Reproductive treatments Flashcards
How do we treat primary hypogonadism?
Difficult to treat
How do we treat secondary hypogonadism?
Treat with Gonadotrophins (ie LH and FSH) to induce Spermatogenesis
How does LH help with sperm induction?
LH stimulates Leydig cells to increases intratesticular testosterone to much higher levels than in circulation (x100)
How does FSH help with sperm induction?
FSH stimulates seminiferous tubule development and spermatogenesis
Give some symptoms of hypogonadism due to opioid abuse?
Low morning Testosterone
Fatigue and reduced shaving frequency
Why do we avoid giving T to those desiring fertility?
Secondary hypogonadism (low sperm and testosterone levels) desiring fertility, giving testosterone treatment will lower LH / FSH further and further reduce spermatogenesis
How can you treat hypogonadism in those desiring fertility?
Give hCG injections (which act on LH-receptors)
If no response after 6 months, then add FSH injections
Why would someone with Kallmann’s have a worse prognosis with treatment?
Congenital Hypogonadotrophic Hypogonadism (CHH) eg Kallmann syndrome have not had mini-puberty.
FSH during mini-puberty important for growing the pool of immature spermatogonia and germ cells
How do we overcome problems with treating those with congenital hypogonadism?
2-4 months pretreatment with FSH before hCG treatment
Which testicular size is better for the affect on treatment?
Pretreatment Testicular size (Seminiferous tubules)
ie testicular volume >6ml have better prognosis
What are the symptoms of low testosterone?
loss of early morning erections, libido, decreased energy, shaving
How do you diagnose low T?
At least 2 low measurements of serum testosterone before 11am.
Investigate the cause of low testosterone.
How do we replace T?
Daily Gel eg Tostran. Care not to contaminate partner. 3 weekly intramuscular injection (eg Sustanon) 3 monthly intramuscular injection (eg Nebido) Less Common (Implants, oral preparations)
What must you bear in mind safety wise whilst replacing T (biochemical risk)?
Increased Haematocrit (risk of hyperviscosity and stroke)
Prostate (Prostate Specific Antigen (PSA) levels)
What is the aim of ovarian induction (product)?
Aim to develop one ovarian follicle
What is the most common cause of anovualtion?
PCOS
Why do we only want to stimulate one follicle?
Multiple pregnancies
Increased risk
How is ovulation induction done? (its aim)
Ovulation induction methods aim to
increase FSH by a small amount
How can we restore ovulation? (from PCOS)
- Lifestyle / Weight Loss / Metformin
- Letrozole (Aromatase inhibitor)
- Clomiphene (Oestradiol receptor antagonist)
- FSH stimulation
Why do we use aromatase inhibitors?
Low oestrodial level which normally causes negative feedback on hypothalamus and pituitary gland
Increase FSH
How do oestrodiol receptor antagonist work?
Decreased negative feedback
Increases FSH
How does IVF work?
Oocyte retrieval
Fertilisation in vitro
(IVF or ICSI)
Embryo incubation
Embryo transfer
What is ICSI?
Intra-cytoplasmic sperm injection
How do we collect eggs?
FSH stimulation (super ovulation)
Egg retrieval directly from ovary
Want to stop premature ovulation
Do this by giving drug that prevents LH surge
Make eggs mature by giving LH
How do we prevent LH surge?
GnRH Antagonist protocol (SHORT protocol)
GnRH agonist (LONG protocol)
How can both a GnRH agonist or a GnRH antagonist be used to block an LH surge?
GnRH is pulsatile so low dose can prevent surge
Non-pulsatile GnRH high dose is a blocker causes desensitisation
What happens when eggs mature (milestone)?
Becomes haploid
Achieves its capability of being fertilised by sperm
How do we mature eggs?
give hCG to trigger egg maturation
What is ovarian hyper-stimulation syndrome?
Main side effect of IVF
Pleural effusion
Ascites
Renal failure
Ovarian Torsion
Summarise a cycle of IVF prep to get oocyte
High dose FSH to induce follicle growth
GnRH to prevent LH surge
Trigger injection to mature eggs (hCG or GnRHa)
Oocyte retrieval from ovary
Embryo transfer to endometrium
What are the pros of barrier contraception (condoms)?
Easy to obtain – free from clinics
No need to see a healthcare professional
Protect against STI’s
No contra-indications as with some hormonal methods
What are the cons of barrier contraception (condoms)?
Can interrupt sex Can reduce sensation Can interfere with erections Some skill to use properly eg ensure no air, not too large or small. Two are not better than one
How does the OCP work?
- Negative feedback on hypothalamus and pituitary
- Thickening of Cervical Mucus
- Thinning of Endometrial Lining
to reduce implantation
What are the pros of the OCP?
Easy to take –
one pill a day (any time of day)
Effective
Doesn’t interrupt sex
Can take several packets back to back and avoid withdrawal bleeds
Reduce endometrial and ovarian cancer
Weight Neutral in 80%
(10% gain, 10% lose)
What are the cons of the OCP?
It can be difficult to remember
No protection against STIs
P450 Enzyme Inducers may reduce efficacy
Not the best choice during breast feeding
What are the possible side effects of the OCP?
Spotting (bleeding in between periods) Nausea Sore breasts Changes in mood or libido Feeling more hungry (try different OCPs to see which suits best)
What are the very rare side effects?
Blood clots in the legs or lungs (2 in 10,000)
What are the non-contraceptive uses of the pill?
Helps make periods lighter and less painful
(eg endometriosis or period pain or menorrhagia)
Withdrawal bleeds will usually be very regular
PCOS: help reduce LH and hyperandrogenism
What are the pros of the mini pill?
Works as OCP but less reliably inhibits ovulation
Often suitable if can’ttake oestrogen
Easy to take – one pill a day, every day with no break It doesn’t interrupt sex Can help heavy or painful periods Periods may stop (temporarily) Can be usedwhen breastfeeding
What are the cons of the mini pill?
Can be difficult to remember
No protection against STIs
Shorter acting – needs to be taken at the same time each day
What are possible side effects of the mini pill?
Irregular bleeding Headaches Sore breasts Changes in mood Changes in sex drive
What is LARCs?
Long acting reversible contraceptives
What are the three LARCs?
IUD (intra-uterine device)
IUS (intra-uterine systems)
Progesterone-Only injectable contraceptives or subdermal implants
What are the features of IUD?
Copper Coil- mechanically prevent implantation,
decrease sperm egg survival. Lasts 5-10yrs.
Can cause heavy periods, and 5% can come out especially during first 3months with periods
What are the features of IUS?
which secretes progesterone (eg Mirena Coil) to thin lining of the womb and thicken cervical mucus (can be used to help with heavy bleeding). Last 3-5yrs
What are the features of coils?
are suitable for most women including Nulliparous (no previous children).
Exclude STI’s and cervical screening up to date before insertion
Prevent implantation of conceptus – important for some religions
rarely can cause ectopic pregnancy
Can be used as emergency contraception
How can an IUD be used as emergency contraception?
Copper intrauterine device (IUD) most effective
can be fitted up to 5 days after unprotected sex (<1% chance of pregnancy)
What are the emergency contraception pills?
Emergency contraceptive pill, ulipristal acetate 30mg (ellaOne)
Ulipristal acetate stops progesterone working normally and prevents ovulation.
Must be taken within 5 days of unprotected intercourse (earlier better).
Emergency contraceptive pill, levonorgestrel 1.5mg (Levonelle) least effective (esp if BMI >27 kg/m2)
Synthetic Progesterone prevents ovulation (don’t cause abortion).
Must be taken within 3 days of unprotected intercourse.
What are the possible side effects of the morning after pill?
headache, abdominal pain, nausea.
Liver P450 Enzyme inducer medications make it less effective.
If vomit within 2-3hrs of taking it, may need to take another.
What are the consideration you should make to choose contraception?
Risk of Venous Thromboembolism (VTE) / CVD / Stroke
Comorbidities
Other conditions that may benefit from OCP eg Menorrhagia / Endometriosis / Fibroids
Need for prevention of Sexually Transmitted Infections
Concurrent medication
When should you avoid the OCP?
Migraine with aura (risk of stroke) Smoking (>15/day) + age >35yrs Stroke or CVD history Current Breast cancer Liver Cirrhosis Diabetes with retinopathy/nephropathy/neuropathy
What concurrent medication should you be aware of with the contraception?
P450 liver enzyme-inducing drugs (eg anti-epileptics,some antibiotics) Teratogenic drugs (eg lithium or warfarin), more effective methods of contraception needed (eg progestogen-only implant, or intrauterine contraception).
What is peri-menopausal?
Within 12 months of last menstrual period (LMP)
What are the risks of HRT?
Venous Thrombo-embolism
Hormone sensitive cancers
Cardiovascular risk (none)
Why are venous thrombosis embolism risks of HRT?
eg Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)
Oral oestrogens undergo first pass metabolism in liver
Oral»_space; Increase SHBG, Triglycerides, CRP
Transdermal estrogens are safer for VTE risk than oral Avoid oral oestrogens in BMI > 30 kg/m2
How can HRT increase cancer risk?
Breast Cancer
Slight increase only in women on Combined HRT (ie oestrogen AND progesterone)
Risk related to duration of treatment and reduces after stopping
Continuous worse than Sequential
Assess Background risk in the individual woman before prescribing
Ovarian cancer- Small increase in risk after long-term use.
Endometrial Cancer-
Must prescribe Progestogens in all women with an endometrium !
How do you assess HRT safety (time periods)?
At 3 months
Then annually
What are the main features of CVD and HRT?
No increased risk if started before age 60 yrs
Increased risk if started 10 years after menopause
Possible benefits of oestrogen supplementation in young women e.g. Premature Ovarian Insufficiency (POI)
What are the main features of stroke and HRT?
Small increased risk
Oral > transdermal oestrogens
Combined > oestrogen only
What are the benefits of HRT?
Relief of symptoms of low oestrogen
eg Flushing, disturbed sleep, decreased libido, low mood,
Less osteoporosis related fractures
decreased by one third
What is the difference between gender or sex?
Gender is social construct, how you see yourself as male, female, or non-binary.
Sex is biologically defined eg male, female, or Intersex.
What is cisgender?
Same Sex and Gender
What does gender non-conforming mean?
Gender does not match assigned sex
What is gender dysphoria?
Identity issues cause depression
What is non-binary?
Gender does not match to traditional binary gender understanding,
includes agender, bigender, pangender, gender fluid
What is transgender?
Transitioning or planning to transition physical appearance from one to another
How can people transition?
Prepubertal young people - GnRH agonist for pubertal suppression and then sex steroids.
Post-treatment regret 1-2%
Gender Reassignment surgery after 1-2 yrs of hormonal treatment
What hormones do you give for transgender men?
Testosterone (injections, gels)
What are the side effects of giving T?
Polycythaemia, lower HDL, Obstructive Sleep Apnoea (OSA). No increase in CVD
What happens after giving T to transgender men?
Balding (depending on your age and family pattern)
Deeper voice / Acne / Increased and coarser facial and body hair
Change in the distribution of your body fat
Enlargement of the clitoris
Menstrual cycle stops
Increased muscle mass and strength
What are the feminising hormones with transgender women?
Estrogen (transdermal, oral, intramuscular)
High dose oestrogen eg 4-5mg per day to aim for estradiol levels of 734 pmol/L.
What are the side effects of giving oestrogen?
VTE dose-related at 2.6%, high BP, Cardio-Vascular Disease, high Triglycerides,
hormone sensitive cancers eg breast cancer, abnormal Liver Function tests 3%
How is T reduced in transgender women?
GnRH agonists (induce desensitization of HPG axis) Ant-Androgen medications (eg Cyproterone acetate, Spirnolactone)
What happens as transgender women feminise?
1 TO 3 MONTHS: Decrease in sexual desire / function (including erections) / Baldness slows / may reverse
3 TO 6 MONTHS: Softer skin and Change in body fat distribution / Decrease in testicular size /
Breast development and tenderness
6 TO 12 MONTHS: Hair may become softer and finer
