Mosaic embryo transfer—first report of a live born with nonmosaic partial aneuploidy and uniparental disomy 15

Schlade-Bartusiak, Kamilla; Strong, Emma; Zhu, Olive; Mackie, Jessica; Salema, Diane; Volodarsky, Michael; Roberts, James W.; Steinraths, Michelle

doi:10.1016/j.xfre.2022.05.003

Cited by 12 publications

(10 citation statements)

References 19 publications

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“…A study assessing more than 2759 mosaic embryo transfers reported only one mosaic pregnancy giving an outcome of a mosaic pregnancy of 0.04% 23 . To date, only 2 mosaic pregnancies and births have been reported after the transfer of a mosaic embryo 26,27 . Therefore, when we describe the risk of an affected mosaic pregnancy, we clearly state that based on current evidence, this seems like the most unlikely scenario.…”

Section: Discussionmentioning

confidence: 83%

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Do reproductive history and information given through genetic counselling influence patients' decisions on mosaic embryo transfer?

et al. 2022

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Objective: To assess patients' and embryonic characteristics that may have an influence on the decision to transfer a mosaic embryo.Method: Single centre retrospective cohort study including 1247 PGT-A cycles.Demographic and clinical factors associated with a decision to transfer a mosaic embryo were studied. Female age, number of previous cycles, previous availability of euploid embryos, history of miscarriages and parity as well as percentage of mosaicism, type of anomaly and chromosome risk were studied in relation to decision-making. Outcomes after mosaic embryo transfer were assessed. Results:To date, in 7.9% of cycles (99/1247), patients have had to make a decision on the fate of their mosaic embryos. In 23.2% of cycles (23/99), patients decided to transfer. In most cases (79.8%; 79/99), patients underwent genetic counselling before the decision. None of the variables analysed were associated with the patients' decision, although parity and the high-degree mosaicism (>50%) seemed to be negatively associated with the decision to transfer (18.2% vs. 29.8%, p = 0.294; 10% vs. 32.2%, p = 0.052). Conclusions:Neither reproductive history nor information on mosaic embryo characteristics through counselling seems to be determinative for patients when deciding to transfer a mosaic embryo. Promising and increasing data on clinical outcomes after mosaic embryo transfer will be of utmost importance to soften risk perception regarding mosaic embryos and give a better, simplified and more evidence-based counselling. Key pointsWhat is already known?� Mosaic blastocysts have reproductive potential and can give rise to healthy children.However, there are potential risks after achieving a pregnancy from a mosaic blastocyst.Counselling and decision-making regarding mosaic embryo transfer are both challenging for genetic counsellors and patients, respectively, and very few studies have assessed this process.

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Section: Discussionmentioning

confidence: 83%

“…23 To date, only 2 mosaic pregnancies and births have been reported after the transfer of a mosaic embryo. 26,27 Therefore, when we describe the risk of an affected mosaic pregnancy, we clearly state that based on current evidence, this seems like the most unlikely scenario.…”

Section: Discussionmentioning

confidence: 91%

Do reproductive history and information given through genetic counselling influence patients' decisions on mosaic embryo transfer?

et al. 2022

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“…There is currently no evidence suggesting that offspring from low-range mosaic embryo transfer are at greater risk for this outcome compared to those conceived from euploid/untested embryos. There are only two published case reports describing the confirmation of the TE mosaic findings at a later stage of the pregnancy and postnatally ( Kahraman et al , 2020 ) or postnatally only ( Schlade-Bartusiak et al , 2022 ). In contrast, studies have reported that the transfer of embryos with a purely euploid TE biopsy result does not prevent mosaicism in the forthcoming pregnancy ( Friedenthal et al , 2020 ; Capalbo et al , 2021 ).…”

Section: Resultsmentioning

confidence: 99%

ESHRE survey results and good practice recommendations on managing chromosomal mosaicism

Rycke

Capalbo²,

Coonen

et al. 2022

Human Reproduction Open

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STUDY QUESTION How should ART/preimplantation genetic testing (PGT) centres manage the detection of chromosomal mosaicism following PGT? SUMMARY ANSWER Thirty good practice recommendations were formulated that can be used by ART/PGT centres as a basis for their own policy with regards to the management of ‘mosaic’ embryos. WHAT IS KNOWN ALREADY The use of comprehensive chromosome screening technologies has provided a variety of data on the incidence of chromosomal mosaicism at the preimplantation stage of development and evidence is accumulating that clarifies the clinical outcomes after transfer of embryos with putative mosaic results, with regards to implantation, miscarriage and live birth rates, and neonatal outcomes. STUDY DESIGN, SIZE, DURATION This document was developed according to a predefined methodology for ESHRE good practice recommendations. Recommendations are supported by data from the literature, a large survey evaluating current practice and published guidance documents. The literature search was performed using PubMed and focused on studies published between 2010 and 2022. The survey was performed through a web-based questionnaire distributed to members of the ESHRE special interest groups (SIG) Reproductive Genetics and Embryology, and the ESHRE PGT Consortium members. It included questions on ART and PGT, reporting, embryo transfer policy and follow-up of transfers. The final dataset represents 239 centres. PARTICIPANTS/MATERIALS, SETTING, METHODS The working group (WG) included 16 members with expertise on the ART/PGT process and chromosomal mosaicism. The recommendations for clinical practice were formulated based on the expert opinion of the WG, while taking into consideration the published data and results of the survey. MAIN RESULTS AND THE ROLE OF CHANCE Eighty percent of centres that biopsy three or more cells report mosaicism, even though only 66.9% of all centres have validated their technology and only 61.8% of these have validated specifically for the calling of chromosomal mosaicism. The criteria for designating mosaicism, reporting and transfer policies vary significantly across the centres replying to the survey. The WG formulated recommendations on how to manage the detection of chromosomal mosaicism in clinical practice, considering validation, risk assessment, designating and reporting mosaicism, embryo transfer policies, prenatal testing and follow-up. Guidance is also provided on the essential elements that should constitute the consent forms and the genetic report, and that should be covered in genetic counselling. As there are several unknowns in chromosomal mosaicism, it is recommended that PGT centres monitor emerging data on the topic and adapt or refine their policy whenever new insights are available from evidence. LIMITATIONS, REASONS FOR CAUTION Rather than providing instant standardized advice, the recommendations should help ART/PGT centres in developing their own policy towards the management of putative mosaic embryos in clinical practice. WIDER IMPLICATIONS OF THE FINDINGS This document will help facilitate a more knowledge-based approach for dealing with chromosomal mosaicism in different centres. In addition to recommendations for clinical practice, recommendations for future research were formulated. Following up on these will direct research towards existing research gaps with direct translation to clinical practice. Emerging data will help in improving guidance, and a more evidence-based approach of managing chromosomal mosaicism. STUDY FUNDING/COMPETING INTEREST(S) The WG received technical support from ESHRE. M.D.R. participated in the EQA special advisory group, outside the submitted work, and is the chair of the PGT WG of the Belgian society for human genetics. D.W. declared receiving salary from Juno Genetics, UK. A.C. is an employee of Igenomix, Italy and C.R. is an employee of Igenomix, Spain. C.S. received a research grant from FWO, Belgium, not related to the submitted work. I.S. declared being a Co-founder of IVFvision Ltd, UK. J.R.V. declared patents related to ‘Methods for haplotyping single-cells’ and ‘Haplotyping and copy number typing using polymorphic variant allelic frequencies’, and being a board member of Preimplantation Genetic Diagnosis International Society (PGDIS) and International Society for Prenatal Diagnosis (ISPD). K.S. reported being Chair-elect of ESHRE. The other authors had nothing to disclose. DISCLAIMER This Good Practice Recommendations (GPR) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and are based on the scientific evidence available at the time of preparation. ESHRE GPRs should be used for information and educational purposes. They should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care, or be exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, or variations based on locality and facility type. Furthermore, ESHRE GPRs do not constitute or imply the endorsement, or favouring, of any of the included technologies by ESHRE.

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“…In this edition, the case presented by Schlade-Bartusia et al. ( 4 ) reports the first known case of a live born diagnosed with a partial trisomy 15 and maternal uniparental disomy (UPD) 15 resulting from a mosaic embryo transfer. This was the result of a double embryo transfer; one embryo with high-level mosaicism for trisomy 15 with a deletion in chromosome 20, and the other embryo was a high-level mosaic for monosomy 21 and X.…”

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confidence: 99%

“…The cells analyzed represent a small sample of the entire embryo. Nonselection studies have shown good predictive value for whole chromosome aneuploidy with the platform used ( 4 ). It should be noted that every nonselection study is PGT-A testing platform specific—the results cannot necessarily be extrapolated to all methods of PGT-A.…”

mentioning

confidence: 99%

Mosaic embryo transfer: a cautionary tale

Franasiak

2022

F&S Reports

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Mosaic embryo transfer—first report of a live born with nonmosaic partial aneuploidy and uniparental disomy 15

Cited by 12 publications

References 19 publications

Do reproductive history and information given through genetic counselling influence patients' decisions on mosaic embryo transfer?

Do reproductive history and information given through genetic counselling influence patients' decisions on mosaic embryo transfer?

ESHRE survey results and good practice recommendations on managing chromosomal mosaicism

Mosaic embryo transfer: a cautionary tale

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