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fertility preservation for young
cancer patients
Kate Stern MIVF and RWH, Melbourne
disclosures
personal
no pharma boards/advisory positions
no travel/educational support
institutional
nondirected grants for ovarian grafting programs and AOFR admin support
Merck-Serono
MSD
Ferring
what we will discuss
• relevance
• infertility
• pregnancy
• options
• new/interesting stuff
• dilemmas
• what’s important
annual changes in incidence and mortality
AIHW 2013 data 2010/11
increasing incidence 0.7%
falling mortality 1.4%
future fertility
more relevant
how common is cancer in young people?
1/570 girls and women <35y 1/490 boys and men < 35y
http://www.aihw.gov.au/index.cfm
common cancers in girls/young women
0
100
200
300
400
500
600
700
800
0 - 14 15 - 29 30 - 39
Melanoma
Breast
Cervix
Other Gynaecological Cancers
Brain
Haematological Cancers
Sarcoma
Thyroid
AIHW Cancer in Australia 2014
blood cancers
breast cancer
relevance of fertility preservation
breast cancer
infertility from cancer treatment
ovarian damage from chemotherapy
age drug dose
ovarian
damage
spectrum of ovarian compromise
no effect
temporary ovarian failure (TOF)
with apparent recovery
permanent ovarian failure(POF)
later onset premature
ovarian failure
(LO-POF)
chemotherapy
age 20 age 40
age 30 after strong chemo
Reproduced with permission from Debra Gook MIVF
reduction in follicular pool with cancer tx
Meirow et al 2010
onset of premature
ovarian failure
infertility after cancer treatment
16105 cancer patients and 85500 controlsPeccatori et al 2013 ESMO
safety of pregnancy after cancer treatment
mother and baby
• no increase in miscarriage or
abnormalities in babies
• heart effects of some chemo agents
so need assessment
• abdo/pelvic radiotherapy could
damage uterus
• risk of recurrence NOT increased in
hormone-sensitive cancers with
low-risk disease
fertility preservation options
tissue freezing oocyte freezing
ovarian tissue preservation
• only option for young girls
• high risk of permanent damage
• not much time
• can’t use hormones
• with other options
process of ovarian tissue harvest
grafting sitespelvic side wall
ovary
anterior abdo wall
hard work!
risk of malignant cell transmission
don’t always get eggs
labor-intensive for patients
preg rate 14%
4 in Australia
egg freezing
• established and available technology
• predictable success
• only after puberty
(youngest reports 13-14 yrs)
• limited number of oocytes
hormone stimulation 10-14 days to get
multiple eggs
excellent results with egg freezing and survival
• >5000 babies born (no increase in abnormalities)
• pregnancy rates same as IVF (30-40 % per embryo < 40 yrs)
how do the options compare?oocyte freezing ovarian tissue freezing
average number
obtained
(range)*
14
(3-45)
140
(28-540)
time required 12-14 days one day
invasiveness minimal moderate
hormones required yes no
survival 90% vitrification excellent
IVF yes usually
livebirths >5000 >100 reported
expectation of success excellent if get enough
eggs
low-moderate
* MIVF/RWH data
ovarian protection during chemotherapy
ovarian toxicity from chemotherapy
possible mechanism and protection
Kalich-Philisoph et al 2013
FSH
GnRH analogue
premature ovarian failure with chemotherapy
protection with GnRH analogues
Lambertini et al 2015
GnRH analogues summary
• biological plausibility and preclinical evidence
• variability in results due to heterogeneity of trials in terms of
endpoints and follow-up period
• no danger
• pts need to be informed about data
most important action likely to be protection of later ovarian reserve
0 10 20 30 40 50 60
Leukaemia
Lymphoma
Neuroblastoma
Brain & CNS
Retinoblastoma
Kidney
0 – 14 y
common cancers in young males
http://www.cancervic.org.au/downloads/cec/cancer-in-vic/CCV-statistics-trends-2011.pdf
0 5 10 15 20 25 30 35
Testis
Lymphoma
Leukaemia
Melanoma
Brain & CNS
15 – 24 y
normal severe atrophy
effect of chemo/radiotherapy on testis
• cancer can cause reduced sperm function
• germinal epithelium damage including spermatogonia
• testosterone production can be impaired
preservation of male fertility
current options
ejac semen freezing for later ICSI
testicular biopsy sperm freezing for later ICSI
testicular tissue freezing
donor sperm if necessary
potential future options
spermatogonial transplant
in vitro spermatogenesis
controversies
collection of sperm from pre and peri-pubertal boys
does cancer adversely affect sperm parameters
new and interesting stuff
genetic testing of embryos for cancer genes
eg breast cancer genes BRCA 1 and 2
birth after graft of tissue taken at age 13
• girl with sickle cell anaemia
• tissue taken age 13 years and 11 months premenarchal but breast development
grafting into abdominal pocket
methods to reduce the risk of tumour cell transmission
xenograft model “artificial ovary” fibrin clot
Nao Suzuki 2015
ovarian strips cultured with PTENi and PI3Ka
strips autografted
9/20 showed follicle growth
oocytes retrieved from 6 patients
finding oocytes in ovarian tissue of
patients with premature ovarian failure
uterine transplant (Brannstrom et al)
better data collection - registry
current dilemmas
affordability and accessibility of FPS for patients
oncologists fertility specialists
surrogacy
access to gestational carriers
preserving altruism
protecting rights of all parties
best interests of child
paramount
posthumous FPS• retrieval of sperm from deceased men or those who can’t
consent eg unconscious
• usage of gametes/embryos from deceased patients
value of preconsent/freezing for those in high-risk
professions or for terminal patients
FPS for young children
• ethical frameworks and processes essential
• guided by best evidence
• informed consent of families
putting it all together
risks associated with doing something
(potential )benefits compared with not doing something
time criticality
individualisation of decision-making
conclusions
where are we at?
well developed programs in Australia
providing full range of services
working on improving our data
collection
working towards evidence-based,
best-practice guidelines
need to improve our collaboration
nationally and internationally
Researchers
Deb Gook
Franca Agresta
Tanya Stewart
Claire Garrett
John McBain
Lyndon Hale
Manuela Toledo
Advisors
Dror Meirow
CY Andersen
thank you
