Preimplantation Genetics

Economic Implications ◽

Genetic Traits ◽

Ethical Implications ◽

Wrongful Life ◽

Wrongful Birth

This chapter highlights the uses and ethical implications of preimplantation genetic testing and addresses the topic of liability as it applies to use of this technology to screen and select embryos for chromosomal abnormalities and genetic traits prior to implantation. When errors or wrongs occur, there may be significant medical, psychological, and economic implications for those individuals who sought preimplantation testing to avoid a genetic disease or to improve the chance of achieving pregnancy. Informed consent, wrongful birth, and wrongful life claims may be available to those who are harmed due to these errors.

Evaluation of chromosomal abnormalities from preimplantation genetic testing to the reproductive outcomes: a comparison between three different structural rearrangements based on next-generation sequencing

Journal of Assisted Reproduction and Genetics ◽

10.1007/s10815-020-02053-5 ◽

2021 ◽

Author(s):

Ping Yuan ◽

Lingyan Zheng ◽

Songbang Ou ◽

Haijing Zhao ◽

Ruiqi Li ◽

...

Keyword(s):

Genetic Testing ◽

Next Generation Sequencing ◽

Structural Rearrangements ◽

Next Generation ◽

Reproductive Outcomes ◽

Generation Sequencing

Haplotyping by linked-read sequencing (HLRS) of the genetic disease carriers for preimplantation genetic testing without a proband or relatives

10.21203/rs.3.rs-16325/v1 ◽

2020 ◽

Author(s):

Qing Li ◽

Yan Mao ◽

Shaoying Li ◽

Hongzi Du ◽

Wenzhi He ◽

...

Keyword(s):

Genetic Testing ◽

Genetic Disease ◽

De Novo ◽

Monogenic Disease ◽

Nucleotide Polymorphisms ◽

De Novo Mutations ◽

Linkage Analyses ◽

Alpha Thalassemia ◽

Polar Bodies

Abstract Background: In order to mitigate the risk of allele dropout (ADO) and ensure the accuracy of preimplantation genetic testing for monogenic disease (PGT-M), it is necessary to construct parental haplotypes.. Typically, haplotype resolution is obtained by genotyping multiple polymorphic markers in both parents and a proband or a relative. Sometimes, single sperm typing, or tests on the polar bodies may also be useful. Nevertheless, this process is time-consuming. At present, there was no simple linkage analysis strategy for patients without affected relatives.Method: To solve this problem, we established a haplotyping by linked-read sequencing (HLRS) method without the requirement for additional relatives. First, the haplotype of the genetic disease carriers in the family was constructed by linked-read sequencing, and then the informative single nucleotide polymorphisms (SNPs) in upstream and downstream mutation region were selected to construct the embryo haplotype and to determine whether the embryo was carrying the mutation. Two families were selected to validate this method; one with alpha thalassemia and the other with NDP gene disorder.Results: The haplotyping by linked-read sequencing (HLRS) method was successfully applied to construct parental haplotypes without recruiting additional family members; the method was also validated for PGT-M. The mutation carriers in these families were sequenced by linked-read sequencing, and their haplotypes were successfully phased. Adjacent SNPs of the mutation gene were identified. The informative SNPs were chosen for linkage analyses to identify the carrier embryos. For the alpha thalassemia family, a normal blastocyst was transferred to the uterus and the accuracy of PGT-M was confirmed by amniocentesis at 16 weeks of gestation. Conclusions: Our results suggest that HLRS can be applied for PGT-M of monogenic disorders or de novo mutations where the mutations haplotype cannot be determined due to absence of affected relatives. Keywords: Preimplantation Genetic Testing for monogenic disease, Linked-read sequencing, Linkage analyses, Haplotype

In vitro fertilization and preimplantation genetic testing methods in infertility treatment of a woman with karyotype 46,XX,ins(13;4)(q34;p14p15.3),inv(4)(p14q12). Case report

GYNECOLOGY ◽

10.26442/20795696.2021.5.201010 ◽

2021 ◽

Vol 23 (5) ◽

pp. 441-444

Author(s):

Zhanna I. Glinkina ◽

Elena V. Kulakova ◽

Elena G. Lebedeva ◽

Varvara S. Kuzmicheva ◽

Nataliya P. Makarova

Keyword(s):

Genetic Testing ◽

High Throughput ◽

High Throughput Sequencing ◽

Reproductive Technologies ◽

Infertility Treatment ◽

Preimplantation Embryos ◽

Sequencing Analysis ◽

And Inversion

The frequency of structural chromosomal transpositions can range from 1.8 to 8% among patients with reproductive disorders. There are several types of the rarest chromosomal abnormalities: insertion (insertion of a chromosomal region) and inversion (rotation of a chromosome region). This article describes a clinical case of the infertility treatment using assisted reproductive technologies in a woman with a rare chromosomal abnormality: simultaneous insertion and inversion of chromosomes 46, XX, ins (13;4)(q34;p14p15.3), inv(4)(p14q12). The structure and frequency of chromosomal aberrations were determined by high-throughput sequencing in preimplantation embryos. The result of the sequencing analysis showed that unbalanced variants for a known pathology were detected in 9 (56.3%) out of 16 observations, while in 6 (37%) only for a pathology known in the karyotype and in 3 (19%) they were presented simultaneously with the pathology of other chromosomes or with mosaicism. According to the results of the study, in preimplantation embryos, where one of the parents had chromosomal abnormalities, in addition to unbalanced variants, there is aneuploidy of other chromosomes not involved in the known pathology. They are described in 3 (21%) out of 14 observations of all identified pathology. In this regard, patients with aberrations in the karyotype are recommended, whenever possible, to carry out preimplantation genetic testing of structural rearrangements by methods allowed to analyze all chromosomes simultaneously. For example, high-throughput sequencing on the Illumina platform may become an alternative for prenatal diagnostics, which is performed in fertile couples with high risk of having a child with hereditary or congenital disorders. In the case of detection of chromosomal changes in the fetus, patients are faced with a number of ethical issues related to the necessity for medical abortion, which may contradict their religious and moral convictions.

Technological platforms for preimplantation genetic testing for aneuplody: comparative effectiveness of diagnosing chromosomal abnormalities

Akusherstvo i ginekologiia ◽

10.18565/aig.2020.4.65-71 ◽

2020 ◽

Vol 4_2020 ◽

pp. 65-71

Author(s):

Маlysheva О.V. Маlysheva ◽

Bichevaya N.K. Bichevaya ◽

Gzgzyan А.М. Gzgzyan ◽

Glotov О.S. Glotov О ◽

Kinunen А.А. Kinunen ◽

...

Keyword(s):

Genetic Testing ◽

Comparative Effectiveness ◽

Technological Platforms

Preimplantation genetic testing

Srpski medicinski casopis Lekarske komore ◽

10.5937/smclk2-30790 ◽

2021 ◽

Vol 2 (2) ◽

pp. 52-63

Author(s):

Ana Jeremić ◽

Dragana Vuković ◽

Srna Subanović ◽

Jovana Broćić ◽

Biljana Macanović

Keyword(s):

Genetic Testing ◽

In Vitro Fertilization ◽

Success Rate ◽

Embryo Transfer ◽

Trinucleotide Repeat ◽

Vitro Fertilization

The application of preimplantation genetic testing (PGT) began in the late 1980s. Pre-implantation genetic testing, as the earliest possible method of prenatal diagnosis, enables the selection of embryos with a normal karyotype for embryo transfer. The use of preimplantation genetic testing has proven to be a useful method in the following three groups of inherited diseases: monogenic disorders (single gene defects), trinucleotide repeat disorders, and chromosomal abnormalities. The success rate of in vitro fertilization (IVF) has increased significantly since the introduction of PGT into clinical practice. This paper presents a literature review with the aim of clearly determining the role of PGT in embryo selection before embryo transfer, as well as the role of this type of testing in increasing the success rate of IVF. One of the goals of the paper is also to review the development of molecular genetic methods that are currently, or have once been, in routine use when performing PGT. The current literature is an indicator of the development and progress of molecular genetics techniques applied in PGT. At the same time, it provides an opportunity and an incentive for further extensive research that will lead to the improvement of preimplantation genetic testing and thus increase the success rate of in vitro fertilization.

Preimplantation Genetic Testing for Chromosomal Abnormalities: Aneuploidy, Mosaicism, and Structural Rearrangements

Genes ◽

10.3390/genes11060602 ◽

2020 ◽

Vol 11 (6) ◽

pp. 602 ◽

Cited By ~ 5

Author(s):

Manuel Viotti

Keyword(s):

Genetic Testing ◽

Clinical Outcomes ◽

Assisted Reproductive Technologies ◽

Reproductive Technologies ◽

Chromosomal Mosaicism ◽

Human Embryos ◽

Chromosomal Anomalies ◽

Structural Rearrangements ◽

Preimplantation Genetic Testing

There is a high incidence of chromosomal abnormalities in early human embryos, whether they are generated by natural conception or by assisted reproductive technologies (ART). Cells with chromosomal copy number deviations or chromosome structural rearrangements can compromise the viability of embryos; much of the naturally low human fecundity as well as low success rates of ART can be ascribed to these cytogenetic defects. Chromosomal anomalies are also responsible for a large proportion of miscarriages and congenital disorders. There is therefore tremendous value in methods that identify embryos containing chromosomal abnormalities before intrauterine transfer to a patient being treated for infertility—the goal being the exclusion of affected embryos in order to improve clinical outcomes. This is the rationale behind preimplantation genetic testing for aneuploidy (PGT-A) and structural rearrangements (-SR). Contemporary methods are capable of much more than detecting whole chromosome abnormalities (e.g., monosomy/trisomy). Technical enhancements and increased resolution and sensitivity permit the identification of chromosomal mosaicism (embryos containing a mix of normal and abnormal cells), as well as the detection of sub-chromosomal abnormalities such as segmental deletions and duplications. Earlier approaches to screening for chromosomal abnormalities yielded a binary result of normal versus abnormal, but the new refinements in the system call for new categories, each with specific clinical outcomes and nuances for clinical management. This review intends to give an overview of PGT-A and -SR, emphasizing recent advances and areas of active development.

Preimplantation Genetic Testing of Aneuploidy by Next Generation Sequencing: Association of Maternal Age and Chromosomal Abnormalities of Blastocyst

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.875 ◽

2019 ◽

Vol 7 (24) ◽

pp. 4427-4431 ◽

Cited By ~ 1

Author(s):

Tien-Truong Dang ◽

Thi Mui Phung ◽

Hoang Le ◽

Thi-Bich-Van Nguyen ◽

Thi Sim Nguyen ◽

...

Keyword(s):

Genetic Testing ◽

Next Generation Sequencing ◽

Maternal Age ◽

Abnormal Chromosome ◽

High Rate ◽

Next Generation ◽

Chromosome 11 ◽

Generation Sequencing

BACKGROUND: Aneuploidy is a major cause of miscarriages and implantation failure. Preimplantation genetic testing for aneuploidy (PGT-A) by Next Generation Sequencing (NGS) is able to detect of the numeral and structural chromosomal abnormalities of embryos in vitro fertilization (IVF). AIM: This study was aimed to assess the relationship between maternal age and chromosomal abnormalities NGS technology. METHODS: 603 human trophectoderm (TE) biopsied samples were tested by Veriseq kit of Illumina. The relation of marternal age and chromosomal abnormality of blastocyst embryo was evaluated. RESULTS: Among the 603 TE samples, 247 samples (42.73%) presented as chromosomal abnormalities. The abnormalities occurred to almost chromosomes, and the most popular aneuploidy observed is 22. Aneuploidy rate from 0.87% in chromosome 11 to 6.06% in chromosome 22. The rate of abnormal chromosome increased dramatically in group of mother's ages over 37 (54.17%) comparing to group of mother's ages less than 37 (38.05%) (p < 0.000). The Abnormal chromosome and maternal age has a positive correlation with r = 0.4783 (p<0.0001). CONCLUSION: These results showed high rate abnormal chromosome and correlated with advanced maternal age of blastocyst embryos.

Chromosomal Concordance between the Baby Produced by Preimplantation Genetic Testing Embryo and the Trophectoderm Biopsy: a Retrospective Study

10.21203/rs.3.rs-364582/v1 ◽

2021 ◽

Author(s):

Zhongyuan Yao ◽

Xiaoxia Wang ◽

Jun Zeng ◽

Jing Zhao ◽

Qiuping Xia ◽

...

Keyword(s):

Genetic Testing ◽

Diagnostic Accuracy ◽

Peripheral Blood ◽

Snp Array ◽

Chromosome Analysis ◽

Clinical Trial Registry ◽

Developmental Potential ◽

Low Sensitivity

Abstract BackgroundChromosomal mosaicism and aneuploidies are routine phenomena throughout human pre- and post-implantation development. The benefit of implanting mosaicism or aneuploidies is still controversial. The purposes of the study are to investigate the developmental potential of embryos with chromosomally segmental or mosaic abnormalities, and whether precise Next Generation Sequencing (NGS) resolution would reduce the development of an abnormal embryo in preimplantation genetic testing (PGT) cycles.MethodsThe peripheral blood of 17 PGT babies were collected for single nucleotide polymorphism (SNP) array and were compared with trophectoderm (TE) biopsy results at different NGS resolutions.Results76.5% (13/17) of babies’ peripheral blood chromosome analysis was consistent with 10Mb TE biopsies and 58.8% (10/17) of babies’ analysis was consistent with 4Mb TE biopsies. 2 babies who had euploid TE showed abnormal peripheral blood chromosome analysis. 17.6% (3/17) embryos with aberrant TE biopsies produced healthy babies. Although the sensitivity of 10Mb was lower than 4Mb (25% vs. 50%), the specificity (100% vs. 76.9%), PPV (100% vs. 40%) and diagnostic accuracy (82.4% vs. 70.6%) of 10Mb showed better results than 4Mb.Conclusion(s)The chromosomal results between peripheral blood samples and TE biopsies of born babies are not completely congruent. Aneuploid and mosaic embryos have potential to produce healthy babies, whereas normal embryos also have chance to produce babies with chromosomal abnormalities. In spite of low sensitivity of both resolutions, 10Mb has higher specificity, PPV and diagnostic accuracy than 4Mb. It is suggested that TE biopsy be analyzed in both 10Mb and 4Mb resolutions to uncover severely adverse chromosomal aberrations but use 10Mb resolution to guide transfer.Trial registrationThe study was retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2100042522).

Preimplantation genetic testing for aneuploidy: state of the art, trends and perspectives

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2019.03.3-12 ◽

2019 ◽

pp. 3-12

Author(s):

И.Н. Лебедев

Keyword(s):

Genetic Testing ◽

Reproductive Medicine ◽

State Of The Art ◽

Vitro Fertilization ◽

Current State ◽

Reproductive Losses ◽

Chromosomal Diseases

Профилактика хромосомных болезней через преимплантационную генетическую диагностику становится актуальным востребованным направлением современной репродуктивной медицины и генетики. Скрининг эмбрионов в рамках циклов экстракорпорального оплодотворения позволяет исключить перенос анеуплоидных бластоцист, обеспечивая повышение вероятности наступления беременности и рождения здорового ребенка, а также снижая риски репродуктивных потерь вследствие хромосомной патологии. В настоящем обзоре обсуждается современное состояние технологий преимплантационного генетического тестирования хромосомного статуса эмбрионов, сохраняющиеся в этой сфере проблемы, а также перспективные направления исследований, призванные дать решение возникающим вызовам. Prevention of chromosomal diseases through preimplantation genetic testing is an edge issue of current reproductive medicine and genetics. Embryo testing during in vitro fertilization cycles is designed to eliminate the transfer of aneuploid blastocysts, providing an increased probability of the take home babies, as well as reducing the risks of reproductive losses due to chromosomal abnormalities. The current state of the preimplantation genetic testing, its trends and perspectives are discussed.

Early pregnancy loss as an indication for preimplantation genetic testing

Journal of obstetrics and women s diseases ◽

10.17816/jowd68575-82 ◽

2019 ◽

Vol 68 (5) ◽

pp. 75-82

Author(s):

Anna A. Smirnova ◽

Natalya A. Zyryaeva ◽

Diana O. Zhordanidze ◽

Margarita B. Anshina ◽

Evgeny F. Kira

Keyword(s):

Genetic Testing ◽

Pregnancy Rate ◽

Early Pregnancy ◽

Pregnancy Loss ◽

Normal Karyotype ◽

Reproductive Technologies ◽

Early Pregnancy Loss ◽

Structural Rearrangements ◽

Preimplantation Genetic Testing

Hypothesis/aims of study. Approximately 1015% of clinical pregnancies end in spontaneous abortions. The main cause of early miscarriages is chromosomal aberrations of the embryos. Chromosomal abnormalities are detected in 70% of sporadic miscarriages and in 3050 % of recurrent miscarriage. Modern assisted reproductive technologies allow not only to treat infertility, but also to provide access to embryos, which makes it possible to test them for hereditary diseases and chromosomal abnormalities before implantation. This study aimed to assess the efficacy of preimplantation genetic testing (PGT) in patients with infertility and early pregnancy loss. Study design, materials and methods. IVF outcomes were studied retrospectively in 84 patients under the age of 39 years. The first group consisted of 22 women with a normal karyotype, who underwent 34 IVF cycles with PGT for aneuploidies and 22 transfers of euploid embryos. The second group comprised 48 women with a normal karyotype, who underwent IVF treatment without PGT. In this group, we preformed 45 frozen and 18 fresh embryo transfers. The third group included 14 couples with chromosomal structural rearrangements, who underwent 22 IVF cycles with PGT for chromosomal structural rearrangements. Results. The cumulative pregnancy rate and the birth rate did not significantly differ between the study groups. The early miscarriage rate and the multiple pregnancy rate were significantly lower in groups with PGT compared to the group without PGT. The aneuploidy rate was significantly higher in women with two or more pregnancy losses in history compared to patients with only one pregnancy loss. Conclusion. The data obtained allow recommending IVF with PGT to women with recurrent pregnancy loss in order to avoid subsequent miscarriage.