Rebecca Johnson, MD Mary Bridge Hospital Tacoma, WA USA

Fertility preservation for AYAs

December 4, 2014

Aims

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

ASCO, 2006

•  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) Fertile Hope (2005). Johnson and Kroon (2013). JNCCN. Linkeviciute et al (2014) Cancer Treatment Reviews 40 1019–1027

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 108:1602-15.

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;94:1652-6.; Goodman LR (2012) Hum Reprod 27:2076-81; 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 25:148-154

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

Risk for infertility varies according to therapy

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)

Both chemotherapy and radiation therapy can cause infertility

Risk for Males

•  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)

Azoospermia of variable duration

Risk for Females

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

Premature ovarian failure (irreversible)

Brougham MF et al. (2006) Br J Hematology 131:143-55 Green DM et al (2009) J Clin Oncol 27: :2374-81 10;27(14):2374-81

Methods of fertility preservation

•  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 60:129–132

Males

•  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

Methods of fertility preservation

Females

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

Results

unknown

90%

83% 82%

92%

8%

68%

75%

67% 64%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Prior to RPIW First 12 months following RPIW

FY 2010 FY 2011 FY 2012

Sperm Banking

Offered Sperm Banking Attempted Sperm Banking

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

Thank You