In the context of a continuously increased delay of motherhood and of an increase of the incidence of premature ovarian failure, it is of the greatest interest to dispose of a predictive marker of the duration of the fertility window. Unfortunately, current available markers of women's fertility (hormonal rates or echography count of small follicles) have a poor predictive value of premature ovarian failure. In the last ten years, some studies have suggested that telomere length may be correlated with premature ovarian failure, but the results of these studies are contradictory. In accordance with guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this systematic review of the literature selected studies evaluating telomere length or telomerase activity in granulosa cells and/or in leukocytes as a premature ovarian failure marker. Five publications (252 premature ovarian failure patients) were included in this review of experimental evidence. Two of them studied telomere length and/or telomerase activity in granulosa cells and 4 in leukocytes in women with premature ovarian failure. For each study, authors determined if there was a positive or a negative correlation between telomeric parameters and premature ovarian failure. 3 studies (178 premature ovarian failure patients) found shorter telomere length in granulosa cells and/or leukocytes and/or lower telomerase activity in premature ovarian failure patients. 2 studies (74 premature ovarian failure patients) presented contradictory results about the correlation of leucocyte telomere length with premature ovarian failure. Shorter telomeres and diminished telomerase activity in granulosa cells appear to be associated with ovarian insufficiency. However, the number of studies and of subjects within are low and the methodology questionable. The confirmation of these results is essential with more subjects, better defined populations and more adapted methodology, in order to consider telomere length in granulosa cells and/or in leucocytes as an early and reliable marker for the decline of ovarian function.

Women’s fertility is characterized both quantitatively and qualitatively mainly by the pool of ovarian follicles. Monthly, gonadotropins cause an intense multiplication of granulosa cells surrounding the oocyte. This step of follicular development requires a high proliferation ability for these cells. Telomere length plays a crucial role in the mitotic index of human cells. Hence, disrupting telomere homeostasis could directly affect women’s fertility. Strongly expressed in ovaries, telomerase is the most effective factor to limit telomeric attrition and preserve ovarian reserve. Considering these facts, two situations of infertility could be correlated with the length of telomeres and ovarian telomerase activity: PolyCystic Ovary Syndrome (PCOS), which is associated with a high density of small antral follicles, and Premature Ovarian Failure (POF), which is associated with a premature decrease in ovarian reserve. Several authors have studied this topic, expecting to find long telomeres and strong telomerase activity in PCOS and short telomeres and low telomerase activity in POF patients. Although the results of these studies are contradictory, telomere length and the ovarian telomerase impact in women’s fertility disorders appear obvious. In this context, our research perspectives aimed to explore the stimulation of ovarian telomerase to limit the decrease in the follicular pool while avoiding an increase in cancer risk.

Male factors are suspected in around half cases of infertility, of which up to 40% are diagnosed as idiopathic. In the context of a continuously increased resort to ART and increased decline of semen parameters, it is of greatest interest to evaluate an additional potential biomarker of sperm quality. According to PRISMA guidelines, this systematic review of the literature selected studies evaluating telomere length in sperm and/or in leukocytes as a potential male fertility biomarker. Twenty-two publications (3168 participants) were included in this review of experimental evidence. For each study, authors determined if there was a correlation between telomere length and semen parameters or fertility outcomes. Of the 13 studies concerning sperm telomere length (STL) and semen parameters, ten found an association between short STL and altered parameters. Concerning the impact of STL on ART results, the data are conflicting. However, eight of the 13 included studies about fertility found significantly longer sperm telomeres in fertile men than in infertile men. In leukocytes, the seven studies reported conflicting findings. Shorter sperm telomeres appear to be associated with altered semen parameters or male infertility. Telomere length may be considered as a new molecular marker of spermatogenesis and sperm quality, and thus is related to male fertility potential. However, additional studies are needed to define the place of the STL in the assessment of individual fertility.