reproductive treatments Flashcards
when is testosterone replacement used?
in people not requiring fertility
treats the symptoms of testosterone deficiency (low libido, loss of early morning erections, decreased shaving)
must have at least 2 measurements of low serum testosterone before 11 am
investigations into the cause should be done
how can testosterone be replaced?
daily gel - take care not to contaminate partner
3 weekly IM injection
3 monthly IM injection
implants, oral preparations - less common
safety monitoring must be carried out:
haematocrit - T increases risk of hyperviscosity and stroke
prostate - prostate specific antigen levels (PSA)
how is sperm induction done?
primary hypogonadism - difficult to treat
secondary hypogonadism - (in hypogonadotrophic hypogonadism) treat with LH and FSH (gonadotrophins) to induce spermatogenesis
LH - stimulates Leydig cells to increase intratesticular testosterone to much higher levels than in circulation. hCG injecitons act on LH receptors
FSH - acts on Sertoli cells to stimulate seminiferous tubule development and spermatogenesis
(avoid giving testosterone to men desiring fertility)
, as this fill further lower the levels of LH and FSH, further reducing spermatogenesis)
what are the most common causes of amenorrhoea?
secondary amenorrhoea (after pregnancy and menopause)
PCOS:
hyperandrogenism clinical (hirsuitism, acne) and biochemical signs
PCO morphology on US
hypothalamic amenorrhoea: low body weight excess exercise stress genetic susceptibility all cause hypothalamus to decrease in function
what is ovulation induction?
aim to develop one ovarian follicle
in >1 develops it risks multiple pregnancy
this has risks for both mother and baby during pregnancy
ovulation induction methods aim to cause a small increase in FSH
how is ovulation induction done in anovulatory PCOS?
restore ovulation:
1. lifestyle/weight loss/metformin
- letrozole (aromatase inhibitor - blocks formation of oestrogen from T. less negative feedback on HPG axis. more kisspeptin, so more GnRH, so more LH/FSH, which induce ovulation)
- clomiphene (oestradiol receptor modulator - decreases negative feedback effect of oestrogen )
- FSH stimulation
how does letrozole induce ovulation?
it is an aromatase inhibitor
blocks testosterone -> oestrogen reaction
less oestrogen means less negative feedback on HPG axis
so more GnRH
:. more LH/FSH
increased FSH stimulates follicle growth
what is a basic overview of IVF?
- oocyte retrieval
- fertilisation in vitro (if male factor infertility - intra-cytoplasmic sperm injection (ICSI))
- embryo incubation for 3-5 days
- embryo transfer into uterus
what hormones are given to start IVF?
- FSH - to stimulate ovulation (day 1-10)
what are the IVF long and short protocols and why are they used?
FSH will cause an LH surge. this has to be prevented or it wall cause premature ovulation
a) Short protocol: GnRH antagonist (days 6-10)
b) Long protocol: GnRH agonist (days -7 - 9)
the long protocol works as normal GnRH secretion is pulsatile, resulting in a pulsatile secretion of LH
however continuous high dose GnRH desensitises the GnRH receptor, this causes an initial flare of LH (but as you start on day -7 this will finish before FSH commences) but it then inhibits LH
what step of IVF comes after prevention of premature ovulation?
day 11 the follicle is made to mature using LH exposure.
this mimics the LH surge seen in normal physiology when ovulation occurs
day 13 - oocyte removal from ovary and fertilisation
day 18 - transfer embryo to endometrium
day 30 - pregnancy blood scan
day 44 - pregnancy US
what are some methods of contraception?
temporary:
barrier (condom/ diaphragm/ cap with spermacide)
combined oral contraceptive pill
progesterone only pill
long acting reversible contraception (IUDs and implant)
emergency contraception
permanent:
vasectomy
female sterilisation
wha tare pros and cons of the barrier method?
pros:
STI protection
easy to obtain
no contra indications as with some hormonal methods
cons:
can interrupt sex
can reduce sensation
can interfere with erection
how does the oral contraceptive pill work?
contains oestrogen and progesterone
these have a negative feedback effect on GnRH and LH/FSH
this leads to anovulation
also mainly progesterone leads to:
thickening of cervical mucus
thinning of endometrial lining to reduce implantation
can also be used to lighten or make periods less painful
or help with PCOS to reduce LH and hyperandrogenism
what are pros and cons of the OCP?
pros: easy to take effective doesnt interrupt sex can take several packs back to back so no bleeding reduces risk of endometrial cancer doesnt actually cause weight gain
cons:
may forget to take
no STI protection
P450 enzyme inducers (eg antibiotics) may reduce efficacy
not best choice during pregnancy
side effects (spotting, nausea, mood and libido changes etc)
blood clots (very rare)
what are the pros and cons of the progesterone only pill?
pros:
works same as OCP but less reliably inhibits ovulation
suitable if you cant take oestrogen
other pros same as OCP
cons:
forget to take
STIs
shorter acting - needs to be taken within the same hour every day
side effects (irregular bleeding, headaches, sore breasts, changes in mood and libido)
what are long acting reversible contraceptives?
LARC for example coils (which are the most suitable for women)
exclude STIs and do cervical screening before insertion
prevents implantation of conceptus
can rarely cause ectopic pregnancy
can be used as emergency contraception
- IUD - copper coil
mechanically prevents implantation
decreases sperm egg survival
lasts 5-10 years (may cause heavier periods so may be taken out earlier - IUS - progesterone secreting pill
thins lining of the womb and thickens cervical mucus
can be used to help with heavy bleeding
lasts 3-5 years - progestogen only injections or implants
what are modes of emergency contraception?
- copper IUD:
most effective
fitted up to 5 days after unprotected sex
emergency contraceptive pill 2. Ulipristal acetate 30mg (ellaOne) stops progesterone working normally and prevents ovulation earlier the better but up to 5 days 3. levongesterel 1.5mg (levonelle) least effective, especially in bmi >27 synthetic progesterone prevents ovulation must take within 3 days
what are the side effects of emergency contraceptives?
headache
abdominal pain
nausea
Liver P450 enzyme inducer medications make is less effective (eg. some antibiotics)
if you vomit within 3-4 hours of taking it you need to take another
what considerations are taken into account when choosing a contraceptive?
1. risk of venous thromboembolism (VTE)/CVD/stroke migraine with aura (stroke risk) smoking history of stroke/CVD current breast cancer liver cirrhosis diabetes with complications
- other conditions that may benefit from OCP
eg menorrhagia/endometriosis/fibroids - need for prevention of STIs
- concurrent medication
P450 liver enzyme inducing drugs (eg. antibiotics)
teratogenic drugs (eg. lithium/warfarin)
more effective contraception needed in these cases
which methods of contraception are the most effective?
the ones which arent user dependant
implant, IUS, IUD
what are the risks of Hormone replacement therapy?
- venous thrombo embolism
DVT or PE (pulmonary embolism)
oral oestrogens undergo first pass metabolism in the liver
oral greatly increases SHBG, triglycerides and CRP. so increases clotting risk
transdermal oestrogens are safer for VTE risks (especially avoid oral in BMI >30)
2. hormone sensitive cancers breast cancer - slight increase only in women on combined HRT risk related to duration of treatment, goes down when stopped continuous is worse than sequential
ovarian cancer - small increase in risk after long term use
endometrial cancer - MUST prescribe progestogens (synthetic progestins and progesterone) in all women with an endometrium
- possible increase in risk of CVD
no increase if started before age 60
increase if started 10 years after menopause
4.stroke risk
oral> transdermal oestrogens
combined >oestrogen only
safety and efficacy should be assessed at 3 months then annually
what are the benefits of HRT?
relieves symptoms of low oestrogen (flushing, disturbed sleep, decreased libido, low mood)
fewer osteoporosis related fractures (decreased by 1/3)
how are prepubertal young people helped to transgender?
GnRH agonist for pubertal suppression and then sex steroids (T or E2)
post treatment regret 1-2%
gender reassignment surgery after 1-2 yrs of hormonal treatment
what masculinising hormones are used for transgender men?
Testosterone (side effects: polycythaemia, lower HDL, obstructive sleep apnoea)
progesterone to suppress menstrual bleeding if needed (may cause endometrial hyperplasia 15%)
in 1-6 months: balding deeper voice acne facial and body hair change in body fat enlargement of clitoris menstrual cycle stops increased muscle mass
what feminising hormones are used for transgender women?
oestrogen:
high dose
(side effects - VTE, high BP, CVD, high triglycerides, hormonal sensitive cancers, abnormal LFts)
reduce testosterone:
GnRH agonists (induce desensitisation of HPG axis)
anti-androgen medications (eg. spironolactone)
1-3 months: decrease in sexual desire and function, slowing in balding
3-6: softer skin, change in body fat, decreased testicular size, breast development
6-12: hair may become softer and finer
