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Cryopreservation of Fertility (Impact of Cancer Treatment (2Gy radiation…
Cryopreservation of Fertility
Introduction
females have fertility regulation option (contraception)
1950s= 8% children survived cancer; now 80% do
Cancer treatment detrimental to overall health and reproductive function
Chow
et al
2016; retrospective study; compared sibling reproduction between survivor and healthy
Impact of Cancer Treatment
Mainly effects ovary although HPGA can be affected
Pre-pubertal girls with radiation on pelvis = uterine growth restriction
2Gy radiation dose= reduce ovarian reserve by 50% (treatment typically 20Gy)
Highly gonadotoxic
Age to determine the effect of treatment on fertility is difficult as everyone different (Wallace-Kelsey Model)
In vivo mouse + In vitro cell cultures
identify effect of chemo on depletion of PFs and causing POI
Lopes
et al
. 2014;
Docetaxel effect on ovarian reserve; perinatal mouse; collected ovaries; treated with drug; reduced number of PFs that reached primary follicle stage + overall follicle health lower due to granulosa cell damage; cell death pathway upregulated in granulosa cells; less follicles; less negative feedback; more PF activation; POI
Normal Reproductive Function
Fixed number PF pool
cyclical release + folliculogenesis
PTEN and AMH control
PTEN KO = no reserve follicles
Durlinger
et al
1999; AMH KO mouse; reduced number PFs and more activated
Culture ovaries in AMH= 40% reduction in folliculogenesis
tight HPG-A and intrafollicular signalling to avoid POI
Changing Treatments
Edinburgh Study
400,000 individuals who required cancer treatment
Aim: reduce number individuals receiving radiation to preserve fertility
Wanted to maintain high survival rates
3 groups; low, medium, high
2 rounds of chemo then PET scan
PET negative-no radiation = less long-term damage to fertility
Different cancer treatments = Different effects to long-term fertility
Important to understand how each treatment effects fertility
Identification of At-Risk Individuals
Age
follicles remaining
Wallace-Kelsey Model
~295,000 follicles
Mother Menopause
AMH levels
Women breast cancer study
<3.8pmol/l = amenorrheic
<20.3pmol/l = menses resumed if <38.9years-old
20.3pmol/l = menses resumed
Fertility Preservation Methods
Patient survival > Fertility
don't want to change treatment to risk death
Adult Females
Oocyte cryopreservation +/or embryo cryopreservation
need hormones; hormone-responsive tumours; delays in treatment
Whole ovary or cortical section cryopreservation
immediate procedure
Worldwide theres been 60 pregnancies
risk of transferring back cancer cells
IVM of oocytes
Epigg 1984; Eggbert
1990s; multistep culture system to produce PFs from cortical biopsies
Telfer
et al
2008; 4-step process; activation, isolation, growth, meiosis
Anderson
et al
. 2013; follicles from pre-pubertal girls; more abnormal follicles