Reproductive Treatments Flashcards
What is primary hypogonadism?
How difficult is it to treat it?
Something directly affecting gonads
Hard to treat
What is the treatment aim for secondary hypogonadism? How do these improve fertility?
Treatments aim to stimulate spermatognesis - e.g. treat with gonadotrophins
LH = stimulates Leydig cells to increase intratesticular testosterone
FSH = stimulates spermatogenesis
35M - opiod abuse = suppress hypothalamus = hypogonadism
LH 3, FSH 5 iU/L
Low morning Testosterone 7 nmol/L (normal 9-30 nmol/L)
Fatigue and reduced shaving frequency.
Trying to conceive with his partner for 2 years with no success.
Sperm sample: Low sperm count i.e. ‘Male Factor’ Infertility
Should testosterone given? to improve fertility? What else could or should be given?
Testosterone should not be given because:
Testosterone = negative feedback = reduces LH and FSH = reduces spermatogenesis
Instead give hCG injections (act on LH receptors), then perhaps FSH injections = improve fertility
30M - anosmic, Kallmann’s Syndrome (XXY)
Presents seeking fertility and has been trying to conceive for 2 years.
Sperm Analysis- Low sperm count
LH 0.5, FSH 0.8, Low morning Testosterone 3 nmol/L
Is the prognosis of congenital or acquired secondary hypogonadism worse?
What is the appropriate treatment option to improve fertility?
Congenital = worse because no puberty, no mini puberty after birth (activation of HPG axis)
Treatment - 2-4mo of FSH to trigger mini puberty before other treatments (i.e. hCG injections)
Low testicular volume = less likely to respond to treatments
When is testosterone replacement given / required?
Not looking for fertility, just wants to improve symptoms (e.g. loss of early morning erections, libido, decreased energy, shaving)
At least 2 low measurements to serum testosterone before 11am, often fasting serum testosterone taken
How is testosterone replacement given?
What are some possible side effects?
Daily Gel e.g. Tostran. Care not to contaminate partner. 3 weekly intramuscular injection (e.g. Sustanon) 3 monthly intramuscular injection (e.g. Nebido) Less Common (implants, oral preparations)
Increased haematocrit (ratio of RBC vol to blood vol) - hyperviscosity and stroke Overstimulation of the prostate
30F - copy off slide
Unsuccessfully trying to conceive for 3 years Irregular periods (Oligomenorrhoea) Hyperandrogenism (hirsutism and acne) US Scan – Polycystic ovarian morphology LH 8.0 iU/L, FSH 4.5 iU/L
What is her diagnosis?
PCOS - symptoms point to this
How can fertility in PCOS be improved?
PCOS = anovulation
Therefore try ovulation induction to increase fertility
Simulate growth of one of her ovarian follicle by:
Lifestyle / Weight Loss / Metformin, Letrozole (Aromatase inhibitor), Clomiphene (Oestradiol receptor antagonist), FSH stimulation
What is the purpose of the aromatase inhibitor? How does it work to increase fertility?
Aromatase = converts testosterone to oestrodial
So aromatase inhibitors reduce negative feedback from oestrodial on HPG axis, stimulate hypothalamus to produce more GnRH, and pituitary to release more FSH / LH which can stimulate egg release
FSH stimulates follicle growth
How does IVF treatment work? What are the steps of IVF?
High doses of FSH to stimulate follicle growth
Eggs collected outside of utero
Sperm and eggs mixed together
Or if male factor infertility, inject sperm into the egg
Incubate embryo for 3-5 days
Select 1-2 embryos, place into uterus
Hopefully results in pregnancy
How can egg release / ovarian stimulation be achieved through hormones?
FSH stimulation for superovulation
Make sure ovulation does not occur as the egg cannot be collected
Medicine prevents pre-mature LH surge, which prevents ovulation occurring too soon
What medication / hormone prevents premature LH surge in IVF patients?
- GnRH antagonist protocol (short protocol) = prevents ovulation happening too soon
- GnRH agonist protocol (long protocol) = given for much longer
How can both, GnRH antagonists and agonists work to prevent premature LH surge?
GnRH works in a pulsatile manner
Prolonged. high dose GnRH agonist = desensitisation = LH inhibition
Low dose GnRH antagonist for short time = GnRH actions suppressed
How can the eggs be matured in IVF treatments?
Prevent LH surge to allow follicles to get to the right size
But once follicles are right size, just before egg maturation (metaphase 1), give LH to make the immature egg mature (becomes haploid)
Give hCG as it acts on the LH receptors
What are some side effects of IVF treatment and hCG?
OHSS (Ovarian Hyper-Stimulation Syndrome) - exaggerated response to excess hormones
Pleural effusion
Ascites - swelling of the abdomen
Insufficient fluid in the blood = renal failure
Ovarian Torsion
Summarise the IVF process:
FSH - stimulate follicle growth GnRH antagonist / agonist - prevents premature egg release Give LH / hCG for egg maturation Eggs collected Combined with sperm 1-2 embryos planted back into uterus
What are common methods of contraception?
What are permanent methods of contraception?
Barrier: male / female condom/ diaphragm or cap with spermicide
Combined Oral Contraceptive Pill (OCP)
Progestogen-only Pill (POP)
Long Acting Reversible Contraception (LARC)
Emergency Contraception
Vasectomy
Female sterilisation
What are common barrier contraceptions?
What are the adv. and disadv. of barrier contraception?
E.g. condoms
Adv - easy to obtain, protects against STI
Disadv - higher failure rated (due to incorrect usage)
What is the oral contraceptive pill?
How does it work by acting on the HPG axis?
Oral contraceptive pill (OCP) - contains oestrogen and progesterone, results in anovulation
Oestrogen - anovulation due to negative feedback on GnRH and gonadotrophins
Progesterone - thickening of the cervical mucus and thinning of endometrial lining
What are the adv. and disadv. of the OCP?
What are some possible side effects?
Adv - easy to take, effective, reduces endometrial and ovarian cancer, weight neutral
Disadv - Difficult to remember, not good during breastfeeding, no protection again STIs, certain enzymes / medications may reduce efficacy
Side effects - progesterone = may increase hunger, therefore switch pills until one works
Enzyme inducers = may increase metabolism of the pill
Spotting
Nausea
Changes to mood / libido / breast tenderness
VTE (venous thromboembolism) - v. rare
What other conditions can the oral contraceptive pill help?
Heavy bleeding - can help make periods lighter / less painful
PCOS - help reduce LH and hyperandrogenism
What is the progesterone only pill (POP)?
What are the adv. and disadv. of the POP?
What are some possible side effects?
POP - like OCP, but only progesterone (no oestrogen)
Adv - works like the OCP, suitable if patient cannot take oestrogen, easy to take, can help heavy periods, can be used when breastfeeding
Disadv - less reliable than OCP, difficult to remember, no protection against STIs, short acting = taken same time each day
Side effects - irregular bleeding, headaches, sore breasts, changes in mood / libido
What are some examples of long acting reversible contraceptives (LARCs)?
IUDs - copper coil, mechanically prevents implantation, decreases sperm egg survival, lasts 5-10 years
IUS - acts as the coil but also secretes progesterone, thickens cervical mucus (Can be helpful for women with heavy bleeding). Lasts 3-5 years
Progestogen-only injectable contraceptives or subdermal implants
What are the advantages of LARCs?
Suitable for most women including those with no previous children
Can be used as emergency contraception
Long lasting
Exclude STI’s and cervical screening up to date before insertion
What are some examples of emergency contraceptions?
What are some possible side effects?
IUD - most effective (less than 1% chance of pregnancy) - fitted up to 5 days after unprotected sex
Emergency contraceptive pill, ulipristal acetate - 30mg, taken within 5 days of unprotected sex
Emergency contraceptive pill, levonorgestrel - synthetic progesterone, 1.5mg, taken within 3 days of unprotected sex
Side effects: Does not cause an abortion, just prevents pregnancy
Nausea within 2-3 hours = require another dose
Heaches, abdominal pain
Liver P450 enzyme inducer = reduces efficacy
What should be taken into account for the choice of contraception?
Risk of Venous Thromboembolism (VTE) / CVD / Stroke Comorbidities - Avoid OCP if: 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
Other conditions that may benefit from a contraception
Need to prevent STIs
Concurrent medication
What is the issue with user dependent contraceptions?
Worse chance of failure due to incorrect use
53F - presents with post-menopausal symptoms Presenting Complaint (PC) – Hot flushes, sweating, disturbed sleep, Low libido, vaginal dryness, low mood. Joint and muscle aches Absent periods for 10 months
What is the diagnosis and treatment?
Menopause
Hormone replacement therapy (HRT) to ease symptoms
What are the risks of HRT (hormone replacement therapy)?
HINT: first pass metabolism, cancers, CVD, strokes
VTEs (venous thrombo-embolisms)
Oral oestrogens - go through liver to undergo first pass metabolism (more risky) VS transdermal = straight into the bloodstream
Breast cancers = slight increased risk with combined HRT (oest and prog)
Ovarian cancer - increased risk after long term use
Endometrial cancers = must prescribe progestogens to minimise risk (post-menopausal bleed may indicate endometrial cancer)
No increased risk of CVD if started before aged 60
Risk of stroke - small increase, most increase with oral combined pill (least = transdermal oestrogen only)
What are the benefits of HRT?
Relieves symptoms caused by low oestrogen
Reduce post-menopausal fractures (osteoporosis)
Define:
Gender Sex Cis Non-comforming Dysphoria Non-binary Transgender
Gender = social construct, how you see yourself as male, female, or non-binary.
Sex = biologically defined e.g. male, female, or intersex.
Cisgender = same sex and gender
Gender non-conforming = gender does not match assigned sex
Gender Dysphoria = when that causes depression
Non-binary = gender does not match to traditional binary gender understanding,
includes agender, bigender, pangender, gender fluid
Transgender = transitioning or planning to transition physical appearance from one to another.
What are some HRTs for transgender and gender non-binary individuals?
GnRH agonist - high dose continuously pre-puberty = delays prepubertal effects to make the decision
Masculising hormones = testosterone
Progesterone to suppress menstrual bleed (if needed)
Feminising hormones = oestrogen
GnRH angonists = reduce testosterone levels
