Submucosal cystic adenomyosis: a report of five cases and review of the literature.

AIM: To investigate the clinical characteristics, diagnosis, and clinical treatment of submucosal cystic adenomyosis. METHODS: The clinical data of five cases of patients with submucosal cystic adenomyosis in our hospital from January 2020 to June 2023 were retrospectively analyzed. RESULTS: The average age of the patients was 37.8 ± 4.5 years old, three of them experienced prolonged menstruation and heavy menstrual bleeding. All patients had a history of abnormal uterine bleeding and mild to moderate dysmenorrhea, with a VAS score of 2.8 ± 1.6. The average Carbohydrate antigen 125 (CA125) value was 29.9 ± 23.6U/ml. Two out of the five patients (40%) had CA125 values above the upper limit of normal. The nodules had a diameter of 3.2 ± 1.3 cm and a cavity size of 1.3 ± 0.7 cm. Color ultrasound revealed hypo or iso or anechoic echoic cysts, and blood flow signals were detected. The magnetic resonance imaging (MRI) findings varied among each patient. All the patients underwent hysteroscopy and resection of uterine cavity-occupying lesions, and no recurrence was observed. CONCLUSIONS: The clinical features of submucosal cystic adenomyosis include abnormal uterine bleeding and menstrual changes, and the degree of dysmenorrhea is generally not severe. The diagnostic utility of CA125 in submucosal cystic adenomyosis may be limited. The three-dimensional ultrasound and MRI are valuable preoperative examination methods currently. Hysteroscopy can not only diagnose submucosal cystic adenomyosis, but also treat it, and preserve the fertility function of the patient.

A new treatment for Robert's uterus with adenomyosis: a case report and review of the literature.

PURPOSE: To provide a method for the differential diagnosis of Robert's uterus with adenomyosis, a rare uterine malformation, and determine the best course of treatment. METHODS: A patient who had Robert's uterus with adenomyosis was admitted to our hospital in December 2022. We analyzed and summarized her case . RESULTS: Our patient complained of progressively worsening primary dysmenorrhea over the course of 3 years and lower abdominal pain lasting for 2 days. Her carbohydrate antigen 125 (CA125) level was 372.10 U/mL. Examinations conducted by several hospitals indicated that she had a single-horned uterus and a residual horned uterus, and our hospital's examination identified Robert's uterus. This malformation was corrected by open abdominal surgery. For the procedure, pelvic adhesions were first isolated, after which the closed uterine cavity and adenomyosis were resected. Subsequently, the left ovarian endometriosis cyst was resected and right tubal ligation was performed. After surgery, three injections of gonadotropin-releasing hormone A (GnRH-A) were administered, which lowered the patient's CA125 level to 14 U/mL and normalized her condition. CONCLUSION: We pioneered a new therapeutic approach for the treatment of Robert's uterus with adenomyosis. Some valuable references are provided for clinical practice.

A rare case of concomitant endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrial deep endometriosis.

BACKGROUND: Carcinomatous changes from the ectopic endometrial glands in endometriosis have been reported in many studies, but malignant transformation from uterine adenomyosis/adenomyoma is rare. And clear cell-like adenocarcinoma represents a seldom-encountered malignant pathological variant of ectopic endometrium. CASE PRESENTATION: This case report presents a case of a 44-year-old nulliparous woman begun with abdominal pain and intestinal obstruction. Past medical history showed laparoscopic ovarian endometriotic cyst excision. Ultrasound indicated adenomyoma and a parametrial hypoechoic nodule with abundant blood flow signals and unclear boundaries. Deep invasive endometriosis was considered preoperatively. The patient underwent laparoscopic subtotal hysterectomy and bilateral adnexa resection. Chocolate cyst-like lesion was observed in the parametral lesion. Postoperative pathological examinations suggested endometrioid adenocarcinoma arising from eutopic endometrium and adenomyoma. Ectopic endometrium in the myometrium combined with atypical hyperplasia and formation of endometrioid adenocarcinoma. Left parametrial lesions suggested poorly differentiated endometrioid adenocarcinoma combined with clear cell carcinoma. CD10 + endometrial stromal cells were observed surrounding tumor cell masses. Combined with surgical founding and pathological characters of the left parametrial adenocarcinoma, the parametrial lesions were more likely to be carcinomatous changes of the original deep endometriosis.The patient underwent subsequent transabdominal tumor cell reduction surgery and chemotherapy. CONCLUSION: We herein present a rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrial deep endometriosis that may help inspire additional studies in the future. The patient underwent robot-assisted laparoscopic subtotal hysterectomy, bilateral adnexa resection, deep endometriosis lesion resection and bilateral ureteral stent placement. Following surgery, a chemotherapy regimen of Taxol and Carboplatin was administered.

The Current Understanding of Molecular Mechanisms in Adenomyosis-Associated Infertility and the Treatment Strategy for Assisted Reproductive Technology.

Adenomyosis, endometriosis of the uterus, is associated with an increased likelihood of abnormal endometrial molecular expressions thought to impair implantation and early embryo development, resulting in disrupted fertility, including the local effects of sex steroid and pituitary hormones, immune responses, inflammatory factors, and neuroangiogenic mediators. In the recent literature, all of the proposed pathogenetic mechanisms of adenomyosis reduce endometrial receptivity and alter the adhesion molecule expression necessary for embryo implantation. The evidence so far has shown that adenomyosis causes lower pregnancy and live birth rates, higher miscarriage rates, as well as adverse obstetric and neonatal outcomes. Both pharmaceutical and surgical treatments for adenomyosis seem to have a positive impact on reproductive outcomes, leading to improved pregnancy and live birth rates. In addition, adenomyosis has negative impacts on reproductive outcomes in patients undergoing assisted reproductive technology. This association appears less significant after patients follow a long gonadotropin-releasing hormone agonist (GnRHa) protocol, which improves implantation rates. The pre-treatment of GnRHa can also be beneficial before engaging in natural conception attempts. This review aims to discover adenomyosis-associated infertility and to provide patient-specific treatment options.

Pain with orgasm in endometriosis: potential etiologic factors and clinical correlates.

BACKGROUND: Pelvic pain worsened by orgasm is a poorly understood symptom in patients with endometriosis. AIM: To assess the prevalence of pelvic pain worsened by orgasm in patients with endometriosis and explore its association with potential etiologic factors, including pelvic floor myalgia, uterine tenderness and adenomyosis, and central nervous system sensitization. METHODS: An analysis was done of a prospective data registry based at a tertiary referral center for endometriosis. Eligible participants were patients aged 18 to 50 years who were referred between January 1, 2018, and December 31, 2019, diagnosed with endometriosis, and subsequently underwent surgery at the center. Clinical features were compared between participants reporting worsening pelvic pain with orgasm and those without worsening pain with orgasm, including patient-reported variables, physical examination findings, and anatomic phenotyping at the time of surgery. Pelvic floor myalgia and uterine tenderness were assessed by palpation on pelvic examination, adenomyosis by ultrasound, and central nervous system sensitization via the Central Sensitization Inventory (range, 0-100). OUTCOMES: Outcomes included pelvic or lower abdominal pain in the last 3 months that worsened with orgasm (yes/no). RESULTS: Among 358 participants with endometriosis, 14% (49/358) reported pain worsened by orgasm while 86% (309/358) did not. Pain with orgasm was significantly associated with pelvic floor myalgia (55% [27/49] vs 35% [109/309]; Cohen's h = 0.40, P = .01) and higher scores on the Central Sensitization Inventory (mean ± SD, 53.3 ± 17.0 vs 42.7 ± 18.2; Cohen's d = 0.60, P < .001) but not with uterine tenderness or adenomyosis. Other clinical features associated with pain with orgasm were poorer sexual health (higher scores: deep dyspareunia, Cohen's h = 0.60; superficial dyspareunia, Cohen's h = 0.34; and Female Sexual Distress Scale-Revised, Cohen's d = 0.68; all P < .05) and poorer mental health (higher scores: Patient Health Questionnaire-9, 12.9 ± 6.7 vs 9.1 ± 6.3, Cohen's d = 0.59, P < .001; Generalized Anxiety Disorder-7, 9.4 ± 5.6 vs 6.8 ± 5.5, Cohen's d = 0.48, P = .002). Anatomic findings at the time of surgery did not significantly differ between the groups. CLINICAL IMPLICATIONS: Interventions targeting pelvic floor myalgia and central nervous system sensitization may help alleviate pain worsened by orgasm in patients with endometriosis. STRENGTHS AND LIMITATIONS: A strength is that pain worsened by orgasm was differentiated from dyspareunia. However, pain with orgasm was assessed by only a binary question (yes/no). Also, the study is limited to a single center, and there were limited data on sexual function. CONCLUSION: Pelvic pain exacerbated by orgasm in people with endometriosis may be related to concurrent pelvic floor myalgia and central sensitization.

Vaginal microbiome differences between patients with adenomyosis with different menstrual cycles and healthy controls.

BACKGROUND: Adenomyosis is a commonly observed benign gynecological disease that affects the quality of life and social psychology of women of childbearing age. However, because of the unknown etiology and incidence of adenomyosis, its pathophysiological mechanism remains unclear; further, because no noninvasive, accurate, and individualized diagnostic methods are available, treatment and efficacy evaluations are limited. Notably, the interaction between the changes in the microecological environment of the female reproductive tract and human immunity, endocrine, and other links leads to the occurrence and development of diseases. In addition, the vaginal microbiome differs in different menstrual cycles; therefore, assessing the differences between the microbiomes of patients with adenomyosis and healthy individuals in different menstrual cycles will improve the understanding of the disease and provide references for the search for noninvasive diagnosis and individualized precision treatment of adenomyosis. This study aimed to explored the data of individuals in different menstrual cycles. RESULTS: Differences in the vaginal microbiome between patients with adenomyosis and healthy individuals were observed. At phylum level, the relative abundance of Firmicutes in the adenomyosis group was higher than that in the control group, which contributed the most to the species difference between the two groups. At the genus level, Lactobacillus was the most dominant in both groups, Alpha-diversity analysis showed significant differences in the adenomyosis and control group during luteal phase (Shannon index, p = 0.0087; Simpson index, p = 0.0056). Beta-diversity index was significantly different between the two groups (p = 0.018). However, based on Weighted Unifrac analysis, significant differences were only observed throughout the luteal phase (p = 0.0146). Within the adenomyosis group, differences between women with different menstrual cycles were also observed. Finally, 50 possible biomarkers including were screened and predicted based on the random forest analyse. CONCLUSIONS: The vaginal microbiome of patients with adenomyosis and healthy individuals differed during menstrual periods, especially during the luteal phase. These findings facilitate the search for specific biological markers within a limited range and provide a more accurate, objective, and individualized diagnostic and therapeutic evaluation method for patients with adenomyosis, compared to what is currently available.

Improvement of early miscarriage rates in women with adenomyosis via oxytocin receptor antagonist during frozen embryo transfer-a propensity score-matched study.

BACKGROUND: Dysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis. METHODS: Between January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses. RESULTS: The study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis. CONCLUSIONS: Administering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.

Prevalence and risk factors for chronic endometritis in patients with adenomyosis and infertility: a retrospective cohort study.

BACKGROUND: To explore the incidence of chronic endometritis (CE) in patients with infertility and different forms of adenomyosis and analyze potential high-risk factors for infection. METHODS: This retrospective cohort study included 154 patients with infertility in the Liuzhou Maternity and Child Healthcare Hospital. Among them, 77 patients with adenomyosis were divided into four subgroups based on magnetic resonance imaging (MRI): internal, exterior, intramural, and full-thickness. Meanwhile, 77 patients did not have adenomyosis. Hysteroscopy and endometrial biopsy were performed in the proliferative phase. The main outcome measures were the morphology of the endometrium, syndecan-1 (CD138) immunohistochemical staining, clinical characteristics, and prevalence of CE in the adenomyosis subgroups. RESULTS: In comparison to the non-adenomyosis group, the adenomyosis group had significantly higher body mass index (BMI) and CA125 levels. The menstrual cycle in the adenomyosis group was significantly shorter, and menarche was significantly earlier. In comparison to the non-adenomyosis group, the adenomyosis group had a significantly higher diagnostic rate of CE (75.3% vs. 46.8% according to hysteroscopy and 74.0% vs. 33.8% according to histopathology, both with p < .050). The incidence of CE was significantly lower in patients with internal adenomyosis when compared with the other three subgroups. Increased BMI contributed to a higher risk of CE. CONCLUSIONS: The prevalence of CE was significantly higher in patients with adenomyosis and infertility. The differences in the incidence of CE are closely associated with the classification of adenomyosis. When patients with infertility are diagnosed with adenomyosis, it is recommended to identify the subtype and screen for endometritis.

Adenomyosis and Abnormal Uterine Bleeding: Review of the Evidence.

BACKGROUND: Thomas Cullen described bleeding abnormalities and dysmenorrhea as the "expected" presentations of adenomyomas. Adenomyosis is included within the FIGO classification of structural causes of abnormal uterine bleeding (AUB). Nevertheless, this long-standing association has been questioned by some authors who reported a high incidence of adenomyosis in uteri removed for indications other than AUB or dysmenorrhea. Here, we examine evidence for the link between adenomyosis and AUB. METHODS: A comprehensive Medline literature review of all publications to October 2023. RESULTS: Sixty-three articles were identified and included in the review. Despite a large body of studies, the available literature does not provide conclusive evidence of a link between adenomyosis and AUB. This is because of unsuitable study design, or poor characterization of the study population or of the inclusion or exclusion criteria. Additional challenges arise because of the lack of agreed criteria for diagnosing adenomyosis and the often absence of detailed assessment of menstrual blood loss. Adenomyosis often coexists with other conditions that have also been linked to similar symptoms, and many cases of adenomyosis are asymptomatic. CONCLUSION: Most of the existing literature and studies that addressed treatment outcome of adenomyosis started from the premise that a link between the condition and AUB had been proven. Yet, published information shows that aspects such a relationship is still uncertain. Further research is needed to address the relation between AUB and adenomyosis burden (or subtypes), distribution, and concomitant pathology.

Factors associated with dysmenorrhoea and menorrhagia improvement in patients with adenomyosis after uterine artery embolisation.

BACKGROUND: This study examined the improvement of dysmenorrhoea and menorrhagia after uterine artery embolisation (UAE) in women with symptomatic adenomyosis and identified factors that could predict the improvement of dysmenorrhoea and menorrhagia. METHODS: This retrospective study included women with adenomyosis who underwent bilateral UAE between December 2014 and December 2016. The percentage of the volume of the absence of contrast enhancement on T1-weighted images was evaluated 5-7 days after UAE. A receiver operating characteristic (ROC) analysis was used to determine a cut-off point and predict the improvement of dysmenorrhoea and menorrhagia. RESULTS: Forty-eight patients were included. At 24 and 36 months after UAE, the improvement rates for dysmenorrhoea and menorrhagia were 60.4% (29/48) and 85.7% (30/35), and the recurrence rates were 19.4% (7/36) and 9.1% (3/33), respectively. Only the percentage of the volume of the absence of contrast enhancement on T1-weighted images was associated with the improvement of dysmenorrhoea (p = 0.001, OR = 1.051; 95% CI: 1.02-1.08) and menorrhagia (p = 0.006, OR = 1.077; 95% CI: 1.021-1.136). When the cut-off value of the ROC analysis was 73.1%, sensitivity, specificity, positive predictive value, and negative predictive value for the improvement of dysmenorrhoea were 58.6%, 94.7%, 94.4%, and 60%, while they were 58.9%, 80%, 100%, 100%, and 45.5% for the improvement of dysmenorrhoea. CONCLUSION: Bilateral UAE for symptomatic adenomyosis led to good improvement of dysmenorrhoea and menorrhagia. The percentage of the volume of the absence of contrast enhancement on T1-weighted images of the uterus in postoperative magnetic resonance imaging might be associated with the improvement of dysmenorrhoea and menorrhagia.

This study examined the improvement of dysmenorrhoea and menorrhagia after uterine artery embolisation in women with symptomatic adenomyosis and identified factors that could predict the improvement of dysmenorrhoea and menorrhagia. This retrospective study included women with adenomyosis who underwent uterine artery embolisation. A total of 48 patients were included. Only the percentage of the volume of the absence of contrast enhancement on T1-weighted images was associated with improvement of dysmenorrhoea and menorrhagia. Bilateral uterine artery embolisation for symptomatic adenomyosis led to good improvement. The percentage of the volume of the absence of contrast enhancement on images in postoperative T1-weighted magnetic resonance imaging of the uterus might be associated with the improvement of dysmenorrhoea and menorrhagia.

The use of dienogest in treatment of symptomatic adenomyosis: A systematic review and meta-analysis.

Adenomyosis is a gynaecological problem that impacts women's quality of life by causing dysmenorrhea, chronic pelvic pain, and menorrhagia. The search continues for the best medical treatment for symptomatic adenomyosis. This systematic review and meta-analysis investigated the role of dienogest, an oral progestin, in reducing pain and bleeding associated with adenomyosis. Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, Scopus, and Web of Science were searched in January 2024. The primary outcome was pain scores for dysmenorrhea, whereas secondary outcomes were chronic pelvic pain (CPP), uterine volume (UV), and menorrhagia. One comparison was performed comparing outcomes in symptomatic adenomyosis before and after treatment with dienogest. Pooled analysis of included studies reported a statistically significant reduction of dysmenorrhea pain score after dienogest treatment (mean difference -5.86 cm on a 10-cm visual analogue scale, 95 % CI -7.20 to -4.53, I2 = 97 %). Regarding chronic pelvic pain, a meta-analysis of included studies showed a significant decline in pain after treatment (standardized mean difference -2.37, 95 % CI -2.89 to -1.86, I2 = 60 %). However, uterine volume did not differ significantly after treatment (mean difference -4.65 cm3, 95 % CI -43.22 to 33.91). Menorrhagia was improved significantly after treatment (Peto odds ratio 0.07, 95 % CI 0.03 to 0.18). In conclusion, dienogest seems to be effective in controlling painful symptoms and uterine bleeding in women with adenomyosis at short and long-term therapy.

Association of Uterine Tissue Innervation and Peripheral Nerve Density with Adenomyosis Related Pain. A Systematic Review.

Adenomyosis is associated with dysmenorrhea and chronic pelvic pain; however, the triggering mechanisms of painful stimuli and the role of uterine nerve fibers in the manifestation of pain remain poorly understood. The objective of this study was to systematically review the role of uterine nerve fibers' presence and density in the occurrence of pain in patients with adenomyosis. An electronic search was performed using the Embase, PubMed/Medline, and Cochrane databases. We included all studies from inception to November 2023. A total of ten studies that compared uterine biopsies samples of women with and without adenomyosis were included. The biomarker antiprotein gene product 9.5 was decreased or absent in the endometrium of most included women with adenomyosis. None of the included studies observed a difference in neurofilament (NF) staining between the adenomyosis and non-adenomyosis groups. Studies that assessed nerve growth factor (NGF) staining were heterogeneous in design. One study reported no difference in immunohistochemistry staining in any endometrial layer between the adenomyosis and non-adenomyosis groups, while another reported increased staining in the adenomyosis functional endometrial layer, and a third study reported overexpression of NGF, synaptophysin (SYN), and microtubule-associated protein 2 mRNA in focal adenomyosis alone. Preliminary data from poor-quality studies suggest an increase in the uterine density of nerve fibers in patients with adenomyosis. Well-designed studies are essential to assess the cause-and-effect relationship between uterine nerve fibers and pain in patients with adenomyosis.

Progression of adenomyosis: Rate and associated factors.

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.

Type and Location of Adenomyosis in Women with Recurrent Pregnancy Loss: A Transvaginal Ultrasonographic Assessment.

The current knowledge on adenomyosis as a risk factor for RPL is very scant. Overall 120 women were included in this retrospective observational study. They were divided in three groups each of which consisted of 40 subjects: Group 1: women with RPL who were diagnosed to have adenomyosis on transvaginal ultrasound (TVS); Group 2: patients with RPL without ultrasonographic findings of adenomyosis; Group 3: patients with ultrasound diagnosis of adenomyosis without RPL and at least one live birth pregnancy. The copresence of endometriosis was also investigated. Among women with RPL, patients with adenomyosis (Group 1) had higher number of pregnancy losses (p = 0.03) and lower age at first pregnancy loss (p = 0.03) than women without adenomyosis (Group 2). Moreover, they had more frequently primary RPL (p = 0.008). Adenomyosis of the inner myometrium was found more frequently (p = 0.04) in patients of Group 1 than in patients of Group 3 in which adenomyosis was mainly in the outer myometrium (p= 0.02). No differences were found in the severity of adenomyosis between these two groups of women. TVS findings for endometriosis were observed more frequently in women with adenomyosis without RPL (Group 3) than in the other two groups of patients. Adenomyosis can be a factor involved in RPL. Differences in adenomyosis localization are associated with different risks for RPL. Patients with RPL should be investigated for the presence of adenomyosis and also for the type and localization of the disease in the different myometrial layers.

Evaluating the development of endometriosis and adenomyosis lesions over time: An ultrasound study of symptomatic women.

INTRODUCTION: There is a gap in knowledge regarding development of endometriosis and adenomyosis lesions visible at transvaginal ultrasound. The objectives were to evaluate if women with symptoms suggestive of endometriosis or adenomyosis but normal ultrasound examination develop endometriosis or adenomyosis lesions visible at ultrasound over time and if alterations of symptoms over time are associated with ultrasound findings at follow-up. MATERIAL AND METHODS: This was a prospective cohort study of 100 symptomatic women with normal initial ultrasound examination during 2014-2017 who underwent follow-up ultrasound examination in 2022. Symptoms suggestive of endometriosis were assessed using visual analog scale at both examinations and minimal clinically important difference of 10 mm was considered as a significant alteration. An examiner with expertise in advanced ultrasound examination of endometriosis performed transvaginal ultrasound examinations in accordance with the consensus protocol by the International Deep Endometriosis Analysis group. RESULTS: At follow-up ultrasound examination of 100 women, 13 (13% [95% CI 7.1-21.2]) had visible endometriosis or adenomyosis lesions, 8 (8% [95% CI 3.5-15.2]) had endometriosis lesions, and 6 (6% [95% CI 2.2-12.6]) had adenomyosis. At follow-up, women with endometriosis or adenomyosis lesions reported lower intensity of dysmenorrhea and chronic pelvic pain compared to women without lesions (48 mm [IQR 16-79] vs. 73 mm [IQR 46-85] and 45 mm [IQR 26-57] vs. 57 mm [IQR 36-75], p = 0.087 and p = 0.026, respectively). None of the women with endometriosis or adenomyosis lesions reported increased intensity of dysmenorrhea at follow-up, compared to 32/86 women (37%) without lesions (p = 0.008). Increased intensity of chronic pelvic pain tended to be less common in women with lesions compared to those without (3/13 [23%] vs. 35/86 [41%], p = 0.223). CONCLUSIONS: Our findings suggest that in symptomatic women, endometriosis and adenomyosis lesions visible at ultrasound may develop over time. However, majority of women remain having normal ultrasound examinations despite symptoms. Exacerbation of dysmenorrhea or chronic pelvic pain during follow-up was not associated with the development of endometriosis or adenomyosis lesions visible at ultrasound, suggesting that even women with less severe symptoms might benefit from a follow-up ultrasound when indicated.

Breast Cancer in Patients with Previous Endometriosis Showed Low Aggressive Subtype.

Background and Objectives: The association between endometriosis and breast cancer still remains controversial. The aim of this study was to investigate the different subtypes of breast cancer, immunohistochemical markers, hormone receptors, and ki67 proliferation indexes in patients with and without endometriosis and/or adenomyosis. Materials and Methods: All patients with endometriosis and breast cancer were enrolled. Women with endometriosis and breast cancer (Group BC+EN+) were compared to patients with breast cancer without endometriosis (group BC+EN-) and those with endometriosis without breast cancer (group BC-EN+). General population characteristics and histological and immunohistochemical subtypes of breast cancer were compared between groups. Results: Our study included 41 cases affected by both endometriosis and/or adenomyosis and breast cancer (Group BC+EN+) that were matched (1:2) with 82 patients affected only by breast cancer (group BC+EN-) and 82 patients affected only by endometriosis and/or adenomyosis (group BC-EN+). Group BC+EN+ presented a higher percentage of ER receptor expression (83% vs. 70%, p = 0.02), as well as lower values of Ki 67% (15% vs. 24%, p < 0.0001) and HER2+ (9.8% vs. 28%, p = 0.022). These findings were more evident when comparing patients with premenopausal status, while in postmenopausal patients, this difference was no longer significant. Regarding endometriosis, no statistical differences were observed in type or specific localization of the disease among the groups with and without breast cancer. Conclusions: Patients with endometriosis presented lower aggressive breast cancer rates with higher values of ER% and lower values of Ki 67 and HER2neu+. The type and severity of endometriotic diseases seemed not to influence breast cancer occurrence.

Macrophage polarization in adenomyosis: A review.

Adenomyosis (AM) is a common gynecological disorder characterized by the presence of endometrial glands and stroma within the uterine myometrium. It is associated with abnormal uterine bleeding (AUB), dysmenorrhea, and infertility. Although several mechanisms have been proposed to elucidate AM, the exact cause and development of the condition remain unclear. Recent studies have highlighted the significance of macrophage polarization in the microenvironment, which plays a crucial role in AM initiation and progression. However, a comprehensive review regarding the role and regulatory mechanism of macrophage polarization in AM is currently lacking. Therefore, this review aims to summarize the phenotype and function of macrophage polarization and the phenomenon of the polarization of adenomyosis-associated macrophages (AAMs). It also elaborates on the role and regulatory mechanism of AAM polarization in invasion/migration, fibrosis, angiogenesis, dysmenorrhea, and infertility. Furthermore, this review explores the underlying molecular mechanisms of AAM polarization and suggests future research directions. In conclusion, this review provides a new perspective on understanding the pathogenesis of AM and provides a theoretical foundation for developing targeted drugs through the regulation of AAM polarization.

Proposed classification of adenomyosis in Infertile women to simplify management options undergoing ART.

OBJECTIVE: Adenomyosis associated with subfertility is a situation of a dilemma for the treating clinician as the treatment is highly controversial and there remains an overall lack of consensus regarding the value of conservative surgery with or without medical management to improve reproductive out-comes. Hence we proposed this classification based on mapping of the size of adenomyoma, its location, distance from the endometrial cavity, and any associated endometriosis by studying 100 women with adenomyosis undergoing IVF. METHODS: We did a prospective study over 2 years in 100 women with adenomyosis who underwent IVF. They were classified into 4 categories based on our management-based proposed classification and the pregnancy outcomes were studied in each group. RESULTS: According to our classification, 56% of women belonged to grade 1, 24% to grade 2, 8% to grade 3, and 12% to Grade 4 Adenomyosis. The Pregnancy rates were 71% in Grade 1, 66% with Medical management, and 33% with surgical management in Grade 2, Grade 3 were offered surrogacy, and 66% in Grade 4 Adenomyosis. CONCLUSIONS: Our classification is simple and allows cost-effective management based on the location and ex-tent of the disease with the help of ultrasonography.

Adenomyosis diagnosis among adolescents and young women with dysmenorrhoea and heavy menstrual bleeding.

RESEARCH QUESTION: What is the prevalence of adenomyosis at ultrasonography among adolescents and young women reporting dysmenorrhoea and/or heavy menstrual bleeding (HMB)? DESIGN: This observational cohort study involved adolescents and young women referred for dysmenorrhoea and/or HMB to the Adolescent Medicine Unit at Careggi University Hospital, Italy. Patients with endometriosis and bleeding disorders were excluded. Transvaginal ultrasonography or transrectal sonography using a transvaginal probe was performed. The myometrium was described according to the Morphological Uterus Sonographic Assessment criteria. Details of baseline characteristics, clinical data and symptoms were collected. The presence of sonographic features of adenomyosis and the association between imaging findings and clinical symptoms were evaluated. RESULTS: The cohort included 95 patients aged between 13 and 25 years, referred for dysmenorrhoea (88.4%), HMB (23.2%) or both (13.7%). According to the MUSA criteria the sonographic diagnosis of adenomyosis was made in 27.4% of patients, with the diffuse type the most prevalent. Uterine wall asymmetry, hyperechoic intramyometrial islands, translesional vascularity and an interrupted junctional zone were the most common features. Patients with imaging findings of adenomyosis had significantly higher rates of HMB than those with a normal myometrial appearance (38.5% versus 17.4%, P = 0.030). In addition, the coexistence of dysmenorrhoea and HMB was significantly associated with adenomyosis (odds ratio 5.68, 95% confidence interval 1.65-19.5). CONCLUSIONS: Adenomyosis may be diagnosed among teenagers and young women referred with dysmenorrhoea and/or HMB. The clinical presentation is relevant for the diagnosis, with HMB alone and HMB plus dysmenorrhoea significantly associated with the sonographic identification of adenomyosis.

Whether surgical procedure can improve the prognosis of endometrial cancer arising in adenomyosis (EC-AIA)? A systematic review and meta-analysis.

PURPOSE: Endometrial cancer arising in adenomyosis (EC-AIA) is frequently detected accidentally following a general hysterectomy for adenomyosis. Whether supplemental lymphadenectomy in patients with EC-AIA can improve the survival outcome remains inconclusive. Herein, the authors summarized the data of patients with EC-AIA and further explored the impact of lymphadenectomy on the prognosis of these patients. METHODS: Five electronic databases, namely MEDLINE, Web of Science, PubMed, Embase, and the Cochrane Library were employed for searching articles from inception to May 2023. RESULTS: In total, 38 eligible studies enrolling 56 patients were included. Of these, 44 patients had a traceable prognosis. Kaplan-Meier curves demonstrated that patients who had undergone lymphadenectomy had a better progression-free survival (PFS) compared with those who had not undergone lymphadenectomy ( P =0.016), but there was no difference in overall survival. Univariable ( P =0.025, HR=0.25, 95% CI=0.08-0.84) and multivariable ( P =0.042, HR=0.13, 95% CI=0.020-0.930) Cox regression analyses revealed that lymphadenectomy was an independent protective factor for PFS. CONCLUSION: For patients diagnosed with EC-AIA following hysterectomy for benign disease, further supplementary lymphadenectomy is recommended to improve PFS.