Abstract
A large proportion of men with normal sperm results as analyzed using conventional techniques have fragmented DNA in their spermatozoa. We performed a prospective study to examine the incidence of DNA fragmentation in sperm in cases of couples with previously unexplained infertility and treated with intrauterine insemination. We evaluated whether there was any predictive value of DNA fragmentation for pregnancy outcome in such couples. The percentage of DNA fragmentation and all classical variables to evaluate sperm before and after sperm treatment were determined. We studied the probable association between these results and pregnancy outcome in terms of clinical and ongoing pregnancy rate per started first cycle. We also assessed the optimal threshold level to diagnose DNA fragmentation in our center. When using threshold levels of 20, 25, and 30%, the occurrence of DNA fragmentation was 42.9, 33.3, and 28.6%, respectively. Receiver operating characteristic (ROC) analysis of all cases revealed an area under the curve of 80% to predict the clinical pregnancy rate per cycle from testing the sperm motility (a + b) before treatment. We failed to generate an ROC curve to estimate pregnancy outcome from the amount of DNA fragmentation before treatment. However, when selecting only those men with a pretreatment DNA fragmentation of at least 20%, the pretreatment result was statistically different between couples who achieved a clinical pregnancy and those who did not. DNA fragmentation is often diagnosed in couples with unexplained infertility. Each center should evaluate the type of test it uses to detect DNA fragmentation in sperm and determine its own threshold values.
Highlights
Recent research has revealed that subtle abnormalities can be found in sperm samples that seem to be normal according to conventional analysis techniques [1, 2]
– apoptosis during the process of spermatogenesis; – DNA strand breaks that occur during the remodeling of sperm chromatin in spermatogenesis; – post-testicular DNA fragmentation induced mainly by oxygen radicals (ROS), including the hydroxyl radical and nitric oxide, during sperm transport through the seminiferous tubules and the epididymis; the effect of ROS on sperm has been known since 1943 [5]; – DNA fragmentation induced by endogenous caspases and endonucleases; – DNA damage induced by radiotherapy and chemotherapy; and – DNA damage induced by environmental toxicants
intrauterine inseminations (IUI) followed without delay because shortening the time period between semen processing and insemination minimizes sperm DNA fragmentation [4]
Summary
Recent research has revealed that subtle abnormalities can be found in sperm samples that seem to be normal according to conventional analysis techniques [1, 2]. The DNA in the sperm head is sometimes fragmented, and this may be the reason why couples with a diagnosis of unexplained infertility do not achieve pregnancy. There seems to be a correlation between sperm fragmentation and aneuploidy [3]. DNA damage in spermatozoa affects both mitochondrial and nuclear DNA [4]. Fifteen percent of men with normal basic semen analysis profiles [6] have been associated with infertility problems [7]. About 8% of men with normal sperm results do have abnormal levels of DNA fragmentation in sperm [8]
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