Novel use of COMET parameters of sperm DNA damage may increase its utility to diagnose male infertility and predict live births following both IVF and ICSI

Hum Reprod. 2019 Oct 2;34(10):1915-1923. doi: 10.1093/humrep/dez151.


Study question: Do the Comet parameters of the proportions of sperm with low or high DNA damage improve the power of the test in the diagnosis of male infertility and/or prediction of IVF and ICSI live birth rates?

Summary answer: The mean Comet score and the scores for proportions of sperm with high or low DNA damage were useful in diagnosing male infertility and provided additional discriminatory information for the prediction of both IVF and ICSI live births.

What is known already: Sperm DNA damage impacts adversely on male fertility and IVF outcomes.

Study design, size, duration: A retrospective study was performed involving a total of 457 participants (381 patients and 76 fertile donors). Data was collected from a fertility clinic between 2015 and 2017.

Participants/materials, setting, methods: A total of 381 consecutive male partners of couples attending for ART and 76 fertile donors were included in the study. DNA fragmentation was measured by the alkaline Comet assay. Receiver operator characteristic curve analysis (area under the ROC curve (AUC)) was used to determine the value of average Comet score (ACS), low Comet score (LCS) and high Comet score (HCS) to diagnose male factor infertility. In total, 77 IVF and 226 ICSI cycles were included to determine thresholds for each parameter (AUC analysis) and to compare live birth rates (LBRs) following each ART.

Main results and the role of chance: ACS, HCS and LCS were predictive of male infertility (AUC > 0.9, P < 0.0001). IVF LBRs declined once DNA damage exceeded the threshold levels. HCS showed the sharpest decline. Following ICSI, the highest LBRs were in men whose DNA damage levels approached the fertile range. Trends differed in IVF. LBRs decreased as damage increased whereas in ICSI the LBRs decreased but then remained stable.

Limitations, reasons for caution: Since this is the first study to show the impact of sperm DNA damage on ICSI live births, a prospective study should be performed (stratifying patients to IVF or ICSI based on these thresholds) to validate this study.

Wider implications of the findings: Our study presents novel information towards elucidating the genetic basis of male infertility and secondly on relevance of the extent of DNA damage as an impending factor in both IVF and ICSI success.

Study funding/competing interest(s): This study was supported by Examenlab Ltd, The Lister Clinic, Cryos International and Imperial College London NHS Trust. No external funding was obtained for this study. SL and KL are employees of Examenlab Ltd, a university spin-out company with a commercial interest in sperm DNA damage. No other author has a conflict of interest to declare.

Trial registration number: Non-applicable.

Keywords: ART; Comet; DNA fragmentation; IVF/ICSI outcomes; live births; male infertility; threshold values.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Comet Assay*
  • DNA Fragmentation*
  • Feasibility Studies
  • Female
  • Healthy Volunteers
  • Humans
  • Infertility, Male / diagnosis*
  • Infertility, Male / genetics
  • Infertility, Male / pathology
  • Infertility, Male / therapy
  • Live Birth
  • Male
  • Middle Aged
  • Pregnancy
  • Pregnancy Rate
  • Prognosis
  • ROC Curve
  • Retrospective Studies
  • Semen Analysis / methods*
  • Sperm Injections, Intracytoplasmic / statistics & numerical data*
  • Spermatozoa / pathology*
  • Treatment Outcome
  • Young Adult