Lec6 Disorders of Fertilisation Flashcards

(32 cards)

1
Q

What are kisspeptin and KNDy neurons potent stimulators of?

A

GnRH

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2
Q

What are kisspeptin and KNDy neurons stimulated by?

A

Oestrogen

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3
Q

Kisspeptin and KNDy neurons cause:

A

Stimulation of GnRH to drive LH production

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4
Q

Kisspeptin, GnRH and LH are all what?

A

Pulsatile - every 60-90mins

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5
Q

Where does the first step in ovulation start?

A

In the Supra Chiasmic Nuclei in the hypothalamus

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6
Q

What is the function of the SCN?

A

Supra chiasmic nuclei govern the circadian clock that interacts with the kisspeptin neurons and KNDy neurons (neurokinin B and dynorphin)

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7
Q

Where are the kisspeptin neurons located?

A

The kisspeptin neurons are located in the arcuate nucleus (ARN) and anteroventral periventricular area (AVPV)

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8
Q

Where is GnRH synthesised?

A

GnRH is synthesised by neurons in the PreOptic Area (POA) which project into the median eminence where they release GnRH into the portal system every 60-90mins

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9
Q

What effect does release of GnRH have?

A

Anterior pituitary gonadotrophin cells secrete FSH

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10
Q

What effect does the FSH have?

A

Acts on Primary Follicle Granulosa Cells which produce oestrogen and inhibin

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11
Q

What other effect does FSH have?

A

Increases the LH receptors on the granulosa cells

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12
Q

What effect does the oestrogen and inhibin secreted by the PFGCs have on FSG

A

Suppresses FSH secretion - due to negative feedback

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13
Q

What happens when the oestrogen levels gets to a critically high point?

A

They stimulate Kisspeptin and KNDy neurons again to cause GnRH secretion

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14
Q

What happens this time following GnRH secretion?

A

LH is produced because of the increased frequency and amplitude of the pulse from GnRH

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15
Q

What is the effect of LH secretion?

A

LH triggers ovulation, resumption of oocyte meiosis and changes the granulosa cells into luteal cells

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16
Q

What is characteristic of the first half of menstrual cycle?

A

FSH falls as oestrogen and inhibin rise
at critical level oestrogen stimulates kisspeptin and KNDy neurons
Stimulates secretion of GnRH increased freq and increased amplitude
Increased pulsatile secretion = LH surge

17
Q

What is characteristic of the second half of the menstrual cycle?

A

LH converts granulosa cells to luteal cells
Hormone production swaps from oestrogen to progesterone
Progesterone peaks at day 21/ seven days before period
Progesterone, oestrogen inhibin all inhibit FSH and LH

18
Q

What is used to diagnose ovulation?

A

Progesterone blood test day 21/ 7 days before period
LH detection urinary kit - from day 10
Transvaginal pelvic ultrasound alternate days from day 10

19
Q

Name three types of causes of ovulation problems

A

Hypothalamic
Pituitary
Ovary

20
Q

Give 4 examples of Hypothalamic causes for ovulation problems

A

Lack of GnRH due to:

  1. Kiss1 gene deficiency - rare
  2. GnRH gene deficiency - rare
  3. Weight loss/ excessive exercise/ stress
  4. Anorexia/ bulimia
21
Q

Give 2 examples of Pituitary causes for ovulation problems

A
  1. Pituitary tumour (prolactinoma or other tumour)

2. Post pituitary surgery/ radiation

22
Q

Give 2 examples of Ovarian causes for ovulation problems:

A
  1. Premature Ovarian insufficiency
    - Genetic/ developmental e.g. Turners Syndrome
    - Autoimmune damage/ destruction of ovaries
    - Cytotoxic/ radiotherapy
    - Surgery
  2. Polycystic Ovarian Syndrome - commonest cause
23
Q

What is Hirsutism?

A

Androgen dependent hirsutism

excess body hair in a male distribution

24
Q

What is the triad of symptoms usually used to diagnose PCOS?

A

Androgen excess
Oligomenorrhoea
Polycystic Ovaries
but only need 2 of these to diagnose PCOS

25
What are the clinical features of PCOS?
Androgen excess- hirsutism/acne Oligomenorrhoea - less than 9 periods a year, subfertility Obesity - but 25% are "lean" Metabolic disturbances are often seen in these pts
26
What is the underlying problem in PCOS?
Insulin resistance
27
What is the effect of high insulin on granulosa cells?
High insulin and high androgens cause the granulosa cells to become less functional - secrete less oestrogen - follicle arrests
28
What is the effect of high insulin on theca cells?
High insulin causes increased LH secretion which causes theca cells to produce excess androgens
29
What are the hormonal abnormalities in PCOS?
Raised LH:FSH ratio - 3:1 Raised androgens and free testoserone Reduced SHBG (SHBG is decreased by testosterone so increased levels of free testosterone = reduced SHBG) Oestrogen usually low but could be normal
30
What is the relationship of PCOS and metabolic syndrome?
Reduced insulin sensitivity - increased insulin causes: Increased androgen production by theca cells Reduced SHBG production by the liver Increased risk of GDM and type 2 diabetes Dyslipidaemia Increased risk of CVD
31
What is the relationship between PCOS and endometrial cancer?
The risk of endometrial hyperplasia is increased in PCOS Lack of progesterone on the endometrium Endometrial cancer is associated with type 2 diabetes and obesity
32
What are treatment options for PCOS?
1. COCP - increases SHBG therefore decreasing testosterone 2. Anti Androgens +/- COCP e.g. cyproterone acetate - stops testosterone and 5 alpha-DHT binding to androgen receptors Spironolactone - antimineralocorticoid and anti androgen properties 3. Lifestyle factors e.g. lose weight, stop smoking, better diet and more exercise - improves SHBG conc, reducing free testosterone - improved fertility outcomes 4. Targeting insulin resistance in PCOS - METFORMIN - biguanide - improve ovulation with CLOMIFENE 5. Hair removal - photoepilation/ laser/ electrolysis/ eflorthinine inhibits orthinine decarboxylase