Journal of Preventive Medicine

Introduction
According to the definition of the World Health Organization, infertility is the inability of couples to have children without using contraceptive methods after one year of regular sexual intercourse. Infertility is a big crisis. Couples with infertility experience various emotional disorders, reduced communication with each other and others, and disruption in activities and decision-making in life. With the development of human societies, changes in lifestyles and individual habits, there is a possibility that the rate of infertility will increase in the future, which, in addition to damaging the family foundation, will cause problems for the society; therefore, medical science is always trying to find ways to identify and prevent this impairment. Epigenetics is the study of change in gene expression that causes a difference in phenotype or effect on the gene without changing the structure and sequence of DNA. As one of the epigenetic factors, miRNAs have an important impact on vital biological processes such as growth and development, differentiation, proliferation, apoptosis, metabolism, and response to stress, which play a role in regulating gene expression and exert their effects through downregulation or upregulation. They can be used as prognostic molecules and for diagnostic purposes, because they have the characteristics of a good biomarker such as high specificity, sensitivity, stability, non-invasiveness, and easy access. Considering the importance of infertility in medical sciences, the purpose of this study is to review the studies conducted on peripheral blood miRNAs for the prevention and diagnosis of male infertility.

Methods
This is a review study that was conducted in 2022. A search was conducted in databases such as ScienceDirect, PubMed, Medline, Google Scholar, SID and MagIran using the keywords: Male infertility, Diagnosis, Identification, miRNAs, Biomarkers, Non-invasive, Peripheral blood, Semen analysis, Testicular biopsy, and Treatment in Persian and English to find related studies conducted in the last 10 years with no limitation in the study country and population. To select the articles, their titles and abstracts were examined based on the inclusion criteria.

Results
Diagnosing and identifying male infertility in the early stages of referral is very important in facilitating the treatment and creating peace in couples for childbearing. In this regard, accurate and reliable methods should be used. Semen analysis in men has many limitations; as a primary diagnostic test in examining male infertility, it cannot directly identify and measure the causes of infertility and there is a need to find new molecular biomarkers for diagnosis and classification. Testicular biopsy lacks the sensitivity and specificity necessary to provide an accurate diagnosis, and it is not successful in some non-obstructive azoospermia patients; an in-vitro fertilization program was thus suggested by donating male gametes. However, so far, no precise test or factor has been identified that can predict the presence of mature spermatozoa in azoospermia. Therefore, non-invasive molecular testing using peripheral blood miRNAs can provide valuable information for prognosis and diagnosis of male infertility. The use of miRNAs, due to their role in cell regulation disorders and infertility, seems necessary to confirm sperm analysis tests, and is suggested as a less invasive, simple and cost-effective method in clinical studies for screening of male infertility. Their use in peripheral blood samples has been less studied; global standardization and correct analyses are needed to avoid errors.

Discussion
The present review study with the aim of investigating the use of peripheral blood miRNAs as a non-invasive biomarker for identifying male infertility indicated that early, rapid and timely diagnosis and screening of infertility in men using accurate and efficient molecular methods along with effective treatments can be useful in reducing the rate of male infertility and increasing childbearing. Peripheral blood miRNAs in infertile men have diagnostic and prognostic value and are proposed as biological biomarkers of male infertility due to their ability to increase or decrease the expression of genes effective in the process of spermatogenesis. Therefore, miRNAs, by determining the gene expression profile, can be useful, because diagnosis and treatment based on these molecular biomarkers, due to the features mentioned in preventing unnecessary biopsies, confirming and increasing the accuracy of sperm analysis results and preventing long treatment processes, seem necessary. In recent years, many efforts have been made to compensate for the decline in growth and fertility rates in Iran. Comprehensive plans for prevention or early screening of infertility can increase the hopes for its treatment. Despite many advances regarding the role of miRNAs as a biomarker in infertility, this topic is in the initial stages of research and needs more information and investigation. We hope that, with the development of technology and techniques for using miRNAs, new methods for prevention, screening, identification and targeted treatment of male infertility be found in the future to bring happiness and peace for the couples who want children.

Ethical Considerations

Compliance with ethical guidelines
The consent of the patients who gave blood samples was taken and all the legal work of the article has been done. But the data and findings were not used in this work, because it was a review and comparison work. The code of ethics is registered in Zahedan University of Medical Sciences (Code: IR.ZAUMS.REC.1399.167).

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. 

Authors' contributions
Reviewing the articles and writing the first version of the article: Nasim Naeimi; Review and approval of the final version of the article: Homa Mohseni Kouchesfehani; Consultation, study design, review and approval of the original version of the article: Zahra Heidari; Extraction of articles, guidance and advice: Hamidreza Mahmoudzadeh Sagheb; Collection and review of articles: Saeed Movahed.

Conflicts of interest
The authors declared no conflict of interest.
 

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