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

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2020 Oct 3

PMID 33007801

Citations 9

Authors

Lorena Rodrigo

Monica Clemente-Ciscar

Inmaculada Campos-Galindo

Vanessa Peinado

Carlos Simon

Carmen Rubio

Affiliations

Soon will be listed here.

Abstract

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 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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References

Silber S, Escudero T, Lenahan K, Abdelhadi I, Kilani Z, Munne S . Chromosomal abnormalities in embryos derived from testicular sperm extraction. Fertil Steril. 2003; 79(1):30-8. DOI: 10.1016/s0015-0282(02)04407-2. View

Forman E, Li X, Ferry K, Scott K, Treff N, Scott Jr R . Oocyte vitrification does not increase the risk of embryonic aneuploidy or diminish the implantation potential of blastocysts created after intracytoplasmic sperm injection: a novel, paired randomized controlled trial using DNA fingerprinting. Fertil Steril. 2012; 98(3):644-9. DOI: 10.1016/j.fertnstert.2012.04.028. View

Sanchez-Castro M, Jimenez-Macedo A, Sandalinas M, Blanco J . Prognostic value of sperm fluorescence in situ hybridization analysis over PGD. Hum Reprod. 2009; 24(6):1516-21. DOI: 10.1093/humrep/dep037. View

Ferraretti A, La Marca A, Fauser B, Tarlatzis B, Nargund G, Gianaroli L . ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011; 26(7):1616-24. DOI: 10.1093/humrep/der092. View

McCulloh D, Alikani M, Norian J, Kolb B, Arbones J, Munne S . Controlled ovarian hyperstimulation (COH) parameters associated with euploidy rates in donor oocytes. Eur J Med Genet. 2019; 62(8):103707. DOI: 10.1016/j.ejmg.2019.103707. View

Kahraman S, Sahin Y, Yelke H, Kumtepe Y, Tufekci M, Yapan C . High rates of aneuploidy, mosaicism and abnormal morphokinetic development in cases with low sperm concentration. J Assist Reprod Genet. 2020; 37(3):629-640. PMC: 7125256. DOI: 10.1007/s10815-019-01673-w. View

Vera-Rodriguez M, Michel C, Mercader A, Bladon A, Rodrigo L, Kokocinski F . Distribution patterns of segmental aneuploidies in human blastocysts identified by next-generation sequencing. Fertil Steril. 2016; 105(4):1047-1055.e2. DOI: 10.1016/j.fertnstert.2015.12.022. View

Rodrigo L, Peinado V, Mateu E, Remohi J, Pellicer A, Simon C . Impact of different patterns of sperm chromosomal abnormalities on the chromosomal constitution of preimplantation embryos. Fertil Steril. 2009; 94(4):1380-1386. DOI: 10.1016/j.fertnstert.2009.05.061. View

Kubicek D, Hornak M, Horak J, Navratil R, Tauwinklova G, Rubes J . Incidence and origin of meiotic whole and segmental chromosomal aneuploidies detected by karyomapping. Reprod Biomed Online. 2019; 38(3):330-339. DOI: 10.1016/j.rbmo.2018.11.023. View

10.

Munne S, Spinella F, Grifo J, Zhang J, Beltran M, Fragouli E . Clinical outcomes after the transfer of blastocysts characterized as mosaic by high resolution Next Generation Sequencing- further insights. Eur J Med Genet. 2019; 63(2):103741. DOI: 10.1016/j.ejmg.2019.103741. View

11.

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

12.

Popovic M, Dheedene A, Christodoulou C, Taelman J, Dhaenens L, Van Nieuwerburgh F . Chromosomal mosaicism in human blastocysts: the ultimate challenge of preimplantation genetic testing?. Hum Reprod. 2018; 33(7):1342-1354. DOI: 10.1093/humrep/dey106. View

13.

Goodrich D, Tao X, Bohrer C, Lonczak A, Xing T, Zimmerman R . A randomized and blinded comparison of qPCR and NGS-based detection of aneuploidy in a cell line mixture model of blastocyst biopsy mosaicism. J Assist Reprod Genet. 2016; 33(11):1473-1480. PMC: 5125146. DOI: 10.1007/s10815-016-0784-3. View

14.

Tarozzi N, Nadalini M, Lagalla C, Coticchio G, Zaca C, Borini A . Male factor infertility impacts the rate of mosaic blastocysts in cycles of preimplantation genetic testing for aneuploidy. J Assist Reprod Genet. 2019; 36(10):2047-2055. PMC: 6823398. DOI: 10.1007/s10815-019-01584-w. View

15.

Aran B, Veiga A, Vidal F, Parriego M, Vendrell J, Santalo J . Preimplantation genetic diagnosis in patients with male meiotic abnormalities. Reprod Biomed Online. 2004; 8(4):470-6. DOI: 10.1016/s1472-6483(10)60932-7. View

16.

Rubio C, Rodrigo L, Garcia-Pascual C, Peinado V, Campos-Galindo I, Garcia-Herrero S . Clinical application of embryo aneuploidy testing by next-generation sequencing. Biol Reprod. 2019; 101(6):1083-1090. DOI: 10.1093/biolre/ioz019. View

17.

Platteau P, Staessen C, Michiels A, Tournaye H, VAN Steirteghem A, Liebaers I . Comparison of the aneuploidy frequency in embryos derived from testicular sperm extraction in obstructive and non-obstructive azoospermic men. Hum Reprod. 2004; 19(7):1570-4. DOI: 10.1093/humrep/deh306. View

18.

Rodrigo L, Meseguer M, Mateu E, Mercader A, Peinado V, Bori L . Sperm chromosomal abnormalities and their contribution to human embryo aneuploidy. Biol Reprod. 2019; 101(6):1091-1101. DOI: 10.1093/biolre/ioz125. View

19.

Girardi L, Serdarogullari M, Patassini C, Poli M, Fabiani M, Caroselli S . Incidence, Origin, and Predictive Model for the Detection and Clinical Management of Segmental Aneuploidies in Human Embryos. Am J Hum Genet. 2020; 106(4):525-534. PMC: 7118577. DOI: 10.1016/j.ajhg.2020.03.005. View

20.

Popovic M, Dhaenens L, Taelman J, Dheedene A, Bialecka M, De Sutter P . Extended in vitro culture of human embryos demonstrates the complex nature of diagnosing chromosomal mosaicism from a single trophectoderm biopsy. Hum Reprod. 2019; 34(4):758-769. DOI: 10.1093/humrep/dez012. View