Does ICSI for in vitro fertilization cause more aneuploid embryos?

Xiangli Niu, Jiamin Long, Fangqiang Gong, Weihua Wang, Xiangli Niu, Jiamin Long, Fangqiang Gong, Weihua Wang

Abstract

Background: High proportion of human embryos produced by in vitro fertilization (IVF) is aneuploidy. Many factors are related to the prevalence of embryonic aneuploidies, such as maternal age, sperm quality, and in vitro manipulation of oocytes. Oocytes are usually inseminated by intracytoplasmic sperm injection (ICSI) procedures for preimplantation genetic testing. There is still no available information whether insemination procedures, regular IVF or ICSI, affect embryonic aneuploidies.

Methods: In this case report, a patient at her age of 47 years old received donated oocytes from a young donor for infertility treatment. Half of oocytes were inseminated by regular IVF and other half of oocytes were inseminated by ICSI. Fertilized oocytes were cultured to blastocyst stage and then biopsied for preimplantation genetic testing for aneuploidies (PGT-A). The proportions of aneuploidies were compared between two insemination procedures.

Results: Forty-seven oocytes were retrieved, 23 were inseminated by regular IVF and 24 were removed from enclosed cumulus cells for ICSI. Out of 24 oocytes, 21 oocytes at metaphase II were inseminated by ICSI. After fertilization assessment, it was found that 12 oocytes from regular IVF fertilized normally. Nine blastocysts (75%) were biopsied and 1 (11.1%) was aneuploidy. By contrast, 19 out of 21 oocytes inseminated by ICSI fertilized normally, 14 blastocysts (73.7%) were obtained and 7 (50.0%) were aneuploidy. Transfer of a euploid blastocyst from regular IVF resulted in a healthy baby delivery.

Conclusion: These results indicate that more embryos produced by ICSI are aneuploidy as compared with embryos produced by regular IVF. The results indicate that in vitro manipulation of oocytes for ICSI procedure may have adverse effect on human oocytes, and it may be one of the reasons causing aneuploid embryos in human IVF.

Keywords: Aneuploidy; Blastocysts; ICSI; Oocytes; Regular IVF.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

© The Author(s) 2020.

References

    1. Adler A, Lee HL, McCulloh DH, Ampeloquio E, Clarke-Williams M, Wertz BH, et al. Blastocyst culture selects for euploid embryos: comparison of blastomere and trophectoderm biopsies. Reprod BioMed Online. 2014;28(4):485–491. doi: 10.1016/j.rbmo.2013.11.018.
    1. Cárdenas-Nieto D, Forero-Castro M, Moreno-Ortiz H, Lucena-Quevedo E, Cuzzi J, Esteban-Pérez C. Analysis of a preimplantation genetic test for aneuploidies in embryos from Colombian couples: a report of cases. J Reprod Infertil. 2020;21(1):17–33.
    1. Subira J, Craig J, Turner K, Bevan A, Ohuma E, Veigh EM. Grade of the inner cell mass, but not trophectoderm, predicts live birth in fresh blastocyst single transfers. Hum Fertil (Camb) 2016;19(4):254–261. doi: 10.1080/14647273.2016.1223357.
    1. Ravichandran K, Guzman L, Escudero T, Zheng XZ, Colls P, Jordan A, et al. Causes and estimated incidences of sexchromosome misdiagnosis in preimplantation genetic diagnosis of aneuploidy. Reprod BioMed Online. 2016;33(5):550–559. doi: 10.1016/j.rbmo.2016.08.011.
    1. Minasi MG, Fiorentino F, Ruberti A, Biricik A, Cursio E, Cotroneo E, et al. Genetic diseases and aneuploidies can be detected with a single blastocyst biopsy: a successful clinical approach. Hum Reprod. 2017;32(8):1770–1777. doi: 10.1093/humrep/dex215.Epub.
    1. Fishel S, Campbell A, Foad F, Davies L, Best L, Davis N, et al. Evolution of embryo selection for IVF from subjective morphology assessment to objective time-lapse algorithms improves chance of live birth. Reprod BioMed Online. 2019;19:30756. doi: 10.1016/j.rbmo.2019.10.005.
    1. Pribenszky C, Nilselid AM, Montag M. Time-lapse culture with morphokinetic embryo selection improves pregnancy and live birth chances and reduces early pregnancy loss: a meta-analysis. Reprod BioMed Online. 2017;35(5):511–520. doi: 10.1016/j.rbmo.2017.06.022.
    1. Pagidas K, Ying Y, Keefe D. Predictive value of preimplantation genetic diagnosis for aneuploidy screening in repeated IVF-ET cycles among women with recurrent implantation failure. J Assist Reprod Genet. 2008;25:103–106. doi: 10.1007/s10815-008-9200-y.
    1. Simon AL, Kiehl M, Fischer E, Proctor JG, Bush MR, Givens C, et al. Pregnancy outcomes from more than 1,800 in vitro fertilization cycles with the use of 24-chromosome single-nucleotide polymorphism–based preimplantation genetic testing for aneuploidy. Fertil Steril. 2018;110(1):113–121. doi: 10.1016/j.fertnstert.2018.03.026.
    1. Kurahashi H, Kato T, Miyazaki J, Nishizawa H, Nishio E, Furukawa H, et al. Preimplantation genetic diagnosis/screening by comprehensive molecular testing. Reprod Med Biol. 2016;15(1):13–19. doi: 10.1007/s12522-015-0216-6.
    1. Cai Y, Ding M, Lin F, Diao Z, Zhang N, Sun H, et al. Evaluation of preimplantation genetic testing based on next-generation sequencing for balanced reciprocal translocation carriers. Reprod BioMed Online. 2019;38(5):669–675. doi: 10.1016/j.rbmo.2018.12.043.
    1. Zheng H, Jin H, Liu L, Liu J, Wang WH. Application of next-generation sequencing for 24-chromosome aneuploidy screening of human preimplantation embryos. Mol Cytogenet. 2015;8:38. doi: 10.1186/s13039-015-0143-6.
    1. Palmerola KL, Vitez SF, Amrane S, Fischer CP, Forman EJ. Minimizing mosaicism: assessing the impact of fertilization method on rate of mosaicism after next-generation sequencing (NGS) preimplantation genetic testing for aneuploidy (PGT-A) J Assist Reprod Genet. 2019;36:153–157. doi: 10.1007/s10815-018-1347-6.
    1. Thornhill AR, de Die-Smulders CE, Geraedts JP, Harper JC, Harton GL, Lavery SA, et al. ESHRE PGD consortium ‘Best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS)’. Hum Reprod. 2005;20(1):35–48. doi: 10.1093/humrep/deh579.
    1. Fragouli E, Wells D, Doshi A, Gotts S, Harper JC, Delhanty JD. Complete cytogenetic investigation of oocytes from a young cancer patient with the use of comparative genomic hybridisation reveals meiotic errors. Prenat Diagn. 2006;26(1):71–76. doi: 10.1002/pd.1350.
    1. Pellestor F, Andreo B, Arnal F, Humeau C, Demaille J. Maternal aging and chromosomal abnormalities: new data drawn from in vitro unfertilized human oocytes. Hum Genet. 2003;112(2):195–203. doi: 10.1007/s00439-002-0852-x.
    1. Scott RT, Jr, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, et al. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013;100(3):697–703. doi: 10.1016/j.fertnstert.2013.04.035.
    1. Scott RT, Jr, Ferry K, Su J, Tao X, Scott K, Treff NR. Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, nonselection study. Fertil Steril. 2012;97(4):870–875. doi: 10.1016/j.fertnstert.2012.01.104.
    1. Haddad G, Deng M, Wang CT, Witz C, Williams D, Griffith J, et al. Assessment of aneuploidy formation in human blastocysts resulting from donated eggs and the necessity of the embryos for aneuploidy screening. J Assist Reprod Genet. 2015;32(6):999–1006. doi: 10.1007/s10815-015-0492-4.
    1. Jones KT. Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age. Hum Reprod Update. 2008;14(2):143–158. doi: 10.1093/humupd/dmm043.
    1. Chiang T, Schultz RM, Lampson MA. Meiotic origins of maternal age-related aneuploidy. Biol Reprod. 2012;86(1):1–7. doi: 10.1095/biolreprod.111.094367.
    1. Liu J, Wang W, Sun X, Liu L, Jin H, Li M, et al. DNA microarray reveals that high proportions of human blastocysts from women of advanced maternal age are aneuploidy and mosaic. Biol Reprod. 2012;87(6):1–9. doi: 10.1095/biolreprod.112.103192.
    1. Battaglia DE, Goodwin P, Klein NA, Soules MR. Influence of maternal age on meiotic spindle assembly in oocytes from naturally cycling women. Hum Reprod. 1996;11(10):2217–2222. doi: 10.1093/oxfordjournals.humrep.a019080.
    1. Franasiak JM, Forman EJ, Hong KH, Werner MD, Upham KM, Treff NR, et al. The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil Steril. 2014;101(3):656–663. doi: 10.1016/j.fertnstert.2013.11.004.
    1. Platteau P, Staessen C, Michiels A, Van Steirteghem A, Liebaers I, Devroey P. Preimplantation genetic diagnosis for aneuploidy screening in women older than 37 years. Fertil Steril. 2005;84(2):319–324. doi: 10.1016/j.fertnstert.2005.02.019.
    1. Spandorfer SD, Chung PH, Kligman I, Liu HC, Davis OK, Rosenwaks Z. An analysis of the effect of age on implantation rates. J Assist Reprod Genet. 2000;17(6):303–306. doi: 10.1023/a:1009422725434.
    1. Forman EJ, Upham KM, Cheng M, Zhao T, Hong KH, Treff NR, et al. Comprehensive chromosome screening alters traditional morphology-based embryo selection: a prospective study of 100 consecutive cycles of planned fresh euploid blastocyst transfer. Fertil Steril. 2013;100(3):718–724. doi: 10.1016/j.fertnstert.2013.04.043.
    1. Baart EB, Martini E, van den Berg I, Macklon NS, Galjaard RJ, Fauser BC, et al. Preimplantation genetic screening reveals a high incidence of aneuploidy and mosaicism in embryos from young women undergoing IVF. Hum Reprod. 2006;21(1):223–233. doi: 10.1093/humrep/dei291.
    1. Yang Z, Liu J, Collins J, Salem SA, Liu X, Lyle SS, et al. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet. 2012;5(1):24–29. doi: 10.1186/1755-8166-5-24.Epub.
    1. Munne S, Sandalinas M, Magli C, Gianaroli L, Cohen J, Warburton D. Increased rate of aneuploid embryos in young women with previous aneuploid conceptions. Prenat Diagn. 2004;24(8):638–643. doi: 10.1002/pd.957.Epub.
    1. Sills E, Li X, Frederick JL, Khoury CD, Potter DA. Determining parental origin of embryo aneuploidy: analysis of genetic error observed in 305 embryos derived from anonymous donor oocyte IVF cycles. Mol Cytogenet. 2014;7(1):68. doi: 10.1186/s13039-014-0068-5.Epub.
    1. Coticchio G, Dal Canto M, Mignini Renzini M, Guglielmo MC, Brambillasca F, Turchi D, et al. Oocyte maturation: gamete-somatic cells interactions, meiotic resumption, cytoskeletal dynamics and cytoplasmic reorganization. Hum Reprod Update. 2015;21(4):427–454. doi: 10.1093/humupd/dmv011.
    1. Munné S, Alikani M, Ribustello L, Colls P, Martínez-Ortiz PA, McCulloh DH. Referring physician group. Euploidy rates in donor egg cycles significantly differ between fertility centers. Hum Reprod. 2017;32(4):743–749. doi: 10.1093/humrep/dex031.
    1. Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001;2(4):280–291. doi: 10.1038/35066065.
    1. Wang WH, Sun QY. Meiotic spindle, spindle checkpoint and embryonic aneuploidy. Front Biosci. 2006;11:620–636. doi: 10.2741/1822.
    1. Bennabi I, Terret ME, Verlhac MH. Meiotic spindle assembly and hromosome segregation in oocytes. J Cell Biol. 2016;215(5):611–619. doi: 10.1083/jcb.201607062.
    1. Liang L, Wang CT, Sun X, Liu L, Li M, Witz C, et al. Identification of chromosomal errors in human preimplantation embryos with oligonucleotide DNA microarray. PLoS One. 2013;8(4):e61838. doi: 10.1371/journal.pone.0061838.
    1. Hourvitz A, Pri-Paz S, Dor J, Seidman DS. Neonatal and obstetric outcome of pregnancies conceived by ICSI or IVF. Reprod BioMed Online. 2005;11(4):469–475. doi: 10.1016/s1472-6483(10)61143-1.
    1. Bonduelle M, Liebaers I, Deketelaere V, Derde MP, Camus M, Devroey P, et al. Neonatal data on a cohort of 2889 infants born after ICSI (1991-1999) and of 2995 infants born after IVF (1983-1999) Hum Reprod. 2002;17(3):671–694. doi: 10.1093/humrep/17.3.671.
    1. Moor RM, Crosby IM. Temperature-induced abnormalities in sheep oocytes during maturation. J Reprod Fertil. 1985;75(2):476–483.
    1. Pickering SJ, Johnson MH. The influence of cooling on the organization of the meiotic spindle of the mouse oocyte. Hum Reprod. 1987;2(3):207–216. doi: 10.1093/oxfordjournals.humrep.a136516.
    1. Aman RR, Parks JE. Effects of cooling and rewarming on the meiotic spindle and chromosomes of in vitro-matured bovine oocytes. Biol Reprod. 1994;50(1):103–110. doi: 10.1095/biolreprod50.1.103.
    1. Ye J, Coleman J, Hunter MG, Craigon J, Campbell KH, Luck MR. Physiological temperature variants and culture media modify meiotic progression and developmental potential of pig oocytes in vitro. Reproduction. 2007;133(5):877–886. doi: 10.1530/REP-06-0318.
    1. Liu RH, Sun QY, Li YH, Jiao LH, Wang WH. Effects of cooling on meiotic spindle structure and chromosome alignment within in vitro matured porcine oocytes. Mol Reprod Dev. 2003;65(2):212–218. doi: 10.1002/mrd.10282.
    1. Wu B, Tong J, Leibo SP. Effects of cooling germinal vesicle-stage bovine oocytes on meiotic spindle formation following in vitro maturation. Mol Reprod Dev. 1999;54(4):388–395. doi: 10.1002/(SICI)1098-2795(199912)54:4<388::AID-MRD9>;2-7.
    1. Almeida PA, Bolton VN. The effect of temperature fluctuations on the cytoskeletal organisation and chromosomal constitution of the human oocyte. Zygote. 1995;3(4):357–365. doi: 10.1017/s0967199400002793.
    1. Pickering SJ, Braude PR, Johnson MH, Cant A, Currie J. Transient cooling to room temperature can cause irreversible disruption of the meiotic spindle in the human oocyte. Fertil Steril. 1990;54(1):102–108. doi: 10.1016/S0015-0282(16)53644-9.
    1. Sun XF, Wang WH, Keefe DL. Overheating is detrimental tomeiotic spindles within in vitro matured human oocytes. Zygote. 2004;12(1):65–70. doi: 10.1017/s0967199404002631.
    1. Wang WH, Meng L, Hackett RJ, Odenbourg R, Keefe DL. Limited recovery of meiotic spindles in living human oocytesafter cooling-rewarming observed using polarized light microscopy. Hum Reprod. 2001;16(11):2374–2378. doi: 10.1093/humrep/16.11.2374.
    1. Wang WH, Meng L, Hackett RJ, Oldenbourg R, Keefe DL. Rigorous thermal control during intracytoplasmic sperm injection stabilizes the meiotic spindle and improves fertilization and pregnancy rates. Fertil Steril. 2002;77(6):1274–1277. doi: 10.1016/s0015-0282(02)03117-5.
    1. Campbell A, Fishel S, Bowman N, Duffy S, Sedler M, Hickman CF. Modelling a risk classification of aneuploidy in human embryos using non-invasive morphokinetics. Reprod BioMed Online. 2013;26(5):477–485. doi: 10.1016/j.rbmo.2013.02.006.
    1. Campbell A, Fishel S, Bowman N, Duffy S, Sedler M, Thornton S. Retrospective analysis of outcomes after IVF using an aneuploidy risk model derived from time-lapse imaging without PGS. Reprod BioMed Online. 2013;27(2):140–146. doi: 10.1016/j.rbmo.2013.04.013.
    1. Guerif F, Lemseffer M, Leger J, Bidault R, Cadoret V, Chavez C, et al. Does early morphology provide additional selection power to blastocyst selection for transfer? Reprod BioMed Online. 2010;21(4):510–519. doi: 10.1016/j.rbmo.2010.06.043.
    1. Ottolini C, Rienzi L, Capalbo A. A cautionary note against embryo aneuploidy risk assessment using time-lapse imaging. Reprod BioMed Online. 2014;28(3):273–275. doi: 10.1016/j.rbmo.2013.10.015.
    1. Forman EJ, Hong KH, Ferry KM, Tao X, Taylor D, Levy B, et al. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril. 2013;100(1):100–107. doi: 10.1016/j.fertnstert.2013.02.056.
    1. Munne S, Chen S, Colls P, Garrisi J, Zheng X, Cekleniak N, et al. Maternal age, morphology, development and chromosome abnormalities in over 6000 cleavage-stage embryos. Reprod BioMed Online. 2007;14(5):628–634. doi: 10.1016/s1472-6483(10)61057-7.
    1. Minasi MG, Colasante A, Riccio T, Ruberti A, Casciani V, Scarselli F, et al. Correlation between aneuploidy, standard morphology evaluation and morphokinetic development in 1730 biopsied blastocysts: a consecutive case series study. Hum Reprod. 2016;31(10):2245–2254. doi: 10.1093/humrep/dew183.
    1. Kaing A, Kroener LL, Tassin R, Li M, Liu L, Buyalos R, et al. Earlier day of blastocyst development is predictive of embryonic euploidy across all ages: essential data for physician decision-making and counseling patients. J Assist Reprod Genet. 2018;35(1):119–125. doi: 10.1007/s10815-017-1038-8.Epub.
    1. Lagalla C, Tarozzi N, Sciajno R, Wells D, Di Santo M, Nadalini M, et al. Embryos with morphokinetic abnormalities may develop into euploid blastocysts. Reprod BioMed Online. 2017;34(2):137–146. doi: 10.1016/j.rbmo.2016.11.008.
    1. Lathi RB, Milki AA. Rate of aneuploidy in miscarriages following in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril. 2004;81:1270–1272. doi: 10.1016/j.fertnstert.2003.09.065.
    1. Ma S, Philipp T, Zhao Y, Stetten G, Robinson WP, Kalousek D. Frequency of chromosomal abnormalities in spontaneous abortions derived from intracytoplasmic sperm injection compared with those from in vitro fertilization. Fertil Steril. 2006;85(1):236–239. doi: 10.1016/j.fertnstert.2005.06.041.
    1. Kushnir VA, Frattarelli JL. Aneuploidy in abortuses following IVF and ICSI. J Assist Reprod Genet. 2009;26:93–97. doi: 10.1007/s10815-009-9292-z.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel