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

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 602 ◽  
Author(s):  
Manuel Viotti
Keyword(s):  
Genetic Testing ◽  
Clinical Outcomes ◽  
Assisted Reproductive Technologies ◽  
Chromosomal Abnormalities ◽  
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.

scholarly journals Early pregnancy loss as an indication for preimplantation genetic testing

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 ◽  
Chromosomal Abnormalities ◽  
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.

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 ◽  
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 ◽  
Chromosomal Abnormalities ◽  
Reproductive Technologies ◽  
Infertility Treatment ◽  
Preimplantation Embryos ◽  
Sequencing Analysis ◽  
Preimplantation Genetic Testing ◽  
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.

scholarly journals Хромосомні аномалії у чоловіків із різним ступенем порушення сперматогенезу

2013 ◽  
Vol 4 (1) ◽  
pp. 14-22 ◽  
Author(s):  
L. Y. Pylyp ◽  
L. A. Spinenko ◽  
V. D. Zukin ◽  
N. M. Bilko
Keyword(s):  
Assisted Reproductive Technologies ◽  
Sex Chromosome ◽  
Chromosomal Abnormalities ◽  
Klinefelter Syndrome ◽  
Sperm Count ◽  
Reproductive Technologies ◽  
Chromosomal Mosaicism ◽  
Male Factor ◽  
Increased Risk ◽  
Cytogenetic Studies

Chromosomal abnormalities are among the most common genetic causes of spermatogenic disruptions. Carriers of chromosomal abnormalities are at increased risk of infertility, miscarriage or birth of a child with unbalanced karyotype due to the production of unbalanced gametes. The natural selection against chromosomally abnormal sperm usually prevents fertilization with sperm barring in cases of serious chromosomal abnormalities. However, assisted reproductive technologies in general and intracytoplasmic sperm injection in particular, enable the transmission of chromosomal abnormalities to the progeny. Therefore, cytogenetic studies are important in patients with male factor infertility before assisted reproduction treatment. The purpose of the current study was to investigate the types and frequencies of chromosomal abnormalities in 724 patients with infertility and to estimate the risk of chromosomal abnormalities detection in subgroups of patients depending on the severity of spermatogenic disruption, aiming at identifying groups of patients in need of cytogenetic studies. Karyotype analysis was performed in 724 blood samples of men attending infertility clinic. Chromosomal preparation was performed by standard techniques. At least 20 GTG-banded metaphase plates with the resolution from 450 to 750 bands per haploid set were analysed in each case. When chromosomal mosaicism was suspected, this number was increased to 50. Abnormal karyotypes were observed in 48 (6.6%) patients, including 67% of autosomal abnormalities and 33% of gonosomal abnormalities. Autosomal abnormalities were represented by structural rearrangements. Reciprocal translocations were the most common type of structural chromosomal abnormalities in the studied group, detected with the frequency of 2.6% (n = 19), followed by Robertsonian translocation, observed with the frequency of 1.2% (n = 9). The frequency of inversions was 0.6% (n = 4). Gonosomal abnormalities included 14 cases of sex chromosome aneuploidy and 2 cases of terminal deletion of Y chromosome. Klinefelter syndrome was detected in 67% of patients with azoospermia. A significant increase in the frequency of numerical chromosomal abnormalities was observed in a group of patients with azoospermia (P < 0.001). No differences were detected in the frequency of structural abnormalities in subgroups of patients. An increase in the frequency of chromosomal abnormalities with the decrease of sperm count was observed. Chromosomal abnormalities were detected with frequency 1.1% in a group of patients with normospermia, 1.9% in a group of patients with asthenozoospermia, 4.3% in patients with asthenoteratozoospermia, 6.5% in patients with oligoasthenozoospermia, 11.6% in patients with oligoasthenoteratozoospermia and 35% in a group of patients with azoospermia. Significant increase of the prevalence of chromosomal abnormalities was detected in subgroups of patients with azoospermia (P < 0.001) and oligozoospermia (P = 0.001) as compared to patients with normozoospermia. These results are considered to be criteria for selection of patients in need of cytogenetic studies before in vitro fertilization cycles because of the highest risk of chromosomal abnormalities detection. 

Preimplantation genetic testing for aneuploidy in various protocols of assisted reproductive technologies with vitrified embryo

2021 ◽  
Vol 3_2021 ◽  
pp. 175-182
Author(s):  
Kvashnina E.V. Kvashnina ◽  
Tutakov M.A. Tutakov ◽  
Vakhlova O.S. Vakhlova ◽  
Tomina E.V. Tomina ◽  
Shilova N.V. Shilova ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Preimplantation Genetic Testing

scholarly journals Clinical outcomes following preimplantation genetic testing and microdissecting junction region in couples with balanced chromosome rearrangement

2021 ◽  
Author(s):  
Dehua Cheng ◽  
Liang Hu ◽  
Fei Gong ◽  
Shimin Yuan ◽  
Keli Luo ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Clinical Outcomes ◽  
Embryo Transfer ◽  
Chromosome Rearrangement ◽  
Normal Embryo ◽  
Structural Rearrangements ◽  
Junction Region ◽  
Preimplantation Genetic Testing ◽  
Developmental Issues ◽  
Generation Sequencing

Abstract Purpose The purpose of this study is to summarize the clinical outcomes of apparently balanced chromosome rearrangement (ABCR) carriers in preimplantation genetic testing (PGT) cycles by next-generation sequencing following microdissecting junction region (MicroSeq) to distinguish non-carrier embryos from balanced carriers. Methods A retrospective study of 762 ABCR carrier couples who requested PGT for structural rearrangements combined with MicroSeq at the Reproductive and Genetic Hospital of CITIC-Xiangya was conducted between October 2014 and October 2019. Results Trophectoderm biopsy was performed in 4122 blastocysts derived from 917 PGT-SR cycles and 3781 blastocysts were detected. Among the 3781 blastocysts diagnosed, 1433 (37.9%, 1433/3781) were balanced, of which 739 blastocysts were carriers (51.57%, 739/1433) and 694 blastocysts were normal (48.43%, 694/1433). Approximately 26.39% of cycles had both carrier and normal embryo transfer, and the average number of biopsied blastocysts was 6.7. In the cumulative 223 biopsied cycles with normal embryo transfer, all couples chose to transfer the normal embryos. In the 225 cycles with only carrier embryos, the couples chose to transfer the carrier embryos in 169/225 (75.11%) cycles. A total of 732 frozen embryo transfer cycles were performed, resulting in 502 clinical pregnancies. Cumulatively, 326 babies were born; all of these babies were healthy and free of any developmental issues. Conclusion Our study provides the first evaluation of the clinical outcomes of a large sample with ABCR carrier couples undergoing the MicroSeq-PGT technique and reveals its powerful ability to distinguish between carrier and non-carrier balanced embryos.

The birth of a healthy child in the assisted reproductive technologies program after autologous co-culture of embryo with cumulus cells and a new CAT transfer technology. Case report

GYNECOLOGY ◽  
2021 ◽  
Vol 23 (3) ◽  
pp. 270-274
Author(s):  
Gunai R. Asfarova ◽  
Veronika I. Smol'nikova ◽  
Natalia P. Makarova ◽  
Iuliia S. Drapkina ◽  
Anastasiia P. Sysoeva ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Healthy Child ◽  
Assisted Reproductive Technologies ◽  
Cumulus Cells ◽  
Reproductive Technologies ◽  
Biologically Active ◽  
Human Embryos ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Art Programs

Cumulus cells are essential during oocytes growth and development, as well as during their maturation and fertilization. Research results have shown that embryo co-cultivation with autologous cumulus cells increases the frequency of blastocyst formation, and also improves the effectiveness of ART programs. Embryo transfer in such programs is recommended to be carried out using the CAT technology (Cumulus-Aided embryo Transfer), which includes embryo cultivation on a layer of cumulus cells and embryo transfer with a certain amount of diluted cumulus cells. Patient G., 38 years old, came to the department with infertility for 15 years and recurrent implantation failure in history. The patient had ART program with autologous co-cultivation of embryos with cumulus cells and a new CAT transfer technology. The patient fell pregnant and gave birth to a healthy child. Autologous cumulus cells can be a source of biologically active substances and improve embryological parameters and implantation rate in ART programs. Embryo co-cultivation with cumulus cells is especially important for patients with recurrent implantation failure. This technique can become an alternative for optimizing human embryos culturing.

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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