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SHARE Presentation: Having Children after Cancer


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Dr. Diana Chavkin, Reproductive Endocrinology and Infertility (REI) specialist at Genesis Fertility and Reproductive Medicine, made this presentation at SHARE about fertility preservation options before and after cancer treatment.

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The information in this presentation is not intended to be a substitute for professional medical advice, diagnosis or treatment. The presentation was given on May 15, 2014.

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SHARE Presentation: Having Children after Cancer

  1. 1. Having Children After Cancer Diana E. Chavkin, MD GENESIS Maimonides Medical Center
  2. 2. Cancer: >130,000 reproductive age patients diagnosed annually Improved Survival: 77% Diagnosed under 45 Survive ≥≥≥≥ 5 years Reproductive Medicine: Improved FP Options Delayed Childbearing: Maternal Age at 1st Birth: 25.2 years (USA) All Time High Oncofertility Landscape
  3. 3. U.S. Cancer Incidence by Site - 2010
  4. 4. Breast cancer and fertility • Breast cancer is the most common malignancy to affect women younger than 45 • 25,000 patients under 45 are diagnosed with breast cancer in the United States annually • Reproductive-aged patients face unique concerns regarding cancer treatment and survivorship goals • 57% concerned about fertility • 29% of concerns influenced treatment plan
  5. 5. Patients at risk National cancer Institute report: 1 out of 250 adults will be a survivor of childhood cancer by 2015 Tangir, 2003
  6. 6. Fertility in Survivors • Approximately 75% of childless cancer survivors want children in the future • Adult survivors of childhood cancer report increased anxiety regarding finding a mate and are not prepared for long-term side effects of treatment • Overall, young men and women have equal concerns regarding fertility • Only 61% of women were informed of fertility preservation options
  7. 7. ASCO Guideline Summary As part of informed consent prior to therapy, oncologists should address the possibility of infertility with patients as early in treatment planning as possible 1 1 Lee SJ, Schover LR, et al., Journal of Clinical Oncology, 2006
  8. 8. The Reproductive Cycle
  9. 9. The Reproductive Cycle
  10. 10. 6,000,000 1,000,000 300,000 “0” 20 weeks in utero Birth Puberty Menopause 51 Numberofeggsintheovaries Fertility Risks for Females Pubertal Failure Premature Menopause <40 years Early Menopause Cancer therapies destroy eggs and accelerate ovarian aging Timing of exposure influences puberty and menstrual function
  11. 11. How does cancer treatment harm the ovaries? • Chemotherapy may cause egg depletion, ovarian failure and chromosomal damage in the egg • Radiation has adverse effects on ovarian function at all ages and may impair hormone production
  12. 12. Chemotherapy effect on ovarian function Increasing toxicity to the ovaries Unknown Low High Taxanes Oxaliplatin Monoclonal Antibodies Tyrosine Kinase Inhibitors Methotrexate 5-Fluorouracil Vincristine Bleomycin Actinomycin-D Cisplatin Adriamycin Cyclophosphamide Chlorambucil Melphalan Busulfan Nitrogen mustard Procarbazine 1. Lee SJ et al. J Clin Oncol. 2006;24:2917-2931. 2. Oktem & Urman. Obstet Gynecol Surv. 2010;65(8):531-542.
  13. 13. Effects of Cancer Treatments: Chemotherapy
  14. 14. How does chemotherapy affect a woman’s menstrual cycle? • Usually, during treatment, a woman does not get her period • Recovery of menses usually takes 6 months-1 year • Return of menses does not imply return of fertility • Different regimens have varying effects on recovery of menses • The younger a woman is at time of exposure the greater the chance of recovery of normal menses
  15. 15. Assessing Fertility After Cancer Blood tests: •Follicle Stimulating Hormone (FSH) •Estradiol •Inhibin B •Anti-Mullerian Hormone (AMH) Ultrasound: •Antral Follicle Count •Ovarian Size
  16. 16. ‘Biological Clock’
  17. 17. Fertility and Cancer Treatment Planning Modification of treatment plans for cancer care • Less aggressive resection for uterine, cervical and ovarian cancer • Planning radiation fields to shield the ovaries • Moving ovaries out of the radiation field prior to treatment (“transposition”) • Chemotherapy drugs that are less toxic to the ovaries • (i.e. less alkylating agents) • Modification of doses • Timing of treatment for breast cancer: can delay chemotherapy one month to allow for fertility preservation
  18. 18. Options for Fertility Preservation
  19. 19. Current Fertility Preserving Options • Embryo Cryopreservation • Egg Cryopreservation • Sperm Cryopreservation • Experimental options
  20. 20. Considerations • Age • Type of cancer and treatment planned • Presence of partner • Willingness to use donor gametes • Available time before cancer treatment • Health of the patient • More than one option may be possible for a given patient
  21. 21. Artificial Reproductive Techniques Freeze Embryos SpermMature Egg Freeze Tissue Freeze Mature Eggs Freeze Mature Eggs Collect Immature Eggs In Vitro Maturation **Most Data on success rates NOT in cancer population
  22. 22. Who Needs Fertility Preservation? • All patients should be informed of the potential risks and options available • Fertility preserving technologies may pose some risk – May delay cancer therapy and can be costly and invasive
  23. 23. Embryo and Egg Banking Requires Ovarian Stimulation • Only possible in post pubertal females • Risks: – Delay in cancer therapy – High estrogen levels – Ovarian hyper-stimulation – Theoretical thrombosis risk – Cost: $5-12K + storage
  24. 24. - In-Vitro Fertilization - IVF
  25. 25. Egg Retrieval • Eggs retrieved transvaginally under ultrasound guidance • Follicular fluid aspirated and sent to the laboratory
  26. 26. Embryo Cryopreservation (freezing) • Most established fertility preservation technique for women with cancer – First birth from Embryo Cryopreservation in 1983 • Requires about 2 weeks of ovarian stimulation, followed by needle aspiration to collect eggs • Eggs are then fertilized in vitro (outside the body), and frozen for later use • Freezing possible at different stages of embryo development
  27. 27. How Successful is Embryo Freezing?
  28. 28. Embryo Banking Success Rates Established Method - Partner or Donor Sperm required Oocyte Donors < 35 35-37 38-40 41-42 > 42 Fresh Cycle: Live birth/Cycle - 41.7 31.9 22.1 12.5 4.1 Cancellations % - 6.6 10.0 12.9 16.5 22.0 Fresh Cycle: Live birth/ET 55.6 47.8 38.4 28.1 16.8 6.3 Thawed Live birth/ET 34.8 38.7 35.1 28.5 21.4 15.3 Ave No. ET 2.0 1.9 1.9 2.1 2.2 2.1 Data from 2010 SART Statistics (146,693 cycles) Thousands of live births in patients without cancer
  29. 29. Embryo Cryopreservation • Requires: –Partner –High estrogen environment –Pubertal –Time (less of an issue for breast cancer) • Is costly
  30. 30. Mature Egg Banking …. reproductive autonomy
  31. 31. American Society of Reproductive Medicine “Evidence indicates that oocyte vitrification and warming should no longer be considered experimental” 2012 ASRM Practice Committee Opinion
  32. 32. Egg Freezing • Frozen eggs seem to be as good as fresh eggs • Result in similar pregnancy rates • Requires: – 2 weeks of daily hormone injections – Office procedure to collect eggs
  33. 33. Egg Cryopreservation Benefits over embryo cryopreservation: • No partner needed • Reproductive autonomy But: • Success rates possibly not as good
  34. 34. Egg Cryopreservation History • Why are eggs more difficult to freeze than embryos? – Large cell size – High water content with ice crystal formation – Potential for chromosomal damage – Hardening of the zona pellucida can effect fertilization • First human pregnancy was reported in 1986 • Early results disappointing – Poor egg survival, fertilization and pregnancy rates – Use of slow freeze rather than vitrification
  35. 35. Live Births from Egg Cryopreservation 0 50 100 150 200 250 300 1986-88 1997-99 2000-02 2003-05 2006-08 Slow Freeze Vitrification Both 936 births: 532 from slow freeze 392 vitrification Noyes et al. Reprod Biomed Online, 2009.
  36. 36. What are the chances of success? 28 year old woman has 6 eggs retrieved.. •If egg fertilized immediately: – Chance of pregnancy is 40-50% •If egg vitrified or ‘flash-frozen’ and fertilized later: – Similar chance of pregnancy •If egg is ‘slow-frozen’ and fertilized later: – Somewhat less chance of pregnancy
  37. 37. Do Babies Born from Frozen Eggs have a Higher rate of Birth Defects? Birth Defect Incidence Birth Defects Unassisted Conception Birth Defects per 936 Egg Cryo Births All 1/33 12 (1/78) Skin hemangioma 1/50-225 1 Cardiac defects 1/125 3 (1/312) Neural tube defects 1/385 0 Cleft lip/palate 1/710 1 Clubfoot 1/735 3 (1/312) Arnold-Chiari malformation 1/1200 1 Coanal atresia 1/7000 1 Biliary atresia 1/10-15,000 1 Rubinstein-Taybi syndrome 1/100-125,000 1 Noyes et al. Reprod Biomed Online 2009;18:769.
  38. 38. Ovarian Stimulation in Cancer Patients • Rapid access and team approach • Hormones used to stimulate the ovaries can theoretically also stimulate breast and uterine cancer • Medications such as Letrozole and Tamoxifen are used to decrease circulating hormone levels
  39. 39. Early breast cancer SurgerySurgery ChemotherapyChemotherapy RadiationRadiation TamoxifenTamoxifen HerceptinHerceptin At diagnosis 4- 6 months 4-6 weeks 5 – 10 years 1 year Refer Here!!
  40. 40. Is fertility preservation possible without administering hormones? • Ovarian tissue freezing • Ovarian tissue biopsy with culture of eggs from tissue
  41. 41. Does Pregnancy After Breast Cancer Increase Chance of Cancer Recurrence? • Studies have shown that women who become pregnant after breast cancer do NOT have an increased risk for disease recurrence or poorer survival • At least 2 studies indicate that pregnancy is in fact protective against disease recurrence
  42. 42. Pregnancy Outcomes in Cancer Survivors • In general, no risk of congenital malformations, genetic diseases or cancer in children of cancer survivors • However, possible risk (miscarriage/birth defects) if conceived within 3 months of chemotherapy • Recommend to delay conception until 3 months after completion of chemotherapy • With increased age there is an increased risk of miscarriage
  43. 43. Weeding out cancer genes…. Preimplantation genetic diagnosis (PGD) Technology that allows for detection of ‘cancer genes’ in embryos ● BRCA1, BRCA2, familial adenomatous polyposis, Gorlin syndrome ● Lynch syndrome/HNPCC, Li-Fraumeni syndrome, MEN, neurofibromatosis ● Retinoblastoma, tuberous sclerosis, Von Hippel-Lindau disease HNPCC = hereditary nonpolyposis colorectal cancer; MEN = multiple endocrine neoplasia
  44. 44. Pregnancy after cancer • Assess health of survivor – Cancer therapies may have significant toxicities – Maternal-fetal medicine (MFM) consultation recommended – Surrogacy may be an option • Legal consultation • Costly • Paid surrogacy not available in all states
  45. 45. Fertility Preservation: Investigational Techniques • Ovarian Tissue Cryopreservation • Transplantation of ovarian tissue • In-vitro maturation of ovarian follicles
  46. 46. Ovarian Tissue Banking … an experimental option
  47. 47. Ovarian Tissue Banking • No ovarian stimulation, minimal delay in treatment, no partner needed, only option in pre-pubertal girls • Autologous transplantation: Surgical removal of ovarian tissue prior to cancer treatment and replacement after treatment • 25 human births to date • Risk of seeding cancer cells in cancer that involve the ovaries (hematologic, ovarian and breast cancers) • Repeat surgeries required • Follicle Maturation in vitro – no human births yet • Ongoing research as part of Oncofertility Consortium
  48. 48. Males: Fertility Preservation • Men should be given the opportunity to bank sperm before cancer treatment • Boys who have started sexual development should be offered this option • There is currently no option to preserve fertility in pre-pubertal boys • Important to obtain adequate volume of semen • Infectious disease screening (based on FDA guidelines) should be offered
  49. 49. Genesis Experience • Embryo Freezing (2012): • 230 embryos in 111 cycles • Sperm Freezing (2012): • 189 samples • Egg Freezing: • (2006-2014): 150 oocytes frozen for 20 patients • (2011-2014): • 9 embryo transfers from frozen/thawed eggs • 4 of those transfers resulted in clinical pregnancies
  50. 50. Oncofertility Guideline Adherence National Survey Data • Typically only 2% to 4% of eligible women pursue fertility preservation • Only 47% of oncologists routinely refer patients to a reproductive endocrinologist Letourneau JM et al. Cancer 2012;4579-4588
  51. 51. Estimated Treatment Costs Type of Treatment Average Cost Sharing Hope Sperm Banking $100 & $100 q6months - Testicular Tissue Freezing/TESE $8,000 - Embryo Freezing $10,000 + meds $5,700 Egg Freezing $7,000 + meds $5,700 Ovarian Tissue Freezing $12,000 Under IRB (usually no charge) GnRH Analog Treatments $500/month - Donor sperm, eggs or embryos $10,000-$30,000 - Adoption (domestic, international, public, private) $2,500 - 35,000 - Surrogacy (Not in NY State) $20,000 -100,000 -
  52. 52. Covering Costs • Sharing Hope program works with REI practices to offer reduced cost to eligible patients • Many programs offer free medications • Insurance coverage is highly variable- It is worth appealing • Flexible strategies for covering cost
  53. 53. Patient Resources
  54. 54. Patient Resources
  55. 55. Summary of Options • Established Fertility Preservation: – Embryo freezing, egg freezing, conservative surgery, and sperm freezing • Experimental Fertility Preservation Options: – Ovarian tissue freezing • Other options: – Adoption, egg donation, surrogacy
  56. 56. Future Directions • Increased Need for Advocacy and Awareness Many patients learn about options for preserving fertility after cancer therapy • Decision making process Only 30% of those who present for an oncofertility consultation pursue treatment
  57. 57. Crucial Points • Fertility treatments and pregnancy do not worsen cancer prognosis • Prior treatment with chemotherapy or radiation has not been show to cause birth defects in offspring • There are multiple options to ease the cost associated with fertility preservation for patients with cancer
  58. 58. Contraception be o Contraception should be offered to all reproductively- aged patients actively undergoing cancer treatment •Irregular cycles or lack of menses during treatment does not necessarily mean that a woman can not conceive •Pregnancy during cancer treatment may alter the course of the disease •Cancer treatment can affect the pregnancy •Non hormonal options for breast cancer survivors
  59. 59. THANK YOU
  60. 60. Physicians: Richard Grazi, MD David Seifer, MD Jennifer Makarov, MD Diana Chavkin, MD Katherine Melzer, MD Administration and Billing Alan Sloane Michael Pagliuca Lisa Scire Christine Malesko Miriam Serrano Charlene Eastington Nicle Shannon Shannon Allen Sarah Alperin Laboratory Henry Malter, PhD , Director Lyudmila Bakunenko Mark Petrisch Cynthia Lay Aya Tal Nursing Joanne Soffing, RN Irena Shvartser, RN Rachel Najiri, RN Natalya Eppel, RN Toby Barsky, RN Roxanne Diaz, RN Nellie Badalova, RN Vahida Gillic, RN Toby Werner Marcy Parker, RN Rosa Fernandez, RN Counseling services Kris Bevilacqua, PhD, Psychological Services Katherine Mah, MS, Genetic Counseling Genesis Team Clinical assistants Marina Yessayan Tara Nieves Cindy Ammirable Christina Jaquez Christina Andon Linh Luong Marcia Morris Diane Piele-Fair
  61. 61. Slide from NAGY Slow freeze vs Vitrification