Which Type of Chromosomal Mosaicism is Compatible for Embryo Transfer: a Systematical Review and Meta-analysis

Overview

Journal Arch Gynecol Obstet

Specialty Gynecology & Obstetrics

Date 2022 Mar 20

PMID 35306582

Authors

Yuanlin Ma

Lok-Wan Liu

Yongxiang Liu

Gaohui Shi

Xixiong Ai

Wenhui Hou

Qingyun Mai

Yanwen Xu

Affiliations

Soon will be listed here.

Abstract

Purpose: Chromosomal mosaicism becomes a common phenomenon in Preimplantaion genetic testing (PGT). This meta-analysis was conducted to study which feature of chromosomal mosaicism was compatible for embryo transfer.

Methods: After searching the database PubMed, Embase, CCTR and related reviews up until May 2021. Two reviewers extracted relevant information and assessed study quality by the Newcastle-Ottawa scale independently. Summary Odd Radios (OR) were calculated using fixed- or random-effects models for clinical outcomes. A network meta-analysis compared the clinical outcomes of different chromosomes.

Results: A total of six studies with 1,106 cycles of single mosaic embryo transferred were included. Significant results of implantation rate (IR), miscarriage rate (MR), and ongoing pregnancy/live birth rate (OP/LBR) were observed when comparing embryos with mosaicism level < 50% and ≥ 50% [OR 1.42, 95% CI (1.06, 1.89); OR 0.45, 95% CI (0.27, 0.75); OR 1.74, 95% CI (1.28, 2.37)], and embryos with mosaicism with only affecting segmental chromosome(s) and only involving whole chromosome(s) [OR 1.31, 95% CI (1.01, 1.71); OR 0.57, 95% CI (0.36, 0.93); OR 1.51, 95% CI (1.15, 2.00)]. Embryos with only mosaic gains or losses had significant higher IR and OP/LBR than complex mosaicism [Gains vs complex: OR 1.75, 95% CI (1.20, 2.54); OR 1.73, 95% CI (1.16, 2.58). Losses vs complex: OR 1.90, 95% CI (1.34, 2.71); OR 2.10, 95% CI (1.44, 3.07)]. Mosaic embryos with only one chromosome involved had significant favorable outcomes of IR and OP/LBR than with three or more chromosomes involved [OR 1.76, 95% CI (1.23, 2.52); OR 1.86, 95% CI (1.25,2.78)]. Chr. 7, Chr. 2, Chr. 1, Chr. 18, Chr. 11, Chr. X, Chr. 13, Chr. 14, Chr. 12, and Chr. 9 were considered as prioritized chromosomes of mosaic embryos for transfer.

Conclusions: This analysis support the embryos with mosaicism level ≥ 50%, whole chromosome(s) involved, multiple mosaic abnormalities were associated with worse pregnancy outcomes. Mosaicism level of 50% could be used as a threshold to assess the mosaic embryos.

Citing Articles

Evaluating the developmental potential of 2.1PN-derived embryos and associated chromosomal analysis.

Wang J, Xiong S, Hao X, Gao Y, Xia F, Liao H J Assist Reprod Genet. 2024; 41(6):1597-1603.

PMID: 38613651 PMC: 11224204. DOI: 10.1007/s10815-024-03113-w.

Mosaic results after preimplantation genetic testing for aneuploidy may be accompanied by changes in global gene expression.

Martin A, Mercader A, Dominguez F, Quinonero A, Perez M, Gonzalez-Martin R Front Mol Biosci. 2023; 10:1180689.

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References

Munne S, Weier H, Grifo J, Cohen J . Chromosome mosaicism in human embryos. Biol Reprod. 1994; 51(3):373-9. DOI: 10.1095/biolreprod51.3.373. View

Taylor T, Gitlin S, Patrick J, Crain J, Wilson J, Griffin D . The origin, mechanisms, incidence and clinical consequences of chromosomal mosaicism in humans. Hum Reprod Update. 2014; 20(4):571-81. DOI: 10.1093/humupd/dmu016. View

Natsuaki M, Dimler L . Pregnancy and child developmental outcomes after preimplantation genetic screening: a meta-analytic and systematic review. World J Pediatr. 2018; 14(6):555-569. DOI: 10.1007/s12519-018-0172-4. View

Rubio C, Bellver J, Rodrigo L, Castillon G, Guillen A, Vidal C . In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study. Fertil Steril. 2017; 107(5):1122-1129. DOI: 10.1016/j.fertnstert.2017.03.011. View

Yan J, Qin Y, Zhao H, Sun Y, Gong F, Li R . Live Birth with or without Preimplantation Genetic Testing for Aneuploidy. N Engl J Med. 2021; 385(22):2047-2058. DOI: 10.1056/NEJMoa2103613. View

Bhatt S, Marchetto N, Roy J, Morelli S, McGovern P . Pregnancy outcomes following in vitro fertilization frozen embryo transfer (IVF-FET) with or without preimplantation genetic testing for aneuploidy (PGT-A) in women with recurrent pregnancy loss (RPL): a SART-CORS study. Hum Reprod. 2021; 36(8):2339-2344. DOI: 10.1093/humrep/deab117. View

Cozzolino M . Recurrent implantation failure might be overestimated without PGT-A. Arch Gynecol Obstet. 2020; 304(3):849-850. DOI: 10.1007/s00404-020-05775-0. View

Fragouli E, Alfarawati S, Daphnis D, Goodall N, Mania A, Griffiths T . Cytogenetic analysis of human blastocysts with the use of FISH, CGH and aCGH: scientific data and technical evaluation. Hum Reprod. 2010; 26(2):480-90. DOI: 10.1093/humrep/deq344. View

Rodrigo L, Mateu E, Mercader A, Cobo A, Peinado V, Milan M . New tools for embryo selection: comprehensive chromosome screening by array comparative genomic hybridization. Biomed Res Int. 2014; 2014:517125. PMC: 4022197. DOI: 10.1155/2014/517125. View

10.

Greco E, Minasi M, Fiorentino F . Healthy Babies after Intrauterine Transfer of Mosaic Aneuploid Blastocysts. N Engl J Med. 2015; 373(21):2089-90. DOI: 10.1056/NEJMc1500421. View

11.

Northrop L, Treff N, Levy B, Scott Jr R . SNP microarray-based 24 chromosome aneuploidy screening demonstrates that cleavage-stage FISH poorly predicts aneuploidy in embryos that develop to morphologically normal blastocysts. Mol Hum Reprod. 2010; 16(8):590-600. PMC: 2907218. DOI: 10.1093/molehr/gaq037. View

12.

Huang J, Yan L, Lu S, Zhao N, Xie X, Qiao J . Validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of blastocysts. Fertil Steril. 2016; 105(6):1532-6. DOI: 10.1016/j.fertnstert.2016.01.040. View

13.

Gleicher N, Vidali A, Braverman J, Kushnir V, Barad D, Hudson C . Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos. Reprod Biol Endocrinol. 2016; 14(1):54. PMC: 5011996. DOI: 10.1186/s12958-016-0193-6. View

14.

Spinella F, Fiorentino F, Biricik A, Bono S, Ruberti A, Cotroneo E . Extent of chromosomal mosaicism influences the clinical outcome of in vitro fertilization treatments. Fertil Steril. 2017; 109(1):77-83. DOI: 10.1016/j.fertnstert.2017.09.025. View

15.

Victor A, Griffin D, Brake A, Tyndall J, Murphy A, Lepkowsky L . Assessment of aneuploidy concordance between clinical trophectoderm biopsy and blastocyst. Hum Reprod. 2018; 34(1):181-192. DOI: 10.1093/humrep/dey327. View

16.

Zhang L, Wei D, Zhu Y, Gao Y, Yan J, Chen Z . Rates of live birth after mosaic embryo transfer compared with euploid embryo transfer. J Assist Reprod Genet. 2018; 36(1):165-172. PMC: 6338591. DOI: 10.1007/s10815-018-1322-2. View

17.

Viotti M, McCoy R, Griffin D, Spinella F, Greco E, Madjunkov M . Let the data do the talking: the need to consider mosaicism during embryo selection. Fertil Steril. 2021; 116(5):1212-1219. PMC: 8585724. DOI: 10.1016/j.fertnstert.2021.09.008. View

18.

Cram D, Leigh D, Handyside A, Rechitsky L, Xu K, Harton G . PGDIS Position Statement on the Transfer of Mosaic Embryos 2019. Reprod Biomed Online. 2019; 39 Suppl 1:e1-e4. DOI: 10.1016/j.rbmo.2019.06.012. View

19.

Grati F, Gallazzi G, Branca L, Maggi F, Simoni G, Yaron Y . An evidence-based scoring system for prioritizing mosaic aneuploid embryos following preimplantation genetic screening. Reprod Biomed Online. 2018; 36(4):442-449. DOI: 10.1016/j.rbmo.2018.01.005. View

20.

De Neubourg D, van Duijnhoven N, Nelen W, DHooghe T . Dutch translation of the ICMART-WHO revised glossary on ART terminology. Gynecol Obstet Invest. 2012; 74(3):233-48. DOI: 10.1159/000342876. View