Modelo predictivo de fragmentación de ADN espermático usando parámetros evaluados en un espermatograma

Jimmy Portella; Rosmary López; Luis Noriega-Hoces; Luis Guzmán

doi:10.31403/rpgo.v60i106

Authors

Jimmy Portella Grupo PRANOR
Rosmary López Reprogenetics Latinoamerica
Luis Noriega-Hoces Clínica Concebir
Luis Guzmán Grupo PRANOR Reprogenetics Latinoamerica

DOI:

https://doi.org/10.31403/rpgo.v60i106

Abstract

Introduction: The spermatogram is used as a test of seminal quality. Recently, the sperm fragmentation test has demonstrated importance as sperm DNA integrity would affect clinical results in assisted reproduction treatments. Objectives: To determine spermatogram variables that would independently predict sperm DNA fragmentation index (SFI). Design: Retrospective, comparative study. Settings: Grupo PRANOR, Reprogenetics Latinoamerica, Clinica Concebir, Lima, Peru. Biologic material: Sperm. Methods: Individual variables and two models were compared: the first model considered percentage of sperm viability and patient’s age; the second model included percentage of motile sperms and age. Logistic regression analysis was done. Main outcome measures: Sperm viability, age. Results: Multivariate analysis showed that both models were significantly superior to individuals variables (p<0.01). The first model had non standardized coefficient values (95%CI) respectively of 0.200 (0.082 to 0.318) and -0.146 (-0.206 to -0.086). The second model had non standardized coefficient values (95%CI) respectively of -0.099 (-0.157 to -0.042) and 0.219 (0.99 to 0.339). Logistic regression analysis showed that the percentage of sperm viability and patient’s age predicted the probability of having an SFI over 30% with age non standardized coefficient values of 95%IC 0.034 (0.015 to 0.053) and viability percentage of

-0.043 (0.034 to 0.052). Additionally the second model had 95%CI respectively of -0.04 (-0.031 to -0.049) and 0.035 (0.017 to 0.053). Finally, a ROC curve to determine the superiority of some model over individual variables showed that areas under the curve (ABC) of model 1 (age and sperm viability) was 0.727 (95%CI = 0.665 to 0.790) and model 2 (age and sperm total motility) 0.675 (95%CI = 0.606 to 0.744), compared with ABC of percentage of sperm viability = 0.295 (95%CI = 0.229 to 0.362), sperm total motility ABC = 0.333 (95%CI = 0.264 to 0.403) and patient’s age with ABC 0.584 (95%CI = 0.510 to 0.658). Conclusions: Age, and sperm motility and viability independently correlated with SFI and consequently these variables could be used as predictors of DNA fragmentation percentage.

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References

Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril. 2009;92(5):1520-4.

Eisenberg ML, Lathi RB, Baker VL, Westphal LM, Milki AA, Nangia AK. Frequency of the male infertility evaluation: data from the national survey of family growth. J Urol. 2013;189(3):1030-4.

World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010, xiv: 271 pp.

Guzick DS, Overstreet JW, Factor-Litvak P, Brazil CK, Nakajima ST, Coutifaris C, et al. Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med. 2001;345(19):1388-93.

Irvine DS. Epidemiology and aetiology of male infertility. Hum Reprod. 1998;13 (Suppl 1):33-44.

Shah K, Sivapalan G, Gibbons N, Tempest H, Griffin DK. The genetic basis of infertility. Reproduction. 2003;126(1):13-25.

Younglai EV, Holloway AC, Foster WG. Environmental and occupational factors affecting fertility and IVF success. Hum Reprod Update. 2005;11(1):43-57.

O’Flynn O’Brien KL, Varghese AC, Agarwal A. The genetic causes of male factor infertility: a review. Fertil Steril. 2010;93(1):1-12.

Hamada A, Esteves SC, Nizza M, Agarwal A. Unexplained male infertility: diagnosis and management. International braz j urol. 2012;38(5):576-94.

DeRouchey J, Hoover B, Rau DC. A comparison of DNA compaction by arginine and lysine peptides: a physical basis for arginine rich protamines. Biochemistry. 2013;52(17):3000-9.

Miller D, Brinkworth M, Iles D. Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA, histones, protamines and epigenetics. Reproduction. 2010;139(2):287-301.

Noblanc A, Damon-Soubeyrand C, Karrich B, Henry-Berger J, Cadet R, Saez F, et al. DNA oxidative damage in mammalian spermatozoa: where and why is the male nucleus affected? Free radical biology & medicine. 2013.

Shamsi MB, Imam SN, Dada R. Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility. J Assist Reprod Genet. 2011;28(11):1073-85.

Schulte RT, Ohl DA, Sigman M, Smith GD. Sperm DNA damage in male infertility: etiologies, assays, and outcomes. J Assist Reprod Genet. 2010;27(1):3-12.

Robinson L, Gallos ID, Conner SJ, Rajkhowa M, Miller D, Lewis S, et al. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod. 2012;27(10):2908-17.

Fernandez JL, Cajigal D, Lopez-Fernandez C, Gosalvez J. Assessing sperm DNA fragmentation with the sperm chromatin dispersion test. Methods Mol Biol. 2011;682:291-301.

Fernandez JL, Muriel L, Goyanes V, Segrelles E, Gosalvez J, Enciso M, et al. Simple determination of human sperm DNA fragmentation with an improved sperm chromatin dispersion test. Fertil Steril. 2005;84(4):833-42.

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. Hum Reprod. 2007;22(1):174-9.

Balasch J. Ageing and infertility: an overview. Gynecol Endocrinol. 2010;26(12):855-60.

Amann RP. The cycle of the seminiferous epithelium in humans: a need to revisit? J Androl. 2008;29(5):469-87.

Handelsman DJ, Staraj S. Testicular size: the effects of aging, malnutrition, and illness. J Androl. 1985;6(3):144-51.

Dain L, Auslander R, Dirnfeld M. The effect of paternal age on assisted reproduction outcome. Fertil Steril. 2011;95(1):1-8.

Kidd SA, Eskenazi B, Wyrobek AJ. Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril. 2001;75(2):237-48.

Lewis SE, John Aitken R, Conner SJ, Iuliis GD, Evenson DP, Henkel R, et al. The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment. Reprod Biomed Online. 2013.

Chohan KR, Griffin JT, Lafromboise M, De Jonge CJ, Carrell DT. Comparison of chromatin assays for DNA fragmentation evaluation in human sperm. J Androl. 2006;27(1):53-9.

Sakkas D, Alvarez JG. Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis. Fertil Steril. 2010;93(4):1027-36.

Velez de la Calle JF, Muller A, Walschaerts M, Clavere JL, Jimenez C, Wittemer C, et al. Sperm deoxyribonucleic acid fragmentation as assessed by the sperm chromatin dispersion test in assisted reproductive technology programs: results of a large prospective multicenter study. Fertil Steril. 2008;90(5):1792-9.

Moskovtsev SI, Willis J, White J, Mullen JB. Sperm DNA damage: correlation to severity of semen abnormalities. Urology. 2009;74(4):789-93.

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. J Assist Reprod Genet. 2009;26(1):41-6.

O’Flaherty C, de Lamirande E, Gagnon C. Positive role of reactive oxygen species in mammalian sperm capacitation: triggering and modulation of phosphorylation events. Free radical biology & medicine. 2006;41(4):528-40.

Koppers AJ, Mitchell LA, Wang P, Lin M, Aitken RJ. Phosphoinositide 3-kinase signalling pathway involvement in a truncated apoptotic cascade associated with motility loss and oxidative DNA damage in human spermatozoa. Biochem J. 2011;436(3):687-98.

Benedetti S, Tagliamonte MC, Catalani S, Primiterra M, Canestrari F, De Stefani S, et al. Differences in blood and semen oxidative status in fertile and infertile men, and their relationship with sperm quality. Reprod Biomed Online. 2012;25(3):300-6.

Aitken RJ, Jones KT, Robertson SA. Reactive oxygen species and sperm function--in sickness and in health. J Androl. 2012;33(6):1096-106..

Roca J, Martinez-Alborcia MJ, Gil MA, Parrilla I, Martinez EA. Dead spermatozoa in raw semen samples impair in vitro fertilization outcomes of frozen-thawed spermatozoa. Fertil Steril. 2013.

Pregl Breznik B, Kovacic B, Vlaisavljevic 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.

Nasr-Esfahani MH, Razavi S, Vahdati AA, Fathi F, Tavalaee M. Evaluation of sperm selection procedure based on hyaluronic acid binding ability on ICSI outcome. J Assist Reprod Genet. 2008;25(5):197-203.