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Journal of Assisted Reproduction and Genetics

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Open Access 01-10-2019 | ICSI | Assisted Reproduction Technologies

A treatment approach for couples with disrupted sperm DNA integrity and recurrent ART failure

Authors: Alessandra Parrella, Derek Keating, Stephanie Cheung, Philip Xie, Joshua D. Stewart, Zev Rosenwaks, Gianpiero D. Palermo

Published in: Journal of Assisted Reproduction and Genetics | Issue 10/2019

Abstract

Objective

To test a novel method to select spermatozoa with high chromatin integrity.

Design

Specimens with high sperm chromatin fragmentation (SCF) were selected by density gradient selection (DGS) and microfluidic sperm sorting (MSS).

Setting

Academic medical center.

Patient(s)

Ejaculates from consenting men were processed by DGS/MSS. Couples underwent ICSI cycles with spermatozoa processed by DGS/MSS. Clinical outcomes were evaluated after embryo transfer.

Intervention(s)

SCF was measured by TUNEL. ICSI with spermatozoa selected by DGS and MSS was performed.

Main outcome measure(s)

Fertilization, embryo implantation, and pregnancy outcomes were compared between DGS and MSS.

Result(s)

A total of 23 men had an average SCF of 20.7 ± 10%. After DGS and MSS, the SCF was 12.5 ± 5% and 1.8 ± 1%, respectively. In couples who underwent ICSI, the average SCF was 28.8 ± 9%, which fell to 21.0 ± 9% after DGS and 1.3 ± 0.7% after MSS. Four couples underwent 11 ICSI cycles with DGS and achieved one (25%) pregnancy that resulted in pregnancy loss. In four subsequent ICSI cycles with MSS, an ongoing clinical pregnancy rate of 50% was achieved. Five additional couples underwent 12 cycles of ICSI with DGS. After preimplantation genetic testing for aneuploidy, 30.3% of the embryos were euploid. One pregnancy was achieved, resulting in pregnancy loss. With MSS, 31.5% of the embryos were euploid and 4 couples obtained a pregnancy. Finally, sixteen couples underwent 20 ICSI cycles solely with MSS at our center. Of these couples, 8 had failed 13 ICSI cycles with DGS elsewhere. These couples achieved an overall implantation of 34.5% (10/29) and a pregnancy rate of 58.8% (10/17).

Conclusion(s)

Microfluidic selection yielded spermatozoa with optimal genomic integrity and improved chances of obtaining a euploid conceptus.

Thoma ME, McLain AC, Louis JF, King RB, Trumble AC, Sundaram R, et al. Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach. Fertil Steril. 2013;99(5):1324–31.e1. https://doi.org/10.1016/j.fertnstert.2012.11.037.PubMedPubMedCentralCrossRef

WHO laboratory manual for the examination and processing of human semen. 5th ed. ed. Geneva : World Health Organization; 2010.

Intracytoplasmic sperm injection (ICSI) in 2006: evidence and evolution. Human reproduction update. 2007;13(6):515–26. doi:https://doi.org/10.1093/humupd/dmm024.

Zini A, Fischer MA, Sharir S, Shayegan B, Phang D, Jarvi K. Prevalence of abnormal sperm DNA denaturation in fertile and infertile men. Urology. 2002;60(6):1069–72.PubMedCrossRef

Belloc S, Hazout A, Zini A, Merviel P, Cabry R, Chahine H, et al. How to overcome male infertility after 40: influence of paternal age on fertility. Maturitas. 2014;78(1):22–9. https://doi.org/10.1016/j.maturitas.2014.02.011.

Palermo GD, Neri QV, Cozzubbo T, Rosenwaks Z. Perspectives on the assessment of human sperm chromatin integrity. Fertil Steril. 2014;102(6):1508–17. https://doi.org/10.1016/j.fertnstert.2014.10.008.

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. Reprod BioMed Online. 2013;26(1):68–78. https://doi.org/10.1016/j.rbmo.2012.09.019.PubMedCrossRef

Zeyad A, Hamad M, Amor H, Hammadeh ME. Relationships between bacteriospermia, DNA integrity, nuclear protamine alteration, sperm quality and ICSI outcome. Reprod Biol. 2018;18(1):115–21. https://doi.org/10.1016/j.repbio.2018.01.010.

Ashwood-Smith MJ, Edwards RG. DNA repair by oocytes. Mol Hum Reprod. 1996;2(1):46–51.PubMedCrossRef

10.

Menezo Y, Dale B, Cohen M. DNA damage and repair in human oocytes and embryos: a review. Zygote. 2010;18(4):357–65. https://doi.org/10.1017/s0967199410000286.PubMedCrossRef

11.

Sakkas D, Alvarez JG. Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis. Fertil Steril. 2010;93(4):1027–36. https://doi.org/10.1016/j.fertnstert.2009.10.046.

12.

Humm KC, Sakkas D. Role of increased male age in IVF and egg donation: is sperm DNA fragmentation responsible? Fertil Steril. 2013;99(1):30–6. https://doi.org/10.1016/j.fertnstert.2012.11.024.

13.

O’Neill CL, Parrella A, Keating D, Cheung S, Rosenwaks Z, Palermo GD. A treatment algorithm for couples with unexplained infertility based on sperm chromatin assessment. J Assist Reprod Genet. 2018;35(10):1911–7. https://doi.org/10.1007/s10815-018-1270-x.PubMedPubMedCentralCrossRef

14.

Greco E, Scarselli F, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, et al. Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa. Hum Reprod. 2005;20(1):226–30. https://doi.org/10.1093/humrep/deh590.PubMedCrossRef

15.

Esteves SC. Testicular versus ejaculated sperm should be used for intracytoplasmic sperm injection (ICSI) in cases of infertility associated with sperm DNA fragmentation | Opinion: Yes. Int braz j Urol : Off J Braz Soc Urol. 2018;44(4):667–75. https://doi.org/10.1590/S1677-5538.IBJU.2018.04.03.CrossRef

16.

Parrella A, O’Neill C, Chow S, Goldstein M, Rosenwaks Z, Palermo GD. Sperm source influences the extent of DNA fragmentation and shapes reproductive outcome. Fertil Steril. 2017;108(3):e309. https://doi.org/10.1016/j.fertnstert.2017.07.914.CrossRef

17.

Nosrati R, Graham PJ, Zhang B, Riordon J, Lagunov A, Hannam TG, et al. Microfluidics for sperm analysis and selection. Nat Rev Urol. 2017;14:707–30. https://doi.org/10.1038/nrurol.2017.175https://www.nature.com/articles/nrurol.2017.175#supplementary-information.PubMedCrossRef

18.

Suarez SS, Wu M. Microfluidic devices for the study of sperm migration. MHR: Basic Sci Reprod Med. 2017;23(4):227–34. https://doi.org/10.1093/molehr/gaw039.CrossRef

19.

Eravuchira PJ, Mirsky SK, Barnea I, Levi M, Balberg M, Shaked NT. Individual sperm selection by microfluidics integrated with interferometric phase microscopy. Methods. 2018;136:152–9. https://doi.org/10.1016/j.ymeth.2017.09.009.

20.

Samuel R, Feng H, Jafek A, Despain D, Jenkins T, Gale BJTA et al. Microfluidic—based sperm sorting & analysis for treatment of male infertility 2018. 2018:S336-SS47.

21.

Quinn MM, Jalalian L, Ribeiro S, Ona K, Demirci U, Cedars MI, et al. Microfluidic sorting selects sperm for clinical use with reduced DNA damage compared to density gradient centrifugation with swim-up in split semen samples. Hum Reprod(Oxford, England). 2018. https://doi.org/10.1093/humrep/dey239.

22.

Huang JYJ, Rosenwaks Z. Assisted reproductive techniques. In: Rosenwaks Z, Wassarman PM, editors. Human fertility: methods and protocols. New York, NY: Springer New York; 2014. p. 171–231.CrossRef

23.

Pereira N, Neri QV, Lekovich JP, Palermo GD, Rosenwaks Z. The role of in-vivo and in-vitro maturation time on ooplasmic dysmaturity. Reprod BioMed Online. 2016;32(4):401–6. https://doi.org/10.1016/j.rbmo.2016.01.007.PubMedCrossRef

24.

Neri QV, Lee B, Rosenwaks Z, Machaca K, Palermo GD. Understanding fertilization through intracytoplasmic sperm injection (ICSI). Cell Calcium. 2014;55(1):24–37. https://doi.org/10.1016/j.ceca.2013.10.006.

25.

Irani M, O’Neill C, Palermo GD, Xu K, Zhang C, Qin X, et al. Blastocyst development rate influences implantation and live birth rates of similarly graded euploid blastocysts. Fertil Steril. 2018;110(1):95–102.e1. https://doi.org/10.1016/j.fertnstert.2018.03.032.PubMedCrossRef

26.

Kuwayama M. Highly efficient vitrification for cryopreservation of human oocytes and embryos: the Cryotop method. Theriogenology. 2007;67(1):73–80. https://doi.org/10.1016/j.theriogenology.2006.09.014.

27.

Kang H-J. Programmed versus natural frozen embryo transfer: which is the best nest? Fertil Steril. 2018;110(4):636–7. https://doi.org/10.1016/j.fertnstert.2018.06.020.

28.

Brandriff B, Pedersen R. Repair of the ultraviolet-irradiated male genome in fertilized mouse eggs. Science. 1981;211(4489):1431–3. https://doi.org/10.1126/science.7466400.

29.

Ashwood-Smith MJ, Edwards RG. Genetics and human conception: DNA repair by oocytes. MHR: Basic Sci Reprod Med. 1996;2(1):46–51. https://doi.org/10.1093/molehr/2.1.46.CrossRef

30.

Esteves SC, Roque M, Bradley CK, Garrido N. Reproductive outcomes of testicular versus ejaculated sperm for intracytoplasmic sperm injection among men with high levels of DNA fragmentation in semen: systematic review and meta-analysis. Fertil Steril. 2017;108(3):456–67.e1. https://doi.org/10.1016/j.fertnstert.2017.06.018.PubMedCrossRef

31.

Schlegel PN, Su LM. Physiological consequences of testicular sperm extraction. Human reproduction (Oxford, England). 1997;12(8):1688–92.CrossRef

32.

Bucar S, Goncalves A, Rocha E, Barros A, Sousa M, Sa R. DNA fragmentation in human sperm after magnetic-activated cell sorting. J Assist Reprod Genet. 2015;32(1):147–54. https://doi.org/10.1007/s10815-014-0370-5.PubMedCrossRef

33.

Cakar Z, Cetinkaya B, Aras D, Koca B, Ozkavukcu S, Kaplanoglu İ, et al. Does combining magnetic-activated cell sorting with density gradient or swim-up improve sperm selection? J Assist Reprod Genet. 2016;33(8):1059–65. https://doi.org/10.1007/s10815-016-0742-0.PubMedPubMedCentralCrossRef

34.

Shirota K, Yotsumoto F, Itoh H, Obama H, Hidaka N, Nakajima K, et al. Separation efficiency of a microfluidic sperm sorter to minimize sperm DNA damage. Fertil Steril. 2016;105(2):315–21.e1. https://doi.org/10.1016/j.fertnstert.2015.10.023.PubMedCrossRef

35.

Amiri I, Ghorbani M, Heshmati S. Comparison of the DNA fragmentation and the sperm parameters after processing by the density gradient and the swim up methods. J Clin Diagnostic Res : JCDR. 2012;6(9):1451–3. https://doi.org/10.7860/JCDR/2012/4198.2530.CrossRef

36.

Aitken RJ, Clarkson JS. Significance of reactive oxygen species and antioxidants in defining the efficacy of sperm preparation techniques. J Androl. 1988;9(6):367–76.PubMedCrossRef

37.

Iwasaki A, Gagnon C. Formation of reactive oxygen species in spermatozoa of infertile patients. Fertil Steril. 1992;57(2):409–16.PubMedCrossRef

38.

Zini A, Finelli A, Phang D, Jarvi K. Influence of semen processing technique on human sperm DNA integrity. Urology. 2000;56(6):1081–4.PubMedCrossRef

39.

Gil M, Sar-Shalom V, Melendez Sivira Y, Carreras R, Checa MA. Sperm selection using magnetic activated cell sorting (MACS) in assisted reproduction: a systematic review and meta-analysis. J Assist Reprod Genet. 2013;30(4):479–85. https://doi.org/10.1007/s10815-013-9962-8.PubMedPubMedCentralCrossRef

40.

Enciso M, Iglesias M, Galán I, Sarasa J, Gosálvez A, Gosálvez J. The ability of sperm selection techniques to remove single- or double-strand DNA damage. Asian J Androl. 2011;13(5):764–8. https://doi.org/10.1038/aja.2011.46.PubMedPubMedCentralCrossRef

41.

García-Peiró A, Navarro J, Ribas-Maynou J, Benet J, Abad C, Amengual MJ. Alkaline and neutral Comet assay profiles of sperm DNA damage in clinical groups. Hum Reprod. 2012;27(3):652–8. https://doi.org/10.1093/humrep/der461.PubMedCrossRef

42.

Ribas-Maynou J, García-Peiró A, Fernandez-Encinas A, Amengual MJ, Prada E, Cortés P, et al. Double stranded sperm DNA breaks, measured by comet assay, are associated with unexplained recurrent miscarriage in couples without a female factor. PLoS One. 2012;7(9):e44679. https://doi.org/10.1371/journal.pone.0044679.PubMedPubMedCentralCrossRef

Title: A treatment approach for couples with disrupted sperm DNA integrity and recurrent ART failure
Authors: Alessandra Parrella
Derek Keating
Stephanie Cheung
Philip Xie
Joshua D. Stewart
Zev Rosenwaks
Gianpiero D. Palermo
Publication date: 01-10-2019
Publisher: Springer US
Keyword: ICSI
Published in: Journal of Assisted Reproduction and Genetics / Issue 10/2019
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-019-01543-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

A treatment approach for couples with disrupted sperm DNA integrity and recurrent ART failure

Abstract

Objective

Design

Setting

Patient(s)

Intervention(s)

Main outcome measure(s)

Result(s)

Conclusion(s)

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objective

Design

Setting

Patient(s)

Intervention(s)

Main outcome measure(s)

Result(s)

Conclusion(s)

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