
| | - Mario Ascione
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Marcello Granata
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | | | | | - Giuseppe Bifulco
- Department of Public Health, University of Naples Federico II, Naples, Italy
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49
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Borghese G, Doglioli M, Orsini B, Raffone A, Neola D, Travaglino A, Rovero G, Del Forno S, de Meis L, Locci M, Guida M, Lenzi J, Seracchioli R, Raimondo D. Progression of adenomyosis: Rate and associated factors. Int J Gynaecol Obstet 2024; 167:214-222. [PMID: 38738458 DOI: 10.1002/ijgo.15572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 04/13/2024] [Accepted: 04/20/2024] [Indexed: 05/14/2024]
Abstract
OBJECTIVE To evaluate the rate of disease progression and the factors associated with such progression in patients with an ultrasound diagnosis of adenomyosis. METHODS This was a single center, prospective, observational, cohort study performed at a tertiary referral center. Patients who obtained an ultrasound diagnosis of adenomyosis from May 2022 to August 2022 were recruited. Demographic, clinical and ultrasound data were recorded at the first visit (T0) and after 12 months (T1) for enrolled patients and compared between T0 and T1. The study population was divided in two groups according to progression (increase in uterine volume >20%) or stability/regression (decrease or increase in uterine volume ≤20%) of adenomyosis at T1. Primary study outcome was the rate of adenomyosis progression, while secondary study outcome was the association of adenomyosis progression with demographic and clinical factors. Post hoc subgroups analyses for primary and secondary study outcomes were performed based on hormonal therapy (untreated and treated). RESULTS A total of 221 patients were enrolled in the study, with no significant difference in terms of baseline data among the two study groups and no patients were lost to follow-up. The overall rate of adenomyosis progression was 21.3% (47/221 patients). The rate was 30.77% in hormonally untreated women, and 18.34% in hormonally treated women. Progression was associated with the presence of focal adenomyosis of the outer myometrium (P = 0.037), moderate to severe dysmenorrhea (P = 0.001), chronic pelvic pain (P = 0.05), dyschezia (P = 0.05), and worsening of chronic pelvic pain (P = 0.04) at T1. CONCLUSION Adenomyosis showed a rate of disease progression of 21.3% at the 12-month follow-up (30.77% in hormonally untreated women, and 18.34% in hormonally treated women). The presence and/or worsening of painful symptoms, such as severe dysmenorrhea, dyschezia and chronic pelvic pain, as well as the presence focal adenomyosis of the outer myometrium, might help identify patients at higher risk of disease progression and tailor their follow-up.
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Affiliation(s)
- Giulia Borghese
- Division of Gynecology and Human Reproduction Physiopathology, IRCCS Azienza Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Marisol Doglioli
- Division of Gynecology and Human Reproduction Physiopathology, IRCCS Azienza Ospedaliero Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, DIMEC, University of Bologna, Bologna, Italy
| | - Benedetta Orsini
- Division of Gynecology and Human Reproduction Physiopathology, IRCCS Azienza Ospedaliero Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, DIMEC, University of Bologna, Bologna, Italy
| | - Antonio Raffone
- Department of Medical and Surgical Sciences, DIMEC, University of Bologna, Bologna, Italy
- Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Daniele Neola
- Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Antonio Travaglino
- Unit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy
| | - Giulia Rovero
- Division of Gynecology and Human Reproduction Physiopathology, IRCCS Azienza Ospedaliero Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, DIMEC, University of Bologna, Bologna, Italy
| | - Simona Del Forno
- Division of Gynecology and Human Reproduction Physiopathology, IRCCS Azienza Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Lucia de Meis
- Division of Gynecology and Human Reproduction Physiopathology, IRCCS Azienza Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Mariavittoria Locci
- Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Maurizio Guida
- Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Jacopo Lenzi
- Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Renato Seracchioli
- Division of Gynecology and Human Reproduction Physiopathology, IRCCS Azienza Ospedaliero Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, DIMEC, University of Bologna, Bologna, Italy
| | - Diego Raimondo
- Division of Gynecology and Human Reproduction Physiopathology, IRCCS Azienza Ospedaliero Universitaria di Bologna, Bologna, Italy
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50
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Athanasiou A, Fruscalzo A, Dedes I, Mueller MD, Londero AP, Marti C, Guani B, Feki A. Advances in Adenomyosis Treatment: High-Intensity Focused Ultrasound, Percutaneous Microwave Therapy, and Radiofrequency Ablation. J Clin Med 2024; 13:5828. [PMID: 39407887 PMCID: PMC11476787 DOI: 10.3390/jcm13195828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 09/11/2024] [Accepted: 09/21/2024] [Indexed: 10/20/2024] Open
Abstract
Background/Objectives: Adenomyosis is a debilitating gynecologic condition that affects both multiparous older women and nulliparous younger women, inducing a variety of symptoms such as dysmenorrhea, menorrhagia, and infertility. Thermal ablation techniques are new procedures that have been proposed for the treatment of adenomyosis. They include high-intensity focused ultrasound (HIFU), percutaneous microwave ablation (PMWA), and radiofrequency ablation (RFA). Because thermal ablation techniques are minimally invasive or noninvasive, fertility is not impaired while symptoms improve. In addition, hospital stays and financial costs are generally reduced, increasing the interest in these alternative management options. Methods: In this narrative review, we conducted a thorough literature search of PubMed/Medline from the database inception to September 2022. In our search, we focused on noninvasive treatment methods such as HIFU ablation, RFA ablation, and PMWA as well as adenomyosis-specific terms and noninvasive techniques (ultrasonography, ultrasound, or magnetic resonance imaging). The queries were a combination of MeSH terms and keywords. The search was limited to the English language. Abstracts were screened according to their content, and relevant articles were selected. Results: Overall, the results showed that the above-mentioned ablation techniques are effective and safe in providing adenomyosis treatment. Lesion size and uterus volume are reduced, leading to considerable symptom alleviation with all three methods. Positive results concerning safety and fertility preservation have been described as well. Conclusions: Nonetheless, more research is required in this field to compare the efficacy and safety of different ablation techniques with traditional therapies. Such research will help improve these procedures and their associated decision-making processes.
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Affiliation(s)
- Adamantios Athanasiou
- Department of Gynecologic Oncology, Agios Savvas General Anti-Cancer Hospital of Athens, 11522 Athens, Greece;
| | - Arrigo Fruscalzo
- Department of Obstetrics and Gynecology, University Hospital of Fribourg, 1708 Fribourg, Switzerland; (C.M.); (B.G.); (A.F.)
| | - Ioannis Dedes
- Department of Obstetrics and Gynecology, University Hospital of Bern, 3010 Bern, Switzerland; (I.D.); (M.D.M.)
| | - Michael D. Mueller
- Department of Obstetrics and Gynecology, University Hospital of Bern, 3010 Bern, Switzerland; (I.D.); (M.D.M.)
| | - Ambrogio P. Londero
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Infant Health, University of Genoa, 16132 Genoa, Italy;
- Obstetrics and Gynecology Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
| | - Carolin Marti
- Department of Obstetrics and Gynecology, University Hospital of Fribourg, 1708 Fribourg, Switzerland; (C.M.); (B.G.); (A.F.)
| | - Benedetta Guani
- Department of Obstetrics and Gynecology, University Hospital of Fribourg, 1708 Fribourg, Switzerland; (C.M.); (B.G.); (A.F.)
| | - Anis Feki
- Department of Obstetrics and Gynecology, University Hospital of Fribourg, 1708 Fribourg, Switzerland; (C.M.); (B.G.); (A.F.)
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