Assisted reproductive techniques do not impact late neurodevelopmental outcomes of preterm children

ObjectiveAssisted reproductive technology (ART) increases the rate of preterm births, though few studies have analyzed outcomes for these infants. No data are available on 4-year-old children born prematurely after ART. The objective was to investigate whether ART affect the neurodevelopmental outcomes at 4 years in preterm infants born before 34 weeks of gestational age (GA).Methods and resultsA total of 166 ART and 679 naturally conceived preterm infants born before 34 weeks GA between 2013 and 2015 enrolled in the Loire Infant Follow-up Team were included. Neurodevelopment was assessed at 4 years using the age and stage questionnaire (ASQ) and the need for therapy services. The association between the socio-economic and perinatal characteristics and non-optimal neurodevelopment at 4 years was estimated. After adjustment, the ART preterm group remained significantly associated with a lower risk of having at least two domains in difficulty at ASQ: adjusted odds ratio (aOR) 0.34, 95% confidence interval (CI) (0.13–0.88), p = 0.027. The factors independently associated with non-optimal neurodevelopment at 4 years were male gender, low socio-economic level, and 25–30 weeks of GA at birth. The need for therapy services was similar between groups (p = 0.079). The long-term neurodevelopmental outcomes of preterm children born after ART are very similar, or even better than that of the spontaneously conceived children

Research response to coronavirus disease 2019 needed better coordination and collaboration: a living mapping of registered trials

Objectives: Researchers worldwide are actively engaging in research activities to search for preventive and therapeutic interventions against coronavirus disease 2019 (COVID-19). Our aim was to describe the planning of randomized controlled trials (RCTs) in terms of timing related to the course of the COVID-19 epidemic and research question evaluated. Study Design and Setting: We performed a living mapping of RCTs registered in the WHO International Clinical Trials Registry Platform. We systematically search the platform every week for all RCTs evaluating preventive interventions and treatments for COVID-19 and created a publicly available interactive mapping tool at https://covid-nma.com to visualize all trials registered. Results: By August 12, 2020, 1,568 trials for COVID-19 were registered worldwide. Overall, the median ([Q1–Q3]; range) delay between the first case recorded in each country and the first RCT registered was 47 days ([33–67]; 15–163). For the 9 countries with the highest number of trials registered, most trials were registered after the peak of the epidemic (from 100% trials in Italy to 38% in the United States). Most trials evaluated treatments (1,333 trials; 85%); only 223 (14%) evaluated preventive strategies and 12 postacute period intervention. A total of 254 trials were planned to assess different regimens of hydroxychloroquine with an expected sample size of 110,883 patients. Conclusion: This living mapping analysis showed that COVID-19 trials have relatively small sample size with certain redundancy in research questions. Most trials were registered when the first peak of the pandemic has passed

Recherche de biomarqueurs par approche métabolomique et cytokinique en assistance médicale à la procréation

During the course of our research, we sought to analyze the pathophysiological mechanisms incriminated in ovarian aging and endometriosis, by studying the possible impact of these conditions on the oocyte micro-environment. We have identified specific signatures for these pathologies in the follicular fluid, andin some cases, potential biomarkers. In cases of infertility secondary to isolated endometriosis, we did not find any alteration of the metabolic profile of the follicular fluid. The absence of an alteration in the oocyte micro-environment in women with endometriosis suggests that there is no impact of the disease on the oocyte quality. However, in cases of severe endometriosis, cytokine analysis showed that, in some patients, there is a different expression of MCP1 in the follicular fluid. We also found a modification of the oocyte micro-environment in severe endometriosis, associated with high levels of MCP1. In cases of low ovarian reserve, we found decreased levels of unsaturated plasmalogens and an increase in the methyl-transferase activity, suggesting oxidative stress in the follicular fluid. Moreover, the analysis of the cytokines profile showed a significant decrease in PDGF-BB concentrations in patients with low ovarian reserve. The alteration of the metabolic pathway simplicating PDGF-BB could negatively impact folliculogenesis and the antioxidant defense mechanisms, and could therefore be linked to the infertility seen in patients with low ovarian reserve. Finally, our future research will look to identify eventual biomarkers and to improve our understanding of the pathophysiologic mechanisms involved in recurrent pregnancy losses and recurrent implantation failures following in vitro fertilization treatment.Nous avons, au cours de nos travaux, tenté d’approcher les mécanismes physiopathologiques liés au vieillissement ovarien et à l’endométriose en étudiant l’impact que ces pathologies pouvaient avoir sur le micro environnement ovocytaire. Nous avons, déterminé dans le fluide folliculaire des signatures spécifiques de la pathologie et, dans certains cas, d’éventuels biomarqueurs. En cas d’infertilité lié à une endométriose isolée, nous n’avons pas retrouvé d’altération du profil métabolique dans le fluide folliculaire. Nos résultats suggèrent qu’il n’existerait pas d’anomalies de l’environnement ovocytaire susceptible d’être lié à une altération de la qualité ovocytaire en cas d’endométriose isolée. En cas d’endométriose sévère, nos données sur l’analyse des cytokines suggèrent que l’endométriose entraine une expression différente de MCP1 dans le fluide folliculaire, en fonction des patientes. Nous constations aussi une modification du micro environnement ovocytaire en cas d’endométriose sévère associé à des niveaux de MCP-1élevé. En cas de réserve ovarienne diminuée, une diminution des plasmalogènes insaturés et une augmentation de l’activité méthyl transférase évoquent un contexte de stress oxydant au sein du fluide folliculaire. L’analyse des profils cytokiniques du FF a permis de constater une diminution significative des concentrations de PDGF-BB en cas de réserve ovarienne diminuée. Par conséquent, une infertilité liée à une réserve ovarienne diminuée pourrait être associée à une altération de voies métaboliques impliquant le PDGF-BB et pouvant être à l’origine de perturbation de la folliculogenèse ou des défenses antioxydantes. Enfin, nos futurs travaux s’intéresseront à la découverte éventuelle de biomarqueurs et à l’amélioration de la compréhension des mécanismes intervenant chez des femmes atteintes de fausses couches à répétition ou ayant vécu des échecs d’implantation répétés lors d’une prise en charge en FIV

Identification of biomarkers in assisted reproductive technologies using metabolomics and cytokinics approach

Nous avons, au cours de nos travaux, tenté d’approcher les mécanismes physiopathologiques liés au vieillissement ovarien et à l’endométriose en étudiant l’impact que ces pathologies pouvaient avoir sur le micro environnement ovocytaire. Nous avons, déterminé dans le fluide folliculaire des signatures spécifiques de la pathologie et, dans certains cas, d’éventuels biomarqueurs. En cas d’infertilité lié à une endométriose isolée, nous n’avons pas retrouvé d’altération du profil métabolique dans le fluide folliculaire. Nos résultats suggèrent qu’il n’existerait pas d’anomalies de l’environnement ovocytaire susceptible d’être lié à une altération de la qualité ovocytaire en cas d’endométriose isolée. En cas d’endométriose sévère, nos données sur l’analyse des cytokines suggèrent que l’endométriose entraine une expression différente de MCP1 dans le fluide folliculaire, en fonction des patientes. Nous constations aussi une modification du micro environnement ovocytaire en cas d’endométriose sévère associé à des niveaux de MCP-1élevé. En cas de réserve ovarienne diminuée, une diminution des plasmalogènes insaturés et une augmentation de l’activité méthyl transférase évoquent un contexte de stress oxydant au sein du fluide folliculaire. L’analyse des profils cytokiniques du FF a permis de constater une diminution significative des concentrations de PDGF-BB en cas de réserve ovarienne diminuée. Par conséquent, une infertilité liée à une réserve ovarienne diminuée pourrait être associée à une altération de voies métaboliques impliquant le PDGF-BB et pouvant être à l’origine de perturbation de la folliculogenèse ou des défenses antioxydantes. Enfin, nos futurs travaux s’intéresseront à la découverte éventuelle de biomarqueurs et à l’amélioration de la compréhension des mécanismes intervenant chez des femmes atteintes de fausses couches à répétition ou ayant vécu des échecs d’implantation répétés lors d’une prise en charge en FIV.During the course of our research, we sought to analyze the pathophysiological mechanisms incriminated in ovarian aging and endometriosis, by studying the possible impact of these conditions on the oocyte micro-environment. We have identified specific signatures for these pathologies in the follicular fluid, andin some cases, potential biomarkers. In cases of infertility secondary to isolated endometriosis, we did not find any alteration of the metabolic profile of the follicular fluid. The absence of an alteration in the oocyte micro-environment in women with endometriosis suggests that there is no impact of the disease on the oocyte quality. However, in cases of severe endometriosis, cytokine analysis showed that, in some patients, there is a different expression of MCP1 in the follicular fluid. We also found a modification of the oocyte micro-environment in severe endometriosis, associated with high levels of MCP1. In cases of low ovarian reserve, we found decreased levels of unsaturated plasmalogens and an increase in the methyl-transferase activity, suggesting oxidative stress in the follicular fluid. Moreover, the analysis of the cytokines profile showed a significant decrease in PDGF-BB concentrations in patients with low ovarian reserve. The alteration of the metabolic pathway simplicating PDGF-BB could negatively impact folliculogenesis and the antioxidant defense mechanisms, and could therefore be linked to the infertility seen in patients with low ovarian reserve. Finally, our future research will look to identify eventual biomarkers and to improve our understanding of the pathophysiologic mechanisms involved in recurrent pregnancy losses and recurrent implantation failures following in vitro fertilization treatment

Cartulaire du Mont Saint-Michel. Fac-similé du manuscrit 210 de la Bibliothèque municipale d’Avranches

International audienc

Embryo and Its Mitochondria

International audienceThe mitochondria, present in almost all eukaryotic cells, produce energy but also contribute to many other essential cellular functions. One of the unique characteristics of the mitochondria is that they have their own genome, which is only maternally transmitted via highly specific mechanisms that occur during gametogenesis and embryogenesis. The mature oocyte has the highest mitochondrial DNA copy number of any cell. This high mitochondrial mass is directly correlated to the capacity of the oocyte to support the early stages of embryo development in many species. Indeed, the subtle energetic and metabolic modifications that are necessary for each of the key steps of early embryonic development rely heavily on the oocyte’s mitochondrial load and activity. For example, epigenetic reprogramming depends on the metabolic cofactors produced by the mitochondrial metabolism, and the reactive oxygen species derived from the mitochondrial respiratory chain are essential for the regulation of cell signaling in the embryo. All these elements have also led scientists to consider the mitochondria as a potential biomarker of oocyte competence and embryo viability, as well as a key target for future potential therapies. However, more studies are needed to confirm these findings. This review article summarizes the past two decades of research that have led to the current understanding of mitochondrial functions in reproduction

Influence of Diminished Ovarian Reserve on Early Embryo Morphokinetics during In Vitro Fertilization: A Time-Lapse Study

There is great controversy as to whether women with Diminished Ovarian Reserve (DOR) exhibit only a quantitative decrease in ovarian reserve or also impaired oocyte and embryo quality. In this retrospective study, we aimed to evaluate the impact of DOR on embryo morphokinetic parameters with a time-lapse system. 1314 embryos were obtained from 256 couples undergoing IVF or ICSI cycles, with 242 embryos in the DOR group as classified by the Bologna and POSEIDON criteria and 1072 embryos derived from the Normal Ovarian Reserve (NOR) group. For each morphokinetic parameter (t2, t3, t4, t5, t8, tB, ECC2, cc2a, ECC3, s2, s3), a generalized linear mixed model was created to control for female age, BMI, smoking status, method of insemination and correlation between oocytes from a same cohort. No significant association was found between DOR and any of the morphokinetic parameters studied. In a secondary analysis, we evaluated the influence of maternal aging, comparing morphokinetic characteristics between two age groups (<37 and ≥37 years). In the univariate analysis, we found that embryos from older women displayed a slower embryo development (in particular for t3, t4, t5, tB, and ECC2), although without statistical significance in the multivariate analysis. In conclusion, our study did not reveal any substantial impact of ovarian aging on early morphokinetic parameters and suggested potential biases that may be a source of controversy in the literature

Surgical treatment of postpartum haemorrhage: national survey of French residents of obstetrics and gynecology

Abstract Background Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and one of the leading causes of maternal mortality worldwide. Many medical treatments and interventions are available nowadays, but surgical treatment is sometimes required when less invasive methods are unsuccessful. This study aimed to assess the theoretical and practical knowledge of French residents of Obstetrics and Gynecology concerning the surgical treatment of postpartum haemorrhage. Study design We performed a questionnaire study for senior residents of Obstetrics and Gynecology in France (fourth and fifth year of training). An anonymous survey was sent by email. Between December 2013 and April 2014, a total of 370 residents responded. Result The response rate was 47.6% (176/370). Only 156 questionnaires were fully completed and included for analysis. In all, 74% (115/156) of residents reported not mastering sufficiently or at all the technique for bilateral ligation of uterine arteries, 79% (123/156) for uterine compression sutures, 95% (148/156) for ligation of the internal iliac arteries, and 78% (122/156) for emergency peripartum hysterectomy. More than half of respondents (55%, 86/156) stated that they had not mastered any of these techniques. Conclusion An alarmingly high number of French senior residents in Obstetrics and Gynecology report that they have not acquired the sufficient surgical skills during their training to be able to perform the surgeries required for the management of PPH