How and when to measure pH in IVF culture media: validation of a portable blood gas analyzer in two IVF culture dishes for time lapse and conventional incubators.

PURPOSE: Maintaining a stable pH at optimal level in human embryo culture media is crucial for embryo development but poses a challenge for all IVF laboratories. We validate analytically reliable conditions for pH measurement that are as close as possible to the embryo microenvironment during IVF. METHODS: This was a multicentric study. A Siemens EPOC portable blood gas analyzer was used. The analytical validation was carried out under the culture medium (Global Total HSA®) conditions of use (microdroplets, under oil overlay, in a IVF incubator with (EmbryoScope®) or without a time lapse system (K system G210+®) and using IVF dishes. The validation included repeatability ("within-run" precision), total precision (between-day precision), trueness based on inter-laboratory comparison, inaccuracy based on external quality assessment and comparison to the reference technique. We also assessed the pre-analytical medium incubation time required to obtain a target value. RESULTS: A measurement after an incubation period of 24 to 48 h is more representative of the pH to which the embryo will be exposed throughout the culture. The "within-run" and "between-day" precision show very low coefficients of variation (CV%): 0.17 to 0.22% and 0.13 to 0.34%, respectively, with IVF culture media. Trueness (% bias) range from - 0.07 to - 0.03%. We demonstrate good correlation between EPOC and reference pH electrode with an overestimation of 0.03 pH units of EPOC. CONCLUSION: Our method demonstrates good analytical performance for IVF laboratories wishing to implement a robust quality assurance system to monitor pH in embryo culture media. Compliance with stringent pre-analytical and analytical conditions is essential.

Successful live birth after in vitro maturation treatment in a patient with autoimmune premature ovarian failure: a case report and review of the literature.

OBJECTIVE: 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 literature of livebirths obtained after oocytes IVM treatment in this indication. METHODS: The 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. RESULTS: The six oocyte-cumulus complexes collected matured in vitro. After intracytoplasmic sperm injection (ICSI), five embryos were obtained. Pregnancy was achieved after the fresh transfer of two embryos and appropriate endometrial preparation. A normal female child was delivered following a 37-weeks pregnancy characterized by the onset of adrenal insufficiency and unstable diabetes. CONCLUSIONS: We 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.

Decrease in pregnancy rate after endometrial scratch in women undergoing a first or second in vitro fertilization. A multicenter randomized controlled trial.

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 Ministère de la Santé Français (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.

[CFTR gene variant screening in gamete donation candidates in France: Which indications? How to screen? Why?] / Dépistage de variant du gène CFTR chez les candidats au don de gamètes en France : quand ? Comment ? Pourquoi ?

OBJECTIVES: According to French recommendations, only the caryotype is carried out as a first line in candidates for gamete donation. The prescription of additional genetic tests for variants responsible for serious monogenic diseases is only recommended in the case of call points. However, cystic fibrosis remains the most common genetic disease with serious consequences in childhood. The purpose is to assess the different screening strategies in the Centres d'Études et de Conservation des Œufs et du Sperme humain (CECOS) regarding abnormalities of the Cystic Fibrosis Transmembrane conductance Regulator gene (CFTR). METHOD: Our study is based on the analysis of data collected using a questionnaire. Private centres authorised to donate have been excluded from this work. RESULTS: Twenty-six centres participated out of the 33 interviewees. Two centres carry out systematic screening in all their sperm donation candidates while only one centre practises it in its oocyte donation candidates. For the other 23 centres, research is carried out in case of strong clinical suspicions according to personal or family history and when one of the two members of the recipient couple has a known variant. Regarding the molecular analysis technique used, 56.5% of centres use PCR with commercial kits, whereas the other centers use next-generation sequencing. CONCLUSION: Targeted screening therefore remains widely practiced in France unlike other countries. Moving to expanded systematic screening raises ethical, financial and organisational issues.

Gynaecological follow-up for women of reproductive age with multiple sclerosis: The GYNESEP study.

BACKGROUND: The gynaecological care of women with Multiple Sclerosis has received little attention; most reports focussed on pregnancy or sexuality. The objective of the present study was to evaluate if gynaecological follow-up for women of reproductive age with Multiple Sclerosis was adequate. METHODS: We performed a cross-sectional study on a large cohort of women with Multiple Sclerosis aged 18-40 years. All participants completed online questionnaires on general health status, gynaecological follow-up, and sexuality. Expanded Disability Status Scale (EDSS) scores were extracted from medical records. The study was registered in clinicaltrials.gov with the number NCT05248438, and in the European database ID-RCB with the number 2021-A02912-39. RESULTS: Of the 192 patients who completed questionnaires, 157 (82.2%) reported gynaecological follow-up. Of the 155 patients on immunosuppressive treatments, only 31 (20%) underwent annual cervical screening. Of the 140 patients who met the French papillomavirus vaccination age recommendations, only 50 (35.7%) were vaccinated. A total of 128 (66.7%) patients used contraception. However, 16 (8.3%) patients reported unplanned pregnancies since the time of diagnosis. CONCLUSION: Women with Multiple Sclerosis require more information on reproductive health and prevention of cancer. Better contraceptive advice would reduce the number of unplanned pregnancies and avoid foetal exposure to potentially teratogenic treatment.

Chromosomal abnormalities in oocyte donor candidates: a French survey of over 8200 karyotypes.

OBJECTIVE: To study karyotypes of more than 8,200 oocyte donor candidates in nulliparous or multiparous women compared to a reference population. DESIGN: A retrospective observational multicentric study. SUBJECTS: The study included two cohorts of oocyte donor candidates recruited between January 2005 and October 2021: multiparous women with at least one child at the time of recruitment, and nulliparous women. Both were compared to a reference population composed of female newborns from literature. EXPOSURE: Not applicable. MAIN OUTCOME MEASURES: Blood lymphocyte karyotype. RESULTS: A total of 8229 oocyte donor candidates from 22 fertility centers were included in this study. Nulliparous women (n=1890) and multiparous ones (n=6339) were compared to 8102 female newborns. Overall, 65 candidates were carriers of chromosomal abnormalities and were therefore excluded from the donation process (0.79%, 95% CI: 0.60-0.98). The occurrence of balanced structural chromosomal rearrangements was globally increased in the study population (0.49%, 95% CI: 0.34-0.64) compared to female newborns (0.24%, 95% CI: 0.34-0.64, p=0.0086). The number of reciprocal translocations was increased 5-fold in nulliparous oocyte donor candidates (0.37%, 95% CI: 0.10-0.64, p=0.013). The incidence of sex chromosome mosaicism was notably increased in multiparous oocyte donor candidates, with 17 cases (0.27%, 95% CI: 0.14-0.40, p=0.0052). Among chromosomal aberration carriers only two nulliparous women (one reciprocal translocation and one sex chromosome mosaicism) had fertility issues with a diagnosis of premature ovarian failure. CONCLUSION: In this comprehensive 16-years French experience of karyotyping in oocyte donor candidates, we confirmed an increased incidence of balanced structural chromosomal rearrangements, especially among those without children at the time of recruitment. Karyotyping could be considered to identify any chromosomal abnormalities that may not be easily detectable through medical questioning. These abnormalities pose an inherent genetic risk for gamete recipients if left undetected.

Effects of air pollution on clinical pregnancy rates after in vitro fertilisation (IVF): a retrospective cohort study.

OBJECTIVE: To 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. DESIGN: Exploratory retrospective cohort study. SETTING: This 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. PARTICIPANTS: This 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 MEASURES: The 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. RESULTS: We found negative associations between cumulative O3 exposure 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. CONCLUSION: Air 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.

[Assisted reproductive technology outcomes of infertile men carrying balanced chromosomal rearrangements or Y-chromosome microdeletions - Retrospective study]. / Résultats de l'assistance médicale à la procréation chez les hommes infertiles porteurs de remaniements chromosomiques équilibrés ou de microdélétions du chromosome Y ­ Étude rétrospective.

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 Réunion. 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 MédiFirst® (la Réunion). 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.

National survey on the opinions of French specialists in assisted reproductive technologies about social issues impacting the future revision of the French Bioethics laws.

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.

Local transgene expression and whole-body transgenesis to model brain diseases in nonhuman primate.

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.

Semen and male genital tract characteristics of patients with Fabry disease: the FERTIFABRY multicentre observational study.

BACKGROUND: Fabry disease (FD) is a rare disorder caused by the deficient activity of α-galactosidase A (α-Gal A). This enzymatic deficit results in the cellular accumulation of globotriaosylceramide (GL-3 or Gb3) and related glycosphingolipids in practically all organs and tissues in the body. The identification of deposits of Gb3 at the reproductive tract level suggests that this part of the body might be involved. We undertook this study to assess the impact of Fabry disease in male gonadal function. MATERIALS AND METHODS: This was a multicentre cross-sectional, prospective study that included patients aged 18 to 65 years with Fabry disease, receiving care in a specialized institution. The prevalence of at least one abnormal category in the semen analysis was presented with 95% confidence intervals (CI). The association between infertility and semen analysis abnormality was assessed by Fisher's exact test. The association of factors associated with fertility or semen analysis abnormality were analysed by a multivariable logistic regression model and expressed by an odds ratio (OR) and its bilateral 95% CI. RESULTS: Overall, 14 (82.4% [95% CI, 56.6-96.2]) of the patients had at least one abnormal category in the semen analysis based on WHO criteria. Sixteen patients responded to the questionnaire on fertility, 11 of whom were classified as fertile. Nine of the 11 fertile patients presented at least one abnormal category in the semen analysis. No association was found between infertility and semen analysis abnormality (p = 1.0000). Age of patient at inclusion (OR, 1.19; 95% CI, 0.98 to 1.45; p = 0.0854) and duration of replacement therapy (OR, 1.28; 95% CI, 0.96 to 1.65; p = 0.1263) were associated with sperm abnormalities. Eleven of the 16 patients had a normal hormonal profile. An ultrasound anomaly of the genital tract was observed in 12 patients. CONCLUSIONS: These results suggest that, while FD might have a detrimental effect on the semen characteristics, the reproductive function diminished only slightly. Further studies are warranted to assess the impact of the disease and of sperm abnormalities in the fertility of male patients with FD.

CONTEXTE: La maladie de Fabry (FD) est. une maladie rare de transmission génétique liée au chromosome X due à un déficit en α-galactosidase A (α-GAL A) lysosomale. Ce déficit enzymatique entraîne l'accumulation de globotriaosylcéramide (GL-3 ou Gb3) dans pratiquement tous les types cellulaires de l'organisme, responsable d'une atteinte multisystémique. Le retentissement sur l'appareil génital étant peu documenté, cette étude a pour objectif d'évaluer l'impact de la maladie de Fabry sur la fonction gonadique masculine. MATÉRIELS ET MÉTHODES: Il s'agit d'une étude observationnelle, prospective, transversale, multicentrique incluant tous les patients suivis dans des centres spécialisés, âgés de 18 à 65 ans, atteints de maladie de Fabry. La prévalence d'au moins une catégorie anormale dans l'analyse du sperme a été présentée avec des intervalles de confiance (IC) de 95%. L'association entre l'infertilité et l'anomalie du sperme a été évaluée par le test exact de Fisher. Les facteurs associés à l'anomalie du sperme ont été analysés par un modèle de régression logistique multivariée et estimés par des rapports de cotes (Odds ratio [OR]) et leurs IC 95%. RÉSULTATS: Au total, 14 patients [82.4% (IC 95%, 56.6­96.2)] présentaient au moins une caractéristique spermatique anormale selon les critères OMS. Seize patients ont répondu au questionnaire sur la fertilité, dont 11 ont été classés comme fertiles. Neuf des 11 patients fertiles présentaient au moins une anomalie des caractéristiques spermatiques. Aucune association n'a été trouvée entre l'infertilité et une analyse anormale du sperme (p = 1.0000). L'âge du patient à l'inclusion (OR, 1.19; IC 95%, 0.98­1.45; p = 0.0854) et la durée du traitement substitutif (OR, 1.28; IC 95%, 0.96­1.65; p = 0.1263) étaient associés à une anomalie des caractéristiques spermatiques. Onze des 16 patients avaient un profil hormonal normal. Une anomalie échographique du tractus genital était observée dans 12 des patients. CONCLUSIONS: Ces résultats suggèrent que bien que des anomalies des caractéristiques séminales puissent être observées chez des patients atteints de maladie de Fabry, la fonction de reproduction est. très peu altérée.

What about αvß3 integrins in molecular imaging in oncology?

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 (αvß3, but also α5ß1 and αvß6). 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, αvß3 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 αvß3-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.

Systemic Gene Delivery by Single-Dose Intracardiac Administration of scAAV2/9 and scAAV2/rh10 Variants in Newborn Rats.

Recombinant 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.

[Method validation of a critical parameter in human embryos culture: culture media pH]. / Validation de la mesure d'un paramètre critique en culture d'embryons humains : le pH.

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.

Sperm aneuploidy and DNA fragmentation in unexplained recurrent pregnancy loss: a multicenter case-control study.

BACKGROUND: Recurrent pregnancy loss (RPL) is defined as the loss of at least three pregnancies in the first trimester. Although the most common cause is embryo aneuploidy, and despite female checkup and couple karyotyping, in about 50% of cases RPL remain unexplained. Male implication has little been investigated and results are discordant. In this context, we conducted a multi-center prospective case-control study to investigate male gamete implication in unexplained RPL. METHODS: A total of 33 cases and 27 controls were included from three university hospitals. We investigated environmental and family factors with a detailed questionnaire and andrological examination, sperm characteristics, sperm DNA/chromatin status using the sperm chromatin structure assay (SCSA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and sperm aneuploidy using fluorescence in situ hybridization (FISH). The Mann-Whitney test and the Wilcoxon or Fisher exact tests were used. A non-parametric Spearman correlation was performed in order to analyze the relationship between various sperm parameters and FISH and sperm DNA fragmentation results. RESULTS: We found significant differences between cases and controls in time to conceive, body mass index (BMI), family history of infertility and living environment. In cases, total sperm motility and the percentage of morphologically normal spermatozoa were significantly decreased. No difference was found between cases and controls in sperm DNA fragmentation or chromatin integrity. In cases, spermatozoa with aneuploidy, hyperhaploidy and chromosome 18 disomy were significantly increased. CONCLUSIONS: This prospective case-control study is one of the largest to examine environmental factors, sperm characteristics, sperm DNA fragmentation and chromatin, and chromosome anomalies in spermatozoa in relation to unexplained recurrent pregnancy loss. The originality of our study lies in the comprehensive andrological examination and search for risk factors and fertility history. Further studies are needed to confirm the links between unexplained RPL and a male family history of infertility or miscarriages. The increased sperm aneuploidy observed in unexplained RPL supports a male etiology. These data pave the way for further studies to demonstrate the value of preimplantation genetic screening in men with increased sperm aneuploidy whose partners experience unexplained RPL.

CONTEXTE: Les fausses couches à répétition (FCR) sont définies lorsqu'au moins trois fausses couches ont eu lieu au cours du premier trimestre. Bien que la cause la plus fréquente soit l'aneuploïdie embryonnaire, et malgré un bilan chez la femme et un caryotype du couple, dans environ 50% des cas, les FCR restent inexpliquées. L'implication masculine a été peu étudiée et les résultats restent discordants. Ainsi, nous avons réalisé une étude cas-témoins prospective et multicentrique afin d'investiguer l'implication du gamète mâle dans les FCR inexpliquées. MÉTHODES: Un total de 33 cas et de 27 témoins ont été inclus recrutés au sein de trois hôpitaux universitaires. Nous avons étudié les facteurs environnementaux et familiaux à partir d'un questionnaire détaillé ainsi que les données de l'examen andrologique, les caractéristiques du sperme, la fragmentation de l'ADN et la chromatine du spermatozoïde en utilisant le sperm chromatine structure assay (SCSA) et le test du TUNEL, ainsi que l'aneuploïdie des spermatozoïdes grâce à la méthode d'hybridation in situ de sonde chromosomique (FISH). Le test de Mann-Whitney et les tests exacts de Wilcoxon ou de Fisher ont été utilisés. Une corrélation de Spearman non-paramétrique a été réalisée afin d'analyser la relation entre les divers paramètres de sperme et les résultats de fragmentation d'ADN du sperme et les résultats de la FISH. RÉSULTATS: Nous avons trouvé des différences significatives entre les cas et les témoins pour le délai de conception, l'indice de masse corporelle (IMC), les antécédents familiaux d'infertilité et le milieu de vie. Chez les cas, la mobilité totale des spermatozoïdes et le pourcentage de spermatozoïdes normaux étaient significativement diminués. Aucune différence n'a été trouvée entre les cas et les témoins concernant la fragmentation de l'ADN des spermatozoïdes ou l'intégrité de la chromatine. Chez les cas, la fréquence des spermatozoïdes présentant une aneuploïdie, une hyperhaploïdie et une disomie du chromosome 18 étaient significativement augmentée. CONCLUSIONS: Cette étude cas-témoins prospective est. l'une des plus importantes ayant investigué à la fois les facteurs environnementaux, les caractéristiques des spermatozoïdes, la fragmentation et la chromatine de l'ADN des spermatozoïdes et les anomalies chromosomiques des spermatozoïdes en rapport avec les fausses couches à répétition inexpliquée. L'originalité de notre étude réside dans l'examen andrologique complet et la recherche des facteurs de risque et des antécédents reproductifs. D'autres études sont nécessaires pour confirmer les liens entre les FCR inexpliquées et les antécédents familiaux masculins d'infertilité ou de fausses couches. L'augmentation de l'aneuploïdie des spermatozoïdes observée chez les cas présentant des FCR inexpliquées plaide en faveur d'une étiologie masculine. Ces données ouvrent la voie à d'autres études pour démontrer l'utilité d'un dépistage génétique préimplantatoire chez les hommes présentant une augmentation de l'aneuploïdie des spermatozoïdes dont les partenaires présentent des FCR inexpliquées.

Evaluation of intrauterine insemination practices: a 1-year prospective study in seven French assisted reproduction technology centers.

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.