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International audience; IntroductionPrimary ovarian insufficiency (POI) affects 1% of women under 40 years old. POI is idiopathic in more than 70% of cases. Though many candidate genes have been identified in recent years, the prevalence and pathogenicity of abnormalities are still difficult to establish.ObjectivesOur primary objective was to evaluate the prevalence of gene variations in a large prospective multicentric POI cohort. Our secondary objective was to evaluate the correlation between phenotype and genotype.Patients and MethodsTwo hundred and sixty-nine well-phenotyped POI patients were screened for variants of 18 known POI genes (BMP15, DMC1, EIF2S2, FIGLA, FOXL2, FSHR, GDF9, GPR3, HFM1, LHX8, MSH5, NOBOX, NR5A1, PGRMC1, STAG3, XPNPEP2, BHLB and FSHB) by next generation sequencing (NGS). Abnormalities were classified as “variant” or “variant of unknown signification” (VUS) according to available functional tests or algorithms (SIFT, Polyphen-2, MutationTaster).ResultsOne hundred and two patients (38%) were identified as having at least 1 genetic abnormality. Sixty-seven patients (25%) presented at least 1 variant. Forty eight patients presented at least 1 VUS (18%). Thirteen patients (5%) had combined abnormalities. NOBOX variants were the most common gene variants involved in POI (9%). Interestingly, we saw no significant differences in the previous family history of POI, ethnic origin, age at onset of POI, primary amenorrhea or secondary menstrual disturbances between the different genotypes.ConclusionIn our study, a high percentage of patients presented gene variants detected by NGS analysis (38%). Every POI patient should undergo NGS analysis to improve medical cares of the patients.

Insulin resistance is known to worsen polycystic ovarian syndrome (PCOS). The management of insulin resistance is crucial in the treatment of PCOS and insulin-sensitizing molecule as myo-inositol (MYO) seems to have promising effects. The aim of our pilot study was to study whether supplementation with MYO can improve patients' sensitivity to clomiphene citrate (CC) in terms of ovulation and pregnancy rates.This study included 26 patients with PCOS, eligible to ovulation induction with CC. All of them received MYO in combination with CC and folic acid, following the usual protocol. Results concerning ovulation and pregnancy rates were compared to those from our historical cohort of PCOS patients treated with CC alone.Ovulation rate was significantly higher with MYO+CC than with CC alone (65.5% vs. 42%, p=0.0001). The number of patients sensitive to 50 mg/d was 54% with MYO vs. 40% in our reference cohort (NS). The total resistance rate was 19% vs. 27% in the reference cohort (NS). Cumulative pregnancy rate with MYO+CC was 53.8% vs. 42.2% with CC alone (NS). Pregnancy rates per initiated cycle were 16.1% with MYO vs. 12.6% in the historical cohort (NS).Although the differences were not significant for most outcomes, probably due to the small number of patients, our pilot study seemed to show a benefit of supplementation with MYO during ovulation induction with CC in PCOS patients.This study proves the great interest of a RCT and re-opens the possibilities of insulin-sensitizing agents in the treatment of anovulatory patients with PCOS, such as natural products like MYO.

The prevalence of female obesity is increasing. Obesity leads to increased infertility and difficulties in the management of Assisted Reproductive Technology (ART). A specialized nutritional consultation was created in 2008 at University Hospital of Lille, to support infertile obese and overweight patients and to achieve a BMI below 35kg/m(2) before pregnancy. The aim of this retrospective study was to evaluate our practice of nutritional support on weight and pregnancy rate.Seventy-eight obese or overweight patients, followed in nutrition and ART for at least two years, were compared to a control group of 119 normal weight patients. The nutritional strategy was mainly based on lifestyle changes, to establish healthier food and higher physical activity.The mean initial BMI was 37.5kg/m(2) vs 35.6kg/m(2) after nutritional support (significant weight loss, [P0.001]). Obese or overweight patients had more frequently metabolic syndrome (P0.01). The chances of pregnancy, after weight loss, were similar to the control group both in IUI and IVF/ICSI. However, gonadotropin doses were increased in the obese and overweight group (P=0.007). The hypocaloric diet was the most effective nutritional strategy to achieve a weight loss greater than 5% of initial weight (P=0.017). Regular physical activity practice allowed also more frequently to achieve this goal (P=0.074). Even after weight loss, a significant number of gestational diabetes (25% of pregnancies in our population) occurred in the obese or overweight group.This nutritional consultation promotes weight loss in infertile obese or overweight patients. The maternity desire is a strong motivational lever to weight loss, which leads to satisfying pregnancy rate.

National audience; L’échographie est nécessaire avec la mammographie pour explorer une masse clinique du sein (grade B), un écoulement unipore coloré du mamelon (grade C), ou une mastite (grade C). La classification BI-RADS est recommandée pour décrire et classer les anomalies en imagerie du sein. Pour les abcès du sein, une biopsie percutanée est recommandée en cas de masse ou de symptômes persistants (grade C). Pour les mastodynies, lorsque l’imagerie du sein est normale, ni l’IRM, ni une biopsie n’est recommandée (grade C). La biopsie percutanée est recommandée pour les masses classées BI-RADS 4-5 (grade B). Pour les lésions érythémateuses persistantes aréolomamelonnaires ou les lésions d’eczéma atypique, une biopsie est recommandée (grade C). Pour la distorsion ou l’asymétrie mammaire, une macrobiopsie est recommandée en raison du risque de sous-estimation par microbiopsie (grade C). Pour les microcalcifications BI-RADS 4-5 sans signal à l’échographie, une macrobiopsie d’au moins 11 jauges est recommandée (grade B) ; en l’absence de microcalcifications sur les clichés des carottes, des prélèvements supplémentaires sont recommandés (grade B). Pour l’hyperplasie canalaire atypique, l’hyperplasie lobulaire atypique, le carcinome lobulaire in situ, la métaplasie cylindrique avec atypies, la cicatrice radiaire avec traduction radiologique, la mucocèle avec atypie, l’exérèse chirurgicale est habituellement recommandée (grade C). L’abstention est possible après concertation multidisciplinaire (grade C). Pour ces lésions, lorsque l’excision n’est pas in sano, aucune excision complémentaire n’est recommandée sauf pour le CLIS pléomorphe ou avec nécrose (grade C). Pour la phyllode de grade 1, la résection chirurgicale in sano est recommandée ; pour la phyllode de grade 2, des marges de 10 mm sont recommandées (grade C). Pour les lésions papillaires sans atypie, la disparition complète du signal radiologique est recommandée (grade C). Pour les lésions papillaires avec atypies, la résection chirurgicale complète est recommandée (grade C). Summary Breast sonography is required with mammogram to explore clinical breast mass (grade B), colored unipore breast nipple discharge (grade C), or mastitis (grade C). Bi-RADS system is recommended to describe and classify breast-imaging abnormalities. For breast abscess, a percutaneous biopsy is recommended in case of mass or persistent symptoms (grade C). For mastodynia, when breast imaging is normal, no MRI neither breast biopsy is recommended (grade C). Percutaneous biopsy is recommended for BI-RADS 4–5 mass (grade B). For persistent erythematous breast nipple or atypical eczema lesion, a nipple biopsy is recommended (grade C). For distortion and asymmetry, a vacuum core needle biopsy is recommended because of the risk of underestimation by simple core needle biopsy (grade C). For BI-RADS 4–5 microcalcifications without ultrasound signal, a vacuum core needle biopsy of at least 11 gauges is recommended (grade B); in the absence of microcalcifications on radiograph carrots, additional samples are recommended (grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial with atypia, radial scar, mucocele with atypia, surgical excision is commonly recommended (grade C). Expectant management is feasible after multidisciplinary concertation. For these lesions, when excision is not in sano, no new excision is recommended except for pleomorphic or with necrosis CLIS (grade C). For grade 1 phyllode tumour, in sano surgical resection is recommended; for grade 2 phyllode, 10-mm margins are recommended (grade C). For breast papillary without atypia, complete disappearance of the radiologic signal is recommended (grade C). For breast papillary with atypia, complete surgical excision is recommended (grade C)

Polycystic ovary syndrome (PCOS) is the most common etiology of menstrual disorders and hyperandrogenism. It is characterized by an excess of ovarian follicles. The mechanisms that underlie folliculogenesis disorder in PCOS appear to arise from primitive ovarian hyperandrogenism. This can be modulated by hormonal factors, such as LH or insulin. Ovarian hyperandrogenism results from a real theca cells dysfunction, whose origin is still poorly understood. It seems that complex genetic factors may be involved, but these have not yet been clearly identified. PCOS also results from granulosa cells dysfunction. For example, intra-ovarian factors, such as anti-mullerian hormone, are possibly involved in ovulation's disorders by blocking the physiological process of follicular recruitment. In turn, the oocyte could also be one of the actors possibly involved in the follicular excess in PCOS.