Early pregnancy loss as an indication for 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.

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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 ◽

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.

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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 ◽

Chromosomal Abnormalities ◽

Structural Rearrangements ◽

Next Generation ◽

Reproductive Outcomes ◽

Preimplantation Genetic Testing ◽

Generation Sequencing

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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 ◽

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.

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