The predictive value of sperm chromatin structure assay

James Nicopoullos1, Carole Gilling-Smith, Paula Almeida and Jonathon Ramsay

Assisted Conception Unit, Chelsea & Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK

1 To whom correspondence should be addressed. Email: james.nicopoullos{at}chelwest.nhs.uk

Sir,

We read with great interest the recent article by Bungum et al. (2004)Go assessing the predictive value of the sperm chromatin structure assay (SCSA) on the outcome of intrauterine insemination, IVF and ICSI. At present we are also performing a prospective study, assessing the predictive value of sperm DNA fragmentation alone and in conjunction with sperm aneuploidy screening on ICSI outcome.

From extensive animal and human studies, Evenson and co-authors, who first described the SCSA, suggested that thresholds of 0–15%, 16–29% and >30% for the DNA fragmentation index (DFI) relate to high, moderate and low fertility potential, respectively. These thresholds also applied to assisted reproduction samples, as despite the use of sperm preparation techniques they reported no IVF or ICSI pregnancies when the DFI of the raw semen sample was >27% (Larson et al., 2000Go).

Thereafter, similar cut-offs of 28% for 33 IUI/IVF/ICSI cycles, 20% in a group of 104 IVF and ICSI cycles and 27% for 113 IVF and ICSI cycles were reported by Saleh et al. (2003)Go, Benchaib et al. (2003)Go and Larson-Cook et al. (2003)Go, respectively. These findings are in keeping with previously published in vivo studies of couples with no previous subfertility, indicating a DFI cut-off level of 30–40% for no pregnancy (reviewed in Evenson et al., 2002Go).

In contrast to these previous reports of no reported pregnancy following assisted reproduction above a DFI of 28%, Bungum et al. (2004)Go reported an IUI pregnancy in a man with a DFI of 34%, and 13 pregnancies following IVF or ICSI with a DFI >27%, suggesting that these techniques can, in fact, overcome such a high level of abnormality. The authors, however, did not, specify the DFI of these individual cases.

It has previously been postulated that, although oocytes have the ability to repair sperm DNA damage, if sperm are selected from a sample with extensively damaged DNA, the oocyte's repair capacity may be inadequate with subsequent effect on embryo development and pregnancy outcome (Evenson et al., 2002Go).

Although this may still be true, the findings of Bungum et al. (2004)Go suggest that, until further series are published, it remains difficult to impose an upper limit above which a couple can be reliably told that assisted reproduction techniques will be unsuccessful.

Our initial data (as yet unpublished) can confirm this, with an ongoing singleton ICSI pregnancy in a couple where the male partner was reported to have a DNA fragmentation index of 56%. Only one previous study has assessed the effect of DFI on ICSI cycles alone (Benchaib et al., 2003Go) and we hope our series will further assess whether there is, in fact, a role for routine DNA fragmentation testing prior to ICSI, and whether the combination of the SCSA with sperm aneuploidy screening can realistically become a valuable tool to help inform a couple of the chance of ICSI success.

References

Benchaib M, Braun V, Lornage J, Hadj S, Salle B, Lejeune H and Guerin JF (2003) Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproduction setting. Hum Reprod 18, 1023–1028.[Abstract/Free Full Text]

Bungum M, Humaidan P, Spano M, Jepson K, Bungum L and Giwercman A (2004) The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination, IVF and ICSI. Hum Reprod 19, 1401–1408.[Abstract/Free Full Text]

Evenson DP, Larson KL and Jost LK (2002) Sperm chromatin structural assay: Its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques. J Androl 23, 25–43.[Free Full Text]

Larson KL, De Jonge CJ, Barnes AM, Jost IK and Evenson DP (2000) Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques. Hum Reprod 15, 1717–1722.[Abstract/Free Full Text]

Larson-Cook KL, Brannian JD, Hansen KA, Kasperson KM, Aarnold ET and Evenson DP (2003) Relationship between the outcomes of assisted reproductive techniques and sperm DNA fragmentation as measured by the sperm chromatin structure assay. Fertil Steril 80, 895–902.[CrossRef][ISI][Medline]

Saleh RA, Agarwal A, Nada EA, El-Tonsy MH, Sharma RK, Meyer A, Nelson DR and Thomas AJ Jr (2003) Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Fertil Steril 79 (Suppl. 3), 1597–1603.[CrossRef][ISI][Medline]





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