Abstract
To evaluate whether telomere length (TL), mitochondrial-DNA (mt-DNA) or epigenetic age estimators based on DNA methylation (DNAm) pattern could be considered reliable predictors of in-vitro-fertilization (IVF) success in terms of live birth rate. Prospective cohort study. Infertility Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. 181 women aged 37-39 years who underwent IVF at a single-centre between January 2017 and December 2018. On the day of recruitment, blood samples were collected, and genomic DNA was isolated from white blood cells. TL, mt-DNA and DNAm assessment was performed using quantitative real-time polymerase chain reaction (qPCR). Biological age (DNAm age) was computed as the algorithm based on methylation pattern of five genes. Epigenetic age acceleration was estimated from the residuals of the linear model of epigenetic age regressed on chronological age. Long Interspersed Nuclear Elements (LINE)-1 methylation pattern was used as a surrogate for global DNA methylation. This study investigated whether peripheral TL, mt-DNA and DNAm could predict live birth in IVF cycles. TL, mt-DNA and LINE-1 methylation were not associated with IVF success. Conversely, DNAm age resulted significantly lower in women who had a live birth compared to women who did not (36.1 ± 4.2 and 37.3 ± 3.3 years, respectively, p = 0.04). For DNAm age, odds ratio (OR) for live birth per year of age was 0.90 (95%CI: 0.82-0.99, p = 0.036) after adjusting for FSH and antral follicle count (AFC) and 0.90 (95%CI: 0.82-0.99, p = 0.028) after adjusting also for number of oocytes retrieved. A significant association also emerged for epigenetic age acceleration after adjustments (OR = 0.91, 95%CI: 0.83-1.00, p = 0.048). DNAm age is associated with IVF success but the magnitude of this association is insufficient to claim a clinical use. However, our findings are promising and warrant further investigation. Assessment of biological age using different epigenetic clocks or focusing on different tissues may reveal new predictors of IVF success.
Highlights
Assisted reproductive technology (ART) has spread worldwide in recent years
This study investigated whether peripheral telomere length (TL), mt-DNA and DNA methylation (DNAm) could predict live birth in in-vitro fertilization (IVF) cycles
TL, mt-DNA and Long Interspersed Nuclear Elements (LINE)-1 methylation were not associated with IVF success
Summary
The chances of pregnancy per cycle have only marginally improved. According to the latest report of the European registers, the clinical pregnancy rate per cycle is only 28% [1]. There is a general consensus that the high rate of aneuploidy observed in embryos derived from in-vitro fertilization (IVF) procedures plays a central role and could explain the sharp decrease of success with age [2,3]. Investigating whether peripheral biomarkers of aging are associated with the IVF success could provide an appealing new tool for counselling and screening. In this scenario, we hypothesised mitochondrial DNA, telomere length and DNAmethylation pattern as possible useful predictors
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