Developing and validating a prediction model of live birth following single vitrified-warmed blastocyst transfer.

RESEARCH QUESTION: Can the developed clinical prediction model offer an accurate estimate of the likelihood of live birth, involving blastocyst morphology and vitrification day after single vitrified-warmed blastocyst transfer (SVBT), and therefore assist clinicians and patients? STUDY DESIGN: Retrospective cohort study conducted at a Spanish university-based reproductive medicine unit (2017-2021) including consecutive vitrified-warmed blastocysts from IVF cycles. A multivariable logistic regression incorporated key live birth predictors: vitrification day, embryo score, embryo ploidy status and clinically relevant variables, i.e. maternal age. RESULTS: The training set involved 1653 SVBT cycles carried out between 2017 and 2020; 592 SVBT cycles from 2021 constituted the external validation dataset. The model revealed that female age and embryo characteristics, including overall quality and blastulation day, is linked to live birth rate in SVBT cycles. Stratification by vitrification day and quality (from day-5A to day-6 C blastocysts) applied to genetically tested and untested embryos. The model's area under the curve was 0.66 (95% CI 0.64 to 0.69) during development and 0.65 (95% CI 0.61 to 0.70) in validation, denoting moderate discrimination. Calibration plots showed strong agreement between predicted and observed probabilities. CONCLUSION: By incorporating essential predictors such as vitrification day, embryo morphology grade, age and preimplantation genetic testing for aneuploidy usage, this predictive model offers valuable guidance to clinicians and patients, enabling accurate forecasts of live birth rates for any given vitrified blastocyst within SVBT cycles. Additionally, it serves as a potentially indispensable laboratory tool, aiding in selecting the most promising blastocysts for optimal outcomes.

Unraveling hallmark suitability for staging pre- and post-implantation stem cell models.

The advent of novel 2D and 3D models for human development, including trophoblast stem cells and blastoids, has expanded opportunities for investigating early developmental events, gradually illuminating the enigmatic realm of human development. While these innovations have ushered in new prospects, it has become essential to establish well-defined benchmarks for the cell sources of these models. We aimed to propose a comprehensive characterization of pluripotent and trophoblastic stem cell models by employing a combination of transcriptomic, proteomic, epigenetic, and metabolic approaches. Our findings reveal that extended pluripotent stem cells share many characteristics with primed pluripotent stem cells, with the exception of metabolic activity. Furthermore, our research demonstrates that DNA hypomethylation and high metabolic activity define trophoblast stem cells. These results underscore the necessity of considering multiple hallmarks of pluripotency rather than relying on a single criterion. Multiplying hallmarks alleviate stage-matching bias.

A comprehensive multiplatform metabolomic analysis reveals alterations of 2-hydroxybutyric acid among women with deep endometriosis related to the pesticide trans-nonachlor.

BACKGROUND: Exposure to persistent organic pollutants (POPs) has been related to the risk of endometriosis however the mechanisms remain unclear. The objective of the present study was to characterize the metabolic profiles underpinning the associations between POPs and endometriosis risk. METHODOLOGY: A hospital-based case-control study was conducted in France to recruit women with and without surgically confirmed deep endometriosis. Women's serum was analyzed using gas and liquid chromatography coupled to high-resolution mass spectrometry (HRMS) to measure the levels of polychlorinated biphenyls (PCBs), organochlorinated pesticides (OCPs) and per-/polyfluoroalkyl substances (PFAS). A comprehensive metabolomic profiling was conducted using targeted HRMS and 1H nuclear magnetic resonance (1H NMR) to cover polar and non-polar fractions. A "meet-in-the-middle" statistical framework was applied to identify the metabolites related to endometriosis and POP levels, using multivariate linear and logistic regressions adjusting for confounding variables. RESULTS: Fourteen PCBs, six OCPs and six PFAS were widely found in almost all serum samples. The pesticide trans-nonachlor was the POP most strongly and positively associated with deep endometriosis risk, with odds ratio (95 % confidence interval) of 2.42 (1.49; 4.12), followed by PCB180 and 167. Women with endometriosis exhibited a distinctive metabolic profile, with elevated serum levels of lactate, ketone bodies and multiple amino acids and lower levels of bile acids, phosphatidylcholines (PCs), cortisol and hippuric acid. The metabolite 2-hydroxybutyrate was simultaneously associated to endometriosis risk and exposure to trans-nonachlor. CONCLUSIONS: To the best of our knowledge, this is the first comprehensive metabolome-wide association study of endometriosis, integrating ultra-trace profiling of POPs. The results confirmed a metabolic alteration among women with deep endometriosis that could be also associated to the exposure to POPs. Further observational and experimental studies will be required to delineate the causal ordering of those associations and gain insight on the underlying mechanisms.

An update on human pre- and peri-implantation development: a blueprint for blastoids.

Despite over 40 years following the first birth from medically assisted reproduction (MAR) technologies, mechanisms underlying the key developmental events during the first 7 days of human development, such as signaling pathway contribution, are remaining a mystery. An in-depth mechanistic understanding of how the human preimplantation embryo develops would support the optimization of embryo quality assessment methods and culturing conditions, thereby increasing the success rate of MAR. However, the limited availability of human embryos, legitimate ethical concerns, and regulations still present an obstacle toward our advancement of knowledge. Stem cell-based embryonic models, including blastoids than model blastocysts, offer unprecedented opportunities to fill knowledge gaps and complement animal models. Blastoids' predictive power depends on how faithfully they recapitulate the blastocyst. Here, we review the state of the art of human pre- and peri-implantation development and outline the specificities of human embryo research to clarify the framework for blastoid research.

Predicting the number of oocytes retrieved from controlled ovarian hyperstimulation with machine learning.

STUDY QUESTION: Can machine learning predict the number of oocytes retrieved from controlled ovarian hyperstimulation (COH)? SUMMARY ANSWER: Three machine-learning models were successfully trained to predict the number of oocytes retrieved from COH. WHAT IS KNOWN ALREADY: A number of previous studies have identified and built predictive models on factors that influence the number of oocytes retrieved during COH. Many of these studies are, however, limited in the fact that they only consider a small number of variables in isolation. STUDY DESIGN, SIZE, DURATION: This study was a retrospective analysis of a dataset of 11,286 cycles performed at a single centre in France between 2009 and 2020 with the aim of building a predictive model for the number of oocytes retrieved from ovarian stimulation. The analysis was carried out by a data analysis team external to the centre using the Substra framework. The Substra framework enabled the data analysis team to send computer code to run securely on the centre's on-premises server. In this way, a high level of data security was achieved as the data analysis team did not have direct access to the data, nor did the data leave the centre at any point during the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: The Light Gradient Boosting Machine algorithm was used to produce three predictive models: one that directly predicted the number of oocytes retrieved and two that predicted which of a set of bins provided by two clinicians the number of oocytes retrieved fell into. The resulting models were evaluated on a held-out test set and compared to linear and logistic regression baselines. In addition, the models themselves were analysed to identify the parameters that had the biggest impact on their predictions. MAIN RESULTS AND THE ROLE OF CHANCE: On average, the model that directly predicted the number of oocytes retrieved deviated from the ground truth by 4.21 oocytes. The model that predicted the first clinician's bins deviated by 0.73 bins whereas the model for the second clinician deviated by 0.62 bins. For all models, performance was best within the first and third quartiles of the target variable, with the model underpredicting extreme values of the target variable (no oocytes and large numbers of oocytes retrieved). Nevertheless, the erroneous predictions made for these extreme cases were still within the vicinity of the true value. Overall, all three models agreed on the importance of each feature which was estimated using Shapley Additive Explanation (SHAP) values. The feature with the highest mean absolute SHAP value (and thus the highest importance) was the antral follicle count, followed by basal AMH and FSH. Of the other hormonal features, basal TSH, LH, and testosterone levels were similarly important and baseline LH was the least important. The treatment characteristic with the highest SHAP value was the initial dose of gonadotropins. LIMITATIONS, REASONS FOR CAUTION: The models produced in this study were trained on a cohort from a single centre. They should thus not be used in clinical practice until trained and evaluated on a larger cohort more representative of the general population. WIDER IMPLICATIONS OF FINDINGS: These predictive models for the number of oocytes retrieved from COH may be useful in clinical practice, assisting clinicians in optimizing COH protocols for individual patients. Our work also demonstrates the promise of using the Substra framework for allowing external researchers to provide clinically relevant insights on sensitive fertility data in a fully secure, trustworthy manner and opens a number of exciting avenues for accelerating future research. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the French Public Bank of Investment as part of the Healthchain Consortium. T.Fe., C.He., J.C., C.J., C.-A.P., and C.Hi. are employed by Apricity. C.Hi. has received consulting fees and honoraria from Vitrolife, Merck Serono, Ferring, Cooper Surgical, Dibimed, Apricity, and Fairtility and travel support from Fairtility and Vitrolife, participates on an advisory board for Merck Serono, was the founder and organizer of the AI Fertility conference, has stock in Aria Fertility, TMRW, Fairtility, Apricity, and IVF Professionals, and received free equipment from Planar in exchange for first user feedback. C.J. has received a grant from BPI. J.C. has also received a grant from BPI, is a member of the Merck AI advisory board, and is a board member of Labelia Labs. C.He has a contract for medical writing of this manuscript by CHU Nantes and has received travel support from Apricity. A.R. haș received honoraria from Ferring and Organon. T.Fe. has received a grant from BPI. TRIAL REGISTRATION NUMBER: N/A.

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

Objective: Assisted 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 results: A 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.

Developmental-stage specific single-cell human embryo dissociation.

Isolation of individual cells ensures detailed analysis of human embryos and promotes our understanding of molecular mechanisms driving embryo development and cell specification. Here, we present a protocol for the processing of human embryos for single-cell analysis. We describe steps for growing embryos and individualizing cells from the polar and the mural parts of trophectoderm at the blastocyst stage using laser dissection. We then detail embryo dissociation followed by steps to pick, wash, and dispense cells in plates.

Does paternal age affect the live birth rate in donor oocyte cycles? A systematic review and meta-analysis.

PURPOSE: While delayed parenthood is increasing worldwide, the effect of paternal age on in vitro fertilization (IVF) outcomes remains unclear. The egg donation model appears to be relevant to studying the independent impact of paternal age on clinical outcome, but the available studies are heterogeneous and contradictory. This systematic review and meta-analysis aimed to assess the relationship between paternal age and live birth rate (LBR) in egg donation cycles. METHODS: A systematic search of the literature was conducted in PubMed, Embase, and the Cochrane Library from inception to June 30, 2021. All studies on egg donation cycles where LBR is reported according to male age were included. Study selection, bias assessment, and data extraction were performed by two independent reviewers according to the Cochrane methods. RESULTS: Eleven studies involving 10,527 egg donation cycles were finally included. The meta-analysis showed a slight but significant and linear decrease in LBR with increasing paternal age (estimate - 0.0055; 95% CI (- 0.0093; - 0.0016), p = 0.006), with low heterogeneity (I2 = 25%). No specific threshold was identified. A similar trend toward decreased clinical pregnancy rate with advancing paternal age was found but did not reach statistical significance (p = 0.07). CONCLUSION: This meta-analysis demonstrates that increasing paternal age is associated with a slight but significant and linear decrease in the live birth rate in egg donation cycles, with no apparent threshold effect. Although this requires further confirmation, this information is important for counseling men who are considering delayed childbearing.

Impact of the duration of oestradiol treatment on live birth rate in Hormonal Replacement Therapy cycle before frozen blastocyst transfer.

Although the duration of progesterone administration in Hormonal Replacement Therapy (HRT) cycles before frozen embryo transfer is standardized, the optimal duration of oestrogen treatment remains controversial. In this monocentric retrospective study conducted in all single frozen blastocyst transfer (FBT) performed with HRT between January 2016 and July 2019, we evaluated the association between the duration of oestradiol treatment before FBT and live birth rate (LBR) in HRT cycles. Cycles were gathered in 3 groups according to quartiles of duration of oestrogen treatment. LBR was compared across the 3 groups and multivariate analysis was performed. We included 2235 single FBT cycles; 507, 1257 and 471 with E2 treatment below 23 days, 23-30 days (reference) and more than 30 days respectively. After multivariate analysis and adjustment, no significant difference in LBR was found between below 23 or more than 30 days and reference groups (OR = 0.93 [0.68-1.27] and OR = 1.29 [0.88-1.89] respectively). Complementary sensitivity analysis led to a non-significant adjusted OR = 1.66 [IC 0.9-3.1]. In conclusion, our study showed that the duration of E2 treatment in HRT cycles before FBT is not associated with LBR.

Naive Pluripotent and Trophoblastic Stem Cell Lines as a Model for Detecting Missing Proteins in the Context of the Chromosome-Centric Human Proteome Project.

The Chromosome-centric Human Proteome Project (C-HPP) aims at identifying the proteins as gene products encoded by the human genome, characterizing their isoforms and functions. The existence of products has now been confirmed for 93.2% of the genes at the protein level. The remaining mostly correspond to proteins of low abundance or difficult to access. Over the past years, we have significantly contributed to the identification of missing proteins in the human spermatozoa. We pursue our search in the reproductive sphere with a focus on early human embryonic development. Pluripotent cells, developing into the fetus, and trophoblast cells, giving rise to the placenta, emerge during the first weeks. This emergence is a focus of scientists working in the field of reproduction, placentation and regenerative medicine. Most knowledge has been harnessed by transcriptomic analysis. Interestingly, some genes are uniquely expressed in those cells, giving the opportunity to uncover new proteins that might play a crucial role in setting up the molecular events underlying early embryonic development. Here, we analyzed naive pluripotent and trophoblastic stem cells and discovered 4 new missing proteins, thus contributing to the C-HPP. The mass spectrometry proteomics data was deposited on ProteomeXchange under the data set identifier PXD035768.

Mixtures of persistent organic pollutants and ovarian function in women undergoing IVF.

RESEARCH QUESTION: Do internal levels of persistent organic pollutants (POP) in serum and follicular fluid affect ovarian function of women attending IVF? DESIGN: This cohort study included 136 women undergoing IVF in the assisted reproductive technology (ART) service of University Hospital from Nantes (France). Representative POP were measured using gas and liquid chromatography coupled with tandem mass spectrometry. Polyfluoroalkylated and perfluoroalkylated substances were measured in serum and polychlorinated biphenyls and organochlorinated pesticides in follicular fluid. Statistical associations between POP and ovarian reserve markers (anti-Müllerian Hormone [AMH] and antral follicle count [AFC], and ovarian responsiveness markers (Ovarian Sensitivity Index [OSI] and Follicular Output RaTe [FORT]), were explored in single and multipollutant regression models. RESULTS: Twenty-seven out of 53 POP congeners were frequently detected in almost all women attending IVF. Adjusted models did not show statistically significant associations between POP and ovarian reserve markers. Positive associations were found between some POP, i.e. hexachlorobenzene with FORT (ß 0.42, 95% CI 0.13 to 0.71, P = 0.005) or PCB52 with Ovarian Sensitivity Index (ß 0.22; 95% CI, 0.07 to 0.38, P = 0.005). Negative associations between some polyfluoroalkylated and perfluoroalkylated substances, PCB189 and trans-nonachlor with AFC and AMH were found among current smokers. CONCLUSIONS: Globally, associations between POP and the markers of ovarian function or responsiveness were lacking. Nonetheless, the stratification analysis suggested that current smoking could be a risk modifier, and extension of the study to a larger population sample size is needed.

Sexual function in heterosexual couples undergoing assisted reproductive technology (ART) cycles with donor sperm.

PURPOSE: Sexuality and the desire for children are closely linked, and infertility can increase the risk of sexual dysfunction (SD). Among heterosexual infertile couples undergoing assisted reproductive technology (ART) cycles, those referred for donor sperm cycles constitute a specific subgroup, potentially different than those undergoing ART with partner's sperm, as giving up on biological parenthood can be difficult to overcome. However, the impact of donor sperm ART on infertile couples' sexuality has been hardly explored in the literature. This study aimed to describe the sexual function in couples undergoing ART with donor sperm. METHODS: This monocentric prospective observational study was conducted in heterosexual couples undergoing ART cycle with sperm donor, using the FSFI and the IIEF15 questionnaires. Seventy-nine couples were solicited to participate in the study. RESULTS: In our sample, 39.3% (n = 24) of women had sexual dysfunction (SD). Among men, 26.5% (n = 13) had erectile dysfunction (ED). No statistically significant difference was found between both groups (with or without SD) in men and women in univariate analysis. Therefore, multivariate analysis was not performed and no specific predictor of SD could be identified. CONCLUSION: Although this should be confirmed in a larger number of participants, our study demonstrates that a significant proportion of infertile patients undergoing ART with donor semen suffer from SD. No significant predictor could, however, be identified. Further research should focus on the evaluation of psychological interventions to treat or improve these disorders.

Associations between internal concentrations of fluorinated and organochlorinated chemicals in women and in vitro fertilization outcomes: A multi-pollutant study.

The impact of persistent organic pollutants (POPs) on reproductive health is still poorly understood, even though infertility management has high associated societal and economical costs. The aims of this study were to characterize the internal levels of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and perfluoroalkylated substances (PFAS) in women undergoing in vitro fertilization (IVF); and evaluate their association with IVF outcomes, individually and as mixtures in a combined multipollutant approach. Thus, 136 women undergoing IVF treatment at Nantes University Hospital (France) were prospectively recruited between 2019 and 2020. Serum samples were analyzed using liquid chromatography with tandem-mass spectrometry for 14 PFAS. Follicular fluid was analyzed with gas chromatography coupled to high resolution mass spectrometry for 14 PCBs and 25 OCPs. Intermediate and clinical IVF outcomes were ascertained by embryologists and clinicians using standardized protocols. Multivariate Poisson regression models and Bayesian Kernel Machine Regressions (BKMR) were used to identify individual and joint associations between POPs and IVF outcomes adjusting for age, body mass index (BMI) and anti-Müllerian hormone. The results showed that most POPs were widely present in women, and globally not associated with clinically relevant IVF outcomes, like live birth rates. Nonetheless, negative associations between PCB138 and trans-nonachlor with useable blastocysts were identified, ß -0.28 (95%CI [-0.52; -0.04] p = 0.02) and ß -0.22 (95%CI [-0.40; -0.03] p = 0.02). Conversely, PCB28 showed positive associations with the number of useable blastocysts, pregnancy rate and live birth rate. The BKMR analysis suggested the lack of association of the mixture with intermediate and clinical outcomes. The study supports the need of conducting further studies in a larger population sample in order to ensure sufficient statistical power to identify modest effects and a robust stratification analysis to account for the large underlying disease heterogeneity.

Adaptive data-driven models to best predict the likelihood of live birth as the IVF cycle moves on and for each embryo transfer.

PURPOSE: To dynamically assess the evolution of live birth predictive factors' impact throughout the in vitro fertilization (IVF) process, for each fresh and subsequent frozen embryo transfers. METHODS: In this multicentric study, data from 13,574 fresh IVF cycles and 6,770 subsequent frozen embryo transfers were retrospectively analyzed. Fifty-seven descriptive parameters were included and split into four categories: (1) demographic (couple's baseline characteristics), (2) ovarian stimulation, (3) laboratory data, and (4) embryo transfer (fresh and frozen). All these parameters were used to develop four successive predictive models with the outcome being a live birth event. RESULTS: Eight parameters were predictive of live birth in the first step after the first consultation, 9 in the second step after the stimulation, 11 in the third step with laboratory data, and 13 in the 4th step at the transfer stage. The predictive performance of the models increased at each step. Certain parameters remained predictive in all 4 models while others were predictive only in the first models and no longer in the subsequent ones when including new parameters. Moreover, some parameters were predictive in fresh transfers but not in frozen transfers. CONCLUSION: This work evaluates the chances of live birth for each embryo transfer individually and not the cumulative outcome after multiple IVF attempts. The different predictive models allow to determine which parameters should be taken into account or not at each step of an IVF cycle, and especially at the time of each embryo transfer, fresh or frozen.

What is the best strategy for slowly developing blastocysts?

Day 5 fresh blastocyst transfers results in higher clinical pregnancy and live birth rates than day 6 fresh blastocyst transfer. This study aimed to identify the strategy to adopt with slowly developing blastocysts. Should not fully expanded blastocyst on day 5 be transferred on day 5, or when expanded on day 6, or be frozen? 1093 single blastocyst transfer cycles performed between January 2016 and December 2018 were divided in 4 groups: day 5 fresh transfers of full or expanded blastocyst (≥B3), day 5 fresh transfers of slowly developing blastocysts (B1 or B2), day 6 fresh transfers of expanded blastocysts (≥B4), day 6 frozen-thawed single blastocyst transfer cycles. Clinical pregnancy rate and live birth rate were significantly higher with fresh expanded blastocyst transfer on day 5 than in any other group. No statistical difference could be found between the other 3 groups. Slowly developing day 5 blastocysts have poorer implantation potential than expanded day 5 blastocysts but can be fresh transferred on day 5 rather than being cultured until day 6 for transfer or freezing when no expanded blastocyst is available on day 5.

A time-lapse embryo dataset for morphokinetic parameter prediction.

One of the most common treatments for infertile couples is In Vitro Fertilization (IVF). It consists of controlled ovarian hyperstimulation, followed by ovum pickup, fertilization, and embryo culture for 2-6 days under controlled environmental conditions, leading to intrauterine transfer or freezing of embryos identified as having a good implantation potential by embryologists. To allow continuous monitoring of embryo development, Time-lapse imaging incubators (TLI) were first released in the IVF market around 2010. This time-lapse technology provides a dynamic overview of embryonic in vitro development by taking photographs of each embryo at regular intervals throughout its development. TLI appears to be the most promising solution to improve embryo quality assessment methods, and subsequently the clinical efficiency of IVF. In particular, the unprecedented high volume of high-quality images produced by TLI systems has already been leveraged using modern Artificial Intelligence (AI) methods, like deep learning (DL). An important limitation to the development of AI-based solutions for IVF is the absence of a public reference dataset to train and evaluate deep learning (DL) models. In this work, we describe a fully annotated dataset of 704 TLI videos of developing embryos with all 7 focal planes available, for a total of 2,4M images. Of note, we propose highly detailed annotations with 16 different development phases, including early cell division phases, but also late cell divisions, phases after morulation, and very early phases, which have never been used before. This is the first public dataset that will allow the community to evaluate morphokinetic models and the first step towards deep learning-powered IVF. We postulate that this dataset will help improve the overall performance of DL approaches on time-lapse videos of embryo development, ultimately benefiting infertile patients with improved clinical success rates.

[Relevance of the theory of High Reliability Organizations in Assisted Reproductive Technology]. / Intérêt de la théorie des organisations à haute fiabilité en Assistance Médicale à la Procréation (AMP).

OBJECTIVES: The objective of this study was to assess the value of applying operating principles for High Reliability Organizations (HROs) to Assisted Reproductive Technology (ART) centres in order to optimise their operation and results. METHODS: Two exploratory qualitative case studies, in the form of ethnographic observations, were conducted in two public hospitals (Antoine-Béclère Hospital, Clamart and Nantes University Hospital). The studies analysed the structural and functional characteristics of these centres compared to HROs. Specific interviews, based on the HRO model from Roberts and Rousseau (1989), were also carried out. RESULTS: The in vitro fertilisation (IVF) procedure is comprised of a sequence of steps for which success depends on the cooperation of a range of medical staff across various specialties. Patients themselves must also play an active part in the protocol. From the different points analysed, the comparison between the characteristics of IVF activity at the ART units and those of HROs reveals structural and functional similarities, however there are also cultural differences. CONCLUSION: The study concluded that ART centres are complex healthcare organisations that face similar challenges to HROs and that they could improve their operational performance by adopting an HRO culture. To confirm the interest of this strategy, it would be useful to clarify these preliminary results by extending the exploratory study to include several public and private ART centres, and to explore the patient/couple dimension before initiating an interventional study.

Is low anti-Mullerian hormone (AMH) level a risk factor of miscarriage in women <37 years old undergoing in vitro fertilization (IVF)?

Anti-Mullerian Hormone (AMH) is considered to be one of the most relevant markers of ovarian reserve. However, its association with oocyte quality, pregnancy occurrence and evolution remain to be further investigated. The objective of this study was to compare miscarriage rate after fresh blastocyst(s) transfer in young women (<37 years old) with or without diminished ovarian reserve (DOR), as reflected by low serum AMH levels. This monocentric retrospective study was conducted in 669 women undergoing 1,891 blastocyst transfers. Patients were divided into 2 groups: (1) 190 transfers performed in 106 women with a 'low' serum AMH (< 10th percentile) (i.e. AMH < 0.85 ng/mL); and (2) 961 transfers performed in 563 patients with a 'normal' serum AMH (25th-75th percentile) (i.e. AMH 1.4-4 ng/mL). Miscarriage rate was comparable in both groups (9.5 and 6.8% respectively; p = 0.2) as well as implantation rate, pregnancy rate, live birth rate per transfer (p = 0.4, p = 0.07 and p = 0.6, respectively). After multivariate analysis, no significant association was found between serum AMH level and miscarriage rate (p = 0.22). In women <37 years, low serum AMH level is not associated with an increase in miscarriage rate after fresh blastocyst transfer.

Human blastoids model blastocyst development and implantation.

One week after fertilization, human embryos implant into the uterus. This event requires the embryo to form a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model that we called a blastoid1. Here we show that naive human pluripotent stem cells cultured in PXGL medium2 and triply inhibited for the Hippo, TGF-ß and ERK pathways efficiently (with more than 70% efficiency) form blastoids generating blastocyst-stage analogues of the three founding lineages (more than 97% trophectoderm, epiblast and primitive endoderm) according to the sequence and timing of blastocyst development. Blastoids spontaneously form the first axis, and we observe that the epiblast induces the local maturation of the polar trophectoderm, thereby endowing blastoids with the capacity to directionally attach to hormonally stimulated endometrial cells, as during implantation. Thus, we propose that such a human blastoid is a faithful, scalable and ethical model for investigating human implantation and development3,4.