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Preimplantation genetic diagnosis (PGD) was introduced in the late 1980s and represents an option for couples at risk of transmitting an inherited, debilitating or neurological disorder to their children. From a cleavage or blastocyst stage embryo, cell(s) are collected and then genetically analyzed for disease; enabling an unaffected embryo to be transferred into the uterus cavity. Nowadays, PGD has been carried out for several hundreds of heritable conditions including myotonic dystrophy, and for susceptibility genes involved in cancers of the nervous system. Currently, advanced molecular technologies with better resolution, such as array comparative genomic hybridisation, quantitative polymerase chain reaction, and next generation sequencing, are on the verge of becoming the gold standard in embryo preimplantation screening. Given this, it may be time for neurological societies to consider the published evidence to develop new guidelines for the integration of PGD into modern preventative neurology. Therefore, the main aim of this review is to illustrate the option of PGD to enable conception of an unaffected baby, and to assist clinicians and neurologists in the counseling of the patient at risk of transmitting an inherited disease, to explore the genetic journey throughout in vitro fertilization IVF with PGD.

BACKGROUND AND OBJECTIVES Preimplantation QRS-T morphology screening (TMS) is a composite tool for selecting subcutaneous implantable cardioverter defibrillator (S-ICD) candidates. However, its role in predicting the patient's response to cardiac resynchronization therapy (CRT) is uncertain. METHODS A total of 55 consecutive de novo CRT candidates were enrolled between January 2016 and March 2017. Electrocardiogram (ECG) and TMS were performed before and soon after implantation. The ECG parameters were recorded, including QRS duration and morphology (such as ΔQRS_Index, QTc during biventricular pacing mode [BiV pacing QTc], and QRS/T ratio during biventricular pacing mode [BiV pacing QRS/T ratio]). TMS monitored three sensory vectors of the S-ICD. Six months after implantation, the responses to CRT were evaluated. RESULTS Thirty-nine patients (70.9%) passed the TMS during biventricular pacing mode. At the six-month follow-up, the number of responders and super-responders was significantly higher in the passing group than in the non-passing group (responders: 31/39 [79.5%] vs. 5/16 [31.3%], p

The majority of embryos created through in vitro fertilization (IVF) do not implant. It seems plausible that rates of implantation would improve if we had a better understanding of molecular factors affecting embryo competence. Currently, the process of selecting an embryo for uterine transfer uses an ad hoc combination of morphological criteria, the kinetics of development, and genetic testing for aneuploidy. However, no single criterion can ensure selection of a viable embryo. In contrast, RNA-sequencing (RNA-seq) of embryos could yield high-dimensional data, which may provide additional insight and illuminate the discrepancies among current selection criteria. Recent advances enabling the production of RNA-seq libraries from single cells have facilitated the application of this technique to the study of transcriptional events in early human development. However, these studies have not assessed the quality of their constituent embryos relative to commonly used embryological criteria. Here, we perform proof-of-principle advancement to embryo selection procedures by generating RNA-seq libraries from a trophectoderm biopsy as well as the remaining whole embryo. We combine state-of-the-art embryological methods with low-input RNA-seq to develop the first transcriptome-wide approach for assessing embryo competence. Specifically, we show the capacity of RNA-seq as a promising tool in preimplantation screening by showing that biopsies of an embryo can capture valuable information available in the whole embryo from which they are derived. Furthermore, we show that this technique can be used to generate a RNA-based digital karyotype and to identify candidate competence-associated genes. Together, these data establish the foundation for a future RNA-based diagnostic in IVF.

Infertility has become an increasingly common health problem and has been estimated to affect approximately 10% of women in the reproductive age. Due to its high prevalence, it has been deemed a social disease by the World Health Organization (WHO). The causes of infertility are numerous and vary from person to person. As for treatment, the three main therapeutic strategies include pharmacological therapy, surgical therapy - mostly endoscopy, and assisted reproductive technology (ART). Recent decades have witnessed great progress in ART, resulting in successful treatment of the previously untreatable cases, particularly in the field of fertility preservation, preimplantation screening for aneuploidy, uterine transplantations and mitochondrial replacement techniques as prevention against a number of severe diseases. Regardless, ART treatment does not guarantee pregnancy and live birth. The success rate is much smaller as compared to the failure rate, it being among its most important limitations. Embryo implantation is an extremely complex process and represents the most critical step of the reproduction process in humans. Attempts to evaluate endometrial receptivity and strategies for its correction have been discussed. The search for new effective predictors of an individual prognosis remains a crucial challenge for the contemporary reproductive medicine.

The purpose of this study is to report a successful twin pregnancy and delivery in a female patient with X-linked dominant incontinentia pigmenti (IP) who underwent assisted reproductive technology followed by preimplantation genetic screening (PGS). A 29-year-old female with IP had a previous history of recurrent spontaneous abortion. A molecular analysis revealed the patient had a de novo mutation, 1308_1309insCCCCTTG(p.Ala438ProfsTer26), in the inhibitor of the kappa B kinase gamma gene located in the Xq28 region. IVF/ICSI and PGS was performed, in which male embryos were sexed using array-based comparative genomic hybridization (aCGH). After IVF/ICSI and PGS using aCGH on seven embryos, two euploid male blastocysts were transferred with a 50% probability of a viable male pregnancy. The dizygotic twin pregnancy was confirmed and the amniocentesis results of each twin were normal with regard to the mutation found in the mother. The pa tient delivered healthy twin babies during the 37th week of gestation. This case shows the beneficial role of PGS in achieving a successful preg nancy through euploid male embryo gender selection in a woman with X-linked dominant IP with a history of multiple male miscarriages.

Chromosomal abnormalities arising after fertilization, are observed at a relatively high rate at the cleavage stage. To evaluate the aneuploidy and mosaicism, microarray comparative genomic hybridization (CGH) of trophectoderm cells from blastocysts has been considered in preimplantation screening. However, 1% or less of live births are children with chromosomal abnormalities. In this paper, cytogenetic features of patients with chromosomal abnormalities and methods for detecting the disorders are described. Consideration of the utilities and limitations of cytogenetic techniques is essential in the clinical setting.

Our objective is to describe a successful live birth from oocyte vitrification followed by thaw, fertilization, blastocyst culture, trophectoderm biopsy, vitrification, and subsequent thaw. Fifteen mature oocytes were frozen from a patient with uterine factor infertility. Thirteen oocytes survived the thaw, and five underwent trophectoderm biopsy and were refrozen. Three euploid embryos were obtained. A single euploid embryo was transferred in the second thaw cycle to a known recipient leading to the delivery of a normal male infant. This case report is proof of the concept that preimplantation screening and diagnosis is an option for fertility preservation patients.

PURPOSE OF REVIEW Embryo implantation remains the rate-limiting step in assisted conception programmes. Factors affecting the interactions between blastocyst and endometrium are subjects of current research and, sadly, have also been the subjects of much confusion. This review aims to present current thinking on factors affecting embryo development, endometrial receptivity during and around the implantation window and the evidence for and against various proposed treatment options RECENT FINDINGS Age-related aneuploidies of the sex chromosomes and several other autosomes are now thought to adversely affect oocyte and embryo quality, leading to repeat in-vitro fertilization failures. Several small controlled trials have suggested improvements in clinical outcomes following preimplantation screening and blastocyst transfer for aneuploidy in older women. These are, however, very costly, wasteful of embryos and do not appear beneficial after the age of 40 years. Factors influencing endometrial receptivity remain largely unresolved. New technology using microarrays for gene expression profiling and progesterone receptor polymorphism may shed more light in the near future. SUMMARY Giant strides have been made in studying the causative factors of implantation failure, but these have not been matched by therapeutic solutions. Many proposed interventions are of unproven value, yet can have harmful side-effects.

We report enrichment in the efficiency of generating mice transgenic for expression of a human protein in their milk using GFP-mediated preimplantation screening. The transgene array consisted of a functional gene (human alpha-1 antitrypsin under the control of the ovine BLG promoter) linked 5' to a reporter gene (GFP under the control of the murine Oct-4 promoter). GFP expression was detected in blastocysts by fluorescence microscopy and green and nongreen embryos were transferred to recipients in separate groups. In the first experiment, of seven pups that resulted from the transfer of blastocysts expressing GFP, five (71%) were transgenic. The experiment was repeated and of 12 pups that resulted from transfer of GFP-expressing blastocysts, 11 were transgenic (92%). The presence of the reporter cassette used for preimplantation screening did not affect the expression level of alpha-1-antitrypsin in the milk of the transgenic mice. In addition, in a related experiment wherein the GFP reporter gene was co-injected with a second mammary-specific transgene, pINC, no effect on transgene expression was observed. For mice transgenic for the mammary-specific gene alone, expression levels for four different lines were 192, 197, 382, and 415 microg/mL. For mice transgenic for both the mammary-specific transgene and the Oct4-GFP reporter cassette, expression levels for seven different lines were 282, 321, 468, 497, 499, 516, and 806 microg/mL.

Robert Nozick, in what is surely one of the most intriguing and provocative footnotes in modern philosophical writing, referred in Anarchy, State and Utopia to the notion of a “genetic supermarket.” In keeping with the central arguments of that text, his suggestion was that choices about the genetic composition of future generations should, as far as possible, be left in the hands of private individuals, and should not be determined or restricted by the state. This free market in genetic screening would meet “the individual specifications (within certain moral limits) of prospective parents,” and would possess “the great virtue that it involves no centralized decision fixing the future human type(s).” In short, prospective parents would be allowed, to whatever extent was rendered possible by current technology, to choose the genetic traits of their future children.

Preimplantation genetic screening of embryos for chromosome abnormalities reduces the success rate of in vitro fertilisation (IVF) by nearly a third in older women, according to a European study ( New England Journal of Medicine 2007;356:9-17). The study looked at the rates of ongoing pregnancies and live births in a total of 408 women aged 35 to 41 years undergoing a total of 862 cycles of in vitro fertilisation. Half of the women (206) were randomised to undergo preimplantation genetic screening, and the other half were a control group and were not screened. Screening involved taking a biopsy of one cell at three days and testing chromosomes to detect trisomies or other abnormalities in chromosome number. Sebastiaan Mastenbroek, from the Center for Reproductive Medicine at the University of Amsterdam, the Netherlands, and lead author of the study, explained the rationale, “Pregnancy rates in women of advanced maternal age undergoing IVF are disappointingly low. A potential cause is the increased incidence of chromosomal abnormalities. It has been suggested that use of preimplantation screening of cleavage stage embryos for aneuploidies may improve the effectiveness of …

Selecting against embryos or fetuses on the basis of predicted disability reinforces the belief that disability is inimical to a worthwhile life. A critique of preimplantation screening and prenatal diagnosis flows from the belief that life with disability can be valuable to individuals, their families and society. Keywords: prenatal diagnosis; abortion; genetic testing; genetic counseling; disability

The genetic manipulation of donor cells before nuclear transfer (NT) enables prior selection for transgene integration. However, selection for genetically modified cells using antibiotic drugs often results in mixed populations, resulting in a mixture of transgenic and nontransgenic donor cells for NT. In this study, we attempted to develop efficient strategies for the generation of human bile salt-stimulated lipase (BSSL) transgenic cows. Preimplantation screening by either biopsy or green fluorescent protein (GFP) expression was used to detect NT-derived BSSL transgenic embryos to ensure that the calf born would be transgenic. We compared the development rates of NT-derived embryos from G418- and GFP-selected donor cells. There were no significant differences (P , 0.001) in cleavage rate (67.2% vs. 60.0%) and blastocyst formation rate (44.9% vs. 41.2%). We also compared the pregnancy rates of the G418/biopsy and GFP preimplantation screened NT-derived blastocysts. The Day 40 pregnancy rate of the G418/biopsy group (40%) was lower than that of the GFP group (57%), but the calf birth rate of the G418/ biopsy group (40%) was higher than that of the GFP group (21%). Healthy BSSL transgenic calves were born after both screening processes. This is the first report of biopsy-screened cloned transgenic animals. The results suggest that both selection methods are useful for detecting transgenic NT embryos without negatively affecting their development into viable transgenic offspring. assisted reproductive technology, early development, embryo, pregnancy

The utility of using psychological assessments as a basis for predicting pain relief after electrode implantation is examined. Two raters independently reviewed the functional pain protocols of chronic pain patients who were candidates for deep brain (n = 13) or spinal cord (n = 17) electrode implants and predicted whether each would have a good or poor treatment response. At follow-up, five deep brain (39%) and four spinal cord (24%) patients were classified as having good responses to treatment. Predictions of outcome based on psychological data were accurate for 80% of the patients. These results suggest that functional pain assessment is useful as a part of preimplantation screening and emphasize the importance of psychological factors in the outcome of treatment for chronic pain.