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Flashcards in ART Deck (29)
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1
Q

causes of infertility

A

Mechanical blockage to egg and sperm meeting.
Infection/occlusion of vas deferens or uterine tubes.
Previous ligation for sterilisation.
Endometriosis.
Congenital defects.

Failure of gamete production or release.
Anovulation, maternal age, PCOS.
Azoospermia, asthenozoospermia, teratozoospermia.

Failure of fertilisation/implantation & miscarriage.
Genetic factors.
Endometrial receptivity, maternal age.

Idiopathic >25%

2
Q

definition of infertility

A

Infertility defined as the failure to conceive after 1 year of regular unprotected intercourse.

3
Q

what is:

  • azoospermia
  • asthenizoospermia
  • teratozoospermia
A

Azoospermia- no sperm
Asthenozoospermia- slow swimming sperm
Teratozoospermia- high numbers morphologically abnormal sperm

4
Q

basic options for ART

A

Inducing ovulation with exogenous hormones.

Bypassing the uterine tube (IVF).

Direct collection of sperm from the testis/epididymis.

Direct insertion of the sperm into the egg (ICSI).

Donor gametes.

Combination of the above.

5
Q

Mechanism for inducing ovulation

A

stimulating the pituitary

Stimulate the pituitary using exogenous GnRH pulses 60-90 minutes.

High frequency pulses favour LH secretion
Low frequency pulses favour FSH secretion.

Given as a subcutaneous infusion.
GnRH loaded into pump.
Pump programmed to give 60-90min injections.
Monitor by ultrasound.
Usually results in single ovulation as stimulation of the ovary is indirect and feedback is intact.

6
Q

Describe inducing ovulation by removing negative feedback

A

Gonadotrophin levels may be normal, but are not cyclical.

Inter-cycle rise in FSH relies on death of the corpus luteum.
ie. fall in levels of progesterone and estradiol.

There is no corpus luteum in the absence of ovulation

Cannot reduce progesterone as there has not been a corpus luteum to make any.

There are follicles in the ovary making estradiol so we can remove the negative feedback of this.

Use anti-oestrogen or aromatase inhibitor

7
Q

example of selective estrogen receptor modultaor

A

Clomid or clomiphene

8
Q

example of aromatase inhibitor

A

letrozole

drugs end in zole

9
Q

outline the IVF cycle

A

Hypothalamic-pituitary down regulation (GnRH)
Ovarian stimulation (monitoring follicles)
hCG trigger
Oocyte retrieval
Fertilisation in vitro
Embryo culture 3 – 5 days
Embryo or Blastocyst Transfer
Pregnancy confirmation
Luteal phase support - Cyclogest (progesterone)

10
Q

describe dominant follicle selection

A

growth of lots of antral follicles
Dominant follicle survives because it has more FSHr and induces LHr helping survival- continues to produce E2, E2 continues to rise, other follicles die

11
Q

describe how exogenous FSH affects the recruitment of follicles

A

Hyperstimulated cycle- injecting FSH, FSH levels stay high so more follicles survive

12
Q

describe the process of controlled ovarian stimulation

A

Downregulate Hypothamic-pituitary-gonadal axis using GnRH antagonist or agonist.

As failure will occur at each stage, we require as many eggs as possible and so hyper-stimulate the ovaries to increase follicle numbers.

Give FSH by subcutaneous injection. Growth of multiple follicles.

Monitor follicle growth with ultrasound until most follicles 12–19mm. At this point hCG trigger given (usually GnRH agonist).

36 hours allowed for completion of meiosis I and initiation of meiosis II before egg collection.

13
Q

How do GnRH agonists work to downregulate the HPG axis

A

Use GnRH antagonists and agonist- agonist same effect because after initial flare period, decoupleing of receptors so switches off endogenous LH and FSH production

14
Q

how do doctors collect the oocyte

A

transvaginally under ultrasound guidance

15
Q

what factors need to be controlled in IVF

A

Control factors such as nutrients, acidity, humidity, temperature, gas composition of air, and exposure to light.

16
Q

what is the first sign of fertilisation in IVF

A

2 pronuclei

17
Q

how are embryos transferred into the uterus

A

Embryo transferred to the patient’s uterus through catheter, which goes through the cervix, usually under ultrasound guidance.

18
Q

when might multiple embryos be transferred

A

Advanced maternal age and failed implantation are indications for transferring more than 1 embryo

19
Q

when is Intracytoplasmic sperm injection - ICSI used?

A

Used in low sperm count, low motility or repeated fertilisation failure.

20
Q

describe ICSI

A

Single sperm used so can collect sperm by needle aspiration from epididymis or testis.

Inject sperm into the egg.

21
Q

when might cryopreservation of ovarian tissue be used?

A

no time to create an embryo
too young
no partner

22
Q

process of ovarian cryopreservation

A

Patient has ovary removed prior to cancer therapy.
After cure, pieces of ovary are re-implanted. Follicle growth monitored by estradiol - successful ovulation and fertilisation.

23
Q

why might you not do an IVF cycle in cancer patients

A

some cancers are hormone dependent

treatment might need to start straight away

24
Q

describe the 2 ways of mitochondrial donation

A

Meiotic spindle transfer (MST)
Meiotic spindle of donor oocyte removed during MII and replaced by patient spindle- patient oocyte fertilised, cytoplasm discarded and nucleus inserted into another donor oocyte

Pronuclear transfer (PNT)
Pronuclei of fertilised patient egg transferred to fertilised donor egg which has had pronuclei removed.
25
Q

3 types of cloning and example

A

Natural cloning
Mitotic division of a cell.
Asexual reproduction…plants, invertebrates.
Identical twins.

Reproductive cloning
Somatic cell nuclear transfer.
Designed to create a new ‘being’.

Therapeutic cloning
Cloning to create stem cells which are compatible with a recipient.

26
Q

therapeutic uses of stem cells

A

Brain or nerve tissue – Parkinsons, Altzheimers or spinal cord injury.
Heart disease – repair ischaemic damage to cardiac muscle.
Bone marrow – restore bone marrow/blood cells in cancer patients.
Skin grafts – replace damaged skin in accident or burn victims.

27
Q

benefit of cloning stem cells for theraeutic use

A

will be genetically identical- no rejection

28
Q

cloning technique

A

Collect a mature oocyte and remove the haploid nucleus.
Take an adult diploid somatic cell and transfer the nucleus into the enucleated egg.
Fusion activation with electricity & chemical stimulus to mimic fertilisation.
The embryo will have identical DNA to the adult from whom the nucleus came.
Harvest inner cell mass and create therapeutic stem cells OR…
Find a friend who will carry the embryo to term, or do it yourself if you have the right anatomy & give birth to your clone.

29
Q

why use foetal cells to create stem cells?

A

We need the entire genome of undamaged DNA

Embryonic cells are easier to re-programme into the cell of choice.

We might create an embryonic clone in order to create cells for donation that will not be rejected. It is possible to re-programme some adult cells but it’s complex and they are not totally pluripotent.