Assisted Reproductive Technology Flashcards
Define infertility
Infertility is defined as the failure to conceive after a year of regular unprotected intercourse
What are some causes of infertility?
- Mechanical blockage to egg and sperm meeting - infection/ occlussion 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, tetrazoospermia
- Failure of fertilisation /implantation and miscarriage-genetic factors, maternal age, endometrial receptivity
- Unknown
What is assisted reproductive technology (ART)
- Inducing ovulation with exogenous hormones :
- By passing the uterine tube (ivf)
- Direct collection of sperm from the testis/epididymis
- Direct insertion of sperm into the egg (ICSI)
- Donor gametes
- Combination of the above
- Inducing ovulation - what are exogenous gonadotrophins used for?
used to treat women who are anovulatory who have oligo/ammenorrhea (few menses/no menses)
LH surge causes you to ovulate , LH surge is caused by the negative feedback from the production of estrogen by dominant follicle
induce a single dominant follicle by injecting FSH (FSH is needed for folliculogenesis)
Need to monitor with US to avoid multiple dominant follicle and get 1 dominant follicle.
Daily injections … monitor by ultrasound during the cycle.
What is an example of exogenous gonadotrophin
Fostimon
Daily injections of FSH and monitored with ultra sound
Why do you need to give FSH gonadotrophins?
Bc high negative feedback so very little FSH and FSH is needed to make one dominant follicle
How can you induce ovulation by negative feedback when levels of LH are too low to induce ovulation?
Gonadotrophin levels may be normal but are not cyclical : stuck in the first half of cycle , enough FSH for folliculogenesis but not enough estrogen produced by the follicle to trigger LH surge which triggers ovulation.
LH needed for the maintenance of corpus luteum so there is no corpus luteum in the absence of ovulation.
progesterone is released by CL so if there is no CL there is no progesterone to cause negative feedback to increase FSH levels.
but there are follicles in the ovary making a little estrogen so we can induce negative feedback to increase FSH levels enough to produce enough oestrogen to trigger LH surge.
What are two ways to remove estrogen feedback?
- Block the E2 receptor on pituitary gonadotroph cells with SERM
- stop E2 being made by using an aromatase inhibitor
What’s an example of SERM?
Clomid
Clomiohene
What’s an example of aromatase inhibitor drug?
letrozole
Drugs ending in -zole
Why do we down regulate HPG axis?
To prevent LH surge = to prevent ovulation straight away at early stage before the follicle is matured.
multiple follicles used in IVF as failure can occur in any stage so 5/6 selected follicle = very high levels of oestrogen = LH surge very early on in the small follicles so downregulate the HPG to decrease LH levels and inject exogenous FSH to allow the selection of one dominate follicle before LH surge and ovulation
Why do we hyperstimulate ovaries = require as many eggs as possible?
Failure will occur at each stage so to maximise the chances of one egg surviving and be able to fertilise
Outline the IVF cycle?
- HPG down regulation (GnRH)
- Ovarian stimulation with FSH
- hCG trigger
- Fertilisation vitro
- Embryo culture 3-5 days
- Embryo or blastocysts transfer
- Pregnancy confirmation
- Luteal phase support progesterone
How do you prepare eggs before collections?
Downregulate hypothalmo pituitary gonadal axis using GnRH antagonist and agonist
As failure will occur in every stage we require as many eggs as possible and so hyper stimulate the ovaries to increase numbers
Give FSH by subcutaneous injection.
Growth of multiple follicles.
Monitor follicle growth with ultrasound until most follicle 12-19 mm, at this point hCG trigger given (GnRH agonist of kisspeptin to trigger ovulation)
36 hours allowed for the competition of meiosis I and initiation of meiosis II before the egg is collected
When and how is oocyte retrieved?
34- 38 hours post hCG trigger
collect mature eggs from ovary using transvaginal needle aspiration under ultrasound guidance
