Skip to main content
Top
Published in: Journal of Assisted Reproduction and Genetics 3/2020

Open Access 01-03-2020 | Infertility | Assisted Reproduction Technologies

High rates of aneuploidy, mosaicism and abnormal morphokinetic development in cases with low sperm concentration

Authors: Semra Kahraman, Yucel Sahin, Hakan Yelke, Yesim Kumtepe, Mehmet A. Tufekci, Cigdem C. Yapan, Mesut Yesil, Murat Cetinkaya

Published in: Journal of Assisted Reproduction and Genetics | Issue 3/2020

Login to get access

Abstract

Purpose

The aim of our study was to evaluate the impact of severe male infertility (SMF) on the chromosomal status of embryos and any possible correlation between chromosomal status and embryo morphokinetics in younger women using data obtained from comprehensive preimplantation genetic tests.

Methods

The trial was conducted in an ART and Reproductive Genetics Centre between 2011 and 2018. A total of 326 cycles in cases with SMF where the female partner’s age was ≤ 35 years were evaluated. SMF is defined as sperm concentration below 5 mil/ml (million per milliliter) and divided into three subgroups according to sperm concentrations: 1–5 mil/ml, < 1mil/ml and testicular sperm. The control group of 190 cycles had normal sperm parameters.

Results

Significantly lower chromosomal euploidy rates were found in the testicular sperm group compared with the normal sperm controls when the female age was ≤ 35 years. In SMF, statistically significantly affected chromosomes were 2, 10, 11, 17, 21 and sex chromosomes. The mosaicism and abnormal morphokinetic development rates were higher in the SMF group than in control group, and this difference was significant when testicular sperm was used.

Conclusion

Lower euploidy rates, higher mosaicism rates and a higher incidence of abnormal morphokinetic development were observed in cases with testicular sperm with female partners ≤ 35 years compared with normal sperm controls. These findings suggest that PGT-A may be advisable in severe male infertility cases. Furthermore, the correlation between morphokinetics and chromosomal status was greatly reduced or absent in these most severe forms of male infertility, thus the need for new morphokinetic models.
Appendix
Available only for authorised users
Literature
1.
go back to reference Punab M, Poolamets O, Paju P, Vihljajev V, Pomm K, Ladva R, et al. Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts. Hum Reprod. 2017;32:18–31.PubMed Punab M, Poolamets O, Paju P, Vihljajev V, Pomm K, Ladva R, et al. Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts. Hum Reprod. 2017;32:18–31.PubMed
2.
go back to reference Rubio C, Gil-Salom M, Simon C, Vidal F, Rodrigo L, Minguez Y, et al. Incidence of sperm chromosomal abnormalities in a risk population: relationship with sperm quality and ICSI outcome. Hum Reprod. 2001;16:2084–92.PubMedCrossRef Rubio C, Gil-Salom M, Simon C, Vidal F, Rodrigo L, Minguez Y, et al. Incidence of sperm chromosomal abnormalities in a risk population: relationship with sperm quality and ICSI outcome. Hum Reprod. 2001;16:2084–92.PubMedCrossRef
3.
go back to reference Rodrigo L, Rubio C, Peinado V, Villamon R, Al-Asmar N, Remohi J, et al. Testicular sperm from patients with obstructive and nonobstructive azoospermia: aneuploidy risk and reproductive prognosis using testicular sperm from fertile donors as control samples. Fertil Steril. 2011;95:1005–12.PubMedCrossRef Rodrigo L, Rubio C, Peinado V, Villamon R, Al-Asmar N, Remohi J, et al. Testicular sperm from patients with obstructive and nonobstructive azoospermia: aneuploidy risk and reproductive prognosis using testicular sperm from fertile donors as control samples. Fertil Steril. 2011;95:1005–12.PubMedCrossRef
4.
go back to reference Magli MC, Gianaroli L, Ferraretti AP, Gordts S, Fredericks V, Crippa A. Paternal contribution to aneuploidy in preimplantation embryos. Reprod BioMed Online. 2009;18:536–42.PubMedCrossRef Magli MC, Gianaroli L, Ferraretti AP, Gordts S, Fredericks V, Crippa A. Paternal contribution to aneuploidy in preimplantation embryos. Reprod BioMed Online. 2009;18:536–42.PubMedCrossRef
5.
go back to reference Silber S, Escudero T, Lenahan K, Abdelhadi I, Kilani Z, Munné S. Chromosomal abnormalities in embryos derived from testicular sperm extraction. Fertil Steril. 2003;79:30.PubMedCrossRef Silber S, Escudero T, Lenahan K, Abdelhadi I, Kilani Z, Munné S. Chromosomal abnormalities in embryos derived from testicular sperm extraction. Fertil Steril. 2003;79:30.PubMedCrossRef
6.
go back to reference Coates A, Hesla J, Hurliman A, Coate B, Holmes E, Matthews R, et al. Use of suboptimal sperm increases the risk of aneuploidy of the sex chromosomes in preimplantation blastocyst embryos. Fertil Steril. 2015;104:866–72.PubMedCrossRef Coates A, Hesla J, Hurliman A, Coate B, Holmes E, Matthews R, et al. Use of suboptimal sperm increases the risk of aneuploidy of the sex chromosomes in preimplantation blastocyst embryos. Fertil Steril. 2015;104:866–72.PubMedCrossRef
7.
go back to reference Mazzili R, Cimadomo D, Vaiarelli A, Capalbo A, Dovere Lalviggi E, et al. Effect of the male factor on the clinical outcome of intracytoplasmic sperm injection combined with preimplantation aneuploidy testing: observational longitudinal study of 1219 consecutive cycles. Fertil Steril. 2017;108:961–72.CrossRef Mazzili R, Cimadomo D, Vaiarelli A, Capalbo A, Dovere Lalviggi E, et al. Effect of the male factor on the clinical outcome of intracytoplasmic sperm injection combined with preimplantation aneuploidy testing: observational longitudinal study of 1219 consecutive cycles. Fertil Steril. 2017;108:961–72.CrossRef
8.
go back to reference Comizzoli P, Wildt DE, Pukazhenthi BS. Poor centrosomal function of cat testicular spermatozoa impairs embryo development in vitro after intracytoplasmic sperm injection. Biol Reprod. 2006;75(2):252–60.PubMedCrossRef Comizzoli P, Wildt DE, Pukazhenthi BS. Poor centrosomal function of cat testicular spermatozoa impairs embryo development in vitro after intracytoplasmic sperm injection. Biol Reprod. 2006;75(2):252–60.PubMedCrossRef
9.
go back to reference Gat I, Tang K, Quach K, Kuznyetsov V, Antes R, Filice M, et al. Sperm DNA fragmentation index does not correlate with blastocyst aneuploidy or morphological grading. PLoS One. 2017;12(6):e0179002.PubMedPubMedCentralCrossRef Gat I, Tang K, Quach K, Kuznyetsov V, Antes R, Filice M, et al. Sperm DNA fragmentation index does not correlate with blastocyst aneuploidy or morphological grading. PLoS One. 2017;12(6):e0179002.PubMedPubMedCentralCrossRef
10.
go back to reference Gat I, Li N, Yasovich N, Antes R, Kuznyetsov V, Zohni K, et al. Sperm DNA fragmentation index does not correlate with blastocyst euploidy rate in egg donor cycles. Gynecol Endocrinol. 2018;34(3):212–6.PubMedCrossRef Gat I, Li N, Yasovich N, Antes R, Kuznyetsov V, Zohni K, et al. Sperm DNA fragmentation index does not correlate with blastocyst euploidy rate in egg donor cycles. Gynecol Endocrinol. 2018;34(3):212–6.PubMedCrossRef
11.
go back to reference Pregl Breznik B, Kovačič B, Vlaisavljević V. Are sperm DNA fragmentation, hyperactivation, and hyaluronan-binding ability predictive for fertilization and embryo development in in vitro fertilization and intracytoplasmic sperm injection? Fertil Steril. 2013;99(5):1233–41.PubMedCrossRef Pregl Breznik B, Kovačič B, Vlaisavljević V. Are sperm DNA fragmentation, hyperactivation, and hyaluronan-binding ability predictive for fertilization and embryo development in in vitro fertilization and intracytoplasmic sperm injection? Fertil Steril. 2013;99(5):1233–41.PubMedCrossRef
12.
go back to reference Virro MR, Larson-Cook KL, Evenson DP. Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. Fertil Steril. 2004;81(5):1289–95.PubMedCrossRef Virro MR, Larson-Cook KL, Evenson DP. Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. Fertil Steril. 2004;81(5):1289–95.PubMedCrossRef
13.
go back to reference Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16:231–45.PubMedCrossRef Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16:231–45.PubMedCrossRef
14.
go back to reference Kahraman S, Cetinkaya CP, Cetinkaya M, Yelke H, Colakoglu YK, Aygun M, et al. The effect of follicle size and homogeneity of follicular development on the morphokinetics of human embryos. J Assist Reprod Genet. 2017;34:895–903.PubMedPubMedCentralCrossRef Kahraman S, Cetinkaya CP, Cetinkaya M, Yelke H, Colakoglu YK, Aygun M, et al. The effect of follicle size and homogeneity of follicular development on the morphokinetics of human embryos. J Assist Reprod Genet. 2017;34:895–903.PubMedPubMedCentralCrossRef
15.
go back to reference Ng FL, Liu DY, Baker HW. Comparison of Percoll, mini-Percoll and swim-up methods for sperm preparation from abnormal semen samples. Hum Reprod. 1992;7:261–6.PubMedCrossRef Ng FL, Liu DY, Baker HW. Comparison of Percoll, mini-Percoll and swim-up methods for sperm preparation from abnormal semen samples. Hum Reprod. 1992;7:261–6.PubMedCrossRef
16.
go back to reference Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73:1155–8.PubMedCrossRef Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73:1155–8.PubMedCrossRef
17.
go back to reference Ebner T, Vanderzwalmen P, Shebl O, Urdl W, Moser M, Zech NH, et al. Morphology of vitrified/warmed day-5 embryos predicts rates of implantation, pregnancy and live birth. Reprod BioMed Online. 2009;19:72–8.PubMedCrossRef Ebner T, Vanderzwalmen P, Shebl O, Urdl W, Moser M, Zech NH, et al. Morphology of vitrified/warmed day-5 embryos predicts rates of implantation, pregnancy and live birth. Reprod BioMed Online. 2009;19:72–8.PubMedCrossRef
18.
go back to reference Nielsen J, Wohlert M. Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Hum Genet. 1991;87:81–3.PubMedCrossRef Nielsen J, Wohlert M. Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Hum Genet. 1991;87:81–3.PubMedCrossRef
19.
go back to reference 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;101:656–63.PubMedCrossRef 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;101:656–63.PubMedCrossRef
20.
go back to reference Capalbo A, Hoffmann ER, Cimadomo D, Maria Ubaldi F, Rienzi L. Human female meiosis revised: new insights into the mechanisms of chromosome segregation and aneuploidies from advanced genomics and time-lapse imaging. Hum Reprod Update. 2017;23:706–22.PubMedCrossRef Capalbo A, Hoffmann ER, Cimadomo D, Maria Ubaldi F, Rienzi L. Human female meiosis revised: new insights into the mechanisms of chromosome segregation and aneuploidies from advanced genomics and time-lapse imaging. Hum Reprod Update. 2017;23:706–22.PubMedCrossRef
21.
go back to reference Mroz K, Hassold T, Hunt PA. Meiotic aneuploidy in the XXY mouse: evidence that a compromised testicular environment increases the incidence of meiotic error. Hum Reprod. 1998;14:1151–6.CrossRef Mroz K, Hassold T, Hunt PA. Meiotic aneuploidy in the XXY mouse: evidence that a compromised testicular environment increases the incidence of meiotic error. Hum Reprod. 1998;14:1151–6.CrossRef
23.
go back to reference Munné S. Chromosome abnormalities and their relationship to morphology and development of human embryos. Reprod BioMed Online. 2006;12(2):234–53.PubMedCrossRef Munné S. Chromosome abnormalities and their relationship to morphology and development of human embryos. Reprod BioMed Online. 2006;12(2):234–53.PubMedCrossRef
24.
go back to reference Chatzimeletiou K, Morrison EE, Prapas N, Prapas Y, Handyside AH. The centrosome and early embryogenesis: clinical insights. Reprod BioMed Online. 2008;16(4):485–91.PubMedCrossRef Chatzimeletiou K, Morrison EE, Prapas N, Prapas Y, Handyside AH. The centrosome and early embryogenesis: clinical insights. Reprod BioMed Online. 2008;16(4):485–91.PubMedCrossRef
25.
go back to reference Sathananthan AH, Kola I, Osborne J, Trounson A, Ng SC, Bongso A, et al. Centrioles in the beginning of human development. Proc Natl Acad Sci U S A. 1991;88(11):4806–10.PubMedPubMedCentralCrossRef Sathananthan AH, Kola I, Osborne J, Trounson A, Ng SC, Bongso A, et al. Centrioles in the beginning of human development. Proc Natl Acad Sci U S A. 1991;88(11):4806–10.PubMedPubMedCentralCrossRef
26.
go back to reference Sathananthan AH. Human centriole: origin, & how it impacts fertilization, embryogenesis, infertility & cloning. Indian J Med Res. 2009;129(4):348–50.PubMed Sathananthan AH. Human centriole: origin, & how it impacts fertilization, embryogenesis, infertility & cloning. Indian J Med Res. 2009;129(4):348–50.PubMed
27.
go back to reference Martin-Ponthieu A, Wouters-Tyrou D, Pudlo B, Buisine E, Sautiere UP. Isolation and characterization of a small putative zinc finger protein from cuttlefish epididymal sperm cells. Eur J Biochem. 1994;220:463–8.PubMedCrossRef Martin-Ponthieu A, Wouters-Tyrou D, Pudlo B, Buisine E, Sautiere UP. Isolation and characterization of a small putative zinc finger protein from cuttlefish epididymal sperm cells. Eur J Biochem. 1994;220:463–8.PubMedCrossRef
28.
go back to reference Carrell DT, Emery BR, Wilcox AL, Campbell B, Erickson L, Hatasaka HH, et al. Sperm chromosome aneuploidy as related to male factor infertility and some ultrastructure defects. Arch Androl. 2004;50:181–5.PubMedCrossRef Carrell DT, Emery BR, Wilcox AL, Campbell B, Erickson L, Hatasaka HH, et al. Sperm chromosome aneuploidy as related to male factor infertility and some ultrastructure defects. Arch Androl. 2004;50:181–5.PubMedCrossRef
29.
go back to reference Vegetti W, Van Assche E, Frias A, Verheyen G, Bianchi MM, Bonduelle M, et al. Correlation between semen parameters and sperm aneuploidy rates investigated by fluorescence in-situ hybridization in infertile men. Hum Reprod. 2000;15(2):351–65.PubMedCrossRef Vegetti W, Van Assche E, Frias A, Verheyen G, Bianchi MM, Bonduelle M, et al. Correlation between semen parameters and sperm aneuploidy rates investigated by fluorescence in-situ hybridization in infertile men. Hum Reprod. 2000;15(2):351–65.PubMedCrossRef
30.
go back to reference Hassold T, Abruzzo M, Adkins K, Griffin D, Merril M, Saker D, et al. Human aneuploidy incidence, origin and etiology. Environ Mol Mutagen. 1996;28:167–75.PubMedCrossRef Hassold T, Abruzzo M, Adkins K, Griffin D, Merril M, Saker D, et al. Human aneuploidy incidence, origin and etiology. Environ Mol Mutagen. 1996;28:167–75.PubMedCrossRef
31.
32.
go back to reference Rodrigo L, Peinado V, Mateu E, Remohi J, Pellicer A, Simon C, et al. Impact of different patterns of sperm chromosomal abnormalities on the chromosomal constitution of preimplantation embryos. Fertil Steril. 2010;94:1380–6.PubMedCrossRef Rodrigo L, Peinado V, Mateu E, Remohi J, Pellicer A, Simon C, et al. Impact of different patterns of sperm chromosomal abnormalities on the chromosomal constitution of preimplantation embryos. Fertil Steril. 2010;94:1380–6.PubMedCrossRef
33.
go back to reference Desai N, Gill P, Tadros N, Goldberg J, Sabanegh E, Falcone T. Azoospermia end embryo morphokinetics: testicular sperm-derived embryos exhibit delays in early cell cycle events and increases arrest prior to compaction. J Assist Reprod Genet. 2018;35:1339–48.PubMedPubMedCentralCrossRef Desai N, Gill P, Tadros N, Goldberg J, Sabanegh E, Falcone T. Azoospermia end embryo morphokinetics: testicular sperm-derived embryos exhibit delays in early cell cycle events and increases arrest prior to compaction. J Assist Reprod Genet. 2018;35:1339–48.PubMedPubMedCentralCrossRef
34.
go back to reference Neyer A, Zintz M, Stecher A, Bach M, Wirleitner B. The impact of paternal factors on cleavage stage and blastocyst development analyzed by time-lapse imaging-a retrospective observational study. J Assist Reprod Genet. 2015;32:1607–14.PubMedPubMedCentralCrossRef Neyer A, Zintz M, Stecher A, Bach M, Wirleitner B. The impact of paternal factors on cleavage stage and blastocyst development analyzed by time-lapse imaging-a retrospective observational study. J Assist Reprod Genet. 2015;32:1607–14.PubMedPubMedCentralCrossRef
35.
go back to reference Lammers J, Splingart C, Catteau A, David L, Barriere P, Freour T. Does sperm origin affect embryo morphokinetic parameters? J Assist Reprod Genet. 2015;32:1325–32.PubMedPubMedCentralCrossRef Lammers J, Splingart C, Catteau A, David L, Barriere P, Freour T. Does sperm origin affect embryo morphokinetic parameters? J Assist Reprod Genet. 2015;32:1325–32.PubMedPubMedCentralCrossRef
36.
go back to reference Mangoli E, Khalili MA, Talebi AR, Ghasemi-Esmailabad S, Hosseini A. Is there a correlation between sperm parameters and chromatin quality with embryo morphokinetics in patients with male infertility? Andrologia. 2018;50(5):e12997.PubMedCrossRef Mangoli E, Khalili MA, Talebi AR, Ghasemi-Esmailabad S, Hosseini A. Is there a correlation between sperm parameters and chromatin quality with embryo morphokinetics in patients with male infertility? Andrologia. 2018;50(5):e12997.PubMedCrossRef
37.
go back to reference Scarselli F, Casciani V, Cursio E, Muzzi S, Colasante A, Gatti S, et al. Influence of human sperm origin, testicular or ejaculated, on embryo morphokinetic development. Andrologia. 2018;50(8):e13061.PubMedCrossRef Scarselli F, Casciani V, Cursio E, Muzzi S, Colasante A, Gatti S, et al. Influence of human sperm origin, testicular or ejaculated, on embryo morphokinetic development. Andrologia. 2018;50(8):e13061.PubMedCrossRef
38.
go back to reference Montag M. Morphokinetics and embryo aneuploidy: has time come or not yet? Reprod BioMed Online. 2013;26:528–30.PubMedCrossRef Montag M. Morphokinetics and embryo aneuploidy: has time come or not yet? Reprod BioMed Online. 2013;26:528–30.PubMedCrossRef
40.
go back to reference Schatten H, Sun QY. The functional significance of centrosomes in mammalian meiosis, fertilization, development, nuclear transfer, and stem cell differentiation. Environ Mol Mutagen. 2009;50(8):620–36.PubMedCrossRef Schatten H, Sun QY. The functional significance of centrosomes in mammalian meiosis, fertilization, development, nuclear transfer, and stem cell differentiation. Environ Mol Mutagen. 2009;50(8):620–36.PubMedCrossRef
41.
go back to reference Schatten H, Sun QY. The role of centrosomes in fertilization, cell division and establishment of asymmetry during embryo development. Semin Cell Dev Biol. 2010;21(2):174–84.PubMedCrossRef Schatten H, Sun QY. The role of centrosomes in fertilization, cell division and establishment of asymmetry during embryo development. Semin Cell Dev Biol. 2010;21(2):174–84.PubMedCrossRef
42.
go back to reference Palermo GD, Colombero LT, Rosenwaks Z. The human sperm centrosome is responsible for normal syngamy and early embryonic development. Rev Reprod. 1997;2(1):19–27.PubMedCrossRef Palermo GD, Colombero LT, Rosenwaks Z. The human sperm centrosome is responsible for normal syngamy and early embryonic development. Rev Reprod. 1997;2(1):19–27.PubMedCrossRef
43.
go back to reference Navara CS, First NL, Schatten G. Phenotypic variations among paternal centrosomes expressed within the zygote as disparate microtubule lengths and sperm aster organization: correlations between centrosome activity and developmental success. Proc Natl Acad Sci U S A. 1996;93(11):5384–8.PubMedPubMedCentralCrossRef Navara CS, First NL, Schatten G. Phenotypic variations among paternal centrosomes expressed within the zygote as disparate microtubule lengths and sperm aster organization: correlations between centrosome activity and developmental success. Proc Natl Acad Sci U S A. 1996;93(11):5384–8.PubMedPubMedCentralCrossRef
Metadata
Title
High rates of aneuploidy, mosaicism and abnormal morphokinetic development in cases with low sperm concentration
Authors
Semra Kahraman
Yucel Sahin
Hakan Yelke
Yesim Kumtepe
Mehmet A. Tufekci
Cigdem C. Yapan
Mesut Yesil
Murat Cetinkaya
Publication date
01-03-2020
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 3/2020
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-019-01673-w

Other articles of this Issue 3/2020

Journal of Assisted Reproduction and Genetics 3/2020 Go to the issue