FERTILITY PRESERVATION Juergen Eisermann, M.D., F.A.C.O.G South Florida Institute for Reproductive Medicine South Miami Florida 1
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Oocyte Cryopreservation Experimental option Offer to single cancer patients with no male partner/or those who do not wish to use a sperm donor Requires ovarian stimulation Many cancer patients may not have time to complete a stimulated cycle 5
Oocyte Cryopreservation 1986 First human live birth from cryopreserved oocytes Early results disappointing Low survival, fertilization, pregnancy rates Very fragile meiotic spindle Ice crystals can form and cause damage to spindle apparatus Mature oocytes are extremely fragile due to their large size, high water content and chromosome arrangement Chen C. Pregnancy after human oocyte cryopreservation. Lancet 1986;1:884-886.. Recent Oocyte Cryopreservation Technology Better post-thaw survival, fertilization, pregnancy rates ICSI has overcome the zona hardening caused by the freezing process preventing fertilization 1997 First human live birth after transferring embryos generated by ICSI of cryopreserved oocytes* Estimated > 200 babies have been born from previously frozen oocytes & # of pts with frozen oocytes is > 1000 *Porcu E, Fabbri R, Seracchioli R, et al. Birth of a healthy female after intracytoplasmic sperm injection of cryopreserved human oocytes. Fertil Steril 1997;68:724-726.. Different Cryopreservation Protocols Available Slow freeze-rapid thaw method Most commonly used and achieved the first pregnancy worldwide Estimated live-birth rate per oocyte thawed 2%* Vitrification Highly concentrated cryoprotectant solution with a high cooling rate used to achieve a glassy, solid, state without causing ice formation Easier and less expensive Does not require a programmable freezer Improved post-thaw survival and fertilization rate and live births have been achieved by vitrification of mature oocytes using ethylene glycol and dimethylsulphoxide as cryoprotectants Estimated live-birth rate per oocyte thawed 4%* *Oktay et al. Efficiency of oocyte cryopreservation; a meta-analysis. Fertil Steril 2006;86:70-80 6
Clinical Utility of Oocyte Cryopreservation Primarily offered to cancer patients Women undergoing ART with extra eggs that prefer not to create embryos Women who are interested in deferring reproductive aging Recent Efficacy of Oocyte Freezing Methods Compared Offered to couples doing IVF with > 9 oocytes If no pregnancy in fresh cycle, use cryopreserved oocytes Oocytes frozen in 165 cases; 63 choose to use oocytes 66% ( SR-F) -73% (V) survived & fertilized with ICSI ( Randomly chosen for SR-F or V) Pregnancy success 18% (SR-F) 34 % (V) Needed 21 (V) oocytes vs 45 ( SR-F) oocytes for clinical pregnancy Fiorvanti et al. Prospective randomized comparison of human oocyte freezing and vitrification: an update. O-35 63 rd Annual Meeting of ASRM, October 2007 Safety of Oocyte Freezing 149 pregnancies observed; 89 pregnancies resulted in live birth of 105 babies conceived with frozen oocytes (SR- F) Average gestation 38.9 weeks Average weight 3.35 kg for singletons and 2.6 kg for twins 35 pregnancies ended in sp ab 1 pregnancy aborted for Trisomy 21 2 of 105 babies born had malformations Borini et al. Survey of 105 babies born after slow-cooling oocyte cryopreservation. O-36 63rd Annual Meeting of ASRM, October 2007 7
Health of Children Born from Cryopreserved Oocytes Literature survey 272 clinical pregnancies up to July 2006 93.8% nl results for eggs that had PGD of second polar body and karyotyping after fertilization 51 sp ab, 2 ectopics, 156 deliveries of 197 babies & 63 ongoing pregnancies 69.5% pts. reported and 99.3% of babies were healthy F/u reported at 6 months to 3 yrs for 31 % of children all developing normally One twin was born with a congenital anomaly Tur-Kaspa et al. Genetics and health of children born from cryopreserved oocytes. O-37 63rd Annual Meeting of ASRM, October 2007 Rate of Ovarian Failure After Chemotherapy 168 young patients with various cancer following chemotherapy Failure rate for entire group was 34% **Age predicted highest chance of ovarian failure All patients treated with combination chemotherapy Alkylating agents imposed highest risk AML 15%; nonhodgkin s lymphoma 44%; Hodgkin s disease 32%; breast cancer 31% Meirow D. Ovarian injury and modern options to persevere fertility in female cancer patients treated with high dose radio-chemotherapy for hemato-oncological neoplasias and other cancers. Leuk Lymphoma 1999;33:65-76. Partial Ovarian Injury Patients menstrual cycle may continue after therapy completed Destruction of primordial follicles is not all or none -- dose related, especially with cyclophosphamide High risk for premature menopause! Recommended that patients who regain ovarian function do not delay childbearing! Should try after a few years of disease-free intervals, but not less than 6-12 after treatment Meirow D, Epstein M, Lewis H, et al. Administration of cyclophosphamide at different stages of follicular maturation in mice: effects on reproductive performance and fetal malformations. Hum Reprod 2001;16:632-637. 8
Effect of Radiation Dose and Age on Ovarian Function. Ovarian cgy Results 60 No deleterious effect 150 No deleterious effect in young women; some risk for sterilization in women older than 40 250-500 In women aged 15 40, 60% permanently sterilized; remainder may suffer temporary amenorrhea. In women older than 40, 100% permanently sterilized 500-800 In women aged 15 40, 60% 70% permanently sterilized; remainder may experience temporary amenorrhea. No data available for women over 40 >800 100% permanently sterilized Damewood MD, Grochow LB. Prospects for fertility after chemotherapy or radiation for neoplastic disease. Fertil Steril. 1986;45:443-459 9