Human Reproduction, Vol. 14, No. 4, 1039-1049,
April 1999
© 1999 European Society of Human Reproduction and Embryology
Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic
1 Department of Chemistry and Biochemistry and 2 Department of Animal and Range Sciences, Box 2170, South Dakota State University, Brookings, SD 57007, USA, 3 Department of Obstetrics and Gynecology, Loyola Medical Center, Maywood, IL 60153, USA, 4 Reproductive and Developmental Toxicology, Environmental Protection Agency, Washington DC, USA and 5 Institute for Pathology, National Hospital, Oslo, Norway 6 Department of Chemistry and Biochemistry and
The sperm chromatin structure assay (SCSA) was used to measure over 500 human semen samples from two independent studies: Study I, 402 samples from 165 presumably fertile couples wishing to achieve pregnancy over 12 menstrual cycles; Study II, samples from 115 patients seeking fertility counselling. The SCSA measures susceptibility to DNA denaturation in situ in spermatozoa exposed to acid for 30 s, followed by acridine orange staining. SCSA data from the male partners of 73 couples (group 1) achieving pregnancy during months 13 of Study I were used as the standard of `sperm chromatin compatible with high fertility' and were significantly different from those of 40 couples (group 3) achieving pregnancy in months 412 (P < 0.01) and those of male partners of 31 couples (group 4) not achieving pregnancy (P < 0.001). Group 2 contained couples who had a miscarriage. SCSA values for Study II were almost twice that of the Study I fertility standards. Within-couple repeatability tended to be less for group 3 than for groups 1, 2 or 4. Based on logistic regression, spermatozoa with denatured DNA (cells outside the main population, COMP
t) were the best predictor for whether a couple would not achieve pregnancy. Some 84% of males in group 1 had COMP
t <15%, while no couples achieved pregnancy in group 1 with
30% COMP
t, a threshold level considered not compatible with good fertility. Using selected cut-off values for chromatin integrity, the SCSA data predicted seven of 18 miscarriages (39%).
Key words: chromatin structure/human fertility/pregnancy loss/SCSA
6 To whom correspondence should be addressed
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
A. Zini, J. M. Boman, E. Belzile, and A. Ciampi Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis Hum. Reprod., August 29, 2008; (2008) den321v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Paul, A. A Murray, N. Spears, and P. T K Saunders A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice Reproduction, July 1, 2008; 136(1): 73 - 84. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. M. Lewis and I. M. Agbaje Using the alkaline comet assay in prognostic tests for male infertility and assisted reproductive technology outcomes Mutagenesis, May 1, 2008; 23(3): 163 - 170. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. O'Flaherty, F. Vaisheva, B.F. Hales, P. Chan, and B. Robaire Characterization of sperm chromatin quality in testicular cancer and Hodgkin's lymphoma patients prior to chemotherapy Hum. Reprod., May 1, 2008; 23(5): 1044 - 1052. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Bungum, M. Spano, P. Humaidan, P. Eleuteri, M. Rescia, and A. Giwercman Sperm chromatin structure assay parameters measured after density gradient centrifugation are not predictive for the outcome of ART Hum. Reprod., January 1, 2008; 23(1): 4 - 10. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Paul, D. W. Melton, and P. T.K. Saunders Do heat stress and deficits in DNA repair pathways have a negative impact on male fertility? Mol. Hum. Reprod., January 1, 2008; 14(1): 1 - 8. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. D. van Beek, M. Smit, M. M. van den Heuvel-Eibrink, F. H. de Jong, F. G. Hakvoort-Cammel, C. van den Bos, H. van den Berg, R. F.A. Weber, R. Pieters, and S. M.P.F. de Muinck Keizer-Schrama Inhibin B is superior to FSH as a serum marker for spermatogenesis in men treated for Hodgkin's lymphoma with chemotherapy during childhood Hum. Reprod., December 1, 2007; 22(12): 3215 - 3222. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. A.H.A. Derijck, G. W. van der Heijden, L. Ramos, M. Giele, J. A.M. Kremer, and P. de Boer Motile human normozoospermic and oligozoospermic semen samples show a difference in double-strand DNA break incidence Hum. Reprod., September 1, 2007; 22(9): 2368 - 2376. [Abstract] [Full Text] [PDF] |
||||
![]() |
I.M. Agbaje, D.A. Rogers, C.M. McVicar, N. McClure, A.B. Atkinson, C. Mallidis, and S.E.M. Lewis Insulin dependant diabetes mellitus: implications for male reproductive function Hum. Reprod., July 1, 2007; 22(7): 1871 - 1877. [Abstract] [Full Text] [PDF] |
||||
![]() |
D.Y. Liu and H.W.G. Baker Human sperm bound to the zona pellucida have normal nuclear chromatin as assessed by acridine orange fluorescence Hum. Reprod., June 1, 2007; 22(6): 1597 - 1602. [Abstract] [Full Text] [PDF] |
||||
![]() |
A.M. Codrington, B.F. Hales, and B. Robaire Exposure of male rats to cyclophosphamide alters the chromatin structure and basic proteome in spermatozoa Hum. Reprod., May 1, 2007; 22(5): 1431 - 1442. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Muriel, V. Goyanes, E. Segrelles, J. Gosalvez, J. G. Alvarez, and J. L. Fernandez Increased Aneuploidy Rate in Sperm With Fragmented DNA as Determined by the Sperm Chromatin Dispersion (SCD) Test and FISH Analysis J Androl, January 1, 2007; 28(1): 38 - 49. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Zini and J. Libman Sperm DNA damage: clinical significance in the era of assisted reproduction. Can. Med. Assoc. J., August 29, 2006; 175(5): 495 - 500. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Erenpreiss, M. Bungum, M. Spano, S. Elzanaty, J. Orbidans, and A. Giwercman Intra-individual variation in sperm chromatin structure assay parameters in men from infertile couples: clinical implications Hum. Reprod., August 1, 2006; 21(8): 2061 - 2064. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J. Wyrobek, B. Eskenazi, S. Young, N. Arnheim, I. Tiemann-Boege, E. W. Jabs, R. L. Glaser, F. S. Pearson, and D. Evenson Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm PNAS, June 20, 2006; 103(25): 9601 - 9606. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. B. Boe-Hansen, J. Fedder, A. K. Ersboll, and P. Christensen The sperm chromatin structure assay as a diagnostic tool in the human fertility clinic Hum. Reprod., June 1, 2006; 21(6): 1576 - 1582. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. A. Makhlouf and C. Niederberger DNA Integrity Tests in Clinical Practice: It Is Not a Simple Matter of Black and White (or Red and Green) J Androl, May 1, 2006; 27(3): 316 - 323. [Full Text] [PDF] |
||||
![]() |
X. Zhang, M. S. Gabriel, and A. Zini Sperm Nuclear Histone to Protamine Ratio in Fertile and Infertile Men: Evidence of Heterogeneous Subpopulations of Spermatozoa in the Ejaculate J Androl, May 1, 2006; 27(3): 414 - 420. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Smith, H. Kaune, D. Parodi, M. Madariaga, R. Rios, I. Morales, and A. Castro Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress Hum. Reprod., April 1, 2006; 21(4): 986 - 993. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Muriel, M. Meseguer, J. L. Fernandez, J. Alvarez, J. Remohi, A. Pellicer, and N. Garrido Value of the sperm chromatin dispersion test in predicting pregnancy outcome in intrauterine insemination: a blind prospective study Hum. Reprod., March 1, 2006; 21(3): 738 - 744. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Evenson Reply to: 'The predictive value of the sperm chromatin structure assay (SCSA)'--a response from the SCSA inventor. Hum. Reprod., February 1, 2006; 21(2): 570 - 572. [Full Text] [PDF] |
||||
![]() |
M. Bungum, L. Bungum, and P. Humaidan A prospective study, using sibling oocytes, examining the effect of 30 seconds versus 90 minutes gamete co-incubation in IVF Hum. Reprod., February 1, 2006; 21(2): 518 - 523. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. R. Chohan, J. T. Griffin, M. Lafromboise, C. J. De Jonge, and D. T. Carrell Comparison of Chromatin Assays for DNA Fragmentation Evaluation in Human Sperm J Androl, January 1, 2006; 27(1): 53 - 59. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Satta, A. Stivala, A. Garozzo, A. Morello, A. Perdichizzi, E. Vicari, M. Salmeri, and A. E. Calogero Experimental Chlamydia trachomatis infection causes apoptosis in human sperm Hum. Reprod., January 1, 2006; 21(1): 134 - 137. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Zini, J. Meriano, K. Kader, K. Jarvi, C. A. Laskin, and K. Cadesky Potential adverse effect of sperm DNA damage on embryo quality after ICSI Hum. Reprod., December 1, 2005; 20(12): 3476 - 3480. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Sergerie, G. Laforest, L. Bujan, F. Bissonnette, and G. Bleau Sperm DNA fragmentation: threshold value in male fertility Hum. Reprod., December 1, 2005; 20(12): 3446 - 3451. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Spano, G. Toft, L. Hagmar, P. Eleuteri, M. Rescia, A. Rignell-Hydbom, E. Tyrkiel, V. Zvyezday, J.P. Bonde, and INUENDO Exposure to PCB and p, p'-DDE in European and Inuit populations: impact on human sperm chromatin integrity Hum. Reprod., December 1, 2005; 20(12): 3488 - 3499. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. W. Aoki, S. I. Moskovtsev, J. Willis, L. Liu, J. B. M. Mullen, and D. T. Carrell DNA Integrity Is Compromised in Protamine-Deficient Human Sperm J Androl, November 1, 2005; 26(6): 741 - 748. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. C Oskam, J. L Lyche, A. Krogenaes, R. Thomassen, J. U Skaare, R. Wiger, E. Dahl, T. Sweeney, A. Stien, and E. Ropstad Effects of long-term maternal exposure to low doses of PCB126 and PCB153 on the reproductive system and related hormones of young male goats Reproduction, November 1, 2005; 130(5): 731 - 742. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Suganuma, R. Yanagimachi, and M. L. Meistrich Decline in fertility of mouse sperm with abnormal chromatin during epididymal passage as revealed by ICSI Hum. Reprod., November 1, 2005; 20(11): 3101 - 3108. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Rubes, S. G. Selevan, D. P. Evenson, D. Zudova, M. Vozdova, Z. Zudova, W. A. Robbins, and S. D. Perreault Episodic air pollution is associated with increased DNA fragmentation in human sperm without other changes in semen quality Hum. Reprod., October 1, 2005; 20(10): 2776 - 2783. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. G.Alvarez The predictive value of sperm chromatin structure assay Hum. Reprod., August 1, 2005; 20(8): 2365 - 2367. [Full Text] [PDF] |
||||
![]() |
R.-M. Laberge and G. Boissonneault On the Nature and Origin of DNA Strand Breaks in Elongating Spermatids Biol Reprod, August 1, 2005; 73(2): 289 - 296. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. W. Silver, B. Eskenazi, D. P. Evenson, G. Block, S. Young, and A. J. Wyrobek Effect of Antioxidant Intake on Sperm Chromatin Stability in Healthy Nonsmoking Men J Androl, July 1, 2005; 26(4): 550 - 556. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Seli and D. Sakkas Spermatozoal nuclear determinants of reproductive outcome: implications for ART Hum. Reprod. Update, July 1, 2005; 11(4): 337 - 349. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Sergerie, G. Laforest, K. Boulanger, F. Bissonnette, and G. Bleau Longitudinal study of sperm DNA fragmentation as measured by terminal uridine nick end-labelling assay Hum. Reprod., July 1, 2005; 20(7): 1921 - 1927. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Greco, M. Iacobelli, L. Rienzi, F. Ubaldi, S. Ferrero, and J. Tesarik Reduction of the Incidence of Sperm DNA Fragmentation by Oral Antioxidant Treatment J Androl, May 1, 2005; 26(3): 349 - 353. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. B. Boe-Hansen, A. K. Ersboll, and P. Christensen Variability and Laboratory Factors Affecting the Sperm Chromatin Structure Assay in Human Semen J Androl, May 1, 2005; 26(3): 360 - 368. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Mitchell, K. Steger, C. Marchetti, J.-C. Herbaut, P. Devos, and J.-M. Rigot Cellular expression of protamine 1 and 2 transcripts in testicular spermatids from azoospermic men submitted to TESE-ICSI Mol. Hum. Reprod., May 1, 2005; 11(5): 373 - 379. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Banks, S. A King, D S. Irvine, and P. T K Saunders Impact of a mild scrotal heat stress on DNA integrity in murine spermatozoa Reproduction, April 1, 2005; 129(4): 505 - 514. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Zini, A. Blumenfeld, J. Libman, and J. Willis Beneficial effect of microsurgical varicocelectomy on human sperm DNA integrity Hum. Reprod., April 1, 2005; 20(4): 1018 - 1021. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Greco, F. Scarselli, M. Iacobelli, L. Rienzi, F. Ubaldi, S. Ferrero, G. Franco, N. Anniballo, C. Mendoza, and J. Tesarik Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa Hum. Reprod., January 1, 2005; 20(1): 226 - 230. [Abstract] [Full Text] [PDF] |
||||
![]() |
U. Paasch, R. K. Sharma, A. K. Gupta, S. Grunewald, E. J. Mascha, A. J. Thomas Jr, H.-J. Glander, and A. Agarwal Cryopreservation and Thawing Is Associated with Varying Extent of Activation of Apoptotic Machinery in Subsets of Ejaculated Human Spermatozoa Biol Reprod, December 1, 2004; 71(6): 1828 - 1837. [Abstract] [Full Text] [PDF] |
||||
![]() |
S.L. Taylor, S.L. Weng, P. Fox, E.H. Duran, M.S. Morshedi, S. Oehninger, and S.J. Beebe Somatic cell apoptosis markers and pathways in human ejaculated sperm: potential utility as indicators of sperm quality Mol. Hum. Reprod., November 1, 2004; 10(11): 825 - 834. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Erenpreiss, K. Jepson, A. Giwercman, I. Tsarev, Je. Erenpreisa, and M. Spano Toluidine blue cytometry test for sperm DNA conformation: comparison with the flow cytometric sperm chromatin structure and TUNEL assays Hum. Reprod., October 1, 2004; 19(10): 2277 - 2282. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Bungum, P. Humaidan, M. Spano, K. Jepson, L. Bungum, and A. Giwercman The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination, IVF and ICSI Hum. Reprod., June 1, 2004; 19(6): 1401 - 1408. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Gandini, F. Lombardo, D. Paoli, F. Caruso, P. Eleuteri, G. Leter, R. Ciriminna, F. Culasso, F. Dondero, A. Lenzi, et al. Full-term pregnancies achieved with ICSI despite high levels of sperm chromatin damage Hum. Reprod., June 1, 2004; 19(6): 1409 - 1417. [Abstract] [Full Text] [PDF] |
||||
![]() |
S.E.M. Lewis, M. O'Connell, M. Stevenson, L. Thompson-Cree, and N. McClure An algorithm to predict pregnancy in assisted reproduction Hum. Reprod., June 1, 2004; 19(6): 1385 - 1394. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Marcon and G. Boissonneault Transient DNA Strand Breaks During Mouse and Human Spermiogenesis:New Insights in Stage Specificity and Link to Chromatin Remodeling Biol Reprod, April 1, 2004; 70(4): 910 - 918. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. I. Peris, A. Morrier, M. Dufour, and J. L. Bailey Cryopreservation of Ram Semen Facilitates Sperm DNA Damage: Relationship Between Sperm Andrological Parameters and the Sperm Chromatin Structure Assay J Androl, March 1, 2004; 25(2): 224 - 233. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Muriel, E. Segrelles, V. Goyanes, J. Gosalvez, and J. L. Fernandez Structure of human sperm DNA and background damage, analysed by in situ enzymatic treatment and digital image analysis Mol. Hum. Reprod., March 1, 2004; 10(3): 203 - 209. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. H. Moustafa, R. K. Sharma, J. Thornton, E. Mascha, M. A. Abdel-Hafez, A. J. Thomas, and A. Agarwal Relationship between ROS production, apoptosis and DNA denaturation in spermatozoa from patients examined for infertility Hum. Reprod., January 1, 2004; 19(1): 129 - 138. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Deane, S. Sharir, K. Jarvi, and A. Zini High Levels of Sperm DNA Denaturation as the Sole Semen Abnormality in a Patient After Chemotherapy for Testis Cancer J Androl, January 1, 2004; 25(1): 23 - 24. [Full Text] [PDF] |
||||
![]() |
R. Hauser, N.P. Singh, Z. Chen, L. Pothier, and L. Altshul Lack of an association between environmental exposure to polychlorinated biphenyls and p,p'-DDE and DNA damage in human sperm measured using the neutral comet assay Hum. Reprod., December 1, 2003; 18(12): 2525 - 2533. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. M. Penfold, L. Jost, D. P. Evenson, and D. E. Wildt Normospermic Versus Teratospermic Domestic Cat Sperm Chromatin Integrity Evaluated by Flow Cytometry and Intracytoplasmic Sperm Injection Biol Reprod, November 1, 2003; 69(5): 1730 - 1735. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Loft, T. Kold-Jensen, N. H. Hjollund, A. Giwercman, J. Gyllemborg, E. Ernst, J. Olsen, T. Scheike, H. E. Poulsen, and J. P. Bonde Oxidative DNA damage in human sperm influences time to pregnancy Hum. Reprod., June 1, 2003; 18(6): 1265 - 1272. [Abstract] [Full Text] [PDF] |
||||








