Desire of Future Parenthood is Significant Fertility Preservation After the • Over 70% express a desire for future offspring Diagnosis of Cancer • Over 70% are concerned about the possibility of becoming infertile Mitchell Rosen, MD, HCLD Director, UCSF Fertility Preservation Program • Almost 1/3 report that infertility concerns and Reproductive Laboratories Program influenced their treatment decisions Partridge et al, J Clin Oncol. 2004 Preview Counseling Benefits Survivors • Fertility preservation – benefits as a survivor • Questions: – Counseled About Risk by Oncology Team? • Treatment effects – previously underestimated – Visited Fertility Specialist? • Options for preserving fertility- considerations – Preserved Fertility? • Survivors- options Letourneau, 2012 1
Counseling Benefits Survivors Less Regret with Counseling Mean DRS Score • Measures: Yes No P-Value – Regret Counseled 10.8 12.6 About Risk by +/- 5.0 +/- 5.4 P<0.001 Oncology (n=499) (n=278) Team? – QOL Visited 8.5 11.6 Fertility +/- 5.2 +/- 4.5 P<0.001 Specialist? (n=42) (n=726) – SWLS 6.5 11.6 Preserved +/- 3.1 +/- 4.2 P<0.001 Fertility? (n=31) (n= 736) ����������������������� Letourneau, 2012 CCR/UCSF Study on Psychosocial Outcomes • Measures: – Regret score – QOL – SWLS Letourneau, 2012 2
Reproductive Impairment-Chemotherapy Risk of Infertility only after Cancer Treatment Age �������������������������� Early Cancer Type Acute Ovarian Infertile but M enopause Failure Menstruating Type of cancer Ovarian reserve Leukemia 3% 30% 9% HD 8% 33% 9% NHL 10% 26% 20% Breast 13% 61% 28% GI 7% 53% 13% Genetics ������������������������������ Reproductive Impairment- Reproductive Impairment- Chemotherapy only Chemotherapy only Letourneau et al., Cancer 2011 Letourneau et al., Cancer 2011 3
Assessment of Ovarian reserve: AFC � ��������� • 26 yo G0 � ������������� – Breast cancer � ��� – HR- � ��� ����!"����� – Stage 1 disease � #���������� – Oncotype-26 � $�% – ACT � ���������������� – Ovarian failure ������� Letourneau et al., Nature Oncology 2010 Ovarian Reserve and Reproductive Risks of infertility after Treatment? Impairment Anticipate fertility window will be reduced in all patients receiving cytotoxic therapy $�!����������� 4
Options for Women Options for Fertility Preservation ��������������������� �������������� ����������������������� �������� �������� ����� !��"�����#��������� �������������� ��������������������� ������ $�%&�������'��������������������� ������ %���������������������()��������)�����* ����� +�������)��������� ����� !��"������������������ ����� �������������������� ����� ��������� (����������������������������������������* ����� ,�������� ����� Embryo/Egg Cryopreservation Ovarian Physiology • Established treatment • Takes 2-6 weeks** Ovulation – Ovarian stimulation, egg retrieval Antral follicle Delay treatment 1 14 28 Cycle Days 5
Ovarian Physiology Ovarian Physiology �"� ���&�'���������"���� Ovulation Ovulation Antral follicle Antral follicle atresia Preovulatory follicles 1 1 14 28 14 28 Cycle Days Cycle Days Ovarian Physiology Ovarian Stimulation 1.Conventional estrogen FSH Ovulation Ovulation Progesterone Antral follicle Antral follicle atresia atresia Preovulatory follicles Preovulatory follicles 1 1 14 28 14 28 Cycle Days Cycle Days 6
Ovarian Stimulation Random Start = Conventional 1.Conventional Conventional Late Follicular Luteal P value 2. Random stimulation Start Phase Start Phase Start (n=88; 103 (n=12; 12 (n=21; 21 cycles) cycles) cycles) Age (yrs) 33.8 ± 5.3 33.3 ± 3.9 34.5 ± 5.1 NS Ovulation Antral follicle count (AFC) 13 (9-19) 11 (5.5-21) 13 (7-18.5) NS Days of ovarian stimulation 9 (8-10) 11 (10-11.5)a 11 (10-12)a <0.001 Total dose of gonadotropins (IU) 3405 ± 1127 3837 ± 1074 4208 ± 1462b 0.014 Gonadotropin dose/day 361 ± 94 366 ± 88 369 ± 87 NS Follicles � 13 mm 12 (6-17) 11.5 (7.5-18.5) 13 (9-19.5) NS Oocytes retrieved NS 15 (9-23) 14 (8.5-27) 16 (10.5-25) Mature oocytes (MII) retrieved 11 (6-16) NS 10.5 (5-16.5) 11 (6-18) MII oocyte / total oocytes Antral follicle ratio NS 0.71 (0.60-0.82) 0.74 (0.59-.80) 0.69 (0.56-.84) Oocyte / AFC ratio NS 1.14 (0.75-1.71) 1.27 (0.92-.73) 1.20 (0.92-.67) Mature oocyte / AFC ratio NS atresia Preovulatory follicles 0.83 (0.46-1.12) 0.84 (0.6-1.3) 0.83 (0.62-.22) Fert. rate after ICSI (2PN/MII) NS 0.83 (0.69-0.91) 0.78 (0.75-.80) 0.96 (0.77-1.0) ��(��(�����) 1 14 28 Cycle Days The PROMISE trial Other considerations…. randomized trial: Triptorelin vs. Placebo • Hormone receptors �������������������- – Modifications ( i.e aromatase inhibitors) !������������������ • Ovarian reserve, desires %������- – Multiple cycles )�����������������-��./01 )������������2������������34/01 – Hormone treatment- delays in building a family ���������-�561 (0.1)!�6/0�����71�89:/::5* • Genetic Risks( i.e BRCA) +�����������- – PGD for prevention of vertical transmission ��������� ������#���������(��������������* *��������������� 7
Ovarian Tissue freezing Post- Treatment Options • Fertility preservation • 20-30 live births – (All Orthotopic transplant) • Infertility therapy +�� • Donor Eggs & Embryos • Challenges/Limitations • Surrogacy – Risk for recurrences – Short life (3-5 yrs) • Adoption • ischemia – General anesthesia Conclusion “ Parenting is unlike anything else I have ever • Fertility preservation – benefits as a survivor experienced. It is the most profoundly life-affirming thing I have ever done. • Treatment effects – previously underestimated I am grateful that -- through all the uncertainty and fear surrounding my cancer diagnosis and • Options for preserving fertility- considerations treatment -- we held on to that dream of becoming parents and made it a reality. ” • Survivors- options 8
Thank You Clinical Team Research Team Marcelle Cedars MD Thom Remble UCSF Fertility Evelyn Mok-Lin MD Hakan Cakmak MD James Smith MD(male) Tomoko Ozawa PHD Preservation Jo Chien MD Eve Harris- Patient Navigator Michelle Melisko MD Program Audra Katz, RN Joe Letourneau MD Cathy Chin, RN Jessica Chan, MD Nanette Lerma, RN Erin Ebbel MD Xinli Yang-embryologist Sai Chan MS Rosemary Benson-Call Center Danielle Cipres MS Meera Shah MD 9
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