December 4, 2014 Rebecca Johnson, MD Mary Bridge Hospital Tacoma, WA USA

Transcription

1 Fertility preservation for AYAs December 4, 2014 Rebecca Johnson, MD Mary Bridge Hospital Tacoma, WA USA

2 Aims Guidelines Barriers to implementation Assessment of risk Methods of preserving fertility Optimising Institutional Standard Practice Counseling

3 Up to 90% of patients with cancer under age 45 are at risk for treatment-related infertility Guidelines mandate fertility risk assessment and referral ASCO (2006/2013) ASRM (2012) JNCCN (2012) ESMO (2013) EUSOMA (2014) ASCO, 2006 Fertile Hope (2005). Johnson and Kroon (2013). JNCCN. Linkeviciute et al (2014) Cancer Treatment Reviews

4 Barriers perceived by oncologists- still the same Discussion with patients: Not enough time Discomfort or perceived ethical issues re: minors What to offer patients with poor prognosis or developmental delay Difficulty finding convenient facilities Concerns: too costly? poor semen quality? Urgency to start treatment Schover et al (2002). Adams E (2013) Br J Cancer 108:

5 Recent Studies of Fertility Preservation Referral 2012 chart reviews: No difference before/after 2006 guidelines Consultation in only 21% of eligible patients 2012 survey of medical oncologists: 95% routinely discuss fertility risk, BUT 61% rarely or never refer 30% rarely consider a woman s desire for future fertility when planning treatment 2011 survey of pediatric oncologists: Acknowledge importance, BUT < 50% refer any patients Only 12% refer female patients prior to treatment Foreman EJ et al, Fertil Steril 2010;94: ; Goodman LR (2012) Hum Reprod 27: ; Kohler TS (2011) J Assist Reprod Genet 28:269-77; Kumar A (2102) Rehab and Survivorship 19; Kim J et al (2014) J Gynecol Oncol 25:

6 Perceptions of Cancer Survivors 75% of patients who were childless at diagnosis want to have children 80% of male AYAs feel that sperm banking helps in the emotional battle against cancer. Males16-30 support sperm banking, including those who declined to bank and those who were not successful. Fertility preservation offers hope...something positive - even if the prognosis is poor. Zakak N (2009) J Ped Nursing Oncol; Cranshaw MA (2008) Hum Fertil; Saito K (2005) Cancer; Shover L (2009) Ped Blood and Cancer

7 Risk for infertility varies according to therapy Both chemotherapy and radiation therapy can cause infertility Alkylators Busulfan Carmustine (BCNU) Lomustine (CCNU) Chlorambucil Cyclophosphamide Ifosfamide Melphalan Procarbazine Thiotepa Heavy metals Cisplatin Carboplatin Non-classic alkylators? Temozolomide Dacarbazine Radiation therapy to brain or gonads Increased risk with higher dose, multiple agents, concurrent radiotherapy with alkylators Accurate prediction of fertility outcome is difficult (COG LTFU Guidelines)

8 Risk for Males Azoospermia of variable duration Virilization fertility Leydig cells, which produce testosterone, are much more resistant to injury than germ cells Chemotherapy alone rarely causes Leydig cell dysfunction Patients may appear well-virilized, yet be infertile Potential for natural recovery of sperm count for up to 14 years after completion of therapy Meistrich et al. (1989)

9 Risk for Females Premature ovarian failure (irreversible) Risk for ovarian damage depends on drug, dose, and age Older AYAs (in 30 s) more susceptible Younger AYAs relatively protected (more primordial follicles) BUT may have shortened reproductive lifespan even if menses and ovulation appear normal following therapy In women who received both alkylating chemotherapy and radiotherapy <age 20: 42% had reached menopause by 31 years of age, compared to 5% of healthy controls Brougham MF et al. (2006) Br J Hematology 131: Green DM et al (2009) J Clin Oncol 27: : ;27(14):23

10 Methods of fertility preservation Males Sperm banking- gold standard Best time is before start of therapy Only 30% of patients have normal sperm count after low risk ALL therapy (prior to BMT) Electroejaculation Prior to puberty Testicular tissue preservation- experimental Testicular sperm extraction (TESE) Early pubertal males Post-therapy option for patients with azoospermia Johnson and Kroon (2013). JNCCN Nahata et al (2013). Pediatr Blood Cancer 60:

11 Methods of fertility preservation Females Embryo Cryopreservation gold standard Ooctye Cryopreservation 2012 ASRM should now be considered standard of care Expensive, but becoming less so Requires 10 days to 2 weeks with current ovarian stimulation protocols If ovarian reserve is spared, can be undertaken post-treatment, anticipating premature ovarian failure Ovarian Tissue- experimental Ovarian suppression- GnRH agonists may increase preservation of ovarian function and conception Johnson and Kroon (2013). JNCCN; Moore HC et al (2014) ASCO abstract LBA505); Z. Blumenfeld X et al (2014) Ann Oncol

12 Optimising Standard Practice: Seattle Children s Experience Fertility preservation team sees all eligible patients within 24 hours of diagnosis Males Sperm Banking offered to all eligible males prior to start of therapy Eligibility criteria: >12 years old, Tanner stage III or above, no physical limitations to masturbation (i.e. acute spinal cord compression), does not need to start therapy emergently Females Post-menarchal females, who can delay start of therapy for 2-3 weeks, are eligible for oocyte cryopreservation

13 Results Sperm Banking 100% 90% 90% 92% 80% 70% 60% 50% 68% 83% 82% 75% 67% 64% Offered Sperm Banking Attempted Sperm Banking 40% 30% 20% 10% 0% 8% unknown Prior to RPIW First 12 months following RPIW FY 2010 FY 2011 FY 2012

14 Tips for counseling AYAs Hold the conversation in private environment Normalize the experience We offer fertility preservation to all our AYA cancer patients. Make patient feel as comfortable as possible Stay matter-of-fact Become comfortable discussing the topic Give patient choices where possible (where they sit, who is present) Acknowledge that discussing this subject can be difficult Reassure that conversation needs to take place only once Chemotherapy birth control Johnson and Kroon (2013). JNCCN

15 Thank You