Oncofertility: preserving generation next. Jill Sullivan MD,PhD First Year Fellow

Transcription

1 Oncofertility: preserving generation next Jill Sullivan MD,PhD First Year Fellow

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3 Ataman, L. M. et al., J. of Glob Oncol. 12/23/2015 (epub

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5 Agenda: Patient Presentations Relevance of Our Discussion Today Population at Risk of Infertility Recommended Strategies ASCO 2013 Update Cost Does Ethnicity/Race Impact Oncofertility?

6 Patient: A 42 yo G1P1 caucasian female PMHx: Psoriasis, Rosacea, otherwise healthy PFHx: Mother deceased Breast Cancer 55 yoa, dx at 47 Soc: Former light smoker quit 20 years ago, negative Etoh/illicits Menarche 14, AFC 34, 6 mos. Fertility treatment, no radiation exposure Dx: T1cNXMX ER+ PR+ HER2 Multifocal Invasive Ductal Carcinoma BRCA 1/2 Negative

7 Patient: B 28 year old Hawaiian/Korean Male PMHx: Anxiety and Tobacco use PFHx: Negative for solid or hematologic malignancy Soc: tob: 5 pack yr history, negative etoh, illicits Married, no children, steady job. Military: 10 years, 3 tours Iraq/Afghanistan, unknown chemical exposures, unprotected exposure to x-ray Dx: Primary Mediastinal B-cell Lymphoma

8 So what is the relevance of this discussion?

9 130, ,000 new diagnosis of cancer in patients of child-bearing age in 2015 (ages 20-45) 26,000 Breast Cancer ½ Million cancer survivors of reproductive age in the US There is an increased emphasis on Quality of Life Infertility and sexual dysfunction are top survivorship concerns Infertility: variable and unpredictable in duration De Moor, J.S. et al., Cancer Epid Biomarkers Prev, 22(4):

10 ncer & Fertility Concerns: Males Fertility is a major concern among male cancer patients 51% of men with cancer report wanting children in the future 77% of these men are childless at diagnosis 1 91% of oncologists agree sperm banking should be offered to eligible men Only 10% offer sperm banking routinely 2 1. Shover LR, Brey K, et al Knowledge and experience regarding cancer, infertility, and sperm banking in younger male survivors. JCO 20: Schover LR, Brey K, et al Oncologists attitudes and practices regarding banking sperm before cancer treatment. JCO 20: Reprinted with permission from Carey Anders, MD

11 Quinn G.P. et al., J. Oncol Pratice, 11(2):

12 Quinn G.P. et al., J. Oncol Pratice, 11(2):

13 So who is at risk?

14 sk Factors pe and Stage of Cancer e eatments Radiation field and cumulative dose Chemotherapy drug class, duration, dose and combination effect BMT high risk, recommend to every patient of reproductive age. Surgery extent of surgical field e-treatment fertility status of patient Often not known or considered

15 Agarwal et al., Transl Androl Urol 3(1):27-40

16 Agarwal et al., Transl Androl Urol 3(1):27-4

17 Lee S. J. et al., J Clin Oncol. 24:

18 MOTHERAPY: PROBABILITY OF AZOOSPERMIA Disease Non-Hodgkin s Lymphoma Testicular Cancer, MOPP, ChIVPP/EVA, COPP become azoospermic PP cycles results in permanent permia 1 /ABV Hybrid (Cyclophosphamide = mg/m 2 ) develop azoospermia 3 Therapy spermia in 46% rary azoospermia in 33% permia in 21% covery in all patients after 18 months 2 n VAPEC-B, VACOP-B, MACOP- B, VEEP - Normospermia >95% n CHOP Therapy - 30% become permanently azoospermic after therapy 1 n BEP x 2-4 cycles -Temporary azoospermia in most - 50% fully recover after 2 years - 80% recover after 5 years 4 ll SJ, Shalet SM Testicular function following chemotherapy. Human Reproduction Update 7(4): son et al European Journal of Cancer 38: e WL, Ginsberg JP, et al Fertility in males treated for Hodgkin s disease with COPP/ABV hybrid. Pediatric Cancer. 44(2): ll SJ, Shalet SM Spermatogenesis after cancer treatment: damage and recovery. Journal of the National r Institute Monographs 34: Reprinted with permission of Carey Anders, M

19 iation Effects: Males ingle Dose Irradiation: Radiation Dose Stage of Germ Cell Damaged Time to onset of azoo/oligospermia Time to Recovery 0-1 Gy Spermatogonia Oligospermia 100% in 9-18 months 2-3 Gy Spermatogonia Spermatocytes 4-6 Gy Spermatogonia Spermatocytes Spermatids Azoospermia 60 days from time of treatment Azoospermia in 60 days or less 14-49% in months Few Recover > 5 years Radiation to Testes (Pelvic/ Gonadal/TBI) Leydig cell dysfunction at >20 Gy (prepubertal) >30 Gy (adolescents and young adults) 6-8 Gy Spermatozoa Permanent Azoospermia No recovery ractionated Dose Irradiation: Radiation Dose Gonadotoxicity Time to Recovery < 0.2 Gy Normospermia NA Gy Dose-dependent azoospermia months 1.2 Gy Azoospermia Likelihood of No Recovery Reprinted with permission of Carey Anders, MD

20 Lee S. J. et al., J Clin Oncol. 24:

21 diation Effects: Females Ovarian Reserve <2Gy destroys up to 50% immature oocytes >6 Gy generally causes ovarian failure in women > 40 >20 Gy permanent loss of function in pre-puebertal girls Gy total abdominal therapy 97% post-pubertal women experience POF 72% pre-pubertal girls lose ovarian function 2 Uterine Function Impaired growth & blood flow Uterine volume correlates with age at irradiation Patients who do conceive are high-risk Spontaneous abortion (early and late) Preterm delivery Low birth weight babies Hypothalamus/Pituitary Gland Function (Head/Brain/TBI) Gy causes GnRH Deficiency Reduced estradiol and progesterone levels 1. Wallace WH, Thomson AB, et al Predicting age of ovarian failure after radiation to a field that includes the ovaries. International Journal of Radiation Oncology Biol. Phys. 62(3): Critchley HOD, Wallace HW Impact of Cancer on Uterine Function. Journal of the National Cancer Institute Monographs 34: Reprinted with permission of Carey Anders, MD

22 wer Drugs: New Dilemnas E AND PREGNANCY Abruzzese, E. et al., Mediterr J. Hematol Infect Dis 6(1):e

23 r risk for spontaneous abortion and fetal abnormality in TKI use. Abruzzese, E. et al., Mediterr J. Hematol Infect Dis 6(1):e

24 So how do we preserve generation next in our patient population?

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26 Loren, A.W. et al, J Clin Oncol 31:

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30 Fertility Options: Men Before During After Status Sperm Banking X Std Testicular Tissue Freezing X Exp Natural Conception X Std Assisted Reproduction X Std Testicular/Epididymal Sperm Extraction X X X Std Sperm Donation X Std Adoption X Std Reprinted with permission of Carey

31 Sperm Banking and ART Goal is to encourage 3 samples to be banked Patients should allow 48 hours of abstinence between collection In close proximity to a facility and collecting at home, samples should be delivered in sterile cups within an hour No lubrication should be used and the sample should be collected into a sterile cup. Alternate approaches are currently being considered including a comercially available NextGen sperm banking kit Samples are then used with ART: IUI: Intrauterine insemination IVF: in vitro fertilization ICSI: intracytoplasmic sperm injection PGD: pre-implantation genetic diagnosis Agarwal et al., Transl Androl Urol 3(1):27-4

32 rithym for Sperm Preservation Modified from Agarwal et al., Transl Androl Urol 3(1):27-40

33 ~ 10% of samples were utilized by patients, the majority in the first 4 years. Sperm quality varies depending on cancer type with testicular cancer having the lowest concentration and motility Conceptions achieved in 25%, live delivery in ~20% Botchan A. et al.,2013. Asian Journal of Andrology, 15:

34 Patient: B Diagnosis in early October 2015 Referral made to Duke Fertility Clinic Low risk for prolonged infertility Day discharge for sperm banking 9 days after biopsy Started Dose-adjusted R-EPOCH 10 days after biopsy Reports erectile dysfunction, low libido starting at cycle 4 Currently cycle 6, otherwise doing well with good response to therapy and minimal side effects

35 rtility Options: Women Before During After Status Embryo Cryopreservation X X Std Oocyte Cryopreservation X X Std Ovarian Tissue Freezing X X Exp In Vitro Maturation X X Exp Ovarian Transposition X Std Radical Trachelectomy X Std GnRHa X Exp Natural Conception X Std In Vitro Fertilization X Std Donor eggs or embryos X Std Adoption X Std Gestational Surrogacy X Std Reprinted with permission of Carey

36 Patient: A Conditional T1NxMx ER+ PR+ HER2- BRCA- IDC Desired more children; Day of her appointment at Duke Cancer Center she was actually scheduled to discuss IVF with another fertility center. Discussed role of surgery, radiation and chemotherapy Due to multifocal disease, mastectomy recommended Due to ER+ PR+ status recommended Endocrine therapy Recommended proceeding with staging prior to surgery and discussion with fertility group about Letrozole containing ovarian stimulation.

37 Oktay, K. et al., J. Clin Endo & Metab 91(10):

38 Majority of patients completed IVF in planned hiatus between surgery& chemo Mean delay from breast surgery to completion of first IVF cycle: days If six patients who underwent second cycle included: days 81% completed IVF cycles within 8 weeks of breast surgery 42 days between diagnosis & referral to fertility preservation Three patients have thawed embryos: One live birth, one biochemical pregnancy; two live births from fresh letrozole/fsh cycles one year post treatment in patients treated for early stage BRCA Oktay, K. et al., J. Clin Endo & Metab 91(10):

39 Kim, J. et al., J. Clin Endocrinol Metab. Jan 11

40 Kim, J. et al., J. Clin Endocrinol Metab. Jan 11

41 LES method for ovarian stimulation is safe and does not decrease relapse free survival Kim, J. et al., J. Clin Endocrinol Metab. Jan 11

42 osed monitoring and fertility planning for women with CML KI therapy with Imatinib. Abruzzese, E. et al., Mediterr J. Hematol Infect Dis 6(1):e

43 t of Preserving Fertility Banking $ /yr cular Tissue Freezing $10,000 ryo Freezing $12,400/cycle yearly storage reezing $11,900/cycle yearly storage ian Tissue Freezing mplantation Genetic Diagnosis $12,000 + yearly storage $2500/cycle H Analog Treatments $500/month r sperm, eggs or embryos $3,000-5,000 tion (domestic, international, public, private) $2,500-35,000 gacy $20, ,000 Reprinted and modified with permission of Carey Anders, MD

44 Does ethnicity/race impact oncofertility?

45 s in Socioeconomic Disparities: n this study, a higher percentage of caucasian women received FP compared with frican American, Asian or Hispanic females. o eligible Hispanic females received FPC. uggested explanations include ethnic disparities in access to care, clinician erceived economic status, language barriers, health literacy and cultural beliefs egarding oncologic and/or reproducive issues. Goodman, L. R Human Reproduction, 27(7):

46 So How Can We Improve: IDENTIFY PATIENTS AT RISK EDUCATE AND TRAIN OUR PROVIDERS: see next slides for resources KNOW WHERE YOUR FERTILITY CENTER IS: DUKE FERTILITY CLINIC: 5704 Fayetteville Rd. Durham (919) STANDARDIZE PROTOCOL FOR FERTILITY PRESERVATION DISCUSSION IN YOUR CLINICS: RISKS, OPTIONS and REFERRALS. THERE ARE LIMITED STANDARD OPTIONS: KNOW WHAT THEY ARE AND IF YOU CAN GET THEM ACCOMPLISHED BASED ON THE TUMOR GROUP YOU WORK WITH

47 Resources: patient and provider education - patient education - Resource Guide: Family planning and Fertility - ASCO University Focus Under Forty Livestrong/Fertile Hope: online risk calculator isavefertility.org: iapplication

48 zese, E. et al., Mediterr J. Hematol Infect Dis 6(1):e Reference al et al., Transl Androl Urol 3(1): an, L. M. et al., J. of Glob Oncol. 12/23/2015 (epub) an A. et al.,2013. Asian Journal of Andrology, 15: or, J.S. et al., Cancer Epid Biomarkers Prev, 22(4): ie WL, Ginsberg JP, et al Fertility in males treated for Hodgkin s disease with COPP/ABV hybrid. Pediatric Blood Cancer. 44(2): ll SJ, Shalet SM Testicular function following chemotherapy. Human Reproduction Update 7(4): ll SJ, Shalet SM Spermatogenesis after cancer treatment: damage and recovery. Journal of the National Cancer Institute Monograph J. et al., J. Clin Endocrinol Metab. Jan 11. J. et al., J Clin Oncol. 24: , A.W. et al, J Clin Oncol 31: , K. et al., J. Clin Endo & Metab 91(10): er LR, Brey K, et al Knowledge and experience regarding cancer, infertility, and sperm banking in younger male survivors. JCO 20: 18 ver LR, Brey K, et al Oncologists attitudes and practices regarding banking sperm before cancer treatment. JCO 20: son et al European Journal of Cancer 38: G.P. et al., J. Oncol Pratice, 11(2):

49 Special Thanks: Dr. Kim Blackwell Dr. Carey Anders Lindsay Nohr Beck Fertile Hope Dr. Susanna Copland Dr. Carlos DeCastro Dr. Richard Riedel My Fellow Fellows My Family

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