Sperm DNA fragmentation index does not correlate with blastocyst aneuploidy or morphological grading

Itai Gat, Katelynn Tang, Kevin Quach, Valeriy Kuznyetsov, Ran Antes, Melissa Filice, Khaled Zohni, Clifford Librach, Itai Gat, Katelynn Tang, Kevin Quach, Valeriy Kuznyetsov, Ran Antes, Melissa Filice, Khaled Zohni, Clifford Librach

Abstract

High DNA fragmentation index (DFI) may be associated with poor outcome after IVF. Our aim was to determine whether DFI impacts blastocyst quality or clinical outcome. This retrospective study included 134 couples who underwent 177 IVF-ICSI and pre-implantation genetic screening (PGS) cycles during January 1st, 2014-March 31st, 2016 and had documented previous DFI. Group 1 (DFI>30%) encompassed 25 couples who underwent 36 cycles; Group 2 (DFI 15-30%) included 45 couples and 57 cycles; group 3 (DFI<15%) included 64 couples and 83 cycles. Male partners within group 1 were older (45.1 compared to 40.6 and 38.3 years, respectively, p<0.05), had higher BMI (32.4 compared to 26.6 and 25.8 respectively, p<0.05) and lower sperm count and motility (46*106/ml and 35.5%, respectively) compared to groups 2 (61.8*106/ml and 46.6%, respectively) and 3 (75.8*106/ml and 55.1%, respectively, p<0.05). Female parameters including ovarian reserve and response and embryo development were similar. Total numbers of biopsied blastocysts were 116, 175 and 259 in groups 1, 2 and 3, respectively. PGS for 24 chromosomes revealed comparable euploidy rate of 46-50.4%, with a similar morphological classification. No significant differences were found regarding pregnancy rates or pregnancy loss. It seems that DFI doesn't correlate with blastocyst aneuploidy or morphological grading.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Male demographic parameters and semen…
Fig 1. Male demographic parameters and semen analysis in multiple sperm DFI levels +.
+ Each parameter is described by specific units in the Y axis as followed: DFI—%; age: years; BMI: Weight in Kilograms / (Height in Meters x Height in Meters); volume—ml; Count: millions sperm cells per ml; motility—% of motile spermatozoa; morphology—normal morphology according to Kruger criteria [22]. *p<0.05.
Fig 2. Pre-transfer embryo development (absolute numbers).
Fig 2. Pre-transfer embryo development (absolute numbers).

References

    1. Zhao J, Zhang Q, Wang Y, Li Y (2014) Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Fertil Steril 102: 998–1005 e1008. 10.1016/j.fertnstert.2014.06.033
    1. Bungum M, Humaidan P, Axmon A, Spano M, Bungum L, et al. (2007) Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod 22: 174–179. 10.1093/humrep/del326
    1. Barratt CL, Aitken RJ, Bjorndahl L, Carrell DT, de Boer P, et al. (2010) Sperm DNA: organization, protection and vulnerability: from basic science to clinical applications—a position report. Hum Reprod 25: 824–838. 10.1093/humrep/dep465
    1. Ni K, Spiess AN, Schuppe HC, Steger K (2016) The impact of sperm protamine deficiency and sperm DNA damage on human male fertility: a systematic review and meta-analysis. Andrology.
    1. Rathke C, Baarends WM, Awe S, Renkawitz-Pohl R (2014) Chromatin dynamics during spermiogenesis. Biochim Biophys Acta 1839: 155–168. 10.1016/j.bbagrm.2013.08.004
    1. Sakkas D, Alvarez JG (2010) Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis. Fertil Steril 93: 1027–1036. 10.1016/j.fertnstert.2009.10.046
    1. Evenson DP, Darzynkiewicz Z, Melamed MR (1980) Relation of mammalian sperm chromatin heterogeneity to fertility. Science 210: 1131–1133.
    1. Avendano C, Franchi A, Taylor S, Morshedi M, Bocca S, et al. (2009) Fragmentation of DNA in morphologically normal human spermatozoa. Fertil Steril 91: 1077–1084. 10.1016/j.fertnstert.2008.01.015
    1. Belloc S, Benkhalifa M, Cohen-Bacrie M, Dalleac A, Amar E, et al. (2014) Sperm deoxyribonucleic acid damage in normozoospermic men is related to age and sperm progressive motility. Fertil Steril 101: 1588–1593. 10.1016/j.fertnstert.2014.02.006
    1. Cohen-Bacrie P, Belloc S, Menezo YJ, Clement P, Hamidi J, et al. (2009) Correlation between DNA damage and sperm parameters: a prospective study of 1,633 patients. Fertil Steril 91: 1801–1805. 10.1016/j.fertnstert.2008.01.086
    1. Simon L, Zini A, Dyachenko A, Ciampi A, Carrell DT (2016) A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome. Asian J Androl.
    1. Dar S, Grover SA, Moskovtsev SI, Swanson S, Baratz A, et al. (2013) In vitro fertilization-intracytoplasmic sperm injection outcome in patients with a markedly high DNA fragmentation index (>50%). Fertil Steril 100: 75–80. 10.1016/j.fertnstert.2013.03.011
    1. Zini A, Boman JM, Belzile E, Ciampi A (2008) Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Hum Reprod 23: 2663–2668. 10.1093/humrep/den321
    1. Bareh GM, Jacoby E, Binkley P, Chang TC, Schenken RS, et al. (2016) Sperm deoxyribonucleic acid fragmentation assessment in normozoospermic male partners of couples with unexplained recurrent pregnancy loss: a prospective study. Fertil Steril 105: 329–336 e321. 10.1016/j.fertnstert.2015.10.033
    1. Robinson L, Gallos ID, Conner SJ, Rajkhowa M, Miller D, et al. (2012) The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod 27: 2908–2917. 10.1093/humrep/des261
    1. Collins JA, Barnhart KT, Schlegel PN (2008) Do sperm DNA integrity tests predict pregnancy with in vitro fertilization? Fertil Steril 89: 823–831. 10.1016/j.fertnstert.2007.04.055
    1. Zini A, Jamal W, Cowan L, Al-Hathal N (2011) Is sperm DNA damage associated with IVF embryo quality? A systematic review. J Assist Reprod Genet 28: 391–397. 10.1007/s10815-011-9544-6
    1. Bronet F, Martinez E, Gaytan M, Linan A, Cernuda D, et al. (2012) Sperm DNA fragmentation index does not correlate with the sperm or embryo aneuploidy rate in recurrent miscarriage or implantation failure patients. Hum Reprod 27: 1922–1929. 10.1093/humrep/des148
    1. Holubcova Z, Blayney M, Elder K, Schuh M (2015) Human oocytes. Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes. Science 348: 1143–1147. 10.1126/science.aaa9529
    1. MacLennan M, Crichton JH, Playfoot CJ, Adams IR (2015) Oocyte development, meiosis and aneuploidy. Semin Cell Dev Biol 45: 68–76. 10.1016/j.semcdb.2015.10.005
    1. Kumar SB, Chawla B, Bisht S, Yadav RK, Dada R (2015) Tobacco Use Increases Oxidative DNA Damage in Sperm—Possible Etiology of Childhood Cancer. Asian Pac J Cancer Prev 16: 6967–6972.
    1. Lu JC, Huang YF, Lu NQ (2010) [WHO Laboratory Manual for the Examination and Processing of Human Semen: its applicability to andrology laboratories in China]. Zhonghua Nan Ke Xue 16: 867–871.
    1. Evenson DP, Jost LK, Marshall D, Zinaman MJ, Clegg E, et al. (1999) Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod 14: 1039–1049.
    1. Evenson DP, Larson KL, Jost LK (2002) Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques. J Androl 23: 25–43.
    1. Lazer T, Dar S, Shlush E, Al Kudmani BS, Quach K, et al. (2014) Comparison of IVF Outcomes between Minimal Stimulation and High-Dose Stimulation for Patients with Poor Ovarian Reserve. Int J Reprod Med 2014: 581451 10.1155/2014/581451
    1. Palermo G, Joris H, Devroey P, Van Steirteghem AC (1992) Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 340: 17–18.
    1. Dor J, Ben-Shlomo I, Levran D, Rudak E, Yunish M, et al. (1992) The relative success of gonadotropin-releasing hormone analogue, clomiphene citrate, and gonadotropin in 1,099 cycles of in vitro fertilization. Fertil Steril 58: 986–990.
    1. Heitmann RJ, Hill MJ, Richter KS, DeCherney AH, Widra EA (2013) The simplified SART embryo scoring system is highly correlated to implantation and live birth in single blastocyst transfers. J Assist Reprod Genet 30: 563–567. 10.1007/s10815-013-9932-1
    1. Balakier H, Sojecki A, Motamedi G, Librach C (2016) Impact of multinucleated blastomeres on embryo developmental competence, morphokinetics, and aneuploidy. Fertil Steril.
    1. Kolte AM, Bernardi LA, Christiansen OB, Quenby S, Farquharson RG, et al. (2015) Terminology for pregnancy loss prior to viability: a consensus statement from the ESHRE early pregnancy special interest group. Hum Reprod 30: 495–498. 10.1093/humrep/deu299
    1. Ahmadi A, Ng SC (1999) Fertilizing ability of DNA-damaged spermatozoa. J Exp Zool 284: 696–704.
    1. Cissen M, Wely MV, Scholten I, Mansell S, Bruin JP, et al. (2016) Measuring Sperm DNA Fragmentation and Clinical Outcomes of Medically Assisted Reproduction: A Systematic Review and Meta-Analysis. PLoS One 11: e0165125 10.1371/journal.pone.0165125
    1. Cimadomo D, Capalbo A, Ubaldi FM, Scarica C, Palagiano A, et al. (2016) The Impact of Biopsy on Human Embryo Developmental Potential during Preimplantation Genetic Diagnosis. Biomed Res Int 2016: 7193075 10.1155/2016/7193075
    1. Orvieto R (2017) Re-analysis of aneuploidy blastocysts with an inner cell mass and different regional trophectoderm cells. J Assist Reprod Genet.
    1. Gleicher N, Orvieto R (2017) Is the hypothesis of preimplantation genetic screening (PGS) still supportable? A review. J Ovarian Res 10: 21 10.1186/s13048-017-0318-3
    1. Greco E, Minasi MG, Fiorentino F (2015) Healthy Babies after Intrauterine Transfer of Mosaic Aneuploid Blastocysts. N Engl J Med 373: 2089–2090. 10.1056/NEJMc1500421
    1. Lin MH, Kuo-Kuang Lee R, Li SH, Lu CH, Sun FJ, et al. (2008) 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. Fertil Steril 90: 352–359. 10.1016/j.fertnstert.2007.06.018
    1. Virro MR, Larson-Cook KL, Evenson DP (2004) 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 81: 1289–1295. 10.1016/j.fertnstert.2003.09.063
    1. Benchaib M, Lornage J, Mazoyer C, Lejeune H, Salle B, et al. (2007) Sperm deoxyribonucleic acid fragmentation as a prognostic indicator of assisted reproductive technology outcome. Fertil Steril 87: 93–100. 10.1016/j.fertnstert.2006.05.057
    1. Wdowiak A, Bakalczuk S, Bakalczuk G (2015) The effect of sperm DNA fragmentation on the dynamics of the embryonic development in intracytoplasmatic sperm injection. Reprod Biol 15: 94–100. 10.1016/j.repbio.2015.03.003
    1. Braude P, Bolton V, Moore S (1988) Human gene expression first occurs between the four- and eight-cell stages of preimplantation development. Nature 332: 459–461. 10.1038/332459a0
    1. Seli E, Gardner DK, Schoolcraft WB, Moffatt O, Sakkas D (2004) Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization. Fertil Steril 82: 378–383. 10.1016/j.fertnstert.2003.12.039
    1. de la Rochebrochard E, Thonneau P (2002) Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study. Hum Reprod 17: 1649–1656.
    1. Agarwal A, Cho CL, Esteves SC (2016) Should we evaluate and treat sperm DNA fragmentation? Curr Opin Obstet Gynecol 28: 164–171. 10.1097/GCO.0000000000000271
    1. Zini A (2011) Are sperm chromatin and DNA defects relevant in the clinic? Syst Biol Reprod Med 57: 78–85. 10.3109/19396368.2010.515704
    1. Ni W, Xiao S, Qiu X, Jin J, Pan C, et al. (2014) Effect of sperm DNA fragmentation on clinical outcome of frozen-thawed embryo transfer and on blastocyst formation. PLoS One 9: e94956 10.1371/journal.pone.0094956
    1. Hassold T, Hunt P (2001) To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2: 280–291. 10.1038/35066065
    1. Katz-Jaffe MG, Parks J, McCallie B, Schoolcraft WB (2013) Aging sperm negatively impacts in vivo and in vitro reproduction: a longitudinal murine study. Fertil Steril 100: 262–268 e261– 262 10.1016/j.fertnstert.2013.03.021
    1. Begueria R, Garcia D, Obradors A, Poisot F, Vassena R, et al. (2014) Paternal age and assisted reproductive outcomes in ICSI donor oocytes: is there an effect of older fathers? Hum Reprod 29: 2114–2122. 10.1093/humrep/deu189
    1. Jones KL, Smith DW, Harvey MA, Hall BD, Quan L (1975) Older paternal age and fresh gene mutation: data on additional disorders. J Pediatr 86: 84–88.
    1. Das M, Al-Hathal N, San-Gabriel M, Phillips S, Kadoch IJ, et al. (2013) High prevalence of isolated sperm DNA damage in infertile men with advanced paternal age. J Assist Reprod Genet 30: 843–848. 10.1007/s10815-013-0015-0
    1. Kidd SA, Eskenazi B, Wyrobek AJ (2001) Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril 75: 237–248.
    1. Gianaroli L, Magli MC, Ferraretti AP (2005) Sperm and blastomere aneuploidy detection in reproductive genetics and medicine. J Histochem Cytochem 53: 261–267. 10.1369/jhc.4B6434.2005
    1. Fonseka KG, Griffin DK (2011) Is there a paternal age effect for aneuploidy? Cytogenet Genome Res 133: 280–291. 10.1159/000322816
    1. Kushnir VA, Darmon SK, Albertini DF, Barad DH, Gleicher N (2016) Effectiveness of in vitro fertilization with preimplantation genetic screening: a reanalysis of United States assisted reproductive technology data 2011–2012. Fertil Steril 106: 75–79. 10.1016/j.fertnstert.2016.02.026
    1. Boe-Hansen GB, Ersboll AK, Christensen P (2005) Variability and laboratory factors affecting the sperm chromatin structure assay in human semen. J Androl 26: 360–368. 10.2164/jandrol.04056

Source: PubMed

3
購読する