Genetic landscape of a large cohort of Primary Ovarian Insufficiency : New genes and pathways and implications for personalized medicine

Background Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yield-ing infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology.Methods 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. Findings A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromo-somal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link.Interpretation We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogene-sis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility.Funding Universite? Paris Saclay, Agence Nationale de Biome?decine.Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

La chirurgie bariatrique est-elle efficace dans l'obésité hypothalamique secondaire au craniopharyngiome ?

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Maintenance of a Gastric Pacemaker in the Excluded Stomach During a Roux-en-Y Gastric Bypass Procedure in a Patient with Obesity, Type 1 Diabetes and Refractory Gastroparesis

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Nutritional Status of Vegetarian Patients Before and After Bariatric Surgery: a Monocentric Retrospective Observational Case–Control Study

International audienceAbstract: The obesity pandemic is associated with an increasing number of bariatric surgeries which allow improvement in obesity-related comorbidities and life expectancy but potentially induce nutritional deficiencies. Vegetarianism becomes more and more popular and exposes as well to vitamin and micronutrient deficiencies. Only one study has explored the impact of vegetarianism on the preoperative nutritional status of eligible patients for bariatric surgery, but none in postoperative care. Materials and Methods: We conducted a retrospective case–control study in our cohort of bariatric patients, matching 5 omnivores for each vegetarian. We compared their biological profile regarding vitamin and micronutrient blood levels before and 3, 6, 12, and 30 months after surgery. Results: We included 7 vegetarians including 4 lacto-ovo-vegetarians (57%), 2 lacto-vegetarians (29%), and one lacto-ovo-pesco-vegetarian (14%). Three years after surgery with equivalent daily standard vitamin supplementation, the two groups showed a similar biological profile including blood levels of ferritin (p = 0.6), vitamin B1 (p = 0.1), and B12 (p = 0.7), while the total median weight loss at 3 years was comparable (39.1% [27.0–46.6] in vegetarians vs 35.7% [10.5–46.5] in omnivores, p = 0.8). We observed no significant difference between vegetarians and omnivores before surgery regarding comorbidities and nutritional status. Conclusion: It seems that, after bariatric surgery, vegetarian patients taking a standard vitamin supplementation do not show an increased risk of nutritional deficiencies compared to omnivores. However, a larger study with a longer follow-up is needed to confirm these data, including an evaluation of different types of vegetarianism such as veganism. Graphical Abstract: [Figure not available: see fulltext.

Laparoscopic Revision of Bariatric Surgeries in Two Patients with Severe Resistant Hypocalcemia After Endocrine Cervical Surgery

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Changes in total sperm count after gastric bypass and sleeve gastrectomy: the BARIASPERM prospective study

International audienceBackground: The massive weight loss induced by bariatric surgery is associated with major benefits, but the effect on semen variables is still uncertain.Objectives: To explore semen modifications with gastric bypass and sleeve gastrectomy.Setting: Five French University Hospitals.Methods: Male candidates for bariatric surgery with no history of infertility were recruited in this controlled prospective study. Sperm characteristics were collected before surgery and then 6 months and up to 12 months after surgery.Results: Forty-six adult men who underwent gastric bypass (n = 20) or sleeve gastrectomy (n = 26) were included. Total sperm count tended to be lower at 6 months and showed a significant decrease at 12 months in both surgery groups, at -69.5 million (-96.8 to -42.2 million; P = 0.0021). Total sperm count at 12 months relative to baseline was -41.4 million (P = .0391) after gastric bypass and -91.1 million (P = .0080) after sleeve gastrectomy. This was counterbalanced by an associated resolution of hypogonadism and decrease of DNA fragmentation in most patients with time after surgery.Conclusion: Improvement in some semen variables after bariatric surgery observed in 3 previous studies is in contrast to the lower mean total sperm count found in this study at 1 year. The possible reversibility of this effect in the long term and the impact of surgery on fertility both remain unknown

Five-Year Changes in Weight and Diabetes Status After Bariatric Surgery for Craniopharyngioma-Related Hypothalamic Obesity: a Case–Control Study

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