How effective is egg freezing as a preventative treatment for young women in securing their ability to reproduce later in life?

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How effective is egg freezing as a preventative treatment for young women in securing their ability to reproduce later in life? Vitaly A. Kushnir MD Center for Human Reproduction New York City

Milestones in ART 1978 Louise Joy Brown, first IVF baby 1981 Elizabeth Carr, first IVF baby in USA 1983 First birth after egg donation 1985 First birth from cryopreserved embryo 1985 Transvaginal ultrasound for follicle monitoring 1990 First report of births after PGD 1992 First human birth after ICSI Oocyte Cryopreservation

Oocyte Cryopreservation Cryopreservation Storage Thawing Women at risk of losing ovarian function Fertility preservation (medical and elective) Eliminating ethical concerns of embryo cryopreservation Solving the dilemma of abandoned frozen embryos in the IVF laboratory Donation

Fertil Steril. 2013 Jan;99(1):37-43.

MYTH: Career

TRUTH: Few Good Men

MYTH: Preventative Medicine goal is to protect, promote, and maintain health and well-being and to prevent disease, disability, and death. Fertility Insurance coverage by contract whereby one party undertakes to indemnify or guarantee another against loss by a specific contingent or peril Informed Consent given by a patient to a doctor for treatment with full knowledge of the possible risks and benefits.

TRUTH: Commercial Product Egg-freezing is being promoted at parties where alcohol is served It s so incredibly different from how you would usually counsel a patient about a medical procedure -The Hastings Center

TRUTH: Commercial Product

Fertility and Sterility To freeze or not to freeze: decision regret and satisfaction following elective oocyte cryopreservation Eleni A. Greenwood, M.D., M.Sc., Lauri A. Pasch, Ph.D., Jordan Hastie, B.S., Marcelle I. Cedars, M.D., Heather G. Huddleston, M.D.

Fertility and Sterility DOI: (10.1016/j.fertnstert.2018.02.127)

TRUTH: Most Women Will Not Experience Infertility Age (years) Infertile 20-24 7.0 25-29 8.9 30-34 14.6 35-39 21.9 40-44 28.7 Science 1986;23:1389

MYTH: Cost Effectiveness Devine et al. Fertility and Sterility 2015 103, 1446-1453.e2

TRUTH: Cost Effectiveness

TRUTH: Cost Effectiveness https://nyulangone.org/locations/fertility-center/egg-freezing-embryo-banking ($13,548+$1,500) x 2,600 OC cycles = $39,124,800 / 104 babies = $376,200 OC cost/per baby (+ oocyte thaw/ivf costs)

NYU Data reported to SART 2014: 11 Live Birth from 33 Transfers 2015: 4 Live Birth from 16 Transfers 2016: 4 Live Birth from 21 Transfers Total: 19 Live Birth from 70 Transfers

MYTH: Live Birth Rates Compare frozen eggs from fertile women to fresh eggs of infertile patients Adjustments in wrong direction! Crawford S, et al. Fertil Steril. 2017 Jan;107(1):110-118

MYTH: Live Birth Rates

MYTH: Live Birth Rates Hum Reprod. 2017;32(4):853-859.

TRUTH: Live Birth Rates Frozen Eggs Frozen Embryos SART 2016 preliminary data

Donor Oocyte Vitrification Program SPAIN (IVI) 2007 2013 (n= 3,467 cycles) Oocyte survival rate was 90.4% Implantation 39% Delivery rate/donation cycle 39.1% CDR/donation cycle was 78.8% Cobo A, Fertil Steril. 2015 Dec;104(6):1426-34.e1-8.

Live Birth Rate per recipient cycle start (%) TRUTH: Oocyte Donation Kushnir et al. JAMA 2015 60 50 40 30 20 10 0 2013 2014 2015^ Fresh Donor Oocytes Cryopreserved Donor Oocytes Kushnir et al. J Ovarian Res. 2018

What Should We Do Instead of Universal Elective Egg Freezing?

(i) pro-fertility advice (ii) knowledge of fertility status (iii) knowledge of female reproductive lifespan

Cumulated incidence of spontaneous pregnancies. a) Yellow, low risk score. b) Orange, medium risk score. c) Red, high risk score. Birch Petersen et al. Acta Obstet Gynecol Scand. 2017 Mar

Premature Ovarian Senescence *Nikolaou and Templeton, Hum Reprod 2003

Normal range for AMH PCO DOR Kelsey TW et al. PLoS ONE 2011

Ovarian Reserve Biomarkers Zarek SM. JCEM, 2015 Steiner AJ. JAMA, 2017

Race/ethnic disparities in reproductive aging Bleil ME; Fertil Steril. 2014 Jan;101(1):199-207.

Tal R, Seifer DB. Int J Endocrinol. 2013.

BMI and Ovarian Reserve Moy V. J Assist Reprod Genet. 2015 Sep;32(9):1305-11

Autoimmunity and Ovarian Reserve Vega M, et al. AMH levels decline with the presence of antiphospholipid antibodies. Am J Reprod Immunol. 2016 Oct;76(4):333-7.

X Chromosome Crossroads of Immunology and Ovarian Function The FMR1 gene is located on the long (q) arm of the X chromosome at position 27.3

Wittenberger et al. Fert Stert 2007; 87:456-465

CHR data, Kushnir et al

Kushnir VA et al. Fertil Steril 2013, 100(3), S114. Gleicher N. et al. Transl Res. 2015, Nov;166(5):502-7

Gleicher N, Kushnir VA, Barad DH. Prospectively assessing risk for premature ovarian senescence in young females: a new paradigm. Reprod Biol Endocrinol. 2015 Apr 18;13:34

Improve Family Planning Fertility Preservation Kushnir VA, et al. Reprod Biomed Online. 2014