Shorter telomere length of white blood cells is associated with higher rates of aneuploidy in women undergoing in vitro fertilization

Abstract

Telomeres are tandem repeats of the sequence TTAGGG located at the ends of chromosomes. Telomere shortening is a key mechanism of cell senescence and aging. Telomere shortening has been associated with decreased oocyte quality through disruption of chromosome alignment and spindle structure. In this study, we sought to evaluate whether the telomere length of cumulus cells (CC) or white blood cells (WBC) in an infertile population is associated with reproductive aging. Prospective cohort study. Women undergoing IVF between July 2017 and December 2018 were recruited for the study under Institutional Review Board approval. Blood and CC were collected at the time of oocyte retrieval. Genomic DNA was isolated and stored at -80°C. Telomere DNA length was measured by quantitative real-time PCR and normalized to AluYa5 sequence as an endogenous control for each sample. Linear regression was applied to determine if telomere length (TL) of WBC or CC was associated with patient age, number of oocytes retrieved, number of mature (M2) oocytes retrieved, blastulation rate, aneuploidy rate, serum anti-mullerian hormone (AMH), and serum estrogen (E2) level on day of hCG or GnRHa administration. TL data was available for WBC samples from 156 individuals and for CC samples from 142 patients. Data was available for both tissue types in 139 patients (age range 25.7 to 45.0 years, mean 35.0 ± 4.0 years). As expected, WBC telomere length declined with increasing age (p=0.006). In contrast, CC TL was equivalent in patients of all ages and failed to show anticipated age-related shortening. As such, CC TL was unrelated to any index of ovarian performance including number of oocytes retrieved (p=0.95), M2 oocytes retrieved (p=0.81), blastulation rate (p=0.98), aneuploidy rate (p=0.30), AMH level (p=0.32), or mid-cycle E2 level (p=0.77). Consistent with these data, CC TL was not associated with patient age (p=0.99). While WBC TL declined with increasing maternal age, it was a poor predictor of quantitative ovarian performance [total oocytes retrieved (p=0.47), number of M2 oocytes retrieved (p=0.30), AMH level (p=0.13), E2 level (p=0.36), and blastulation rate (p=0.48)]. However, TL of WBC samples was associated with embryonic competence as evidenced by aneuploidy rate (p=0.02), with shorter TL associated with higher aneuploidy. The TL of CC was not associated with patient age or any index of ovarian or embryonic performance. Declining WBC TL was associated with increasing maternal age and increasing rates of embryonic aneuploidy. Further studies are necessary to determine if changes in peripheral somatic cell TL are truly prognostic for aneuploidy rate within a given maternal age group or if this finding is simply reflective of a simultaneous change which occurs with age.