Support for the contention that sperm with abnormal sperm chromatin structure assays are associated with reduced embryo implantation potential

Jerome H. Check1 and Robert Wood Johnson

Medical School Camden, Division of Reproductive, Endocrinology and Infertility, 7447 Old York Road, Melrose Park, PA-1902, New Jersey, USA

1 To whom correspondence should be addressed. Email: laurie{at}ccivf.com

Sir,

When a couple has failed to conceive despite apparent correction of all factors that could lead to infertility, in vitro fertilization (IVF) is often suggested. Success rates for unexplained infertility with IVF have been equal to the pregnancy rates with IVF for known male factor and/or tubal factor. The IVF could be correcting some unknown factor preventing sperm from meeting the oocyte or some occult tubal factor.

There is always the fear, however, that there may be some occult oocyte or sperm factor that could account for the failure to conceive which would not even be corrected by IVF or IVF with intracytoplasmic sperm injection (ICSI). If this occult factor results in failed fertilization, then at least the women would only waste one expensive, invasive IVF cycle.

However, the possibility exists that a male or female factor can still result in apparent normal looking embryos that may still result in implantation failure or increased risk of miscarriage (Check et al., 1995Go). The sperm chromatin structure assay from initial studies appeared to be a test of the sperm that could predict absolute pregnancy failure despite transfer of embryos that appeared morphologically normal (Larson et al., 2000Go; Larson-Cook, 2003Go; Saleh et al., 2003Go). Based on these data, this test would seem to be a must for patients undergoing IVF, especially for unexplained infertility, so that they do not waste their time and money.

However, the studies reported by Gandini et al. (2004)Go and Bungum et al. (2004) not only demonstrate that live pregnancies are possible but question whether this test has any value in predicting poor outcome following conventional IVF or IVF with ICSI.

The group that published some of the original studies finding no pregnancies with high DNA fragmentation indices ave now modified their original enthusiasm for the notion that an abnormal sperm chromatin structure assay indicates no chance of live pregnancy (Virro et al., 2004Go). Nevertheless, they still concluded that high DFI scores correlated with lower ongoing pregnancy rates at 12 weeks (47% vs 28%).

I write this letter to provide data that we presented at the 2004 meeting of the American Society of Andrology that would support the contention of Virro et al. as opposed to Gandini et al. and Bungum et al. Evaluating patients with failure to achieve a live pregnancy despite several embryo transfers, the ongoing pregnancy rate at 12 weeks was 10.3% for females whose male partners had DNA fragmentation index (DFI) scores >30% vs 19.4% for 15–30%, vs 19.5% for <15%. The respective miscarriage rates were 62.5%, 38.4% and 46.1%. The three groups were composed of 29, 41 and 36 couples.

Probably, however, most women would proceed with IVF with ICSI for unexplained infertility even if this procedure would be less successful with sperm with abnormal sperm chromatin structure assays. At present, the best reason for subjecting a man to this test would be to determine if the couple can persist with intrauterine insemination or whether they should proceed with IVF. The data from Gandini et al. (2004)Go would also support switching to IVF and not continuing with IUI if DFI scores were high.

References

Check JH, Stumpo L, Lurie D, Benfer K and Callan C (1995) A comparative prospective study using matched samples to determine the influence of subnormal hypo-osmotic test scores of spermatozoa on subsequent fertilization and pregnancy rates following in-vitro fertilization. Hum Reprod 10, 1197–1200.[Abstract]

Gandini L, Lombardo F, Paoli D et al. (2004) Full-term pregnancies achieved with ICSI despite high levels of sperm chromatin damage. Hum Reprod 19, 1409–1417.[Abstract/Free Full Text]

Larson-Cook KL, Brannian JD, Hansen KA, Kasperson KM, Aamold 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]

Larson KL, De Jonge CJ, Barnes AM, Jost LK 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]

Saleh RA, Agarwal A, Nada EA, El-Tonsy MH, Sharma RK, Meyer A, Nelson DR and Thomas AJ (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), 1597–1605.[CrossRef][ISI][Medline]

Virro MR, Kjersten L, Larson-Cook KL and Evenson DP (2004) Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplamic sperm injection cycles. Fertil Steril 81, 1289–1295.[CrossRef][ISI][Medline]