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.

Single-Molecule Sequencing: A New Approach for Preimplantation Testing and Noninvasive Prenatal Diagnosis Confirmation of Fetal Genotype.

We investigated the potential of next-generation sequencing (NGS) as an alternative method for preimplantation genetic testing of monogenic disease (PGT-M) with human leukocyte antigen (HLA) matching and for noninvasive prenatal diagnosis follow-up. The case involved parents who were carriers of the Fanconi anemia complementation group G (FANCG) 260delG mutation. After clinical PGT using conventional short tandem repeat and mutation analysis, two euploid disease-free embryos were transferred, resulting in a twin pregnancy.

Before the beginning: the genetic risk of a couple aiming to conceive.

Disorders of genetic etiology exist in 2%-3% of live-born infants. Identifying couples with increased susceptibility for offspring with anomalies or genetic disorders is increasingly effective as a result of molecular advances. Preimplantation genetic testing (PGT) with the use of trophectoderm biopsy, 24-chromosome testing, and molecular testing have allowed wider applicability for avoiding a clinical pregnancy termination.

Overview of Preimplantation Genetic Diagnosis (PGD): Historical Perspective and Future Direction.

Preimplantation genetic diagnosis (PGD) can be considered the earliest form of prenatal testing. It was first used in humans over 26 years ago. At its inception, PGD could only be performed for a limited number of genetic disorders.

Preimplantation genetic testing: current challenges and future prospects.

Preimplantation genetic testing (PGT) is now a widely applied procedure in genetic practices and ART, with more than one third of ART Centers in US already utilizing PGT technology. Its indications have also been significantly extended to include common late-onset disorders and non-genetic conditions, such as testing for HLA match. Areas covered: This is a critical review of the developments in PGT, with emphasis on their outstanding limitations and directions for the future research and practice in the area of PGT.

First experience of hematopoietic stem cell transplantation treatment of Shwachman-Diamond syndrome using unaffected HLA-matched sibling donor produced through preimplantation HLA typing.

The only proven cure for Shwachman-Diamond syndrome (SDS) bone marrow failure is allogeneic hematopoietic stem cell transplantation (HSCT). However HSCT with donors other than HLA-identical siblings is associated with high mortality and unfavorable prognosis. This paper presents the first experience of HSCT treatment of SDS using an unaffected HLA-identical sibling produced through preimplantation genetic diagnosis (PGD).

First systematic experience of preimplantation genetic diagnosis for single-gene disorders, and/or preimplantation human leukocyte antigen typing, combined with 24-chromosome aneuploidy testing.

Objective: To study the feasibility, accuracy, and reproductive outcome of 24-chromosome aneuploidy testing (24-AT), combined with preimplantation genetic diagnosis (PGD) for single-gene disorders (SGDs) or human leukocyte antigen (HLA) typing in the same biopsy sample.

Design: Retrospective study.

Setting: Preimplantation genetic diagnosis center.

PGD for cystic fibrosis patients and couples at risk of an additional genetic disorder combined with 24-chromosome aneuploidy testing.

Preimplantation genetic diagnosis (PGD) for inherited disorders is presently applied for more than 300 different conditions. The most frequent PGD indication is cystic fibrosis (CF), the largest series of which is reviewed here, totalling 404 PGD cycles. This involved testing for 52 different CFTR mutations with almost half of the cases (195/404 cycles) performed for ΔF508 mutation, one-quarter (103/404 cycles) for six other frequent mutations and only a few for the remaining 45 CFTR mutations.

PGD for inherited cardiac diseases.

Preimplantation genetic diagnosis (PGD) has been applied for more than 200 different inherited conditions, with expanding application to common disorders with genetic predisposition. One of the recent indications for PGD has been inherited cardiac disease, for which no preclinical diagnosis and preventive management may exist and which may lead to premature or sudden death. This paper presents the first, as far as is known, cumulative experience of PGD for inherited cardiac diseases, including familial hypertrophic and dilated cardiomyopathy, cardioencephalomyopathy and Emery-Dreifuss muscular dystrophy.

Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage.

The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups.

Preimplantation genetic diagnosis for hemoglobinopathies.

Hemoglobinopathies are the most frequent indications for preimplantation genetic diagnosis (PGD), allowing couples at-risk of bearing offspring with thalassemia and sickle cell disease to reproduce without fear of having an affected child. The present experience includes PGD for sickle cell disease, α- and β-thalassemia (α- and β-thal). We present here the results of the world's largest experience of over 395 PGD cycles for hemoglobin (Hb) disorders, resulting in the birth of 98 healthy, hemoglobinopathy-free children, with seven pregnancies still ongoing.

First systematic experience of preimplantation genetic diagnosis for de-novo mutations.

Standard preimplantation genetic diagnosis (PGD) cannot be applied for de-novo mutations (DNM), because neither origin nor relevant haplotypes are available for testing in single cells. PGD strategies were developed for 80 families with 38 genetic disorders, determined by 33 dominant, three recessive and two X-linked DNM. All three recessive mutations were of paternal origin, while of 93 dominant mutations, 40 were paternal, 46 maternal and seven detected in affected children.

Polar body-based preimplantation genetic diagnosis for Mendelian disorders.

Introduced >20 years ago, the use of polar bodies (PBs), involving sequential removal and genetic analysis of the first (PB1) and second (PB2) PB, provides the option for pre-embryonic diagnosis, when the objection to the embryo biopsy procedures makes preimplantation genetic diagnosis (PGD) non-applicable. PB-based approach has presently been utilized in PGD for genetic and chromosomal disorders, applied either separately, or together with embryo biopsy approaches, especially if there are two or more PGD indications. We present here the world's largest experience of 938 PGD cycles for single-gene disorders performed by PB testing for 146 different monogenic conditions, which resulted in the birth of 345 healthy children (eight pregnancies are still ongoing), providing strong evidence that PB-based PGD is a reliable and safe procedure, with an extremely high accuracy rate of over 99%.

Single-gene testing combined with single nucleotide polymorphism microarray preimplantation genetic diagnosis for aneuploidy: a novel approach in optimizing pregnancy outcome.

Objective: To describe a method of amplifying DNA from blastocyst trophectoderm cells (two or three cells) and simultaneously performing 23-chromosome single nucleotide polymorphism microarrays and single-gene preimplantation genetic diagnosis.

Design: Case report.

Setting: IVF clinic and preimplantation genetic diagnostic centers.

Meiosis errors in over 20,000 oocytes studied in the practice of preimplantation aneuploidy testing.

This study presents the world’s largest series of over 20,000 oocytes tested for aneuploidies, involving chromosomes 13,16, 18, 21 and 22, providing the data on the rates and types of aneuploidies and their origin. Almost every second oocyte (46.8%) is abnormal, with predominance of extra chromatid errors predicting predominance of trisomies (53%) over monosomies (26%) in the resulting embryos (2:1), which is opposite to monosomy predominance observed in embryo testing.

Conversion and non-conversion approach to preimplantation diagnosis for chromosomal rearrangements in 475 cycles.

Due to the limitations of preimplantation genetic diagnosis (PGD) for chromosomal rearrangements by interphase fluorescent in-situ hybridization (FISH) analysis, a method for obtaining chromosomes from single blastomeres was introduced by their fusion with enucleated or intact mouse zygotes, followed by FISH analysis of the resulting heterokaryons. Although this allowed a significant improvement in the accuracy of testing of both maternally and paternally derived translocations, it is still labour intensive and requires the availability of fertilized mouse oocytes, also creating ethical issues related to the formation of interspecies heterokaryons. This method was modified with a chemical conversion procedure that has now been clinically applied for the first time on 877 embryos from PGD cycles for chromosomal rearrangements and has become the method of choice for performing PGD for structural rearrangements.

Correlation between preimplantation genetic diagnosis for chromosomal aneuploidies and the efficiency of establishing human ES cell lines.

There are several sources from which human embryonic stem cell (hESC) lines can be generated: surplus embryos after in vitro fertilization procedures, one- and three-pronuclear zygotes, early arrested or highly fragmented embryos that have reached the blastocyst stage, or otherwise chromosomally or genetically abnormal embryos after preimplantation genetic diagnosis (PGD). We report on the efficiency of establishing hESC lines from blastocysts with proven meiotic or mitotic errors after sequential testing of both polar bodies and blastomere analysis on day 3. The success rate of establishing hESC lines originating from blastocysts carrying a meiotic error was as low as 2.

Impact of meiotic and mitotic non-disjunction on generation of human embryonic stem cell lines.

At least 50-60% of oocytes derived from IVF procedures are chromosomally abnormal due to meiotic I or II errors. Through the use of polar body and blastomere diagnosis, euploid embryos suitable for transfer can be identified. Those embryos that are aneuploid are usually discarded, or otherwise can be used to generate chromosomally abnormal human embryonic stem cell (hESC) lines.

Preimplantation genetic diagnosis: technological advances to improve accuracy and range of applications.

Preimplantation genetic diagnosis (PGD) is an option for couples who are at risk that enables them to have unaffected progeny without facing the risk of pregnancy termination after prenatal diagnosis as currently practiced. It is also one of the practical tools used in assisted reproduction technology to improve the chance of conception for infertility cases with poor prognosis. Because PGD is performed using a single biopsied cell, technological advances are important to improving PGD accuracy.

Impact of preimplantation genetic diagnosis for chromosomal disorders on reproductive outcome.

Despite recent controversy, existing experience suggests that aneuploidy testing has had a significant impact on the reproductive outcome of poor prognosis IVF patients, which is based on the experience of over 20,000 cases of PGD for chromosomal disorders. The clinical impact was demonstrated in the improved implantation and pregnancy rates, reduction of spontaneous abortions and improved take-home baby rate in patients of advanced reproductive age, those with repeated IVF failures and recurrent spontaneous abortions. The lack of positive effect of aneuploidy testing in a few smaller series may be due to potential detrimental effect of two blastomere removal, reducing the implantation potential of the biopsied embryos, or exclusion from testing a few key chromosomes and poor outcome of aneuploidy testing, affecting the appropriate pre-selection of embryos for transfer.

Cytoplasmic cell fusion: Stembrid technology for reprogramming pluripotentiality.

Recent progress in somatic cell nuclear transfer (SCNT) provides the evidence for the presence of reprogramming factors in human embryonic stem cells (hESC). Hybrid hESC with donor human somatic nuclei have been established, but the resulting hybrid hESC contained DNA originating from both hESC and donor somatic cells. There is still no method to completely replace the hESC nuclei by the nuclei of somatic cells and to obtain the pure colonies of hESC with donor genotype.