Epigenetic clock measuring age acceleration via DNA methylation levels in blood is associated with decreased oocyte yield. 2020

Brent Monseur, and Gayathree Murugappan, and Jason Bentley, and Nelson Teng, and Lynn Westphal
Department of Obstetrics & Gynecology, Thomas Jefferson University Hospital, 833 Chestnut Street, Suite 301, Philadelphia, PA, 19107, USA. bmonseur@stanford.edu.

OBJECTIVE To investigate how biologic age (phenotypic age at which your body functions) greater than chronologic age, (age acceleration (AgeAccel)), correlates with oocyte yield. METHODS Thirty-nine women undergoing ovarian stimulation, inclusive of all infertility diagnoses, were included in this pilot study. Methylome analysis of peripheral blood was utilized to determine biologic age. AgeAccel was defined as biologic age > 2 years older than chronologic age. A negative binomial model was used to obtain the crude association of AgeAccel with number of oocytes. A parsimonious adjusted model for the number of oocytes was obtained using backwards selection (p < 0.05). RESULTS Measures of age were negatively correlated with number of oocytes (chronological age Pearson ρ = - 0.45, biologic age Pearson ρ = - 0.46) and AMH was positively correlated with number of oocytes (Pearson ρ = 0.91). Patients with AgeAccel were noted to have lower AMH values (1.29 ng/mL vs. 2.29, respectively (p = 0.049)) and lower oocyte yield (5.50 oocytes vs. 14.50 oocytes, respectively (p = 0.0030)). A crude association of a 7-oocyte reduction in the age-accelerated group was found (- 6.9 oocytes (CI - 11.6, - 2.4)). In a model with AMH and antral follicle count, AgeAccel was associated with a statistically significant 3.3 reduction in the number of oocytes (- 3.1; 95% CI - 6.5, - 0.1; p = 0.036). CONCLUSIONS In this small pilot study, AgeAccel is associated with a lower AMH and lower oocyte yield providing preliminary evidence that biologic age, specifically AgeAccel, may serve as an epigenetic biomarker to improve the ability of predictive models to assess ovarian reserve.

UI MeSH Term Description Entries
D007247 Infertility, Female Diminished or absent ability of a female to achieve conception. Sterility, Female,Sterility, Postpartum,Sub-Fertility, Female,Subfertility, Female,Female Infertility,Female Sterility,Female Sub-Fertility,Female Subfertility,Postpartum Sterility,Sub Fertility, Female
D009865 Oocytes Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM). Ovocytes,Oocyte,Ovocyte
D010062 Ovulation Induction Techniques for the artifical induction of ovulation, the rupture of the follicle and release of the ovum. Ovarian Stimulation,Ovarian Stimulations,Stimulation, Ovarian,Stimulations, Ovarian
D010865 Pilot Projects Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. Pilot Studies,Pilot Study,Pilot Project,Project, Pilot,Projects, Pilot,Studies, Pilot,Study, Pilot
D005260 Female Females
D005307 Fertilization in Vitro An assisted reproductive technique that includes the direct handling and manipulation of oocytes and sperm to achieve fertilization in vitro. Test-Tube Fertilization,Fertilizations in Vitro,In Vitro Fertilization,Test-Tube Babies,Babies, Test-Tube,Baby, Test-Tube,Fertilization, Test-Tube,Fertilizations, Test-Tube,In Vitro Fertilizations,Test Tube Babies,Test Tube Fertilization,Test-Tube Baby,Test-Tube Fertilizations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D044127 Epigenesis, Genetic A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression. Epigenetic Processes,Epigenetic Process,Epigenetics Processes,Genetic Epigenesis,Process, Epigenetic,Processes, Epigenetic,Processes, Epigenetics
D054304 Anti-Mullerian Hormone A glycoprotein that causes regression of MULLERIAN DUCTS. It is produced by SERTOLI CELLS of the TESTES. In the absence of this hormone, the Mullerian ducts develop into structures of the female reproductive tract. In males, defects of this hormone result in persistent Mullerian duct, a form of MALE PSEUDOHERMAPHRODITISM. Mullerian-Inhibiting Hormone,Anti-Muellerian Hormone,Anti-Mullerian Factor,Antimullerian Hormone,Mullerian Inhibiting Hormone,Mullerian Inhibiting Substance,Mullerian Regression Factor,Mullerian-Inhibiting Factor,Mullerian-Inhibitory Substance,Anti Muellerian Hormone,Anti Mullerian Factor,Anti Mullerian Hormone,Hormone, Anti-Muellerian,Mullerian Inhibiting Factor,Mullerian Inhibitory Substance

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