ART Flashcards
causes of infertility
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%
definition of infertility
Infertility defined as the failure to conceive after 1 year of regular unprotected intercourse.
what is:
- azoospermia
- asthenizoospermia
- teratozoospermia
Azoospermia- no sperm
Asthenozoospermia- slow swimming sperm
Teratozoospermia- high numbers morphologically abnormal sperm
basic options for ART
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.
Mechanism for inducing ovulation
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.
Describe inducing ovulation by removing negative feedback
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
example of selective estrogen receptor modultaor
Clomid or clomiphene
example of aromatase inhibitor
letrozole
drugs end in zole
outline the IVF cycle
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)
describe dominant follicle selection
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
describe how exogenous FSH affects the recruitment of follicles
Hyperstimulated cycle- injecting FSH, FSH levels stay high so more follicles survive
describe the process of controlled ovarian stimulation
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.
How do GnRH agonists work to downregulate the HPG axis
Use GnRH antagonists and agonist- agonist same effect because after initial flare period, decoupleing of receptors so switches off endogenous LH and FSH production
how do doctors collect the oocyte
transvaginally under ultrasound guidance
what factors need to be controlled in IVF
Control factors such as nutrients, acidity, humidity, temperature, gas composition of air, and exposure to light.
