Publication
Vanhie A, Meuleman C, Tomassetti C, Timmerman D, D'Hoore A, Wolthuis A, Van Cleynenbreugel B, Dancet E, Van den Broeck U, Tsaltas J, Renner SP, Ebert AD, Carmona F, Abbott J, Stepniewska A, Taylor H, Saridogan E, Mueller M, Keckstein J, Pluchino N, Janik G, Zupi E, Minelli L, Cooper M, Dunselman G, Koh C, Abrao MS, Chapron C, D'Hooghe T
• 11/2016
Erratum for Hum Reprod. 2016 Jun;31(6):1219-23. doi: 10.1093/humrep/dew067.
Publication
Marcellin L, Morin C, Santulli P, Marzouk P, Bourret A, Dousset B, Borghese B, Chapron C
• 11/2016
STUDY OBJECTIVE: To analyze whether a history of uterine surgery correlates with disease severity in patients with bladder deep infiltrating endometriosis (DIE). DESIGN: This was an observational, cross-sectional study using data collected prospectively (Canadian Task Force classification II-2). SETTING: A single university tertiary referral center. PATIENTS: We included all nonpregnant women younger than age 42 years who had undergone complete surgical exeresis of endometriotic lesions. For each patient, a standardized questionnaire was completed during a face-to-face interview that was conducted by the surgeon in the month preceding the surgery. INTERVENTIONS: One hundred seven women with histologically proven bladder DIE were enrolled in this study. For the purpose of the study, the women were assigned to 2 groups before surgery: a study group that included women with a history of a scarred uterus (SU) (SU+, n = 16) and a control group that included women without SU (SU-, n = 99). Both groups were compared in terms of their general characteristics, medical histories, surgical findings, and the severity of the disease. MEASUREMENTS AND MAIN RESULTS: Patient age and body mass index were higher for the SU+ group as compared to the SU- group (37.9 ± 5.6 vs 32.2 ± 4.7, p < .01, and 24.7 ± 4.9 vs 21.9 ± 2.9, p = .03, respectively). Preoperative painful symptom scores did not differ between the 2 groups. No significant difference was observed in the rates of history for surgery for endometriosis (n = 11 [68.7%] vs n = 49 [53.8], p = .27). Comparison of the anatomic distribution of the lesions did not reveal a significant difference. The total American Society for Reproductive Medicine score did not differ between the groups (32.0 ± 34.4 vs 35.5 ± 34.5, p = .71). The incidence rate of isolated bladder DIE did not differ between the 2 study groups (n = 6 [37.5%] vs n = 40 [43.9%], p = .79). CONCLUSION: SU before surgery for endometriosis was observed in 14.9% of cases of bladder DIE; however, this was not related to an increased severity of the disease. This observational study hence does not appear to support the pathophysiologic hypothesis of a transmyometrial source for bladder DIE.
Publication
Rousset P, Gregory J, RoussetJablonski C, HugonRodin J, Regnard JF, Chapron C, Coste J, Golfier F, Revel MP
• 11/2016
PURPOSE: To evaluate magnetic resonance imaging (MRI) for diaphragmatic endometriosis diagnosis. MATERIALS AND METHODS: Over a 2-year period, all diaphragmatic MRI performed in the context of diaphragmatic endometriosis were reviewed. Axial and coronal fat-suppressed T1- and T2-weighted sequences were analyzed by two independent readers for the presence of nodules, plaque lesions, micronodule clustering, or focal liver herniation. MR abnormalities were correlated to surgical findings in women surgically treated. Interobserver agreement was assessed by κ statistics. RESULTS: Twenty-three women with diaphragmatic endometriosis criteria comprised the population; 14 had surgical confirmation and nine had symptoms relief with hormonal treatment. MRI sensitivity was 83 % (19/23; 95 % confidence interval [CI]: 68, 98) for reader 1 and 78 % (18/23; 95 % CI: 61, 95) for reader 2. Kappa value was 0.86 (95 % CI: 0.47, 1.00). Readers 1 and 2 detected 35 and 36 lesions, respectively, all right-sided and agreed for 32 lesions on the type, location, and signal. Lesions were mostly nodules (23/32, 72 %), predominantly posterior (28/32, 87.5 %) and hyperintense on T1 (20/32, 63 %). MRI was negative for both readers in 2 surgically treated patients with small nodules or isolated diaphragmatic holes. CONCLUSION: MRI allows diaphragmatic endometriosis diagnosis with 78 to 83 % sensitivity and excellent interobserver agreement. KEY POINTS: • MRI allows the diagnosis of diaphragmatic endometriosis with up to 83 % sensitivity. • Diaphragmatic endometriosis lesions are better depicted on fat-suppressed T1-weighted sequences. • Diaphragmatic lesions, mostly hyperintense nodules, are right-sided and predominantly posterior. • MRI can help in timely diagnosis of diaphragmatic endometriosis.
Publication
VincentRohfritsch A, Marszalek A, Santulli P, Gayet V, Chapron C, Goffinet F, Le Ray C
• 10/2016
OBJECTIVES: In France, egg donation is covered by Social insurance among women<43 years old. Because of shortage of egg donor, women aged 43 years or more cannot resort to egg donation in French infertility centers, leading them to turn to the foreign centers having practices different and less regulated than in France. We are thus brought to take care of the pregnancy and of the delivery of these women. Our objective was to estimate if the perinatal risks are more important after egg donation abroad than in case of egg donation in a French center. MATERIAL AND METHODS: Retrospective study between January, 2010 and April, 2013, comparing women having had an egg donation to Cochin then having delivered in the maternity hospital of their choice (n=88) and the women having had an egg donation abroad then having delivered in the Port-Royal maternity (n=121). First, the modalities of egg donation were compared between the Cochin hospital and the foreign centers. Second, the obstetric and perinatal outcomes were compared between both groups, then by stratifying according to the type of pregnancy (singleton or multiple). RESULTS: Among women having had an egg donation abroad, the age of the donor was lower (25.7 vs. 31.7, P=0.001), the average number of embryos transferred higher (2.1±0.6 vs. 1.7±0.5, P=0.001) and the rate of multiple pregnancies higher (47.9% vs. 9.1%, P=0.001) than among women having had an egg donation at Cochin. We observed after egg donation abroad compared to egg donation at Cochin, a birth weight significantly lower (2678±745g vs. 3045±682g, P=0.001) and a prevalence of intrauterine growth retardation higher (11.1% vs. 4.2%, P=0.04). Among singletons, abnormal placentation was more frequent in case of egg donation abroad (17.5% vs. 5.1%, P=0.02). In case of twin pregnancy, we highlighted very high rates of complications, without significant difference according to the place where egg donation was practiced. CONCLUSION: We observed an increased risk of intrauterine growth retardation after egg donation abroad, which could essentially be explained by the association between advanced maternal age and multiple gestation. For other obstetric and perinatal complications, the differences between both groups were less important than expected, but very high in both groups, whether the egg donation was realized in France or abroad. The complications seem mainly due to the multiple gestations, justifying the transfer of a single embryo whenever possible.
Publication
Carrarelli P, Luddi A, Funghi L, Arcuri F, Batteux F, Dela Cruz C, Tosti C, Reis FM, Chapron C, Petraglia F
• 10/2016
Ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) are the most severe forms of endometriosis, but different pathogenetic mechanisms and clinical symptoms distinguish these two forms. Corticotrophin-releasing hormone (CRH) and urocortin (Ucn) are endometrial neuropeptides involved in tissue differentiation and inflammation. The expression of CRH, Ucn, Ucn2, CRH-receptors (type-1 and type-2) and inflammatory enzymes phospholipase-A2 group IIA (PLA2G2A) and cycloxygenase-2 (COX2) were evaluated in OMA (n = 22) and DIE (n = 26). The effect of CRH or Ucn on COX2 mRNA expression was evaluated in cultured human endometrial stromal cells. In DIE lesions, CRH, Ucn and CRH-R2 mRNA levels were significantly higher than in OMA (P < 0.01, P < 0.001 and P < 0.05, respectively); DIE lesions showed a higher expression of COX2 (P < 0.01) and PLA2G2A (P < 0.05) mRNA than OMA, which was positively correlated with CRH-R2 mRNA expression (P < 0.05). Intense immunostaining for CRH and Ucn was shown in DIE. Treatment of cultured endometrial stromal cells with Ucn significantly increased COX2 mRNA expression (P < 0.01); this effect was reversed by the CRH-R2 antagonist astressin-2B. In DIE, DIE lesions highly express neuropeptide and enzyme mRNAs, supporting a strong activation of inflammatory pathways.
Publication
Vinci G, Arkwright S, Audebourg A, Radenen B, Chapron C, Borghese B, Dousset B, Mehats C, Vaiman D, VacherLavenu MC, Gogusev J
• 09/2016
The current study aimed to identify and validate an applicable immunohistochemistry panel including Ki-67, c-MYC, estrogen receptor-α (ER-α), and progesterone receptor isoforms A/B (PR-A/B) in correlation with clinicopathological parameters in patients affected by deep infiltrating endometriosis. Tissue microarrays were prepared from a cohort of 113 patients. Phenotypic profile of the panel molecules was evaluated in glands and stroma in parallel with microvessels and stroma density measurements. Principal component analysis was performed on 8 immunohistochemical variables, 2 histological variables, and 8 subgroups of clinical parameters. The immunohistochemical profiling showed consistent Ki-67 immunostaining in 17.9% of the samples and c-MYC in 83.1%, while intense ER-α immunoreactivity was detected in 84% of the samples and PR-A/B isoforms in 24.1% of them. The combination of clinical parameters and tissue phenotype allowed a stratification of endometriosis-affected patients. Such novel phenotypical and clinical correlation could be helpful in the future studies for a better stratification of the disease aiming at a personalized patient care.
Publication
Chapron C, Lang JH, Leng JH, Zhou Y, Zhang X, Xue M, Popov A, Romanov V, Maisonobe P, Cabri P
• 08/2016
INTRODUCTION: The present study aimed to investigate clinical, lifestyle, and environmental factors associated with endometrioma (OMA) and/or deep infiltrating endometriosis (DIE) as determined by case-control comparison [women with superficial peritoneal endometriosis (SUP) or no endometriosis], and compare differences between factor associated with endometriosis at a national level. METHODS: This was three countries (China, Russia, and France), case-control study in 1008 patients. Patients were identified and enrolled during their first routine appointment with their physician post-surgery for a benign gynecologic indication, excluding pregnancy. Retrospective information on symptoms and previous medical history was collected via face-to-face interviews; patients also completed a questionnaire to provide information on current habits. For every DIE patient recruited (n = 143), two women without endometriosis (n = 288), two SUP patients (n = 288), and two OMA patients (n = 288) were recruited. RESULTS: For the overall population, factors significantly associated (P ≤ 0.05) with DIE or OMA [Odds ratio (OR) >1] were: previous use of hormonal treatment for endometriosis [OR 6.66; 95% confidence interval (CI) 4.05-10.93]; previous surgery for endometriosis (OR 1.95; 95% CI 1.11-3.43); and living or working in a city or by a busy area (OR 1.66; 95% CI 1.09-2.52). Differences between regions with regard to the diagnosis, symptomatology, and treatment of endometriosis exist. CONCLUSION: The findings provide insight into potential risk factors for endometriosis and differences between regions in terms of endometriosis management and symptomatology. Further investigations are required to confirm the associations found in this study. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01351051. FUNDING: Ipsen.
Publication
Villette C, Bourret A, Santulli P, Gayet V, Chapron C, de Ziegler D
• 08/2016
OBJECTIVE: To study possible associations among endometriosis, pelvic infectious disease, and ART. DESIGN: Retrospective cohort analysis over 4 consecutive years, based on medical records and insurance coding in a tertiary endometriosis reference center. SETTING: Tertiary university-based reference center for endometriosis. PATIENT(S): We retrieved all charts carrying the diagnoses infectious process and endometriosis in 2009-2012. Each chart was individually analyzed for categorization of the infectious episode and determining whether ART had been performed. MAIN OUTCOME MEASURE(S): Hospitalization for acute infection in women with known endometriosis and possible past ART. INTERVENTION: Retrospective insurance codes-triggered chart analysis. RESULT(S): Ten patients were admitted for an acute infection with fever, acute abdomen syndrome, elevated white blood cell count, and adnexal mass. Three women had oocyte retrieval, and an endometrioma was present 16, 57, and 102 days earlier. In one patient, the complication occurred 37 days after a cesarean section without prior ART. In the remaining six cases tubo-ovarian abscesses (TOAs) occurred spontaneously in endometriosis women who never had ART. Medical treatment succeeded in only two patients, and the remaining eight needed laparoscopic drainage. In 6 out of those 8 cases, laparoscopic drainage was a second-stage measure justified by failure to respond to antibiotic therapy. CONCLUSION(S): Our data indicate that some putative complications of ART and endometrioma may actually not be linked to ART, but rather constitute sporadic occurrences in endometriosis. Furthermore, TOAs occurring in women with endometriosis are best treated by early surgical drainage together with intravenous antibiotics.
Publication
Santulli P, Marcellin L, Chouzenoux S, Boulard V, Just PA, Nicco C, Chereau C, Tosti C, Chapron C, Batteux F
• 08/2016
OBJECTIVE: Mitogen-activated protein kinases (MAPKs) are involved in the proliferation and survival of endometriotic lesions. Vemurafenib (PLX4032) is a novel protein kinase inhibitor that targets BRAF, a member of the MAPK pathway. The present study tested the in vitro and in vivo effects of PLX4032 on endometriotic cells. RESEARCH DESIGN AND METHODS: We conducted a laboratory study in a tertiary-care university hospital from January 2013 to September 2013. We enrolled a cohort of 40 patients: 20 with histologically proven endometriosis and 20 unaffected women. A thorough surgical examination of the abdominopelvic cavity was performed on all of the study participants. Ex vivo stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from both sets of patients. Proliferation, apoptosis, pERK/ERK ratio, cell cycle regulation (Cyclin D1 and CDK4) and inflammation (PTGS2) were explored with and without PLX4032 treatment. Human endometriotic lesions were implanted into 40 nude mice that were separated into two groups according to PLX4032 or vehicle treatment, which they received for four weeks, before sacrifice and histological examination. RESULTS: Treating endometriotic cells with PLX4032 abrogated the phosphorylation of ERK, significantly reducing the pERK/ERK ratio in both epithelial and stromal cells from endometriotic women compared to the controls (p < 0.05). In addition, treatment with PLX4032 significantly decreased proliferation in both stromal and epithelial cells with a concomitant decrease in Cyclin D1/CDK4 complex and PTGS2 levels. Using a murine model of endometriosis, we observed that PLX4032-treated mice displayed a significant decrease in implant volume compared to the initial size; a slight, but non-significant, increase in size was observed in the vehicle-treated mice. CONCLUSION: Our data suggest that MAPKs and BRAF are involved in the pathogenesis of endometriosis. PLX4032-induced inhibition of BRAF controlled endometriotic growth, both in vitro and in vivo, and could constitute a promising target for the treatment of endometriosis.
