A pilot study of transcriptomic preimplantation genetic testing (PGT-T): towards a new step in embryo selection?

Study Question: Is it possible to predict an euploid chromosomal constitution and identify a transcriptomic profile compatible with extended embryonic development from RNA sequencing (RNA-Seq) data?

Summary Answer: It has been possible to obtain a karyotype comparable to preimplantation genetic testing for aneuploidy (PGT-A), in addition to a transcriptomic signature of embryos which might be suggestive of improved implantation capacity.

What Is Known Already: Conventional assessment of embryo competence, based on morphology and morphokinetic, lacks knowledge of molecular aspects and faces controversy in predicting ploidy status. Understanding the embryonic transcriptome is crucial, as gene expression influences development and implantation.

Endometrial extracellular vesicles regulate processes related to embryo development and implantation in human blastocysts.

Study Question: What is the transcriptomic response of human blastocysts following internalization of extracellular vesicles (EVs) secreted by the human endometrium?

Summary Answer: EVs secreted by the maternal endometrium induce a transcriptomic response in human embryos that modulates molecular mechanisms related to embryo development and implantation.

What Is Known Already: EVs mediate intercellular communication by transporting various molecules, and endometrial EVs have been postulated to be involved in the molecular regulation of embryo implantation. Our previous studies showed that endometrial EVs carry miRNAs and proteins associated with implantation events that can be taken up by human blastocysts; however, no studies have yet investigated the transcriptomic response of human embryos to this EV uptake, which is crucial to demonstrate the functional significance of this communication system.

Impact of autologous mitochondrial transfer on obstetric and neonatal health of offspring: A small single-center case series.

Introduction: A pilot study was carried out to test the efficacy of the autologous mitochondrial transfer therapy (AUGMENT) technique. No improvements in pregnancy rate, development, or embryo quality were observed in the AUGMENT-treated group versus the Control group in this study. The main objective of this research is to analyze whether AUGMENT technology did have any impact on the obstetric and perinatal outcomes of pregnancies and children resulting from treated oocytes.

Oocyte Competence, Embryological Outcomes and miRNA Signature of Different Sized Follicles from Poor Responder Patients.

Poor ovarian response (POR) patients often face the risk of not having enough competent oocytes. Then, aspirating small follicles could serve as a strategy to increase their number. Many efforts have been addressed to associate follicular size with oocyte competence, but results are controversial.

Embryo long-term storage does not affect assisted reproductive technologies outcome: analysis of 58,001 vitrified blastocysts over 11 years.

Background: Recently, the potential detrimental effect that the duration of storage time may have on vitrified samples has raised some concerns, especially when some studies found an association between cryostorage length and decreased clinical results.

Objective: This study aimed to evaluate the effects of the storage time length of day-5 vitrified blastocysts in 2 study groups: freeze-all cycles and nonelective frozen embryo transfers.

Study Design: This was a retrospective study that included 58,001 vitrified/warmed day-5 blastocysts from 2 different populations, according to the reason for frozen embryo transfer.

Trophectoderm cells of human mosaic embryos display increased apoptotic levels and impaired differentiation capacity: a molecular clue regarding their reproductive fate?

Study Question: Are there cell lineage-related differences in the apoptotic rates and differentiation capacity of human blastocysts diagnosed as euploid, mosaic, and aneuploid after preimplantation genetic testing for aneuploidy (PGT-A) based on concurrent copy number and genotyping analysis?

Summary Answer: Trophectoderm (TE) cells of mosaic and aneuploid blastocysts exhibit significantly higher levels of apoptosis and significantly reduced differentiation capacity compared to those of euploid blastocysts.

What Is Known Already: Embryos diagnosed as mosaic after PGT-A can develop into healthy infants, yet understanding the reasons behind their reproductive potential requires further research. One hypothesis suggests that mosaicism can be normalized through selective apoptosis and reduced proliferation of aneuploid cells, but direct evidence of these mechanisms in human embryos is lacking.

The effect of vitrification on blastocyst mitochondrial DNA dynamics and gene expression profiles.

Purpose: Does vitrification/warming affect the mitochondrial DNA (mtDNA) content and the gene expression profile of blastocysts?

Methods: Prospective cohort study in which 89 blastocysts were obtained from 50 patients between July 2017 and August 2018. mtDNA was measured in a total of 71 aneuploid blastocysts by means of real-time polymerase chain reaction (RT-PCR). Transcriptomic analysis was performed by RNA sequencing (RNA-seq) in an additional 8 aneuploid blastocysts cultured for 0 h after warming, and 10 aneuploid blastocysts cultured for 4-5 h after warming.

Human embryo polarization requires PLC signaling to mediate trophectoderm specification.

Apico-basal polarization of cells within the embryo is critical for the segregation of distinct lineages during mammalian development. Polarized cells become the trophectoderm (TE), which forms the placenta, and apolar cells become the inner cell mass (ICM), the founding population of the fetus. The cellular and molecular mechanisms leading to polarization of the human embryo and its timing during embryogenesis have remained unknown.

Elevated serum progesterone does not impact euploidy rates in PGT-A patients.

Purpose: Some women undergoing stimulated cycles have elevated serum progesterone (P) on the day of ovulation trigger, but its effect on embryo quality is unclear. We analyze embryo quality among patients with high and low serum P undergoing preimplantation genetic testing for aneuploidy (PGT-A).

Methods: This retrospective study included 1597 patients divided into two groups by serum P values: < 1.

The morphokinetic signature of mosaic embryos: evidence in support of their own genetic identity.

Objective: To provide full morphokinetic characterization of embryos ranked with different degrees of chromosomal mosaicism.

Design: Retrospective cohort study.

Setting: University-affiliated private in vitro fertilization clinic.

Number needed to freeze: cumulative live birth rate after fertility preservation in women with endometriosis.

Research Question: How does the number of oocytes used affect the cumulative live birth rate (CLBR) in endometriosis patients who had their oocytes vitrified for fertility preservation?

Design: Retrospective observational study including data from 485 women with endometriosis who underwent fertility preservation from January 2007 to July 2018. Survival curves and Kaplan-Meier plots were used to analyse the CLBR according to the number of vitrified oocytes used. Endometriosis curves were compared with plots developed using elective fertility preservation (EFP) patients as control group.

The influence of oxygen concentration during embryo culture on obstetric and neonatal outcomes: a secondary analysis of a randomized controlled trial.

Study Question: Does oxygen concentration during 3-day embryo culture affect obstetric and neonatal outcomes?

Summary Answer: Oxygen concentration during 3-day embryo culture does not seem to affect the obstetric and neonatal outcomes measured.

What Is Known Already: Atmospheric oxygen appears to be harmful during extended embryo culture. Embryo culture conditions might therefore be a potential risk factor for subsequent fetal development and the health of future children.

Mitochondrial DNA content decreases during in vitro human embryo development: insights into mitochondrial DNA variation in preimplantation embryos donated for research.

Objective: To assess the mitochondrial DNA (mtDNA) load and variation in human oocytes and during preimplantation embryo development using specimens donated for research.

Design: Prospective cohort study.

Setting: Not applicable.

Mitochondria as a tool for oocyte rejuvenation.

Ovarian aging leads to a decrease in the quantity and quality of oocytes. Aged oocytes have significantly reduced amounts of mitochondria, the energy factories of cells, leading to lower fertilization rates and poor embryonic development. Various techniques have tried to use heterologous or autologous sources of mitochondria to reestablish oocyte health by providing more energy.

Autologous mitochondrial transfer as a complementary technique to intracytoplasmic sperm injection to improve embryo quality in patients undergoing in vitro fertilization-a randomized pilot study.

Objective: To study if autologous mitochondrial transfer (AUGMENT) improves outcome in patients with previously failed in vitro fertilization (IVF).

Design: Randomized, controlled, triple-blind, experimental study.

Setting: Private infertility center, Valencian Institute of Infertility (IVI-RMA), Valencia, Spain.

Variables associated with mitochondrial copy number in human blastocysts: what can we learn from trophectoderm biopsies?

Objective: To study the potential variables that affect the mitochondrial DNA (mtDNA) content of trophectoderm (TE) cells in blastocysts that have undergone TE biopsy.

Design: Observational retrospective single-center analysis.

Setting: University-affiliated private in vitro fertilization center.

Revised guidelines for good practice in IVF laboratories (2015).

Study Question: Which recommendations can be provided by the European Society of Human Reproduction and Embryology Special Interest Group (ESHRE SIG) Embryology to support laboratory specialists in the organization and management of IVF laboratories and the optimization of IVF patient care?

Summary Answer: Structured in 13 sections, the guideline development group formulated recommendations for good practice in the organization and management of IVF laboratories, and for good practice of the specific procedures performed within the IVF laboratory.

What Is Known Already: NA.

Study Design, Size, Duration: The guideline was produced by a group of 10 embryologists representing different European countries, settings and levels of expertise.

Morphokinetic analysis and embryonic prediction for blastocyst formation through an integrated time-lapse system.

Objective: To describe the events associated with the blastocyst formation and implantation that occur in embryos during preimplantation development based on the largest sample size ever described with time-lapse monitoring.

Design: Observational, retrospective, single-center clinical study.

Setting: University-affiliated private IVF center.

The Metabolomic Profile of Spent Culture Media from Day-3 Human Embryos Cultured under Low Oxygen Tension.

Despite efforts made to improve the in vitro embryo culture conditions used during assisted reproduction procedures, human embryos must adapt to different in vitro oxygen concentrations and the new metabolic milieu provided by the diverse culture media used for such protocols. It has been shown that the embryo culture environment can affect not only cellular metabolism, but also gene expression in different species of mammalian embryos. Therefore we wanted to compare the metabolic footprint left by human cleavage-stage embryos under two types of oxygen atmospheric culture conditions (6% and 20% O2).

A multicenter prospective study to assess the effect of early cleavage on embryo quality, implantation, and live-birth rate.

Objective: To investigate the impact of early cleavage (EC) on embryo quality, implantation, and live-birth rates.

Design: Prospective cross-sectional study.

Setting: Multicenter study.