Mosaicism per chromosomes per age

absolutely necessary, 33% cited a multidisciplinary team, 33% ability to perform OTC and/or TTC, 33% ability to offer or refer for REI services, and 11% mental health support. CONCLUSIONS: Even within the PIN of the oncofertility consortium, there is wide programmatic variation in pediatric FP services among member institutions. The majority of pediatric FP programs are still facing major barriers, particularly financial. Referrals for fertility counseling remain inconsistent and obtaining IRB approval for tissue preservation remains problematic at many centers. Consensus guidelines, as well as improved financial resources for FP programs and patients, would help provide consistent and effective FP care for pediatric patients facing potentially gonadotoxic conditions and therapies. O-210 Wednesday, November 1, 2017 12:15 PM CO-TRANSPLANTATION OF HUMAN OVARIAN TISSUE WITH IGF-1 PRODUCING ENDOTHELIAL CELLS IMPROVES SURVIVAL OF EARLY STAGE FOLLICLES AND IS ASSOCIATED WITH ACCELERATED FOLLICULAR GROWTH IN VIVO. J. Lekovich, L. Man, N. Pereira, Z. Rosenwaks, D. James. The Ronald O. Perelman and Claudia Cohen CRM, Weill Cornell Medicine, New York, NY. OBJECTIVE: Most of the follicles in human ovaries remain dormant and only a small proportion is activated into the growing pool. Mobilization of these follicles is possible via upregulation of Akt pathway. IGF-1 is a potent activator of Akt pathway. We sought to investigate if addition of endothelial cells (ECs) that continuously produce IGF1 to human ovarian tissue transplant activated Akt pathway and mobilized early stage follicles. DESIGN: Prospective randomized control trial MATERIALS AND METHODS: Human ovarian tissue was co-transplanted with ECs previously transfected with human IGF-1 gene (IGFECs) into 3-month old immunocompromised, oophorectomized mice (study group). Blank ECs were co-transplanted with human ovarian tissue in the control group. Animals were sacrificed after 3 weeks and the tissue was analyzed histologically and by immunostaining (phospho-Akt (pAkt) as a marker of Akt activation and Ki67 as a marker of proliferation). Primary outcomes: total number of follicles/graft, mean proportion of primordial, primary and secondary follicles. Secondary outcomes: mean proportion of simple (
PREIMPLANTATION GENETIC TESTING - MOSAICISM O-211 Wednesday, November 1, 2017 11:00 AM MOSAICISM PER CHROMOSOMES PER AGE. T. Escudero,a E. M. Armenti,a A. Jordan,a L. Ribustello,a S. S. Sawarkar,b S. Munne.c aReprogenetics, Livingston, NJ; b Research, Reprogenetics, a CooperSurgical Company, Livingston, NJ; cCooperGenomics, Livingston, NJ. OBJECTIVE: This study aims to compare the differences between mosaicism and aneuploidy in regards to the influence of maternal age at the chromosomal level. DESIGN: Retrospective study of 44608 blastocyst-stage embryos from 8453 cycles from fertility centers throughout the US, analyzed by NGS. MATERIALS AND METHODS: Samples from each embryo underwent Illumina NGS protocol and mosaic information for each chromosome was obtained. For this study, only chromosomes diagnosed as full chromosome mosaic or aneuploid were considered; no partial chromosomal abnormalities were considered. The total number of chromosomes analyzed was 1,025,984.These embryos were further subdivided in five maternal age groups: <35 year old (yo), 35 to 37 yo, 38 to 40 yo, 41 to 42, >42 yo; and an additional group of egg donors. Pearson test was calculated for each chromosome to ascertain the correlation for age for each chromosome for mosaicism and aneuploidy. RESULTS: Out of the 1,025,984 chromosome pairs analyzed, 12,545 pairs presented whole chromosome mosaicism, with an overall chance of mosaicism of 1.2% per chromosome. Pearson test showed correlation with age for 5 chromosomes (12, 16, 19, 21, and 22). In regards to aneuploidy, 49,910 chromosome pairs were aneuploid, with an overall chance of aneuploidy of 4.9% per chromosome. Pearson test showed correlation with age for all chromosomes but 5 chromosomes (1, 2, 7, 12, and XY). CONCLUSIONS: Only 5 chromosomes showed maternal age effect in mosaicism. Chromosome size may be a factor as most of the chromosomes influenced by age are of small size, although other chromosomes of comparable size do not show maternal effect. In regards to aneuploidy, the majority of the chromosomes showed maternal age effect and only a few did not. Surprisingly, chromosome 12, which showed maternal effect for mosaicism, did not show maternal effect for aneuploidy. Although mosaicism and aneuploidy are originated by similar mechanisms (anaphase lag and non-disjunction), their outcomes are quite different. The correct segregation of chromosomes in meiosis is affected by two factors: an active cohesin complex and the presence of at least one crossover per pair of homologous chromosomes. The results of this study are concordant with these two factors. As an egg ages, the smaller chromosomes show more aneuploidy as they cannot maintain the cohesin complex and have less crossovers. For the segregation of chromosomes in mitosis, the cohesin complex also has an active role, but the crossover of chromosomes is not needed. After fertilization, the soluble fraction of the cohesin complex is activated and ready to be used for the following mitotic divisions. As the cohesin complex is replenished, mosaicism does not show an age effect for most of the chromosomes. Also, the more active role of the cohesin complex in mitosis could be the reason why the aneuploidy rate is 4 times higher than the mosaicism rate.

Table

Study group IGF-1 in supernatant of cultured ECs (ng/mL) Total follicles/graft Primordial follicles (%) Primary follicles (%) Secondary follicles (%) Simple secondary follicles (% of all secondary follicles) Multi-layer (pre-antral)follicles (% of all secondary folllicles)

Control group

P

1275.3  67.1 16.2  8.2

<0.01

76  34.1 23 48 28 37

28.3  13.5 30 51 19 68

0.01 0.08 0.4 0.07 <0.01

63

32

<0.01

CONCLUSIONS: Short term treatment of human ovarian tissue with IGF1 in vivo was associated with improved survival of all follicles, accelerated follicular growth to pre-antral stage, and activation of a greater proportion of primordial follicles, likely via activation of Akt pathway. Supported by: Institutional. ASRM.

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ASRM Abstracts

O-212 Wednesday, November 1, 2017 11:15 AM TRANSFER OF EMBRYOS WITH SEGMENTAL MOSAICISM IS ASSOCIATED WITH A SIGNIFICANT REDUCTION IN LIVE BIRTH RATE COMPARED TO L. Kroener,a EUPLOID CONTROLS. T. Zore,a C. Wang,b L. Liu,c R. P. Buyalos,a,b G. Hubert,a,b M. Shamonki.a,b aObstetrics and Gynecology, University of California Los Angeles, Los Angeles, CA; bFertility and Surgical Associates of California, Thousand Oaks, CA; c PacGenomics, Agoura Hills, CA. OBJECTIVE: Segmental mosaicism is a complex issue with minimal to no data on established thresholds for labeling an embryo euploid versus aneuploid, or on pregnancy outcomes on the transfer of embryos with segmental mosaicism. We aim to evaluate the impact of segmental mosaicism on pregnancy and live birth rates (LBR) from the transfer of embryos previously designated as euploid. DESIGN: Retrospective cohort analysis. MATERIALS AND METHODS: All PGS-screened frozen single embryo transfers from January 2015 - December 2015 from a high-volume fertility center were included. Transferred embryos were all designated euploid by

Vol. 108, No. 3, Supplement, September 2017