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Reproductive System > Ovulation Induction Drugs > Flashcards

Ovulation Induction Drugs Flashcards

1
Q

modulation of hypothalamic-pituitary-ovarian axis

A
  • hypothalamus: pulsatile release GnRH to stimulate anterior pituitary gland
  • anterior pituitary gland: stimulated by GnRH to secrete FSH
  • FSH acts in ovaries to stimulate follicles to grow
  • growing follicles produce oestrogen
  • oestrogen (released by growing follicles in ovary) creates negative feedback loop to hypothalamus and anterior pituitary to suppress FSH secretion -> preventing excessive follicle growth; contributing to one dominant follicle / egg release each month
  • oestrogen (released by growing follicles in ovary) when at its peak creates positive feedback loop to anterior pituitary to release LH as a surge which induces ovulation
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2
Q

in the modulation of the hypothalamic-pituitary-ovarian axis what are 3 areas are targets for pharmacological intervention to help eggs be released from ovary and to induce ovulation

A
  • FSH release from anterior pituitary gland to ovaries
  • release of oestrogen from growing follicles in ovaries
  • negative feedback loops of oestrogen on hypothalamic and anterior pituitary receptors that suppress FSH secretion (Letrozole, Clomiphene)
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3
Q

before inducing ovulation what do you need to check

A
  • that your patient is anovulatory or infrequent ovulation
  • by assessing ovulation
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4
Q

best way to assess ovulation (history)

A
  • ask about regularity of menstrual cycle
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5
Q

between what days make up a menstrual cycle

A

1st day of period to next 1st day of period

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6
Q

[assessing ovulation] regarding regularity of menstrual cycle, if cycle length is between 25-35 days
what does this mean for ovulation

A

almost all people are ovulating
- indicates regular ovulation
- cycle length generally considered normal and healthy

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7
Q

[assessing ovulation] regarding regularity of menstrual cycle, if cycle length is shorter than 25 days or longer than 35 days
what does this mean for ovulation

A
  • usually not ovulating
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8
Q

what investigation can be performed to assess ovulation
what are we looking for

A
  • blood test on day 21 of 28-day cycle
  • if their cycle is longer or shorter by x days, perform blood test at day 21 +/- x days.
    ie/ take into account different cycle lengths
    ie/ total number of days in their cycle minus 7
    => should find elevated progesterone (released by corpus luteum to prepare the endometrium for implantation ~day 20; corpus luteum is the remnants from released follicle / oocyte released at ovulation at day 14)
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9
Q

at what day in cycle does progesterone usually peak

A

7 days after ovulation ~day 21

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10
Q

what can be done and charted by patient to assess ovulation
what is expected
note: hard assessment, prone to error

A
  • basal body temperature
  • stable and relatively low BBT during follicular phase, ovulation BBT slight decrease (due LH surge) followed by significant increase BBT (corpus luteum formed and making progesterone), luteal phase BBT remains elevated thru remainder of menstrual cycle
  • expected see 0.5 degree incr BBT post-ovulation
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11
Q
  • what BBT is oestrogen associated with
  • what BBT is progesterone associated with
A
  • lower
  • higher
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12
Q

when does follicular phase start and end

A
  • first day of menstruation / period
  • lasts until ovulation occurs
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13
Q

What test kit can patients use if close to / currently ovulating
what can be expected

A

LH kit
- LH kit positive w LH surge
why: LH surge triggers ovulation
note: can use if trying to conceive - fertile window: days leading up to ovulation + ovulation day

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14
Q

what ovulation assessment is done in IVF clinics

A
  • blood tests for cycle tracking
  • check oestrogen, progesterone (steroid hormones), LH -> tell exactly where someone is in cycle
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15
Q

list 5 ways to assess ovulation

A
  • ask about cycle length to know if they do ovulate
  • blood test day 21 for elevated progesterone
  • tracking basal body temperature for higher post ovulation
  • LH kits for positive reading with LH surge
  • blood test for cycle tracking
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16
Q

[assessing ovulation] in blood tests for cycle tracking, what do all hormones at baseline indicate

A
  • anovulation
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17
Q

anovulation can be associated broadly with (3)

A
  • high egg numbers
  • normal egg numbers
  • low egg numbers
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18
Q

of people with anovulation, it is more common that they have high or normal egg numbers

A
  • higher egg numbers than average
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19
Q

list 4 conditions that result in high egg numbers which are associated with anovulation

A
  • PCOS
  • hypothalamic dysfunction
  • hypothalamic hypogonadism
  • athletic amenorrhoea or low BMI
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20
Q

describe PCOS regarding potential causal hormone imbalances, high egg numbers, symptoms

A
  • many cysts (fluid-filled sacs) develop on outer edge of ovaries - actually immature eggs / follicles that fail to get released regularly
  • very high ovarian reserve
  • endocrinology change such as has higher androgen levels -> symptoms: acne, hair fall out, facial hair, growth of hair in wrong places
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21
Q

describe how PCOS can lead to anovulation

A
  • condition where have insulin resistance
  • high insulin seems to put block between FSH & oocyte growing
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22
Q

how can hypothalamic hypogonadism or athletic amenorrhoea or low BMI lead to anvoulation but have high egg numbers

A
  • if caloric intake insufficient to support a pregnancy
  • then FSH and LH are low in pituitary
    -> they don’t signal ovary to make eggs grow
  • lose their periods (BMI <18)
  • but have high number of eggs in ovaries
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23
Q

describe hypothalamic dysfunction occurrence

A
  • often occurs temporarily when in relatively stressful situation
    eg/ exams, war, pandemic
  • get amenorrhoea => can’t conceive when overwhelmed by env
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24
Q

describe how amenorrhoea occurs in hypothalamic dysfunction

A
  • suppression of wave secretion by hypothalamus
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25
Q

how do levels appear when measured in hypothalamic dysfunction

A
  • appear normal when measure them
  • amenorrhoea is very temporary
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26
Q

when can menstruation return in hypothalamic dysfunction

A
  • when stress removed, periods go back to regular cycle
27
Q

list 3 conditions that result in normal egg numbers which are associated with anovulation

A
  • thyroid disorders (hyper/hypothyroidism)
  • hyperprolactinaemia
  • adrenal disorders
28
Q

list 2 conditions that result in low egg numbers which are associated with anovulation

A
  • premature ovarian insufficiency
  • peri-menopause
29
Q

conditions causing anovulation which have normal egg numbers typically reflect what disorders

A

endocrine disorders
(adrenal disorders also cause)

30
Q

describe what hyperprolactinaemia & what impact this can have on ovulation

A
  • when prolactin levels are very high which can suppress ovulation
31
Q

some causes of hyperprolactinaemia

A
  • after pregnancy during breastfeeding
  • from an adenoma (benign tumour in gland tissue - tissue that secretes chemical substance)
32
Q

if someone has hyperprolactinaemia and is not breastfeeding, what investigation would you do

A

MRI of pituitary gland to check for there is not a small pituitary adenoma pressing on optic nerve

33
Q

in people with normal egg numbers associated with anovulation who have adrenal disorders, are androgens high or low

A

high

34
Q

give examples of 2 adrenal disorders

A
  • cushings
  • addisons
35
Q

in people with low egg numbers associated with anovulation a cause could be premature menopause / premature ovarian insufficiency (POI) resulting in low egg numbers. what are some common causes of POI

A
  • genetic conditions like Turner Syndrome, fragile X syndrome
36
Q

why does cause of ovulation disorder need to be determined before inducing ovulation

A
  • because cannot induce ovulation if very low egg numbers or no eggs present
  • because if people have high number of eggs need to be careful when inducing ovulation such that only 1 egg comes out or could get high order multiple pregnancy (3 or more kids)
37
Q

what are the 4 steps to managing anovulation

A
  1. Determine cause of anovulation (blood tests)
  2. Determine number of eggs present (AMH test or antral follicle count on transvaginal US)
  3. Induce ovulation - if endocrine problems corrected (thus previously anovulatory person can ovulate on their own) and there is good egg numbers, esp in younger people
  4. Increase FSH (thru manipulation of hypothalamic-pituitary-ovarian axis) ie/ give meds
38
Q

what is AMH produced by & what does it indicate

A
  • hormone produced by granulosa cells around egg
  • give idea of how many eggs present in ovary
39
Q

type of drug Clomiphene is

A
  • selective oestrogen receptor modulator
40
Q

MoA of Clomiphene

A
  • binds to oestrogen receptors in hypothalamus and pituitary
  • blocks oestrogen’s negative feedback
    -> increasing FSH
41
Q

type of drug Letrozole is

A
  • aromatase inhibitor
  • blocking conversion of androgens to oestradiol
42
Q

MoA of Letrozole

A
  • reduce oestrogen production (by blocking conversion of androgens to oestradiol)
    => less hypothalamic and pituitary negative feedback from reduced oestrogen levels
    => FSH secretion is not suppressed
    -> increase FSH
43
Q

what is aromatase

A
  • enzyme that helps conversion of androgens to oestradiol (oestrogens)
44
Q

is Letrozole or Clomiphene more effective agent & which is more modern

A
  • Letrozole is more effective agent
  • Letrozole is more modern
45
Q

Which drug (Letrozole or Clomiphene) is first choice ovulation induction agent (to increase FSH)

A
  • Letrozole
46
Q

what treatment is given for people who have particularly low levels of FSH in pituitary

A
  • given FSH as injectable medication
  • very powerful medication
47
Q

low FSH in pituitary would occur in what conditions (list 2) & explain how

A
  • hypothalamic hypogonadism: hypothalamus or pituitary gland do not produce the hormones that signal to testes or ovaries to make sex hormones
  • athletic amenorrhoea aka functional hypothalamic amenorrhoea: suppression of GnRH release from hypothalamus leading to reduced FSH levels
48
Q

when giving FSH as an injection to people with low FSH levels to induce ovulation, what do we need to track and why

A
  • track cycles carefully
  • as do not have natural feedbacks
  • which would limit number of eggs being released from ovary
  • just want one released
    potential risk: ovarian hyperstimulation syndrome
49
Q

what is the natural feedback you would have from FSH

A
  • FSH stimulate follicles in ovary to grow
  • growing follicles produce oestrogen
    -> oestrogen would negatively feedback to hypothalamus and anterior pituitary gland to reduce FSH production => stop stimulating follicle growth
50
Q

when giving injected FSH, what happens to natural negative feedback signal

A
  • FSH overrides hypothalamic and pituitary axis / negative feedback
  • FSH remains increased
51
Q

what is process around injected FSH

A
  • start very slowly
  • if egg not being released, increase dosage very slowly until override hypothalamo-pituitary axis & egg comes out
  • hope its one egg
52
Q

with injected FSH, what happens if more than one egg comes out

A
  • cancel the cycle
53
Q

medication use guidance for Letrozole and Clomiphene

A
  • one tablet daily on day 5-9 of cycle
  • have intercourse “around time of ovulation” every other day from day 12-16 of cycle
  • check blood progesterone day 21 / one week before period - to see if one egg has been induced
    consider assessing ovulation for patient’s cycle length and dates
54
Q

risks & side effects of Letrozole and Clomiphene or FSH

A
  • twins or more <- risk much higher with FSH
  • (rare) ovarian hyperstimulation syndrome with FSH
55
Q

what is ovarian hyperstimulation syndrome

A
  • too many follicles growing
  • when ovulation is triggered, each of those follicles makes pregnancy hormones -> many blood vessels grow to transport those hormones around body to make such bodily changes (eg/ lung volume, more blood made, slow down gut to absorb more food for pregnancy, kidney function)
  • hormones initiated by ovary from production of hormones by corpus luteum after ovulated
  • when blood vessels grow into ovary they do not have covers on them -> leak
  • one follicle -> little leakage
  • lots of follicles -> lots leakage ->lots of fluid in intraperitoneal cavity -> can get ascites (abdominal swelling from fluid accumulation) and dry veins
  • rare
  • mainly seen in IVF
56
Q

[how to manage risks of Letrozole or Clomiphene or FSH] dosage

A
  • start on low dose
  • if required, increase dose slowly until get desired (one egg, potentially two)
57
Q

if you release two eggs what is there the risk of

A

twins

58
Q

[how to manage risks of Letrozole or Clomiphene or FSH] how are cycles monitored (important to track - ovarian hyperstimulation risk) + allow us see egg release amount? (multiple pregnancy risk)

A
  • transvaginal ultrasound and oestrogen levels
59
Q

[how to manage risks of Letrozole or Clomiphene or FSH] too many follicles released at ovulation (multiple pregnancy and ovarian hyperstimulation risk)

A
  • cancel cycle
  • avoid sexual intercourse so don’t get high order multiple pregnancy
60
Q

why is ovarian hyperstimulation syndrome more severe with pregnancy

A

hCG (present due to implanted blastocyst) drives blood vessel growth into ovaries

61
Q

ovulation induction agents act to increase FSH by inhibiting oestrogen’s negative feeback by:

A
  • blocking oestrogen receptors (Clomiphene - selective oestrogen receptor modulator)
  • suppressing oestrogen production (Letrozole - aromatase inhibitor)
62
Q

or ovulation induction agents act to increase FSH through

A

direct introduction of FSH injections which override FSH secretion by the pituitary

63
Q

monitoring cycles (transvaginal US and oestrogen levels) reduces risk of:

A
  • multiple pregnancy
  • ovarian hyperstimulation
64
Q

ovulation induction is a successful treatment for

A
  • many young anovulatory people with adequate ovarian reserve
  • many people not require IVF if done well

Reproductive System (21 decks)

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