Reproductive Treatments Flashcards
How to diagnose low testosterone?
At least 2 low measurements of testosterone before 11am
When is testosterone replacement done?
- when fertility is not desired
- used to treat the symptoms of low testosterone
What are the symptoms of low testosterone?
- loss of early morning erections
- low libido
- decreased energy
- reduced frequency of shaving
What are the options for testosterone replacement?
- Daily (gel - contact awareness)
- 3 x week IM injection
- 3 x monthly IM injection
LESS COMMON: - implants
- oral preparations
What is an example of daily gel testosterone treatment?
Tostran
What is an example of 3 x weekly IM injection?
Sustanon
What is an example of 3 x monthly IM injections?
Nebido
What needs to be monitored when on testosterone replacement therapy?
- Increased haematocrit (increased risk of hyperviscosity and stroke)
- Prostate (Prostate Specific Antigen/PSA) levels
How to induce spermatogenesis in primary hypogonadism?
Difficult to treat
How to induce spermatogenesis in secondary hypogonadism?
treat with Gonadotrophins (LH and FSH)
How does LH induce spermatogenesis?
stimulates Leydig cells to increase intratesticular testosterone to much higher levels than circulation (100x)
How does FSH induce spermatogenesis?
FSH stimulates seminiferous tubule development and spermatogenesis
What to avoid when treating low testosterone in those desiring fertility?
testosterone
Why should you avoid using testosterone to treat those low in testosterone and desiring fertility?
- additional testosterone will further lower LH/FSH
- also will reduce spermatogenesis
What is the treatment for men low in testosterone desiring fertility?
- hCG injections (act on LH receptors)
- if no response after 6 months, add FSH injections
What are the physiological features of PCOS?
- hyperandrogenism (hirstuism or acne)
- PCO morphology on Ultrasounds
- irregular periods
What are the clinical and biochemical features of hypothalamic amenorrhoea?
- low body weight
- excessive exercise
- stress
- genetic susceptibility
What is the aim of ovulation induction?
- develop one ovarian follicle (more risks multiple pregnancy)
- by causing a small increase in FSH
How to restore ovulation in Anovulatory PCOS?
- lifestyle/weight loss/metformin
- letrozole (aromatase inhibitor)
- clomiphene (oestradiol receptor modulator)
- FSH stimulation
What is the mechanism of action of letrozole for ovulation induction?
FIRST LINE
- inhibits aromatase
- stops the conversion of testosterone to oestradiol
- low concentrations of oestradiol, means decreased negative feedback for the hypothalamus and pituitary gland
- therefore, increase FSH and LH
- high FSH stimulates follicle growth
What is the mechanism of action of clomiphene?
- blocks oestradiol receptors
- reduced negative feedback
- increased LH and FSH from the pituitary
- Increased FSH stimulates follicle growth
What is the process of IVF?
- oocyte retrival
- fertilisation in vitro
- embryo incubation
- embryo transfer
What is Intra-cytoplasmic Sperm Injection (ICSI)?
injection of sperm due to male factor failure
What are the two main things involved in hormone therapy for transgender women?
- Oestrogen
- reduce testosterone
How is Oestrogen administered for transgender women?
- transdermal, oral and IM
- high dose (4-5mg/day)
- aim: estradiol levels of 734pmol/L
What are the side effects of administering Oestrogen for transgender women?
- VTE
- hypertension
- CVD
- high triglycerides
- hormone sensitive cancers (breast)
- abnormal liver function tests (3%)
How is testosterone reduced in transgender women?
- GnRH agonists (induces desensitisation of HPG axis)
- Anti-Androgen medications (eg: Cyproterone acetate, Spironolactone)
What will not change due to testosterone reduction in transgender women?
- height
- voice
- adam’s apple
What is important to consider before starting hormone therapy in transgender women?
Sperm Banking
What will happen in the first 3 months of reduced testosterone levels in trans women?
- reduced sexual desire
- reduced function (incl: erections)
- slowed or reversed baldness
What happens 3-6 months after starting to reduce testosterone levels in trans women?
- softer skin
- change in body fat distribution
- reduced testicular size
- breast development
- tenderness
What happens 6-12 months post starting testosterone reduction therapy in trans women?
softer and finer hair
What is given to transgender individuals pre puberty?
GnRH agonist to supress puberty, and then sex steroids
What is the rate of regret post hormone therapy?
1-2%
When is gender reassignment surgery an option?
after 1-2 years of hormonal therapy
What masculinising hormones are given to transgender men?
testosterone (injections or gels)
What are the side-effects of giving testosterone to trans men?
- polycythaemia
- lower HDL
- Obstructive sleep apnoea (OSA)
- NO increase in CVD
What can be given to suppress menstrual bleeding in trans men?
- progesterone
What is the risk of taking progesterone to stop menstrual bleeding in trans men?
endometrial hyperplasia (15%)
What can happen in the 6 months post starting masculinising hormones?
- balding (family and age dependent)
- deeper voice
- acne
- increased and coarser facial and body hair
- change in body fat distribution
- clitoris enlargement
- menstrual cycle stops
- increased muscle mass and strength
What is gender?
- social construct
- male, female or non-bonary
What is sex?
- biological sex
- male, female or intersex
What is cisgender?
same sex and gender
What is gender non-conforming?
gender and assigned sex do NOT match
What is gender dysphoria?
When gender and sex are mismatched and causes distress
What is non-binary?
- gender doesn’t match traditional binary gender
- includes: agender, bigender, pangender and gender fluid
What is transgender?
transitioning or planning to transition physical appearance from one gender to another
What is the general prevalence of transgender individuals?
- trans women 3 x more common than trans men
What are the benefits of HRT?
- relief of low oestrogen symptoms
(flushing, disturbed sleep, low libido, low mood) - less osteoporosis related fractures
(reduced by a third)
What are the risks of HRT?
- VTE (DVT or PE)
- Hormone-sensitive cancers
- Increased risk (if started 10 years post menopause)
- Risk of stroke (CVD)
Why is there an increased risk of VTE with HRT?
oral oestrogens first pass metabolism in the liver, increases:
- SHBG
- triglycerides
- CRP
What can reduce the risk of VTE in HRT?
- using transdermal estrogens
- USE WHEN BMI>30
What is the general dosage used when starting HRT?
- 0.025mg transdermal prep
- 0.5mg oral estradiol/day
What is the dosage if an increase of HRT is required?
Dose is increased at monthly intervals to:
- 0.05mg transdermal estradiol
- 1mg oral estradiol
What is the starting dosage for those with severe hormone failure?
0.05mg transdermal estradiol
Why is there an increased risk of hormone sensitive cancers in HRT?
breast cancer:
- slight increase in those on combined HRT (progesterone and oestrogen)
- dependent on duration (falls once stopped)
- continuous use is worse than sequential use
- INDIVIDUAL RISK ASSESSMENT NECESSARY
ovarian cancer:
- small increase after LT use
endometrial cancer:
- avoidable if progestogens are prescribed
What MUST be an adjunct prescription during HRT if an endometrium is present?
- progestogens
What are progestogens?
synthetic progestins and the natural hormone progesterone
How to assess HRT safety and efficacy?
- at 3 months, then annually
- unscheduled bleeding is common in first 3 months
- post-menopausal bleeding could indicate endometrial cancer
Who does the increased risk of CVD in HRT apply to?
- if started 10 years post menopause
- NO increased risk if started pre-60yo
- possible benefits of oestrogen supplementation in young women (POI)
What is the increased risk of stroke in HRT associated with?
- small increased risk
- risk higher in oral than transdermal oestrogens
- risk higher in combined than oestrogen only
What proportion of pregnancies are unplanned?
19-30%
What are the temporary methods of birth control?
- barrier (condom, diaphragm/cap with spermacide)
- combined oral contraceptive pill (OCP)
- progestogen-only pill (POP)
- long acting reversible contraception (LARC)
- emergency contraception
What are the permanent methods of birth control?
- vasectomy
- female sterilisation
What are the positives of condoms?
- STI protection
- easy to obtain
- no contraindications
What are the negatives of condoms?
- interrupts sex
- reduced sensation
- interferes with erections
- requires skill to use
- two are not better than one
What is the impact of the Combined Oral Contraceptive pill (OCP) on the HPG axis?
- negative feedback on hypothalamus and pituitary gland by progesterone and oestrogen
- decreased GnRH
- decreased LH and FSH
- anovulation
- thickening of cervical mucus
- thinning of endometrial lining to reduce implantation
What are the positives of the OCP?
- easy to take (1 x daily, any time)
- effective
- can take several packets back to back, avoid withdrawal bleeds
- reduce ovarian and endometrial cancer
- weight neutral in 80% (10% gain, 10% lose)
What are the negatives of the OCP?
- difficult to remember
- no STI protection
- P450 enzyme inducers may reduce efficacy
- not great while breastfeeding
What are the possible side effects of taking the OCP?
- spotting (in between periods)
- nausea
- sore breasts
- changes in mood and libido
- increased hunger
EXTREMELY RARE - blood clots in legs or lungs (2/10,000)
What are the non-contraceptive uses of the OCP?
- lighter and less painful periods (endometriosis, period pain or menorhagia) - regular withdrawal bleeds PCOS - reduce LH and hyperandrogenism
What are the positives of the Progesterone Only pill (POP)?
- less reliably inhibits ovulation
- easy to take (1 x daily)
- help heavy/painful periods
- possibly stop periods
- can be used while breastfeeding
What are the negatives of taking the POP?
- difficult to remember
- no STI protection
- short acting, needs to be taken at the same time everyday
What are the possible side effects of the POP?
- irregular bleeding
- headaches
- sore breasts
- mood changes
- sex drive changes
What does Nulliparous mean?
no previous children
When are Coils suitable?
- STI and cervical screening are suitable
- emergency contraception
Why are coils preferred in some religions?
prevents the implantation of the conceptus
What is the main risk involved in coils?
can cause ectopic pregnancy
How do IUDs work?
- mechanically prevent implantation
- decreases sperm-egg survival
- lasts 5-10 years
What are the negatives of IUDs?
- can cause heavy periods
- 5% come out, particularly during the first 3 months
What are Intra-uterine systems (IUS)?
- coils that secrete progesterone (mirena coil)
How do IUS’ work?
progesterone secretion thins the lining of the womb and thickens cervical mucus
What are the benefits of using an IUS?
- help with heavy bleeding
- lasts 3-5 years
What are the 3 main types of Long-Acting Reversible Contraceptives (LARC)?
- IUD
- IUS
- progestogen-only injectable contraceptives or subdermal implants
What is the most effective emergency contraceptive?
- copper IUD
- can be fitted 5 days after sex
- <1% chance of pregnancy
What are the 2 types of emergency contraceptive pill?
MOST EFFECTIVE: - Ulipristal Acetate 30mg (ellaOne) LEAST EFFECTIVE (BMI>27) - Levonogestrel 1.5mg (Levonelle)
How does Ulipristal Acetate work?
- stops progesterone working, prevents ovulation
- must be taken within 5 days (the earlier the better)
How does Levonogestrel work?
- synthetic progesterone prevents ovulation (no abortion)
- must be taken within 3 days
What are the side-effects of the morning-after pill?
- liver P450 enzyme inducer medications makes it less effective
- if vomit within 2-3 hours of taking it, need to take another one
- headache
- abdominal pain
- nausea
What needs to be considered when choosing a contraceptive?
- Risk of VTE/CVD/stroke
- Other conditions that will benefit from OCP
(menorrhagia/endometriosis/fibroids) - Need for STI protection
- Concurrent medication
How to assess the risk of VTE/CVD/stroke when choosing a contraceptive?
AVOID OCP IF:
- Migraine with aura (stroke)
- Smoking (>15/day) + age (>35yo)
- Stroke or CVD history
- Current breast cancer
- Liver Cirrhosis
- Diabetes with complications
What concurrent medication should you be aware of when choosing a contraceptive?
- P450 liver enzyme-inducing drugs (anti-epileptics, antibiotics)
- Teratogenic drugs (lithium, warfarin)
Consider LARCs NOT the PILL
What is the first step of IVF?
- induce the growth of multiple follicles
- large dose of FSH given
What is done once the eggs are collected?
- In Vitro Fertilisation
- IntraCytoplasmic Sperm Injection
What is intracytoplasmic sperm injection?
- direct injection of a single sperm into the egg
When is ICSI done?
When there is male factor failure/insufficiency
Once fertilised, what happens?
3-5 days incubation
transfer to endometrium
What does the large dose of FSH cause?
Superovulation
When egg removal is happening, what needs to be stopped?
- prevent premature ovulation
- done by preventing a premature LH surge
How do you prevent premature LH surge?
- SHORT protocol
- LONG protocol
What is the SHORT protocol/GnRH antagonist protocol?
- FSH (day 2)
- GnRH antagonist (day 6)
- prevents LH surge
What is the LONG protocol/GnRH agonist?
- GnRH agonist from day 21 of PREVIOUS cycle
- FSH from day 2 of current cycle
How can both a GnRH agonist and antagonist to block an LH surge?
GnRH is given in a pulsatile manner to stimulate LH,
but CONTINUOUS GnRH causes desensitisation of the GnRH receptors (leads to `LH inhibition)
What is the trigger of oocyte maturation?
LH exposure
What happens in oocyte maturation?
immature (M1): diploid
- post maturation
mature (M2): haploid
- can now be fertilised by the sperm
What is used to induce oocyte maturation?
hCG
- occasionally GnRH agonists
Why is hCG used to induce oocyte maturation?
- long lasting
- acts on LH receptor
When is oocyte induced?
on day 11
When can a pregnancy test be done?
11 days after the embryo transfer to the endometrium
