Publications by authors named "Philippe Descamps"

96 Publications

External cephalic version: Predictors for success.

J Gynecol Obstet Hum Reprod 2021 May 15;50(9):102165. Epub 2021 May 15.

Department of Obstetrics & Gynecology, University Hospital of Angers, Angers, France. Electronic address:

Objectives: The objective of this study was to identify the factors predictive of the success of external cephalic version (ECV).

Methods: A single-centre retrospective observational study was performed in the maternity ward of the Angers University Hospital, France, between January 2010 and May 2020. The study included all patients (n = 613) for whom an ECV was performed for a breech or transverse foetus. The primary endpoint was measured by the success of the ECV, defined by the visualisation, using pelvic ultrasound, of the foetus in cephalic presentation immediately after the manoeuvre. Following to the ECV, the cohort was separated into two groups; ECV Success and ECV Failure. In order to determine the predictive factors of success, a logistic regression model was performed, including the parameters of: parity, foetal presentation during ECV, the side of the foetal back, placental location, type of operator and maternal age. The results are presented as (odds ratio [confidence intervals]; p-value). The significance threshold was defined by a p-value < 0.05.

Results: The ECV success rate was 21.4% (131/613). The factors predictive of the success of ECV were: transverse foetal presentation (2.7 [1.3-5.6]; p<0.01); a senior physician operator (1.6 [1.2-2]; p<0.01); multiparity (1.6 [1.2-2]; p<0.01); non anterior placental localization (1.4 [1.1-2]; p<0.01). A number of attempts greater than 3 were significantly associated with reduced chances of success (0.3 [0.2-0.4]; p<0.01).

Conclusion: The study shows that transverse foetal presentation, a senior physician operator, multiparity, as well as a non-anterior placental location are factors predictive of the success of ECV. Knowledge of these factors can improve the information given to patients.
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http://dx.doi.org/10.1016/j.jogoh.2021.102165DOI Listing
May 2021

Surgical management of urinary tract endometriosis: a one-year longitudinal multicenter pilot study in 31 French hospitals (by the FRIENDS group).

J Minim Invasive Gynecol 2021 May 5. Epub 2021 May 5.

Department of Obstetrics and Gynecology, Hôpital Universitaire de la Croix Rousse, Hospices Civils de Lyon, Université Lyon 1, France.

Study Objectives: To describe the surgical management and the risks of postoperative complications of patients suffering from urinary tract endometriosis (UTE) in France in 2017.

Design: Multicentric retrospective cohort pilot study.

Setting: Department of Gynecology in 31 expert endometriosis centers.

Patients: All women managed surgically for UTE, from January 1 to December 31 2017. We distinguished patient with isolated bladder endometriosis (IBE) or isolated ureteral endometriosis (IUE) and patients associating both locations (mixed locations, ML).

Intervention: Surgeons belonging to the FRIENDS group enrolled patients by filling a 24 items questionnaire on the day of the inclusion and three month later. Data were collected on operative routes, surgical management and postoperative complications according to the Clavien-Dindo classification, in a single anonymized database.

Measurement And Main Results: A total of 232 patients from 31 centers were included. IBE was found in 82 patients (35.3%), IUE in 126 patients (54.4%) 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 cases respectively. Among the 150 ureteral lesions (IUE and ML), 114 were managed with ureterolysis (76%), 28 with ureteral resections (18.7%), 4 with nephrectomies (2.7%) and 23 with cystectomies (15.3%). Concerning bladder endometriosis, a partial cystectomy was performed in 94.3% of 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 one 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 compared to other procedures. Prospective controlled studies are still mandatory to assess the best surgical management for the patients.
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http://dx.doi.org/10.1016/j.jmig.2021.04.020DOI Listing
May 2021

Delivery Mode After Manual Rotation of Occiput Posterior Fetal Positions: A Randomized Controlled Trial.

Obstet Gynecol 2021 06;137(6):999-1006

Department of Obstetrics, the Department of Biostatistics and Methodology, the Department of Neonatal Medicine, the Department of Reproductive Medicine, Angers University Hospital, and the MITOVASC Institute, CNRS 6015, INSERM U1083, Angers University, Angers, and CESP-INSERM, U1018, Team 7, Reproductive and Sexual Health, Paris-Sud University, Kremlin-Bicêtre, France.

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.
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http://dx.doi.org/10.1097/AOG.0000000000004386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132900PMC
June 2021

The impact of the COVID-19 coronavirus pandemic on the surgical management of gynecological cancers: Analysis of the multicenter database of the French SCGP and the FRANCOGYN group.

J Gynecol Obstet Hum Reprod 2021 Mar 28;50(8):102133. Epub 2021 Mar 28.

Departement of Obstetrics and Gynecology, Angers University Hospital, Angers, France; CESP-INSERM, U1018, Team 7, Reproductive and sexual health, Paris-Sud University, 94276 Villejuif, France. Electronic address:

Introduction: The coronavirus SARS-CoV-2 (COVID-19) pandemic has put tremendous pressure on the French healthcare system. Almost all hospital departments have had to profoundly modify their activity to cope with the crisis. In this context, the surgical management of cancers has been a topic of debate as care strategies were tailored to avoid any delay in treatment that could be detrimental to patient wellbeing while being careful not to overload intensive care units. The primary objective of this study was to observe changes in the surgical management of pelvic cancers during the COVID-19 pandemic in France.

Material And Methods: This study analyzed data from the prospective multi-center cohort study conducted by the French Society for Pelvic and Gynecological Surgery (SCGP) with methodological support from the French (FRANCOGYN) Group. All members of the SCGP received by e-mail a link allowing them to include patients who were scheduled to undergo gynecological carcinologic surgery between March 16th 2020 and May 11th 2020. Demographic data, the characteristics of cancers and the impact of the crisis in terms of changes to the usual recommended coarse of care were collected.

Results: A total of 181 patients with a median age 63 years were included in the cohort. In total, 31 patients had cervical cancer, 76 patients had endometrial cancer, 52 patients had ovarian or tubal cancer, 5 patients had a borderline tumor of the ovary, and 17 patients had vulvar cancer. During the study period, the care strategy was changed for 49 (27%) patients with postponed for 35 (19.3%) patients, and canceled for 7 (3.9%) patients. Surgical treatment was maintained for 139 (76.8%) patients. Management with neoadjuvant chemotherapy was offered to 19 (10,5%) patients and a change in surgical choice was made for 5 (2,8%) patients. In total, 8 (4,4%) patients tested positive for COVID-19. Data also shows a greater number of therapeutic changes in cases of ovarian cancer as well as a cancelation of a lumbo-aortic lymphadenectomy in one patient with cervical cancer. Hospital consultants estimated a direct detrimental impact of the COVID-19 pandemic for 39 patients, representing 22% of gynecological cancers.

Conclusion: This study provided observational data of the impact of the COVID-19 health crisis on the surgical management of gynecological cancers.
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http://dx.doi.org/10.1016/j.jogoh.2021.102133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004475PMC
March 2021

Female urine incontinence: (VEL) effectiveness and safety.

Horm Mol Biol Clin Investig 2020 Oct 30;41(4). Epub 2020 Oct 30.

Vaginal Erbium Laser Academy Italia, Livorno, Italy.

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.
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http://dx.doi.org/10.1515/hmbci-2020-0012DOI Listing
October 2020

Effects of clitoral reconstruction for female genital mutilation on perinatal outcomes: A retrospective case-control study.

J Gynecol Obstet Hum Reprod 2021 May 17;50(5):101954. Epub 2020 Oct 17.

Department of Obstetrics & Gynecology, University Hospital of Angers, Angers, France. Electronic address:

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.

Material And Methods: Retrospective case-control study at Angers University Hospital, between 2005 and 2017.

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. At birth, the main outcomes were the need for episiotomy and having an intact perineum after delivery.

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 < 0.01). CR reduces the risk of episiotomy (aOR = 0.15, 95 %CI [0.04-0.56]; p < 0.01) after adjusting on the infant weight and the need for instrumental delivery. In the CR group, 47 % of the patients had an intact perineum after delivery, compared to 20.4 % in the control group (p = 0.04). CR increases the odds of having an intact perineum at birth by 3.46 times (CI95 %[1.04-11.49]; p = 0.04).

Conclusion: CR after FGM increases the chances of having an intact perineum after delivery by 3.46 times and reduces the risk of episiotomy by 0.15 times compared to women with FGM who did not underwent CR.
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http://dx.doi.org/10.1016/j.jogoh.2020.101954DOI Listing
May 2021

Quality of advanced ovarian cancer surgery: A French assessment of ESGO quality indicators.

Eur J Surg Oncol 2021 02 11;47(2):360-366. Epub 2020 Aug 11.

Department of Surgical Oncology, Institut Cancérologie de L'Ouest, Nantes, Saint Herblain, France.

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.
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http://dx.doi.org/10.1016/j.ejso.2020.08.003DOI Listing
February 2021

Benefits of an oocyte pickup simulation training program using a high-fidelity simulator (PickUpSim) for obstetrics and gynaecology residents: an observational survey study.

J Obstet Gynaecol 2020 Aug 18:1-6. Epub 2020 Aug 18.

Department of Obstetrics and Gynaecology, Angers University Hospital, Angers, France.

The aim of this study was to evaluate an oocyte pick-up (OPU) simulation training program for residents using the high fidelity PickUpSim (Accurate, Cesena, Italy) simulator. The authors carried out an observational study during an OPU simulation workshop. A successful scenario was defined as an oocyte retrieval rate ≥70% without any complications. Forty-six residents affiliated to 23 different French university hospitals were included, and 37/46 (80.4%) of them successfully completed the scenario with a mean time of 3.4 ± 1.1 minutes. The oocyte retrieval rate was 442/561 (78.8%). All residents found training beneficial and 41/46 (87%) were in favour of having simulation-based training programs for OPU in their reproductive medicine departments. All residents who had previous experience with OPU (11/11) recommended the use of a simulator before performing OPU. This study confirms that high-fidelity OPU simulation is a simple and efficient method for training residents.Impact statement Simulator-based training has been shown to be effective and useful for oocyte pick-up (OPU) training. All residents found the simulation program beneficial and formative, with 80% successfully completing their scenarios in a mean time of 3.4 ± 1.1 minutes. All residents who had previous experience with OPU recommended the use of a simulator before performing OPU. Prospective studies are needed to confirm the short- and long-term positive clinical impact of OPU simulation training programs.
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http://dx.doi.org/10.1080/01443615.2020.1789951DOI Listing
August 2020

Endometriosis Lowers the Cumulative Live Birth Rates in IVF by Decreasing the Number of Embryos but Not Their Quality.

J Clin Med 2020 Aug 1;9(8). Epub 2020 Aug 1.

Reproductive Biology Unit, Angers University Hospital, 49000 Angers, France.

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 [0.66-1.12]; = 0.3). The implantation rate and the live birth rate per cycle were comparable between the two groups ( = 0.05), but the cumulative live births rate was significantly lower in in the endometriosis group (32.1% versus 50.7%, = 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.
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http://dx.doi.org/10.3390/jcm9082478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464781PMC
August 2020

Conversion of in vitro fertilization cycles to intrauterine inseminations in patients with a poor ovarian response: Risk of multiple pregnancies.

J Gynecol Obstet Hum Reprod 2020 Oct 11;49(8):101831. Epub 2020 Jun 11.

Department of Reproductive Medicine, Angers University Hospital, Angers, France. Electronic address:

Purpose: To determine the risk of multiple pregnancies (MP) following conversion of in vitro fertilization (IVF) cycles to intrauterine insemination (IUI) when a poor ovarian response (POR) is diagnosed during controlled ovarian stimulation (COS).

Methods: We undertook a retrospective study in our teaching hospital from January 2012 to December 2017. We included all IVF cycles with POR that were converted to IUI (<5 follicles ≥ 14 mm and peak estradiol level < 1000 pg/mL on trigger day).

Results: Overall, 205 IVF cycles that were converted to IUI in 128 patients were analyzed. Mean age was 34.1 ± 4.6 years, mean antral follicle count was 11 ± 5.3 and mean AMH was 1.8 ± 2.9 ng/L. The main causes of infertility were unexplained (41 %) (84/205) and diminished ovarian reserve (35 %) (72/205). Of all the cycles converted to IUI, 53 (26 %) had one mature follicle on trigger day, 56 (27 %) had 2, 56 (27 %) had 3, and 40 (20 %) had 4. The live birth rate (LBR) was 7.3 % (15/205), and the miscarriage rate was 28.6 % (6/21). There were 3 twin pregnancies, but no higher order pregnancies; the MP rate was 14.3 % (3/21). There was no significant difference in the MP rate between patients with 1-2 mature follicles and patients with 3-4 mature follicles (18.2 % vs 10 %, p = 0.99, respectively).

Conclusion: In IVF cycles converted to IUI for poor response, the risk of MP is acceptable (14 %) with no higher order pregnancies, even with 3 or 4 follicles ≥14 mm on trigger day.
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http://dx.doi.org/10.1016/j.jogoh.2020.101831DOI Listing
October 2020

Elevated Levels of Monocyte Chemotactic Protein-1 in the Follicular Fluid Reveals Different Populations among Women with Severe Endometriosis.

J Clin Med 2020 May 1;9(5). Epub 2020 May 1.

Unité Mixte de Recherche MITOVASC, équipe Mitolab, Centre National de la Recherche Scientifique 6015, Institut National de la Santé et de la Recherche Médicale U1083, Université d'Angers, 49000 Angers, France.

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 ( = 23), which had FF MCP-1 levels comparable to the control group, and MCP-1-high ( = 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 ( = 0.002) and a significantly lower number of oocytes recovered ( = 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.
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http://dx.doi.org/10.3390/jcm9051306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291127PMC
May 2020

The cytokine profile of follicular fluid changes during ovarian ageing.

J Gynecol Obstet Hum Reprod 2020 Apr 3;49(4):101704. Epub 2020 Feb 3.

Reproductive Biology Unit, Angers University Hospital, 49000, Angers, France; MITOVASC Institute, CNRS 6015, INSERM U1083, Angers University, 49000, Angers, France.

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 ± 16.11 pg/mL) than in the NOR group (24.39 ± 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.
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http://dx.doi.org/10.1016/j.jogoh.2020.101704DOI Listing
April 2020

Endometrial preparation for frozen-thawed embryo transfer in an artificial cycle: transdermal versus vaginal estrogen.

Sci Rep 2020 01 22;10(1):985. Epub 2020 Jan 22.

Department of Reproductive Medicine, Angers University Hospital, 4 rue Larrey, 49100, Angers, France.

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 < 0.001). The rate of cycle cancelation was comparable between the two groups (12.6% vs 8.5%, p = 0.24). Serum estradiol levels were significantly lower (268 vs 1332 pg/ml, p < 0.001), and serum LH levels were significantly higher (12.1 ± 16.5 vs 5 ± 7.5 mIU/ml, p < 0.001) in the T-group. Patient satisfaction was higher in the T-group (p = 0.04) and 85.7% (36/42) of women who had received both treatments preferred the transdermal over the vaginal route. Live birth rates were comparable between the two groups (18% vs 19%, p = 0.1). Transdermal estrogen in artificial FET cycles was associated with higher ET, shorter treatment duration and better tolerance.
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http://dx.doi.org/10.1038/s41598-020-57730-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976623PMC
January 2020

Lactic Acidosis Together with GM-CSF and M-CSF Induces Human Macrophages toward an Inflammatory Protumor Phenotype.

Cancer Immunol Res 2020 03 10;8(3):383-395. Epub 2020 Jan 10.

Université d'Angers, CHU d'Angers, Inserm U1232, CRCINA, Angers, France.

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 (VEGF 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.
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http://dx.doi.org/10.1158/2326-6066.CIR-18-0749DOI Listing
March 2020

Metabolomics shows no impairment of the microenvironment of the cumulus-oocyte complex in women with isolated endometriosis.

Reprod Biomed Online 2019 Dec 12;39(6):885-892. Epub 2019 Aug 12.

Department of Reproductive Medicine, Angers University Hospital, Angers 49000, France; MITOVASC Institute, CNRS 6015, INSERM U1083, Angers University, Angers 49000, France; Reproductive Biology Unit, Angers University Hospital, Angers 49000, France.

Research Question: Is there any metabolomic evidence of impairment of the cumulus-oocyte complex (COC) microenvironment in the follicular fluid of women with endometriosis?

Design: A prospective observational study from January to July 2018 at the Angers University Hospital, France. Seventy-nine women undergoing IVF with or without intracytoplasmic sperm injection (ICSI) were included: 39 for endometriosis-related infertility and 40 controls with other causes of infertility. A targeted quantitative metabolomic and lipidomic analysis was performed.

Results: Patient characteristics (age, body mass index, smoking status, hormonal profile and ovarian reserve markers) were comparable between the endometriosis and the control groups. There was no significant difference in the cumulative FSH dose used for stimulation between the endometriosis and the control groups (2732 versus 2257 IU, respectively). There were no differences in the oocyte maturity rates (72.2% versus 77.7%), or in the fertilization rates in IVF and ICSI (49.4% versus 50.2% and 76.4% versus 68.8%, respectively) between the endometriosis and control groups. Among the 188 metabolites analysed, 150 were accurately measured. Univariate analysis did not reveal any significant modification of metabolite concentrations, and none of the multivariate models discriminated between the two groups of patients, even when the study was restricted to the most severe form of endometriosis.

Conclusions: No specific metabolomic signature of endometriosis was found in the follicular fluid of women undergoing IVF. These results suggest that there is no microenvironmental impairment of the COC in cases of isolated endometriosis among women with infertility.
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http://dx.doi.org/10.1016/j.rbmo.2019.08.001DOI Listing
December 2019

A mathematical model to predict mean time to delivery following cervical ripening with dinoprostone vaginal insert.

Sci Rep 2019 07 9;9(1):9910. Epub 2019 Jul 9.

Department of Obstetrics and Gynecology, Angers University Hospital, Angers, France.

The main objective of our study was to analyze the mean time to delivery following cervical ripening with a 10 mg dinoprostone vaginal insert. We performed a retrospective observational study at the level III maternity ward of Angers university hospital. We included all women who had cervical ripening with dinoprostone between January 1, 2015 and September 30, 2016. Overall, 405 patients were included, and 59.3% (240/405) were nulliparous. The mean time to delivery was 20h39 min ± 10h49 min. 21% of deliveries (86/405) occurred between midnight and 6 h a.m., and the cesarean section rate was 33% (132/405). Multiple regression analysis showed that nulliparity, overweight (BMI ≥ 25), a closed cervix on initial examination and the absence of premature rupture of membranes (PRM) all significantly increased the mean time to delivery. We developed a mathematical model integrating the aforementioned factors and their impact to help predict the mean time to delivery following cervical ripening with dinoprostone vaginal insert: Y = 961.188-80.346 × parity + 21.437 × BMI-165.263 × cervical dilation-241.759 × PRM. This equation allows obstetricians to calculate a personalized time to delivery for each patient, allowing a precise scheduling of dinoprostone insert placement, and thus improving the organization in busy maternity wards.
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http://dx.doi.org/10.1038/s41598-019-46101-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616328PMC
July 2019

The surgical treatment of idiopathic abnormal uterine bleeding: An analysis of 88 000 patients from the French exhaustive national hospital discharge database from 2009 to 2015.

PLoS One 2019 11;14(6):e0217579. Epub 2019 Jun 11.

Hôpital Bicêtre, Le Kremlin-Bicêtre, France.

Objective: The objective of the study was to compare success rates, complications and management costs of different surgical techniques for abnormal uterine bleeding (AUB).

Methods: This was a retrospective analysis of the French national hospital discharge database. All hospital stays with a diagnostic code for AUB and an appropriate surgical procedure code between 2009 and 2015 inclusive were identified, concerning 109,884 women overall. Outcomes were compared between second generation procedures (2G surgery), first-generation procedures (1G surgery), curettage and hysterectomy. Clinical outcomes were treatment failure and complications during the follow-up period. Costs were attributed using standard French hospital tariffs.

Results: 7,863 women underwent a 2G procedure (7.2%), 39,935 a 1G procedure, (36.3%), 38,923 curettage (35.4%) and 23,163 hysterectomy (21.1%). Failure rates at 18 months were 9.9% for 2G surgery, 12.7% for 1G surgery, 20.6% for curettage and 2.8% for hysterectomy. Complication rates at 18 months were 1.9% for 2G surgery, 1.5% for 1G surgery, 1.4% for curettage and 5.3% for hysterectomy. Median 18-month costs were € 1 173 for 2G surgery, € 1 059 for 1G surgery, € 782 for curettage and € 3 090 for hysterectomy.

Conclusion: Curettage has the highest failure rate. Hysterectomy has the lowest failure rate but the highest complication rate and is also the most expensive. Despite good clinical outcomes and relatively low cost, 1G and 2G procedures are not widely used. Current guidelines for treatment of AUB are not respected, the recommended 2G procedures being only used in <10% of cases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217579PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559634PMC
February 2020

ConFIRM trial - conversion of in vitro fertilization cycles to intrauterine inseminations in patients with a poor ovarian response to stimulation: a protocol for a multicentric, prospective randomized trial.

Trials 2018 Oct 17;19(1):565. Epub 2018 Oct 17.

Department of Reproductive Medicine, Angers University Hospital, 4 rue Larrey, 49000, Angers, France.

Background: To date, there is no consensus on the ideal management strategy of patients with poor ovarian response (POR) to controlled ovarian stimulation (COS) for in vitro fertilization (IVF). Currently, these patients are given the choice of: (1) canceling the cycle; (2) proceeding with COS regardless of the poor response, and performing the oocyte retrieval and transfer of embryos when available; or (3) conversion to an intrauterine insemination (IUI). When the decision to proceed with the COS cycle is taken, it is not clear whether IVF or conversion to IUI is the best choice. If live birth rates were comparable between the two strategies, conversion to IUI would be the better option for poor responders, since it is less invasive and is associated with a lower cost.

Methods: We designed a non-inferiority, multicentric, randomized controlled trial that will be conducted in 18 French Reproductive Medicine centers. We defined POR as the presence of only two or four mature follicles ≥ 14 mm on ovulation trigger day. Patients with POR will be randomized into two parallel arms: "IVF" and "conversion to IUI." Our main objective is to compare the efficiency of IVF and conversion to IUI in patients with POR to COS. The primary outcome is the live birth rate, defined as the birth of a living infant after 22 weeks' gestational age, or weighing ≥ 500 g. One of the secondary objectives is to compare the cost-efficiency of both strategies at 12 months. We will need to include 940 patients (470 in each arm), and the duration of the inclusion period is estimated to be 36 months.

Discussion: This is the first randomized controlled trial to compare the outcomes of IVF and embryo transfer to conversion to IUI in patients with POR to COS. If our study shows that conversion to IUI is non-inferior to IVF in terms of clinical efficiency and live birth rate, it would confirm IUI as a better alternative for patients, both individually (less invasive and more patient-friendly) and collectively (lower cost).

Trials Registration: ClinicalTrials.gov, ID: NCT03362489 . Registered on January 10th, 2018.
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http://dx.doi.org/10.1186/s13063-018-2936-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192099PMC
October 2018

Giant condyloma acuminatum of the vulva: Successful management with imiquimod.

JAAD Case Rep 2018 Aug 15;4(7):692-694. Epub 2018 Aug 15.

Department of Obstetrics and Gynecology, Angers University Hospital, Angers, France.

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http://dx.doi.org/10.1016/j.jdcr.2018.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098202PMC
August 2018

Recurrent pregnancy loss: current perspectives.

Int J Womens Health 2017 17;9:331-345. Epub 2017 May 17.

Department of Obstetrics and Gynecology, Angers University Hopsital, Angers, France.

Recurrent pregnancy loss is an important reproductive health issue, affecting 2%-5% of couples. Common established causes include uterine anomalies, antiphospholipid syndrome, hormonal and metabolic disorders, and cytogenetic abnormalities. Other etiologies have been proposed but are still considered controversial, such as chronic endometritis, inherited thrombophilias, luteal phase deficiency, and high sperm DNA fragmentation levels. Over the years, evidence-based treatments such as surgical correction of uterine anomalies or aspirin and heparin for antiphospholipid syndrome have improved the outcomes for couples with recurrent pregnancy loss. However, almost half of the cases remain unexplained and are empirically treated using progesterone supplementation, anticoagulation, and/or immunomodulatory treatments. Regardless of the cause, the long-term prognosis of couples with recurrent pregnancy loss is good, and most eventually achieve a healthy live birth. However, multiple pregnancy losses can have a significant psychological toll on affected couples, and many efforts are being made to improve treatments and decrease the time needed to achieve a successful pregnancy. This article reviews the established and controversial etiologies, and the recommended therapeutic strategies, with a special focus on unexplained recurrent pregnancy losses and the empiric treatments used nowadays. It also discusses the current role of preimplantation genetic testing in the management of recurrent pregnancy loss.
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http://dx.doi.org/10.2147/IJWH.S100817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440030PMC
May 2017

Papillomavirus and cancers: should we extend vaccination to boys in France?

J Public Health (Oxf) 2017 12;39(4):e229-e234

Service de Gynécologie-Obstétrique, Clinique Universitaire, Maternité Régionale Universitaire, Nancy, France.

Background: In 2006, the HPV (Human papillomavirus) 6/11/16/18 quadrivalent vaccine was approved by the European Medicines Agency and obtained its marketing authorization in both girls and boys. Currently, the French guidelines recommend and refund vaccination of girls aged 11 to 14 with a catch-up program for females from 15 to 19 years old.

Discussion: In France, HPV vaccination coverage tends to decrease. At the end of 2015, the vaccination coverage with three doses reached only 14% in 16-year-old girls (three doses). Although men are also affected by HPV-related diseases such as anal cancer, ano-genital warts, penile cancer or upper aerodigestive tract cancer, vaccine recommendations in France are for girls only. To face the high prevalence of anal cancer and related diseases, the best option is vaccination. Moreover, by offering men a way to prevent diseases against which they do not have any protection yet, universal vaccination could better take into account the ethical issues of prevention. In this paper, we present the point of view of different medical specialties concerning the potential benefit of extending vaccination to boys.

Conclusion: HPV vaccination of both genders could benefit from a better public acceptance and contribute to a better coverage, especially in countries with low vaccination rates.
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http://dx.doi.org/10.1093/pubmed/fdw099DOI Listing
December 2017

The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27.

Oncoimmunology 2016 Jul 28;5(7):e1178025. Epub 2016 Apr 28.

CRCNA, INSERM, CNRS, Université de Nantes, Université d'Angers, Angers, France; LabEx ImmunoGraftOnco, Angers, France; Equipe labellisée Ligue contre le Cancer, Angers, France.

Tumor-associated macrophages (TAM) are immunosuppressive cells that can massively accumulate in the tumor microenvironment. In patients with ovarian cancer, their density is correlated with poor prognosis. Targeting mediators that control the generation or the differentiation of immunoregulatory macrophages represents a therapeutic challenge to overcome tumor-associated immunosuppression. The ectonucleotidase CD39 hydrolyzes ATP into extracellular adenosine that exhibits potent immunosuppressive properties when signaling through the A2A adenosine receptor. We report here that CD14(+) CD163(+) TAM isolated from ovarian cancer patients and macrophages generated in vitro with M-CSF, express high levels of the membrane ectonucleotidase CD39 compared to classically activated macrophages. The CD39 inhibitor POM-1 and adenosine deaminase (ADA) diminished some of the immunosuppressive functions of CD14(high) CD163(high) CD39(high) macrophages, such as IL-10 secretion. We identified the cytokine IL-27, secreted by tumor-infiltrating neutrophils, located close to infiltrating CD163(+) macrophages, as a major rheostat of CD39 expression and consequently, on the acquisition of immunoregulatory properties by macrophages. Accordingly, the depletion of IL-27 downregulated CD39 and PD-L1 expression as well as IL-10 secretion by M-CSF-macrophages. Collectively, these data suggest that CD39, drived by IL-27 and CD115 ligands in ovarian cancer, maintains the immunosuppressive phenotype of TAM. This work brings new information on the acquisition of immunosuppressive properties by tumor-infiltrating macrophages.
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http://dx.doi.org/10.1080/2162402X.2016.1178025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006905PMC
July 2016

Ovarian ageing: the role of mitochondria in oocytes and follicles.

Hum Reprod Update 2016 11 25;22(6):725-743. Epub 2016 Aug 25.

PREMMi/Pôle de Recherche et d'Enseignement en Médecine Mitochondriale, Institut MITOVASC, CNRS 6214, INSERM U1083, Université d'Angers, Angers, France.

Background: There is a great inter-individual variability of ovarian ageing, and almost 20% of patients consulting for infertility show signs of premature ovarian ageing. This feature, taken together with delayed childbearing in modern society, leads to the emergence of age-related ovarian dysfunction concomitantly with the desire for pregnancy. Assisted reproductive technology is frequently inefficacious in cases of ovarian ageing, thus raising the economic, medical and societal costs of the procedures.

Objective And Rational: Ovarian ageing is characterized by quantitative and qualitative alteration of the ovarian oocyte reserve. Mitochondria play a central role in follicular atresia and could be the main target of the ooplasmic factors determining oocyte quality adversely affected by ageing. Indeed, the oocyte is the richest cell of the body in mitochondria and depends largely on these organelles to acquire competence for fertilization and early embryonic development. Moreover, the oocyte ensures the uniparental transmission and stability of the mitochondrial genome across the generations. This review focuses on the role played by mitochondria in ovarian ageing and on the possible consequences over the generations.

Search Methods: PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews concerning mitochondria and ovarian ageing, in animal and human species. Searches were performed using keywords belonging to three groups: 'mitochondria' or 'mitochondrial DNA'; 'ovarian reserve', 'oocyte', 'ovary' or 'cumulus cells'; and 'ageing' or 'ovarian ageing'. These keywords were combined with other search phrases relevant to the topic. References from these articles were used to obtain additional articles.

Outcomes: There is a close relationship, in mammalian models and humans, between mitochondria and the decline of oocyte quality with ageing. Qualitatively, ageing-related mitochondrial (mt) DNA instability, which leads to the accumulation of mtDNA mutations in the oocyte, plays a key role in the deterioration of oocyte quality in terms of competence and of the risk of transmitting mitochondrial abnormalities to the offspring. In contrast, some mtDNA haplogroups are protective against the decline of ovarian reserve. Quantitatively, mitochondrial biogenesis is crucial during oogenesis for constituting a mitochondrial pool sufficiently large to allow normal early embryonic development and to avoid the untimely activation of mitochondrial biogenesis. Ovarian ageing also seriously affects the dynamic nature of mitochondrial biogenesis in the surrounding granulosa cells that may provide interesting alternative biomarkers of oocyte quality.

Wider Implications: A fuller understanding of the involvement of mitochondria in cases of infertility linked to ovarian ageing would contribute to a better management of the disorder in the future.
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http://dx.doi.org/10.1093/humupd/dmw028DOI Listing
November 2016

Mortality and morbidity in early preterm breech singletons: impact of a policy of planned vaginal delivery.

Eur J Obstet Gynecol Reprod Biol 2015 Sep 26;192:61-5. Epub 2015 Jun 26.

Department of Obstetrics and Gynecology, Angers University Hospital, Angers, France.

Objective: To compare neonatal morbidity and mortality rates in preterm singleton breech deliveries from 26(0/7) to 29(6/7) weeks of gestation in centers with a policy of either planned vaginal delivery (PVD) or planned cesarean delivery (PCD).

Study Design: Women with preterm singleton breech deliveries occurring after preterm labor or preterm premature rupture of membranes (pPROM) were identified from the databases of five perinatal centers and classified as PVD or PCD according to the center's management policy. The independent association between planned mode of delivery and the risk of neonatal hospital death or morbidity was tested and quantified with ORs through two-level multivariable logistic regression modeling.

Results: Of 142 782 deliveries during the study period, 626 (0.4%) were singletons in breech presentation from 26(0/7) to 29(6/7) weeks of gestation: after exclusions, 130 were in the PVD group and 173 in the PCD group. Severe newborn morbidity was similar in the two groups. Newborn mortality was 12% in the PCD group and 16% in the PVD group. Three neonates (1.7%, 95% CI: 0.34-5.0) died from head entrapment after vaginal delivery in the PVD group. Nonetheless, the policy of PVD was not associated with increased risks of neonatal death (aOR: 1.01, 95% CI: 0.33-2.92) or severe morbidity.

Conclusion: Risks of mortality and severe morbidity in preterm breech were not increased by a policy of vaginal delivery. Head entrapment leading to death is however possible in cases of vaginal delivery but its rarity should be balanced with the maternal consequences of early preterm cesarean delivery.
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http://dx.doi.org/10.1016/j.ejogrb.2015.06.019DOI Listing
September 2015

Policy of high-dose tranexamic acid for treating postpartum hemorrhage after vaginal delivery.

J Matern Fetal Neonatal Med 2016 29;29(10):1617-22. Epub 2015 Jun 29.

a Department of Obstetrics and Gynecology , Angers University Hospital , Angers , France.

Objective: To assess whether a policy of routine administration of high-dose tranexamic acid (TA) at the diagnosis of postpartum hemorrhage (PPH) reduces blood loss after vaginal birth.

Methods: This controlled single-center before-and-after study of all women with PPH ≥ 500 ml after vaginal birth took place from January 2011 through March 2012; the control group included those seen from January 2011 through August 2011, and the case patients those from September 2011 through March 2012. Our protocol for the management of PPH was modified effective September 2011 to include administration of high-dose TA (4 g of TA intravenously then 1 g/h for 6 h) once blood loss reached 800 ml. Our primary objective was to assess the efficacy of this policy in reducing blood loss in PPH.

Results: Maternal characteristics did not differ between the two groups. Mean estimated blood loss was not significantly lower in the TA group (n = 138) than in the control group (n = 151) (respectively, 915.7 ± 321 ml versus 944.8 ± 313.8 ml; p = 0.47). The difference between pre- and post-delivery hemoglobin levels were lower in the TA group (-2.6 g/dl ± 1.2 versus -2.9 g/dl ± 1.3; p = 0.09), but it was not significant. Postpartum iron sucrose injections were significantly less frequent in the TA than the control group (2.2% versus 9.9%; p < 0.05).

Conclusions: A policy of high-dose TA in PPH after vaginal deliveries was not associated with a significant reduction of blood loss.
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http://dx.doi.org/10.3109/14767058.2015.1056731DOI Listing
December 2016

Amniotic fluid embolism after uterine artery embolization for uterine fibroids.

Eur J Obstet Gynecol Reprod Biol 2015 Aug 3;191:144-5. Epub 2015 Jun 3.

Department of Obstetrics and Gynecology, Angers University Hospital, Angers, France.

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http://dx.doi.org/10.1016/j.ejogrb.2015.05.006DOI Listing
August 2015

Acute renal colic during pregnancy: management and predictive factors.

Can J Urol 2015 Apr;22(2):7732-8

Angers University Hospital, Angers, France.

Introduction: The aim of this study was to identify predictive factors of urolithiasis etiology for acute renal colic (ARC) during pregnancy.

Materials And Methods: We performed a retrospective review of all pregnant women hospitalized for an ARC between January 2007 and October 2012 in the department of Obstetrics and Gynecology of a University Hospital. Univariate and multivariate regression models were used to assess potential predictive factors of urolithiasis etiology.

Results: We included 82 patients. A urolithiasis was identified in 24 (29.3%) patients. In univariate analysis, we identified the following predictive factors for a urolithiasis etiology: primiparity (p = 0.017), leukocyturia (p = 0.021), left hydronephrosis > 10 mm and > 15 mm (p = 0.009; p = 0.02) and right hydronephrosis > 15 mm (p = 0.019). In multivariate analysis, only left hydronephrosis > 10 mm remained predictive for a urolithiasis etiology (p = 0.036; HR 7.45). A ureteral stenting was necessary for 23 patients (28.0%). Three patients (3.7%) had a premature membrane rupture and two patients (2.4%) delivered prematurely. After delivery, 10 patients (12.2%) required surgical treatment.

Conclusion: Left hydronephrosis was related to urolithiasic etiology for ARC. Obstetrical consequences of ARC were minor.
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April 2015