In vitro maturation of oocytes from stimulated IVF-ICSI cycles using autologous cumulus cell co-culture: A preliminary study.

PURPOSE OF THE STUDY: In stimulated IVF-ICSI cycles, follicles at different stages of maturation can be aspirated during oocyte pickup. Nowadays, only mature oocytes (metaphase 2 stage) are used and immature oocytes (germinal vesicle and metaphase 1 stages), which are judged unfit for fertilization, are non-used at day 0. In our IVF center, the rate of immature oocytes recovered is around 25%. A significant number of this precious resource is therefore non-used every day in IVF laboratories. The objective of our study was to evaluate the competence of our in vitro maturation autologous coculture method on the maturation and developmental potential of immature oocytes obtained from stimulated IVF-ICSI cycles, in order to obtain additional embryos for the couple as a rescue system to increase the changes of cumulative pregnancy. PATIENTS AND METHODS: This is a prospective study, carried out in the Reproductive Medicine and Biology Unit of the Amiens-Picardy University Hospital (France). It was included 14 couples, managed in IVF-ICSI in our center, from January to March 2020. Thirty-eight oocytes, identified as immature after cumulus-oocyte complexes (COC) stripping for ICSI, were placed in our in vitro maturation medium with the addition of autologous cumulus cells. Oocytes that had reached the metaphase II stage after a maximum of 36 hours of maturation were microinjected. The fertilization and embryonic development potential of the in vitro matured oocytes were compared to those of 148 in vivo matured "siblings" oocytes from the same oocyte retrieval, and then also compared to those of 127 in vivo matured oocytes from different patients (control group). MAIN OUTCOME MEASURE(S): Maturation rate, fertilization rate, early cleavage rate and developmental activity to blastulation rate. SECOND OUTCOME MEASURE(S): Embryo quality at cleavage and blastocyst stages, blastulation rate, and useful blastulation rate. RESULTS: No significant difference was found in the main and secondary criteria of the study compared to the "siblings" in vivo matured oocytes from the same oocyte retrieval. However, a significant difference was obtained on the rate of early cleavage and useful blastulation when our cohort was compared to mature in vivo oocytes from different patients (control group). CONCLUSION: This study has shown that after incubation in our in vitro maturation autologous cumulus cell co-culture with cumulus-oocyte cells, immature oocytes recovered during stimulated cycles can give rise to competent oocytes, i.e., capable of being fertilized, of cleaving, and of developing into embryos up to the blastocyst stage. Our study therefore seems to be in the direction of a favorable use of these immature oocytes obtained after stimulated IVF-ICSI cycles. The continuation of this study by including a larger number of oocytes is necessary in order to evaluate the real contribution of this technique in routine.

Efficacy of assisted reproductive technology after ovarian tissue transplantation in a cohort of 11 patients with or without associated infertility factors.

PURPOSE: IVF treatment in women with grafted frozen-thawed ovarian tissue is associated with poor reproductive outcomes. The aim of this study was to evaluate the efficacy of ovarian tissue transplantation (OTT) followed by assisted reproductive technology (ART) in women with or without associated infertility factors. METHODS: This is a prospective cohort study with retrospective data collection including eleven women, four of whom having an infertility factor (IF), who had undergone OTT in one university center between 2005 and 2017, followed by ART in six in vitro fertilization (IVF) centers. RESULTS: In total, 25 of the 85 cycles initiated (29%) were canceled, resulting in 60 oocyte retrievals. Ninety-five oocytes were retrieved: 36 were abnormal or immature, 29/39 fertilized (74%) after ICSI and 13/20 (65%) after IVF. Thirty-five embryos were transferred in seven patients (5/7 patients without IF and 2/4 patients with IF). After ART, one patient with IF experienced two pregnancies, one resulting in a live birth. For all patients, pregnancy rates and live birth rates were 7.4% and 3.7% per embryo transfer, respectively. Nine pregnancies and four live births occurred after spontaneous conception in five patients without IF, none in the infertility group. CONCLUSION: This study confirms that IVF treatment in women with grafted frozen-thawed ovarian tissue is associated with poor outcomes. However, the chances of natural conception are high in women without IF. Patients with IF, without the possibility of spontaneous pregnancy, should be informed of poor reproductive outcomes after OTT followed by ART. TRIAL REGISTRATION NUMBER: NCT02184806.

Relationship between changes in metabolic syndrome constituent components over 12 months of treatment and cognitive performance in first-episode schizophrenia.

Few studies have investigated the longitudinal effects of treatment-emergent metabolic syndrome changes on cognitive performance in first-episode psychosis. The aim of the present study was to determine the associations between changes in metabolic syndrome constituent component over 12 months of treatment and end-point cognitive performance in schizophrenia spectrum disorders. This single site-cohort study included 72 minimally treated or antipsychotic-naïve first-episode patients. Cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Our primary objective of interest was the relationship between metabolic syndrome constituent component changes over 12 months of treatment and end-point cognitive performance. Secondary objectives included investigating whether this relationship was affected by age, sex, antipsychotic dose, treatment duration and substance use. Weight gain predicted better overall cognition (p = 0.02) at end-point, adjusting for age, sex, substance use, baseline cognitive score and BMI, modal antipsychotic dose and treatment duration. Weight loss (p = 0.04) and substance use (p = 0.01) were both associated with poorer working memory performance at end-point. Low baseline BMI showed differential effects on end-point working memory performance in substance users (unfavorable) compared to non-users (favorable) (p < 0.05). In conclusion, weight gain over the course of antipsychotic treatment is associated with better overall cognitive performance and the working memory domain in first-episode schizophrenia spectrum disorder patients. In contrast, low baseline BMI may represent an unfavorable marker in substance users, who demonstrated weight loss compared to non-users.

Childhood adversity and cognitive function in schizophrenia spectrum disorders and healthy controls: evidence for an association between neglect and social cognition.

BACKGROUND: Childhood adversity is associated with cognitive impairments in schizophrenia. However, findings to date are inconsistent and little is known about the relationship between social cognition and childhood trauma. We investigated the relationship between childhood abuse and neglect and cognitive function in patients with a first-episode of schizophrenia or schizophreniform disorder (n = 56) and matched healthy controls (n = 52). To the best of our knowledge, this is the first study assessing this relationship in patients and controls exposed to similarly high levels of trauma. METHODS: Pearson correlational coefficients were used to assess correlations between Childhood Trauma Questionnaire abuse and neglect scores and cognition. For the MCCB domains displaying significant (p < 0.05) correlations, within group hierarchical linear regression, was done to assess whether abuse and neglect were significant predictors of cognition after controlling for the effect of education. RESULTS: Patients and controls reported similarly high levels of abuse and neglect. Cognitive performance was poorer for patients compared with controls for all cognitive domains except working memory and social cognition. After controlling for education, exposure to childhood neglect remained a significant predictor of impairment in social cognition in both patients and controls. Neglect was also a significant predictor of poorer verbal learning in patients and of attention/vigilance in controls. However, childhood abuse did not significantly predict cognitive impairments in either patients or controls. CONCLUSION: These findings are cross sectional and do not infer causality. Nonetheless, they indicate that associations between one type of childhood adversity (i.e. neglect) and social cognition are present and are not illness-specific.

[Electronic cigarettes and fertility: True or false friends?] / Cigarette électronique et fertilité : vrais ou faux amis ?

While electronic cigarettes have been on the rise in France for the past ten years, data on their prevalence, use patterns and safety have remained fragmented and controversial. Electronic cigarettes seem to not be a harmless product to use, because although they contain fewer harmful substances than traditional cigarettes, they still contain toxic products such as endocrine disruptors, which appear to have a negative impact on hormonal homeostasis, morphology and functioning of the animal reproductive system. Mostly presented as a harmless alternative to traditional cigarettes by industry lobbies, electronic cigarettes are often offered as an aid to smoking cessation in the same way as nicotinic substitutes. This strategy is especially proposed without knowledge of its effects on human reproductive health. Indeed, there are currently very few scientific publications, which study the impact of the use of electronic cigarettes, nicotine and the vapours it delivers on fertility and the functioning of the human female and male reproductive systems. Thus, the great majority of the data we have to date come from studies carried out in animal populations and show that electronic cigarettes exposure affect fertility. There is, to our knowledge, no scientific publication on the results in Assisted Reproductive Technology in case of use of electronic cigarettes, motivating the realization of the study IVF-VAP currently underway in the department of Medicine and Biology of Reproduction of the Amiens Picardie University Hospital.

Associations between BMI and brain structures involved in food intake regulation in first-episode schizophrenia spectrum disorders and healthy controls.

Structural brain differences have been described in first-episode schizophrenia spectrum disorders (FES), and often overlap with those evident in the metabolic syndrome (MetS). We examined the associations between body mass index (BMI) and brain structures involved in food intake regulation in minimally treated FES patients (n = 117) compared to healthy controls (n = 117). The effects of FES diagnosis, BMI and their interactions on our selected prefrontal cortical thickness and subcortical gray matter volume regions of interest (ROIs) were investigated with hierarchical multivariate regressions, followed by post-hoc regressions for the individual ROIs. In a secondary analysis, we examined the relationships of other MetS risk factors and psychopathology with the brain ROIs. Both illness and BMI significantly predicted the grouped prefrontal cortical thickness ROIs, whereas only BMI predicted the grouped subcortical volume ROIs. For the individual ROIs, schizophrenia diagnosis predicted thinner left and right frontal pole and right lateral OFC thickness, and increased BMI predicted thinner left and right caudal ACC thickness. There were no significant main or interaction effects for diagnosis and BMI on any of the individual subcortical volume ROIs. Secondary analyses suggest associations between several brain ROIs and individual MetS risk factors, but not with psychopathology. Our findings indicate differential, independent effects for FES diagnosis and BMI on brain structures. Limited evidence suggests that the BMI effects are more prominent in FES. Exploratory analyses suggest associations between other MetS risk factors and some brain ROIs.

Cannabis use and hippocampal subfield volumes in males with a first episode of a schizophrenia spectrum disorder and healthy controls.

BACKGROUND: Both schizophrenia and cannabis use are associated with structural brain changes. The hippocampus is a region of particular interest due to its role in memory and select cognitive functions, impairment of which is a core feature of schizophrenia and has also been observed in substance abuse. This study aimed to explore the effects of recent/current cannabis use on hippocampal subfield volumes in male patients with first-episode schizophrenia spectrum disorders and matched controls. METHODS: This cross-sectional, case-control study included 63 patients and 58 controls scanned on 3T MRI scanners, with hippocampal segmentation performed using recently validated Freesurfer v6.0 software. Cannabis use status was determined by self and carer report together with urine toxicology screening, and patients were categorised as recent/current users or non-users. We used multivariate analysis of covariance (MANCOVA) with age, scan sequence, scan quality, and total intracranial volume as covariates, with subsequent analysis of variance (ANOVA) to test the effects of diagnosis and cannabis use status on individual hippocampal subfields. RESULTS: We found a group (patient/control) by cannabis use interaction effect in the subiculum, with decreased volumes observed in the cannabis non-using patients compared to the cannabis using patients, and decreased volumes in the cannabis using controls compared to the cannabis non-using controls. CONCLUSION: The increased subiculum volume in cannabis using patients compared to cannabis non-using patients raises important questions regarding the pathophysiology of schizophrenia and the role of cannabis use therein.

Gender role endorsement in first-episode schizophrenia spectrum disorders.

Sex (a biological distinction) and gender (a social construct) are inter-related, but semi-independent measures. The aim of our research was to compare gender role endorsement between first-episode schizophrenia spectrum disorder patients (n=77) and matched controls (n=64). The Bem Sex Role Inventory (BSRI) was used to assess masculinity and femininity scores as separate linear measures. This well-known research instrument also allowed us to examine gender as a categorical measure based on sex-specific cut-off scores calculated for controls as our normative reference sample using a median-split technique. First, we found that both masculinity and femininity scores differed between patients and controls. The distribution of gender as a categorical measure also differed between the two groups. Post-hoc testing with correction for multiple comparisons identified masculinity scores in particular as being lower in both male and female patients compared to controls of the corresponding sex. In conclusion, lower masculinity scores reported for chronic schizophrenia also affects first-episode patients with minimal prior treatment exposure irrespective of their biological sex. Future studies would do well to examine the associations of sex and gender with clinical and treatment outcomes from the perspective of the neurodevelopmental model of schizophrenia as a proposed "disorder of the self".

Mg or Zn for Ca substitution improves the sintering of bioglass 45S5.

Bioglass 45S5 is well-known for its bioactivity, but it possesses poor sintering behaviour owing to viscous flow being inhibited by the crystallisation of sodium calcium silicate phases. Mg or Zn were partially (0, 25, 50, 75%) or fully (100%) substituted for Ca on a molar base, and thermal properties (differential scanning calorimetry, dilatometry) and sintering (heating microscopy, SEM and X-ray diffraction) were investigated. Here we show that sintering can be improved significantly by partial or complete substitution of Mg or Zn for Ca, owing to a pronounced decrease in crystallisation tendency. Glass transition temperature and dilatometric softening point went through minima for mixed compositions, with random mixing of Mg/Ca or Zn/Ca ions in the glass structure and the resulting effect on configurational entropy being a likely explanation. As the onset of crystallisation did not vary much with substitution, substituted glasses possessed a wider temperature range for sintering, resulting in up to 57% and 27% sample height reduction for Mg and Zn substituted glasses, respectively, compared to only 3% height reduction for Bioglass 45S5. Taken together, these results suggest that using a combination of modifiers, particularly alkaline earths or zinc, may be a promising approach for improving the sintering of Bioglass 45S5.

Hippocampal subfield volumes and change in body mass over 12 months of treatment in first-episode schizophrenia spectrum disorders.

In this study, we explored the relationship between baseline hippocampal subfield volumes and change in body mass over 12 months of treatment in 90 first-episode schizophrenia spectrum disorder patients (66 males, 24 females; mean age= 24.7 ± 6.8 years). Body mass index was assessed in patients at baseline, and at months 3, 6, 9 and 12. Hippocampal subfields of interest were assessed at baseline using a segmentation algorithm included in the FreeSurfer 6.0 software program. Linear regression revealed a significant interactive effect between sex and anterior hippocampus size as predictors of change in body mass over 12 months, adjusting for age, substance use, and treatment duration. In an exploratory post-hoc sub-analysis, partial correlations showed a significant association between weight gain and smaller CA1, CA3 and subiculum volumes in females, but not males, adjusting for age and substance use, with similar trends evident for the CA4 and presubiculum subfields. In conclusion, our findings suggest that smaller anterior hippocampal subfields at baseline are associated with the development of weight gain over the course of treatment in first-episode schizophrenia spectrum disorders in a sex-specific fashion. This may be related to the greater increase in body mass evident for female patients in our study.

Fronto-limbic white matter fractional anisotropy and body mass index in first-episode schizophrenia spectrum disorder patients compared to healthy controls.

In this diffusion tensor imaging study, we explored the associations of body mass index (BMI) with white matter microstructure in first-episode schizophrenia spectrum disorder patients (n = 69) versus healthy controls (n = 93). We focused on fractional anisotropy (FA) measures for fronto-limbic white matter tracts known to connect brain regions which form part of a "core eating network". Secondary objectives included the associations of body mass with global illness severity, psychopathology and depressive symptoms. In a multivariate analysis of covariance (MANCOVA) model, there was a significant interaction between BMI and group (patient versus control) across the fronto-limbic white matter tracts of interest (F(1,155)= 4.91, p = 0.03). In a sub-analysis, BMI was significantly inversely correlated with FA measures for the genu and body of the corpus callosum, left and right tapetum, and left superior fronto-occipital fasciculus in controls. In patients, BMI was significantly positively correlated with white matter FA for the genu of the corpus callosum and left tapetum. Lower BMI was significantly correlated with more severe negative symptoms, as was earlier age of illness onset. Body mass may be differentially associated with fronto-limbic white matter microstructure in first-episode schizophrenia spectrum disorder compared to controls.

Weight gain and metabolic change as predictors of symptom improvement in first-episode schizophrenia spectrum disorder patients treated over 12 months.

BACKGROUND: Treatment-emergent weight gain is associated with antipsychotic efficacy in schizophrenia patients treated with clozapine and olanzapine. However, few studies have investigated this relationship in first-episode patients treated with other antipsychotics, in particular those with a lower obesogenic potential. Aim To investigate the relationships between weight gain and associated metabolic changes with psychopathology improvement in relation to age, sex, ethnicity, substance use, treatment duration and antipsychotic dose in first-episode schizophrenia spectrum disorder patients. METHODS: This single site cohort study included 106 minimally treated or antipsychotic-naive patients treated with flupenthixol decanoate over 12 months. Psychopathology was evaluated using the Positive and Negative Syndrome Scale (PANSS) and BMI, fasting blood lipids and glucose were assessed at regular intervals. Linear regression models were constructed to determine the effects of socio-demographic, clinical and metabolic factors as predictors of change in total PANSS score and factor-derived domains. RESULTS: BMI change scores were inversely correlated with change in PANSS total (R = -0.25; p = 0.011), positive (R = -0.23; p = 0.019), depressive anxiety (R = -0.21; p = 0.031) and disorganized symptoms (R = -0.32; p < 0.001). Linear regression analysis showed that increased BMI and treatment duration both predicted improvement in global psychopathology and disorganized symptoms independent of age, sex, ethnicity, substance use, co-medication with antidepressants and/or anticholinergics, as well as the dose and duration of antipsychotic exposure. CONCLUSIONS: Our findings suggest that the relationship between treatment-emergent weight gain and psychopathology improvement is not limited to patients treated with antipsychotics most associated with weight gain, and is not confounded by treatment duration and dose.

[Additional non-contraceptive effects of contraception: CNGOF Contraception Guidelines]. / Bénéfices non contraceptifs des contraceptions. RPC Contraception CNGOF.

Hormonal and intrauterine contraceptive methods provide women with highly efficient protection against undesired pregnancy. Additional non-contraceptive effects are now well documented. Combined hormonal contraceptives use, either through the oral transdermal and vaginal route, allow a reduction in menorrhagia, dysmenorrhea, functional ovarian cysts, benign breast and uterine disease, endometriosis-related pain and recurrence. A reduction in ovarian cancer risks, including in women with BRCA syndrome, endometrial and colon cancer is documented. This effect is prolonged for years after contraception discontinuation. Non-contraceptive benefits of progestin-only contraceptives are less documented. Use of the levonorgestrel IUD is associated with a reduction in menorrhagia, dysmenorrhea including in case of endometriosis. Copper IUD use is associated with a decrease in cervix and endometrial cancer risk.

Effects of cannabis use on body mass, fasting glucose and lipids during the first 12 months of treatment in schizophrenia spectrum disorders.

While acute cannabis use stimulates appetite, general population studies suggest that chronic use is associated with reduced risk of obesity and other cardiometabolic risk factors. In this study we investigated changes in body mass index (BMI), fasting blood glucose and lipids, and rates of metabolic syndrome risk factors in cannabis users vs. non-users in 109 minimally treated patients with first-episode schizophrenia, schizophreniform or schizo-affective disorder who were treated according to a standardized treatment regime with depot antipsychotic medication over 12 months. Participants underwent repeated urine toxicology tests for cannabis and those testing positive at any time during the study (n = 40), were compared with those who tested negative at all time points (n = 69). There was a significant group*time interaction effect (p = 0.002) with the cannabis negative group showing a greater increase in BMI than the cannabis positive group, after adjusting for age, sex, methamphetamine use and modal dose of antipsychotic. There were no group*time interaction effects for fasting blood glucose or lipids. Post hoc tests indicated significant increases in fasting blood glucose and triglycerides and a decrease in high-density lipoprotein cholesterol for the cannabis negative group, with no significant changes in the cannabis positive group. Rates of metabolic syndrome did not differ significantly between groups, although more cannabis negative patients had elevated waist-circumference at endpoint (p = 0.003). It may be that chronic cannabis use directly suppresses appetite, thereby preventing weight gain in users. However, other indirect effects such as dietary neglect and smoking may be contributory and could explain our findings.

Detection of Loa loa Microfilariae in Follicular Fluid During Assisted Reproductive Technology: Case Report and Review of the Literature.

We report on a case of loiasis revealed during an assisted reproductive technology (ART) cycle. Loa loa could limit implantation outcome. We propose to focus on an ART strategy with frozen embryos to treat the patient before any transfer.

[Evaluation of theoretical teaching of the French diploma of medical gynecology]. / Enseignement théorique du Diplôme d'études spécialisées de gynécologie médicale en France: évaluation nationale.

OBJECTIVES: As far as the reform of the "Diplômes d'études spécialisées" (DES) is approaching, a first national evaluation of the Medical Gynecology diploma was necessary. The objective was to evaluate the practices of the theoretical teaching with the whole students, by receiving their opinions and their wishes of changing, and by proposing some improving measures. PATIENTS AND METHODS: The self-evaluation form made by members of the Association of residents (AIGM) and the Teacher's College (CNEGM) was submitted to the students during the national teaching session of June 2014. RESULTS: Fifty-six results were gathered among 145 students enrolled at the DES (38.6 %). Twelve half days of national theoretical training are yearly scheduled. The accordance of the national theoretical training to the level of the students was assessed on average at 7.8 (VAS from 0 to 10). The scientific and pedagogical skills of the speakers are evaluated at 8.9 and 7.8. The theoretical training of the diploma was considered as satisfying for 76.6 % of the respondents. DISCUSSION AND CONCLUSION: Despite a globally satisfying evaluation, some points can be improved in the organization of the diploma. The introduction of courses about establishment, medical acts and imaging, the implementation of gradual progress teaching, the development of hands-on training and practical works, reciprocal evaluation of the students and the teachings/teachers, should be set up.

[What is mild stimulation?]. / Qu'est-ce que la mild stimulation ?

Mild stimulation is the administration of low doses (150 IU/day) of FSH, continuously, from the fifth day of the cycle, associated with the administration of GnRH antagonists. Despite the lower number of oocytes collected during mild stimulation, they are better for pregnancy rates on with an endometrium nearest closer to the natural cycle, and reducing the risk of ovarian hyperstimulation. Although the number of IVF ± ICSI attempts is limited to 4 in France, the Mild stimulation may be proposed in young women, those with a polycystic ovary syndrome or "low responder" women.