Controversies in ART: can the IVF laboratory influence preimplantation embryo aneuploidy?

Swain, Jason E.

doi:10.1016/j.rbmo.2019.06.009

Cited by 49 publications

(31 citation statements)

References 80 publications

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“…Next-generation sequencing (NGS)-based platforms are most commonly used in PGT-A programs; however, differences in platform sensitivity and specificity, the threshold established for data interpretation and the cut-offs applied for low-level mosaicism classification affect the percentage of mosaicism reported among genetic laboratories and the number of euploid embryos deemed suitable for transfer [ 2 ]. Other factors related to biopsy technique, the number of cells biopsied, and the conditions surrounding the cell loading can also affect the results [ 3 ]. Studies by Popovic et al [ 4 , 5 ] on the inner cell mass (ICM) and TE analysis from aneuploid and mosaic embryos suggest limitations in the accuracy of diagnosing mosaicism in PGT-A due to difficulty distinguishing technical bias from biological mosaicism.…”

Section: Introductionmentioning

confidence: 99%

“…Ovarian stimulation protocols during the IVF cycle can influence the incidence of euploid embryos [ 9 ]. Additionally, the fertilization method [ 10 ] and conditions in the clinical IVF laboratory, such as the embryo culture media, pH, oxygen, osmolality, temperature or plastics, are linked to increased aneuploidy and mosaicism [ 3 ]. Accurate mosaicism determination describes incidences of euploid/aneuploid mosaicism from 31% at the cleavage stage to 4–5% at the blastocyst stage [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Characteristics of the IVF Cycle that Contribute to the Incidence of Mosaicism

Rodrigo

Clemente-Císcar

Campos‐Galindo

et al. 2020

Genes

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Highly sensitive next-generation sequencing (NGS) platforms applied to preimplantation genetic testing for aneuploidy (PGT-A) allow the classification of mosaicism in trophectoderm biopsies. However, the incidence of mosaicism reported by these tests can be affected by a wide number of analytical, biological, and clinical factors. With the use of a proprietary algorithm for automated diagnosis of aneuploidy and mosaicism, we retrospectively analyzed a large series of 115,368 trophectoderm biopsies from 27,436 PGT-A cycles to determine whether certain biological factors and in vitro fertilization (IVF) practices influence the incidence of overall aneuploidy, whole uniform aneuploidy, mosaicism, and TE biopsies with only segmental aneuploidy. Older female and male patients showed higher rates of high-mosaic degree and whole uniform aneuploidies and severe oligozoospermic patients had higher rates of mosaicism and only segmental aneuploidies. Logistic regression analysis identified a positive effect of female age but a negative effect of embryo vitrification on the incidence of overall aneuploid embryos. Female age increased whole uniform aneuploidy rates but decreased only segmental aneuploidy and mosaicism, mainly low-mosaics. Conversely, higher ovarian response decreased whole uniform aneuploidy rates but increased only segmental aneuploidies. Finally, embryo vitrification decreased whole uniform aneuploidy rates but increased mosaicism, mainly low-mosaics, compared to PGT-A cycles with fresh oocytes. These results could be useful for clinician’s management of the IVF cycles.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characteristics of the IVF Cycle that Contribute to the Incidence of Mosaicism

Rodrigo

Clemente-Císcar

Campos‐Galindo

et al. 2020

Genes

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“…Variation in rates of mosaicism, segmental abnormalities, and no call results has only been compared between IVF centers (9-11). Although it has been suggested that laboratory practices and technical aptitude of the embryologist may influence PGT-A results (12), there has been no study thus far to examine whether interembryologist differences exist within the same laboratory while following a uniform protocol.…”

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confidence: 99%

“…Cohorts with a higher proportion of poor quality blastocysts may therefore increase unamplified and nonconcurrent results. It has been hypothesized that altered culture conditions, such as aberrations in osmolality, pH, temperature, or mechanical stress on the embryo may lead to improper chromosomal segregation and disjunction during mitosis (12). Many studies have investigated whether rates of mosaicism and segmental abnormalities increase with the use of monophasic as opposed to sequential media (4, 14, 15) with conflicting results.…”

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confidence: 99%

Consistency in rates of diagnosis of embryonic mosaicism, segmental abnormalities, and “no call” results among experienced embryologists performing preimplantation genetic testing for aneuploidy

et al. 2020

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Objective: To determine whether differences exist in rates of subchromosomal abnormalities, mosaicism, and ''no call'' results among embryologists performing and loading trophectoderm biopsies for preimplantation genetic testing for aneuploidy (PGT-A). Design: Retrospective cohort. Setting: Large infertility center. Patient(s): All patients undergoing in vitro fertilization with PGT-A. Intervention(s): The NexCCS next generation sequencing platform was used for PGT-A. The c 2 testing assessed differences in rates of primary outcomes between embryologists. Intraclass correlation coefficients evaluated inter-embryologist reliability in rates of abnormal and no call results. Median absolute performance difference (MAPD) scores, which quantify the impact of technical variation on analytical performance, were averaged for individual embryologists. Analysis of variance assessed differences in mean MAPD scores. Main Outcome Measure(s): Interoperator variability in rates of mosaic, segmental, and no call results. Result(s): Four embryologists performed 30,899 biopsies and 6 embryologists loaded specimens into designated tubes. Among individuals performing trophectoderm sampling, rates of mosaicism were 4.3% to 6.1%, segmental errors were 9.0% to 10.7%, and inconclusive results were 1.1% to 2.9%. For those loading, the incidence of mosaicism was 4.2% to 5.9%, subchromosomal abnormalities was 9.7% to 10.4%, and no call results was 1.2% to 2.2%. The intraclass correlation coefficient was 0.978 for embryologists performing biopsies and 0.981 for those loading. Differences in mean MAPD scores were within 0.6% and 0.2% of each other for doing biopsies and loading embryologists, respectively. Conclusion(s): Rates of mosaicism, segmental, and no call PGT-A results are consistent among experienced embryologists. Due to the large sample size included, differences within 1% of the mean were deemed clinically irrelevant despite statistical significance. (Fertil Steril Rep Ò 2020;1:119-24. Ó2020 by American Society for Reproductive Medicine.

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“…Yet, UPD appears to be a very uncommon event. The accuracy of technologies used to detect these chromosome abnormalities has been challenged, 37 and there are also biological explanations that could contribute to erroneous interpretation of the results of pre‐implantation genetic testing, for example, contamination by micronuclei and degraded polar bodies, 11 asynchronous replication, 38 and induction by in vitro culture conditions 39 . There is therefore some uncertainty about the true in vivo levels of mitotic instability present in early embryos.…”

Section: Discussionmentioning

confidence: 99%

Uniparental disomy: Origin, frequency, and clinical significance

Benn

2021

Prenatal Diagnosis

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Uniparental disomy (UPD) is defined as two copies of a whole chromosome derived from the same parent. There can be multiple mechanisms that lead to UPD; these are reviewed in the context of contemporary views on the mechanism leading to aneuploidy. Recent studies indicate that UPD is rare in an apparently healthy population and also rare in spontaneous abortion tissues. The most common type of UPD is a maternal heterodisomy (both maternal allele sets present). Isodisomy (a duplicated single set of alleles) or segmental loss of heterozygosity is sometimes encountered in SNP‐based microarray referrals. Decisions regarding the most appropriate follow‐up testing should consider the possibility of consanguinity (that will generally involve multiple regions), an imprinted gene disorder (chromosomes 6, 7, 11, 14, 15, 20), expression of an autosomal recessive disorder, and an occult aneuploid cell line that may be confined to the placenta. Upd(16)mat, per se, does not appear to be associated with an abnormal phenotype. UPD provides an insight into the history of early chromosome segregation error and understanding the rates and fate of these events are of key importance in the provision of fertility management and prenatal healthcare.

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Controversies in ART: can the IVF laboratory influence preimplantation embryo aneuploidy?

Cited by 49 publications

References 80 publications

Characteristics of the IVF Cycle that Contribute to the Incidence of Mosaicism

Characteristics of the IVF Cycle that Contribute to the Incidence of Mosaicism

Consistency in rates of diagnosis of embryonic mosaicism, segmental abnormalities, and “no call” results among experienced embryologists performing preimplantation genetic testing for aneuploidy

Uniparental disomy: Origin, frequency, and clinical significance

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