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Study Question: Does the metabolomic profile of the follicular fluid (FF) of patients with a diminished ovarian reserve (DOR) differ from that of patients with a normal ovarian reserve (NOR)?Summary Answer: The metabolomic signature of the FF reveals a significant decrease in polyunsaturated choline plasmalogens and methyl arginine transferase activity in DOR patients compared to NOR patients.What Is Known Already: The composition of the FF reflects the exchanges between the oocyte and its microenvironment during its acquisition of gametic competence. Studies of the FF have allowed identification of biomarkers and metabolic pathways involved in various pathologies affecting oocyte quality, but no large metabolomic analysis in the context of ovarian ageing and DOR has been undertaken so far.Study Design, Size, Duration: This was an observational study of the FF retrieved from 57 women undergoing in vitro fertilization at the University Hospital of Angers, France, from November 2015 to September 2016. The women were classified in two groups: one including 28 DOR patients, and the other including 29 NOR patients, serving as controls.Participants/materials, Setting, Methods: Patients were enrolled in the morning of oocyte retrieval after ovarian stimulation. Once the oocytes were isolated for fertilization and culture, the FF was pooled and centrifuged for analysis. A targeted quantitative metabolomic analysis was performed using high-performance liquid chromatography coupled with tandem mass spectrometry, and the Biocrates Absolute IDQ p180 kit. The FF levels of 188 metabolites and several sums and ratios of metabolic significance were assessed by multivariate and univariate analyses.Main Results and the Role Of Chance: A total of 136 metabolites were accurately quantified and used for calculating 23 sums and ratios. Samples were randomly divided into training and validation sets. The training set, allowed the construction of multivariate statistical models with a projection-supervised method, i.e. orthogonal partial least squares discriminant analysis (OPLS-DA), applied to the full set of metabolites, or the penalized least absolute shrinkage and selection operator with logistic regression (LASSO-LR), applied to the ratios and sums of the metabolites. Both multivariate models showed good predictive performances when applied to the validation set. The final penalized model retained the three most significant variables, i.e. the total dimethylarginine-to-arginine ratio (Total DMA/Arginine), the sum of the polyunsaturated choline plasmalogens (PUFA ae), and the patient's age. The negative coefficients of Total DMA/Arginine and PUFA ae indicated that these FF variables had lower values in DOR patients than in NOR patients.Large Scale Data: N/A.Limitations Reasons For Caution: This study presents two limitations. First, with this targeted metabolomics analysis, we have explored only a limited portion of the FF metabolome. Second, although the signature found was highly significant, the mechanism underlying the dysfunction remains undetermined.Wider Implications Of the Findings: The understanding of the mechanisms implied in ovarian ageing is essential for providing an adequate response to affected women desiring pregnancy. Our study proposes an incoming signature that may open new paths towards this goal.Study Funding/competing Interest(s): This study was supported by the University Hospital of Angers, the University of Angers, and the French national research centers, INSERM and the CNRS. There were no competing interests. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: Although the clinical value of time-lapse imaging (TLI) systems in in vitro fertilization (IVF) cycles is still debated, its prevalence worldwide seems to be expanding. The situation of TLI in the USA has been recently surveyed, but these results might not be transposable to other countries with different IVF regulation and funding such as France. This study evaluated the TLI situation in French IVF laboratories., Methods: An anonymous online cross-sectional survey was sent by email to 210 embryologists in September and October 2017. Laboratories, demographics, TLI clinical use, purchasing plan, and embryologists' opinions were analyzed using logistic regression to calculate odds ratio., Results: Of the 210 lab directors surveyed, 78 responded (37.1%), 43 (55%) working in private IVF laboratories and 35 (45%) in public hospitals. Thirty (38.5%) were TLI users. The odds of TLI possession were not statistically different according to laboratory sector or size. Most embryologists (n = 21, 70%) used TLI for unselected patients. Cost was the main reason given by non-users for not implementing TLI (n = 24, 50%). Most respondents were convinced that TLI is superior to standard morphology (n = 52, 73.2%) and that TLI improves culture conditions (n = 62, 84.9%). However, half (n = 39, 54.9%) indicated that evidence was still lacking to assert TLI clinical usefulness., Conclusion: The prevalence of TLI systems and embryologists' opinion in France was slightly different from the American situation. The different regulation and funding policy might account for some differences in terms of TLI use and perception.

We report the case of a newborn with neonatal hypotonia associated to a micropenis and a bilateral cryptorchidia. The discovery of severe hypoglycemia at 0.22 mmol/L led to further biological investigations that revealed sharply decreased levels of several hypophyseal hormones. Altered corticotropic, somatotropic, thyreotropic, and gonadotropic axes finally suggested congenital hypophyseal insufficiency. This diagnostic was confirmed by a brain MRI (magnectic resonance imaging), which revealed a total interruption of the pituitary stalk. Immediate substitutive hormonal treatment allowed a clinical improvement of the condition and limited the risk of further episodes of hypoglycemia. The pituitary stalk interruption syndrome (PSIS), a very rare congenital disorder, has an estimated incidence of about 1:200.000. This developmental anomaly of the hypophysis calls for urgent diagnosis since prognosis depends on the rapid implementation of substitutive hormonal therapy. The hormonal deficit in the newborn affected by PSIS is often of a multiple nature with a constant somatotropic deficit, thus requiring the exploration of the different antehypophyseal axes. Despite the fact that PSIS is a rare disorder, it should always be kept in the differential diagnosis of newborn presenting with hypoglycemia. Since the interpretation of hormonal assays is particularly delicate at birth, close clinico-biological cooperation is essential for rapid diagnosis of PSIS and appropriate adaptation of the short- and long-term therapeutic management of the newborn.