Module 6: Frontiers in Reproductive Health and Technology Flashcards
Oncofertility
-specialty field bridging the gap between oncology and reproductive medicine
-focuses on expanding the methods of fertility preservation in cancer survivors
What is cancer
-abnormal and malignant growth of any of the body’s own cells
What percent of cancer cases are prostate
-21%
What percent of cancer cases are breast
-25%
How many people are expected to develop cancer in their lifetime
-1 in 2
Impact of childhood cancer
-future physical development and fertility prospects
Types of cancer treatments
-surgery
-chemotherapy
-radiation
-hormone therapy
-immunotherapy
-targeted therapy
Effect of surgery on fertility
-reproductive organ surgeries may damage innervation and sexual function
Effect of chemotherapy on fertility
-can be affected by DNA damaging drugs, can be temporary or permanent
Effect of radiation on fertility
-x-ray energy damages DNA, leading to cell necrosis
Affect of hormone therapy on fertility
-blocking the production of reproductive hormones causes temporary fertility loss
Effect of immunotherapy on fertility
-long term fertility effects are unknown, since this is a new form of therapy which enhances the immune response to cancer cells
Effect of targeted therapy on fertility
-long term fertility effects are unknown, since this is a new form of therapy being introduced to target specific molecules in cancer cells
Fertility preservation methods
-used to protect and manage patient fertility
Current methods of family preservation
-gonadal shielding
-cryopreservation
Gonadal shielding
-procedure used to help keep a person fertile by preventing damage to reproductive organs during radiation therapy
How does gonadal shielding work
-protective shield is placed on the outside of the body to cover the area of the gonads and other parts of the reproductive system during radiation therapy
Crypreservation
-involves freezing gametes or embryos, for use in the future with the aid of assisted reproductive technologies
How does cryopreservation work
-holds tissues at temperatures between -140 and -200 degrees celcius at which no biological activity can occur
-produces a state of suspended animation
Risks of cryopreservation
-process of cooling and warming causes damage to the cells
Cryopreservation tissue damage
-dehydration/osmotic damage
-mechanical changes
-pH changes
-rehydration damage
-oxidative stress
-temperature stress
Dehydration/osmotic damage of cryopreservation
-increased solute concentration interruption of ion exchange
Mechanical changes of cryopreservation
-excessive folding of membrane as cell volume is reduced
pH changes cryopreservation
-changes in electrochemical gradients
-alterations to enzyme activity
Rehydration damage cryopreservation
-lysis of damaged cells
-loss of electrolytes
Oxidative stress cryopreservation
-free radical damage
-lipid peroxidation
Temperature stress cryopreservation
-denaturation of proteins
-breached membranes due to formation of ice crystals
Ovarian tissue cryopreservation
-method in which individual follicles or strips of ovarian can be cryopreserved directly for future use in either tissue transplantation or in vitro follicle maturation
Risk of ovarian tissue cryopreservation
-associated with a risk of reintroducing cancer cells from the transplanted tissue and is thus considered a last option for the preservation of fertility in patients
Oocyte cryopreservation
-ideal for women who do not have a male partner or sperm donor at time of preservation
Step one of oocyte cryopreservation
-hormonal stimulation used to induce superovulation
Step two of oocyte cryopreservation
-oocytes are collected via transvaginal oocyte retrieval
Step three of oocyte cryopreservation
-harvested oocytes are cryopreserved
Step four of oocyte cryopreservation
-can be thawed and fertilized by in vitro fertilization
Step five of oocyte cryopreservation
-resulting embryos are transferred into patient during disease remission
Embryo cryopreservation
-most successful method of fertility preservation
Step one embryo cryopreservation
-superovulation occurs due to hormonal stimulation
Step two embryo cryopreservation
-oocytes are collected via transvaginal oocyte retrieval
Step three embryo cryopreservation
-harvested oocytes are fertilized in vitro
Step four embryo cryopreservation
-embryos are cryopreserved
Step five embryo cryopreservation
-cryopreserved embryos will be thawed and transferred into patient at remission
Testicular tissue preservation
-can be used in prepubertal boys who do not yet produce mature sperm
-testicular tissue containing immature sperm is removed and frozen before cancer therapy
Mature sperm preservation
-mature semen samples can be collected from post pubertal men
-spermatozoa seem to be less sensitive to cryopreservation damage because of high fluidity of membrane and low water content
Testicular sperm aspiration
-collection method for men who are unable to ejaculate or who produce low amounts of semen with ejaculation
The oncofertility consortium
-major advancement in advocacy for the devastating effects that cancer can have on the possibility of having children
Embryo selection
-techniques focus on the evaluation and pre-selection of embryos that are most viable for conception
Embryo modification
-involves the direct genetic editing of the DNA sequence of an embryo
Preimplantation genetic screening
-used to aid embryo selection for certain groups of patients, such as those with advanced maternal age, repeated IVF failure, severe male factor infertility, or repeated miscarriage
Preimplantation genetic diagnosis
-diagnostic test used to select genetically or chromosomally normal embryos for patients at high risk of transmitting a specific genetic abnormality to their children before proceeding with IVF
When is preimplantation genetic diagnosis used
-in cases where both prospective parents are carriers of an autosomal recessive mutation
-or when one of parents is heterozygous for an autosomal dominant mutation
What are types of autosomal recessive mutations
-cystic fibrosis
-sickle cell anemia
What are types of autosomal dominant mutations
-huntingtons disease
-neurofibromatosis
Ethical issues of preimplantation genetic screening
-mosaic embryos
What are mosaic embryos
-embryos that contain both normal and abnormal cells
Ethical issues of preimplantation genetic diagnosis
-debate over which inheritable conditions are serve and debilitating enough to be acceptable for treatment
Genome editing
-comprises all the technologies that allow scientists to change DNA of a cell or organism in a targeted manner
Applications of genome editing
-crops and livestock
-biomedicine
-industrial technology
-reproduction
Crops and livestock genome editing
-used to increase yield
-for example by introducing resistance to disease and pests, and tolerance of different environmental conditions
Biomedicine genome editing
-used in pharmaceutical development, xenotransplantation, gene and cell-based therapies, and control of insect-borne diseases
Industrial technology genome editing
-developing third generation biofuels, producing chemicals, materials and pharmaceuticals
Reproduction genome editing
-used for preventing the inheritance of a disease trait
Embryo editing technologies
-mitochondrial replacement
-CRISPR/Cas9 system
Mitochondrial modification
-method used to treat conditions caused by mutations of mitochondrial DNA
Mitochondrial diseases
-most common group of inherited metabolic disorders
-most common forms of inherited neurological disorders
Inheritance of mitochondrial DNA
-mitochondria have their own mitochondrial DNA, which is inherited exclusively from the mother
Why is mitochondrial DNA inherited only from the mother
-mitochondria are lost during fertilization because only the head of the sperm fertilizes the egg
-the mitochondria is located in the midpiece
Mitochondrial modification methods
-mitochondrial transfer
-mitochondrial gene editing
Mitochondrial transfer
-extract chromosomes in metaphase II from mothers egg to then transfer to healthy donor egg
-hybrid egg is then transferred to mothers uterus
-often called the 3 parent embryo because it contains genetic material from 3 individuals
Mitochondrial gene editing
-gene editing technology is used to directly remove and replace the DNA section containing the mutation
CRISPR/Cas9 system
-genome editing tool that is capable of recognizing specific DNA sequences, cutting them, and even replacing them with a new sequence
Ethical issue of selection in embryo manipulation
-these technologies could be used for non-medial modifications such as race, height, weight, and even math inclination
-could also reinforce prejudice against those with disabilities or other undesirable traits
Ethical issue of modification in embryo manipulation
-may be greater consequences of changes on a large scale that are still unknown
-could be misused for introducing new traits etc.
Ethical issues of long term health and unborn offspring in embryo manipulation
-there are many questions about the health and future identity of unborn offspring produced by these technologies
-the oldest IVF child is only about 35 so it is unknown what the long-term concequences are
Barkers hypothesis
-he examined that the poorest areas of england were those with the highest rates of heart disease
-was able to demonstrate a predicative relationship between low birth weight and heart disease in adults
Epigenetic mechanisms
-make changes possible and elements including histones, the proteins that package the DNA strand, and proteins that control gene transcription
What does the genome refer to
-our DNA sequence
What does the epigenome refer to
-elements that regulate gene expression without altering the DNA sequence
Transgenerational health
-health choices and experiences may seem to only affect us but may have an impact across several generations
How may genome editing technologies effect the DNA sequence
-may additionally be influencing the epigenome
