Impact of Paternal Genome with a High DNA Fragmentation Index(>60%) on Early Embryonic Development

Authors

  • A. Zoghmar
  • L. Ounisa
  • L. Rouabah Pr
  • M Bensaada
  • S. Benbouhedia
  • A. Rouabah Pra1a
  • M. Hachemi

DOI:

https://doi.org/10.31907/2309-4400.2021.09.03

Keywords:

DNA Fragmentation Index, ICSI, Fertilization Rate, Embryos Quality.

Abstract

Objectives: The objective of this study is to propose thresholds of the sperm DNA fragmentation rate (IFA≤30% IFA31%-60% IFA>60%), in order to assess the clinical effects of the paternal genome on intra cytoplasmic sperm injection parameters, in particular the effect of the latter on early embryonic development. Materials and Methods: The procedure is a retrospective study, which involved 101 patients enrolled in an ICSI program with their partners. The index of spermatic DNA fragmentation rate was measured using the Sperm Chromatin Dispersion assay. Results: There is a negative correlation between high levels of the spermatic DNA fragmentation index and spermiological characteristics: Concentration P=0.002 and mobility P=0.0001. For ICSI results, there are different observations on the existence of a correlation between the spermatic DNA fragmentation index and fertility rate. On the other hand, the rate of sperm DNA fragmentation does not seem to influence early embryonic development, and even couples whose partners have a high fragmentation index manage to obtain the best quality embryos (P=0.002). We observe a decrease in the rate of implantation with an increase in the rate of alteration of the sperm genome, but this remains insignificant P > 0.05. Conclusion: ICSI remains the only alternative for men with a high rate of sperm DNA fragmentation. Moreover, the operator seems to influence the results more than is suggested. This does not exclude the paternal effect which may influence the quality of the concepltus later on.

References

Lewis SE, Aitken RJ, Conner SJ, De Iuliis G, Evenson DP, Henkel R, et al. The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment. Reproductive biomedicine online. 2013;27 (4):325–337. https://doi.org/10.1016/j.rbmo.2013.06.014

Evenson DP, Darzynkiewicz Z, Melamed MR. Relation of mammalian sperm chromatin heterogeneity to fertility. Science. 1980;210 (4474):1131–1133. https://doi.org/10.1126/science.7444440

Gorczyca W, Traganos F, Jesionowska H, Darzynkiewicz Z. Presence of DNA strand breaks and increased sensitivity of DNA in situ to denaturation in abnormal human sperm cells: analogy to apoptosis of somatic cells. Experimental cell research. 1993;207 (1):202– 205. https://doi.org/10.1006/excr.1993.1182

Klaude M, Eriksson S, Nygren J, Ahnström G. The comet assay: mechanisms and technical considerations. Mutation Research/DNA Repair. 1996;363 (2):89–96. https://doi.org/10.1016/0921-8777(95)00063-1

Fernández JL, Muriel L, Rivero MT, Goyanes V, Vazquez R, Alvarez JG. The Sperm Chromatin Dispersion Test: A Simple Method for the Determination of Sperm DNA Fragmentation. Journal of Andrology. 2003;24 (1):59–66.

Benchaib M, Braun V, Lornage J, Hadj S, Salle B, Lejeune H, et al. Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique. Human Reproduction. 2003;18 (5):1023–1028. https://doi.org/10.1093/humrep/deg228

López G, Lafuente R, Checa MA, Carreras R, Brassesco M. Diagnostic value of sperm DNA fragmentation and sperm high-magnification for predicting outcome of assisted reproduction treatment. Asian journal of andrology. 2013;15(6):790. https://doi.org/10.1038/aja.2013.81

Simon L, Murphy K, Shamsi MB, Liu L, Emery B, Aston KI, et al. Paternal influence of sperm DNA integrity on early embryonic development. Human Reproduction. 2014;29 (11):2402–2412. https://doi.org/10.1093/humrep/deu228

Simon L, Proutski I, Stevenson M, Jennings D, McManus J, Lutton D, et al. Sperm DNA damage has a negative association with live-birth rates after IVF. Reproductive biomedicine online. 2013;26 (1):68–78. https://doi.org/10.1016/j.rbmo.2012.09.019

Irvine DS, Twigg JP, Gordon EL, Fulton N, Milne PA, Aitken RJ. DNA integrity in human spermatozoa: relationships with semen quality. Journal of andrology. 2000;21(1):33–44.

Erenpreiss J, Elzanaty S, Giwercman A. Sperm DNA damage in men from infertile couples. Asian journal of andrology. 2008;10 (5):786–790. https://doi.org/10.1111/j.1745-7262.2008.00417.x

Marchetti C, Obert G, Deffosez A, Formstecher P, Marchetti P. Study of mitochondrial membrane potential, reactive oxygen species, DNA fragmentation and cell viability by flow cytometry in human sperm. Human Reproduction. 2002; 17 (5):1257–1265. https://doi.org/10.1093/humrep/17.5.1257

Guerin P, Matillon C, Bleau G, Levy R, Menezo Y. Impact of sperm DNA fragmentation on ART outcome. Gynecologie, obstetrique & fertilite. 2005;33 (9):665–668. https://doi.org/10.1016/j.gyobfe.2005.07.015

Simon L, Castillo J, Oliva R, Lewis SE. Relationships between human sperm protamines, DNA damage and assisted reproduction outcomes. Reproductive biomedicine online. 2011;23 (6):724–734. https://doi.org/10.1016/j.rbmo.2011.08.010

Speyer BE, Pizzey AR, Ranieri M, Joshi R, Delhanty JDA, Serhal P. Fall in implantation rates following ICSI with sperm with high DNA fragmentation. Human Reproduction. 2010;25 (7):1609–1618. https://doi.org/10.1093/humrep/deq116

Benchaib M, Lornage J, Mazoyer C, Lejeune H, Salle B, Guerin JF. Sperm deoxyribonucleic acid fragmentation as a prognostic indicator of assisted reproductive technology outcome. Fertility and sterility. 2007;87 (1):93–100. https://doi.org/10.1016/j.fertnstert.2006.05.057

Evenson DP, Kasperson K, Wixon RL. Analysis of sperm DNA fragmentation using flow cytometry and other techniques. Society of Reproduction and Fertility supplement. 2007;65 93–113.

Zini A, Boman JM, Belzile E, Ciampi A. Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Human reproduction. 2008;23 (12):2663–2668. https://doi.org/10.1093/humrep/den321

Meseguer M, Martinez-Conejero JA, O’Connor JE, Pellicer A, Remohí J, Garrido N. The significance of sperm DNA oxidation in embryo development and reproductive outcome in an oocyte donation program: a new model to study a male infertility prognostic factor. Fertility and sterility. 2008;89 (5):1191–1199. https://doi.org/10.1016/j.fertnstert.2007.05.005

Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. The Lancet. 1992;340 (8810):17–18. https://doi.org/10.1016/0140-6736(92)92425-f

Fragouli E, Alfarawati S, Spath K, Wells D. Morphological and cytogenetic assessment of cleavage and blastocyst stage embryos. Molecular human reproduction. 2013;20 (2):117– 126. https://doi.org/10.1093/molehr/gat073

Fernández JL, Muriel L, Goyanes V, Segrelles E, Gosálvez J, Enciso M, et al. Simple determination of human sperm DNA fragmentation with an improved sperm chromatin dispersion test. Fertility and Sterility. 2005 1;84 (4):833–42. https://doi.org/10.1016/j.fertnstert.2004.11.089

Evenson, D. P., Jost, L. K., Marshall, D., Zinaman, M. J., Clegg, E., Purvis, K., Claussen, O. P. (1999)- Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Human Reproduction, 14 (4), 1039–1049. https://doi.org/10.1093/humrep/14.4.1039

Zini, A., Bielecki, R., Phang, D., & Zenzes, M. T. (2001)-Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men. Fertility and Sterility, 75(4), 674–677. https://doi.org/10.1016/s0015-0282(00)01796-9

Borini A, Tarozzi N, Bizzaro D, Bonu MA, Fava L, Flamigni C, et al. Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Human reproduction. 2006;21 (11):2876–2881. https://doi.org/10.1093/humrep/del251

Bungum M, Humaidan P, Axmon A, Spano M, Bungum L, Erenpreiss J, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Human reproduction. 2007;22 (1):174–179. https://doi.org/10.1093/humrep/del326

Zhang Z, Zhu L-L, Jiang H-S, Chen H, Chen Y, Dai Y-T. Predictors of pregnancy outcome for infertile couples attending IVF and ICSI programmes. Andrologia. 2016;48 (9):962–969. https://doi.org/10.1111/and.12525

Simon, Luke, Emery, B. R., & Carrell, D. T. (2017)- Diagnosis and impact of sperm DNA alterations in assisted reproduction. Best Practice & Research Clinical Obstetrics & Gynaecology, 44, 38–56. https://doi.org/10.1016/j.bpobgyn.2017.07.003

Winkle T, Rosenbusch B, Gagsteiger F, Paiss T, Zoller N. The correlation between male age, sperm quality and sperm DNA fragmentation in 320 men attending a fertility center. Journal of assisted reproduction and genetics. 2009;26 (1):41–46. https://doi.org/10.1007/s10815-008-9277-3

Klonoff-Cohen, H. S., & Natarajan, L. The effect of advancing paternal age on pregnancy and live birth rates in couples undergoing in vitro fertilization or gamete intrafallopian transfer. American Journal of Obstetrics and Gynecology, 2004; 191(2), 507–514. https://doi.org/10.1016/j.ajog.2004.01.035

Yatsenko, A. N., & Turek, P. J. - Reproductive genetics and the aging male. Journal of Assisted Reproduction and Genetics, 2018:1–9. https://doi.org/10.1007/s10815-018-1148-y

Shamsi MB, Venkatesh S, Tanwar M, Talwar P, Sharma RK, Dhawan A, et al. DNA integrity and semen quality in men with low seminal antioxidant levels. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2009;665 (1):29–36. https://doi.org/10.1016/j.mrfmmm.2009.02.017

Chi H-J, Chung D-Y, Choi S-Y, Kim J-H, Kim G-Y, Lee J-S, et al. Integrity of human sperm DNA assessed by the neutral comet assay and its relationship to semen parameters and clinical outcomes for the IVF-ET program. Clinical and experimental reproductive medicine. 2011;38 (1):10–17. https://doi.org/10.5653/cerm.2011.38.1.10

Ganzer LM, Larcher JS, Avramovich VI, Tissera AD, Estofan GM. Relationship between semen parameters and sperm DNA fragmentation. Fertility and Sterility. 2017;108 (3):e137–e138. https://doi.org/10.1016/j.fertnstert.2017.07.415

Lu J-C, Jing J, Chen L, Ge Y-F, Feng R-X, Liang Y-J, et al. Analysis of human sperm DNA fragmentation index (DFI) related factors: a report of 1010 subfertile men in China. Reproductive Biology and Endocrinology. 2018;16 (1):23. https://doi.org/10.1186/s12958-018-0345-y

Lin M-H, Lee RK-K, Li S-H, Lu C-H, Sun F-J, Hwu Y-M. Sperm chromatin structure assay parameters are not related to fertilization rates, embryo quality, and pregnancy rates in in vitro fertilization and intracytoplasmic sperm injection, but might be related to spontaneous abortion rates. Fertility and sterility. 2008;90 (2):352–359. https://doi.org/10.1016/j.fertnstert.2007.06.018

Payne JF, Raburn DJ, Couchman GM, Price TM, Jamison MG, Walmer DK. Redefining the relationship between sperm deoxyribonucleic acid fragmentation as measured by the sperm chromatin structure assay and outcomes of assisted reproductive techniques. Fertility and sterility. 2005;84 (2):356–364. https://doi.org/10.1016/j.fertnstert.2005.02.032

Jiang HH, He XJ, Song B, Cao YX. Sperm chromatin integrity test for predicting the outcomes of IVF and ICSI. Zhonghua Nan Ke Xue. 2011 ;17 (12):1083–6.

Esbert M, Pacheco A, Vidal F, Florensa M, Riqueros M, Ballesteros A, et al. Impact of sperm DNA fragmentation on the outcome of IVF with own or donated oocytes. Reproductive BioMedicine Online. 2011 ; 23(6):704–10. https://doi.org/10.1016/j.rbmo.2011.07.010

Dar S, Grover SA, Moskovtsev SI, Swanson S, Baratz A, Librach CL. In vitro fertilization– intracytoplasmic sperm injection outcome in patients with a markedly high DNA fragmentation index (> 50%). Fertility and sterility. 2013;100 (1):75–80. https://doi.org/10.1016/j.fertnstert.2013.03.011

Plachot, M., & Crozet, N. Fertilization abnormalities in human in-vitro fertilization. Human Reproduction, 1992; 7 (1), 89–94. https://doi.org/10.1093/humrep/7.suppl_1.89

Host, E., Lindenberg, S., & Smidt-Jensen, S. (2000)- The role of DNA strand breaks in human spermatozoa used for IVF and ICSI. Acta Obstetricia et Gynecologica Scandinavica, 79 (7), 559–563. https://doi.org/10.1034/j.1600- 0412.2000.079007559.x

Sakkas D, Urner F, Bianchi PG, Bizzaro D, Wagner I, Jaquenoud N, et al. Sperm chromatin anomalies can influence decondensation after intracytoplasmic sperm injection. Human Reproduction. 1996;11 (4):837–843. https://doi.org/10.1093/oxfordjournals.humrep.a0 19263

Bazrgar M, Gourabi H, Yazdi PE, Vazirinasab H, Fakhri M, Hassani F, Valojerdi MR. DNA repair signalling pathway genes are overexpressed in poor-quality pre-implantation human embryos with complex aneuploidy. Eur J Obstet Gynecol Reprod Biol 2014;175:152–156. https://doi.org/10.1016/j.ejogrb.2014.01.010

Braude, P., Bolton, V., & Moore, S. (1988)- Human gene expression first occurs between the four-and eight-cell stages of preimplantation development. Nature, 332 (6163), 459. https://doi.org/10.1038/332459a0

Cooke MS, Evans MD, Dizdaroglu M, Lunec J. Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 2003;(17) :1195–214. https://doi.org/10.1096/fj.02-0752rev

Schmid TE, Eskenazi B, Baumgartner A, Marchetti F, Young S, Weldon R, et al. The effects of male age on sperm DNA damage in healthy non-smokers. Human Reproduction. 2006;22 (1):180–187. https://doi.org/10.1093/humrep/del338

Poncelet, C., & Sifer, C. (2011)-Physiologie, pathologie et thérapie de la reproduction chez l’humain. Springer Science & Business Media. https://doi.org/10.1007/978-2-8178-0061-5

Guerin JF and Benchaib M. Tests d'exploration de la qualité nucléaire du spermatozoïde : relations avec la fertilité et la qualité du conceptus Gynécologie Obstétrique & Fertilité 2004 ; 32 (9) :799-802. https://doi.org/10.1016/j.gyobfe.2004.07.008

Hachemi M, Bensaada M, Rouabah A,Zoghmar A, Benbouhedja S, Rouabah L, Benchaib M. Effect of Spermatic Nuclear Quality on Live Birth Rates in Intracytoplasmic Sperm Injection 2019 12 (2): 123-129. https://doi.org/10.4103/jhrs.jhrs_81_18

Ji B-T, Shu X-O, Zheng W, Ying D-M, Linet MS, Wacholder S, et al. Paternal cigarette smoking and the risk of childhood cancer among offspring of nonsmoking mothers. Journal of the National Cancer Institute. 1997;89 (3):238–243. https://doi.org/10.1093/jnci/89.3.238

Bungum, M., Bungum, L., Lynch, K.-F., Wedlund, L., Humaidan, P., & Giwercman, A. - Spermatozoa DNA damage measured by sperm chromatin structure assay (SCSA) and birth characteristics in children conceived by IVF and ICSI. International Journal of Andrology, 2012; 35 (4), 485–490. https://doi.org/10.1111/j.1365-2605.2011.01222.x

Dhawan, V., Kumar, M., Deka, D., Malhotra, N., Singh, N., Dadhwal, V., & Dada, R. Paternal factors and embryonic development: Role in recurrent pregnancy loss. Andrologia, 2019; 51 (1), e13171. https://doi.org/10.1111/and.13171

Downloads

Published

2021-11-04 — Updated on 2022-04-25

Issue

Section

Articles