Preimplantation genetic testing for balanced complex chromosomal rearrangement carriers by comprehensive chromosome screening

2019 ◽  
Author(s):  
Gang Li ◽  
Weiyi Shi ◽  
Wenbin Niu ◽  
Jiawei Xu ◽  
Yihong Guo ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Snp Array ◽  
Chromosome Analysis ◽  
High Rate ◽  
Normal Embryo ◽  
Ovum Donation ◽  
Preimplantation Genetic Testing ◽  
Abnormal Embryo ◽  
Comprehensive Chromosome Screening ◽  
Structural Aberrations

Abstract Background: Balanced complex rearrangements (BCCRs) are balanced chromosomal structural aberrations that involve two or more chromosomes and at least three breakpoints. It is very rare in the population. Whether the couple of BCCRs benefit from preimplantation genetic testing (PGT) need to be further explored. Here, we reported the outcome of PGT in BCCRs carriers. Results: A total of 141 oocytes were retrieved from 7 couples within 10 PGT cycles, including 116 mature oocytes (MII), and 94 (81.03%) oocytes normally fertilized after intracytoplasmic sperm injection (ICSI). Then, 47 embryos were biopsied, including 8 embryos at the cleavage stage and 39 (41.49%) blastocysts. After comprehensive chromosome analysis, the balanced or normal embryo rate was 11.36% (5), the abnormal embryo rate was 88.63% (39), and 3 failed to amplify. Among them, the balanced or normal embryo rate was 33.33% (3) and the abnormal embryo rate was 66.67% (6) in the three-way rearrangements. The balanced or normal embryo rate was 5.6% (1) and the abnormal embryo rate was 94.4% (17) in double two-way translocations. The balanced or normal embryo rate was 5.9% (1) in exceptional CCRs, and the abnormal embryo rate was 94.1% (16). There were no significant differences among the three groups (P=0.11). In the 10 PGT cycles, there were 7 cycles in which no embryo could be transplanted and 3 cycles in which balanced or normal embryos underwent frozen-thawed embryo transplantation. One of the 3 cycles was clinically pregnant, and the prenatal diagnosis of amniocytes using G-band and SNP array at 16 weeks of gestation was 46, XN, and a boy was born alive and healthy. Conclusions: BCCR carriers have a high rate of obtaining abnormal embryos, but they can also have healthy offspring. For BCCR carriers with fertility needs, PGT is recommended to have related offspring, or they can choose sperm donor or ovum donation-assisted reproduction.

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

2021 ◽  
Author(s):  
Zhongyuan Yao ◽  
Xiaoxia Wang ◽  
Jun Zeng ◽  
Jing Zhao ◽  
Qiuping Xia ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Diagnostic Accuracy ◽  
Peripheral Blood ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Chromosome Analysis ◽  
Clinical Trial Registry ◽  
Preimplantation Genetic Testing ◽  
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).

scholarly journals Preimplantation Genetic Testing for Monogenic Disorders

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 871 ◽  
Author(s):  
Martine De Rycke ◽  
Veerle Berckmoes
Keyword(s):  
Genetic Testing ◽  
Whole Genome Amplification ◽  
State Of The Art ◽  
Snp Array ◽  
Genetic Data ◽  
Monogenic Disorder ◽  
Preimplantation Genetic Testing ◽  
Monogenic Disorders ◽  
The Cost ◽  
Concurrent Analysis

Preimplantation genetic testing (PGT) has evolved into a well-established alternative to invasive prenatal diagnosis, even though genetic testing of single or few cells is quite challenging. PGT-M is in theory available for any monogenic disorder for which the disease-causing locus has been unequivocally identified. In practice, the list of indications for which PGT is allowed may vary substantially from country to country, depending on PGT regulation. Technically, the switch from multiplex PCR to robust generic workflows with whole genome amplification followed by SNP array or NGS represents a major improvement of the last decade: the waiting time for the couples has been substantially reduced since the customized preclinical workup can be omitted and the workload for the laboratories has decreased. Another evolution is that the generic methods now allow for concurrent analysis of PGT-M and PGT-A. As innovative algorithms are being developed and the cost of sequencing continues to decline, the field of PGT moves forward to a sequencing-based, all-in-one solution for PGT-M, PGT-SR, and PGT-A. This will generate a vast amount of complex genetic data entailing new challenges for genetic counseling. In this review, we summarize the state-of-the-art for PGT-M and reflect on its future.

Preimplantation genetic testing of Robertsonian translocation by SNP array-based preimplantation genetic haplotyping

2018 ◽  
Vol 38 (8) ◽  
pp. 547-554 ◽  
Author(s):  
Jing Wang ◽  
Yanhong Zeng ◽  
Chenhui Ding ◽  
Bin Cai ◽  
Baomin Lu ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Robertsonian Translocation ◽  
Snp Array ◽  
Preimplantation Genetic Testing ◽  
Preimplantation Genetic Haplotyping

scholarly journals Case Report: Preimplantation Genetic Testing and Pregnancy Outcomes in Women With Alport Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei-Hui Shi ◽  
Mu-Jin Ye ◽  
Song-Chang Chen ◽  
Jun-Yu Zhang ◽  
Yi-Yao Chen ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Pregnancy Outcomes ◽  
Alport Syndrome ◽  
Kidney Diseases ◽  
High Rate ◽  
Singleton Pregnancy ◽  
Fetal Outcomes ◽  
Preimplantation Genetic Testing ◽  
Monogenic Diseases

BackgroundAlport syndrome, a monogenic kidney disease, is characterized by progressive hemorrhagic nephritis, sensorineural hearing loss, and ocular abnormalities. Mutations in COL4A5 at Xq22 accounts for 80–85% of X-linked Alport syndrome patients. Three couples were referred to our reproductive genetics clinic for prenatal or preconception counseling.MethodsPrenatal diagnoses were performed by amplifying targeted regions of COL4A5. Targeted next-generation sequencing (NGS)-based haplotype analysis or karyomapping was performed in two patients. Pregnancy outcomes in the three patients were collected and analyzed. Published Alport syndrome cases were searched in Pubmed and Embase.ResultsPrenatal diagnoses in two cases showed one fetus harbored the same pathogenic mutation as the proband and the other was healthy. The couple with an affected fetus and the patient with a family history of Alport syndrome chose to take the preimplantation genetic testing (PGT) procedure. One unaffected embryo was transferred to the uterus, and a singleton pregnancy was achieved, respectively. Two patients presented non-nephrotic range proteinuria (<3 g/24 h) during pregnancy and the three cases all delivered at full-term. However, published Alport cases with chronic kidney disease or proteinuria during pregnancy were came with a high rate (75%) of adverse maternal and fetal outcomes.ConclusionThe PGT procedure performed in this study was proven to be practicable and might be expanded to be applied in other monogenic diseases. Moderate or severe renal impairments in Alport syndrome were strongly associated with adverse maternal and fetal outcomes, and baseline proteinuria was a potential predictor for pregnancy outcomes of Alport syndrome as other kidney diseases.

scholarly journals Improved clinical outcomes of preimplantation genetic testing for aneuploidy using MALBAC-NGS compared with MDA-SNP array

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wenbin Niu ◽  
Linlin Wang ◽  
Jiawei Xu ◽  
Ying Li ◽  
Hao Shi ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Clinical Outcomes ◽  
Snp Array ◽  
Preimplantation Genetic Testing

Comprehensive preimplantation genetic testing by massively parallel sequencing

2020 ◽  
Author(s):  
Songchang Chen ◽  
Xuyang Yin ◽  
Sijia Zhang ◽  
Jun Xia ◽  
Ping Liu ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Genome Sequencing ◽  
Massively Parallel Sequencing ◽  
Science And Technology ◽  
Family Members ◽  
Snp Array ◽  
Massively Parallel ◽  
Preimplantation Genetic Testing ◽  
Parallel Sequencing ◽  
Genome Wide

Abstract STUDY QUESTION Can whole genome sequencing (WGS) offer a relatively cost-effective approach for embryonic genome-wide haplotyping and preimplantation genetic testing (PGT) for monogenic disorders (PGT-M), aneuploidy (PGT-A) and structural rearrangements (PGT-SR)? SUMMARY ANSWER Reliable genome-wide haplotyping, PGT-M, PGT-A and PGT-SR could be performed by WGS with 10× depth of parental and 4× depth of embryonic sequencing data. WHAT IS KNOWN ALREADY Reduced representation genome sequencing with a genome-wide next-generation sequencing haplarithmisis-based solution has been verified as a generic approach for automated haplotyping and comprehensive PGT. Several low-depth massively parallel sequencing (MPS)-based methods for haplotyping and comprehensive PGT have been developed. However, an additional family member, such as a sibling, or a proband, is required for PGT-M haplotyping using low-depth MPS methods. STUDY DESIGN, SIZE, DURATION In this study, 10 families that had undergone traditional IVF-PGT and 53 embryos, including 13 embryos from two PGT-SR families and 40 embryos from eight PGT-M families, were included to evaluate a WGS-based method. There were 24 blastomeres and 29 blastocysts in total. All embryos were used for PGT-A. Karyomapping validated the WGS results. Clinical outcomes of the 10 families were evaluated. PARTICIPANTS/MATERIALS, SETTING, METHODS A blastomere or a few trophectoderm cells from the blastocyst were biopsied, and multiple displacement amplification (MDA) was performed. MDA DNA and bulk DNA of family members were used for library construction. Libraries were sequenced, and data analysis, including haplotype inheritance deduction for PGT-M and PGT-SR and read-count analysis for PGT-A, was performed using an in-house pipeline. Haplotyping with a proband and parent-only haplotyping without additional family members were performed to assess the WGS methodology. Concordance analysis between the WGS results and traditional PGT methods was performed. MAIN RESULTS AND THE ROLE OF CHANCE For the 40 PGT-M and 53 PGT-A embryos, 100% concordance between the WGS and single-nucleotide polymorphism (SNP)-array results was observed, regardless of whether additional family members or a proband was included for PGT-M haplotyping. For the 13 embryos from the two PGT-SR families, the embryonic balanced translocation was detected and 100% concordance between WGS and MicroSeq with PCR-seq was demonstrated. LIMITATIONS, REASONS FOR CAUTION The number of samples in this study was limited. In some cases, the reference embryo for PGT-M or PGT-SR parent-only haplotyping was not available owing to failed direct genotyping. WIDER IMPLICATIONS OF THE FINDINGS WGS-based PGT-A, PGT-M and PGT-SR offered a comprehensive PGT approach for haplotyping without the requirement for additional family members. It provided an improved complementary method to PGT methodologies, such as low-depth MPS- and SNP array-based methods. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the research grant from the National Key R&D Program of China (2018YFC0910201 and 2018YFC1004900), the Guangdong province science and technology project of China (2019B020226001), the Shenzhen Birth Defect Screening Project Lab (JZF No. [2016] 750) and the Shenzhen Municipal Government of China (JCYJ20170412152854656). This work was also supported by the National Natural Science Foundation of China (81771638, 81901495 and 81971344), the National Key R&D Program of China (2018YFC1004901 and 2016YFC0905103), the Shanghai Sailing Program (18YF1424800), the Shanghai Municipal Commission of Science and Technology Program (15411964000) and the Shanghai ‘Rising Stars of Medical Talent’ Youth Development Program Clinical Laboratory Practitioners Program (201972). The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A.

scholarly journals The Influence of Chromosomal Polymorphism on Embryo Development and Embryonic Molecular Karyotype in Preimplantation Genetic Testing for Chromosomal Translocation

2020 ◽  
Vol 11 ◽  
Author(s):  
Gang Li ◽  
Weiyi Shi ◽  
Wenbin Niu ◽  
Jiawei Xu ◽  
Yihong Guo ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Statistical Difference ◽  
Chromosomal Translocation ◽  
Fertilization Rate ◽  
Cleavage Rate ◽  
High Quality ◽  
Preimplantation Genetic Testing ◽  
Abnormal Embryo ◽  
Molecular Karyotype ◽  
Blastocyst Rate

Traditionally, chromosomal polymorphisms (CPMs) are normal genetic variants in individuals with no phenotypic variations. However, some studies have shown that CPM is related to reproductive diseases. We explored the influence of CPM on embryonic development and molecular karyotype in chromosomal translocation (CT) patients undergoing preimplantation genetic testing (PGT) between February 2013 and May 2019. Twenty-six cases with CPM and 56 controls with normal chromosomes were included. Furthermore, a 1:4 match pair analysis by female age included 39 cases with CTCPM and 185 controls with CT. There was no statistical difference in fertilization rate (78.48% vs. 78.33%), cleavage rate on Day 3 (90.32% vs. 89.16%), blastocyst rate (60.00% vs. 60.80%), and the high-quality blastocyst rate (36.31% vs. 35.22%) between CPM and normal chromosomes. The high-quality blastocyst rate of CTCPM was significantly lower than that for CT (26.78% vs. 38.89%). Moreover, there was no statistical difference in fertilization rate (70.65% vs. 70.37%), cleavage rate on Day 3 (88.67% vs. 89.53%), and blastocyst rate (48.48% vs. 53.17%) between CTCPM and CT. In addition, one CTCPM spouse had a lower high-quality blastocyst rate, especially of males with CTCPM. Abnormal embryo rates of CTCPM were significantly higher than those for CT (78.64% vs. 68.93%). Abnormal embryo rates were higher in both CTCPM and CPM paternal carriers with CT partners, respectively. For CT, CTCPM may have an impact on the high-quality blastocyst rate and embryonic molecular karyotype, especially in male patients. Patients with CTCPM are relatively rare, but this population would benefit from being explored using a larger sample size.

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

2019 ◽  
Vol 7 (24) ◽  
pp. 4427-4431 ◽  
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 ◽  
Chromosomal Abnormalities ◽  
Abnormal Chromosome ◽  
High Rate ◽  
Next Generation ◽  
Chromosome 11 ◽  
Preimplantation Genetic Testing ◽  
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.

scholarly journals Ovum donation in an era of preimplantation genetic testing: how should we counsel patients?

2017 ◽  
Vol 108 (3) ◽  
pp. e100
Author(s):  
S. Yerkes ◽  
L. Sekhon ◽  
J.A. Lee ◽  
M. Daneyko ◽  
A.B. Copperman
Keyword(s):  
Genetic Testing ◽  
Ovum Donation ◽  
Preimplantation Genetic Testing

scholarly journals The First Live Birth in Lithuania After Application of Preimplantation Genetic Testing

2020 ◽  
Vol 28 (2) ◽  
pp. 35-42
Author(s):  
Živilė Gudlevičienė ◽  
Raminta Baušytė ◽  
Evelina Dagytė ◽  
Danutė Balkelienė ◽  
Algirdas Utkus ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Married Couple ◽  
Semen Analysis ◽  
Transvaginal Ultrasound ◽  
Normal Karyotype ◽  
Chromosome Analysis ◽  
Oocyte Retrieval ◽  
Antral Follicle ◽  
Testing Procedure ◽  
Preimplantation Genetic Testing

Background. Preimplantation genetic testing (PGT) is a genetic testing procedure that is performed before the implantation of embryos for the identification of genetic abnormalities. It is commonly performed when one or both expecting parents have such abnormalities and are at a high risk of passing them to their offspring. The aim of this case report is to describe the first successful IVF/ICSI/PGT procedure in Lithuania.Case report. A 27-year-old woman and a 31-year-old man, a married couple, were referred to VUHSK Santaros Fertility Center after trying to conceive for 4 years. In a previous relationship, the woman got pregnant spontaneously and decided to terminate the pregnancy. The husband does not have any children. During the medical examination, the transvaginal ultrasound revealed a low antral follicle count and low anti-Müllerian hormone level for the woman. Semen analysis for the male patient showed severe oligoastenospermia, which confirmed the previous abnormal spermogram results. Chromosome analysis revealed normal karyotype for the woman (46,XX) and Robertsonian translocation for the husband (45,XY,der(13;14)(q10;q10)). After the interdisciplinary medical team counselling, an ICSI with PGT-SR was suggested for the couple. The woman underwent controlled ovarian hyperstimulation with GnRH antagonist protocol for 11 days. Only one embryo with no unbalanced rearrangements was identified and transferred to the woman. On the 14th day post oocyte retrieval, the first serum β-hCG result was received – 39.5 mIU/ml, and the normal gestational sac at 5 weeks and 3 days was confirmed by ultrasound examination.Conclusion: the first successful pregnancy was achieved in Lithuania and the first IVF/ICSI/PGT-SR newborn in Lithuania was born in 2019 – a vaginal birth of a healthy girl with gestational age of 38 weeks and 4 days and a weight of 2820 g; the Apgar score was 10/10. The IVF/ICSI/PGT procedure was successfully implemented by the multidisciplinary team in VUHSK.

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