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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

D.P. Evenson1,6,6, L.K. Jost1, D. Marshall2, M.J. Zinaman3, E. Clegg4, K. Purvis5, P. de Angelis5 and O.P. Claussen5

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 1–3 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 4–12 (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{alpha}t) were the best predictor for whether a couple would not achieve pregnancy. Some 84% of males in group 1 had COMP{alpha}t <15%, while no couples achieved pregnancy in group 1 with >=30% COMP{alpha}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


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S. Francavilla, M. A. Bianco, G. Cordeschi, P. D'Abrizio, C. De Stefano, G. Properzi, and F. Francavilla
Ultrastructural analysis of chromatin defects in testicular spermatids in azoospermic men submitted to TESE-ICSI
Hum. Reprod., July 1, 2001; 16(7): 1440 - 1448.
[Abstract] [Full Text] [PDF]

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S. Emiliani, M. Van den Bergh, A.-S. Vannin, J. Biramane, M. Verdoodt, and Y. Englert
Evidence of reduced single-stranded testicular sperm DNA from obstructive azoospermic men after 3 days of in-vitro culture
Hum. Reprod., June 1, 2001; 16(6): 1200 - 1203.
[Abstract] [Full Text] [PDF]

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J. Molina, J.A. Castilla, J.L. Castano, J. Fontes, N. Mendoza, and L. Martinez
Chromatin status in human ejaculated spermatozoa from infertile patients and relationship to seminal parameters
Hum. Reprod., March 1, 2001; 16(3): 534 - 539.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
M. Reichart, I. Kahane, and B. Bartoov
In Vivo and In Vitro Impairment of Human and Ram Sperm Nuclear Chromatin Integrity by Sexually Transmitted Ureaplasma urealyticum Infection
Biol Reprod, October 1, 2000; 63(4): 1041 - 1048.
[Abstract] [Full Text]

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K.L. Larson, C.J. DeJonge, A.M. Barnes, L.K. Jost, and D.P. Evenson
Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques
Hum. Reprod., August 1, 2000; 15(8): 1717 - 1722.
[Abstract] [Full Text] [PDF]

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E. T. Donnelly, M. O'Connell, N. McClure, and S. E.M. Lewis
Differences in nuclear DNA fragmentation and mitochondrial integrity of semen and prepared human spermatozoa
Hum. Reprod., July 1, 2000; 15(7): 1552 - 1561.
[Abstract] [Full Text] [PDF]

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 Hum ReprodHome page
G. Barroso, M. Morshedi, and S. Oehninger
Analysis of DNA fragmentation, plasma membrane translocation of phosphatidylserine and oxidative stress in human spermatozoa
Hum. Reprod., June 1, 2000; 15(6): 1338 - 1344.
[Abstract] [Full Text] [PDF]

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D. Sakkas, G.C. Manicardi, M. Tomlinson, M. Mandrioli, D. Bizzaro, P.G. Bianchi, and U. Bianchi
The use of two density gradient centrifugation techniques and the swim-up method to separate spermatozoa with chromatin and nuclear DNA anomalies
Hum. Reprod., May 1, 2000; 15(5): 1112 - 1116.
[Abstract] [Full Text] [PDF]

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A.D. Esterhuizen, D.R. Franken, J.G.H. Lourens, E. Prinsloo, and L.H. van Rooyen
Sperm chromatin packaging as an indicator of in-vitro fertilization rates
Hum. Reprod., March 1, 2000; 15(3): 657 - 661.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
D. M. de Kretser and H. W. G. Baker
Infertility in Men: Recent Advances and Continuing Controversies
J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3443 - 3450.
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 Hum ReprodHome page
K.L. Larson, J.D. Brannian, B.K. Timm, L.K. Jost, and D.P. Evenson
Density gradient centrifugation and glass wool filtration of semen remove spermatozoa with damaged chromatin structure
Hum. Reprod., August 1, 1999; 14(8): 2015 - 2019.
[Abstract] [Full Text] [PDF]


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