Abstract

Abstract Study question is there correlation between the mtDNA copy number in cumulus cells and anti-Mullerian hormone level,female age, oocyte quality, embryo morphology, ploidy and blastocyst implantation rate? Summary answer A positive correlation of mtDNA quantity in CCs with the AMH,female age was revealed.There was no correlation between mtDNA quantity and embryo morphology,ploidy,implantation rate What is known already Recent studies have suggested that age-related decreased competence of oocytes may be due to low quantity of mtDNA copy number. Moreover, quantification of mtDNA in CCs may serve as an predictor of blastocysts viability. The purpose of this study is to investigate relative levels of mtDNA in the OCCCs in association with female age, ovarian reserve, embryo morphology, ploidy and blastocyst implantation rate. Study design, size, duration Prospective clinical study performed on 470 CCs retrieved from 72 advanced reproductive age patients undergoing ART treatment with intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidy (PGT-A). Out of the 130 obtained blastocysts 56 embryos were diagnosed as aneuploid, and 74 as euploid. Presently, 51 frozen euploid embryos were transferred (FET). All transferred euploid blastocysts (n = 51) divided into 2 groups: 1 group (n = 21) - implanted embryos, 2 group (n = 30) - non-implanted. Participants/materials, setting, methods Inclusion criteria: age 35-45years;BMI: 18 – 24,9kg/m2; FSH ≤15IU/ml; normal female/male karyotype; non-smokers. Exclusion criteria: genital endometriosis III-IV;severe extragenital pathology; polycystic ovary syndrome; chronic endometritis; > 96% of sperm with abnormal morphology (WHO criteria). MtDNA was assessed by using a quantitative real-time polymerase chain reaction technique. DNA from the trophectoderm samples were amplified and subjected to aneuploidy analysis using array comparative genomic hybridization. In statistic analysis was used Pearson’s correlation coefficients and Fisher’s exact test; p < 0.05 was considered significant. Main results and the role of chance The median age was 37.8 years old (range, 35–45), the mean level of anti-Mullerian hormone (AMH) was 2.66±1.09, and the mean body mass index was 22.3±1.5. A positive correlation of the relative level of mtDNA in the CCs with the patients' age (p = 0.008) and AMH levels (p = 0.003) was revealed. There was no statistically significant correlation between mtDNA copy number and embryo morphology on day 5 (p = 0.7). There was a tendency to increase mtDNA copy number in group 1 vs. group 2, 390 and 299, respectively (p > 0.05). In this study we didn’t find relationship between median mtDNA content of CCs and embryos ploidy (356 vs. 325, in euploid (n = 74) and aneuploidy (n = 56) blastocyst, respectively, p > 0.05). Limitations, reasons for caution Our study was carried out in a relatively small subset of participants and obtained embryos. Correspondingly, the results obtained cannot be readily extrapolated on other groups of patients and need to be confirmed in larger trials. Wider implications of the findings This study showed that mtDNA quantification in CCs isn’t a useful biomarker for prediction embryos implantation potential or ploidy. MtDNA content in CCs correlated only with female age and AMH level. Trial registration number *

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