The association between gynecological complaints and the uterine sonographic features in women with a history of cesarean section.

PURPOSE: The aim of this study is to investigate the association between post-cesarean sonographic uterine measures, dysmenorrhea, and bleeding disorders. METHODS: This is a cross-sectional study where 500 women with a history of only one cesarean section (CS) were recruited. A transvaginal transducer, GE RIC6-12-D was used for the acquisition of volumetric datasets 18 ± 7 months postpartum. Uterine length (UL), cervical length (CL), niche length (L), niche depth (D), niche width (W), fibrosis length (FL), fibrosis depth (FD), residual myometrial thickness (RMT), endometrial thickness (EM), scar to internal os distance (SO), anterior myometrial thickness superior (sAMT) and inferior (iAMT) to the scar, and the posterior myometrial thickness opposite the scar (PMT), superior (sPMT), and inferior to it (iPMT) were measured. Logistic regression with odds ratios (OR), 95% confidence intervals (CI) and ROC curves were utilized. RESULTS: The proportion of patients with incident post-cesarean bleeding disorders and dysmenorrhoea was 36% (CI 32%, 40%) and 17% (CI 14%, 21%) respectively. Univariate logistic regression showed that only UL was associated with bleeding disorders [OR 1.04 (CI 1.01,10.7) p value 0.005], whereas dysmenorrhea was associated with RMT [OR 0.82 (CI 0.71,0.95) p value 0.008], SO [OR 0.91 (CI 0.86,0.98) p value 0.01], and RMT ratio [OR 0.98 (CI 0.97,0.99) p value 0.03]. Multivariate logistic regression for dysmenorrhoea including SO and RMT remains statistically significant with p values <0.05 and area under the curve of 0.66. CONCLUSION: There is an association between sonographic appearance of CS scars and dysmenorrhoea. Nevertheless, the association is weak and other biological post-cesarean characteristics should be explored as potential causes.

Individual differences of white matter characteristic along the anterior insula-based fiber tract circuit for pain empathy in healthy women and women with primary dysmenorrhea.

Pain empathy, defined as the ability of one person to understand another person's pain, shows large individual variations. The anterior insula is the core region of the pain empathy network. However, the relationship between white matter (WM) properties of the fiber tracts connecting the anterior insula with other cortical regions and an individual's ability to modulate pain empathy remains largely unclear. In this study, we outline an automatic seed-based fiber streamline (sFS) analysis method and multivariate pattern analysis (MVPA) to predict the levels of pain empathy in healthy women and women with primary dysmenorrhoea (PDM). Using the sFS method, the anterior insula-based fiber tract network was divided into five fiber cluster groups. In healthy women, interindividual differences in pain empathy were predicted only by the WM properties of the five fiber cluster groups, suggesting that interindividual differences in pain empathy may rely on the connectivity of the anterior insula-based fiber tract network. In women with PDM, pain empathy could be predicted by a single cluster group. The mean WM properties along the anterior insular-rostroventral area of the inferior parietal lobule further mediated the effect of pain on empathy in patients with PDM. Our results suggest that chronic periodic pain may lead to maladaptive plastic changes, which could further impair empathy by making women with PDM feel more pain when they see other people experiencing pain. Our study also addresses an important gap in the analysis of the microstructural characteristics of seed-based fiber tract network.

Ultrasound and magnetic resonance imaging-based investigation of the role of perfusion and oxygen availability in menstrual pain.

BACKGROUND: The mechanisms responsible for menstrual pain are poorly understood. However, dynamic, noninvasive pelvic imaging of menstrual pain sufferers could aid in identifying therapeutic targets and testing novel treatments. OBJECTIVE: To study the mechanisms responsible for menstrual pain, we analyzed ultrasonographic and complementary functional magnetic resonance imaging parameters in dysmenorrhea sufferers and pain-free controls under multiple conditions. STUDY DESIGN: We performed functional magnetic resonance imaging on participants with and those without dysmenorrhea during menses and outside menses. To clarify whether regional changes in oxygen availability and perfusion occur, functional magnetic resonance imaging R2∗ measurements of the endometrium and myometrium were obtained. R2∗ measurements are calculated nuclear magnetic resonance relaxation rates sensitive to the paramagnetic properties of oxygenated and deoxygenated hemoglobin. We also compared parameters before and after an analgesic dose of naproxen sodium. In addition, we performed similar measurements with Doppler ultrasonography to identify if changes in uterine arterial velocity occurred during menstrual cramping in real time. Mixed model statistics were performed to account for within-subject effects across conditions. Corrections for multiple comparisons were made with a false discovery rate adjustment. RESULTS: During menstruation, a notable increase in R2∗ values, indicative of tissue ischemia, was observed in both the myometrium (beta ± standard error of the mean, 15.74±2.29 s-1; P=.001; q=.002) and the endometrium (26.37±9.33 s-1; P=.005; q=.008) of participants who experienced dysmenorrhea. A similar increase was noted in the myometrium (28.89±2.85 s-1; P=.001; q=.002) and endometrium (75.50±2.57 s-1; P=.001; q=.003) of pain-free controls. Post hoc analyses revealed that the R2∗ values during menstruation were significantly higher among the pain-free controls (myometrium, P=.008; endometrium, P=.043). Although naproxen sodium increased the endometrial R2∗ values among participants with dysmenorrhea (48.29±15.78 s-1; P=.005; q=.008), it decreased myometrial R2∗ values among pain-free controls. The Doppler findings were consistent with the functional magnetic resonance imaging (-8.62±3.25 s-1; P=.008; q=.011). The pulsatility index (-0.42±0.14; P=.004; q=.004) and resistance index (-0.042±0.012; P=.001; q=.001) decreased during menses when compared with the measurements outside of menses, and the effects were significantly reversed by naproxen sodium. Naproxen sodium had the opposite effect in pain-free controls. There were no significant real-time changes in the pulsatility index, resistance index, peak systolic velocity, or minimum diastolic velocity during episodes of symptomatic menstrual cramping. CONCLUSION: Functional magnetic resonance imaging and Doppler metrics suggest that participants with dysmenorrhea have better perfusion and oxygen availability than pain-free controls. Naproxen sodium's therapeutic mechanism is associated with relative reductions in uterine perfusion and oxygen availability. An opposite pharmacologic effect was observed in pain-free controls. During menstrual cramping, there is insufficient evidence of episodic impaired uterine perfusion. Thus, prostaglandins may have protective vasoconstrictive effects in pain-free controls and opposite effects in participants with dysmenorrhea.

Magnetic Resonance Imaging-Based Classification Systems for Informing Better Outcomes of Adenomyosis After Ultrasound-Guided High-Intensity Focused Ultrasound Ablating Surgery.

BACKGROUND: A referenced MRI-based classification associated with focused ultrasound ablation surgery (FUAS) outcomes is lacking in adenomyosis. PURPOSE: To identify an MRI-based classification system for informing the FUAS outcomes. STUDY TYPE: Retrospective. POPULATION: Patients with FUAS for adenomyosis, were divided into a training set (N = 643; 355 with post-FUAS gonadotropin-releasing hormone/levonorgestrel, 288 without post-FUAS therapy) and an external validation set (N = 135; all without post-FUAS therapy). FIELD STRENGTH/SEQUENCE: 1.5 T, turbo spin-echo T2-weighted imaging and single-shot echo-planar diffusion-weighted imaging sequences. ASSESSMENT: Five MRI-based adenomyosis classifications: classification 1 (C1) (diffuse, focal, and mild), C2 (intrinsic, extrinsic, intramural, and indeterminate), C3 (internal, adenomyomas, and external), C4 (six subtypes on areas [internal or external] and volumes [<1/3 or ≥2/3]), and C5 (internal [asymmetric or symmetric], external, intramural, full thickness [asymmetric or symmetric]) for FUAS outcomes (symptom relief and recurrence). STATISTICAL TESTS: The optimal classification was significantly associated with the most subtypes of FUAS outcomes. Relating to the timing of recurrence was measured using Cox regression analysis and median recurrence time was estimated by a Kaplan-Meier curve. A P value <0.05 was considered statistically significant. RESULTS: Dysmenorrhea relief and recurrence were only associated with C2 in training patients undergoing FUAS alone. Compared with other subtypes, the extrinsic subtype of C2 was significantly associated with dysmenorrhea recurrence in the FUAS group. Besides, the median dysmenorrhea recurrence time of extrinsic subtype was significantly shorter than that of other subtypes (42.0 months vs. 50.3 months). In the validation cohort, C2 was confirmed as the optimal system and its extrinsic subtype was confirmed to have a significantly shorter dysmenorrhea recurrence time than other subtypes. DATA CONCLUSION: Classification 2 can inform dysmenorrhea relief and recurrence in patients with adenomyosis undergoing FAUS only. Itsextrinsic subtype was associated with an earlier onset of dysmenorrhea recurrence after treatment. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

Altered cognitive control network mediates the association between long-term pain and anxiety symptoms in primary dysmenorrhea.

Neuroimaging studies have demonstrated the association of the cognitive control network (CCN) with the maintenance of chronic pain. However, whether and how dorsolateral prefrontal cortex (DLPFC), a key region within the CCN, is altered in menstrual pain is unclear. In this study, we aimed to investigate alterations in the DLPFC functional connectivity network in patients with primary dysmenorrhea (PDM). The study comprised 41 PDM patients and 39 matched healthy controls (HCs), all of whom underwent a resting-state functional MRI scan during the menstrual stage. All participants were instructed to complete the clinical assessment before the MRI scan. We used the DLPFC as the seed in resting-state functional connectivity (rsFC) analysis to investigate the difference between PDM patients and HCs. Compared to HCs, PDM patients showed increased right DLPFC rsFC at the bilateral lingual gyrus, dorsal anterior cingulate cortex (dACC), and middle cingulate cortex, and decreased left DLPFC rsFC at the right orbital frontal cortex. In addition, increased right DLPFC-bilateral dACC connectivity mediated the association between disease duration and the self-rating anxiety scale (SAS) scores in PDM patients. We confirmed that the DLPFC-dACC rsFC was associated with higher SAS scores, which could mediate the association between disease duration and anxiety symptoms in patients with PDM. Our findings provide central pathological evidence for an abnormal rsFC of the CCN in PDM patients, which may contribute to a better understanding of the neuropathophysiological mechanisms underlying PDM.

Application of elastography to diagnose adenomyosis and evaluate the degree of dysmenorrhea: a prospective observational study.

BACKGROUND: To determine whether there is a correlation between stiffness measured by strain elastography and the severity of dysmenorrhea and to determine the value of elastography in evaluating severe dysmenorrhea in patients with adenomyosis. METHODS: The correlation between tissue stiffness and dysmenorrhea was analyzed by performing elastography on premenopausal women diagnosed with adenomyosis. Expression levels of transforming growth factor-ß (TGF-ß), α-smooth muscle actin (α-SMA), and protein gene product 9.5 (PGP9.5) were detected by immunohistochemistry; the correlation of TGF-ß and α-SMA levels with the tissue stiffness and the degree of fibrosis was further analyzed. Also, the relationship of the PGP9.5 expression level with the tissue stiffness and degree of dysmenorrhea was determined. RESULTS: The degree of dysmenorrhea was significantly positively correlated with lesion stiffness in patients with adenomyosis but not with the uterine or lesion volume. The cutoff for the strain ratio was > 1.36 between the adenomyosis and control groups, with an area under the curve (AUC) of 0.987. For severe dysmenorrhea, the cutoff for the strain ratio was > 1.65 in patients with adenomyosis, with an AUC of 0.849. TGF-ß, α-SMA, and PGP9.5 expression levels were higher in adenomyotic lesions than in the endometrium of the adenomyosis and control groups. Both TGF-ß and α-SMA levels were positively correlated with the tissue stiffness and degree of fibrosis. Additionally, the expression level of PGP9.5 showed a positive correlation with the tissue stiffness and degree of dysmenorrhea. CONCLUSIONS: Elastography can be used to evaluate the degree of dysmenorrhea; the greater the tissue stiffness, the greater the degree of dysmenorrhea. In addition, elastography performed well in the diagnosis of adenomyosis and the evaluation of severe dysmenorrhea in patients with adenomyosis.

Assessment of neurotransmitter imbalances within the anterior cingulate cortex in women with primary dysmenorrhea: An initial proton magnetic resonance spectroscopy study.

PURPOSE: The neural pathophysiology underlying primary dysmenorrhea (PDM), which leads to poor mode and changes in central pain modulatory systems, remains largely unknown. The objective of this study was to investigate the changes in glutamate/glutamine (Glx) and gamma-aminobutyric acid (GABA+) levels within anterior cingulate cortex (ACC), and their associations with clinical indicators in PDM women. METHODS: Using 3 T proton magnetic resonance spectroscopy (1H-MRS), we acquired and compared ACC-Glx and ACC-GABA+ levels in PDMs (N = 41) and age- and education-matched healthy controls (HCs) (N = 39) during both the menstrual and periovulatory phases, and between menstrual and periovulatory phases within each group. Total creatine (Cr referencing) level was used as an endogenous reference. The correlations of ACC-neurotransmitter levels with clinical characteristics and the correlations of ACC-Glx with ACC-GABA+ levels in the two groups were analyzed. RESULTS: Compared to HCs or the periovulatory phase, PDMs exhibited significantly increased ACC-Glx levels (p < 0.05) during the menstrual phase. Positive correlations between GABA+ and Glx levels (r = 0.385, p = 0.025) were found in PDMs during the menstrual phase. ACC-GABA+ levels were associated with self-rating distress scale (SDS) scores (GABA+/Cr: r = 0.369, p = 0.045) and pain catastrophizing scale (PCS) scores (GABA+/Cr: r = 0.373, p = 0.042) in PDM group in only the menstrual phase. CONCLUSION: Our study represents the first report of ACC-GABA+/Glx imbalances in PDMs during the menstrual phase, which may underlie the mechanisms mediating depression and painful catastrophic symptoms.

[Analysis of the relationship between MRI imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients].

Objective: To investigate the relationship between magnetic resonance imaging (MRI) imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients. Methods: The clinical characteristics of the adenomyosis questionnaire was self-designed. This was a retrospective study. From September 2015 to September 2020, totally 459 patients were diagnosed with adenomyosis and underwent pelvic MRI examination at Peking University Third Hospital. Clinical characteristics and treatment were collected, MRI was used to determine the lesion location, and to measure the maximum lesion thickness, the maximum myometrium thickness, uterine cavity length, uterine volume, the minimum distance between the lesion and serosa or endometrium, and whether combined with ovarian endometrioma. The difference of MRI imaging characteristics in patients with adenomyosis and its relationship with clinical symptoms and therapeutic efficacy were analyzed. Results: (1) Among the 459 patients, the age was (39.1±6.4) years. There were 376 patients (81.9%, 376/459) with dysmenorrhea. Whether patients had dysmenorrhea were related to uterine cavity length, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness, and whether patients had ovarian endometrioma (all P<0.001). Multivariate analysis suggested that ovarian endometrioma was the risk factor for dysmenorrhea (OR=0.438, 95%CI: 0.226-0.850, P=0.015). There were 195 patients (42.5%, 195/459) with menorrhagia. Whether patients had menorrhagia were related to age, whether patients had ovarian endometrioma, uterine cavity length, the minimum distance between lesion and endometrium or serosa, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness (all P<0.001). Multivariate analysis suggested that ratio of the maximum lesion thickness to the maximum myometrium thickness was the risk factor for menorrhagia (OR=774.791, 95%CI: 3.500-1.715×105, P=0.016). There were 145 patients (31.6%, 145/459) with infertility. Whether the patients had infertility were related to age, the minimum distance between lesion and endometrium or serosa, and whether patients had ovarian endometrioma (all P<0.01). Multivariate analysis suggested that young and large uterine volume were risk factors for infertility (OR=0.845, 95%CI: 0.809-0.882, P<0.001; OR=1.001, 95%CI: 1.000-1.002, P=0.009). (2) The success rate of in vitro fertilization-embryo transfer (IVF-ET) was 39.2% (20/51). Dysmenorrhea, high maximum visual analogue scale score and large uterine volume affected the success rate of IVF-ET (all P<0.05). The smaller the maximum lesion thickness, the smaller the distance between the lesion and serosa, the larger the distance between the lesion and endometrium, the smaller the uterine volume, and the smaller the ratio of the maximum lesion thickness to the maximum myometrium thickness, the better the therapeutic efficacy of progesterones (all P<0.05). Conclusions: Concomitant ovarian endometrioma increases the risk of dysmenorrhea in patients with adenomyosis. The ratio of the maximum lesion thickness to the maximum myometrium thickness is an independent risk factor for menorrhagia. Young and large uterine volume may increase the risk of infertility. Severe dysmenorrhea and large uterine volume affect the success rate of IVF-ET. The therapeutic efficacy of progesterones is relatively better when the lesion is small and far away from the endometrium.

High intensity focused ultrasound treatment for adenomyosis: comparison of efficacy based on MRI features.

OBJECTIVE: To compare the clinical efficacy of High intensity-focused ultrasound(HIFU) for different types of adenomyosis classified by magnetic resonance imaging (MRI). METHODS: A total of 227 patients with adenomyosis who underwent HIFU treatment in Suining Central Hospital from January 2014 to December 2019 were included. Based on the preoperative pelvic MRI examination and Kishi isometric classification method, the patients were divided into 4 types according to the location of lesions. There were 82 cases of type I (endogenous type), 75 cases of type II (exogenous type), 34 cases of type III (nodular type), and 36 cases of type IV (heterogeneous type). The results of HIFU treatment for four types of adenomyosis and intraoperative adverse effects were analyzed. The changes of lesion size, dysmenorrhea, and menstrual volume were analyzed at 3 and 6 months after the operation. RESULT: (1) adverse effects: All patients successfully accepted HIFU treatment under sedation and analgesia. Grade A adverse effects occurred in 51 cases (22.47%) and grade B adverse effects in 3 cases (1.32%). The incidence of adverse effects in type I-IV patients was 21.95%, 22.66%, 23.53%, and 30.56%, respectively. There was no significant difference in the incidence of grade A and B adverse effects in all types, and no grade C-F adverse effects occurred. (2) Ablation effect: The ablation rate of type III(nodular type)patients was (74.7 ± 20.3) %, which was significantly higher than that of the other three types (p < .05). (3) Changes in lesion size: the lesion size of all patients decreased after treatment and the reduction rate gradually increased with time. At 6 months after the operation, the lesion reduction rate of type III patients was (70.8 ± 14.8) %, higher than that of the other three types patients (p < .05). There was no significant difference in the reduction rate of type I, type II and type IV. (4) Remission of menorrhagia: At 6 months after the operation, the total remission rate of type III patients was 100%, while the total remission rate of type IV patients (65.4%, 17/26) that was lower than that of type I, II and III patients(p < .05). (5) Dysmenorrhea relief: At 6 months after the operation, the total dysmenorrhea relief rate of type III patients was 100% and the complete relief rate (28.1%, 18/31) was higher than that of the other three types, which was significant differences (p < .05). CONCLUSIONS: HIFU is safe and effective in the treatment of different types of adenomyosis, the therapeutic effect of HIFU in patients with type III adenomyosis is better than that of the other three types.

Revealing the Central Mechanism of Acupuncture for Primary Dysmenorrhea Based on Neuroimaging: A Narrative Review.

Objective: The central mechanism of acupuncture for primary dysmenorrhea was explored by summarizing the changes in different regional networks of the brain induced by acupuncture stimulation by analyzing the existing studies. Methods: The original studies were collected and selected from three English databases such as PubMed and four Chinese databases as China Knowledge Network (CNKI). The main keyword clusters are neuroimaging, acupuncture, and primary dysmenorrhea. Results: The literature review yielded 130 possibly qualified studies, and 23 articles fulfilled the criteria for inclusion. Regarding the type of acupuncture studies, 6 moxibustion studies and 17 manual acupuncture studies for primary dysmenorrhea were included. Based on functional magnetic resonance imaging (fMRI), perfusion-weighted imaging (PWI), and positron emission tomography-computer tomography techniques (PET-CT), one or more analysis methods such as amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), functional connectivity (FC), and independent components analysis (ICA) were used. The results are summarized. To summarize the high-frequency brain area alterations observed in patients with acupuncture-induced primary dysmenorrhea were the anterior cingulate gyrus, thalamus, insula, precentral gyrus, middle frontal gyrus, postcentral gyrus, putamen, and cerebellum. Conclusion: The results suggest that the mechanism of acupuncture in the treatment of primary dysmenorrhea is the involvement of networks regulating different areas of the brain in the analgesic effects of acupuncture. The brain regions involved in primary dysmenorrhea acupuncture analgesia were mainly located in the pain matrix, default mode network, salience network, and limbic system.

Clinical and sonographic impact of oral contraception in patients with deep endometriosis and adenomyosis at 2 years of follow-up.

Nowadays, combined oral contraceptives (COCs) are successfully employed for the treatment of endometriosis (END) and adenomyosis (AD) in a large proportion of patients. However, literature focusing on the clinical and sonographic response to treatment in the long-term follow-up of patients with deep endometriosis (DE) and AD is scarce. The aim of this study was to evaluate the changes in the symptoms and the sonographic exams at 12 and 24 months of follow-up in patients who had received a flexible extended COC regimen containing 2 mg of dienogest/30 µg ethinyl estradiol. This prospective, longitudinal, observational study included women diagnosed with DE and AD presenting no surgical indication and were candidates to treatment with COCs. The presence and severity of dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria were evaluated using the Numerical Rating Scale (NRS) at baseline, and at 12 and 24 months of treatment. Transvaginal ultrasound was also performed at these check points searching for criteria of AD and reporting the size of the DE nodules and ovarian endometriomas (OE). Sixty-four patients were included. A significant decrease in the number of patients with severe dysmenorrhea and non-menstrual pelvic pain was reported during follow-up. The mean NRS score for dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria was also significantly lower at follow-up. There was a significant reduction in the sonographic number and type of AD criteria during follow-up after treatment. Similarly, a significant decrease in the size of OE and uterosacral ligament involvement in DE was observed at the 12-month follow-up, with a further, albeit not statistically significant, decrease in the 12- to 24-month follow-up. Additionally, torus and rectosigmoid DE decreased in size, although the reduction was not statistically significant at any study point. This prospective study suggests a clinical and sonographic improvement after a flexible extended COC regimen in DE and AD patients, which was significant at 12 months of follow-up. The improvement was more evident in AD and OEs compared with DE. Further research with a longer follow-up, larger sample size and comparison with other treatments is needed.

Adolescent endometriosis: prevalence increases with age on magnetic resonance imaging scan.

OBJECTIVE: To evaluate the prevalence on magnetic resonance imaging (MRI) of ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) in adolescents presenting with severe dysmenorrhea. DESIGN: Prospective study. SETTING: Clinic. PATIENT(S): A total of 345 adolescents aged 12-20 years referred to the radiologic MRI department unit between September 2019 and June 2020. INTERVENTION(S): Multiplanar pelvic MRI with cine MRI was performed. Data on the medical history with systematic questioning were collected for each patient before the scan. MAIN OUTCOME MEASURE(S): Data on the endometriosis phenotypes (OMA and/or DIE), distribution of anatomical lesions, and adenomyosis were evaluated and recorded using a dedicated MRI spreadsheet. Myometrial contractions were systematically reported for each case. The data were correlated with the characteristics of the patients and severity of painful symptoms evaluated using a visual analog scale. RESULT(S): The prevalence rates of endometriosis and adenomyosis were 39.3% (121 patients) and 11.4% (35 patients), respectively. Among the adolescents with endometriosis, 25 (20.7%) presented with OMA, and 107 (88.4%) presented with DIE. The odds ratios (confidence intervals) for each pairwise comparison between the age distributions were 2.3 (1.4-3.8) for 15-18 vs. <15 years of age and 3.3 (1.2-8.5) for 18-20 vs. <15 years of age, highlighting a predominance of cases after 18 years of age. Uterine contractions were visualized in 34.4% of cases, with no particular association with endometriosis. No clinical risk factor was identified as being particularly associated with endometriosis. Notably, the visual analog scale score was the same for cases with and without endometriosis. CONCLUSION(S): Severe endometriosis phenotypes (OMA and/or DIE) can be observed in adolescents with intense dysmenorrhea, with a linear increase in prevalence over time resulting in a clear predominance after 18 years of age. Endometriosis in adolescents is a challenging clinical problem with a long delay in diagnosis. Imaging can help reduce this delay in young patients with suggestive symptoms. CLINICAL TRIAL REGISTRATION NUMBER: NCT05153512.

Early noninvasive diagnosis of endometriosis: dysmenorrhea and specific ultrasound findings are important indicators in young women.

OBJECTIVES: To diagnose endometriosis in young patients ≤25y with severe dysmenorrhea through specific ultrasonographic examination findings and to correlate the symptoms to its different forms: ovarian, deep infiltrating endometriosis, and adenomyosis. DESIGN: A retrospective observational study. SETTING: University Hospital. PATIENT(S): Women aged 12-25 years with severe dysmenorrhea and a visual analog scale score ≥7. INTERVENTION(S): This study included 371 women aged 12-25 years referred to our gynecological ultrasound (US) Unit between January 2016 and December 2021 with severe dysmenorrhea and a visual analog scale score ≥7. Two dimensional, 3 dimensional, and power Doppler US pelvic examinations (transvaginal or transrectal in presexually active girls) were performed on all patients. Medical history and symptoms were collected routinely for each patient before the scan. MAIN OUTCOME MEASURE(S): All possible locations of endometriosis, isolated or combined occurrence, were evaluated, and recorded using an US dedicated mapping sheet. Painful symptoms were evaluated by visual analog scale and correlated to the different endometriosis forms. RESULT(S): At least one US endometriosis feature was identified in 131 (35.3%) patients, whereas the US findings of 170 (45.8%) were normal despite the referred dysmenorrhea. Of the 131 patients with endometriosis, ovarian endometrioma was found in 54 (41.2%), and 22 (16.8%) had an isolated endometrioma. Adenomyosis was detected in 67 (51.1%) patients, and 28 (21.4%) showed its isolated indications. Posterior deep infiltrating endometriosis was found in 70 (53.4%) patients, and uterosacral ligament (USL) fibrotic thickening was found in 63 (48.1%). In 23 patients, the USL lesion was completely isolated. The combined occurrence of dysmenorrhea with dyspareunia, bowel symptoms, and heavy menstrual bleeding increases the presence of endometriosis up to 59%, 63%, and 45%, respectively. CONCLUSION(S): In young patients with severe dysmenorrhea, the US-based detection rate of pelvic endometriosis was one-third. USL fibrotic thickening and mild adenomyosis are often the only findings, so an accurate pelvic US scan can provide an early diagnosis by identifying small endometriotic lesions. Young patients with dysmenorrhea should be referred to an expert sonographer to minimize the delay between the onset of symptoms and diagnosis.

Uterine Anteroposterior Diameter Measured by Transvaginal Sonography is a Predictor for Dysmenorrhea in Patients With and Without Endometriosis: A Pilot Study.

PURPOSE: The aim of this study was to determine the correlation between uterine diameters and menstrual abdominal pain intensity in patients with and without endometriosis (EM), and the independent influence of EM on the pain intensity. METHODS: Uterine diameters and the diagnosis of adenomyosis were ascertained by transvaginal ultrasonography (TVS). Menstrual abdominal pain intensity was estimated by visual analog scale (VAS). Linear regression was used to figure out the impact of uterine diameters and EM on the VAS scores. Logistic regression was used to calculate the correlation between uterine diameters and the diagnosis of adenomyosis. The cutoff values of uterine anteroposterior diameter (AD) to predict dysmenorrhea (VAS ≥ 4) and the diagnosis of adenomyosis were determined by receiver operating characteristic curves. RESULTS: There were 220 patients with and 233 patients without EM included. Uterine AD independently correlated with the VAS scores in patients with (B = .230, P = .000) and without (B = .203, P = .000) EM. A uterine AD of 39.5 mm predicted dysmenorrhea in both groups. The presence of EM increased the VAS scores by 1.151 points when controlling for uterine diameters. Uterine AD also independently correlated with the diagnosis of adenomyosis under TVS in patients with (OR = 1.212, 95% CI = 1.130-1.301; P = .000) and without (OR = 1.192, 95% CI = 1.123-1.263; P = .000) EM. A uterine AD of 38.5 and 39.5 mm predicted the diagnosis of adenomyosis under TVS in patients with and without EM, respectively. CONCLUSIONS: Increased uterine AD, which is probably ascribed to adenomyosis, plays an important role in augmented menstrual abdominal pain intensity. Meanwhile, the presence of EM reinforces the pain.

Classification of primary dysmenorrhea by brain effective connectivity of the amygdala: a machine learning study.

BACKGROUND: The amygdala plays a crucial role in the central pathogenesis mechanism of primary dysmenorrhea (PDM). However, the detailed pain modulation principles of the amygdala in PDM remain unclear. Here, we applied the Granger causality analysis (GCA) to investigate the directional effective connectivity (EC) alterations in the amygdala network of PDM patients. METHODS: Thirty-seven patients with PDM and 38 healthy controls were enrolled in this study and underwent resting-state functional magnetic resonance imaging scans during the pain-free stage. GCA was employed to explore the amygdala-based EC network alteration in PDM. A multivariate pattern analysis (MVPA)-based machine learning approach was used to explore whether the altered amygdala EC could serve as an fMRI-based marker for classifying PDM and HC participants. RESULTS: Compared to the healthy control group, patients with PDM showed significantly decreased EC from the amygdala to the right superior frontal gyrus (SFG), right superior parietal lobe/middle occipital gyrus, and left middle cingulate cortex, whereas increased EC was found from the amygdala to the bilateral medial orbitofrontal cortex. In addition, increased EC was found from the bilateral SFG to the amygdala, and decreased EC was found from the medial orbitofrontal cortex, caudate nucleus to the amygdala. The increased EC from the right SFG to the amygdala was associated with a plasma prostaglandin E2 level in PDM. The MVPA based on an altered amygdala EC pattern yielded a total accuracy of 86.84% for classifying the patients with PDM and HC. CONCLUSION: Our study is the first to combine MVPA and EC to explore brain function alteration in PDM. The results could advance understanding of the neural theory of PDM in specifying the pain-free period.

[Effect of acupuncture on brain functional connectivity strength in patients with primary dysmenorrhea].

OBJECTIVE: To investigate the effect of acupuncture on the brain functional activities of the patients with primary dysmenorrhea based on the resting-state functional magnetic resonance imaging (rs-fMRI), and to provide visual evidence for the central mechanism of acupuncture in treatment of primary dysmenorrhea. METHODS: Forty-two patients of primary dysmenorrhea were enrolled and randomly divided into an observation group (21 cases, 1 case dropped off) and a control group (21 cases, 2 cases dropped off, 3 cases withdrawal). In the observation group, acupuncture was exerted at Sanyinjiao (SP 6) and Guanyuan (CV 4), started 5-7 days before menstrual flow, once a day till menstrual onset, for a total of 3 menstrual cycles. No intervention was applied in the control group. The scores of visual analogue scale (VAS) and Cox menstrual symptom scale (CMSS) were observed in both groups before and after treatment. Based on rs-fMRI, the data of resting-state functional magnetic resonance were collected from two groups before and after treatment. Combined with functional connectivity strength (FCS) and functional connectivity (FC) analysis, the differences of brain regions before and after treatment were compared between the two groups and the correlation was analyzed between their functional connectivity changes and the improvements in VAS and CMSS scores of the patients in the observation group. RESULTS: In the observation group, the scores of VAS and CMSS were all decreased after treatment (P<0.05), while the scores related to the symptom time in CMSS was reduced in comparison with that before treatment in the control group (P<0.05). The score reducing ranges of VAS and CMSS in the observation group were larger than the control group (P<0.05). Compared before treatment, FCS of the right middle cingulate cortex and the left cuneus was increased, while FCS of the left inferior parietal lobule was decreased after treatment in the observation group. In the control group, FCS of the left orbital frontal cortex was increased after treatment. Compared with the control group, FCS of the left anterior insula was increased in the observation group after treatment. FC analysis was performed using the left anterior insula as the seed point. In comparison with the control group, FC of the left anterior insula was increased either with the inferior temporal gyrus or with the right hippocampus; and was decreased either with the middle occipital lobe or with the right dorsolateral prefrontal cortex in the observation group after treatment. In the observation group, FC between the left anterior insula and the right hippocampus was positively correlated with the improvements in symptom severity (r =0.385, P<0.05) and symptom time (r =0.510, P<0.05) of CMSS, and FC between the right dorsolateral prefrontal cortex and the left anterior insula was negatively correlated with the improvement in symptom severity of CMSS after treatment (r =-0.373, P<0.05). CONCLUSION: The anterior insula may be the key brain region in treatment of primary dysmenorrhea with acupuncture. Acupuncture may relieve dysmenorrhea and the related symptoms through strengthening the functional connectivity of anterior insula-limbic system and anterior insula-control network.

The hypertrophic amygdala shape associated with anxiety in patients with primary dysmenorrhea during pain-free phase: insight from surface-based shape analysis.

BACKGROUND: Primary dysmenorrhea (PDM) is highly associated with mood symptoms. However, the neuropathology of these comorbidities is unclear. In the present study, we aimed to investigate the structural changes in the amygdala of patients with PDM during the pain-free phase using a surface-based shape analysis. METHODS: Forty-three PDM patients and forty healthy controls were recruited in the study, and all participants underwent structural magnetic resonance imaging scans during their periovulatory phase. FMRIB's Integrated Registration and Segmentation Tool (FIRST) was employed to assess the subcortical volumetric and surface alterations in patients with PDM. Moreover, correlation and mediation analyses were used to detect the clinical significance of the subcortical morphometry alteration. RESULTS: PDM patients showed hypertrophic alteration of the amygdala in the left superficial nuclei and right basolateral and superficial nuclei but not for the whole amygdala volume. The hypertrophic amygdala was associated with disease duration, pain severity and anxiety symptoms during the menstrual period. Furthermore, the hypertrophic left amygdala could mediate the association between disease duration and anxiety severity. CONCLUSIONS: The results of the current study demonstrated that the localized amygdala shape hypertrophy was present in PDM patients even in the pain-free phase. In addition, the mediator role of the hypertrophic amygdala indicates the potential target of amygdala for anxiety treatment in PDM treatment in the pain-free phase.

Prevalence of endometriosis and adenomyosis at transvaginal ultrasound examination in symptomatic women.

INTRODUCTION: Prevalence of endometriosis is commonly reported based on surgery findings and varies widely depending on study population and indication for surgery. Symptoms such as dysmenorrhea, pelvic pain, dyspareunia, dysuria, and dyschezia can be associated with endometriosis and adenomyosis. Transvaginal ultrasound examination is proposed to be the first-line diagnostic method, nevertheless there are no published ultrasound-based studies reporting prevalence of endometriosis and adenomyosis in symptomatic women other than those scheduled for surgery. The aim of this study was to determine the prevalence of endometriosis and adenomyosis as assessed by transvaginal ultrasound in women with symptoms suggestive of endometriosis and adenomyosis. MATERIAL AND METHODS: This is a retrospective cross-sectional study performed at a tertiary-care center including 373 symptomatic women who were systematically examined with transvaginal ultrasound by an experienced ultrasound examiner. Before ultrasound examination women filled in a questionnaire including self-assessment of the severity of their symptoms (dysmenorrhea, chronic pelvic pain, dyspareunia, dysuria, dyschezia) using a visual analog scale. Abnormal findings in the uterus, ovaries, bowel, urinary bladder, uterosacral ligaments, and rectovaginal septum were noted, and their size and location were described. Prevalence of endometriosis, adenomyosis, endometrioma, and deep endometriosis in different anatomical locations was reported. RESULTS: Prevalence of ovarian endometrioma and/or deep endometriosis was 25% and of adenomyosis was 12%. Prevalence of endometrioma was 20% and of deep endometriosis was 9%, for each location being 8% in the bowel, 3% in the uterosacral ligaments, 3% in the rectovaginal septum and 0.5% in the urinary bladder. CONCLUSIONS: In symptomatic women examined with transvaginal ultrasound by an experienced ultrasound examiner, ovarian endometrioma and/or deep endometriosis was found in one of four women and adenomyosis in one of nine women. Deep endometriosis was present in one of 11 women. Despite having symptoms, half of the women had no abnormal ultrasound findings.

Ultrasound Findings of Adenomyosis in Adolescents: Type and Grade of the Disease.

STUDY OBJECTIVE: To evaluate the ultrasound features, types, and degrees of adenomyosis among adolescents and to correlate these findings with clinical symptoms DESIGN: A retrospective observational study. SETTING: Gynecological ultrasound units from January 2014 to June 2020. PATIENTS: A total of 43 adolescents (aged 12-20 years) who were diagnosed as having adenomyosis at a pelvic ultrasound examination. INTERVENTIONS: Ultrasound features and location and type of adenomyosis within the uterus were evaluated on stored 2-dimensional images and videos and 3-dimensional volumes. Adenomyosis was classified as mild, moderate, and severe according to the extension of the disease in the uterus as described in our previous published classification. MEASUREMENTS AND MAIN RESULTS: Adenomyotic features recorded among our population were myometrial hyperechoic areas, uterine wall asymmetry, intramyometrial cystic areas, and some types of junctional zone alterations. The posterior uterine wall (58%) and the outer myometrial layer (93%) were mostly affected. In 44% of adolescents (19/43) with adenomyosis, at least 1 location of pelvic endometriosis was documented. Dysmenorrhea was the most commonly reported symptoms (88%), and it was associated with adenomyosis of the outer myometrium, myometrial hyperechoic areas, uterine wall asymmetry, and intramyometrial cystic areas. Adolescents with dyspareunia showed diffuse adenomyosis (9/9 patients) including both the inner and outer myometrium (7/9 patients) and in the posterior wall (7/9 patients). Heavy menstrual bleeding was associated with diffuse adenomyosis (18/23 patients) mostly of the outer myometrium (22/23 patients). Scoring system showed predominantly mild disease and no severe adenomyosis was found. Adolescents with diffuse adenomyosis were significantly older and showed a high percentage of heavy menstrual bleeding compared with those with the focal disease of the inner myometrium. CONCLUSION: This study shows that adenomyosis is not only a pathology of adult life, but it involves young patients mostly in a mild-to-moderate form and is associated with typical painful symptoms. In adolescents, the diagnosis of adenomyosis is feasible through a noninvasive way with ultrasound and a proper management can be set.

The treatment with Levonorgestrel Releasing Intrauterine System (LNG-IUS) in patients affected by menometrorrhagia, dysmenorrhea and adenomimyois: clinical and ultrasonographic reports.

OBJECTIVE: Adenomyosis is the consequence of the myometrial invasion by endometrial glands and stroma. Transvaginal ultrasonography plays a decisive role in the diagnosis and monitoring of this pathology. Our study aims to evaluate the efficacy of LNG-IUS (Levonorgestrel Releasing Intrauterine System) as medical therapy. We analyzed both clinical symptoms and ultrasonographic aspects of menometrorrhagia and dysmenorrhea in patients with adenomyosis and the control group. PATIENTS AND METHODS: A prospective cohort study was carried out on 28 patients suffering from symptomatic adenomyosis treated with LNG-IUS. Adenomyosis was diagnosed through transvaginal ultrasonography by an expert sonographer. A control group of 27 symptomatic patients (menorrhagia and dysmenorrhea) without a transvaginal ultrasonographic diagnosis of adenomyosis was treated in the same way. The two cohorts were compared to the efficacy of LNG-IUS on menorrhagia and dysmenorrhea.  Patients are evaluated at the time of LNG-IUS insertion and six months after for: increased uterine volume, globulous uterine morphology, uterine symmetry, alterations in the junctional zone, heterogeneous myometrial texture, presence of myometrial cysts, hyperechogenic lines crossing the myometrium, adenomyomas, menstrual blood loss and dysmenorrhea. RESULTS: After six months, the uterine volume decreased significantly in both cohorts (p=0.005; p=0.005). Furthermore, uterine symmetry, visibility of the junctional zone, heterogeneity of myometrial texture, presence of myometrial cysts, hyperechogenic lines and adenomyomas improved in patients affected by adenomyosis (p>0.001; p>0.001; p>0.001; p=0.014; p=0.025; p=0.014). The blood loss decreased significantly in both the cohorts (p<0.001) and particularly in adenomyotic patients. Pain relief was observed in all the patients (p<0.001). CONCLUSIONS: LNG-IUS can be considered an effective treatment for managing symptoms and improving uterine morphology.