Effect of sperm DNA fragmentation on the clinical outcomes for in vitro fertilization and intracytoplasmic sperm injection in women with different ovarian reserves

Capsule:
The negative effect of sperm DNA fragmentation on clinical outcomes of IVF and ICSI is greater in women with reduced ovarian reserve compared with those with normal ovarian reserve.

Authors:
Jianyuan Jin, M.S., Chengshuang Pan, M.D., Qianjin Fei, M.D., Wuhua Ni, M.S., Xu Yang, M.S., Liya Zhang, M.S., Xuefeng Huang, M.D., Ph.D.

Volume 103, Issue 4, Pages 910-916

Abstract:

Objective:
To investigate effect of sperm DNA fragmentation (SDF) on clinical outcomes of assisted reproductive technology in women with normal ovarian reserve (NOR) versus reduced ovarian reserve (ROR).

Design:
Retrospective clinical study.

Setting:
University-affiliated tertiary teaching hospital.

Patient(s):
A total of 2,865 consecutive couples undergoing their first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle.

Intervention(s):
SDF assessed using sperm chromatin dispersion in sperm samples 1–2 months before treatment.

Main Outcome Measure(s):
SDF, IVF, and ICSI outcomes.

Result(s):
The grouping criteria were [1] basal follicle stimulating hormone >10 IU/L, [2] antral follicle count <6, and [3] female age ≥38 years. Women fulfilling two of the three criteria were considered to have ROR, and those not meeting any criteria were considered to have NOR. The area under the receiver operating characteristic curve was 0.594 (0.539–0.648) for the ROR group and 0.510 (0.491–0.530) for the NOR group. A cutoff value for SDF to predict the clinical pregnancy rate (CPR) in the ROR group was 27.3%. When the SDF exceeded 27.3%, the live-birth and implantation rates in the ROR group were statistically significantly decreased, but the clinical pregnancy, live-birth, and implantation rates were not affected in the NOR group. The risk of early abortion increased significantly in the NOR group when the SDF exceeded 27.3%.

Conclusion(s):
Sperm DNA fragmentation has a greater impact on IVF and ICSI outcomes among women with ROR, so SDF testing may be of particular clinical significance for these couples.

  • Ali Dabaja

    As Mike stated earlier, a follow up study that evaluates the benefit of surgical intervention (varicocelectomy or testicular sperm extraction) on these patients will be warranted. Could the authors discuss their experience on surgical intervention for patients with an elevated DFI?

  • Shvetha Zarek

    This is a retrospective cohort study to evaluate the effect of sperm DNA fragmentation by the sperm chromatin dispersion test on pregnancy outcomes in couples with normal and reduced ovarian reserve in a cohort of 2,865 of first ART cycles of women. ICSI was utilized when the sperm concentration was less than 5 x106/mL or when the motility was 10 IU/L, antral follicle count 38 years. ROC analysis was utilized to determine a cut point of percentage of SDF for predicting pregnancy. The authors report the cutoff value for SDF to predict the clinical pregnancy rate (CPR) in the ROR group was 27.3%. The risk of early abortion increased significantly in the NOR group when the SDF exceeded 27.3%.

    Although this is an intriguing concept, the ROC curves for both ROR and NOR do not demonstrate a high true positive with a concomitant low false positive rate, thus suggesting that SDF is not a clinically useful marker for clinical outcomes in ART. Thus, utilizing the authors’ cutoff value of 27.3% should be done with caution. Can the authors kindly comment if they are actively using the 27.3% cut point value in their clinical practice and if it had an impact on outcomes?

  • Xuefeng Huang

    Actually, we currently undergo researches to see if some treatments impoving oocyte quality or sperm DNA integrity would be useful in clinical practice to increase the clinical outcomes in our defined subgroup patients.

  • The treatments for or abstaining from obvious etiologies that can increase oxidative stress (i.e. varicocele, tobacco exposure/use, ionizing radiation, etc.) are relatively obvious. However, men without risk factors or anatomic abnormalities may be more difficult to address. Antioxidant therapy may be an option, but the literature is quite mixed as to the outcomes. There are trends towards improving DNA fragmentation levels when ROS levels decrease. As Dr. Hsieh addressed in his comments, going directly to the testicle for sperm may be a good option.

    • Xuefeng Huang

      Although some researches found the DNA damage is less severe in sperm from testis than from ejaculated, we find for those patients with severe abnormal sperm parameters have very high percentage of DNA damage sperm in their testis. This would not support the use of testicular sperm in these patients.

  • msamplaski

    How did the authors determine the cutoff of 27% for SDF, since 30% is a more commonly utilized clinical value? In addition, how do the authors propose that these couples should be counseled to decrease their DNA fragmentation levels? Regardless, these data support the role of SDF testing in couples with low ovarian reserve.

    • Xuefeng Huang

      The cutoff value of 27% was obtained using ROC analysis. We undergo research to see if some treatments could decrease the level of DNA damage and, furthermore, increase the clinical results of IVF.

  • despite the wide availability of sperm DNA fragmentation testing, we all struggle on what to do with the result. this study attempt to identify a sub-group of couples who appeared to have worse outcomes. a potential follow-up study of practical significance would be to identify a sub-set of couple that might benefit from intervention for abnormal sperm DNA fragmentation (varicocelectomy vs testicular sperm retrieval)

    • Xuefeng Huang

      Although some researches found the DNA damage is less severe in sperm from testis than from ejaculated, we find for those patients with severe abnormal sperm parameters have very high percentage of DNA damage sperm in their testis. This would not support the use of testicular sperm in these patients.

  • Jason M. Franasiak

    A very interesting article. In the portion of the analysis where confounders were adjusted when comparing groups, I did not see that paternal age was adjusted. This would be of interest to see if the DFI was still predictive above and beyond simply looking at paternal age. Was this considered?

    • Xuefeng Huang

      Actually, in our research we did not found paternal age is a confounding factor, possibly because most of our male patients is younger than 45 years old.

      • Jason M. Franasiak

        Thank you for your reply.

  • ranjithrama

    The authors highlight an important use for sperm DNA fragmentation (sDF) – setting of poor ovarian reserve. Unfortunately, despite its validity, the indications for sDF still remains unclear (? recurrent pregnancy loss / IVF failure). It would be interesting to know whether increasing sDF, beyond 27%, is associated with worse outcomes on a linear scale.

    • Xuefeng Huang

      We examin SDF in all patients undergoing IVF. There is no linear relation between the outcomes and SDF beyond 27%.

  • jimdupree4

    Thanks to the authors for sharing this information about sperm DNA fragmentation and fertility outcomes in different groups of women. Could the authors describe the causes for increased sperm DNA fragmentation that they typically find in their male patients as well as the treatments they typically use in those situations?

    • Xuefeng Huang

      Actually, most of these patients had unknown reason for their high DNA damage. We are now using antioxidants such as carnitine and lycopene.

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