Infertility is a pathological condition of the male or female reproductive system, defined by the inability to achieve clinical pregnancy after 12 months or more of regular, unprotected sexual intercourse. Globally, it is estimated that approximately 17% of individuals experience infertility at some point in their lives, indicating a widespread public health concern.

The etiology of infertility is multifactorial and equally distributed between the sexes. In males, infertility can arise from abnormalities such as oligospermia, asthenozoospermia, or genetic factors impacting spermatogenesis. In females, infertility may result from disorders like anovulation, tubal factor infertility, or uterine anomalies. Notably, epidemiological data over recent decades indicate a rising prevalence of infertility among both sexes, suggesting an increasing burden of reproductive health issues globally.

The standard for evaluation of infertility is quantitative. It is based on the quantity of ovarian follicles and sperm. The age-related decrease in fertility in women correlates with ovarian aging, diminished ovarian reserves, and decreased developmental competence of oocytes, while male infertility is related to low sperm concentration, poor sperm motility, and abnormal sperm morphology. However, this basic examination sometimes fails to detect any abnormality and to clearly distinguish fertile from infertile women and men.  20–40% of people evaluated for infertility will have no identified cause, termed idiopathic infertility. Individuals with idiopathic infertility face a lengthy guesswork based, costly, and emotionally challenging journey with low chances of conception.

Telomere attrition is a primary hallmark of aging and has been proposed as a qualitative biomarker for infertility diagnosis, idiopathic included. Serving as a crucial factor in understanding idiopathic infertility and guiding personalized treatment approaches.

In fact, several studies have assessed the association between telomere length and fertility. However, the substantial intrinsic variability of the telomere measurement techniques hampers comparisons between them.

Using qFISH to investigate the relationship between female fertility and telomere length, studies found that telomere length in oocytes predicted the risk of apoptosis in preimplantation embryos and decreased oocyte telomere length portended poor reproductive outcome in infertile women undergoing in vitro fertilization. Moreover, telomere intensity measured in ovaries was found to shorten as women age.

In male, sperm telomere length of male partners of couples with primary infertility was lower than sperm telomere length of male partners of fertile couples and sperm telomere length correlated negatively with motility and sperm concentration. In addition, it was found that infertile men have shorter sperm telomere length and higher percentage of telomere aggregates. Furthermore, the telomere length in spermatogonia and spermatocytes in testicular biopsy samples were found to be higher in patients whose intracytoplasmic sperm injection cycles resulted in a birth.

Telomeres in peripheral blood leukocytes have been demonstrated to be highly correlated with reproductive organs tissues of male and female. Using qFISH, it was found that leukocyte telomere length was positively associated with length of reproductive lifespan from menarche to menopause. Moreover, our published clinical studies have demonstrated the presence of telomere aberrations (telomere loss, telomere doublets), in addition to telomere shortening, in women and men with infertility and that telomere loss and/or short telomere ratio is superior as a diagnostic tool for identifying couples with infertility than conventional measurements of telomere length. Therefore, leukocyte telomere length, telomere loss, and proportion of short telomeres measured with qFISH is a reliable biomarker that can support personalized fertility counseling and tailored treatments.