Preimplantation genetic testing to reduce preterm births in assisted reproductive technology.

The 10% rate of preterm birth rate worldwide has not been proved amenable to reduction. Avoiding multiple embryo transfer in assisted reproductive technologies (ART) using in vitro fertilization is one unassailable method. Preimplantation genetic testing (PGT) to select only a single euploid embryo for transfer is one unequivocal way, maintaining 50%-60% pregnancy rates while avoiding twins.

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.

Prenatal genetic testing and treatment for congenital adrenal hyperplasia.

Couples at risk for autosomal recessive congenital adrenal hyperplasia often request anticipatory guidance and genetic counseling. Initially, hormones in amniotic fluid were measured to distinguish affected female fetuses from unaffected fetuses. With the molecular era, more-targeted approaches became possible.

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.

Preimplantation diagnosis and other modern methods for prenatal diagnosis.

Prenatal treatment of congenital adrenal hyperplasia (CAH) has long involved prenatal treatment with dexamethasone, administered to the pregnant woman to prevent genital masculinization of an affected female fetus. Although it is unnecessary to treat unaffected or affected males because their genital development would not be disturbed, there has only been incremental progress in determining fetal gender sufficiently each to avoid treating males and unaffected females. Invasive procedures were initially necessary, with first-trimester amniocentesis at 15-20 weeks and then chorionic villus sampling (CVS) at 10-12 weeks gestation.

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.

Preimplantation genetic diagnosis (PGD) for genetic prion disorder due to F198S mutation in the PRNP gene.

Importance: To describe the first case of preimplantation genetic diagnosis (PGD) and in vitro fertilization (IVF) performed for the prevention of genetic prion disease in the children of a 27-year-old asymptomatic woman with a family history of Gerstmann-Sträussler-Sheinker syndrome (GSS).

Observations: PGD and fertilization cycles resulted in detection of 6 F198S mutation-free embryos. Of these, 2 were selected for embryo transfer to the patient's uterus, yielding a clinical twin pregnancy and birth of healthy but slightly premature offspring with normal development at age 27 months.

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.

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.

Preimplantation diagnosis for immunodeficiencies.

Preimplantation genetic diagnosis (PGD) has become an established procedure for the detection of single gene disorders, and has recently been performed together with human leukocyte antigen (HLA) typing for couples with children affected by genetic disorders that require HLA-identical stem cell transplantation therapy. For these couples, PGD can ensure the birth of an unaffected child, and because HLA-matched stem cell transplantation improves or completely restores the immune system, this child may also serve as a potential stem cell donor for affected siblings. This paper presents the first cumulative experience (18 cycles) of PGD for detection of the following immunodeficiencies: Wiscott-Aldrich syndrome, X-linked hyper-IgM syndrome (HIGM), X-linked hypohidrotic ectodermal dysplasia with immune deficiency (HED-ID), ataxia telangiectasia and Omenn syndrome, resulting in the transfer of unaffected embryos in 13 cycles and the birth of seven unaffected children, with one healthy pregnancy ongoing.

Pre-embryonic diagnosis for Sandhoff disease.

Embryos found to be abnormal during preimplantation genetic diagnosis (PGD) are discarded or analysed to confirm the diagnosis. To overcome this limitation, which is unacceptable in some communities and ethnic groups, pre-embryonic genetic diagnosis has been introduced, involving sequential first and second polar body analysis followed by transfer of embryos deriving from the mutation-free oocytes, while removing from culture and freezing the mutant oocytes at the pronuclear stage. The technique is applied here to PGD of Sandhoff disease caused by 16-kb deletion of the hexosaminidase B gene for a couple with a religious objection to discarding embryos irrespective of embryo genotype.

Preimplantation HLA typing with aneuploidy testing.

Preimplantation HLA typing has been introduced for the treatment of affected siblings, requiring HLA-identical stem cell transplantation. This was applied either in combination with preimplantation genetic diagnosis (PGD) to ensure that the preselected HLA-matched embryos were also free of the genetic disorder, or without PGD, with the only purpose of selecting and transferring the HLA-matched embryos. Because patients requesting preimplantation HLA typing are usually of advanced reproductive age, aneuploidy testing allows not only the avoidance of the birth of children with chromosomal disorders, but also improvement of the reproductive outcome, which is still not sufficiently high in preimplantation HLA typing at the present time.

Preimplantation genetics: Improving access to stem cell therapy.

There has been progress in the application of stem cell transplantation for treatment of an increasing number of severe congenital and acquired bone marrow disorders, currently restricted by the availability of human leukocyte antigen (HLA)-matched related donors. Preimplantation HLA typing has recently been introduced to improve the access to stem cell therapy for inherited bone marrow failures. Preimplantation genetic diagnosis (PGD) provides an option not only for avoiding an affected pregnancy with thalassemia and other inherited disorders but also for preselection of the HLA-compatible donors for affected siblings.

Fusion as the etiology of chimerism in monochorionic dizygotic twins.

In a dizygotic pregnancy within monochorionic placenta, findings consistent with chimerism were detected. Monochorionicity was confirmed by a combination of ultrasound, histological evaluation and DNA technology. Etiologic hypotheses are offered to explain this rare circumstance.

Preimplantation genetic diagnosis for polycystic kidney disease.

Objective: To use preimplantation genetic diagnosis for achieving a polycystic kidney disease (PKD)-free pregnancy for a couple in which the female partner was affected by PKD but whose PKD1 or PKD2 carrier status was not established.

Design: Case report.

Setting: The IVF program of Reproductive Genetics Institute, Chicago, Illinois.