0000000000383636
AUTHOR
Patricia Fauque
Combined effects of increasing maternal age and nulliparity on hypertensive disorders of pregnancy and small for gestational age
The mean age of women delivering for the first time is increasing, and this combination could lead to an increased risk of perinatal complications.The objective was to evaluate the potential combined effects of nulliparity and increasing maternal age on small for gestational age (SGA 10th percentile) and hypertensive disorders of pregnancy (HDP).A population-based cohort study was conducted using data routinely collected on all births in 11 hospitals in the Burgundy perinatal network between 2007 and 2016. Pregnant women with singleton deliveries aged 20 years or older were included at delivery and divided into groups according to maternal age (20 to 24-year-old group as a reference). Mult…
The Gpr1/Zdbf2 locus provides new paradigms for transient and dynamic genomic imprinting in mammals
Many loci maintain parent-of-origin DNA methylation only briefly after fertilization during mammalian development: Whether this form of transient genomic imprinting can impact the early embryonic transcriptome or even have life-long consequences on genome regulation and possibly phenotypes is currently unknown. Here, we report a maternal germline differentially methylated region (DMR) at the mouse Gpr1/Zdbf2 (DBF-type zinc finger-containing protein 2) locus, which controls the paternal-specific expression of long isoforms of Zdbf2 (Liz) in the early embryo. This DMR loses parental specificity by gain of DNA methylation at implantation in the embryo but is maintained in extraembryonic tissue…
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…
Is the nuclear status of an embryo an independent factor to predict its ability to develop to term?
Objective To determine the prognostic impact of the embryo nuclear status at day 2 among other major morphologic parameters (first cleavage at day 1, number of blastomeres and anuclear fragmentation at day 2) on the birth rate. Design Retrospective study. Setting Hospital IVF department. Patient(s) Women undergoing 1,629 day 2 transfers of 2,732 embryos from May 2006 to November 2008. Intervention(s) Four groups according to the embryo nuclear status. Main Outcome Measure(s) Implantation, miscarriage, and birth rates. Result(s) Univariate analysis indicated significantly higher birth rates when all blastomeres were mononucleated (15.0%) compared with embryos with not all blastomeres mononuc…
Clinical success of intrauterine insemination cycles is affected by the sperm preparation time.
Objective To determine the impact of the time interval from the end of sperm preparation (TSP) to intrauterine insemination (IUI) on the outcome. Design Prospective multicentre cohort study. Setting Seven French centers (assisted reproduction group in northeastern France, four academic centers, and three clinics). Patient(s) Eight hundred sixty-two IUI cycles (709 patients) managed by gonadotropins were studied. Intervention(s) Cycles were stimulated by either FSH or hMG, and hCG was administrated when the leading follicle diameter measured >15 mm. IUIs were performed ∼36 hours after ovulation triggering. Main Outcome Measure(s) Generalized linear mixed models for binary outcomes were used …
Optimal Timing for Oocyte Denudation and Intracytoplasmic Sperm Injection
Objectives. To analyze the impact of oocyte denudation and microinjection timings on intracytoplasmic sperm injection (ICSI) outcomes.Study Design. We included ICSI cycles with the following parameters: rank 1 or 2, female age years, male factor infertility, long protocol using GnRH agonist and rFSH for ovarian stimulation, and use of freshly ejaculated sperm (). Several ICSI parameters were analyzed according to the time between oocyte retrieval and denudation () and the time between denudation and ICSI () using a statistical logistic regression analysis.Results. Neither nor had a significant influence on the Metaphase II (MII) rate but the fertilisation rate (FR) showed a significant impr…
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…
Outcomes with intracytoplasmic sperm injection of cryopreserved sperm from men with spinal cord injury
Erectile dysfunction, ejaculatory dysfunction and poor semen quality are the main causes of infertility in men with spinal cord injury (SCI). Different sperm retrieval techniques such as penile vibratory stimulation (PVS), electro-ejaculation (EEJ) or surgical sperm retrieval (SSR) associated or not with sperm cryopreservation can be offered to these patients to preserve their fertility. If fatherhood cannot be achieved naturally, assisted reproductive techniques can be offered to these patients using either fresh or frozen/thawed sperm. The aim of the study was to report in SCI patients from Dijon (Burgundy) and in the literature, intracytoplasmic sperm injection (ICSI) outcomes using froz…
Ovulation induction and epigenetic anomalies
In this systematic review of ovulation induction and epigenetic control, studies mainly done in the mouse model highlight how hormone treatments may be prejudicial to the epigenetic reprogramming of gametes as well as early embryos. Moreover, the hormone protocols used in assisted reproduction may also modify the physiologic environment of the uterus, a potential link to endometrial epigenetic disturbances. At present, the few available data in humans are insufficient to allow us to independently determine the impact of a woman's age and infertility problems and treatment protocols and hormone doses on such processes as genomic imprinting.
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…
Deciphering the Early Mouse Embryo Transcriptome by Low-Input RNA-Seq
Early preimplantation embryos are precious and scarce samples that contain limited numbers of cells, which can be problematic for quantitative gene expression analyses. Nonetheless, low-input genome-wide techniques coupled with cDNA amplification steps have become a gold standard for RNA profiling of as minimal as a single blastomere. Here, we describe a single-cell/single-embryo RNA sequencing (RNA-seq) method, from embryo collection to sample validation steps prior to DNA library preparation and sequencing. Key quality controls and external Spike-In normalization approaches are also detailed.
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…
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…