Sperm DNA fragmentation testing: Summary evidence and clinical practice recommendations.

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

doi:10.1111/and.13874

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.

Highlights

We propose a new nomenclature to embrace the tests into two groups, that is, (1) sperm DNA fragmentation (SDF) tests, namely TUNEL, ISNT, shown to help reduce SDF rates (SCSA), sperm chromatin dispersion test (SCD), and Comet, and (2) Sperm chromatin compaction tests, namely, chromomycin A3 staining, acridine orange staining, toluidine blue staining and aniline blue staining
The results provided by the most common SDF tests do not necessarily line up, there is a good correlation between SDF rates reported by TUNEL, SCSA, SCD and alkaline Comet
We believe that the SDF testing shortcomings should not restrain healthcare providers from taking advantage of its clinical value, provided the information supporting that particular test for clinical decision-making has been made clear to the patient

Summary

| BACKGROUND

Infertility affects over 180 million people worldwide. The male factor is found in nearly 10% of all couples and is responsible for about 50% of infertility cases (Agarwal et al, 2015). SDF values greater than 20%–30% (by SCSA, alkaline Comet and SCD, obtained in neat semen) are clinically useful for classifying infertile couples into a statistical probability of prolonged time to achieve natural pregnancy, decreased likelihood of pregnancy by IUI, IVF or ICSI and increased risk of miscarriage (Bungum et al, 2008; Evenson, 2013; Gosálvez et al, 2013; Majzoub, Agarwal, Cho, Esteves 2017; Nicopoullos et al, 2019; Oleszczuk et al, 2016; Vandekerckhove et al, 2016). TA B L E 2 Sperm DNA fragmentation testing: methods, thresholds and interpretation

Methods

Findings

| DISCUSSION

| CONCLUSIONS