methods of ovulation induction (6)
- Clomiphene citrate (PCOS)
- Aromatase inhibitors (PCOS)
- Gonadotrophins; low dose FSH (hypothalamic/pituitary causes, PCOS)
- Pulsatile GnRH (hypothalamic amenorrhoea)
- Dopamine agonists (hyperprolactinaemia)
- Laparoscopic ovarian drilling
clomiphene citrate MOA
SERM: binds to hypothalamic oestrogen receptors and inhibits -ve feedback
letrozole MOA
aromatase inhibitor: blocks conversion of androstenedione + testosterone to oestrogen
laparoscopic ovarian drilling MOA
destroys ovarian stroma to reduce androgen production
complications of laparoscopic ovarian drilling (2)
adhesions
ovarian failure
induction of ovulation vs superovulation
induction of ovulation: restore physiological single follicle ovulation
superovulation: multiple follicle development for IVF
give gonadotrophins: recombinant FSH (rFSH) or human menopausal gonadotrophins (hMGs)
complications of superovulation (2)
multiple pregnancy
OHSS: ovarian hyperstimulation syndrome (life-threatening condition: fluid build-up → dehydration)
Insulin sensitising/lowering drugs in treatment of PCOS (4)
Metformin
Thiazolidinediones
d-chiro-inositol
Diazoxide
current methods of embryo selection (3)
- morphology
- time-lapse
- PGS
how is embryo transfer performed
embryos aspirated into catheter and inserted into uterus under ultrasound guidance
factors for selection of embryos for transfer (3)
- fragmentation
- apoptotic bodies
- stage of development (4 cells by day 2, blastocyst by day 5
possible causes of fragmentation (4)
- apoptotic bodies
- abnormal cytokinesis and adhesions
- cytoskeleton abnormalities
- membrane abnormalities
indications for intra-uterine insemination (4)
- those who cannot/would find it very difficult to have vaginal intercourse e.g. clinically diagnosed physical disability or psychosexual problem
- those using partner or donor sperm
- those who require sperm washing where man is HIV positive
- those in same-sex relationships
stages in process of IVF (7)
- Pituitary downregulation:
GnRH agonist (2 weeks) → initial surge of LH/FSH, receptor internalisation → “temporary menopause” (→ hot flushes, emotional lability etc.)
OR GnRH antagonist → immediate downregulation (acts more quickly) - Ovarian stimulation: supraphysiological levels of FSH → recruitment of multiple follicles
- Ovulation trigger: hCG injection → maturation of eggs & ovulation (after ~37 hours)
- Egg collection: transvaginal, laparoscopically if not possible
- Fertilisation: intra-cytoplasmic sperm injection (ICSI)
- Embryo culture (for 5 days) and transfer
- Luteal support: need progesterone to maintain endometrium
indications for IVF (4)
- azoospermia
- bilateral tubal occlusion
- 2 years unexplained infertility
- woman must be aged 23-42 years
- > offer up to 3 IVF cycles
risks of IVF (4)
Multiple births
Ovarian hyperstimulation syndrome (OHSS)
Drug reactions
Ectopic pregnancy
factors affecting outcome of IVF (11)
- Age: ↓chance of live birth following IVF w ↑female age
- Ovarian reserve
- Duration of infertility
- Cause of infertility (male factor, fibroids, endometriosis, etc.)
- Obstetric history: IVF more effective in women who have previously been pregnant and/or had a live birth
- ↑number of unsuccessful cycles → ↓overall chance of live birth following IVF
- Concurrent medical problems
- BMI: optimal 19-30
- Smoking
- Caffeine
alternatives to hCG in IVF stimulation of ovulation (surrogate LH surge) (2)
- single dose GnRH
2. Kisspeptin
prevention of premature ovulation in IVF (2)
- GnRH agonist: initially causes “flare up” of LH & FSH, later downregulation of receptors → ↓LH & FSH (more effective)
- GnRH antagonist: block pituitary receptors → ↓LH & FSH (safer)
functions of cryoprotectants (4)
- Lower melting point of water so that larger proportion remains in liquid state
- Ice growth stops when CPA (cryoprotective agent) is high enough
- Increase viscosity
- Promote dehydration through osmosis
indications for egg freezing (5)
Irreplaceable number of oocytes
- Cancer patients ahead of chemo/radiotherapy; oocytes, granulosa and theca cells very sensitive to cytotoxic drugs
- Premature ovarian failure
- Lifestyle choice for delaying childbirth
- Surplus embryos saved for future pregnancies or if first IVF cycle fails
- egg donation
options for pt when fertility is decreasing (6)
- Elect to do nothing
- Ovarian transposition: surgery to move ovaries out of field of radiation
- Egg or embryo freezing, or a combination
- Ovarian cortex cryopreservation
- GnRH agonist ‘ovarian protection’
- Egg donation and or surrogacy
indications for PGD (6)
- X-linked conditions e.g. haemophilia
- Single gene defects e.g. cystic fibrosis
- Predisposition genes e.g. BRCA
- Chromosomal translocations
- Aneuploidy
- HLA typing: child could be donor for life-saving transplant
karyomapping
SNP (single nucleotide polymorphisms) arrays used to identify parental origin of chromosomes at SNP loci
