Clinical Research Directory

Migraine and Endometriosis: The FEMININE Study

Migraine and endometriosis are common conditions that mainly affect females of reproductive age. Both can cause significant pain and have a strong impact on the quality of life. Increasing evidence suggests that these two conditions often occur together, and that females who have both may experience more severe symptoms than those with only one of them. However, the reasons why migraine and endometriosis are linked are still not well understood. Some biological factors may help explain this connection. One of them is a molecule called calcitonin gene-related peptide (CGRP), which plays an important role in migraine and may also be involved in pain and inflammation in endometriosis. In addition, hormonal changes during the menstrual cycle, especially fluctuations in estrogen levels, may influence symptoms in both conditions. Genetic and epigenetic factors may also contribute to this association. The main hypothesis of this study is that females who have both migraine and endometriosis have a distinct clinical and biological profile compared to females who have only migraine or only endometriosis. In particular, it is expected that differences will be observed in CGRP levels and hormonal patterns across the menstrual cycle. The FEMININE study is a prospective observational study that will follow females over several menstrual cycles. It will include three groups: females with both migraine and endometriosis, females with migraine only, and females with endometriosis only. Participants will record their symptoms in diaries and will provide blood samples at specific times of the menstrual cycle. The main goal of the study is to compare CGRP levels between groups. Additional goals include describing differences in symptoms, menstrual-related migraine, hormonal levels, and selected genetic and epigenetic markers. By improving the understanding of how migraine and endometriosis are related, this study aims to support better diagnosis and more personalized care for females affected by these conditions.

Intraoperative vs Transvaginal Ultrasound in Rectosigmoid Endometriosis

Deep infiltrating endometriosis (DIE) of the rectum and rectosigmoid colon represents one of the most severe forms of endometriosis and often requires surgical management when symptomatic and unresponsive to medical therapy. Accurate preoperative assessment of lesion size, extent, and depth of bowel infiltration is essential to guide surgical planning and minimize complications. Transvaginal ultrasound (TVUS) is the first-line imaging technique for the diagnosis of pelvic endometriosis and has high diagnostic accuracy for detecting rectosigmoid lesions. However, its ability to precisely assess infiltration depth and guide the choice of surgical technique may be limited by anatomical distortion and technical factors. Intraoperative ultrasound (IO-US) is a real-time imaging modality that can be performed during laparoscopic surgery after adhesiolysis, allowing direct evaluation of bowel lesions. It may improve the assessment of lesion characteristics and support intraoperative decision-making, potentially reducing unnecessary bowel resections. This prospective single-center comparative study aims to evaluate the agreement between preoperative TVUS and intraoperative ultrasound in measuring rectal and rectosigmoid DIE nodules. Secondary objectives include assessing measurement differences, identifying factors associated with discordance, and evaluating the reproducibility of ultrasound measurements. The findings of this study may improve preoperative counseling, optimize surgical planning, and support the integration of intraoperative ultrasound into the management of bowel endometriosis.

Intraoperative Sono-assessment In Deep Endometriosis

Deep infiltrating endometriosis (DIE) involving the bowel, particularly the rectosigmoid region, is associated with significant gastrointestinal symptoms and impaired quality of life. Rectal shaving is a conservative surgical technique aimed at removing endometriotic lesions while preserving bowel integrity; however, it may result in residual disease or excessive thinning of the bowel wall, potentially leading to recurrence or complications. Intraoperative ultrasound (IOUS) allows real-time assessment of residual nodule thickness and bowel wall thickness after shaving. This prospective observational study aims to evaluate the relationship between intraoperative ultrasound measurements and postoperative clinical outcomes, including gastrointestinal symptoms and quality of life. The study also seeks to identify ultrasound cut-off values that may guide intraoperative surgical decision-making and optimize the balance between radicality and safety.

Efficacy of Physical Therapy Treatment in Endometriosis and Its Relationship to Adherence Rates.

The main objective of this study is to know if the application of both therapies, neuroscience pain education plus therapeutic exercise will modify pain, catastrophizing and quality of life in endometriosis.

Anti-TNFα Therapy for Improving Pregnancy Rates in Endometriosis Patients With Failed ICSI

This prospective study targets infertile women with endometriosis (EM) who have experienced a previously failed Intracytoplasmic Sperm Injection (ICSI) trial. Using the P-I-C-O framework, the study evaluates whether the administration of an anti-TNF-α therapy (Intervention) 4-5 days before a frozen blastocyst transfer (FBT) improves reproductive outcomes compared to standard protocols (Comparison). The primary outcome is the clinical pregnancy rate, with secondary outcomes focusing on implantation, ongoing pregnancy, and neonatal health. The goal is to determine if mitigating pro-inflammatory cytokines like TNF-α can enhance endometrial receptivity in this specific high-risk population.

Efficacy and Tolerability of TENS in Endometriosis-related Pain

ELECTRE is a single-center, randomized, prospective, longitudinal, controlled, two-arm, single-blind study lasting 4 weeks (P1 investigation phase) after a 4-week run-in period. The study is followed by a 4-week extension phase (P2) in which all participants will be treated with active TENS. Randomization will be balanced according to a 1:1 ratio.

Evaluating the Impact of a Novel Cannabinoid Product for Endometriosis

Despite the proliferation of cannabis and cannabinoid products in recent years, little research has been done to determine the impact of these products on womens health conditions, including endometriosis. This study is designed to assess the impact of a custom-formulated, hemp-derived, full-spectrum, high-CBD product vs. placebo on clinical symptoms and biomarkers over the course of 12 weeks of treatment in patients with endometriosis. This project will provide information that does not currently exist on the potential efficacy of a cannabinoid-based sublingual product for endometriosis.

Virtual Mindfulness and Endometriosis

Endometriosis is a common gynecologic disease affecting 5-10% of women during their reproductive years.1 Symptoms are variable but can include debilitating pelvic pain, pain with intercourse, menstrual cycles, bowel movements and urination. This can interfere with patients' ability to work, attend school or have intimate relationships leading to serious effects on quality of life and mental health.2-5 Current management of endometriosis is predominantly medical and surgical. Unfortunately, these medications can come with potent side effects that may be intolerable to some patients. They can also be prohibitively expensive for patients without prescription coverage. Mindfulness is a psychological approach to bring the mind to the present moment and to enhance self-awareness. It includes the use of emotional regulation, reduced reactivity, and enhanced response flexibility.6 Mindfulness-based psychological treatments have shown to improve both pain and quality of life in patients with chronic pelvic pain.7-9 Despite the evidence for mindfulness-based therapy there is still limited use of this in the treatment of pelvic pain. The reasons for this are multifactorial and include financial and accessibility barriers. Virtual platforms can help bridge these inequities and support marginalized patient populations in getting access to treatments for endometriosis pain. Virtual mindfulness resources have been shown to improve health and decrease stress, anxiety, and depression.10,11 There is minimal evidence about online mindfulness platforms for chronic pain and none relating to endometriosis. There is great potential to use this medium to overcome many barriers to access, but more research is needed on its effectiveness in treating endometriosis pain. The primary objective of this research study is to determine if virtual mindfulness-based therapy improves quality of life in patients with endometriosis following completion of the ten-week virtual mindfulness-based workshop.

Use of a New Diagnostic Tool in the Detection and Characterization of Endometriosis Lesions

Diagnostic wandering is one of the characteristics of endometriosis due to great anatomical and clinical variability but also due to poorly relevant diagnostic examinations. \[18F\]-FES PET/CT could on the one hand improve diagnosis by showing greater sensitivity than MRI and on the other hand make it possible to quantify and characterize the expression of ER from diagnosis and thus helping to guide therapeutic care. We will thus attempt to correlate the intensity of \[18F\]-FES PET/CT with the expression of estrogen receptors and the intensity of pain.

Impact of Ziwig Endotest® on the Management of Patients With Clinical Symptoms of Endometriosis Inconsistent With Their Imaging Work-up

The goal of this study is to evaluate the impact of Ziiwg Endotest on patient management decisions before and after the test. The main questions it aims to answer are: * Does the test reduce the intention and number of laparoscopies in women whose decision to undergo laparoscopy was made before the test result was obtained? * Does the test change management decisions in women with no prior indication for diagnostic laparoscopy? Study will compare the patient management decision before and after the test. The acts and procedures performed as part of this research are : * Aa saliva sampling (Ziwig Endotest) at inclusion * A mutidisciplinary meeting post test (if applicable) * Completion at inclusion and 6 month of a quality-of-life questionnaire (EHP-5) * Completion at inclusion and 6 month of a VAS for pain * Completion at inclusion and 6 month of a Likert satisfaction scale * A test results Announcement consultation * A visit at 6 months.

Laparoscopic Sclerotherapy for the Management of Ovarian Endometriomas

The objective of this study is to evaluate the effect of laparoscopic sclerotherapy on ovarian reserve and its overall efficacy in the treatment of endometriomas. Ovarian reserve will be assessed using preoperative and postoperative anti-Müllerian hormone (AMH) levels and antral follicle count (AFC). Traditionally, ovarian endometriomas are managed by complete cystectomy; however, multiple studies including a large systematic review and meta-analysis-have demonstrated that cystectomy significantly reduces ovarian reserve, with an average decline in AMH of 1.77 ng/mL within one to six weeks postoperatively without recovery to baseline after many months. Sclerotherapy has historically been a potential alternative, typically performed by interventional radiology via transvaginal, transabdominal, or transgluteal drainage. This percutaneous approach, however, precludes direct visualization of the cyst and surgical management of concurrent conditions including endometriosis peritoneal disease, excision, adhesions, or tubal disease. Several studies have explored the feasibility and effectiveness of laparoscopic sclerotherapy, reporting encouraging results regarding its safety, increased AFC compared with cystectomy, and comparable pregnancy rates. Nonetheless, none of these studies have been conducted in the United States, and few have utilized a laparoscopic approach. Further research is therefore warranted to establish the accessibility and reproducibility of this technique. We aim to conduct the first U.S.-based study evaluating the impact of laparoscopic sclerotherapy on ovarian reserve. The primary outcome will be the change in AMH and AFC at six weeks postoperatively. Consistent with prior evidence, we hypothesize that laparoscopic sclerotherapy will result in a smaller decline in ovarian reserve compared with traditional cystectomy.

Determination of Lipocalin Type-prostaglandin (L-PGDS) in Blood, Urine, Vaginal Samples and Endometrial Ablation by Enzyme-linked Immunosorbent Assay

Prostaglandin D2 (PGD2) has anti-inflammatory activity, particularly via Lipocalin type-prostaglandin (L-PGDS). L-PGDS has been studied in pathologies such as sleep apnea, rheumatoid arthritis, asthma and allergic phenomena, but never in adenomyosis. Adenomyosis is a estrogen-dependent multifactorial pathology whose pathophysiology is still poorly defined. This hyperestrogenism causes chronic inflammation, particularly via the activation of the prostaglandin H2 (PGH2) signaling pathway. This would lead to the excess production of prostaglandins E2 (PGE2) and F2a (PGF2a) and the decrease of PGD2 and therefore of L-PGDS, leading to the proliferation of endometrial cells in the myometrium by the epithelial-mesenchymal transition via aromatase. A preliminary study comparing the expression of L-PGDS found a significant decrease in L-PGDS in the uterus of women with adenomyosis lesions versus healthy controls. However, during this study, some information was not collected, including the patients' symptoms, preoperative radiological data and surgical indication. The study authors hypothesize that L-PGDS could be a potential tissue and circulating diagnostic marker of adenomyosis in its early stages. L-PGDS appears to be a good candidate to aid in the diagnosis of adenomyosis via a minimally invasive assay for patients (blood or urine).

Study on the Outcomes of Patients Treated in Gynecological Emergency Departments for Pelvic Endometriosis or Suspected Pelvic Endometriosis

Adult patients consulting the gynecological emergency department of CHI Créteil during the inclusion period for endometriosis or symptoms suggestive of endometriosis

Impact of Surgery for Deep Posterior Endometriosis on Ovarian Reserve (ENDORO)

Endometriosis is a chronic condition typically affecting women of reproductive age and often responsible for chronic pelvic pain and/or infertility. Its prevalence is estimated at 10% of the female population. Deep endometriosis is a specific phenotype of the disease, defined histologically by infiltration of the peritoneum exceeding 5 mm or by fibromuscular plaques infiltrating the muscularis propria of the abdominopelvic organs. It affects approximately 12 to 20% of patients with endometriosis. Surgery is one of the treatment options. Its aim is anatomical restoration, notably through complete macroscopic resection of the lesions and the release of adhesions, particularly those affecting the adnexa. While the negative impact of cystectomies on ovarian reserve is well known, the impact of surgery for severe deep endometriosis without ovarian involvement has never been studied. Yet, these procedures are regularly performed, and in the vast majority of cases on women of reproductive age. Moreover, the impression gathered in routine practice suggests a decrease in reserve parameters of around 5%. Therefore, understanding the actual impact of the procedure on ovarian reserve would, if it were concrete, allow for expanding the indications for preoperative fertility preservation to this subgroup of patients. The main objective is to evaluate the impact of complete macroscopic resection of severe deep posterior pelvic endometriosis on the change in AMH levels at 12 months compared to an unexposed group.

Pesticides and Infertility: Oxidative Stress Via Circulating Cell-free DNA and Gut/Genital Microbiome Signatures in Women With Endometriosis

This project PestiEndoMicro aims to provide an innovative approach, studying endometriosis under the genital and gut microbiota scope. To realize this project, the investigators are planning to dose cfDNA to assess the oxidative stress caused by endometriosis and study its epigenetics. At the same time, the investigators will take a pragmatic approach by assessing pesticide exposure in these patients and estimate the correlation between gut or genital dysbiosis and chemical agent exposure. Also, the investigators will take the initiative to use classic culture, qPCR techniques, and NGS to establish signatures in vaginal, endometrial and gut microbiota in patients with endometriosis. With these approaches, the goal is to gain more knowledge about endometriosis and optimize early diagnosis by establishing a signature in the genital and gut microbiota, but also by dosing the cfDNA. By doing so the investigators could open new opportunities to develop new therapeutic strategies for endometriosis.

PET/MRI for Evaluation of Endometriosis

This study aims to determine if PET/MRI can detect endometriosis and potentially improve upon currently available non-invasive diagnostic capabilities. Specifically, the authors will investigate the ability of PET/MRI to detect and quantify endometriosis, as well as differentiate among subcategories such as inflammatory peritoneal lesions, fibrotic deep infiltrating endometriosis lesions (DIE), and ovarian endometriomas. The authors will compare \[68Ga\]CBP8 or \[18F\]-FAPI-74 PET/MRI imaging versus the current gold standard diagnostic methods, including laparoscopic surgery, clinical follow-up, and follow-up imaging.

A Phase 2 Trial to Investigate Efficacy and Safety of Vipoglanstat in Women With Endometriosis

The main objective of the trial is to evaluate the efficacy of vipoglanstat on endometriosis-related non-menstrual pelvic pain (NMPP).

Mechanisms of Uterine Fluid Absorption During Early Pregnancy ( ELF Study)

The researchers are evaluating mechanisms of uterine fluid absorption during early pregnancy

Hugo™ Robotic-Assisted Surgery (RAS) System in Gynecological Subjects (Embrace Gynecology)

The purpose of this research is to evaluate the safety and performance of the investigational Medtronic Hugo™ Robotic Assisted Surgery (RAS) system when used during hysterectomy procedures, including patients being treated for cancer.

A Clinical Study of KLH-2109 in Patients With Endometriosis

To verify the non-inferiority of KLH-2109 to leuprorelin acetate in a double-blind manner in terms of efficacy in endometriosis patients with pelvic pain.

Reproductive Prognosis in Women Seeking Offspring After Medical or Surgical Therapy for Endometriosis

The study aims to compare the percentage of women with endometriosis who undergo PMA after medical vs surgical treatment and to describe conception patterns, pregnancy rates, and number of live vessels in women seeking offspring with endometriosis.

Relugolix for Endometriosis Associated Pain

Endometriosis is a chronic, estrogen-dependent condition frequently associated with pelvic pain and reduced quality of life. Relugolix combination therapy (CT), an oral GnRH receptor antagonist-based treatment, has demonstrated efficacy in randomized clinical trials, but real-world data remain limited. The RELAX study is a single-center, ambispective observational study evaluating the effectiveness of relugolix CT in reducing endometriosis-associated pain over 24 weeks in routine clinical practice. The primary endpoint is the change from baseline in pelvic pain measured by the Visual Analog Scale (VAS). Secondary outcomes include changes in pain-related symptoms, ultrasonographic findings, patient satisfaction, and safety.

The Developmental Origins of Endometriosis

Introduction: Endometriosis is a common pathology affecting one in 10 women, characterized by the ectopic development of endometrium, which can cause pain and/or infertility. This pathology is primarily determined by hereditary factors, but it is also susceptible to environmental influences, such as the age of the onset of menstruation or exposure to chemical substances that modify the endocrine system. Recent studies have highlighted that endometriosis is more common in women with relatively short ano-genital distances (AGD), and that sensitivity to pain is closely linked to adult levels of testosterone (T) or oxytocin (OT). Aim: The main objective is to compare the anogenital distance (AGD) between two groups of women: one with stage III or IV endometriosis (ENDO +) and another group without endometriosis confirmed by laparoscopy (ENDO -). The secondary objectives are to compare various factors between the 2 groups : * Basal testosterone levels in blood. * Variations in blood testosterone levels before and after a video stimulating empathy. * Basal oxytocin levels in saliva. * Variations in oxytocin levels in saliva before and after an empathy-stimulating video. * Pelvic pain, between D2 and D5 after the start of the menstrual cycle. For the ENDO + group only: * Evaluate patients' quality of life, between D2 and D5 after the start of the menstrual cycle. * Correlate pain experienced over the last 4 weeks with hormonal markers (AGD, T, OT). Methods: Participants in the ENDO+ group will fill in a questionnaire assessing the impact of pain experienced over the past 4 weeks on their quality of life. D0 is defined as the day when participants experience a menstrual bleed before 10 am. All participants will return for project-specific hospital appointment between D2 and D5 after the start of their menstrual cycle to measure T, Sex Hormone-Binding Globulin (SHBG) and OT. During this consultation, the following samples will be taken: * 10mL blood sample * 2mL saliva sample Both samples will be taken at t0 (before watching the video) and t1 (20 minutes after watching the video).

Identify a Specific Immune Profile in Patients With Chronic Pelvic Pain Resistant to First-line Treatments by Measuring Th1, Th2, Th17, and Treg Cytokines Produced After Non-specific Functional Cell Stimulation - ImmunoCPP

Chronic pelvic pain (CPP) affects more than one in four women. An immune imbalance in the Th1/Th2 balance has been reported in multiple CPP situations, particularly in patients with endometriosis, but with mixed results. The use of a functional immune test, already validated in previous indications and particularly in infertility, could simulate an immune stimulation similar to that of painful attacks.