A prospective study of non-invasive preimplantation genetic testing for aneuploidies (NiPGT-A) using next-generation sequencing (NGS) on spent culture media (SCM)

Yeung, Queenie Sum Yee; Zhang, Ying Xin; Chung, Jacqueline Pui Wah; Lui, Wai Ting; Kwok, Yvonne K.; Gui, Baoheng; Kong, Grace; Cao, Ye; Li, Tin‐Chiu; Choy, Kwong Wai

doi:10.1007/s10815-019-01517-7

Cited by 72 publications

(70 citation statements)

References 41 publications

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“…The NGS-based PGT-A method is characterized by having high detection resolution for segmental aneuploidies [ 19 , 20 ]. Based on in-house validation, the resolution of segmental aneuploidy was set as 10 Mb for both CMA and NGS PGT-A platforms [ 21 , 22 ]. The level of mosaicism was calculated by the copy number ratio (Equation (1)) and reported with a range of 20% to 80% mosaic level.…”

Section: Methodsmentioning

confidence: 99%

The Pregnancy Outcome of Mosaic Embryo Transfer: A Prospective Multicenter Study and Meta-Analysis

Zhang

Chen²,

Nabu³

et al. 2020

Genes

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Chromosomal mosaicism is at high occurrence in early developmental-stage embryos, but much lower in those at prenatal stage. Recent studies provided evidence on the viability of mosaic embryos by reporting pregnancy outcomes. Expanded research is warranted to evaluate its clinical significance. This is a multi-center prospective cohort study on 137 mosaic, 476 euploid and 835 non-preimplantation genetic testing (non-PGT) embryos from three in vitro fertilization (IVF) providers of three countries in Asia, applying the same preimplantation genetic testing for aneuploidies (PGT-A) reporting criteria. Mosaic embryo transfers (METs) resulted in a significantly lower clinical pregnancy rate (40.1% versus 59.0% versus 48.4%), lower ongoing/live birth rate (27.1% versus 47.0% versus 35.1%) and higher miscarriage rate (33.3% versus 20.5% versus 27.4%) than euploid and non-PGT transfers, respectively. Pregnancy losses after METs were different between embryos carrying numerical and segmental chromosomal abnormalities (p = 0.04). Our meta-analysis concluded that METs gave rise to pregnancies but were associated with a reduced ongoing/live birth rate and a higher miscarriage rate. All 37 MET live births were confirmed viable, among which 8 completed prenatal genetic testing with normal results. Longitudinal investigation on one MET pregnancy evidenced the aneuploidy depletion hypothesis. This is the first multi-center prospective study reporting a full MET pregnancy outcome with complementary information from prenatal genetic testing as compared to euploid and non-PGT cohorts.

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Section: Methodsmentioning

confidence: 99%

The Pregnancy Outcome of Mosaic Embryo Transfer: A Prospective Multicenter Study and Meta-Analysis

Zhang

Chen²,

Nabu³

et al. 2020

Genes

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“…Given the expanding use of PGT for various indications, it is important to monitor the incidence of monozygotic twinning and to accumulate evidence to aid pre‐conceptional counselling further. Due to concerns about potential implication following embryo biopsy, research is being undertaken on non‐invasive PGT by testing for free embryonic DNA in the spent culture media, and robust data are awaited to adopt this technique routinely.…”

Section: Resultsmentioning

confidence: 99%

Zygotic splitting following embryo biopsy: a cohort study of 207 697 single‐embryo transfers following IVF treatment

Kamath

Antonisamy

Sunkara

2019

BJOG

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Objective To evaluate the risk of monozygotic splitting with embryo biopsy during in vitro fertilisation (IVF). Design A cohort study. Setting Anonymised assisted reproductive technology national data from the Human Fertilisation and Embryology Authority, UK. Population Women undergoing single‐embryo transfer (SET) following either pre‐implantation genetic testing (PGT) involving embryo biopsy or IVF without PGT. Methods Data on women undergoing SET either following PGT and non‐PGT IVF treatment in 2000–2016 were analysed to compare the risk of zygotic splitting and monozygotic twining. Logistic regression analysis was performed adjusting for potential confounders. Main outcomes Monozygotic spitting, monozygotic twin birth. Results Data comprising a total of 207 697 SET cycles (4544 following PGT and 203 153 following non‐PGT IVF) were analysed. The live birth rate per embryo transfer was 31.9% (95% confidence interval [CI] 30.5–33.2%) following PGT and 26.9% (95% CI 26.7–27.1%) following non‐PGT IVF. The incidence of zygotic splitting following PGT was 2.4% (95% CI 1.7–3.3%) versus 1.5% (95% CI 1.4–1.6%) following non‐PGT IVF. There was a significantly higher risk of zygotic splitting with PGT versus non‐PGT IVF cycles (odds ratio [OR] 1.64, 95% CI 1.19–2.27). The higher risk of zygotic splitting with PGT cycles remained significant after adjusting for potential confounders (adjusted OR 1.51, 95% CI 1.06–2.15). Conclusions The present study demonstrated an increased risk of monozygotic splitting with embryo biopsy. Given the current sparse literature, it is important to accumulate further evidence to validate the findings. Tweetable abstract A likely increased risk of monozygotic splitting following embryo biopsy.

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“…The biggest caveat in many of the publications to date is that embryos were subjected to some form of manipulation before SCM was collected [217][218][219][220][221]. Putting embryos through Day 3/4 assisted hatching, a freeze-thaw cycle, and/or a cellular biopsy prior to SCM collection provides a source of added DNA in the medium, confounding the subsequent analysis of amplification rate and concordance to the embryo.…”

Section: The Prospect Of Non-invasive Pgt-amentioning

confidence: 99%

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

Viotti

2020

Genes

106

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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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A prospective study of non-invasive preimplantation genetic testing for aneuploidies (NiPGT-A) using next-generation sequencing (NGS) on spent culture media (SCM)

Cited by 72 publications

References 41 publications

The Pregnancy Outcome of Mosaic Embryo Transfer: A Prospective Multicenter Study and Meta-Analysis

The Pregnancy Outcome of Mosaic Embryo Transfer: A Prospective Multicenter Study and Meta-Analysis

Zygotic splitting following embryo biopsy: a cohort study of 207 697 single‐embryo transfers following IVF treatment

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

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