scholarly journals Preimplantation Genetic Testing Prevented Intergenerational Transmission of X-Linked Alport Syndrome

2021 ◽  
pp. 1-7
Author(s):  
Xiaoling Hu ◽  
Jiahui Zhang ◽  
Yuan Lv ◽  
Xijing Chen ◽  
Guofang Feng ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Intergenerational Transmission ◽  
Alport Syndrome ◽  
Human Embryos ◽  
Radical Cure ◽  
Preimplantation Genetic Testing ◽  
Monogenic Disorders ◽  
Targeted Ngs ◽  
Stage Renal Disease

<b><i>Background:</i></b> Alport syndrome (AS) is a hereditary renal basement membrane disease that can lead to end-stage renal disease in young adults. It can be diagnosed by genetic analysis, being mostly caused by mutations in <i>COL4A3</i>, <i>COL­4A4</i>, and <i>COL4A5</i>. To date, there is no radical cure for this disease. <b><i>Objectives:</i></b> The aim of this study was to avoid the transmission of AS within an affected family by selecting healthy embryos for uterine transfer. The embryos were identified by preimplantation genetic testing for monogenic disorders (PGT-M). <b><i>Methods:</i></b> We used next-generation sequencing (NGS) to identify mutations in the proband and his parents. The results of NGS were confirmed by Sanger sequencing. Targeted NGS combined with targeted single-nucleotide polymorphism haplotyping was used for the in vitro identification of <i>COL4A5</i> mutations in human embryos to prevent their intergenerational transmission. <b><i>Results:</i></b> The c.349_359delGGACCTCAAGG and c.360_361insTGC mutations in <i>COL4A5</i> were identified in a family affected by X-linked AS. Whole-genome sequencing by NGS with targeted haplotyping was performed on biopsied trophectoderm cells. A healthy baby was born after transfer of a single freeze-thawed blastocyst. <b><i>Conclusions:</i></b> The use of targeted NGS for identifying diagnostic markers combined with targeted haplotyping is an easy and efficient PGT-M method for preventing intergenerational transmission of AS.

scholarly journals PREIMPLANTATION GENETIC TESTING: Chromosome abnormalities in human embryos

Reproduction ◽  
2020 ◽  
Vol 160 (5) ◽  
pp. A33-A44
Author(s):  
Carmen Rubio ◽  
Lorena Rodrigo ◽  
Carlos Simón
Keyword(s):  
Genetic Testing ◽  
Culture Media ◽  
Sperm Concentration ◽  
Early Embryo ◽  
Chromosome Abnormalities ◽  
Critical Event ◽  
Human Embryos ◽  
Preimplantation Genetic Testing ◽  
Frequent Event

Aneuploidy is a frequent event in human embryos, and its incidence is higher in oocytes and embryos from women of advanced maternal age. Aneuploidy may also be a contributing factor in infertile populations, such as couples with recurrent miscarriages, repetitive implantation failure, or male infertility. For these reasons, preimplantation genetic testing for aneuploidy (PGT-A) has been proposed to prevent miscarriages and increase live birth rates in infertile couples undergoing in vitro fertilisation. Next-generation sequencing is currently being applied for the detection of aneuploidies in human embryos, including whole chromosome aneuploidies, segmental aneuploidies, uniform, and mosaic aneuploidies. More recently, this technology has been incorporated for the analysis of the cell-free DNA secreted by the embryo to the culture media. Chromosome abnormalities mostly originate in female meiosis. Recombination between homologous chromosomes is a critical event that occurs in the foetal ovary. The importance of altered recombination pertains to paternally as well as maternally derived trisomies, but as most aneuploidy arises during oogenesis, the female is at greater risk. For males, sperm concentration is associated with a higher risk of aneuploid sperm and thus aneuploid embryos. Mitosis errors can occur at all stages of early embryo development that result in chromosomally distinct cell populations. The clinical impact of mosaicism depends on the mosaicism type, location, and number of aneuploid cells. Transfer of mosaic embryos has been proposed when no euploid embryos are available in the PGT-A cycle.

scholarly journals A Non-invasive Chromosome Screening Strategy for Prioritizing in vitro Fertilization Embryos for Implantation

2021 ◽  
Vol 9 ◽  
Author(s):  
Li Chen ◽  
Qin Sun ◽  
Juanjuan Xu ◽  
Haiyan Fu ◽  
Yuxiu Liu ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Predictive Value ◽  
Large Scale ◽  
Human Embryos ◽  
Clinical Practices ◽  
Preimplantation Genetic Testing ◽  
Invasive Approach ◽  
Vitro Fertilization ◽  
Non Invasive

Preimplantation genetic testing for aneuploidy (PGT-A) is widely used to select embryos having normal ploidy for transfer, but they require an invasive embryo biopsy procedure that may cause harm to the embryos and offspring. Therefore, a non-invasive approach to select embryos with normal ploidy for implantation is highly demanded. Non-invasive chromosome screening (NICS) methods have been proposed and applied in clinical practices, but a large-scale validation versus invasive preimplantation genetic testing (PGT) and the whole embryo ploidy has not yet been reported. In this study, by using the whole embryo as a gold standard, we validated NICS assay in a total of 265 donated human embryos and compared its performance with conventional trophectoderm (TE) biopsy PGT. The NICS assay showed promising performance, which is comparable to PGT-TE [sensitivity: 87.36 versus 89.66%; specificity: 80.28 versus 82.39%; negative predictive value (NPV): 91.2 versus 92.86%; positive predictive value (PPV): 73.08 versus 75.73%]. Additionally, NICS provides a scoring system for prioritizing embryo: embryos can be categorized into three groups with euploid prediction probabilities of 90.0, 27.8, and 72.2% for group euploid (A), aneuploid (B), and multiple abnormal chromosomes (MAC) (C), respectively. When an addition of TE assay is provided as a secondary validation, the accuracy significantly increases from 72.2 to 84.3% for group B and from 27.8 to 83.3% for group C. Our results suggest that NICS is a good rule in assay for identifying chromosomal normal embryos for transfer and might serve as a non-invasive approach for prioritizing embryos instead of preventing transfer of aneuploid and MAC embryos. It will help to ensure the safety of offspring and efficient utilization of embryos.

scholarly journals Preimplantation genetic testing for aneuploidy in uterus transplant patients

2021 ◽  
Vol 15 ◽  
pp. 263349412110098
Author(s):  
Rhea Chattopadhyay ◽  
Elliott Richards ◽  
Valerie Libby ◽  
Rebecca Flyckt
Keyword(s):  
Genetic Testing ◽  
In Vitro Fertilization ◽  
Immunosuppressive Agents ◽  
Live Birth Rate ◽  
Preimplantation Genetic Testing ◽  
Vitro Fertilization ◽  
Uterus Transplantation ◽  
Advantages And Disadvantages ◽  
Dilation And Curettage

Uterus transplantation is an emerging treatment for uterine factor infertility. In vitro fertilization with cryopreservation of embryos prior is required before a patient can be listed for transplant. Whether or not to perform universal preimplantation genetic testing for aneuploidy should be addressed by centers considering a uterus transplant program. The advantages and disadvantages of preimplantation genetic testing for aneuploidy in this unique population are presented. The available literature is reviewed to determine the utility of preimplantation genetic testing for aneuploidy in uterus transplantation protocols. Theoretical benefits of preimplantation genetic testing for aneuploidy include decreased time to pregnancy in a population that benefits from minimization of exposure to immunosuppressive agents and decreased chance of spontaneous abortion requiring a dilation and curettage. Drawbacks include increased cost per in vitro fertilization cycle, increased number of required in vitro fertilization cycles to achieve a suitable number of embryos prior to listing for transplant, and a questionable benefit to live birth rate in younger patients. Thoughtful consideration of whether or not to use preimplantation genetic testing for aneuploidy is necessary in uterus transplant trials. Age is likely a primary factor that can be useful in determining which uterus transplant recipients benefit from preimplantation genetic testing for aneuploidy.

scholarly journals Pericentric inversion (Inv) 9 variant—reproductive risk factor or benign finding?

2019 ◽  
Vol 36 (12) ◽  
pp. 2557-2561 ◽  
Author(s):  
Katrina Merrion ◽  
Melissa Maisenbacher
Keyword(s):  
Genetic Testing ◽  
Pericentric Inversion ◽  
Chromosome Rearrangement ◽  
Cohort Analysis ◽  
Chromosome 9 ◽  
Structural Rearrangements ◽  
Preimplantation Genetic Testing ◽  
Vitro Fertilization ◽  
Aneuploidy Rate

Abstract Purpose To report the unbalanced chromosome rearrangement rate and overall aneuploidy rate in day 5/6 embryos from a series of patients who underwent in vitro fertilization (IVF) with preimplantation genetic testing for structural rearrangements (PGT-SR) for the pericentric inversion 9 variant, inv(9)(p11q13) or inv(9)(p12q13), with concurrent 24 chromosome preimplantation genetic testing for aneuploidy (PGT-A). Methods This was a retrospective cohort analysis. IVF cycles and embryo biopsies were performed by referring clinics. Fifty-two trophectoderm biopsy samples from seven couples were sent to a single lab for PGT-SR for an inversion 9 variant with concurrent 24 chromosome PGT-A using single-nucleotide polymorphism (SNP) microarrays with bioinformatics. Results The unbalanced rearrangement rate for this embryo cohort was 0/52 (0.0%); mean maternal age per embryo was 33.3 years (range 21–39 years). The overall euploid rate was 61.5% and aneuploidy rate was 38.5%. Conclusions Chromosome 9 pericentric inversions did not result in unbalanced structural rearrangements in day 5/6 embryo samples, supporting that this population variant is not associated with increased reproductive risks.

scholarly journals Polygenic Risk Scoring of Human Embryos: a Qualitative Study of Media Coverage

2021 ◽  
Author(s):  
Tiny Pagnaer ◽  
Maria Siermann ◽  
Pascal Borry ◽  
Olga Tšuiko
Keyword(s):  
Media Coverage ◽  
Well Being ◽  
Reproductive Technologies ◽  
Media Analysis ◽  
Human Embryos ◽  
Preimplantation Genetic Testing ◽  
Vitro Fertilization ◽  
Polygenic Risk ◽  
Risk Scoring

Abstract Background Current preimplantation genetic testing (PGT) technologies enable embryo genotyping across the whole genome. Consequently, this has led to the development of polygenic risk scoring of human embryos (PGT-P). Recent implementation of PGT-P, including screening for intelligence, has been extensively covered by the media, raising major controversy. Considering the increasing demand for assisted reproduction, we evaluated how information about PGT-P is communicated in press media and explored the diversity of ethical themes present in the public debate.Methods LexisNexis Academic database and Google News were searched to identify articles about polygenic embryo screening. This led to 535 news articles. 59 original articles met the inclusion criteria. Inductive content analysis was used to analyse these articles.Results 8.8% of articles gave embryo polygenic scoring a positive portrayal, while 36.8% expressed a negative attitude. 54.4% were neutral, mostly highlighting limited practical value of the technology in in vitro fertilization (IVF) settings. We identified five main ethical themes that are also present in academic literature and the broader debate on reproductive technologies: a slippery slope towards designer babies, well-being of the child and parents, impact on society, deliberate choice and societal readiness.Conclusions Implementation of embryo polygenic profiling engenders a need for specific recommendations. Current media analysis discloses important ethical themes to consider when creating future guidelines for PGT-P.

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