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Preimplantation genetic testing (PGT) refers to the set of techniques for testing whether embryos obtained through In Vitro fertilization have genetic defect. There is a lack of global standardization regarding practices between countries... more
Preimplantation genetic testing (PGT) refers to the set of techniques for testing whether embryos obtained through In Vitro fertilization have genetic defect. There is a lack of global standardization regarding practices between countries or even from one center to another. In ours, biopsies are preferably performed on day 3 embryos, but also at the blastocyst stage on day 5. The blastocyst biopsy often requires systematic freezing of the embryos before obtaining the genetic results, whereas day 3 biopsy allows fresh embryo transfer of the healthy or balanced embryo after getting the genetic results. We wanted to compare the chances of success for couples performing PGT in our center according to the day of the biopsy. For this, we carried out a retrospective monocentric study including all PGT cycles performed between 2016 and 2019 divided into two groups: day 3 or day 5 biopsy. There was no significant difference in terms of live birth rate (p = 0.7375) after fresh embryo transfers, as well for pregnancy rates, clinical pregnancy rates, implantation rates and miscarriage rates. On the other hand, we observed higher live birth rates after frozen-thawed embryo transfer when the biopsy was performed on day 5 rather on day 3 (p = 0.0001). We also wanted to assess what was the most efficient biopsy strategy in our laboratory. Our rates of useful embryos were similar regardless of the day of the biopsy (34% in D3 and 37.7% in D5, p = 0.244). No statistical difference was found in the number of unnecessarily biopsied embryos in the two groups. But still, the percentage of embryos biopsied on D5 and immediately frozen was 42.8% (118 blastocysts), while no embryo biopsied on D3 led to this case. Therefore, our results are in favor of generalization of the D5 biopsy as the international standard. However, the organizational, financial and logistical implications that this technic would impose makes it unsystematic in our center.
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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... more
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-β 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 eth...
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Biology, Cell Biology, Medicine, Multidisciplinary, Nature, and 3 moreEmbryo, Blastocyst, and Inner Cell mass
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PURPOSE The exploration of male infertility is mainly based on semen analysis, but its evaluation might be affected by the operator's competence and subjectivity. This led to the development of automated semen analyzing systems.... more
PURPOSE The exploration of male infertility is mainly based on semen analysis, but its evaluation might be affected by the operator's competence and subjectivity. This led to the development of automated semen analyzing systems. Despite continuous improvement, the precision and correlation of these automated systems with manual sperm assessment performed strictly according to WHO guidelines remains variable in the literature, and their role in daily practice is debated. METHODS In this double blind prospective study, we compared the results provided by 2 automated systems based on different concepts (CASA and electro-optical signal) with manual sperm assessment. Sperm concentration, motility and morphology were performed simultaneously and independently by different operators, blinded to each other. RESULTS A total of 102 unselected men attending the andrology department for routine sperm analysis were included in the study. We found no significant difference between each automated method and manual assessment for all sperm parameters, except for sperm morphology assessment where the electro-optical system gave higher results and performed slightly poorer than CASA. Correlation was moderate to high between manual assessment and each automated methods for all sperm parameters, with randomly distributed differences. CONCLUSIONS Overall, these results show that both types of automated systems can be implemented in andrology laboratory for routine sperm analysis.
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Study question Does a serum progesterone level higher than 1.3 ng/mL on the day of ovulation trigger have an impact on blastocyst development? Summary answer Elevated progesterone level has no significant impact on top blastocyst rate,... more
Study question Does a serum progesterone level higher than 1.3 ng/mL on the day of ovulation trigger have an impact on blastocyst development? Summary answer Elevated progesterone level has no significant impact on top blastocyst rate, usable blastocyst rate and on morphokinetics. What is known already Premature elevation of progesterone level on the day of ovulation trigger prior to IVF is common and causes a decrease in endometrial receptivity. A freeze all strategy is then recommended. However, cumulative live birth rates have also been described as lower in cases of high progesterone levels. Study design, size, duration This was a retrospective bicentric cohort follow-up study, including 1150 IVF/ICSI cycles performed between 2016 and 2018 with at least 1 day–5 blastocyst available for transfer or freezing. Among these cycles, 524 were performed with use of a time-lapse system (Embryoscope). Serum Progesterone level was measured on the day of ovulation trigger, and a value >1...
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STUDY QUESTION Is it possible to develop an automated annotation tool for human embryo development in time-lapse devices based on image analysis? SUMMARY ANSWER We developed and validated an automated software for the annotation of human... more
STUDY QUESTION Is it possible to develop an automated annotation tool for human embryo development in time-lapse devices based on image analysis? SUMMARY ANSWER We developed and validated an automated software for the annotation of human embryo morphokinetic parameters, having a good concordance with expert manual annotation on 701 time-lapse videos. WHAT IS KNOWN ALREADY Morphokinetic parameters obtained with time-lapse devices are increasingly used for the assessment of human embryo quality. However, their annotation is time-consuming and can be slightly operator-dependent, highlighting the need to develop fully automated approaches. STUDY DESIGN, SIZE, DURATION This monocentric study was conducted on 701 videos originating from 584 couples undergoing IVF with embryo culture in a time-lapse device. The only selection criterion was that the duration of the video must be over 60 h. PARTICIPANTS/MATERIALS, SETTING, METHODS An automated morphokinetic annotation tool was developed base...
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Study QuestionIs it possible to automatically annotate human embryo development in time-lapse devices, with results comparable to manual annotation?Summary AnswerWe developed an automated tool for the annotation of embryo morphokinetic... more
Study QuestionIs it possible to automatically annotate human embryo development in time-lapse devices, with results comparable to manual annotation?Summary AnswerWe developed an automated tool for the annotation of embryo morphokinetic parameters having a high concordance with expert manual annotation in a large scale-study.What is Known AlreadyMorphokinetic parameters obtained with time-lapse devices are increasingly used for human embryo quality assessment. However, their annotation is timeconsuming and can be operator-dependent, highlighting the need of developing automated approaches.Study Design, Size, DurationThis monocentric pilot study was conducted using 701 blastocysts originating from 584 couples undergoing IVF with embryo culture in a time-lapse device and on 4 mouse embryos.Participants/Materials, Setting, MethodsAn automated annotation tool was developed based on grey level coefficient of variation and detection of the thickness of the zona pellucida. The timings of ce...
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Recent technological advances such as single-cell RNAseq1-3and CRISPR-CAS9-mediated knock-out4have allowed an unprecedented access into processes orchestrating human preimplantation development5. However, the sequence of events which... more
Recent technological advances such as single-cell RNAseq1-3and CRISPR-CAS9-mediated knock-out4have allowed an unprecedented access into processes orchestrating human preimplantation development5. However, the sequence of events which occur during human preimplantation development are still unknown. In particular, timing of first human lineage specification, the process by which the morula cells acquire a specific fate, remains elusive. Here, we present a human preimplantation development model based on transcriptomic pseudotime modelling of scRNAseq biologically validated by spatial information and precise time-lapse staging. In contrast to mouse, we show that trophectoderm (TE) / inner cell mass (ICM) lineage specification in human is only detectable at the transcriptomic level at the blastocyst stage, just prior to expansion. We validated the expression profile of novel markers enabling precise staging of human preimplantation embryos, such as IFI16 which highlights establishment ...
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Embryo morphology assessment performs relatively poorly in predicting implantation. Embryo aneuploidy screening (PGS) has recently improved, but its clinical value is still debated, and the development of a cheap non-invasive method for... more
Embryo morphology assessment performs relatively poorly in predicting implantation. Embryo aneuploidy screening (PGS) has recently improved, but its clinical value is still debated, and the development of a cheap non-invasive method for the assessment of embryo ploidy status is a highly desirable goal. The growing implementation of time-lapse devices led some teams to test the effectiveness of morphokinetic parameters as predictors of embryo ploidy, with conflicting results. The aim of this study was to conduct a comprehensive review of the literature on the predictive value of morphokinetic parameters for embryo ploidy status. A systematic search on PubMed was conducted using the following key words: time-lapse, morphokinetic, aneuploidy, IVF, preimplantation genetic screening, PGS, chromosomal status. A total of 13 studies were included in the analysis. They were heterogeneous in design, patients, day of embryo biopsy, statistical approach and outcome measures. No single or combin...
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Biology, Medicine, Embryo, Aneuploidy, Team, and 3 morePloidy, Crti, and Paediatrics and reproductive medicine
Induced pluripotent stem cells (iPSCs) have considerably impacted human developmental biology and regenerative medicine, notably because they circumvent the use of cells of embryonic origin and offer the potential to generate... more
Induced pluripotent stem cells (iPSCs) have considerably impacted human developmental biology and regenerative medicine, notably because they circumvent the use of cells of embryonic origin and offer the potential to generate patient-specific pluripotent stem cells. However, conventional reprogramming protocols produce developmentally advanced, or primed, human iPSCs (hiPSCs), restricting their use to post-implantation human development modeling. Hence, there is a need for hiPSCs resembling preimplantation naive epiblast. Here, we develop a method to generate naive hiPSCs directly from somatic cells, using OKMS overexpression and specific culture conditions, further enabling parallel generation of their isogenic primed counterparts. We benchmark naive hiPSCs against human preimplantation epiblast and reveal remarkable concordance in their transcriptome, dependency on mitochondrial respiration and X-chromosome status. Collectively, our results are essential for the understanding of p...
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Reprogramming, Biology, Cellular Reprogramming, Regenerative Medicine, Medicine, and 15 moreMultidisciplinary, Transcriptome, Humans, Mice, Female, Animals, Embryonic Stem Cell, Male, Blastocyst, Embryonic Stem Cells, Embryonic Development, Induced Pluripotent Stem Cells, Nature Communications, fibroblasts, and Human Induced Pluripotent Stem Cells
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Andrology, Biology, Cryopreservation, Spinal Cord Injury, Medicine, and 10 moreIntracytoplasmic Sperm Injection, Assisted Reproductive Technology, Sperm, In Vitro Fertilization, Clinical Sciences, Semen, Insemination, electroejaculation, Testicular sperm extraction, and Paediatrics and reproductive medicine
ABSTRACT
The purpose of our study was to use time-lapse in order to evaluate the impact of sperm origin (fresh ejaculate or surgically retrieved) on embryo morphokinetic parameters and clinical outcome in intracytoplasmic sperm injection (ICSI)... more
The purpose of our study was to use time-lapse in order to evaluate the impact of sperm origin (fresh ejaculate or surgically retrieved) on embryo morphokinetic parameters and clinical outcome in intracytoplasmic sperm injection (ICSI) cycles. This retrospective monocentric study was conducted in 485 unselected couples undergoing 604 ICSI cycles with embryo culture in the Embryoscope®. Among them, 445 couples underwent ICSI cycle with fresh ejaculated sperm and 40 with surgically retrieved sperm (26 with testicular sperm and 14 with epididymal sperm). Embryo morphokinetic parameters and clinical cycle outcome were compared between fresh ejaculated sperm and surgically retrieved sperm. A subgroup analysis was also conducted between testicular and epididymal sperm ICSI cycles. Clinical outcome was comparable between groups according to sperm origin. Although most early morphokinetic parameters were comparable between ejaculated and surgical sperm groups, a few parameters were signific...
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To study the performance of a previously published implantation prediction model based on morphokinetics in a different setting, in an unselected population and with various embryo transfer strategies. Retrospective monocentric study.... more
To study the performance of a previously published implantation prediction model based on morphokinetics in a different setting, in an unselected population and with various embryo transfer strategies. Retrospective monocentric study. University-based assisted reproduction technology (ART) center. 450 unselected couples undergoing intracytoplasmic sperm injection (ICSI) cycle with embryo culture in the EmbryoScope (Unisense Fertilitech), corresponding to 528 embryos with known implantation. None. Implantation rates (IR) in embryo categories defined by the model in the overall population and in subgroups according to the day of embryo transfer. The distribution of IR among detailed morphokinetic categories in the overall population and in subgroups according to the day of embryo transfer was more heterogeneous than expected according to the published model. The distribution corresponded better to the original when a simplified version of the model was used, although it worked better ...