Sperm DNA fragmentation testing: Summary evidence and clinical practice  recommendations

Sandro C Esteves; Armand Zini; Robert Matthew Coward; Donald P Evenson; Jaime Gosálvez; Sheena E M Lewis; Rakesh Sharma; Peter Humaidan

doi:10.1111/and.13874

Male Fertility Semen Analysis

Sperm DNA fragmentation testing: Summary evidence and clinical practice recommendations

Esteves SC, Zini A, Coward RM, Evenson DP, Gosálvez J, Lewis SEM, Sharma R, Humaidan P

Published March 2021 Andrologia, 53(2), e13874

DOI 10.1111/and.13874 PMID 33108829 PMC PMC7988559

RRM Academy Synopsis

Expert guideline sets out when to test sperm DNA fragmentation

A 2020 guideline with 41 recommendations says a poor sperm DNA test result should send the man to a urology specialist for a full evaluation. Thirteen recommendations cover testing technique and 28 cover who should be tested and how to manage the findings.

Key Findings

Of the 41 recommendations, 13 concern testing technique, covering sample handling, thresholds and reading results, and 28 concern who should be tested and how to manage the findings.
The recommendations address men with varicocele, couples with unexplained infertility or recurrent pregnancy loss, couples heading into insemination or IVF, men with infertility risk factors, and sperm banking.
Supporting evidence has grown in recent years, the authors write, yet remains of moderate to low quality.
One strong recommendation, resting on the lowest evidence grade (D), says an abnormal result should prompt a full male workup by a reproductive urologist or andrologist.
Another strong recommendation states that the tests cannot perfectly separate fertile from infertile men, or predict with certainty which couples will succeed with IUI, IVF or ICSI.

Interpretation

This clinical practice guideline draws on reviews, trials and cohort studies gathered in a PubMed search that ended 31 May 2020. A multidisciplinary author group graded each recommendation for strength and evidence quality. The guideline says sperm DNA fragmentation testing may add new information alongside semen analysis and other standard tests. The authors frame infertility as a couple's condition, so a test on one partner predicts outcome only in part. The authors note that evidence quality is mostly moderate to low, so several recommendations also rest on expert consensus.

RRM Context

Restorative reproductive medicine looks for the cause in both partners, and the guideline supports that step for the man. An abnormal result leads to a full male workup for correctable conditions such as varicocele. The paper says ICSI, which injects one sperm into an egg, may be considered if no correctable male factor is found or abnormal results persist after treatment (a conditional recommendation). ICSI works around the male factor and leaves its cause untreated.

Our editorial summary of this paper, not the article's abstract.

Abstract

We herein summarise the evidence concerning the impact of sperm DNA fragmentation in various clinical infertility scenarios and the advances on sperm DNA fragmentation tests. The collected evidence was used to formulate 41 recommendations. Of these, 13 recommendations concern technical aspects of sperm DNA fragmentation testing, including pre-analytical information, clinical thresholds and interpretation of results. The remaining 28 recommendations relate to indications for sperm DNA fragmentation testing and clinical management. Clinical scenarios like varicocele, unexplained infertility, idiopathic infertility, recurrent pregnancy loss, intrauterine insemination, in vitro fertilisation/intracytoplasmic sperm injection, fertility counselling for men with infertility risk factors and sperm cryopreservation have been contemplated. The bulk evidence supporting the recommendations has increased in recent years, but it is still of moderate to low quality. This guideline provides clinicians with advice on best practices in sperm DNA fragmentation testing. Also, recommendations are provided on possible management strategies to overcome infertility related to sperm DNA fragmentation, based on the best available evidence. Lastly, we identified gaps in knowledge and opportunities for research and elaborated a list of recommendations to stimulate further investigation.

Topics

Male Fertility › Semen Analysis › Sperm Function Testing · Clinical Guidelines and Standards › Guidelines by Clinical Area › Fertility and Infertility Guidelines · Research Methods › Evidence Synthesis › Systematic Reviews

Sandro C Esteves, Armand Zini, Robert Matthew Coward, Donald P Evenson, Jaime Gosálvez, Sheena E M Lewis, Rakesh Sharma, Peter Humaidan

S Esteves, A Zini, Bob Coward, Rob Coward, Bobby Coward, R Coward, Don Evenson, D Evenson, J Gosálvez, S Lewis, R Sharma, Pete Humaidan, P Humaidan

PMID 33108829 33108829 DOI 10.1111/and.13874 10.1111/and.13874 Esteves et al. 2021, Esteves 2021