Assisted reproductive technologies Flashcards
What is ART? (2)
- Assisted reproductive technology
- Fertility treatments that handle eggs/embryos outside of the body
What are examples of ARTs? (7)
- IVF
- IVM
- ICSI
- CT
- GIFT
- ZIFT
- NT
What is IVF?
In vitro fertilisation
What is IVM?
In vitro maturation
What is ICSI?
Intra-cytoplasmic sperm injection
What is CT?
Cytoplasmic transfer
What is GIFT?
Gamete intra-fallopian transfer
What is ZIFT?
Zygote intra-fallopian transfer
What is NT?
Nuclear transfer
What is the impact of IVF? (3)
- First IVF baby born in 1978 in the UK
- Success rates have risen from 14% in 1991 to 23% in 2018 for parents under 43
- 20 000 births from IVF in 2018
What are the stages of IVF treatment? (8)
- Female patient takes drugs to override the HPG axis and suppress the cycle
- Cocktail of drugs including FSH to stimulate maturation of a large number of follicles, aiming for 15/16 mature oocytes
- Drugs taken to prevent ovulation
- Eggs surgically removed and matured in vitro
- Sperm sample is cultured in appropriate conditions to stimulate capacitation
- Sperm and oocytes are co-incubated for fertilisation
- Embryos develop to the blastocyst stage (day 5/6) and transferred to the uterus
- Used to be that multiple embryos were implanted but now only 2 to prevent multiple pregnancies
How is IVM different from IVF? (3)
- Follows the IVF process but oocytes are harvested earlier, when follicles are at the antral stage
- Rest of maturation occurs in vitro in the presence of FSH etc prior to fertilisation using IVF or ICSI
- This limits the amount of drugs that the female needs to take which is important if vulnerable to ovarian hyperstimulation syndrome e.g. in PCOS
How does ICSI work? (5)
- A single sperm (or spermatid) is selected and injected directly into the egg cytoplasm rather than co-incubation with a large number of sperm
- Bypasses normal fertilisation i.e. the changes that sperm undergo
- Allows the use of non-motile sperm
- Success rates are lower than IVF but are improving
- Associated with a higher incidence of developmental abnormalities than normal conception, maybe due to the absence of normal sperm-egg interactions
How can spermatids be used for ICSI rather than mature sperm? (3)
- ICSI was performed using late-stage spermatids obtained via testicular biopsy in men with azoospermia resulting in live birth for 3 out of 36 males (Araki et al., 1997)
- Spermatids have finished meiosis so are the same genetically (haploid) as mature sperm but haven’t undergone spermiation
- Useful for overcoming male factor infertility
How does GIFT work? (3)
- Eggs and sperm are combined in vitro and then immediately inserted into the fallopian tubes through a small incision in the abdomen
- Fertilisation happens inside the body and the embryo implants naturally
- Fertilisation occurring inside the body can be important for cultural/religious reasons
How does ZIFT work? (2)
- Eggs and sperm are combined in vitro
- Wait for fertilisation to occur before transferring the embryos to the fallopian tubes
What is cryopreservation? (5)
- Freezing gametes and embryos
- Couples undergoing IVF will often freeze remaining oocytes/embryos to avoid having to do the whole drug cycle again
-707% increase in embryo storage and 202% increase in egg storage between 2013 and 2018 - Nothing to suggest that frozen embryos are of poorer quality
- Common before undergoing cancer treatments
What are the 2 methods of cryopreservation?
- Slow freezing with cryoprotectants
- Vitrification which is rapid freezing
What are the ethical and legal considerations that go along with gamete/embryo cryopreservation? (4)
- What happens to unclaimed embryos? Destruction? Research? Adoption?
- What happens if a couple breaks up? Embryos must be destroyed if one partner withdraws consent
- What happens if a partner dies? E.g. Diane Blood
- Questions that need to be addressed at the point of storage
How does cytoplasmic transfer work? (3)
- Follows the ICSI procedure where a sperm is injected into a recipient oocyte, along with cytoplasm from a donor oocyte containing mitochondria
- Results in a 3 parent baby with normal chromosomal contributions from the 2 parents but a mixed mitochondrial population (heteroplasmy)
- Developed specifically to treat infertility and then quickly banned due to an increased incidence of miscarriages and developmental abnormalities
How does mitochondrial transfer differ from cytoplasmic transfer? (4)
- Mitochondrial transfer is aimed at women with mitochondrial disease at high risk of passing it on to their children, not specifically for infertility
- Uses donor eggs to replace the diseased mitochondrial DNA
- Legal in the UK but no other country, and licenced in Newcastle Fertility Centre
- Can be recurrence of mitochondrial disease later in generations
What techniques are used in mitochondrial transfer? (3)
- Spindle transfer
- Pronuclear transfer
- Polar body transfer
How does spindle transfer work? (6)
- Spindle and associated chromosomes are removed from the unfertilised donor egg
- Spindle and associated chromosomes are removed from the patient egg and fused into the enucleated unfertilised donor egg
- Reconstituted egg is fertilised by ICSI with the father’s sperm
- Embryo is implanted into the mother’s uterus
- Possible that some diseased mitochondria can be transferred with the spindle and re-establish disease in the embryo
- Resulted in a baby born in 2016 to a Jordanian couple with the procedure carried out by US doctors in Mexico
How does pro-nuclear transfer work? (4)
- Both the donor and patient eggs are fertilised with the father’s sperm
- Develop to the stage of fusion of pronuclei
- Patient’s pronuclei is transferred to the enucleated fertilised donor zygote with normal mitochondria
- Reconstituted zygote develops to an embryo and is implanted into the mother’s uterus
What is somatic cell nuclear transfer (SCNT)? (4)
- Enucleated donor oocyte is fused with an entire somatic cell from nuclear donor so no recombination of genetic material
- Blastocyst is implanted into a surrogate
- Effectively cloning e.g. Dolly the sheep
- Associated with increased rate of developmental abnormalities, cardiovascular disease, obesity etc so not used in humans
What is therapeutic cloning? (4)
- Embryo is created using SCNT
- Pluripotent embryonic stem cells (ESCs) are harvested from the inner cell mass of the blastocyst
- ESCs are differentiated in vitro into specific lineages e.g. cardiac muscle cells, neurons, islet cells etc for personalised disease treatment
- Alternatively can use adult stem cells