Reliability of the sperm chromatin dispersion assay to evaluate sperm deoxyribonucleic acid damage in men with infertility

Esteves, Sandro C.; López‐Fernández, Carmen; Martínez, Mercedes González; Silva, Ellen A.; Gosálvez, Jaime

doi:10.1016/j.fertnstert.2021.08.045

Cited by 20 publications

(14 citation statements)

References 52 publications

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“…With respect to a recent study which claims to be the first to assess the intraclass agreement amongst testers of the SCD assay to evaluate DFI in men shows >80% agreement with normal and high DFI categories, 60% intermediate DFI categories. [ 16 ] Our model shows agreement of 90% of normal sperms and 81% of DEG sperms, 65 and 66% of intermediate DFI, seen in the confusion matrix. The setback of the study is that only 400 sperms were assessed from each recipient.…”

Section: Discussionsupporting

confidence: 59%

Deep learning-based robust automated system for predicting human sperm DNA fragmentation index

Kumar¹,

Sharma²,

Halder³

et al. 2023

J Hum Reprod Sci

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A BSTRACT Background: Determining the DNA fragmentation index (DFI) by the sperm chromatin dispersion (SCD) test involves manual counting of stained sperms with halo and no halo. Aims: The aim of this study is to build a robust artificial intelligence-based solution to predict the DFI. Settings and Design: This is a retrospective experimental study conducted in a secondary in vitro fertilisation setup. Materials and Methods: We obtained 24,415 images from 30 patients after the SCD test using a phase-contrast microscope. We classified the dataset into two, binary (halo/no halo) and multiclass (big/medium/small halo/degraded (DEG)/dust). Our approach consists of a training and prediction phase. The 30 patients’ images were divided into training (24) and prediction (6) sets. A pre-processing method M was developed to automatically segment the images to detect sperm-like regions and was annotated by three embryologists. Statistical Analysis Used: To interpret the findings, the precision-recall curve and F1 score were utilised. Results: Binary and multiclass datasets containing 8887 and 15,528 cropped sperm image regions showed an accuracy of 80.15% versus 75.25%. A precision-recall curve was determined and the binary and multiclass datasets obtained an F1 score of 0.81 versus 0.72. A confusion matrix was applied for predicted and actuals for the multiclass approach where small halo and medium halo confusion were found to be highest. Conclusion: Our proposed machine learning model can standardise and aid in arriving at accurate results without using expensive software. It provides accurate information about healthy and DEG sperms in a given sample, thereby attaining better clinical outcomes. The binary approach performed better with our model than the multiclass approach. However, the multiclass approach can highlight the distribution of fragmented and non-fragmented sperms.

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Section: Discussionsupporting

confidence: 59%

Deep learning-based robust automated system for predicting human sperm DNA fragmentation index

Kumar¹,

Sharma²,

Halder³

et al. 2023

J Hum Reprod Sci

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“…This leads to a highly condensed nucleus, which functions to protect the paternal genome from genotoxic agents during its transit toward the oocyte. This protection, however, is not totally effective since sperm with fragmented DNA are often observed after ejaculation, with different incidences among species ( Castro et al , 2018 ; Peris-Frau et al , 2019 ; Crespo et al , 2020 ; Ribas-Maynou et al , 2021 ; Esteves et al , 2022 ). In vitro experiments, which attempted to actively damage sperm DNA, have shown that sperm chromatin limits chromatin breaks caused by nucleases to the TLRs ( Sotolongo et al , 2003 ), while damage caused by reactive oxygen species may affect both toroidal regions and TLRs, thus leading to a more localized damage when double-strand breaks (DSBs) are produced by enzymes, and more extensive damage when DNA is oxidized ( Villani et al , 2010 ; Ribas-Maynou and Benet, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Sperm degradation after vasectomy follows a sperm chromatin fragmentation-dependent mechanism causing DNA breaks in the toroid linker regions

Ribas-Maynou

Nguyen

Valle

et al. 2022

Molecular Human Reproduction

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Vasectomy is a widely used surgical technique creating an obstructive azoospermia. Although sperm cannot be ejaculated, the testis maintains sperm production in vasectomized males. The continuous accumulation of sperm deposited in the epididymis and the vas deferens fraction necessarily need to be degraded and eliminated. While the elimination process is carried out by granulomas that form after vasectomy, the detailed mechanisms of sperm degradation are still not known. The aim was to assess whether sperm chromatin fragmentation (SCF), a mechanism that degrades the entire sperm genome at the toroid linker regions (TLR), is activated after vasectomy in sperm cells. We vasectomized mice and evaluated the presence of TLR-specific double-strand breaks through pulsed-field gel electrophoresis and the Comet assay at 1, 2 and 3 weeks after surgery. Results for DNA damage (Olive tail moment) at single-cell level showed an increase of double-strand breaks after vasectomy for vas deferens sperm after 1, 2 and 3 weeks post-vasectomy (21.78 ± 2.29; 19.71 ± 1.79 and 32.59 ± 1.81, respectively), compared to mock surgery (7.04 ± 1.03; 10.10 ± 1.29 and 8.64 ± 0.85, respectively; P < 0.001). Similar findings were obtained for cauda epididymis sperm (P < 0.001), but not for caput epididymis (P > 0.05). Pulsed-field gel electrophoresis showed the presence of double-stranded breaks between 15 kb and 145 kb, indicating that DNA breaks were produced mainly in the sperm TLRs. Results presented here suggest that SCF is a mechanism activated in vas deferens after vasectomy to degrade sperm DNA when they cannot be ejaculated, preventing their function.

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“…75 Testing should be carried out in andrology laboratories applying validated protocols and strict quality control for the reliable use of SDF tests as biomarkers of sperm DNA damage. 75,128 Although diagnostic tests are usually assessed by their specificity, sensitivity, and predictive values, these metrics are inadequate for assessing the clinical utility of SDF in the context of MAR. The reason is that ICSI outcomes depend on the fertility of both partners, and as a result, SDF testing alone cannot perfectly distinguish between couples that will have a successful ICSI outcome and those that will not.…”

Section: Sdf Testsmentioning

confidence: 99%

“…On this basis, it has been suggested that clinicians may use any of the assays mentioned above to quantify sperm DNA damage in the neat semen, provided that the characteristics and limitations of the chosen SDF test for clinical decision‐making are well‐understood, as detailed elsewhere 75 . Testing should be carried out in andrology laboratories applying validated protocols and strict quality control for the reliable use of SDF tests as biomarkers of sperm DNA damage 75,128 …”

Section: Biomarkers For Identifying Surgical Sperm Retrieval Candidatesmentioning

confidence: 99%

Surgically retrieved spermatozoa for ICSI cycles in non‐azoospermic males with high sperm DNA fragmentation in semen

2023

Self Cite

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Intracytoplasmic sperm injection (ICSI) using surgically retrieved spermatozoa outside the classic context of azoospermia has been increasingly used to overcome infertility. The primary indications include high levels of sperm DNA damage in ejaculated spermatozoa and severe oligozoospermia or cryptozoospermia, particularly in couples with ICSI failure for no apparent reason. Current evidence suggests that surgically retrieved spermatozoa for ICSI in the above context improves outcomes, mainly concerning pregnancy and miscarriage rates. The reasons are not fully understood but may be related to the lower levels of DNA damage in spermatozoa retrieved from the testis compared with ejaculated counterparts. These findings are consistent with the notion that excessive sperm DNA damage can be a limiting factor responsible for the failure to conceive. Using testicular in preference of low‐quality ejaculated spermatozoa bypasses post‐testicular sperm DNA damage caused primarily by oxidative stress, thus increasing the likelihood of oocyte fertilization by genomically intact spermatozoa. Despite the overall favorable results, data remain limited, and mainly concern males with confirmed sperm DNA damage in the ejaculate. Additionally, information regarding the health of ICSI offspring resulting from the use of surgically retrieved spermatoa of non‐azoospermic males is still lacking. Efforts should be made to improve the male partner's reproductive health for safer ICSI utilization. A comprehensive andrological evaluation aiming to identify and treat the underlying male infertility factor contributing to sperm DNA damage is essential for achieving this goal.

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Reliability of the sperm chromatin dispersion assay to evaluate sperm deoxyribonucleic acid damage in men with infertility

Cited by 20 publications

References 52 publications

Deep learning-based robust automated system for predicting human sperm DNA fragmentation index

Deep learning-based robust automated system for predicting human sperm DNA fragmentation index

Sperm degradation after vasectomy follows a sperm chromatin fragmentation-dependent mechanism causing DNA breaks in the toroid linker regions

Surgically retrieved spermatozoa for ICSI cycles in non‐azoospermic males with high sperm DNA fragmentation in semen

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