Comparative analysis of endometrial, vaginal, and gut microbiota in patients with and without adenomyosis.

INTRODUCTION: Alterations in microbiota composition have been implicated in a variety of human diseases. Patients with adenomyosis present immune dysregulation leading to a persistent chronic inflammatory response. In this context, the hypothesis that alterations in the microbiota may be involved in the pathogenesis of adenomyosis, by affecting the epigenetic, immunologic, and biochemical functions of the host, has recently been postulated. The aim of the present study was to compare the microbiota composition in the vagina, endometrium, and gut of individuals with and without adenomyosis. MATERIAL AND METHODS: Cross-sectional study including 38 adenomyosis patients and 46 controls, performed between September 2021 and October 2022 in a university hospital-based research center. The diagnosis of adenomyosis was based on sonographic criteria. Fecal, vaginal, and endometrial samples were collected. Study of the microbiota using 16S rRNA gene sequencing. RESULTS: Patients with adenomyosis exhibited a significant reduction in the gut microbial alpha diversity compared with healthy controls (Chao1 p = 0.012, Fisher p = 0.005, Observed species p = 0.005). Beta-diversity analysis showed significant differences in the compositions of both gut and vaginal microbiota between adenomyosis patients and the control group (Adonis p-value = 0.001; R2 = 0.03 and Adonis p-value = 0.034; R2 = 0.04 respectively). Specific bacterial taxa were found to be either overrepresented (Rhodospirillales, Ruminococcus gauvreauii group, Ruminococcaceae, and Actinomyces) or underrepresented in the gut and endometrial microbiota of adenomyosis patients compared with controls. Distinct microbiota profiles were identified among patients with internal and external adenomyosis phenotypes. CONCLUSIONS: The study revealed reduced gut microbiota diversity in adenomyosis patients, accompanied by distinct compositions in gut and vaginal microbiota compared with controls. Overrepresented or underrepresented bacterial taxa were noted in the gut and endometrial microbiota of adenomyosis patients, with variations in microbiota profiles among those with internal and external adenomyosis phenotypes. These findings suggest a potential association between microbiota and adenomyosis, indicating the need for further research to comprehensively understand the implications of these differences.

Evaluation of menstrual symptoms after Coronavirus disease 2019 vaccination in women with endometriosis.

BACKGROUND: Vaccination can have an impact on menstruation, and this impact may be more notable in women with inflammatory gynecological pathologies such as endometriosis. OBJECTIVES: We aimed to investigate the impact of mRNA-based SARS-CoV-2 vaccines on menstrual cycle-related symptoms in women with endometriosis and assess the effect of hormonal therapy on potential SARS-CoV-2 vaccination-induced menstrual changes. DESIGN: A total of 848 women who received at least two doses of mRNA-based COVID-19 vaccines were prospectively recruited: 407 with endometriosis (endometriosis group) and 441 healthy controls (non-endometriosis group). METHODS: Data regarding demographics, clinical characteristics, hormonal treatment, and menstrual-associated symptoms in the first and second cycle after vaccination were collected through an online survey. RESULTS: A similar percentage of patients in both the endometriosis and the non-endometriosis group self-reported menstrual-associated changes the first (52.6% versus 48.8%, respectively) and second cycle after vaccination (29.0% versus 28.1%, respectively). Although the total symptoms recorded were not different between the two groups, several specific symptoms were statistically more frequent in the endometriosis group. These were pain disorders and fatigue in the first cycle after vaccination and pain disorders, menstrual headache and fatigue in the second cycle after vaccination. Bleeding frequency/regularity disorders were found to be more frequent in the non-endometriosis group in the first cycle after vaccination. Patients under hormonal treatment reported fewer changes in menstrual symptoms in the first and second cycle after vaccination compared with those not receiving this treatment. Similarly, patients in the endometriosis group receiving hormonal treatment reported fewer changes in menstrual-associated symptoms compared with those not following any hormonal treatment in the first and second menstrual cycle after the last vaccination. CONCLUSION: Women with endometriosis immunized with mRNA-based SARS-CoV-2 vaccines did not perceive greater worsening or new menstrual-associated symptoms after complete COVID-19 vaccination compared with healthy controls. Hormonal treatment may have a protective effect against worsened or new menstrual symptoms induced by COVID-19 vaccination.

Adenomyosis is an independent risk factor for complications in deep endometriosis laparoscopic surgery.

Deep endometriosis (DE) occurs in 15-30% of patients with endometriosis and is associated with concomitant adenomyosis in around 25-49% of cases. There are no data about the effect of the presence of adenomyosis in terms of surgical outcomes and complications. Thus, the aim of the present study was to evaluate the impact of adenomyosis on surgical complications in women with deep endometriosis undergoing laparoscopic surgery. A retrospective cohort study including women referred to the endometriosis unit of a referral teaching hospital. Two expert sonographers preoperatively diagnosed DE and adenomyosis. DE was defined according to the criteria of the International Deep Endometriosis Analysis group. Adenomyosis was considered when 3 or more ultrasound criteria of the Morphological Uterus Sonographic Assessment group were present. Demographical variables, current medical treatment, symptoms, DE location, surgical time, hospital stay and difference in pre and post hemoglobin levels were collected. The Clavien-Dindo classification was used to assess surgical complications, and multivariate analysis was performed to compare patients with and without adenomyosis. 157 DE patients were included into the study; 77 (49.05%) had adenomyosis according to transvaginal ultrasound (TVS) and were classified in the A group, and 80 (50.95%) had no adenomyosis and were classified in the noA group. Adenomyosis was associated with a higher rate of surgical complications: 33.76% (A group) vs. 12.50% (noA group) (p < 0.001). Multivariate analysis showed a 4.56-fold increased risk of presenting complications in women with adenomyosis (CI 1.90-11.30; p = 0.001) independently of undergoing hysterectomy. There was a statistically significant association between the number of criteria of adenomyosis present in each patient and the proportion of patients presenting surgical complications (p < 0.001). Adenomyosis is an independent preoperative risk factor for surgical complications in DE surgery after adjustment for known demographic, clinical and surgical risk factors.

Recommendations on the management of pudendal nerve entrapment syndrome: A formalised expert consensus.

BACKGROUND: Since the development and publication of diagnostic criteria for pudendal nerve entrapment (PNE) syndrome in 2008, no comprehensive work has been published on the clinical knowledge in the management of this condition. The aim of this work was to develop recommendations on the diagnosis and the management of PNE. METHODS: The methodology of this study was based on French High Authority for Health Method for the development of good practice and the literature review was based on the PRISMA method. The selected articles have all been evaluated according to the American Society of Interventional Pain Physicians assessment grid. RESULTS: The results of the literature review and expert consensus are incorporated into 10 sections to describe diagnosis and management of PNE: (1) diagnosis of PNE, (2) patients advice and precautions, (3) drugs treatments, (4) physiotherapy, (5) transcutaneous electrostimulations (TENS), (6) psychotherapy, (7) injections, (8) surgery, (9) pulsed radiofrequency, and (10) Neuromodulation. The following major points should be noted: (i) the relevance of 4+1 Nantes criteria for diagnosis; (ii) the preference for initial monotherapy with tri-tetracyclics or gabapentinoids; (iii) the lack of effect of opiates, (iv) the likely relevance (pending more controlled studies) of physiotherapy, TENS and cognitive behavioural therapy; (v) the incertitudes (lack of data) regarding corticoid injections, (vi) surgery is a long term effective treatment and (vii) radiofrequency needs a longer follow-up to be currently proposed in this indication. CONCLUSION: These recommendations should allow rational and homogeneous management of patients suffering from PNE. They should also allow to shorten the delays of management by directing the primary care. SIGNIFICANCE: Pudendal nerve entrapment (PNE) has only been known for about 20 years and its management is heterogeneous from one practitioner to another. This work offers a synthesis of the literature and international experts' opinions on the diagnosis and management of PNE.

Management of symptomatic uterine fibroids after ulipristal acetate suspension and identification of high risk patients for surgery at 6-months of follow-up.

OBJECTIVE: The use of ulipristal acetate (UPA) was indicated for the treatment of uterine fibroids. Following UPA suspension in March 2020, some patients presented worsening and required surgery. We aimed to identify patients at high-risk for undergoing surgery after UPA suspension. METHODS: We evaluated 85 women receiving intermittent UPA treatment until March 2020. Following UPA suspension, patients received other medical treatments or surgery. The clinico-pathological features were recoded and a quality of life health survey was completed by patients at the time of UPA suspension and at 6-months thereafter. RESULTS: After the suspension of UPA, 17 of the 85 patients receiving intermittent UPA (20%) required surgery, and 68 (80%) required other medical treatments. Patients who underwent surgery were younger and had greater fibroid volume. CONCLUSIONS: In our series, 20% of clinically stable patients receiving intermittent UPA required surgery following UPA suspension. These women should be considered for future medical strategies.

Impact of endometrioma surgery on ovarian reserve: a prospective, randomized, pilot study comparing stripping with CO2 laser vaporization in patients with bilateral endometriomas.

OBJECTIVE: To assess ovarian reserve through antral follicle count (AFC) and ovarian volume (OV) determination after decapsulation (stripping technique) or CO2 laser vaporization in the surgical treatment of patients with bilateral ovarian endometriomas. METHODS: This prospective, randomized, blinded, self-controlled pilot study was set in a tertiary university hospital between January 2017 and December 2017, and included consecutive patients with bilateral ovarian endometriomas ≥3 cm. The study was registered with ClinicalTrials.gov under the title 'Impact on ovarian reserve according to the type of ovarian endometrioma excision: laser versus conventional cystectomy'; NCT03826355. For each patient, the endometrioma on one side was randomly selected to undergo CO2 laser vaporization and the contralateral endometrioma to undergo laparoscopic decapsulation. RESULTS: A total of 16 patients were included. There were no statistically significant between-group differences in OV and AFC levels at baseline. At the 6-month follow-up, OV and AFC levels were significantly higher in the laser-treated group versus the stripping technique. CONCLUSION: Lower OV and AFC levels following excisional surgery for endometrioma versus CO2 laser vaporization suggest a higher impact on ovarian reserve after the stripping procedure.

Use of Radioactive Seed Localization to Guide Removal of a Nonpalpable Endometriotic Lesion: A Case Report.

Extrapelvic endometriosis is a rare and usually misdiagnosed entity. Some extrapelvic endometriotic lesions are small and nonpalpable, which makes them difficult to locate and remove. Here, we report the use of radioactive seed localization to locate and guide the excision of a small, nonpalpable endometriotic lesion. A 32-year-old woman presented with disabling pain in the right inguinal area. Magnetic resonance imaging and abdominal ultrasound results showed an 11-mm nodule in the abdominal wall, in the vicinity of the groin, consistent with an endometriotic lesion. The radioactive seed was placed within the lesion with the help of ultrasonography, and excision was guided with a portable gamma camera. Complete excision of the endometriotic nodule was achieved. We propose radioactive seed localization as an accurate and feasible technique for the treatment of nonpalpable endometriotic lesions.

Prevalence of fibromyalgia among women with deep infiltrating endometriosis.

OBJECTIVE: To estimate the prevalence of fibromyalgia among women with endometriosis and analyze the effect of fibromyalgia on health-related quality of life (HRQoL). METHODS: An observational case-control study conducted at a tertiary hospital in Barcelona between April 2015 and March 2017 among women with deep infiltrating endometriosis (DIE; n=80), women with superficial endometriosis or ovarian endometrioma (non-DIE; n=76), and control women without endometriosis (n=73). Fibromyalgia was assessed via the London Fibromyalgia Epidemiological Study Screening Questionnaire (LFESSQ). HRQoL was evaluated with the 36-Item Short Form (SF-36) questionnaire. The impact of fibromyalgia and other clinical characteristics was assessed by multivariate regression analysis. RESULTS: More women fulfilled the criteria for fibromyalgia in the DIE group than in the non-DIE and control groups by LFESSQ-4 (31 [39%], 12 [16%], and 6 [8%], respectively; P=0.009) and LFESSQ-6 (22 [28%], 8 [11%], and 4 [5%], respectively; P=0.008). The DIE group reported significantly poorer HRQoL for all SF-36 dimensions. Women with DIE who fulfilled the criteria for fibromyalgia had lower physical component scores (-31.6; 95% confidence interval, -50.8 to -12.3; P=0.003). CONCLUSION: The estimated prevalence of fibromyalgia was higher among women with DIE. Women with DIE and positive fibromyalgia screening had lower HRQoL.

Sonographic and hysteroscopic endometrial examination in women treated with ulipristal acetate: Exploratory findings at a tertiary referral center.

OBJECTIVE: Ulipristal acetate (UPA) is a progesterone receptor modulator (PRM) agent that has shown benefits in women with symptomatic uterine fibroids. However, its effects on the endometrium are complex and not fully understood. We describe exploratory findings on macroscopic observation of the endometrium at transvaginal sonography (TVS) and hysteroscopy. The aim of the study is to characterize endometrial patterns commonly observed after UPA treatment. STUDY DESIGN: We performed a prospective longitudinal study at a tertiary referral center with 100 women with symptomatic uterine fibroids who received a 12-week treatment with UPA (5 mg/day). Patients underwent TVS before and after the treatment, and also a hysteroscopy examination was performed. Main outcome was to compare sonographic and hysteroscopic findings to histology after UPA treatment. RESULTS: Twenty one out of 100 (21%) women showed PAEC confirmed by histology after UPA treatment. Ultrasound findings were normal in most women after UPA treatment, but 18/100 (18%) showed an endometrial pattern suggestive of PRM effects (non-uniform, homogeneous endometrium with regular cystic areas). Endometrial thickness ≥16 mm was detected in 6/100 patients (6%), and all of them also presented sonographic PRM pattern. No patient presented malignancy according to histology in this subgroup, and 100% of them had PAEC pattern at histology. Among total patient population showing PAEC at histology, only 33% of these were identified by hysteroscopy, while 57% were identified by TVS with the PRM suggestive pattern. Of note, visibility of endometrium was improved at TVS after UPA. CONCLUSION: Identification of increased endometrial thickness together with the categorized endometrial PRM pattern at TVS may be correlated to benign lesions and may not be a cause of concern. This study is exploratory and further research is necessary to support these conclusions. Nevertheless, TVS seems to be feasible to plan adequate follow-up protocols by avoiding unnecessary interventional procedures such as hysteroscopy.