Single Nucleotide Polymorphism array analysis for fetuses from balanced translocation carriers at the second trimester.

Prenatal diagnosis is crucial for pregnancies from couples with a carrier of a balanced translocation. We retrospectively reviewed 195 pregnancies from 189 couples with a balanced translocation carrier. Of these, 126 were from natural conception, while 69 were conceived through assisted reproductive technology (ART) with preimplantation genetic diagnosis (PGD).

A novel approach to detecting microduplication in split hand/foot malformation type 3 at the single-cell level: SHFM as a case study.

Background: Split hand/foot malformation (SHFM) is a congenital limb deficiency characterized by missing or shortened central digits. Several gene loci have been associated with SHFM. Identifying microduplications at the single-cell level is challenging in clinical practice, and traditional detection methods may lead to misdiagnoses in embryos and pregnant women.

The frontier of precision medicine: application of single-cell multi-omics in preimplantation genetic diagnosis.

The advent of single-cell multi-omics technologies has revolutionized the landscape of preimplantation genetic diagnosis (PGD), offering unprecedented insights into the genetic, transcriptomic, and proteomic profiles of individual cells in early-stage embryos. This breakthrough holds the promise of enhancing the accuracy, efficiency, and scope of PGD, thereby significantly improving outcomes in assisted reproductive technologies (ARTs) and genetic disease prevention. This review provides a comprehensive overview of the importance of PGD in the context of precision medicine and elucidates how single-cell multi-omics technologies have transformed this field.

Case report: Successful PGT-M based on the identification of a spliceogenic variant in the gene through Minigene assay.

With the development of high-throughput sequencing, the genetic etiology of many diseases has been revealed. However, this has also led to the categorization of many variants as variants of uncertain significance (VUSs), presenting a major challenge in genetic counseling. A couple with a history of adverse pregnancies sought assisted reproductive technology.

Preimplantation genetic testing for Cockayne syndrome with a novel ERCC6 variant in a Chinese family.

Background: Cockayne syndrome (CS) is a rare, multisystem, autosomal recessive disorder characterized by cachectic dwarfism, nervous system abnormalities, and premature aging. Mutations in the ERCC6 and ERCC8 genes are the predominant causes of Cockayne syndrome, with ERCC6 gene mutations present in approximately 75% of cases.

Methods: Trio-based whole-exome sequencing (trio-WES) was employed to identify potential pathogenic variants associated with CS.

The clinical application of affected-embryo-based SNP haplotype analysis for patients with de novo pathogenic mutations in PGT-M cycles.

Purpose: In preimplantation genetic testing for monogenic/single gene disorders (PGT-M) cycles, direct detection of the pathogenic mutation combined with indirect haplotype analysis are recommended to achieve accurate diagnosis. However, it poses a challenge to conduct haplotype analysis for patients carried de novo pathogenetic mutations or without no identified haplotype in families. Herein, the strategy of affected-embryo-based haplotype analysis was implemented in clinical practice to provide a convenient, economical and effective way for such patients.

Non-invasively predicting euploidy in human blastocysts via quantitative 3D morphology measurement: a retrospective cohort study.

Background: Blastocyst morphology has been demonstrated to be associated with ploidy status. Existing artificial intelligence models use manual grading or 2D images as the input for euploidy prediction, which suffer from subjectivity from observers and information loss due to incomplete features from 2D images. Here we aim to predict euploidy in human blastocysts using quantitative morphological parameters obtained by 3D morphology measurement.

Current research status and clinical applications of noninvasive preimplantation genetic testing: A review.

Noninvasive preimplantation genetic testing (ni-PGT) is conducted by obtaining genetic information from embryos through the analysis of free DNA released by embryos in spent embryo culture medium or blastocoel fluid. Compared to conventional preimplantation genetic testing relying on trophectoderm biopsy, ni-PGT is characterized by its noninvasiveness. It has demonstrated early advancements in the detection of embryonic chromosomal aneuploidies and the diagnosis of monogenic diseases, showcasing considerable potential for clinical application.

Comparative Analysis of Fluorescence In Situ Hybridization and Next-Generation Sequencing in Sperm Evaluation: Implications for Preimplantation Genetic Testing and Male Infertility.

Pre-implantation genetic testing (PGT) is a crucial process for selecting embryos created through assisted reproductive technology (ART). Couples with chromosomal rearrangements, infertility, recurrent miscarriages, advanced maternal age, known single-gene disorders, a family history of genetic conditions, previously affected pregnancies, poor embryo quality, or congenital anomalies may be candidates for PGT. Preimplantation genetic testing for aneuploidies (PGT-A) enables the selection and transfer of euploid embryos, significantly enhancing implantation rates in assisted reproduction.

Time will tell: time-lapse technology and artificial intelligence to set time cut-offs indicating embryo incompetence.

Study Question: Can more reliable time cut-offs of embryo developmental incompetence be generated by combining time-lapse technology (TLT), artificial intelligence, and preimplantation genetics screening for aneuploidy (PGT-A)?

Summary Answer: Embryo developmental incompetence can be better predicted by time cut-offs at multiple developmental stages and for different ranges of maternal age.

What Is Known Already: TLT is instrumental for the continual and undisturbed observation of embryo development. It has produced morphokinetic algorithms aimed at selecting embryos able to generate a viable pregnancy, however, such efforts have had limited success.

A method for determining potential parental contamination: linkage disequilibrium-based log-likelihood ratio analysis for IVF-PGT.

Background: At present, embryologists are attempting to use conventional in vitro fertilization (cIVF) as an alternative to intracytoplasmic sperm injection (ICSI) for preimplantation genetic testing (PGT). However, the potential parental contamination origin of sperm cells and cumulus cells is considered the main limiting factor in the inability of cIVF embryos to undergo PGT.

Methods: In this study, we established an IVF-PGTA assay for parental contamination tests with a contamination prediction model based on allele frequencies and linkage disequilibrium (LD) to compute the log-likelihood ratio (LLR) under competing ploidy hypotheses, and then verified its sensitivity and accuracy.

Perinatal outcomes of women with recurrent pregnancy loss undergoing frozen embryo transfer from the Society of Assisted Reproductive Technology database.

Objective: To assess whether infants born to women with a history of recurrent pregnancy loss (RPL) have an increased risk of adverse perinatal outcomes after frozen embryo transfer (FET) compared with women without a history of infertility or RPL.

Design: Retrospective cohort study utilizing the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System database between 2014 and 2020.

Setting: Not applicable.

Multi-omics PGT: re-evaluation of euploid blastocysts for implantation potential based on RNA sequencing.

Study Question: In addition to chromosomal euploidy, can the transcriptome of blastocysts be used as a novel predictor of embryo implantation potential?

Summary Answer: This retrospective analysis showed that based on differentially expressed genes (DEGs) between euploid blastocysts which resulted and did not result in a clinical pregnancy, machine learning models could help improve implantation rates by blastocyst optimization.

What Is Known Already: Embryo implantation is a multifaceted process, with implantation loss and pregnancy failure related not only to blastocyst euploidy but also to the intricate dialog between blastocyst and endometrium. Although in vitro studies have revealed the characteristics of trophectoderm (TE) differentiation in implanted blastocysts and the function of TE placentation at the implantation site, the precise molecular mechanisms of embryo implantation and their clinical application remain to be fully elucidated.

Feasibility of preimplantation genetic testing for aneuploidy on frozen-thawed embryos following conventional IVF insemination.

Objective: Intracytoplasmic sperm injection (ICSI) is commonly employed in preimplantation genetic testing (PGT) to minimize the risk of foreign sperm DNA contamination. Cryopreserved embryos from patients with recurrent miscarriage or repeated implantation failure, who have undergone conventional fertilization (IVF), can be thawed and biopsied for PGT. Therefore, we aimed to assess the accuracy and effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) on frozen embryos using conventional IVF (c-IVF) insemination methods.

Blastocysts originated from oocytes with smooth endoplasmic reticulum aggregates have a reduced euploidy rate: a retrospective cohort study.

Research Question: Does the presence of smooth endoplasmic reticulum aggregates (SERa) in oocytes adversely impact the euploidy rate of subsequent blastocysts?

Design: We performed a retrospective cohort study with 671 young patients (< 38 years) undergoing their first preimplantation genetic testing for aneuploidy (PGT-A) between January 2019 and October 2022 at a reproductive medical center of university affiliated teaching hospitals in China. Cycles were categorized as either SERa(+) cycles (containing at least one SERa(+) oocyte) or SERa(-) cycles (all oocytes without SERa). In SERa(+) cycles, oocytes were further subdivided into the SERa(+) oocyte group and the sibling SERa(-) oocyte group, comprising oocytes with normal morphology.

Healthy live births achieved from embryos diagnosed as non-mosaic segmental aneuploid.

Purpose: To investigate pregnancy outcomes resulting from transfer of embryos with non-mosaic (NM) segmental aneuploid (SA) results following preimplantation genetic testing for aneuploidy (PGT-A).

Methods: All patients who underwent frozen embryo transfer (FET) of at least one embryo with a NM-SA between March 2021 and April 2024 were retrospectively reviewed. Primary outcomes included live birth rate (LBR) and results of prenatal diagnosis.