Association between male (in)fertility and telomeric dysfunction: a systematic review and meta-analysis

Abstract Background The telomere is essential for protecting the stability and chromosomal integrity of the human chromosome and has been proposed as a biological biomarker for cancer and ageing-related diseases. Telomeres have received a lot of interest in the last decade because of their possible...

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Main Authors: Sunny Kumar Jignesh Kumar Patel, Amit Roy Chowdhury, Sujata Kar, Purna Chandra Mohapatra, Birendranath Banerjee
Format: Article
Language:English
Published: SpringerOpen 2025-08-01
Series:Egyptian Journal of Medical Human Genetics
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Online Access:https://doi.org/10.1186/s43042-025-00763-y
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author Sunny Kumar Jignesh Kumar Patel
Amit Roy Chowdhury
Sujata Kar
Purna Chandra Mohapatra
Birendranath Banerjee
author_facet Sunny Kumar Jignesh Kumar Patel
Amit Roy Chowdhury
Sujata Kar
Purna Chandra Mohapatra
Birendranath Banerjee
author_sort Sunny Kumar Jignesh Kumar Patel
collection DOAJ
description Abstract Background The telomere is essential for protecting the stability and chromosomal integrity of the human chromosome and has been proposed as a biological biomarker for cancer and ageing-related diseases. Telomeres have received a lot of interest in the last decade because of their possible role in human (in)fertility. Numerous investigations have been carried out in the past to look at the connections between the clinical outcome, male sperm parameters, telomere length (TL), and embryonic development. However, the results appear to be definitive regarding the potential relationship between male (in)fertility, sperm quality, and leukocyte telomere length (LTL) and/or sperm telomere length (STL). Objective The aim of this meta-analysis was to evaluate the clinical significance and sperm cell reliability for TL assessment (sperm/leukocytes) as a novel predictive biomarker in male (in)fertility, with an overview of general trends. Methods A comprehensive systematic search was carried out for relevant research. This evaluation comprised 34 scientific research publications that examined the association between sperm/LTL and sperm quality, male (in)fertility, DNA Fragmentation Index, reactive oxygen species (ROS), embryonic development, Shelterin complex participation, and protamine insufficiency. Results The meta-analysis revealed that altered sperm parameters with high DNA Fragmentation Index, increased level of ROS, protamine insufficiency, and short STL are all positively correlated with male (in)fertility. The receiver operating characteristic (ROC) analysis was performed to evaluate the effectiveness of the STL assay as a diagnostic tool. The optimal cut-off value for STL in determining male (in)fertility is 1.0, which demonstrates a sensitivity and specificity of 73%. However, there is limited consistency in the data regarding the effects of STL on clinical pregnancy rates and embryonic development. Short conclusion As per reported literatures, altered STL is positively correlated with sperm parameters, a high DNA Fragmentation Index, increased level of ROS, protamine insufficiency, and male (in)fertility. This correlation indicates a strong prognostic potential for male (in)fertility issues. With the evolving an advancing scientific knowledge, STL might be adopted as a novel biomarker for detecting sperm quality, male (in)fertility, and forecasting embryonic development in the near future. A larger cohort of infertile populations must be studied for a better correlation, even if this analysis may provide an overview of trends in the relationship between TL and infertility attributes. Trial registration Registered in the PROSPERO international prospective registry of systematic reviews (CRD42024569515).
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spelling doaj-art-a041b6927f874704a1fcc040bc77ed782025-08-20T03:05:09ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412025-08-0126113310.1186/s43042-025-00763-yAssociation between male (in)fertility and telomeric dysfunction: a systematic review and meta-analysisSunny Kumar Jignesh Kumar Patel0Amit Roy Chowdhury1Sujata Kar2Purna Chandra Mohapatra3Birendranath Banerjee4Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT Deemed to Be UniversityinDNA Center for Research and Innovation in Molecular Diagnostics, inDNA Life Sciences Private LimitedKar Clinic and Hospitals Pvt LtdPrachee Clinic and Nursing HomeinDNA Center for Research and Innovation in Molecular Diagnostics, inDNA Life Sciences Private LimitedAbstract Background The telomere is essential for protecting the stability and chromosomal integrity of the human chromosome and has been proposed as a biological biomarker for cancer and ageing-related diseases. Telomeres have received a lot of interest in the last decade because of their possible role in human (in)fertility. Numerous investigations have been carried out in the past to look at the connections between the clinical outcome, male sperm parameters, telomere length (TL), and embryonic development. However, the results appear to be definitive regarding the potential relationship between male (in)fertility, sperm quality, and leukocyte telomere length (LTL) and/or sperm telomere length (STL). Objective The aim of this meta-analysis was to evaluate the clinical significance and sperm cell reliability for TL assessment (sperm/leukocytes) as a novel predictive biomarker in male (in)fertility, with an overview of general trends. Methods A comprehensive systematic search was carried out for relevant research. This evaluation comprised 34 scientific research publications that examined the association between sperm/LTL and sperm quality, male (in)fertility, DNA Fragmentation Index, reactive oxygen species (ROS), embryonic development, Shelterin complex participation, and protamine insufficiency. Results The meta-analysis revealed that altered sperm parameters with high DNA Fragmentation Index, increased level of ROS, protamine insufficiency, and short STL are all positively correlated with male (in)fertility. The receiver operating characteristic (ROC) analysis was performed to evaluate the effectiveness of the STL assay as a diagnostic tool. The optimal cut-off value for STL in determining male (in)fertility is 1.0, which demonstrates a sensitivity and specificity of 73%. However, there is limited consistency in the data regarding the effects of STL on clinical pregnancy rates and embryonic development. Short conclusion As per reported literatures, altered STL is positively correlated with sperm parameters, a high DNA Fragmentation Index, increased level of ROS, protamine insufficiency, and male (in)fertility. This correlation indicates a strong prognostic potential for male (in)fertility issues. With the evolving an advancing scientific knowledge, STL might be adopted as a novel biomarker for detecting sperm quality, male (in)fertility, and forecasting embryonic development in the near future. A larger cohort of infertile populations must be studied for a better correlation, even if this analysis may provide an overview of trends in the relationship between TL and infertility attributes. Trial registration Registered in the PROSPERO international prospective registry of systematic reviews (CRD42024569515).https://doi.org/10.1186/s43042-025-00763-yTelomere lengthShelterin complexSperm telomereMale (in)fertilityLeukocyte telomereSperm analysis
spellingShingle Sunny Kumar Jignesh Kumar Patel
Amit Roy Chowdhury
Sujata Kar
Purna Chandra Mohapatra
Birendranath Banerjee
Association between male (in)fertility and telomeric dysfunction: a systematic review and meta-analysis
Egyptian Journal of Medical Human Genetics
Telomere length
Shelterin complex
Sperm telomere
Male (in)fertility
Leukocyte telomere
Sperm analysis
title Association between male (in)fertility and telomeric dysfunction: a systematic review and meta-analysis
title_full Association between male (in)fertility and telomeric dysfunction: a systematic review and meta-analysis
title_fullStr Association between male (in)fertility and telomeric dysfunction: a systematic review and meta-analysis
title_full_unstemmed Association between male (in)fertility and telomeric dysfunction: a systematic review and meta-analysis
title_short Association between male (in)fertility and telomeric dysfunction: a systematic review and meta-analysis
title_sort association between male in fertility and telomeric dysfunction a systematic review and meta analysis
topic Telomere length
Shelterin complex
Sperm telomere
Male (in)fertility
Leukocyte telomere
Sperm analysis
url https://doi.org/10.1186/s43042-025-00763-y
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