Publication
Bourdon M, Santulli P, Marcellin L, Maignien C, MaitrotMantelet L, Chapron C
• 02/2022
Adenomyosis is a chronic benign uterine disease characterized by the presence of endometrial glands and stroma within the myometrium. It is a heterogeneous disease, presenting various clinical forms, depending on the location of the ectopic lesions within the myometrium. Adenomyosis can be responsible for several symptoms such as dysmenorrhea, abnormal uterine bleeding and/or infertility. Its pathophysiology is a real conundrum and several theories have been proposed: development of adenomyosis lesion could initiate de novo from Mullerian rests or from stem cells. Moreover, multiple factors could be involved in initiating lesions, including specific hormonal, immune and/or genetic changes. The objective of this review is to provide an update on adenomyosis pathophysiology, in particular on the various theories proposed concerning the invasion of the myometrium by endometrial cells and the inducing mechanisms, and to study the link between the physiopathology, the symptoms and the medical treatments.
Publication
Maignien C, Bourdon M, ScaranoPereira JP, Martinino A, Cheloufi M, Marcellin L, Chapron C, Santulli P
• 02/2022
The objective of this paper is to compare assisted reproductive technology (ART) cumulative live birth rates after hysteroscopic proximal tubal occlusion and laparoscopic salpingectomy in endometriosis patients, for management of hydrosalpinx. This is an observational cohort study at a university hospital, including all endometriosis patients with hydrosalpinges undergoing ART, between January 2013 and December 2018. The patients underwent either laparoscopic salpingectomy or hysteroscopic proximal tubal occlusion with Essure® when laparoscopy was not an option (extensive pelvic adhesions at exploratory laparoscopy or a history of multiple abdominal surgeries with frozen pelvis). The diagnosis of endometriosis was based on published imaging criteria using transvaginal sonography (TVUS) and magnetic resonance imaging (MRI). Endometriosis patients with hydrosalpinges diagnosed by hysterosalpingography and/or TVUS and/or MRI were included. The primary outcome was the cumulative live birth rate. A total of 104 patients were included in the study; 74 underwent laparoscopic salpingectomy and 30 underwent proximal tubal occlusion with Essure®. The Essure® group had longer infertility durations (58.9 ± 30.0 months vs. 39.5 ± 19.1 months, p = 0.002) and a higher incidence of associated adenomyosis (76.7% vs. 39.1%, p < 0.001) than the salpingectomy group. The cumulative live birth rate was 56.6% after 44 ART cycles in the Essure® group and 40.5% after 99 ART cycles in the salpingectomy group (p = 0.13). In a population of endometriosis patients undergoing ART, women treated by Essure® for management of hydrosalpinx have similar cumulative live birth rates as women treated by laparoscopic salpingectomy.
Publication
Chapron C, LafayPillet MC, Santulli P, Bourdon M, Maignien C, GaudetChardonnet A, MaitrotMantelet L, Borghese B, Marcellin L
• 01/2022
BACKGROUND: The time between symptoms onset and endometriosis diagnosis is usually long. The negative impacts of delayed endometriosis diagnosis can affect patients and health outcomes. METHODS: We conducted a case-control study using clinical symptoms and epidemiological data extracted from a prospective pre-operative patient questionnaire compared between patients with histologically proven endometriosis and patients with no endometriosis at surgical exploration from 2005 to 2018, in a French referral center. We used the beta coefficients of the significant variables introduced in a multiple regression model to devise a score (score 1), evaluated by the area under the curve (or C-index), with three levels, defined by a score between 1 and ≥ 25: (i) highly specific, identifying correctly the patients without the disease; (ii) highly sensitive, identifying the patients with the disease; and (iii) a level maximizing sensitivity and specificity for the best classification of the whole population. To minimize patient self-evaluation of pain, we devised a second score (score 2) with the same method and levels and scores definition, excluding visual analog scale pain scores, except for dysmenorrhea. These scores were validated on an internal and external population. FINDINGS: Score 1 had a C-index of 0.81 (95% CI [0.79-0.83]). Results for the three score 1 levels were: ≥ 25: specificity of 91% (95% CI [89-93]); < 11: sensitivity of 91% (95% CI [89-93]); ≥ 18: specificity of 75% (95% CI [72-78]) and sensitivity of 73% (95% CI [70-76]). Score 2 had a C-index of 0.75 (95% CI [73-77]). The three levels of score 2 were: ≥ 24: specificity of 82% (95% CI [80-85]); < 7: sensitivity of 92% (95% CI [90-94]); ≥ 17: specificity of 62% (95% CI [58-65]) and sensitivity of 78% (95% CI [75-81]). The two scores were internally and externally validated. INTERPRETATION: A score based only on a patient questionnaire could allow identification of a population at high risk of endometriosis. This strategy might help referral to specialized radiologists for a non-surgical endometriosis scan. FUNDING: None.
Publication
Bourdon M, Pham B, Marcellin L, Bordonne C, Millischer AE, Maignien C, Santulli P, Chapron C
• 01/2022
RESEARCH QUESTION: In women with radiologically diagnosed adenomyosis, is the presence of endometriosis associated with a higher rate of miscarriage? DESIGN: An observational cohort study of women who received medical care for benign gynaecological conditions between May 2005 and May 2018. Women who had adenomyosis lesions visualized by uterine magnetic resonance imaging (MRI) were included. Women who had never been pregnant were excluded. Women with adenomyosis identified by MRI but who did not have endometriosis lesions (control group) were compared with women with adenomyosis and endometriosis lesions (study group). Primary outcome was rate of a previous history of early miscarriage. RESULTS: A total of 214 pregnancies in the study group and 53 pregnancies in the control group were analysed. The rate of a previous miscarriage was significantly higher among women with adenomyosis and endometriosis lesions compared with women in the control group (61/214 [28.5%] versus 6/53 [11.3%], respectively, P = 0.009). A multivariable generalized estimating equation logistic regression model, adjusted for adenomyosis and endometriosis phenotypes, found that the association between endometriosis and adenomyosis significantly increased the risk of miscarriage (OR 3.2, 95% CI 1.1 to 9.65). The risk was significantly higher with deep infiltrating endometriosis (OR 4.37, 95% CI 1.32 to 14.53). CONCLUSIONS: Women affected by endometriosis had a significantly higher rate of previous spontaneous miscarriage than women without endometriosis with adenomyosis lesions identified by MRI. Mechanistic studies are needed to establish the complex link between the presence of endometriosis and adenomyosis and the rate of spontaneous miscarriage.
Publication
Bourdon M, Santulli P, Marcellin L, Maignien C, MaitrotMantelet L, Bordonne C, Plu Bureau G, Chapron C
• 12/2021
Adenomyosis is a common gynecologic disease characterized by invasion of endometrial glands and stroma within the myometrium. Clinically, it can result in abnormal uterine bleeding, pelvic pain, and infertility. Adenomyosis has historically been diagnosed by histology of hysterectomy specimens. As a result of the development of imaging techniques, the diagnosis is nowadays possible by means of transvaginal pelvic ultrasound or pelvic magnetic resonance imaging. The use of pelvic imaging has demonstrated the existence of different forms of adenomyosis, notably allowing distinction between lesions of the external myometrium and those of the internal myometrium. The epidemiological and clinical characteristics may depend on the anatomical location of the adenomyosis lesions. In order to provide the best management for women with adenomyosis, the objective of this review is to provide an update regarding the diagnosis of adenomyosis and its clinical features according to the different adenomyosis phenotypes.
Publication
Just PA, Moret S, Borghese B, Chapron C
• 11/2021
Diffuse adenomyosis, focal adenomyosis, ovarian endometrioma, superficial endometriosis and deep infiltrating adenomyosis are all defined by the presence of an endometrioid tissue in an ectopic location that is at distance from the endometrium. Although frequently associated, these lesions represent different clinico-pathological entities that the pathologist should recognized. Herein, we review the clinical and pathological features of these entities, as well as related current physiopathological understandings and differential diagnoses that could be raised by some morphological variants. The statistical association between endometriosis and several ovarian tumors, mainly endometrioid and clear cell carcinomas and seromucinous borderline tumors is well established and we present some molecular and morphological features that support this transformation potential.
Publication
Santulli P, Bourdon M, Koutchinsky S, Maignien C, Marcellin L, MaitrotMantelet L, Pocate Cheriet K, Patrat C, Chapron C
• 11/2021
RESEARCH QUESTION: What prognostic factors relate to a high oocyte yield in fertility preservation for women affected by endometriosis? DESIGN: Observational cohort study conducted in a tertiary care university hospital between April 2015 and January 2019. Women who had undergone fertility preservation with ovarian stimulation for oocytes and embryo vitrification for endometriosis were included. Prognostic factors associated with the number of oocytes retrieved after the first ovarian stimulation were analysed. RESULTS: A total of 146 women who had undergone 258 ovarian stimulation cycles were included; 82 (56.2%) had undergone more than one ovarian stimulation cycle; 72.6% had at least one endometrioma lesion; and 36.3% had previously undergone surgery for endometriosis. After adjustment by multiple linear regression, the factors that significantly reduced the number of oocytes retrieved were previous history of surgery for ovarian endometriosis (coefficient -1.08; 95% CI -2.02 to -0.15; P = 0.024); women's age (-0.21; 95% CI -0.41 to -0.01; P = 0.039); and total dose of gonadotrophin used (-0.01; 95% CI -0.01 to -0.00; P = 0.047). Anti-Müllerian hormone serum level and gravidity positively correlated with an increase in the number of oocytes retrieved (1.65; 95% CI 1.13 to 2.17; P < 0.001 and 3.30; 95% CI 0.91 to 5.68; P = 0.007, respectively) after the first ovarian stimulation cycle. CONCLUSION: A history of surgery for ovarian endometriosis was associated with significantly lower oocyte yields. Fertility preservation should be integrated into endometriosis management. Fertility preservation should ideally be made available to the patient before surgery.
Publication
Philip CA, Froc E, Chapron C, Hebert T, Douvier S, Filipuzzi L, Descamps P, Agostini A, Collinet P, von Theobald P, Roman H, Dubernard G
• 11/2021
STUDY OBJECTIVE: To describe the surgical management and risks of postoperative complications of patients with urinary tract endometriosis in France in 2017. DESIGN: Multicenter retrospective cohort pilot study. SETTING: Departments of gynecology at 31 expert endometriosis centers. PATIENTS: All women managed surgically for urinary tract endometriosis from January 1, 2017, to December 31, 2017. We distinguished patients with isolated bladder endometriosis or isolated ureteral endometriosis (IUE) from those with endometriosis in both locations (mixed locations [ML]). INTERVENTIONS: Surgeons belonging to the French Colorectal Infiltrating Endometriosis Study (FRIENDS) group enrolled patients who filled a 24-item questionnaire on the day of the inclusion and 3 months later. Data were collected on operative routes, surgical management, and postoperative complications according to the Clavien-Dindo classification in a single anonymized database. MEASUREMENTS AND MAIN RESULTS: A total of 232 patients from 31 centers were included. Isolated bladder endometriosis was found in 82 patients (35.3%), IUE in 126 patients (54.4%), and ML in 24 patients (10.3%). Surgery was performed by laparoscopy, laparotomy, or robot-assisted laparoscopy in 74.1%, 11.2%, and 14.7% of the cases, respectively. Among the 150 ureteral lesions (IUE and ML), 114 were managed with ureterolysis (76%), 28 with ureteral resection (18.7%), 4 with nephrectomy (2.7%), and 23 with cystectomy (15.3%). Concerning bladder endometriosis, a partial cystectomy was performed in 94.3% of the cases. We reported 61 postoperative complications (26.3%): 44 low-grade complications according to the Clavien-Dindo classification (18%), 16 grade III complications (7%), and 1 grade IV complication (peritonitis). CONCLUSION: The surgical management of ureteral and bladder endometriosis is usually feasible and safe through laparoscopic surgery. Ureteral resection, when necessary, is more strongly associated with laparotomy and with more complications than other procedures. Prospective controlled studies are still mandatory to assess the best surgical management for patients.
Publication
Netter A, Dechaud H, Chêne G, Hebert T, Dubernard G, Faller É, Benichou R, Chapron C, Canis M, Roman H
• 10/2021
OBJECTIVE: To provide a snapshot of the surgical management of endometriosis in French high-volume activity centers. METHODS: Analysis of prospectively collected data between November 2015 and May 2017 in 21 centers with a high volume of endometriosis surgery in France. Each facility could include up to 40 patients undergoing laparoscopy for endometriosis. Data were collected before and two months after surgery. RESULTS: 361 patients were enrolled in the study. Twenty-seven patients (7.48%) were lost to follow-up at the month 2 visit. Endometriosis stage was I-II in 33.70% of patients and III-IV in 66.30%. Uterosacral ligament resection was the most frequently performed procedure (50.97%) followed by rectal surgery (31.58%), ovarian procedures for endometrioma, procedures for ureters (21.33%) and the bladder (11.91%). Antiadhesion agents were employed in 215/361 (59.56%) patients. The median length of hospital stay after surgery was 2 (IQR 1 - 4) days. Post-operative complications were recorded in 9.34% of patients. Rectovaginal fistulae occurred in 8 patients (2.41%), pelvic abscess in 4 (1.20%) and bladder atony in 3 (0.90%). 17 patients (5.14%) required a second surgical procedure after a median time of 31 days (IQR 9 - 81). Two months after surgery, 95.09% of patients reported being satisfied or very satisfied with the surgery. CONCLUSION: Our study shows that surgical management of endometriosis in centers with a high volume of endometriosis surgery, mainly concerns women presenting with severe disease and deep localizations, with an overall risk of major complications inferior to 10% and a high rate of patient satisfaction.
Publication
Bourdon M, Santulli P, Doridot L, Jeljeli M, Chêne C, Chouzenoux S, Nicco C, Marcellin L, Chapron C, Batteux F
• 09/2021
The epithelial to mesenchymal transition (EMT) has been implicated in the development of adenomyosis, along with dysregulated immune responses. Inflammation potentially induces Notch signaling, which could promote this EMT. The objective of this study was to investigate the involvement of immune cells and Notch1-mediated EMT in the development of adenomyosis. Adenomyosis was induced in 18 CD-1 mice by neonatal oral administration of tamoxifen (TAM group), while 18 neonates received vehicle only (Control group). Their uteri were sampled at 30, 60 or 90 days of age. Immune cell markers (Cd45, Ly6c1, Cd86, Arginine1, Cd19, Cd4, Cd8), Notch1 and its target genes (Hey1, Hey2, Hes1, Hes5) and biomarkers of EMT (E-Cadherin, Vimentin, Tgfb, Snail1, Slug, Snail3) were analyzed by quantitative RT-PCR and immunohistochemistry. Activated-Notch1 protein was measured by western blot. Aberrant expression of immune cell markers was observed in the uteri of mice as they developed adenomyosis. The expression of inflammatory cell markers, notably M1 macrophages and natural killer cells, was increased from Day 30 in the TAM group compared to controls, followed by an increase in the Cd4 marker (T cells) at Day 60. Conversely, expression of the Cd19 marker (B cells) was significantly reduced at all of the stages studied. Notch1 signaling was also highly activated compared to controls at Day 30 and Day 60. Concomitantly, the levels of several markers for EMT were also higher. Therefore, the activation of Notch1 coincides with aberrant expression of immune and EMT markers in the early development of adenomyosis.
