Earlier studies have indicated that spermatozoa of infertile men possess considerably more sperm DNA damage than that of fertile men, which could adversely affect both natural reproduction and assisted reproduction technology (ART) outcomes. Since the use of ART to treat infertility has increased substantially from its introduction in the US, in 1981, there is a huge concern regarding the safety of using DNA-damaged spermatozoa. Now, a recent study published online in the journal, Human Reproduction, demonstrates that sperm DNA damage is associated with a significantly enhanced risk of pregnancy loss following in vitro fertilization (IVF) and intra cytoplasmic sperm injection (ICSI).
Armand Zini from the St Mary’s Hospital Center, Canada and coworkers conducted a systematic review and meta-analysis of studies involving sperm DNA damage and pregnancy loss after IVF and/or ICSI treatment to determine the relationship between the two. The researchers analyzed 11 studies, which included 808 IVF and 741 ICSI cycles of treatment, resulting in 640 pregnancies (345 with IVF and 295 with ICSI) and 122 pregnancy losses. From the estimates of pregnancy loss, two by two tables were constructed and odds ratios (ORs) were calculated to examine the association. It was found that the combined odds ratio was 2.48, suggesting that damage to spermatozoa DNA raises the risk of pregnancy loss in IVF and ICSI cycles. The data indicates that sperm DNA damage has to be evaluated prior to ARTs to achieve better outcomes and also forms a basis for further investigations to validate the findings.
Recently, Bhattacharya SM (International Urology and Nephrology, 2008) conducted a study to examine the link between different sperm parameters and repeated unexplained early pregnancy loss. Semen samples obtained from male partners of 74 couples with a history of repeated pregnancy loss were assessed according to WHO criteria and the DNA integrity in each case was evaluated using Acridine Orange staining test. A comparison of the results was also drawn by studying semen samples obtained from 65 husbands of proven fertility. It was noted that there were a lack of statistically significant differences between the two groups in the following criteria: age of husbands, total count per ejaculate, sperm concentration, and rapid progressive motility of sperms. However, DNA integrity value, percentage of motile sperm and total motile sperms per ejaculate, were different in the two groups. Based on the findings, it was concluded that repeated embryonic or early fetal loss is associated with sperm DNA-integrity damage, implying that sperm DNA damage may be a key paternal factor for predicting pregnancy outcomes.
To determine the relationship between sperm DNA fragmentation in IVF/ICSI patients, ART outcome, and sperm parameters, Borini and colleagues (Human Reproduction, 2006) conducted a study on 132 men undergoing ART. The scientists found that the embryo post-implantation development in ICSI procedures is affected by sperm DNA fragmentation; with a high fragmentation rate compromising embryo viability, and thereby leading to pregnancy loss.
Sperm DNA damage is attributed to various intra-or extratesticular factors such as chemotherapy, radiation therapy, genital tract inflammation, testicular hyperthermia, varicoceles, cigarette smoking and environmental toxins. Although previous studies have found no consistent relation between sperm DNA damage and fertilization rates during IVF or ICSI, the recent research provides evidence that sperm DNA damage may be associated with an increased risk of significant spontaneous abortion. Substantiating the current research with further larger trials may help in the development of stringent processes for selecting sperms and embryos during ART to alleviate the adverse effects related to sperm DNA damage.
References
1. Zini A, Boman JM, Belzile E, Ciampi A. Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Hum Reprod. 2008 Dec;23(12):2663-8. Epub 2008 Aug 29.
2. Bhattacharya SM. Association of various sperm parameters with unexplained repeated early pregnancy loss–which is most important? Int Urol Nephrol. 2008;40(2):391-5.
3. Borini A, Tarozzi N, Bizzaro D, et al. Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Hum Reprod. 2006 Nov;21(11):2876-81. Epub 2006 Jun 22.
