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Reproduction > Lec6 Disorders of Fertilisation > Flashcards

Lec6 Disorders of Fertilisation Flashcards

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
Q

What are the clinical features of PCOS?

A

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
Q

What is the underlying problem in PCOS?

A

Insulin resistance

27
Q

What is the effect of high insulin on granulosa cells?

A

High insulin and high androgens cause the granulosa cells to become less functional

  • secrete less oestrogen
  • follicle arrests
28
Q

What is the effect of high insulin on theca cells?

A

High insulin causes increased LH secretion which causes theca cells to produce excess androgens

29
Q

What are the hormonal abnormalities in PCOS?

A

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
Q

What is the relationship of PCOS and metabolic syndrome?

A

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
Q

What is the relationship between PCOS and endometrial cancer?

A

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
Q

What are treatment options for PCOS?

A
  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

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