New Insights From One Thousand Mosaic Embryo Transfers: Features of Mosaicism Dictating Rates of Implantation, Spontaneous Abortion, and Neonate Health

Viotti, Manuel; Victor, Andrea; Barnes, Frank L.; Zouves, Christo; Besser, Andria G.; Grifo, James A.; Cheng, En‐Hui; Lee, Maw‐Sheng; Lin, Pin‐Yao; Corti, Laura; Fiorentino, Francesco; Spinella, Francesca; Minasi, Maria Giulia; Greco, Ermanno; Munné, Santiago

doi:10.1016/j.fertnstert.2020.08.029

Cited by 11 publications

(8 citation statements)

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“…We believe that these data are in good accordance with reported results (Spinella et al 2018;Viotti et al 2020): mosaic embryos with an aneuploidy rate of < 50% had more favorable clinical outcomes than those containing > 50% aneuploidy. However, other authors reported that the degree of trophectoderm mosaicism was a poor prediction of ongoing pregnancy and miscarriage (Kushnir et al 2018;Victor et al 2019;Viotti et al 2020). Moreover, Popovic et al (2020) claimed to estimate the precise degree and prevalence of mosaicism based on a single biopsy to be conceptually unachievable.…”

Section: Extent Of Mosaicism For Unbalanced Rearrangementsupporting

confidence: 91%

Factors affecting clinical manifestation of chromosomal imbalance in carriers of segmental autosomal mosaicism: differential impact of gender

Kovaleva¹,

Cotter²

2022

J Appl Genetics

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Mosaicism for unbalanced chromosomal rearrangements segmental mosaicism (SM) is rare, both in patients referred for cytogenetic testing and in prenatal diagnoses. In contrast, in preimplantation embryos SM is a frequent finding and, therefore, is even more challenging. However, there is no consistency among results of published studies on the clinical outcomes of embryos with SM, primarily due to the small number of reported cases. Moreover, there is the problem of predicting the potential for the optimal development of a mosaic embryo to a healthy individual. Therefore, we suggested comparing factors predisposing to favorable and poor prognoses, identified in postnatal and prenatal cohorts of SM carriers, with those obtained from studies on preimplantation embryos. We analyzed 580 published cases of SM including (i) postnatally diagnosed affected carriers, (ii) clinically asymptomatic carriers, (iii) prenatally diagnosed carriers, and (iv) miscarriages. We observed a concordance with preimplantation diagnoses regarding the clinical significance of the extent of mosaicism as well as a predominance of deletions over other types of rearrangements. However, there is no concordance regarding excessive involvement of chromosomes 1, 5, and 9 in unbalanced rearrangements and a preferential involvement of larger chromosomes compared to short ones. Paternal age was not found to be associated with SM in postnatally disease-defined individuals. We have identified maternal age and preferential involvement of chromosome 18 in rearrangements associated with clinical manifestations. Male predominance was found among normal pregnancy outcomes and among disease-defined carriers of rearrangements resulting in a gain of genomic material. Female predominance was found among abnormal pregnancy outcomes, among disease-defined carriers of loss and gain/loss rearrangements, and among transmitting carriers of gonadal SM, both affected and asymptomatic. According to data obtained from “post-embryo” studies, clinical manifestations of chromosomal imbalance are associated with a high proportion of abnormal cells, female gender, the type of rearrangement and involved chromosome(s), and maternal age. We believe these data are instructive in the challenging medical genetic counseling of parents faced with no option other than transfer of an embryo with segmental mosaicism.

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Section: Extent Of Mosaicism For Unbalanced Rearrangementsupporting

confidence: 91%

Factors affecting clinical manifestation of chromosomal imbalance in carriers of segmental autosomal mosaicism: differential impact of gender

Kovaleva¹,

Cotter²

2022

J Appl Genetics

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“…Comparison of AI scores and PGT-A outcomes revealed that the average AI score was significantly higher for euploid embryos than for aneuploid embryos, corresponding with a higher potential for successful clinical pregnancy (Figure 4A). For mosaic embryos, the average AI score fell between the scores for euploid and aneuploid groups, consistent with an intermediate proportion of abnormal cells making up these embryos and a higher potential for successful clinical outcomes due to the process of self-correction (Greco et al, 2015;Victor et al, 2019;Viotti et al, 2020). Given the high proportion of non-euploid embryos generally identified by PGT-A (~30-60% based on age; Viotti, 2020), experts in the field have turned towards defining specific chromosomal abnormalities that have a lower risk profile for mosaic embryos on transfer, as an alternative option for when there are no euploid embryos available for use (CoGEN, 2017;Cram et al, 2019;Grati et al, 2018).…”

Section: Ai Scores Correlate With Embryo Ploidy and Specific Chromoso...mentioning

confidence: 70%

An artificial intelligence model correlated with morphological and genetic features of blastocyst quality improves ranking of viable embryos

Diakiw¹,

Hall

VerMilyea

et al. 2022

Reproductive BioMedicine Online

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“…Our observed rate is likely due to our method of reporting, in which embryos with mosaic-only abnormalities are classified as mosaic, rather than reporting mosaicism for each individual abnormality. Future analyses defining mosaic embryos with WCA versus SA would provide more knowledge to the field, especially in light of recent studies demonstrating an increased likelihood of "rescue" of mosaic SAs in comparison to mosaic WCAs (Tiegs et al, 2020;Viotti et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Experience analysing over 190,000 embryo trophectoderm biopsies using a novel FAST-SeqS preimplantation genetic testing assay

Walters-Sen

Neitzel

Bristow

et al. 2022

Reproductive BioMedicine Online

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Research Question: Is FAST-SeqS an accurate methodology for preimplantation genetic testing for whole-chromosome aneuploidy (PGT-A), what additional types of chromosomal abnormalities can be assessed, and what are the observed aneuploidy rates in a large clinical cohort?Design: FAST-SeqS, a next-generation sequencing-(NGS-) based assay amplifying genomewide LINE1 repetitive sequences, was validated using reference samples. Sensitivity and specificity were calculated. Clinically-derived trophectoderm biopsies submitted for PGT-A were assessed, and aneuploidy and mosaicism rates among biopsies were determined. Clinicianprovided outcome rates were calculated.Results: Sensitivity and specificity were >95% for all aneuploidy types tested in the validation.Comparison of FAST-SeqS to VeriSeq showed high concordance (98.5%). Among embryos with actionable results (n=182,827), 46.2% were aneuploid. Whole-chromosome aneuploidies were most commonly observed (72.9% without or 8.7% with a segmental aneuploidy [SA]), with rates increasing with egg age, while SA rates did not. SAs (n=20,557) were observed on all chromosomes (most commonly deletions), with frequencies roughly correlated with chromosome length. Mosaic-only abnormalities constituted 10.1% (n=3,862/38,145) of samples. Abnormal ploidy constituted 1.8% (n=2,370/128,991) of samples, triploidy being the most common (73.6%). Across 3,297 frozen embryo transfers, the mean clinical pregnancy rate was 62% (range 38-80%); the mean combined ongoing pregnancy and live birth rate was 57% (range 38-72%). Conclusion:FAST-SeqS is a clinically reliable and scalable method for PGT-A, is comparable to whole genome amplification-based platforms, and detects additional information related to ploidy using SNP analysis. Clinical outcomes suggest an ongoing benefit of PGT-A using FAST-SeqS, consistent with other platforms.

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New Insights From One Thousand Mosaic Embryo Transfers: Features of Mosaicism Dictating Rates of Implantation, Spontaneous Abortion, and Neonate Health

Cited by 11 publications

References 0 publications

Factors affecting clinical manifestation of chromosomal imbalance in carriers of segmental autosomal mosaicism: differential impact of gender

Factors affecting clinical manifestation of chromosomal imbalance in carriers of segmental autosomal mosaicism: differential impact of gender

An artificial intelligence model correlated with morphological and genetic features of blastocyst quality improves ranking of viable embryos

Experience analysing over 190,000 embryo trophectoderm biopsies using a novel FAST-SeqS preimplantation genetic testing assay

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