Lecture 13 + 14 ; Infertility and Assisted Reproductive technologies, part 2

Question 1

What are some ARTs?

Answer 1

Artificial insemination
Ovulation induction
IVF
Cryopreservation
Uterus transplantation
Ovarian tissue transplantation
ICSI

Question 2

Write some short notes on artificial inseminatation;

Answer 2

• Cheap ($1500) + drugs ($500)

- Might be used for men with low sperm concentration or women with cervical mucous problem

Question 3

Write some short notes on IUI methodology

Answer 3

Sperm is collected washed and placed directly into the uterus by passing possible cervical blocks

Question 4

Why would ovulation induction be used in infertility?

Answer 4

Many women who are infertile fail to ovulate

Question 5

What does ovulation induction do?

Answer 5

Increases the number of follicles produced to be collected for IVF

i.e Clomiphene citrate is used to induce GnRH secretion. Achieved by being an antioestrogen, lowers oestrogen levels, removes negative feedback to the pituitary/hypothalamus, thus FSH/LH secretion

Question 6

Whats the success of ovulation induction

Answer 6

Approximately 30-50% of infertile women treated with clomiphene will ovulate and become pregnant

Downside; increased twinning rate (1 to 5%) b/c increased double ovulations (fraternal twins)

Question 7

What are some alternative ovulation induction drugs?

Answer 7

Injected FSH

Leterozole (aromatase inhibitor) reduces estrogen

Question 8

Whats a problem with ovulation induction?

Answer 8

A problem with ovulation induction particularly when it is used in conjunction with IVF is that naturally occuring gonadotrophins may stimulate early ovulation (thus loss of potential oocytes or multiple pregnancies)

GnRH agonists and antagonists are used to down regulate natural FSH/LH secretion

Question 9

Whats a condition that can arise from ovulation induction?

Answer 9

Ovarian hyperstimulation syndrome (OHSS)

Endometrium can also become asynchronous with natural cycle while on these drugs

Question 10

Write some short notes on OHSS

Answer 10

In OHSS capillary permeability is increased such that albumin moves into the extra vascular space and causes colloid osmotic pressure gradient. Thus

• Circulating Hypovolemia
• Abdominal distension with ascites
• Shortness of breath b/c plural effusion
• Severe cases are fatal

Question 11

Whats a condition that can be treated by drug antagonism?

Answer 11

Hyperprolactemia (prolactinoma, on the pituitary)

• Excess prolactin in blood leads to anovulation
• Treated by bromocriptine, prevents with pituitary release

Question 12

When was the first IVF baby born?

Answer 12

1978

Question 13

Describe IVF

Answer 13

Oocytes are removed from the women and incubated in-vitro with sperm.

Once fertilisation has occurred the zygote is then returned to the uterus to implant

Question 14

How many babies are born in the UK via IVF?

Answer 14

2.2%

Question 15

Write some short notes on the IVF technique

Answer 15

• Drug induced ovulation
• Invasive surgery to collect many occytes
• Ex vivo culture for several days (system is very sensitive to temperature)

Question 16

What the consequence of many oocytes being collected?

Answer 16

• The more oocytes collected, the poorer the average quality is
• Question of how many and which ones to return
• Want to avoid multiple pregnancies (4+ can occur some times)

Question 17

Why are multiple pregnancies bad?

Answer 17

• Multiple pregnancies especially high order pregnancies are not good b/c
  
  • high morbidity due to smaller baby size
  • More likely to be delivered earlier
  • Require longer time on NICU

Question 18

Whats the cost of IVF?

Answer 18

$7995 per cycle

2-4k drugs

Question 19

When it was normal for four embryos to be palced (early ivf) what was the multiple pregnancy rate?

Answer 19

25%

Question 20

What are the guidelines now to avoid multiple pregnancies?

Answer 20

• Return only two maybe three embryos
• Or selective abortion of foetuses once the pregnancies are clearly established
• or Single Embryo Transfer (SET)

Question 21

Whats the success rates of IVF?

Answer 21

20-25% not better than natural conception rates

Question 22

What is cryopreservation?

Answer 22

The cryogenic freezing of tissues, using liquid nitrogen or co2

Question 23

What can be cryogenically preserved?

Answer 23

Sperm
Oocytes (more difficult than sperm)
Embryos

Question 24

Why may embryos be cryogenically preserved?

Answer 24

To reduce the number of retrievals in case they want more IVF children

Question 25

Does cryogenic preservation harm the tissues?

Answer 25

It can do, but this is to do with the process. Mostly it doesnt

Question 26

Do frozen embyros change the success rates of IVF?

Answer 26

Frozen embryos have a lower success rate than fresh

Question 27

Describe success rates of frozen embyros;

Answer 27

85% survive

26. 3% delivery rate
27. 8% live birth rate per an embryo transfer

Each year of maternal age reduced delivery rate by 7%

~20 vitrified oocytes required per a live birth (this is becoming better now)

Question 28

Describe ovarian cortical transplantation

Answer 28

Transplanted strips of ovarian cortex into arms (at first). (ovaries removed)

but they found follicles growing and menstrual cycle occurring. FSH declined!

Question 29

What was the second step following ovarian cortical transplantation?

Answer 29

They transplanted ovarian cortical tissue between twins, one of which had POF.

Natural menstrual cycle continued in POF patient was receiving tissue and menstruation occurred.

There were also a number of live births from it too

Ovarian cortical tissue could be frozen first! for later if necessary

Question 30

What is the committee opinion about ovarian tissue cryopreservation?

Answer 30

• Ovarian tissue cryopreservation and transplantation is experimental
• Should not be offered to patients with benign conditions or for the purpose of delaying child bearing
• Ovarian tissue cryopreservation and subsequent transplant may be offered to carefully selected patients as an experimental protocol.

Question 31

Describe the results from the first clinical uterus transplantation;

Answer 31

• Nine transplants of uteri from live donors
• All have immunosuppression
• 2 uteri lost to thrombosis and uterine infection
• 7 regained menstrual function
• Aim to start pregnancies 12-18 months post op

Question 32

Describe the follow up results from the first clinical uterus transplantation;

Answer 32

• One live birth
• Normal pregnancy until 31 weeks then c section delivery due to pre-eclampsia
• babe in excellent condition at 1 year
• three more babies were born and all doing well.

Question 33

What is ICSI?

Answer 33

A single sperm is drawn up into a micropipette and injected directly into the oocytes cytoplasm.

Question 34

Whats a major advantage of ICSI?

Answer 34

• Sperm quality doesnt matter i.e motility
• Polyspermy cant occur
• 34% success
• The fact only one sperm is needed, so testicles of men with severe oligiospermia (low sperm in ejaculate) or azoospermia (i.e cycstic fibrosis = no VD) can be searched for one.

Question 35

What is preimplantation diagnosis?

Answer 35

The removal of once cell from the (trophectoderm) zygote-morula stage to detect genetic disorders

Does not appear to harm development

Question 36

What are other techniques for preimplantation diagnosis?

Answer 36

Array cGH and next generation sequencing can be used for diagnostic aspects