Oncofertility Preserving the Future

1. OncofertilityPreserving the Future Nicole C. Rosipal, RN, MSN, PNP

2. Objectives • Incidence of cancer and survivorship among Adolescent and Young Adult (AYA) population • Survivorship and significance of fertility • Effects of cancer and cancer treatment on fertility • Assessment of fertility • Age appropriate fertility preservation options • Standard and Experimental • Key considerations when discussing fertility with patients and families

3. Cancer and Survivorship Among Adolescent and Young Adults Approximately 70,000 Adolescent and Young Adult (15-39) and 10,000 children (<15) are diagnosed with cancer each year Childhood cancer survivorship > 70% 1 of 900 individuals in U.S. between 15-45 is a childhood cancer survivor Approximately 270,000 cancer survivors originally diagnosed less than 21 years of age are currently living in the United States

4. Infertility “Inability to conceive after 1 year of intercourse without contraception” • Azoospermia • No measurable level of sperm in semen • Obstructive vs. issue with spermatogenesis • Damage to oocyte, follicles or uterus • Immediate menopause • Premature menopause

5. Infertility and General Population • Statistics • 6.1 million Americans • In 2002, 7% of women infertile • Multi-factorial causes • Men • Women • Both • Sexually transmitted diseases • Lifestyle factors – smoking, alcohol, obesity

6. American Society of Clinical Oncology (ASCO) Guidelines Panel reviewed literature spanning 1997 to 2005 Fertility preservation is of great importance Lack of knowledge and comfort of health care team Effects of infertility resulting from cancer treatment: Psychosocial and emotional distress Loss of masculinity or femininity Most survivors prefer to have biological children Survivors as Parents Experience with illness can enrich their role High value on family closeness

7. 2006 ASCO Guidelines “Oncologists should address the possibility of infertility with patients treated during their reproductive years and should be considered as early as possible in the treatment planning”

8. Urban Legends and CautionMales • Azoospermia is potentially for life, not short term • Can still get someone pregnant! • Sperm production can return immediately or many years after cancer treatments • Pubertal development does not equal fertility • Caution! • Sexually transmitted diseases

9. Urban Legends and CautionFemales • A “period” does not define fertility • Amenorrhea is not a definite sign of infertility • Return of a period does not equal fertility • Cancer treatment can take years off of the biological clock • Caution! • STD’s

10. Cancer and Infertility Men • Risk is multifactorial • Age • Disease • Cancer treatment regimen • Pre-existing conditions • Function of testicle effected • Currently 15-30% of survivors are sterile • Cancer has been documented to have effect on quantity and quality of sperm.

11. A Word About Prepubertal Males • Radiation less damaging than chemotherapy • No protective effect against chemotherapy induced gonadal damage

12. Assessment of FertilityPrior to Beginning Cancer Treatment Male • Tanner Staging • Related to secondary sexual characteristics • Average age • Spermatogenesis - 13 y.o. • Completion of puberty - 15 y.o. • Semen Analysis

13. Proportion of Patients with a Normal Semen Analysis Overall – 21.1% with normal semen analysis

14. High Risk for Azoospermia

15. High Risk for Azoospermia

16. Intermediate Risk for Azoospermia

17. Intermediate Risk for Azoospermia

18. Low Risk for Azoospermia

19. Very Low/No Risk for Azoospermia

20. Unknown Risk for Azoospermia • Irinotecan • Bevacizumab (Avastin) • Cetuximab (Erbitux) • Erlotinib (Tarceva) • Imatinib (Gleevec)

21. Preventative Measures Shielding during radiation Pre and post pubertal Hormonal manipulation (GnRH analogs) has not proven successful in gonadoprotection

22. Banking Options • Pre vs. Post Pubertal • Standard vs. Experimental

23. Banking Options: Post Pubertal MaleStandard Sperm Banking: Most effective Obtained through masturbation then frozen Outpatient procedure Success rate is generally high Reports of 50% successful pregnancy rate Potentially compromised sperm count and increased risk of genetic damage after a single treatment

24. Banking Options: Post Pubertal MalesStandard • Sperm Banking Process • MD/APN/PA order • Collection PRIOR to chemotherapy and/or radiation is vital • 2-3 samples are recommended • A sample can be provided every 24 hours. • Collected in a sterile container • At clinic location, hospital, home • Kept at body temperature and brought to lab within one hour

25. Sperm Banking Process Continued Semen Analysis Sperm count and movement Morphology Semen is placed in individual plastic vials for freezing Cost $125-$250 for analysis $225-$375 for one year storage

26. Mandatory Infectious Disease Testing • Serum: • HIV • Hepatitis A, B and C • RPR (Syphilis) • HTLV 1 and 2 (Human T-lymphotropic virus) • CMV IgG and IgM • Gonorrhea and Chlamydia (IgG and IgM) • AST • Cost • Approximately $325

27. Banking Options: Post Pubertal MalesExperimental Electroejaculation Penile or Rectal Mechanical vibrator is placed at the base of the penis or in rectum and set to vibrate at a designated frequency and wave amplitude. Vibration travels along the sensory nerves to the spinal cord and may induce a reflex ejaculation. Approx 50 - 100% success rate of ejaculation Cost varies greatly

28. Banking Options: Post Pubertal MalesExperimental • Testicular sperm extraction • Outpatient procedure • Testicular mapping • Success Rate • 30-70% • 45% of azoospermic ejaculate after cancer treatment • Cost • $4,000 - $16,000

29. Banking Options: Prepubertal MalesExperimental Only Cryopreservation of testicular tissue and stem cells Tissue obtained via biopsy and frozen In Vitro culture Maturation of testicular stem cells Animal studies only Autotransplantation Risk of recurrence?

30. Options after Cancer Treatment • Use of Frozen Sperm • In Vitro Fertilization (IVF) • Intra Cytoplasmic Sperm Injection (ICSI) • Donor Sperm • $200 - 500 per vial • Adoption • $2,500 - $35,000

31. Options in Houston

32. Assessment of FertilityAfter Cancer Treatment • Semen analysis • Blood Work • FSH • Inhibin B

33. Cancer and InfertilityWomen • Cancer itself does not appear to affect fertility in women. • Cancer treatments pose spectrum of risk • Immediate infertility • Premature menopause • Compromised ability to carry a pregnancy • Multifactoral process • Drug type & dose • Radiation location & dose • Patient age & pubertal status • Pre-treatment fertility

34. A Word About Prepubertal Females • Early age at time of cancer treatment has a protective effect • Younger age with larger number of oocytes requiring more radiation to cause damage • Less mitotic activity

35. Cancer and InfertilityWomen • Surgery can impair ability to become pregnant and/or carry pregnancy • Radiation can damage uterus and increase risk of miscarriage • Advise survivors who have received pelvic radiation should seek high-risk OB

36. Cancer and InfertilityWomen • Damage to oocytes and follicles can lead to immediate menopause or premature menopause years after treatment. • Menstruation does not equal fertility • Treatment affect on stromal function and ovarian blood vessels

37. High Risk >80% of women develop amenorrhea post-treatment

38. High Risk>80% of women develop amenorrhea post-treatment

39. Intermediate Risk~30-70% of women develop amenorrhea post-treatment

40. Low Risk<20% of women develop amenorrhea post-treatment

41. Very Low RiskNegligible effect on menses

42. Unknown Risk

43. Standard Female Reproductive Options • Embryo freezing • Radiation shielding of ovaries • Ovarian transposition • Radical trachelectomy • Donor embryos • Donor eggs • Gestational surrogacy • Adoption

44. Embryo Freezing • Eggs are harvested and undergo in vitro fertilization. Embryos are frozen for later implantation. • Time requirement • Cost: ~ $8,000-12,000 per cycle / $350/year storage fees • Donor sperm $200-$500 / vial • Success rate: 20-33%, babies born • Special considerations: partner, donor sperm

45. Radiation Shielding of Ovaries • Shielding reduces scatter to reproductive options • Time requirement: non-issue • Cost: included in cost of radiation • Success rate: limited to selected radiation fields • Special considerations: No protection from chemotherapy

46. Ovarian Transposition • Surgical repositioning of ovaries away from radiation field • Time requirement: Outpatient procedure • Cost: Maybe covered by insurance • Success rate: Approximately 50% • Special considerations: Expertise required

47. Radical Trachelectomy • Surgical removal of the cervix with preservation of uterus • Time requirement: During treatment • Cost: Included in treatment cost • Success rate: No evidence of higher recurrence rate • Special considerations: Early stage cervical cancer, limited centers

48. Standard Female Reproductive Options • Donor embryos • Not biologic child • Donor eggs • Offers opportunity for biologic child for father • Gestational surrogacy • Legal implications • Adoption • Inaccessibility to cancer survivors

49. Experimental Options • Egg/oocyte freezing • Ovarian tissue preservation • GnRH

50. Experimental Options for Females Oocyte cryopreservation Process the same, sperm not needed Oocytes are more sensitive to freeze/thaw process and more prone to damage Average 2% (range 1-5%) chance of pregnancy per oocyte (3-4 times less than with embryo) 200+ live births to date ~$12,000/cycle