Accuracy of polar body mean telomere length and polar body shortest telomere length of human oocytes obtained after controlled ovarian stimulation for assisted reproduction techniques in predicting embryonic euploidia and aneuploidy

• Grant number: 15/21907-0
• Support Opportunities: Scholarships abroad - Research
• Start date: May 16, 2016
• End date: May 15, 2017
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Paula Andrea de Albuquerque Salles Navarro
• Grantee: Paula Andrea de Albuquerque Salles Navarro
• Host Investigator: David Lawrence Keefe
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: NYU Langone Medical Center, United States

Abstract

The understanding of the effect of maternal age on meiotic nondisjunction is an urgent priority since women are postponing the attempt to become pregnant, a fact that may favor the occurrence of infertility, worse results of assisted reproduction technique (ART) and increase of embryo aneuploidies. It has been suggested that the mean telomere length of human oocyte polar bodies (PB) can predict subsequent embryo development and the implantation of embryos generated by in vitro fertilization (IVF). However, it has been questioned whether shortest telomere length is more accurate than mean telomere length in determining embryo viability and aneuploidy. Primary objective: To compare the accuracy of mean length of all telomeres and of the shortest telomere of oocyte PB of women submitted to controlled ovarian stimulation (COS) for IVF in predicting embryo euploidy and viable and lethal embryo aneuploidies determined by comparative genomic hybridization (CGH) of unviable embryos in the cleavage stage and of blastocysts. Methodology: A randomized, controlled double-blind clinical trial with random subject allocation to parallel groups at a 1:1 ratio [group 1: assay for the measurement of mean length of all PB telomeres by Single Cell Telomere Measurement by qPCR (SCqPCR), and group 2: assay for the measurement of only the shortest PB telomeres by Universal Single Cell Single Telomere Elongation Length Analysis (UScSTELA)]. We plan to include a total of 30 women per group (150 to 180 PB per group). All PB of oocytes obtained after COS will be biopsied and stored individually in liquid nitrogen for SCqPCR or UScSTELA. The 24 chromosome pairs of all unviable embryos on the third day of development and of the trophoectoderm of blastocysts biopsied on the fifth or sixth day of development will be analyzed by CGH for the determination of euploidy and of viable and unviable aneuploidy. We will evaluate the accuracy of the mean length of all telomeres and of the shortest PB telomeres in predicting embryo euploidy and viable and lethal embryo aneuploidies determined by CGH in all unviable embryos in the cleavage and blastocyst stage. The secondary outcomes evaluated will be: maternal age, body mass index, smoking history, number of previous IVF/ICSI cycles, total dose of gonadotropins used and COS duration, serum anti-Müllerian hormone (AMH) and follicle stimulating hormone (FSH) before the beginning of the cycle, number of oocytes retrieved and fertilized, of cleaved embryos and blastocysts, clinical pregnancy, abortion, and liveborns. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NAVARRO, PAULA A.; WANG, FANG; PIMENTEL, RICARDO; ROBINSON, JR., LEROY GEORGE; BERTELI, THALITA S.; KEEFE, DAVID L.. Zidovudine inhibits telomere elongation, increases the transposable element LINE-1 copy number and compromises mouse embryo development. MOLECULAR BIOLOGY REPORTS, v. 48, n. 12, OCT 2021. (15/21907-0)

DA BROI, M. G.; GIORGI, V. S. I.; WANG, F.; KEEFE, D. L.; ALBERTINI, D.; NAVARRO, P. A.. Influence of follicular fluid and cumulus cells on oocyte quality: clinical implications. JOURNAL OF ASSISTED REPRODUCTION AND GENETICS, v. 35, n. 5, p. 735-751, MAY 2018. (15/21907-0)

WANG, F. H.; NAVARRO, P. A.; ROBINSON, L. G.; KRAMER, Y. G.; PIMENTEL, R. N.; RADJABI, R. A.; KEEFE, D. L.. TELOMERIC REPEAT-CONTAINING RNA ( TERRA) IS ACTIVATED DURING EARLY MOUSE DEVELOPMENT, FROM 2-CELL TO BLASTOCYST STAGES, IN A CELL CYCLE-DEPENDENT MANNER.. Fertility and Sterility, v. 108, n. 3, p. 2-pg., 2017-09-01. (15/21907-0)

NAVARRO, P. A.; WANG, F. H.; ROBINSON, L. G.; PIMENTEL, R. N.; RADJABI, R. A.; KRAMER, Y. G.; KEEFE, D. L.. ZIDOVUDINE INHIBITS TELOMERE ELONGATION, INCREASES THE TRANSPOSABLE ELEMENT LINE1 COPY NUMBER AND COMPROMISES MOUSE EMBRYO DEVELOPMENT.. Fertility and Sterility, v. 108, n. 3, p. 2-pg., 2017-09-01. (15/21907-0)

PIMENTEL, R. N.; WANG, F. H.; ROBINSON, L. G.; RADJABI, R. A.; NAVARRO, P. A.; KEEFE, D. L.. IDENTIFICATION AND CHARACTERIZATION OF AMYLOID-LIKE SUBSTANCE IN MOUSE OOCYTES AND EMBRYOS.. Fertility and Sterility, v. 108, n. 3, p. 1-pg., 2017-09-01. (15/21907-0)

RADJABI, R. A.; NAVARRO, P. A.; WANG, F. H.; ROBINSON, L., JR.; PIMENTEL, R.; KEEFE, D. L.. THE WIDELY USED REVERSE TRANSCRIPTASE INHIBITOR, ZIDOVUDINE (AZT), ALTERS MICRO RNA (MIRNA) EXPRESSION IN PREIMPLANTATION MOUSE EMBRYOS.. Fertility and Sterility, v. 108, n. 3, p. 2-pg., 2017-09-01. (15/21907-0)