0000000000466821
AUTHOR
Céline Bruno
Does Embryo Culture Medium Influence the Health and Development of Children Born after In Vitro Fertilization?
International audience; In animal studies, extensive data revealed the influence of culture medium on embryonic development, foetal growth and the behaviour of offspring. However, this impact has never been investigated in humans. For the first time, we investigated in depth the effects of embryo culture media on health, growth and development of infants conceived by In Vitro Fertilization until the age of 5 years old. This single-centre cohort study was based on an earlier randomized study. During six months, in vitro fertilization attempts (No. 371) were randomized according to two media (Single Step Medium—SSM group) or Global medium (Global group). This randomized study was stopped prem…
Germline correction of an epimutation related to Silver-Russell syndrome.
Like genetic mutations, DNA methylation anomalies or epimutations can disrupt gene expression and lead to human diseases. However, unlike genetic mutations, epimutations can in theory be reverted through developmental epigenetic reprograming, which should limit their transmission across generations. Following the request for a parental project of a patient diagnosed with Silver-Russell syndrome (SRS), and the availability of both somatic and spermatozoa DNA from the proband and his father, we had the exceptional opportunity to evaluate the question of inheritance of an epimutation. We provide here for the first time evidence for efficient reversion of a constitutive epimutation in the sperm…
Can novel early non-invasive biomarkers of embryo quality be identified with time-lapse imaging to predict live birth?
AbstractSTUDY QUESTIONCan time-lapse imaging systems make it possible to identify novel early non-invasive biomarkers to predict live birth?SUMMARY ANSWERFrom mostly high-grade embryos, out of 35 morphometric, morphologic and morphokinetic variables, only pronuclei (PN) position at time of PN juxtaposition and the absence of multinucleated blastomeres at the 2-cell stage (MNB2cell), were potentially associated with live birth.WHAT IS KNOWN ALREADYPrevious studies indicate that some kinetic markers may be predictive of blastocyst development and embryonic implantation. Certain teams have suggested including some of them in decisional algorithms for embryo transfers.STUDY DESIGN, SIZE, DURATI…
Differential long non-coding RNA expression profiles in human oocytes and cumulus cells
AbstractProgress in assisted reproductive technologies strongly relies on understanding the regulation of the dialogue between oocyte and cumulus cells (CCs). Little is known about the role of long non-coding RNAs (lncRNAs) in the human cumulus-oocyte complex (COC). To this aim, publicly available RNA-sequencing data were analyzed to identify lncRNAs that were abundant in metaphase II (MII) oocytes (BCAR4, C3orf56, TUNAR, OOEP-AS1, CASC18, and LINC01118) and CCs (NEAT1, MALAT1, ANXA2P2, MEG3, IL6STP1, and VIM-AS1). These data were validated by RT-qPCR analysis using independent oocytes and CC samples. The functions of the identified lncRNAs were then predicted by constructing lncRNA-mRNA co…
Embryo multinucleation at the two-cell stage is an independent predictor of intracytoplasmic sperm injection outcomes.
Objective To determine the prognostic impact of the nuclear status at the two-cell stage on intracytoplasmic sperm injection (ICSI) outcomes. Design Retrospective study. Setting Hospital. Patient(s) Only ICSI cycles with time-lapse monitoring of transferred embryos with known implantation/delivery data from November 2012 to December 2014 were included. A total of 2,449 embryos were assessed for multinucleation rates at the two- and four-cell stage, and 608 transferred embryos were studied for ICSI outcomes. Intervention(s) None. Main Outcome Measure(s) Implantation rate (IR) and live birth rate (LBR) according to the number of multinucleated blastomeres at the two-cell stage: none (Without-…
The placenta: phenotypic and epigenetic modifications induced by Assisted Reproductive Technologies throughout pregnancy
International audience; Today, there is growing interest in the potential epigenetic risk related to assisted reproductive technologies (ART). Much evidence in the literature supports the hypothesis that adverse pregnancy outcomes linked to ART are associated with abnormal trophoblastic invasion. The aim of this review is to investigate the relationship between epigenetic dysregulation caused by ART and subsequent placental response. The dialogue between the endometrium and the embryo is a crucial step to achieve successful trophoblastic invasion, thus ensuring a non-complicated pregnancy and healthy offspring. However, as described in this review, ART could impair both actors involved in t…
Diagnostic genetic screening for assisted reproductive technologies patients with macrozoospermia
International audience; Macrozoospermia is characterized by a high proportion of abnormal spermatozoa with enlarged heads. So far, it has been associated with mutations only in the Aurora Kinase C gene (AURKC) in some cases. Although many publications have reported failure to conceive in couples with macrozoospermia, a few others have described successful pregnancies, thus raising questions as to whether ICSI and AURKC genetic screening should be recommended in all patients with macrozoospermia. First, we report on two monozygotic twins presenting macrozoospermia for whom the genetic status was explored (Aurora Kinase C sequencing) and whole semen and gradient-selected spermatozoa were anal…
Mechanisms involved in the transmission of epigenetic deregulation : analyses of transmission in human sperm
The notion that environmental exposure can be memorized and promote epimutation (defined as defects on DNA methylation) raises the question of possible epigenetic transgenerational transmission in humans. To address whether an epimutation could be transmitted in humans, we pursued two axes. First, the evaluation of intergenerational transmission in the family of a Silver-Russell patient has shown, for the first time, the efficiency of epigenetic reprogramming in humans, specifically on imprinted regions. Indeed, no imprinted defect on causal H19/IGF2 locus was detected in the patient’s spermatozoa or in the DNA of his daughter. The second axis was to assess the presence of sperm epimutation…
Randomized controlled trial comparing embryo culture in two incubator systems: G185 K-System versus EmbryoScope
Objective To study whether the closed culture system, as compared with a benchtop incubator with similar culture conditions, has a positive impact on intracytoplasmic sperm injection (ICSI) outcomes. Design Randomized controlled trial. Setting University hospital. Patient(s) A total of 386 patients undergoing ICSI cycles with at least six mature oocytes were randomized. Intervention(s) Of these patients, 195 were assigned to the group with culture in a time-lapse imaging (TLI) system (EmbryoScope) and 191 to the group with culture in the G185 K-System (G185). Main Outcome Measure(s) Rate of implantation (primary endpoint) and embryo morphology grade. Result(s) No significant differences wer…
Impact on ICSI outcomes of adding 24 h of in vitro culture before testicular sperm freezing: a retrospective study.
To compare sperm parameters and intracytoplasmic sperm injection (ICSI) outcomes for testicular spermatozoa frozen on the day of the biopsy (DO) with those frozen after 24 h of in vitro culture (D1).In this retrospective study, from 1999 to 2012, forty-nine azoospermic patients were included to compare sperm (motility and viability) and outcomes (fertilization (FR), implantation (IR), pregnancy (PR) and delivery rates (DR)).The in vitro culture increased total motility (+2.8 %, p = 0.0161) but decreased viability (-8.3 %, p = 0.007). After 24 h of culture, the post-thaw changes in motility and viability were not significant. Twenty-six couples underwent ICSI: thirty-four ICSI were performed…