Assisted reproductive technology Flashcards
How is infertility defined as?
as the failure to conceive after 1 year of regular unprotected intercourse
Reasons for infertility?
- Mechanical blockage to egg and sperm meeting
- Failure of gamete production or release.
- Failure of fertilisation/implantation & miscarriage.
- Unknown/unexplained – Idiopathic
How does Mechanical blockage to egg and sperm meeting cause infertility?
- Infection/occlusion of vas deferens or uterine tubes - fertilisation and early development of embryo takes place in the uterine tubes
- Previous ligation for sterilisation.
- Endometriosis – can cause inflammation in the pelvis
- Congenital defects – ie congenital absence of vas deferens
How does Failure of gamete production or release cause infertility?
- Anovulation, maternal age, PCOS.
- Azoospermia (no sperm) , asthenozoospermia (sperm don’t swim well), teratozoospermia (too many sperm have an abnormal morphology), oligospermia (when there’s a low sperm count)
How does failure of fertilisation/implantation & miscarriage infertility?
- Genetic factors – ie egg and sperm quality might not be good enough
- Endometrial receptivity (caused by hormonal abnormalities), maternal age.
What can be done to treat infertility?
- Inducing ovulation with exogenous hormones.
- By-passing the uterine tube (IVF).
- Direct collection of sperm from the testis/epididymis – insert a fine needle in the testis and aspirate the sperm
- Direct insertion of the sperm into the egg (ICSI).
- Donor gametes.
- Combination of the above.
What can be used to induce ovulation?
- gonadotrophins
- remove negative feedback
How do exogenous gonadotrphins induce ovulation?
- Used to treat women who are anovulatory/ oligo/amenorrhoea – Not enough oestrogen produced to cause ovulation
- The aim is to induce single dominant follicle.
- Daily injections of exogenous gonadotrophins– monitor by ultrasound during the cycle because too much FSH means may lead to multiple dominant follicles
- LH and FSH stimulate follicle growth and cause more oestrogen to be produced – helps select a dominant follicle
Post-menopausal women have low oestrogen and thus have more FSH – FSH found in urine
How does removing negative feedback induce ovulation?
- 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.
What are the 2 ways of blocking oestradiol feedback?
- Block the E2 receptor on the pituitary gonadotroph cells with SERM: Clomid/Clomiphene.
- Stop E2 being made by using an aromatase inhibitor. Drugs ending in ‘zole’ eg. Letrozole.
When is IVF used?
when the exogenous gonadotrophins don’t work
What is the IVF cycle outline?
- Hypothalamic pituitary down regulation (GnRH) – to prevent immature ovulation through an LH surge
- Ovarian stimulation (monitoring follicles) – to grow follicles
- hCG trigger – for ovulation
- Oocyte retrieval
- Fertilisation in vitro
- Embryo culture 3 – 5 days
- Embryo or Blastocyst Transfer
- Pregnancy confirmation
- Luteal phase support - Cyclogest (progesterone)
How is a single follicle selected normally?
Rise in FSH
• In the ovaries, there’s small antral follicles (left the primordial pool 3 months before, independent of LH and FSH)
• After folliculogenesis they get to the small antral stage – they express FSH receptors
• During the next menstrual cycles, they get recruited
• FSH causes oestrogen to be produced – E2 reduces FSH levels
• This causes the follicles to undergo atresia – except for one dominant follicles
How do exogenous gonadotrophins cause multiple follicle selection in IVF?
- HPG axis is off by giving the patient GnRH
- FSH is administered daily, oestrogen from the antral follicles have no effect on the FSH
- Multiple follicles selected as the dominant follicle (about 12)
- Must avoid selecting too many follicles
- Female will have high oestrogen because of follicles – this can trigger LH surge very quickly if the HPG axis isn’t turned off
Explain the steps of IVF from ovarian stimulation to egg collection?
- Downregulate Hypothamo-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 (GnRH agonist or Kisspeptin may be used).
- LH not given because it’s expensive and has a short half-life
- 36 hours allowed for completion of meiosis I and initiation of meiosis II before egg collection.
