AGE IS NOTHING BUT A NUMBER: MATERNAL AGE AS A PREDICTOR OF EMBRYONIC MITOCHONDRIAL DNA CONTENT

Abstract

Maternal age has long been established as the leading indicator of a woman's fertility. As reproductive technologies continue to advance, new methodologies must be investigated to optimize the success of this ever-growing patient population. With a limited number of ways to appropriately assess embryo quality for optimal success, quantifying mitochondrial DNA (mtDNA) offers a promising new parameter in assisted reproductive technologies (ART). Increased mtDNA have been linked to decreased pregnancy rates and is thought to be indicative of poor embryo quality potentially due to oxidative stress; while lower mtDNA scores have been associated with improved outcomes. Yet, in order to better understand mtDNA score, investigation into the underlying biological causes associated with elevated levels is warranted. To determine if there is any correlation between age and the quantification of mtDNA. Retrospective chart review at a private, multi-site fertility clinic. All euploid embryos from patients who underwent in-vitro fertilization (IVF) with PGT-A from January to September 2019 utilizing a PGT lab that reports mtDNA (MitoScore; Igenomix) were included. Baseline characteristics were measured, and IVF cycle statistics recorded. Patients were then divided into groups based on age: <35, 35-37, 38-40, >40. T-tests, linear regression and chi-square analysis were used to analyze the data using SPSS (SPSS Inc., Chicago, IL, USA). A total of 465 embryos were analyzed. The age of patients ranged from 21 to 43, with the average age being 32.75 years old. Linear regression analysis showed there was no statistically significant correlation between age and mtDNA quantity, with an r-squared value of 0.011. When divided into groups based on age, there was no statistically significant difference in the average mtDNA quantity, where average scores were 22.45, 23.27, 21.66, and 21.82, respectively (p>0.05). Pregnancy rates between all the groups were also similar. Our results demonstrate that maternal age and the quantification of mtDNA are not related. Accordingly, our data shows a patient's age is not an indicator of mtDNA content in the developing embryo, and thus does not predict embryonic metabolic health. These results indicate that cytoplasmic environment of an otherwise euploid embryo is not dependent on age. Though age has been well established to be correlated with increased rates of chromosomal aneuploidy, it does not seem to impact embryo quality of euploid status. Further studies on the clinical application of mtDNA quantification is warranted.