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ObjectiveTo evaluate the effect of air pollution, from oocyte retrieval to embryo transfer, on the results of in vitro fertilisation (IVF) in terms of clinical pregnancy rates, at two fertility centres, from 2013 to 2019.DesignExploratory retrospective cohort study.SettingThis retrospective cohort study was performed in the Reproductive Biology Department of Bordeaux University Hospital localised in Bordeaux, France and the Jean Villar Fertility Center localised in Bruges, France.ParticipantsThis study included 10 763 IVF attempts occurring between January 2013 and December 2019, 2194 of which resulted in a clinical pregnancy.Primary and secondary outcome measuresThe outcome of the IVF attempt was recorded as the presence or absence of a clinical pregnancy; exposure to air pollution was assessed by calculating the cumulative exposure of suspended particulate matter, fine particulate matter, black carbon, nitrogen dioxide and ozone (O3), over the period from oocyte retrieval to embryo transfer, together with secondary exposure due to the presence of the biomass boiler room, which was installed in 2016, close to the Bordeaux University Hospital laboratory. The association between air pollution and IVF outcome was evaluated by a random-effects logistic regression analysis.ResultsWe found negative associations between cumulative O3exposure and clinical pregnancy rate (OR=0.92, 95% CI = (0.86 to 0.98)), and between biomass boiler room exposure and clinical pregnancy rate (OR=0.75, 95% CI = (0.61 to 0.91)), after adjustment for potential confounders.ConclusionAir pollution could have a negative effect on assisted reproductive technology results and therefore precautions should be taken to minimise the impact of outdoor air on embryo culture.

We report a successful live birth after oocytes in vitro maturation (IVM) and fresh embryo transfer in a patient with autoimmune premature ovarian failure (POF) and performed a review of the litera...

The aim of this study was to evaluate the ART outcomes for infertile males carrying a balanced structural chromosomal rearrangement or a Y-chromosome microdeletion, and to compare the results with a control group. The primary outcome was the clinical pregnancy rate. A retrospective case-control study has been carried out in the ART departments of the university hospitals of Bordeaux and la Reunion. Results of karyotypes and Y-chromosome microdeletions analysis of infertile men with sperm concentration lower than 5 millions/mL have been extracted from the softwares Jfiv® (Bordeaux) and MediFirst® (la Reunion). The clinical pregnancy rate for carriers of balanced chromosomal rearrangements and Y-chromosome microdeletions was 28% and 43% respectively. The clinical pregnancy rate for the controls was 24% (non-significant difference). According to this study, balanced chromosomal rearrangements and Y-chromosome microdeletions are not found to affect the clinical pregnancy rate in conventional ART. Further larger scale studies are required to confirm these results.

We report a successful live birth after oocytesThe patient was a 24-year-old woman with autoimmune POF diagnosed post-partum, who developed autoimmune polyglandular syndrome with serum anti-ovarian and anti-21-hydroxylase antibodies. The patient had typical symptoms of POF: secondary amenorrhea with hypoestrogenism, elevated gonadotropins and infertility; however, the serum anti-Müllerian hormone level and total antral follicle count remained normal. IVM of immature oocytes was performed after the administration of 150 IU highly purified human menopausal gonadotropin for three consecutive days and an injection of 10,000 IU human chorionic gonadotropin to trigger ovulation.The six oocyte-cumulus complexes collected maturedWe report a successful livebirth after IVM treatment in a patient with autoimmune premature ovarian failure (POF). Management of reproductive age women with autoimmune pathology requires fertility counseling. Early diagnosis of autoimmune POF is important for early conception and oocyte preservation, because the only other option at present is ovum donation.

Animal model is an essential tool in the life sciences research, notably in understanding the pathogenesis of the diseases and for further therapeutic intervention success. Rodents have been the most frequently used animals to model human disease since the establishment of gene manipulation technique. However, they remain inadequate to fully mimic the pathophysiology of human brain disease, partially due to huge differences between rodents and humans in terms of anatomy, brain function, and social behaviors. Nonhuman primates are more suitable in translational perspective. Thus, genetically modified animals have been generated to investigate neurologic and psychiatric disorders. The classical transgenesis technique is not efficient in that model; so, viral vector‐mediated transgene delivery and the new genome‐editing technologies have been promoted. In this review, we summarize some of the technical progress in the generation of an ad hoc animal model of brain diseases by gene delivery and real transgenic nonhuman primate.

Introduction France is known for its conservative and unique position in assisted reproductive technologies (ARTs). At the eve of the future revision of French Bioethics laws, we decided to conduct a national survey to examine the opinions of French specialists in ARTs about social issues. Material and methods Descriptive study conducted in May 2017 in a university teaching hospital using an anonymous online questionnaire on current issues in ARTs. The questionnaire was sent by email to 650 French ARTs specialists, both clinicians and embryologists. Results After 3 reminders, 408 responses were collected resulting in a participation rate of 62.7% (408/650). Concerning pre-implantation genetic testing, 80% of the physicians were in favor of expanding the indications, which in France are presently limited to incurable genetic diseases. Authorizing elective Fertility Preservation was supported by 93.4% of the specialists, but without social coverage for 86.3% of them. Concerning gamete donation, 77.4% of the French ARTs specialists were in favor of giving a financial compensation to donors, 92% promoted preserving their anonymity and 80.9% were against a directed donation. ARTs for single heterosexual women were supported by 63.4% of the French specialists and by 72.5% for lesbian couples. The legalization of surrogacy was requested by 55.2%. Discussion Pending the revision of the French Bioethics laws, this survey provides an overview of the opinion of the specialists in ARTs on expanding ARTs for various social indications.Because of the evolution of social values, a more liberal and inclusive ART program is desired by the majority of ART specialists in France.

Non-invasive investigation of integrin expression is an interesting approach in nuclear medicine department. Indeed, integrins are overexpressed in a wide array of diseases, including tumor neoangiogenesis, cardiovascular pathologies, immune dysfunction, etc. Different targets have been identified in order to be detected and quantified for angiogenesis and vascular remodeling, among them VEGF, matrix metalloproteases, and integrins (αvβ3, but also α5s1 and αvβ6). Their targeting appears of great interest either for early diagnosis, aggressiveness staging of the disease or for selection of responders to new-targeted therapies. Thus, αvβ3 is a biomarker of angiogenesis that specifically binds to RGD containing peptides. Many different strategies were attempted to develop RGD peptides for single photon emission tomography (SPECT) and positron emission tomography (PET) imaging. This review is mainly focused on αvβ3-targeting in oncology. We will present an overview of the tracers mostly used on nuclear imaging techniques, those in clinical trials, the recent development concerning the 18F-labeling strategies, the 68Ga-complex chemistry and different approaches of therapy.

STUDY QUESTION: Does endometrial scratch in women undergoing a first or second IVF/ICSI attempt improve the clinical pregnancy rate (CPR)? SUMMARY ANSWER: Endometrial scratch (ES) in women undergoing their first or second IVF/ICSI attempt does not enhance the CPR under the technical conditions of our study. WHAT IS KNOWN ALREADY: Several studies have suggested that physical scratch of the endometrium before an IVF attempt could improve embryo implantation. STUDY DESIGN, SIZE, DURATION: This was a randomized controlled multi-center, two-arm, parallel trial. Inclusions started in February 2010 and stopped prematurely in July 2014 after an unplanned interim analysis. At the time of study closure, 191 of the planned 358 patients had been included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients included in the study were randomly assigned to either the ES arm or the non-ES arm. Local ES was performed between Day 20 and Day 24 of the cycle preceding ovarian stimulation using a device for endometrial biopsy. Ovarian stimulation used a combination of recombinant FSH and either an GnRH agonist protocol or a GnRH antagonist protocol without any estrogen pre-treatment. CPR was analyzed on an intent-to-treat basis. All comparisons between the two groups were done using a logistic regression model adjusted for age, BMI and infertility etiology. Differences between the two arms were considered statistically significant at P value of less than 0.0446 for the primary outcome only. MAIN RESULTS AND THE ROLE OF CHANCE: Sixty-eight embryo transfers were performed in the ES arm and sixty-four in the non-ES arm. CPR was 23.5% (16/68) in the ES arm and 35.9% (23/64) in the non-ES arm (hazard ratio (HR) = 0.43; 95% CI, 0.18-1.02; P = 0.0568). The implantation rate was 19.1% and 24.0% in the ES arm and in the non-ES arm, respectively. Two miscarriages and one ectopic pregnancy were reported in each arm. The multiple pregnancy rate was higher in the scratch arm (50.0% vs 20.0%), but the difference was not statistically significant (odds ratio (OR) = 4.54; 95% CI, 0.50-40.93; P = 0.1349). The endometrial biopsy procedure was well tolerated in most women. Of 50 patients in the ES arm having received the embryo transfer, 40 (80.0%) patients reported having felt pain during the procedure, the pain resolving quickly for 31 of them. LIMITATIONS, REASONS FOR CAUTION: An interim analysis of the primary endpoint was conducted and an independent data monitoring committee agreed on stopping the inclusions. This analysis was prompted by the tendency towards lower pregnancy rates observed in the ES arm. Consequently, the study suffered from a lower inclusion rate and failed to reach the planned sample size. WIDER IMPLICATIONS OF THE FINDINGS: Under the technical condition employed in this study, ES in the luteal phase of the cycle preceding the ovarian stimulation does not improve CPR in patients undergoing a first or second IVF/ICSI attempt. STUDY FUNDING/COMPETING INTERESTS: This study was supported by a grant from Ministere de la Sante Francais (Programme Hospitalier de Recherche Clinique 2009). There are no conflicts of interest. TRIAL REGISTRATION NUMBER: NCT01064193. TRIAL REGISTRATION DATE: 08-Feb-2010. DATE OF FIRST PATIENT'S ENROLMENT: 08-Feb-2010.

Objective To determine the best practices of intrauterine insemination with the partner's fresh sperm. Design Prospective multicenter observational study. Setting Assisted reproduction technology (ART) centers. Patient(s) Seven hundred and seven patients entering the program, regardless of age or cause of infertility. Intervention(s) Intrauterine insemination by standard procedures. Main Outcome Measure(s) Effect of patient characteristics (duration of infertility, indications, age, parity, body mass index, semen parameters) as well as IUI parameters on delivery rates per couple or per attempt. Result(s) The overall live birth rate was 11.4% per cycle, varying from 8.4% to 17.6% between centers. The main differences in practice that had a statistically significant impact on the delivery rate were the use of gonadotropin-releasing hormone (GnRH) antagonists (15.2% with versus 9.4% without) and the number of mature recruited follicles (9.4% for one versus 15.2% for two). Conclusion(s) Our results indicate that the use of GnRH antagonists has a positive effect on the delivery rate, especially in the multifollicular stimulations that are required when women are older than 27 years.

International audience; AbstractRecombinant adeno-associated virus serotype 9 (rAAV2/9) and pseudotype rhesus-10 (rAAV2/rh10) are used for gene delivery, especially into the central nervous system. Both serotypes cross the blood-brain barrier and mediate stable long-term transduction in dividing and nondividing cells. Among possible routes of administration, intracardiac injection holds the potential for widespread vector diffusion associated with a relatively simple approach. In this study adopting the intracardiac route, we compare the cell-specific tropism and transfection efficacy of a panel of engineered rAAV2/9 and rAAV2/rh10 vectors encoding the enhanced green fluorescent protein. We observed transduction in the brain and peripherally, with a predominant neuronal tropism while the various serotypes achieved different expression patterns.

In vitro human embryos culture depends largely on the atmospheric conditions within the incubators of the laboratory. The pH of culture media, an indirect reflection of the CO2 content inside these incubators, is a critical parameter. Collaboration between the biochemistry and reproductive biology departments enabled the automated measurement of the pH in the culture medium on a blood gas analyzer. This method has been validated and evaluated. It is applicable in all laboratories whatever the medium and the conditions of culture. It allows strict monitoring of this parameter for the optimization of the culture conditions necessary to improve the results of in vitro fertilization attempts.

Non-invasive investigation of integrin expression is an interesting approach in nuclear medicine department. Indeed, integrins are overexpressed in a wide array of diseases, including tumor neoangiogenesis, cardiovascular pathologies, immune dysfunction, etc. Different targets have been identified in order to be detected and quantified for angiogenesis and vascular remodeling, among them VEGF, matrix metalloproteases, and integrins (α

RAD50 has a major role in double strand breaks’ (DSB) repair, which is essential for homologous chromosome pairing during meiosis. While RAD50 seems to be a good candidate gene in hereditary infertility, there are few publications on its possible role. The aim was to study the impact of RAD50’s expression on male mice’s fertility and then on its role in repairing DSBs within human cells. The mutated mice had reduced testicles and histological sections revealed that they had seminiferous epithelium architecture abnormalities. No spermatozoa was present in seminiferous tubules. Spermatocytes seemed to be locked in the first prophase, which is when RAD50 plays its role. To evaluate DSB’s impact in human RAD50-deficient cells, we altered RAD50’s expression by shRNA and genome editing in human primary foreskin fibroblasts (hFF). We then induced a DSB by CRISPR-Cas9 and studied viability/cell death in this cell model. We observed that RAD50 is essential for human cell survival and that low RAD50’s expression compromise cellular proliferation, and induce excessive apoptosis after DSB. Our preliminary results suggest that the exploration of RAD50 in fertility needs to be further developed, with the study of mutated female’s fertility and by reproducing these experiments under meiotic conditions.; RAD50 est un acteur de prise en charge des cassures doubles brins (CDB) indispensables à la ségrégation des chromosomes homologues durant la méiose. Alors que ce gène semble être un bon candidat, peu de publications étudient un possible rôle de RAD50 dans l’infertilité. L’objectif a été d’étudier l’impact de la modulation de l’expression de RAD50 sur la fertilité des souris mâles et sur la prise en charge d’une cassure double brin dans des cellules humaines. Dans une première approche, des coupes histologiques testiculaires provenant d’un modèle murin muté pour Rad50 ont été effectuées pour l’analyse de l’architecture de l’épithélium séminifère. La deuxième approche in vitro, a consisté en l’étude de l’impact d’une cassure double brin induite par CRISPR-Cas9, réalisées dans des fibroblastes humains dans lesquels l’expression de RAD50 a été modulée par deux approches (shRNA et édition génomique). Les souris mâles mutantes présentent une diminution de la taille de leur testicule et de leurs tubes séminifères (TS). Dans la lumière des TS, aucun spermatozoïde n’a été observé et les spermatocytes semblent bloqués en prophase I, moment où RAD50 intervient au cours de la méiose. Par ailleurs, un seuil d’expression de RAD50 inférieur à 10%, obtenu par le shRNA anti-RAD50, impacte la prolifération cellulaire, par excès d'apoptose, majoré par l’induction d’une CDB. Ainsi, l’exploration de RAD50 dans la fertilité doit être poursuivie, par étude de la fertilité des femelles mutantes et en tentant de reproduire ces expérimentations en conditions méiotiques.

Introduction : A lot of environmental factors can influence our own health and fertility. These last few years, their mechanism and method have been more and more described in scientific literature. In parallel, we can also observe a decrease in fertility in the general population. Our goal is to assess the relationship between environmental risk factors and assisted reproductive technology (ART) outcomes and parameters of men and women fertility. Methodology: Prospective cohort in Bordeaux University Hospital Center. The population studied is patients exposed to environmental risk factors vs non exposed patients (couples involved in ART procedure) (n=115). Exposure is evaluated by a questionnaire given to the patients before ovarian puncture. Primary study endpoint is clinical pregnancy rate by puncture. Results: No significant difference was observed between patients exposed vs patients non exposed on all studied criteria (primary and secondary). Conclusion : Our study has not identified any influence of environmental factors on ART outcomes or women and men fertility. Further studies are needed in order to improve scientific knowledge about the effects of environmental factors on fertility and to create preventive measures for couples ongoing ART procedures.; Introduction : Depuis de nombreuses années, la communauté scientifique évalue la fertilité humaine et le constat est une baisse potentielle de la fertilité dans sa globalité. De plus en plus d’études s’intéressent ainsi aux effets de certains toxiques environnementaux sur la fertilité. L’objectif principal de notre étude est de chercher à déterminer les effets éventuels des expositions environnementales professionnelles et extraprofessionnelles sur les critères de succès d’assistance médicale à la procréation (AMP) ainsi que sur les caractéristiques féminines et masculines liées à la fertilité. Matériels et méthodes : Il s’agit d’une cohorte prospective non interventionnelle avec comparaison des couples exposés versus les couples non exposés en déterminant au préalable un seuil d’exposition. La population d’étude correspond à l’ensemble des couples en parcours d’AMP au CHU de Bordeaux (n=115). Les données d’analyses sont recueillies via un questionnaire distribué aux couples le jour de la ponction ovocytaire. Le critère d’évaluation principale est le taux de grossesse clinique par ponction. Résultats : Aucune différence significative n’est retrouvée entre les couples exposés et les non exposés, quelle que soit l’exposition (professionnelle et extra-professionnelle) sur l’ensemble des critères étudiés. Conclusion : Notre étude n’a pas permis d’identifier l’impact de l’exposition environnementale sur les critères liés à la fertilité. Néanmoins, il est nécessaire de continuer les travaux sur le sujet pour améliorer les connaissances scientifiques concernant l’effet des toxiques de l’environnement sur la fertilité et renforcer la mise en place d’actions de prévention auprès des couples en parcours d’AMP.

Introduction: the etiologies of azoospermia are numerous and multifactorial. However, the latter remains unexplained in many cases. Reproductive medicine is essential in the care of these men with a desire for children. Methods: the study focused on all molecular genetic analyzes made at Bordeaux University Hospital as part of male infertility. After a balance sheet of the results, eight patients for whom two mutations of CFTR gene were not identified, were selected. They presented all the criteria for azoospermia related to congenital bilateral absence of vas deferens, defined by hypospermia, acidic pH, fructose level collapsed in the seminal plasma and clinical and echographic absence of vas deferens. Results: among the selected patients for second-line analyzes, one had a mutation in ADGRG2 gene. There was no evidence of deep intronic mutation of CFTR gene. Conclusion: genetics and reproductive medicine are intimately linked. The first allows an etiological diagnosis while the second proposes a therapeutic care. In the context of a congenital bilateral absence of vas deferens, the first genetic examination is the analysis of CFTR gene. In addition, deep intronic mutations could be sought systematically. The analysis of ADGRG2 gene is interesting in second intention. High throughput sequencing of the exome and genome are interesting perspectives for the genetic diagnosis of male infertility., Introduction : les étiologies de l’azoospermie sont nombreuses et multifactorielles. Cependant, cette dernière reste inexpliquée dans de nombreux cas. L’assistance médicale à la procréation est essentielle dans la prise en charge de ces hommes ayant un désir d’enfant. Matériels et méthodes : l’étude a porté sur l’ensemble des analyses de génétique moléculaire faites au CHU de Bordeaux dans le cadre de l’infertilité masculine. Après un état des lieux des résultats, huit patients pour lesquels deux mutations du gène CFTR n’ont pas été identifiées, ont été sélectionnés. Ils présentaient tous les critères de l’azoospermie liée à une agénésie bilatérale des canaux déférents, définie par l’hypospermie, le pH acide, le taux de fructose effondré dans le plasma séminal et l’absence clinique et échographique des canaux déférents. Résultats : parmi les patients sélectionnés pour les analyses de seconde intention, un était porteur d’une mutation du gène ADGRG2. Il n’a pas été mis en évidence de mutation intronique profonde du gène CFTR. Conclusion : la génétique et l’assistance médicale à la procréation sont intimement liées. La première permet un diagnostic étiologique tandis que la seconde propose une prise en charge thérapeutique. Dans le cadre d’une agénésie bilatérale des canaux déférents, l’examen génétique de première intention est l’analyse du gène CFTR. En complément, les mutations introniques profondes pourraient être recherchées de manière systématique. L’analyse du gène ADGRG2 est intéressante en seconde intention. Les séquençages haut débit de l’exome et du génome sont des perspectives intéressantes pour le diagnostic génétique de l’infertilité masculine.