Development of a Novel Non-invasive Metabolomics Assay to Predict Implantation Potential of Human Embryos.

Can a set of metabolites present in embryo culture media correlate with embryo implantation? Case-control study in two phases: discovery phase (101 samples) and validation phase (169 samples), collected between 2018 and 2022, with a total of 218 participants. Culture media samples with known implantation outcomes were collected after blastocyst embryo transfer (including both PGT and non-PGT cycles) and were analyzed using chromatography followed by mass spectrometry. The spectra were processed and analyzed using statistical and machine learning techniques to identify biomarkers associated with embryo implantation, and to develop a predictive model.

First babies conceived with Automated Intracytoplasmic Sperm Injection.

Research Question: Can an automated sperm injection robot perform Automated Intracytoplasmic Sperm Injection (ICSIA) for use in human IVF?

Design: The ICSIA robot automated the sperm injection procedure, including injection pipette advancement, zona pellucida and oolemma penetration with piezo pulses, and pipette removal after sperm release. The robot was first tested in mouse, hamster and rabbit oocytes, and subsequently using discarded human oocytes injected with microbeads. A small clinical pilot trial was conducted with donor oocytes to study the feasibility of the robot in a clinical setting.

Human Uterine Lavage: First Live Births from In Vivo Conceived Genetically Screened Blastocysts.

Introduction: We wish to report the first live births from genetically screened human euploid blastocysts obtained by uterine lavage. The embryos transferred to infertile women were previously obtained using a novel fully automated uterine lavage catheter and fluid recovery device developed for this indication. The objective of this portion of the research was to confirm embryo implantation and live births with these unique in vivo conceived blastocysts obtained by uterine lavage.

Embryologist agreement when assessing blastocyst implantation probability: is data-driven prediction the solution to embryo assessment subjectivity?

Study Question: What is the accuracy and agreement of embryologists when assessing the implantation probability of blastocysts using time-lapse imaging (TLI), and can it be improved with a data-driven algorithm?

Summary Answer: The overall interobserver agreement of a large panel of embryologists was moderate and prediction accuracy was modest, while the purpose-built artificial intelligence model generally resulted in higher performance metrics.

What Is Known Already: Previous studies have demonstrated significant interobserver variability amongst embryologists when assessing embryo quality. However, data concerning embryologists' ability to predict implantation probability using TLI is still lacking.

PGDIS position statement on the transfer of mosaic embryos 2021.

Chromosome testing strategies, such as preimplantation genetic testing for aneuploidy (PGT-A), improve initial IVF outcomes by avoiding unwitting transfer of aneuploid embryos in morphology-based selection practices. Newer technologies have revealed that some embryos may appear to have intermediate whole chromosome (or parts of a chromosome termed segmental) copy number results suggesting trophectoderm mosaicism. An embryo with a trophectoderm mosaic-range result may be the only option for transfer for some patients.

Using outcome data from one thousand mosaic embryo transfers to formulate an embryo ranking system for clinical use.

Objective: To study how the attributes of mosaicism identified during preimplantation genetic testing for aneuploidy relate to clinical outcomes, in order to formulate a ranking system of mosaic embryos for intrauterine transfer.

Design: Compiled analysis.

Setting: Multi-center.

Aneuploidy and recombination in the human preimplantation embryo. Copy number variation analysis and genome-wide polymorphism genotyping.

Research Question: What are the incidence and patterns of meiotic trisomies and recombination separately and in relation to each other at the blastocyst stage via single nucleotide polymorphism genotyping combined with array comparative genomic hybridization.

Design: Single nucleotide polymorphism microarrays were carried out on a total of 1442 blastocyst stage embryos derived from 268 fertile couples undergoing preimplantation genetic diagnosis for the purposes of avoiding transmittance of known single gene disorders to their offspring; 24-chromosome aneuploidy screening via array comparative genomic hybridization was carried out in parallel.

Results: One hundred per cent of meiotic trisomies identified in these embryos were of maternal origin and their incidence increased significantly with advancing maternal age (P < 0.

Follicle size indicates oocyte maturity and blastocyst formation but not blastocyst euploidy following controlled ovarian hyperstimulation of oocyte donors.

Study Question: Is there is an association between follicle size and the quality of oocytes retrieved from them as judged by ability to achieve the blastocyst stage, blastocyst grades and blastocyst ploidy?

Summary Answer: Although follicle size is a valuable predictor of oocyte maturity and is a significant predictor of the ability of a fertilized oocyte to become a quality blastocyst, the ploidy of each quality blastocyst is not related to the size of the follicle from which its oocyte was retrieved.

What Is Known Already: It is unclear whether the oocytes within larger follicles are the best oocytes of the cohort. Although there have been studies examining follicle size in relation to embryo quality, there has been no study relating the incidence of euploidy in embryos to follicle size.

Clinical error rates of next generation sequencing and array comparative genomic hybridization with single thawed euploid embryo transfer.

We investigated clinical error rates with single thawed euploid embryo transfer (STEET) diagnosed by next generation sequencing (NGS) and array comparative genomic hybridization (aCGH). A total of 1997 STEET cycles after IVF with preimplantation genetic testing for aneuploidy (PGT-A) from 2010 to 2017 were identified; 1151 STEET cycles utilized NGS, and 846 STEET cycles utilized aCGH. Any abortions, spontaneous or elective, in which products of conception (POCs) were collected were reviewed.

First PGT-A using human in vivo blastocysts recovered by uterine lavage: comparison with matched IVF embryo controls†.

Study Question: After controlled ovarian stimulation (COS) and IUI, is it clinically feasible to recover in vivo conceived and matured human blastocysts by uterine lavage from fertile women for preimplantation genetic testing for aneuploidy (PGT-A) and compare their PGT-A and Gardner scale morphology scores with paired blastocysts from IVF control cycles?

Summary Answer: In a consecutive series of 134 COS cycles using gonadotrophin stimulation followed by IUI, uterine lavage recovered 136 embryos in 42% (56/134) of study cycles, with comparable in vivo and in vitro euploidy rates but better morphology in in vivo embryos.

What Is Known Already: In vivo developed embryos studied in animal models possess different characteristics compared to in vitro developed embryos of similar species. Such comparative studies between in vivo and in vitro human embryos have not been reported owing to lack of a reliable method to recover human embryos.

Clinical outcomes after the transfer of blastocysts characterized as mosaic by high resolution Next Generation Sequencing- further insights.

Objective: To determine the pregnancy outcome potential of euploid, mosaic and aneuploid embryos.

Design: Retrospective study.

Setting: Reference genetics laboratories.

Controlled ovarian hyperstimulation (COH) parameters associated with euploidy rates in donor oocytes.

Although oocyte donors are young and are expected to provide a high rate of euploid oocytes, significant differences of euploidy rates for donor embryos exist between different IVF centers (1). Laboratory conditions can lead to differences of euploidy (2,3,4,5,6,7); but, the role of COH has not been investigated. In this study, we investigated whether euploidy rates in the embryos created from donor oocytes are influenced by controlled ovarian hyperstimulation parameters used during assisted reproduction.

The cytogenetic constitution of human blastocysts: insights from comprehensive chromosome screening strategies.

Background: Embryos that are able to form blastocysts have succeeded in activating their genome and differentiating into two cell types-an external layer of trophectoderm cells, which will go on to form extra-embryonic tissues such as the placenta, and the inner cell mass, which will give rise to the embryo proper. Culturing embryos to the blastocyst stage has become an increasingly popular IVF practice over the past decade. Additionally, it has been proposed that the identification and transfer of euploid blastocysts could significantly improve IVF outcomes.

The number of biopsied trophectoderm cells may affect pregnancy outcomes.

Objective: To study if the number of trophectoderm (TE) biopsied cells has an impact on implantation rates.

Design: A retrospective cohort study in a single-center study.

Setting: In vitro fertilization center.

Status of preimplantation genetic testing and embryo selection.

At the recent 2018 PGDIS congress, a review of randomized controlled trials of preimplantation genetic testing for aneuploidies (PGT-A) showed improved ongoing pregnancy rates per transfer in experienced centres and in women aged 35 years and older. Young women produce 40% abnormal embryos (20-60% range), but not all centres see a selection advantage; this indicates the need for more emphasis in improving biopsy and case management. Some chromosome abnormalities are iatrogenic; PGT-A could, therefore, be used as assisted reproductive technology (ART) quality control.

Forty years of IVF.

This monograph, written by the pioneers of IVF and reproductive medicine, celebrates the history, achievements, and medical advancements made over the last 40 years in this rapidly growing field.