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Can a saliva-based miRNA signature for endometriosis-associated infertility be designed and validated by analysing the human miRNome?The prospective ENDOmiARN study (NCT04728152) included 200 saliva samples obtained between January 2021 and June 2021 from women with pelvic pain suggestive of endometriosis. All patients underwent either laparoscopy, magnetic resonance imaging, or both. Patients diagnosed with endometriosis were allocated to one of two groups according to their fertility status. Data analysis consisted of identifying a set of miRNA biomarkers using next-generation sequencing, and development of a saliva-based miRNA signature of infertility among patients with endometriosis based on a random forest model.Among the 153 patients diagnosed with endometriosis, 24% (n = 36) were infertile and 76% (n = 117) were fertile. Small RNA-sequencing of the 153 saliva samples yielded approximately 3712 M raw sequencing reads (from ∼13.7 M to ∼39.3 M reads/sample). Of the 2561 known miRNAs, the feature selection method generated a signature of 34 miRNAs linked to endometriosis-associated infertility. After validation, the most accurate signature model had a sensitivity, specificity and area under the curve of 100%.A saliva-based miRNA signature for endometriosis-associated infertility is reported. Although the results still require external validation before using the signature in routine practice, this non-invasive tool is likely to have a major effect on care provided to women with endometriosis.

Figure S2

In established tumors, tumor-associated macrophages (TAM) orchestrate nonresolving cancer-related inflammation and produce mediators favoring tumor growth, metastasis, and angiogenesis. However, the factors conferring inflammatory and protumor properties on human macrophages remain largely unknown. Most solid tumors have high lactate content. We therefore analyzed the impact of lactate on human monocyte differentiation. We report that prolonged lactic acidosis induces the differentiation of monocytes into macrophages with a phenotype including protumor and inflammatory characteristics. These cells produce tumor growth factors, inflammatory cytokines, and chemokines as well as low amounts of IL10. These effects of lactate require its metabolism and are associated with hypoxia-inducible factor-1α stabilization. The expression of some lactate-induced genes is dependent on autocrine M-CSF consumption. Finally, TAMs with protumor and inflammatory characteristics (VEGFhigh CXCL8+ IL1β+) are found in solid ovarian tumors. These results show that tumor-derived lactate links the protumor features of TAMs with their inflammatory properties. Treatments that reduce tumor glycolysis or tumor-associated acidosis may help combat cancer.

Table S1

International audience; INTRODUCTION: Hemostasis Hysterectomy (HH) is a last resort surgical procedure performed in situations of uncontrolled post-partum hemorrhage in maternity wards. The chances of being confronted with this situation are scarce during residency, and the situation is not well suited for teaching. Nevertheless, every obstetrician-gynecologist can be confronted with this stressful situation, and should therefore possess the surgical competence required, regardless of his routine practice. The aim of the present study is to evaluate clinical exposure and self-awareness concerning HH amongst obstetrics and gynecology residents and fellows. MATERIEL AND METHODS: We performed a survey amongst French obstetrics and gynecology fellows. An anonymous survey was sent by email between December 1, 2020 to July 1, 2021. RESULTS: Half of the interrogated fellows had practiced (as operator) an HH during residency with a senior and only 22,6% in post-residency. During the last year of residency 70% of them had performed less than 10 scheduled hysterectomies as primary operator. The laparoscopic approach was the most frequently practiced. Very few hysterectomies were performed as primary operator. Fellows with a surgical or mixed activity (both gynecological surgery and obstetrical activity in current practice) felt significantly more capable of performing HH compared to those with exclusive obstetrical or reproductive medicine activity; respectively 60% vs 36%, p = 0.008; Odds Ratio: 2.629 (95% CI 1.2214; 5.8094). CONCLUSION: The number of scheduled hysterectomies or HH performed as primary operator is very low during residency or fellowship. It remains largely inferior to the number deemed necessary in previous publications about the learning curve for scheduled hysterectomy, which varies from 18 to 80 interventions. Nowadays, the increasing number of residents, added to the decrease of hemostasis hysterectomies through better management of post-partum hemorrhage, pushes towards the development of specific training, such as "damage control simulation".

To validate a mathematical model to predict the mean time to delivery (TTD) following cervical ripening with dinoprostone vaginal insert (DVI), and assess its impact on the risk of nocturnal deliveries.We performed a case-control retro-prospective study at Angers University Hospital. In the control group, we retrospectively included 405 patients who underwent cervical ripening with DVI between 01/2015 and 09/2016. Based on the delivery outcomes, we developed a mathematical model that integrates all the factors influencing TTD following cervical ripening with DVI. In the study group, we prospectively included 223 patients who underwent cervical ripening with DVI between 11/2017 and 11/2018. The timing of insertion was calculated using the mathematical model developed in the control group, in order to prevent the occurrence of nocturnal deliveries.The calculated mean TTD was significantly shorter than the real mean TTD (21h46 min ± 3h28 min versus 25h38 min ± 12h10 min, p 0.001), and for 44% of patients, there was at least 10 h difference between the two. The real TTD (25h38 min ± 12H10 min versus 20h39 min ± 10h49, p 0.001), and the rate of nocturnal deliveries (30.5% versus 21.2%, p = 0.01) were significantly higher in the study group compared to the control group.The mathematical model did not help predicting TTD following cervical ripening with DVI, and or reducing the number of nocturnal deliveries.

Objective: To assess the impact of an oocyte retrieval simulation training program (ORSTP) on the clinical performance of residents. Design: Prospective comparative study. Setting: A tertiary care center. Population: All OR performed by residents between May 2017 and November 2020. Methods & main outcome measures: The Simulation (S) group included OR performed by residents who had undergone an ORSTP before performing them on patients (n=422) and the control (C) group included OR performed by residents who had not received prior simulation training (n= 329). Our main outcome measure was the OR rate (ORR) (number of oocytes collected/number of follicles aspirated) during the first 3 months of the rotation. Results: In the S group, 6 residents aspirated 657 ovaries while in the C group, 5 residents aspirated 508 ovaries. The mean ORR during the first 3 months of rotation were comparable between the S and C groups (59% vs 58%). ORR during the first and second month, and at the end of the rotation were also comparable between the S and C groups (54% vs 63%, 58% vs 59% et 58% vs 58%, respectively). There was no significant difference in the rate of failed OR (3.3% vs 1.8%) between the S and C groups. Finally, 16% of residents in the S group reported being stressed before their first OR compared to 40% in the C group. Conclusions: The ORSTP does not improve the residents’ clinical performance, but it could decrease their stress in clinical practice.

Introduction Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the detection of metastatic disease, but benefits of omitting pelvic lymph node dissection in terms of decreased morbidity have not been demonstrated. Materials and methods In an open-label study, patients with early cervical carcinoma (FIGO 2009 stage IA2 to IIA1) were randomly assigned to SN resection alone (SN arm) or SN and pelvic lymph node dissection (SN + PLND arm). SN resection was followed by radical surgery of the tumour (radical hysterectomy or radical trachelectomy). The primary end-point was morbidity related to the lymph node dissection; 3-year recurrence-free survival was a secondary end-point. Results A total of 206 patients were eligible and randomly assigned to the SN arm (105 patients) or SN + PLND arm (101 patients). Most patients had stage IB1 lesion (87.4%). No false-negative case was observed in SN + PLND arm. Lymphatic morbidity was significantly lower in the SN arm (31.4%) than in the SN + PLND arm (51.5%; p = 0.0046), as was the rate of postoperative neurological symptoms (7.8% vs. 20.6%, p = 0.01, respectively). However, there was no significant difference in the proportion of patients with significant lymphoedema between the two groups. During the 6-month postoperative period, the difference in morbidity decreased over time. The 3-year recurrence-free survival was not significantly different (92.0% in SN arm and 94.4% in SN + PLND arm). Conclusion SN resection alone is associated with early decreased lymphatic morbidity when compared with SN + PLND in early cervical cancer.

Resume Objectifs En appui sur les donnees issues d’une vaste recherche medico-psychopathologique proposee a des jeunes filles atteintes d’une agenesie utero-vaginale — syndrome de Rokitansky ou Mayer-Rokitansky-Kuster-Hauser (MRKH) — notre travail propose l’analyse psychodynamique de la valeur et de la fonction pour l’economie psychosomatique d’une reaction frequente a l’annonce diagnostique : le developpement d’un desordre alimentaire de type prise de poids chez 4 patientes sur 40. La mise en perspective de l’analyse de deux cas de patientes permet d’affiner la comprehension du sens de cette emergence alimentaire dont nous faisons l’hypothese qu’elle constitue a la fois une modalite defensive signalant les impasses du processus de construction du feminin mais aussi possiblement un levier de transformation psychique de ses incidences traumatiques. Methode Quarante jeunes femmes MRKH âgees de 19 a 34 ans (avec un âge moyen de 25 ans ½) ont ete rencontrees. La recherche leur a ete proposee de 2 a 17 ans apres leur annonce diagnostique et le travail clinique a consiste en une analyse retrospective de leur experience traumatique adolescente. Le recit des patientes a ete recueilli a l’aide d’un entretien clinique a visee de recherche non directif. Deux epreuves projectives (Rorschach et Thematic Apperception Test – TAT) leur ont egalement ete proposees pour apprehender plus finement les modalites de leur fonctionnement psychique. Les donnees des entretiens font l’objet d’une analyse clinique thematique ; les protocoles du Rorschach et du TAT sont analyses selon la methode d’interpretation de l’Ecole Francaise referee a la theorie psychanalytique du fonctionnement psychique. Le materiel issu des rencontres avec deux patientes diagnostiquees a l’âge de 17 ans et ayant presente dans la suite de cette annonce une prise de poids de 10 kg est ici compare de maniere approfondie. Resultats Le reperage de contrastes en termes de problematiques et de niveaux d’elaboration entre l’entretien et les protocoles projectifs est saisissant pour chaque patiente. A travers l’analyse de l’entretien, le symptome alimentaire de la patiente 1 parait survenir dans un contexte psychique ou l’interiorite feminine semble irrepresentable. Les protocoles projectifs revelent a l’inverse l’acces a un travail du feminin conflictuel et symbolise. De meme, le discours de la patiente 2 sur son symptome est a premiere vue bien plus elabore que celui de la patiente 1 puisque celle-ci etablit un lien subjectif entre le renoncement au projet de maternite implique par l’annonce du MRKH et la dimension compensatoire procuree par la prise de poids. Pourtant, le contraste offert par les tests projectifs dont les productions traduisent au contraire les fragilites identitaires et une insuffisante symbolisation du sexuel temoigne de la valeur defensive de l’exces de symbolisation de son discours manifeste dans l’entretien. Discussion Ces contrastes amenent a envisager le remplissage alimentaire comme une tentative de traitement d’une sexualite feminine deja conflictuelle voire en impasse avant la decouverte du MRKH. Ses accents traumatiques sont reactualises et potentialises a la faveur de l’annonce diagnostique. Les differents niveaux de problematiques reperes peuvent cohabiter chez une meme femme, qu’il s’agisse d’un feminin ni construit ni integre, d’un impossible investissement du corps interne ou d’un contre-investissement de l’impossible maternite. Dans ce contexte, l’etiopathogenie de la prise de poids qui succede a l’annonce du diagnostic est pour chaque jeune fille singuliere mais toujours en lien avec un feminin et/ou un maternel atteint. Conclusion En conclusion, si la prise de poids qui suit le diagnostic traduit une entrave voire une impasse (eventuellement ponctuelle) du traitement psychique de ses effets, cette annonce medicale a l’adolescence peut constituer une nouvelle chance pour ces jeunes filles, celle d’un apres-coup a la valeur potentiellement mutative.

The aim of this study was to evaluate an oocyte pick-up (OPU) simulation training program for residents using the high fidelity PickUpSimTM (Accurate, Cesena, Italy) simulator. The authors carried ...

Objectives: To compare the neonatal morbidity of caesarean sections (CS) performed after conversion from neuraxial (NA) to general anaesthesia (GA) with CS performed under GA from the outset, and to assess whether the increase in DDI in urgent and extremely urgent cases with conversion from NA to GA increased the risk of neonatal morbidity. Design: Retrospective cohort study. Setting: University-affiliated hospital. Population: All CS performed under GA between 2015 and 2019. Methods & main outcome measures: Our main criteria used for assessing neonatal morbidity were: neonatal pH

Ovarian tumors are the most frequent adnexal mass, raising diagnostic and therapeutic issues linked to a large spectrum of tumors, with a continuum from benign to malignant. Thus far, none of the available diagnostic tools have proven efficient in deciding strategy, and no consensus exists on the best strategy between “single test”, “dual testing”, “sequential testing”, “multiple testing options” and “no testing”. In addition, there is a need for prognostic tools such as biological markers of recurrence and theragnostic tools to detect women not responding to chemotherapy in order to adapt therapies. Non-coding RNAs are classified as small or long based on their nucleotide count. Non-coding RNAs have multiple biological functions such as a role in tumorigenesis, gene regulation and genome protection. These ncRNAs emerge as new potential tools to differentiate benign from malignant tumors and to evaluate prognostic and theragnostic factors. In the specific setting of ovarian tumors, the goal of the present work is to offer an insight into the contribution of biofluid non-coding RNAs (ncRNA) expression.

International audience; Background: Endometriosis diagnosis constitutes a considerable economic burden for the healthcare system with diagnostic tools often inconclusive with insufficient accuracy. We sought to analyze the human miRNAome to define a saliva-based diagnostic miRNA signature for endometriosis. Methods: We performed a prospective ENDO-miRNA study involving 200 saliva samples obtained from 200 women with chronic pelvic pain suggestive of endometriosis collected between January and June 2021. The study consisted of two parts: (i) identification of a biomarker based on genome-wide miRNA expression profiling by small RNA sequencing using next-generation sequencing (NGS) and (ii) development of a saliva-based miRNA diagnostic signature according to expression and accuracy profiling using a Random Forest algorithm. Results: Among the 200 patients, 76.5% (n = 153) were diagnosed with endometriosis and 23.5% (n = 47) without (controls). Small RNA-seq of 200 saliva samples yielded ~4642 M raw sequencing reads (from ~13.7 M to ~39.3 M reads/sample). Quantification of the filtered reads and identification of known miRNAs yielded ~190 M sequences that were mapped to 2561 known miRNAs. Of the 2561 known miRNAs, the feature selection with Random Forest algorithm generated after internally cross validation a saliva signature of endometriosis composed of 109 miRNAs. The respective sensitivity, specificity, and AUC for the diagnostic miRNA signature were 96.7%, 100%, and 98.3%. Conclusions: The ENDO-miRNA study is the first prospective study to report a saliva-based diagnostic miRNA signature for endometriosis. This could contribute to improving early diagnosis by means of a non-invasive tool easily available in any healthcare system.

Las sinequias son una de las principales causas de infertilidad secundaria. La prevalencia de las sinequias probablemente este subestimada debido a la heterogeneidad de la sintomatologia. Existen varias clasificaciones de las sinequias. Es preciso realizar una actualizacion sobre el origen, las consecuencias, el diagnostico, el tratamiento y los metodos de prevencion de las adherencias intrauterinas. Se ha realizado una revision de la literatura utilizando Medline, Pubmed, la biblioteca Cochrane y la Web of Science para actualizar los origenes, las consecuencias y los metodos de prevencion de las sinequias. Las sinequias son susceptibles de producirse despues de cualquier procedimiento endouterino debido a una disregulacion de la cadena de activacion de la coagulacion relacionada con el proceso inflamatorio. Tambien se sabe que las sinequias causan complicaciones obstetricas precoces y tardias. La tecnica recomendada actualmente para una histeroscopia diagnostica es la vaginoscopia con histeroscopio rigido, de diametro menor o igual a 3,5 mm, con una distension mediante suero fisiologico a temperatura ambiente, sin aplicar ninguna anestesia ni preparacion farmacologica, asi como sin desinfeccion vaginal ni profilaxis antibiotica. Se han desarrollado varias vias de investigacion inspiradas en la via intraabdominal para la prevencion de las adherencias pelvicas. Sin embargo, ningun metodo de prevencion actual ha demostrado ser eficaz en terminos de mejora de la fertilidad espontanea. La mejora de las practicas quirurgicas, el diseno de nuevos dispositivos medicos intrauterinos y las nuevas vias de investigacion, en particular en el ambito de las celulas madre endometriales, tal vez permitiran reducir la tasa de sinequias y sus complicaciones despues de una intervencion quirurgica endouterina.

Population screening programmes must make good use of resources for the health system and users. To evaluate impacts of the type of diagnostic test in the new French cervical screening programme, an messenger ribonucleic acid (mRNA) high-risk human papillomavirus assay was compared to a deoxyribonucleic acid (DNA) high-risk human papillomavirus assay for a hypothetical cohort of women aged 25 to 65 years.This evaluation takes the perspective of the French healthcare system.France.A decision tree model reflecting the French cervical screening algorithms was parametrised using French cost and population data and the Danish Horizon study. The outcomes were total costs, and number of colposcopies, HPV tests and cytology tests for the cohort. One-way and probabilistic sensitivity analyses and scenarios analyses were conducted to test the robustness of results to parameter and structural uncertainty.Adopting an mRNA versus DNA assay as part of national cervical screening in France is estimated to save €6.5 million (95% credibility intervals €-1.3 - €13.5 million) and prevent 47,795 (95% credibility intervals 35,309 - 60,139) unnecessary colposcopies, 38,666 unnecessary HPV tests and 121,670 cytology tests over two years for a cohort of 2,168,806 million women aged 25 to 65 years. Sensitivity analyses indicated robust results across a range of inputs.The choice of high-risk human papillomavirus assay makes a significant difference to resource use and costs and is important to consider when implementing cervical screening in France. Using an mRNA versus DNA assay can result in cost savings and reductions in unnecessary testing and procedures, which in turn benefits women and the health care system.

Introduction Serum oestradiol concentration at the time of frozen embryo transfer (FET) in artificial cycle are lower when using transdermal administration of oestrogen for endometrial preparation compared to the vaginal route. This difference could have consequences for placentation and establishment of maternal-foetal circulation. The aim of our study was to compare the birth weight of newborns and the perinatal issues after FET in an artificial cycle with regard to the route of administration of oestrogens. Methods Retrospective monocentric cohort study in the medically assisted reproduction department of the University Hospital of Angers, France, between January 2017 and October 2020. Inclusion criteria were age >18 years old and one live birth after FET in an artificial cycle. The main outcome was the birth weight of the newborns. The choice of oestrogens administration (transdermal or vaginal) was left to the patient. Results 804 FET in artificial cycle were included in our study. Oestrogens were administrated in 356/804(36.6%) patients using transdermal route and in 448/804(45.9%) patients using vaginal route. There were 68/345 (19.1%) live births in the transdermal group and 85/448 (19%) in the vaginal group. There was no difference in the birth weight of the newborns (3320[2100-4165] grams in the transdermal group vs 3327.5[915-4650] grams in the vaginal group, p=0.72). All the other perinatal issues were comparable between the two groups. Conclusion Birth weights and perinatal issues were comparable with regard to the route of administration of oestrogens (vaginal or transdermal) in the context of endometrial preparation before FET in an artificial cycle.

The aim of the present study was to assess factors associated with a repeat operative vaginal delivery (OVD) in women with a previous history of OVD.A single-centre retrospective observational study was performed in the maternity ward of the Angers University Hospital between 20/09/2010 and 01/04/2021. All the patients who underwent an OVD between 01/09/2010 and 31/10/2013 (delivery n°1, n = 1215) and who subsequently delivered up to the 01/04/2021 (delivery n°2, n = 652) were included. Multivariate logistic regression was used to assess the risk of subsequent recurrent OVD, adjusted for clinical potential confounder based on univariate analysis.Among the 520/652 (79.7%) patients who delivered vaginally during delivery n°2, 51/520 (9.8%) had undergone a repeated OVD. Gestational age, parity, history of uterine scars, percentage of labour's induction and the duration of labor were similar between patients who delivered spontaneously and those who required an OVD during delivery n°2. There were 7/51 (13.7%) patients who underwent an OVD during delivery n°2 with a newborn in cephalic posterior presentation compared to 20/469(4.3%) in cases of spontaneous vaginal delivery n°2 (p 0.01). A posterior cephalic presentation increased the risk of subsequent OVD by 3.7 [Confidence Interval 95% (1.4-9.6), p 0.01] CONCLUSION: In the case of a history of OVD, a low proportion of women required a repeated OVD (9.8%). The only factor associated with the need for repeated OVD was a persistent fetal cephalic posterior presentation at the time of delivery.

Objective To evaluate whether manual rotation of fetuses in occiput posterior positions at full dilation increases the rate of spontaneous vaginal delivery. Methods In an open, single-center, randomized controlled trial, patients with a term, singleton gestation, epidural analgesia, and ultrasonogram-confirmed occiput posterior position at the start of the second stage of labor were randomized to either manual rotation or expectant management. Our primary endpoint was the rate of spontaneous vaginal delivery. Secondary endpoints were operative vaginal delivery, cesarean delivery, and maternal and neonatal morbidity. Analyses were based on an intention-to-treat method. A sample size of 107 patients per group (n=214) was planned to detect a 20% increase in the percent of patients with a spontaneous vaginal delivery (assuming 60% without manual rotation vs 80% with manual rotation) with 90% power and alpha of 0.05. Results Between February 2017 and January 2020, 236 patients were randomized to either manual rotation (n=117) or expectant management (n=119). The success rate of the manual rotation maneuver, defined by conversion to an anterior position as confirmed by ultrasonogram, was 68%. The rate of the primary endpoint did not differ between the groups (58.1% in manual rotation group vs 59.7% in expectant management group (risk difference -1.6; 95% CI -14.1 to 11.0). Manual rotation did not decrease the rate of operative vaginal delivery (29.9% in manual rotation group vs 33.6% in expectant management group (risk difference -3.7; 95% CI -16.6 to 8.2) nor the rate of cesarean delivery (12.0% in manual rotation group vs 6.7% in expectant management group (risk difference 5.3; 95% CI -2.2 to 12.6). Maternal and neonatal morbidity was also similar across the two groups. Conclusion Manual rotation of occiput posterior positions at the start of second stage of labor does not increase the rate of vaginal delivery without instrumental assistance. Clinical trial registration ClinicalTrials.gov, NCT03009435.

Urinary incontinence is a common health problem that impacts the quality of life of women at different ages. Its physiopathology is not unequivocal, and it is necessary to consider the stress urinary incontinence (SUI), the overactive bladder syndrome and the mixed incontinence (MUI). According to the type of incontinence, its impact on the quality of life and age of the patients, therapeutic strategies are currently summarized in physiotherapy, surgery and drug treatments. We already know the benefit/risk ratio of each of these strategies. Our objective is to evaluate the potential effectiveness and safety of the VEL, an innovative vaginal laser technique (VEL – Vaginal Erbium Laser, erbium yttrium-aluminum-garnet -Er: YAG) a non-invasive laser proposed as a treatment for SUI, overactive bladder syndrome and MUI. The mechanisms of action of lasers are discussed in general and those of VEL in particular with the description of the Smooth® mode. To do this, we have collected the 21 published studies including the first randomized vs. placebo and two pilot studies of intra-urethral VEL. In conclusion: VEL procedures already have their place between the rehabilitation of the perineal floor and surgery. Further properly sized, randomized studies are needed to evaluate the laser treatments in comparison with other therapies, as well as to assess the duration of the therapeutic effects and the safety of repeated applications.

The aim of this study was to evaluate an oocyte pick-up (OPU) simulation training program for residents using the high fidelity PickUpSim

International audience; Objectives: In 2016, the European Society of Gynecology Oncology (ESGO) published indicators defining the quality of surgical management of advanced ovarian cancer. The objective of the study was to assess the quality of ovarian cancer patient management in regional centers authorized for gynecological cancer, based on the ESGO list of quality indicators. Methods: A multicenter retrospective observational cohort study was conducted from January 1 to June 30, 2016. The following quality indicators 1 "rate of complete surgical resection", 4 "center participating in clinical trials in gynecologic oncology", 5 "treatment planned and reviewed at a multidisciplinary team meeting", 6 "required preoperative workup", 8 "minimum required elements in operative reports" and 9 "minimum required elements in pathology reports" were selected. Results: 91 patients were evaluated in 16 centers. The required preoperative workup was incomplete in 25% of cases. Treatment was not planned at a multidisciplinary team meeting for 24%. An evaluation score of peritoneal involvement was included in 40% of the operative reports and the quality of surgical resection was reported in 72%. Primary surgery was most often performed in a peripheral hospital (48%), interval surgery in a private center (37%), and closure surgery in a regional cancer center (43%). No institution respected the six quality indicators evaluated. One regional cancer center respected five items and two private centers did not respect any. Conclusion: Whilst the ESGO quality indicators provide objective, validated and evaluable support which centers can use to improve quality of care, we observed heterogeneous practices amongst the centers evaluated.

Objectives: To investigate the perinatal outcomes of women with a history of female genital mutilation (FGM) who underwent clitoral reconstruction (CR) compared with women with FGM who did not undergo CR. Design: Retrospective case-control study Setting: Angers University Hospital, between 2005 and 2017 Methods: Inclusion criteria: pregnant women >18 years who underwent CR after FGM. Only the first subsequent delivery after CR was included. Each woman with CR was matched for age, ethnicity, FGM type, parity, and gestational age at the time of delivery with two women with FGM who did not undergo CR during the same period of time. Main outcome measures: at birth: need for episiotomy and intact perineum Results: 84 women were included (28 in the CR group; 56 in the control group). In the CR group, patients required significantly fewer episiotomies (5/17[29.4%]) compared to the control group (28/44[63.6%], p=0.02), even after excluding operative vaginal deliveries (2/13[15.4%] vs 21/36[58.3], p

Objective: AUB-O,E,N is treated first with medical management, followed by surgery, which failure or complications have significant burden. The objective was to perform a cost-effectiveness analysis of four surgical strategies, comparing cost and avoided failure rate, using the French PMSI database. Design: Retrospective analysis performed using the French exhaustive national hospital discharge database (PMSI). Population: All incident 35-55 year-old women operated on for four types of AUB-O,E,N surgery (2nd generation, 1st generation, curettage or hysterectomy) between 2009 and 2014 were included. Methods : They were followed to collect rehospitalizations related to failure or complication and their cost, during at least 18 months. Hospital costs were estimated using the French tariffs in 2017\euro. Main Outcome measures : A cost-effectiveness analysis was performed comparing each surgical procedure to 2G, in hospitalization costs and rate of patients without failure. Results : The study included 88,154 patients. At 18 months, mean cost per patient was \euro2,448 for 2G, \euro2,100 for 1G, \euro2,275 for curettage and \euro4,157 for hysterectomy. Hysterectomy was the most effective strategy in terms of absence of failure, but also the most expensive, with an incremental cost of \euro24,008 per additional % of patient without failure. Even with a mean cost similar to 2G, curettage was the least effective strategy with a failure rate reaching 20.6% at 18 months. 1G was less expensive but also less effective than 2G, with an economy of \euro13,078 per % of patient without failure loss. Conclusion: 1G and 2G techniques are the most efficient strategie

Endometriosis and infertility are closely linked, but the underlying mechanisms are still poorly understood. This study aimed to evaluate the impact of endometriosis on in vitro fertilization (IVF) parameters, especially on embryo quality and IVF outcomes. A total of 1124 cycles with intracytoplasmic sperm injection were retrospectively evaluated, including 155 cycles with endometriosis and 969 cycles without endometriosis. Women with endometriosis had significantly lower ovarian reserve markers (AMH and AFC), regardless of previous ovarian surgery. Despite receiving significantly higher doses of exogenous gonadotropins, they had significantly fewer oocytes, mature oocytes, embryos, and top-quality embryos than women in the control group. Multivariate analysis did not reveal any association between endometriosis and the proportion of top-quality embryo (OR = 0.87, 95% CI [0.66&ndash, 1.12], p = 0.3). The implantation rate and the live birth rate per cycle were comparable between the two groups (p = 0.05), but the cumulative live births rate was significantly lower in in the endometriosis group (32.1% versus 50.7%, p = 0.001), as a consequence of the lower number of frozen embryos. In conclusion, endometriosis lowers the cumulative live birth rates by decreasing the number of embryos available to transfer, but not their quality.

To determine if a modification of the cytokine profile occurs in the follicular fluid (FF) of women with endometriosis undergoing in vitro fertilization (IVF), we performed a prospective observational study from January 2018 to February 2019. In total, 87 women undergoing IVF were included: 43 for severe endometriosis-related infertility and 40 controls with other causes of infertility. The cytokine profile of the FF was determined by multiplex fluorescent-bead-based technology allowing the measurement of 59 cytokines. Monocyte Chemoattractant Protein 1 (MCP-1) was the only variable retained in the multivariate analysis. We identified two subgroups of patients in the endometriosis group: MCP-1-low group (n = 23), which had FF MCP-1 levels comparable to the control group, and MCP-1-high (n = 20), which had significantly higher FF levels. Only patients in the MCP-1-high group had a significantly altered cytokine profile in the FF, and had a significantly higher serum estradiol level (p = 0.002) and a significantly lower number of oocytes recovered (p = 0.01) compared to the MCP-1-low and the control group. Our study has shown an alteration of the oocyte microenvironment in women with endometriosis associated with high follicular fluid levels of MCP-1, allowing the identification of a subgroup of endometriosis patients with a potentially worse prognosis.

Urinary incontinence is a common health problem that impacts the quality of life of women at different ages. Its physiopathology is not unequivocal, and it is necessary to consider the stress urinary incontinence (SUI), the overactive bladder syndrome and the mixed incontinence (MUI). According to the type of incontinence, its impact on the quality of life and age of the patients, therapeutic strategies are currently summarized in physiotherapy, surgery and drug treatments. We already know the benefit/risk ratio of each of these strategies. Our objective is to evaluate the potential effectiveness and safety of the VEL, an innovative vaginal laser technique (VEL - Vaginal Erbium Laser, erbium yttrium-aluminum-garnet -Er: YAG) a non-invasive laser proposed as a treatment for SUI, overactive bladder syndrome and MUI. The mechanisms of action of lasers are discussed in general and those of VEL in particular with the description of the Smooth® mode. To do this, we have collected the 21 published studies including the first randomized vs. placebo and two pilot studies of intra-urethral VEL. In conclusion: VEL procedures already have their place between the rehabilitation of the perineal floor and surgery. Further properly sized, randomized studies are needed to evaluate the laser treatments in comparison with other therapies, as well as to assess the duration of the therapeutic effects and the safety of repeated applications.

International audience; Objective: Ovarian ageing is one of the commonest causes of infertility in patients consulting for assisted reproductive technology. The composition of the follicular fluid (FF), which reflects the exchanges between the oocyte and its microenvironment, has been extensively investigated to determine the metabolic pathways involved in various ovarian disorders. Considering the importance of cytokines in folliculogenesis, we focused on the cytokine profile of the FF during ovarian ageing. Material and methods: Our cross-sectional study assesses the levels of 27 cytokines and growth factors in the FF of two groups of women undergoing in vitro fertilization. One group included 28 patients with ovarian ageing clinically characterized by a diminished ovarian reserve (DOR), and the other group included 29 patients with a normal ovarian reserve (NOR), serving as controls. Results: With univariate analysis, the cytokine profile was found to differ significantly between the two groups. After adjustment of the p-values, platelet-derived growth factor-BB (PDGF-BB) was the only cytokine with a significantly lower concentration in the DOR group (7.34 AE 16.11 pg/mL) than in the NOR group (24.39 AE 41.38 pg/mL) (p = 0.005), independently of chronological age. Conclusion: Thus, PDGF-BB would seem to be implicated in the physiopathology of DOR, potentially in relation to its role in folliculogenesis or in the protection against oxidative stress.

In established tumors, tumor-associated macrophages (TAM) orchestrate nonresolving cancer-related inflammation and produce mediators favoring tumor growth, metastasis, and angiogenesis. However, the factors conferring inflammatory and protumor properties on human macrophages remain largely unknown. Most solid tumors have high lactate content. We therefore analyzed the impact of lactate on human monocyte differentiation. We report that prolonged lactic acidosis induces the differentiation of monocytes into macrophages with a phenotype including protumor and inflammatory characteristics. These cells produce tumor growth factors, inflammatory cytokines, and chemokines as well as low amounts of IL10. These effects of lactate require its metabolism and are associated with hypoxia-inducible factor-1α stabilization. The expression of some lactate-induced genes is dependent on autocrine M-CSF consumption. Finally, TAMs with protumor and inflammatory characteristics (VEGFhigh CXCL8+ IL1β+) are found in solid ovarian tumors. These results show that tumor-derived lactate links the protumor features of TAMs with their inflammatory properties. Treatments that reduce tumor glycolysis or tumor-associated acidosis may help combat cancer.

The objective was to compare the endometrial thickness (ET) in a frozen embryo transfer (FET) cycle between transdermal and vaginal estrogen. Our secondary objectives were to compare the patient satisfaction and the pregnancy outcomes. Prospective monocentric cohort study between 01/2017 and 12/2017 at a single institution. Choice of administration was left to the patient. 119 cycles had transdermal estrogen (T-group) and 199 had vaginal estrogen (V-group). The ET at 10 ± 1 days of treatment was significantly higher in the T-group compared to the V-group (9.9 vs 9.3 mm, p = 0.03). In the T-group, the mean duration of treatment was shorter (13.6 vs 15.5 days, p

A congenital malformation of the head, neck or thorax can lead to upper airway compression with a risk of asphyxia or neonatal death. To secure and protect the upper airway, the Ex Utero Intrapartum Therapy (EXIT) procedure has been developed. The procedure allows delivery of the fetus via a hysterotomy while relying on the placenta as the organ of respiration for the fetus prior to clamping of the umbilical cord. A high level of expertise is necessary for successful completion of the EXIT procedure, which is not void of maternal and fetal risks. In this literature review, we present the indications, procedure methods and materno-fetal complications associated with the EXIT procedure.