Fertility Preservation the Diagnosis of Cancer Desire of Future Parenthood is Significant Over 70% express a desire for future offspring Over 70% are concerned about the possibility of becoming infertile Mitchell Rosen, MD, HCLD Director, UCSF Fertility Preservation Program and Reproductive Laboratories Program Almost /3 report that infertility concerns influenced their treatment decisions Partridge et al, J ClinOncol. 2004 Preview Fertility preservation benefits as a survivor Treatment effects previously underestimated Options for preserving fertility- considerations Survivors- options Counseling Benefits Survivors Questions: Counseled About Risk by Oncology Team? Visited Fertility Specialist? Preserved Fertility? Letourneau, 202
Counseling Benefits Survivors Less Regret with Counseling Measures: Regret QOL SWLS Counseled About Risk by Oncology Team? Visited Fertility Specialist? Preserved Fertility? Yes 0.8 +/-5.0 (n=499) 8.5 +/-5.2 (n=42) 6.5 +/-3. (n=3) Mean DRS Score No 2.6 +/-5.4 (n=278).6 +/-4.5 (n=726).6 +/-4.2 (n= 736) P-Value P<0.00 P<0.00 P<0.00 Letourneau, 202 Letourneau, 20 Cancer Measures: Regret score QOL SWLS CCR/UCSF Study on Psychosocial Outcomes Letourneau, 202 2
Risk of Infertility after Cancer Treatment Age Reproductive Impairment-Chemotherapy only Menses after chemotherapy Cancer Type Acute Ovarian Failure Infertile but Menstruating Early Menopause Type of cancer Ovarian reserve Leukemia 3% 30% 9% HD 8% 33% 9% NHL 0% 26% 20% Breast 3% 6% 28% Genetics GI 7% 53% 3% Letourneau et al., 20 Cancer Reproductive Impairment- Chemotherapy only Reproductive Impairment- Chemotherapy only Letourneau et al., Cancer 20 Letourneau et al., Cancer 20 3
26 yo G0 Breast cancer HR- Stage disease Oncotype-26 ACT 26 yo G0 Breast cancer HR- Stage disease Oncotype-26 ACT Assessment of Ovarian reserve: AFC Ovarian failure 2 children post therapy Letourneau et al., Nature Oncology 200 Ovarian Reserve and Reproductive Impairment Risks of infertility after Treatment? Anticipate fertility window will be reduced in all patients receiving cytotoxic therapy Anderson, 20 4
Options for Fertility Preservation Options for Women Embryo & Egg Freezing Ovarian Tissue Freezing In Vitro Maturation Ovarian Transposition GnRH Analog/Antagonist Treatments Radical Trachelectomy (Cervical Cancer) Natural Conception In Vitro Fertilization Donor eggs or embryos Adoption (domestic, international, public, private) Surrogacy Before & Before, During & Before & Before Before During Embryo/Egg Cryopreservation Ovarian Physiology Established treatment Takes 2-6 weeks** Ovarian stimulation, egg retrieval Delay treatment Cycle Days 4 28 5
Ovarian Physiology Ovarian Physiology Single wave of follicles Preovulatory follicles atresia Cycle Days 4 28 Cycle Days 4 28 Ovarian Physiology Ovarian Stimulation.Conventional FSH estrogen Progesterone Preovulatory follicles atresia Preovulatory follicles atresia Cycle Days 4 28 Cycle Days 4 28 6
Ovarian Stimulation.Conventional 2. Random stimulation Preovulatory follicles atresia Cycle Days 4 28 Random Start = Conventional Conventional Late Follicular Luteal P value Start Phase Start Phase Start (n=88; 03 cycles) (n=2; 2 cycles) (n=2; 2 cycles) Age (yrs) 33.8 ± 5.3 33.3 ± 3.9 34.5 ± 5. NS count (AFC) 3 (9-9) (5.5-2) 3 (7-8.5) NS Days of ovarian stimulation 9 (8-0) (0-.5)a (0-2)a <0.00 Total dose of gonadotropins (IU) 3405 ± 27 3837 ± 074 4208 ± 462b 0.04 Gonadotropin dose/day 36 ± 94 366 ± 88 369 ± 87 NS Follicles 3 mm 2 (6-7).5 (7.5-8.5) 3 (9-9.5) NS Oocytes retrieved 5 (9-23) 4 (8.5-27) 6 (0.5-25) NS Mature oocytes (MII) retrieved (6-6) 0.5 (5-6.5) (6-8) NS MII oocyte / total oocytes ratio 0.7 (0.60-0.82) 0.74 (0.59-.80) 0.69 (0.56-.84) NS Oocyte / AFC ratio.4 (0.75-.7).27 (0.92-.73).20 (0.92-.67) NS Mature oocyte / AFC ratio 0.83 (0.46-.2) 0.84 (0.6-.3) 0.83 (0.62-.22) NS Fert. rate after ICSI (2PN/MII) 0.83 (0.69-0.9) 0.78 (0.75-.80) 0.96 (0.77-.0) NS Cakmak, 203 Other considerations. Hormone receptors Modifications ( i.e aromatase inhibitors) Ovarian reserve, desires Multiple cycles Hormone treatment- delays in building a family Genetic Risks( i.e BRCA) PGD for prevention of vertical transmission The PROMISE trial randomized trial: Triptorelinvs. Placebo The primary outcome: Immediate menopause Results: Chemotherapy alone: 25.9% Chemotherapy + triptorelin-8.9% Difference: 7% (95%CI 7.9 vs 26% P<0.00) Not assessed: Fertility Early Menopause (after recovery) Del Mastro, 20 7
Ovarian Tissue freezing Post- Treatment Options 20-30 live births (All Orthotopic transplant) Challenges/Limitations Risk for recurrences Short life (3-5 yrs) ischemia General anesthesia VS. Fertility preservation Infertility therapy Donor Eggs & Embryos Surrogacy Adoption Conclusion Fertility preservation benefits as a survivor Treatment effects previously underestimated Options for preserving fertility- considerations Survivors- options Parentingis unlike anything else I have ever experienced. It is the most profoundly life-affirming thing I have ever done. I am grateful that --through all the uncertainty and fear surrounding my cancer diagnosis and treatment --we held on to that dream of becoming parents and made it a reality. 8
Clinical Team Marcelle Cedars MD Evelyn Mok-Lin MD James Smith MD(male) Eve Harris- Patient Navigator Audra Katz, RN Cathy Chin, RN Nanette Lerma, RN Xinli Yang-embryologist Rosemary Benson-Call Center Thank You UCSF Fertility Preservation Program Research Team Thom Remble Hakan Cakmak MD Tomoko Ozawa PHD Jo Chien MD Michelle Melisko MD Joe Letourneau MD Jessica Chan, MD Erin Ebbel MD SaiChan MS Danielle Cipres MS Meera Shah MD 9