Disorders of Ovulation Flashcards

1
Q

Ovarian Microanatomy:
- Hilum
- Medulla
- Outer Cortex

A
  • Hilum = the route through
    which vessels, lymphatics and
    nerve enter and leave the ovary
    *steroid producing cells
  • Medulla = central to the ovary,
    connected to cortex and hilum,
    enables flow of blood and
    lymph, no follicles
  • Outer Cortex = made up of
    stromal and gamete producing
    cells. Stromal cells are dense
    and haphazard, collagen filled
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2
Q

Ovarian Microanatomy:

A

insert diagram

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3
Q

Gamete Production and Maturation:

A
  • gametes form from primordial
    germ cells (mitosis)
  • gametes migrate to ovary
    during gestation
  • in the second trimester, mitosis
    stops, oogonia either increase
    in size forming the primary
    oocyte or degenerate
  • then are arrested at the
    prophase of the first meiotic
    division. Granulosa cells will
    surround the oocyets, forming
    primordial follicles
  • at puberty some of the
    primordial follicles develop into
    primary follicles due to FSH
  • continuing FSH exposure
    encourages granulosa cells to
    divide producing zonal
    pellucida
  • surrounded by ovarian stromal
    cells, the follicles
    enlarge/degenerate
  • those that survive
    enlargement develop into
    secondary follicles
  • granulosa cells of secondary
    follicles increase in thickness
  • stromal cells differentiate into
    two layers; theca interna and
    theca externa
  • theca interna: steroid
    producing cells, oestrogen
  • theca externa: compact, non-
    secretory
  • granulosa cell layers split
    further and fill with antrum
    (fluid) and oocyte lies to one
    side of the follicle separated
    from it by cumulus oophorus
  • now represents a fully mature
    follicle ready for ovulation ->
    tertiary follicle
  • first stage of meiosis then
    occurs to produce a haploid
    gamete and small polar body
    (now a secondary oocyte)
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4
Q

HPG Axis:

A
  • starts during gestation
  • stops after birth
  • begins again at puberty
  • at puberty, the hypothalamus
    produces GnRH in a pulsatile
    manner stimulating the release
    of FSH and LH from the
    anterior pituitary (pulsatilly)
  • LH and FSH act on theca cells
    and granulosa cells respectively
    to secrete oestrogen and
    progesterone
  • oestrogen inhibits the
    secretion of FSH/LH and hence
    progesterone, which amplifies
    the effects of oestrogen
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4
Q

What occurs during ovulation?

A
  • pituitary LH surge induces
    completion of first mitotic
    stage
  • wall between ovary and oocyte
    is broken and corona radiata
    (follicular fluid + granulosa
    cells) are released into the
    peritoneal cavity = mid-
    menstrual cycle
  • oocyte is then encouraged to
    enter the fallopian tube and
    continues toward potential
    fertilisation
  • rupture of the follicle produces
    blood, under influence of LH
    the follicle re-organises
  • LH leutenises remnants into a
    corpus luteum, which secretes
    progesterone and theca cells
    continue to produce oestrogen
  • helps with fibrosis and corpus
    luteum involutes unless
    fertilisation/hormonal action
    prevents involution
  • as corpus luteum involutes the
    ability of the granulosa and
    theca cells to produce
    oestrogen and progesterone
    reduce with eventual drop in
    both hormones associated with
    menstruation
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5
Q

The menstrual cycle related to ovarian cells and hormones:

A
  • D1: first day of period, necrosis
    of endometrium leaving only
    the basal layer to reform the
    endometrium
  • first few days = low secretion of
    FSH/LH and large drop in
    Oestrogen and progesterone
  • proliferative phase day 4-16,
    part of cycle which is variable in
    length
  • with maturation and mitosis,
    increase in FSH,LH and
    oestrogen, increasing
    granulosa cell and theca cell
    proliferation
  • increases endometrial gland
    columnar/pseudostratified cells
  • ovulation is triggered by LH
    surge into the secondary
    phase
  • the secretory phase lasts
    from D15-25 and is driven
    by progesterone production
    secreted mostly from
    corpus luteum
  • secretory phase is marked
    by secretory changes like
    shedding of secretory
    materials into the
    endometrium, enabling
    gland cells to become
    tortuous
  • the premenstrual phase
    D25-28 so total secretory
    phase is a constant 14 days
    corpus luteum involution
    begins, reduction in
    secretory activity of
    endometrial glands/changes
    in stroma means
    breakdown of endometrium
    is beginning
  • associated increase in
    inflammatory cells
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5
Q

Ovulation Refresher:

A

insert diagram

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5
Q

Amenorrhoea: Definition:

A

Absence of periods at expected time

primary = have not begun by 16

secondary = stopped for more than 6 months in the absence of pregnancy

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6
Q

Primary Amenorrhea Causes:

A
  • constitutional delay: some
    people have later onset of
    menstruation than the
    average often runs in
    families
  • low body weight/excessive
    exercise -> hypothalamic
  • delayed puberty -> almost
    always accompanied by lack
    of secondary sexual
    characteristics
  • congenital absence of the
    uterus
  • imperforate hymen (hymen
    is such that it has not split
    and builds up behind the
    hymen)
  • PCOS
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7
Q

Investigations for Primary Amenorrhea:

A

progesterone is given for a period of time then withdrawn

if there is a period and other pathology ruled out then likely is a constitutional delay and no abnormality anatomically

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8
Q

Secondary Amenorrhea: Causes:

A

Physiological: Pregnancy, lactation, menopause (by far the most common causes)

Hypothalamic: Weight loss/ excessive exercise, stress

Pituitary: Hyperprolactinaemia, hypopituitarism, trauma, surgery

Ovarian: Premature ovarian insufficiency (premature menopause), radio/chemotherapy, resistant ovary syndrome, ovarian tumours

Other endocrine: thyroid disease, CAH, adrenal tumours

Uterine/ vaginal: hysterectomy, endometrial ablation (undertaken for menorrhagia), IUD, Asherman syndrome (acq.
Uterine scarring).

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9
Q

Oligomenorrhoea:

A
  • irregular/inconsistent
    menstruation outside of
    normal
  • cycle lasting >35 days
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10
Q

Primary Oligomenorrhoea: Causes:

A
  • low body weight/excessive
    exercise
  • congenital absence of
    uterus/ anatomical
    abnormalities
  • other causes: brain
    tumours, chemo
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11
Q

Causes of Secondary Oligomenorrhoea:

A

Physiological: Pregnancy, lactation, menopause, contraceptive effects.

Hypothalamic: Weight loss/ excessive exercise, stress

Pituitary: Hyperprolactinaemia, hypopituitarism, trauma, surgery

Ovarian: Premature ovarian insufficiency (premature menopause), radio/chemotherapy, resistant ovary syndrome, ovarian tumours

Other endocrine: thyroid disease, CAH, adrenal tumours, Diabetes, Cushing Syndrome,

Uterine/ vaginal: hysterectomy, endometrial ablation (undertaken for menorrhagia), IUD, Asherman syndrome (acq. Uterine scarring), PID.

Medications: contraception, some antipsychotics, some antiepileptics.

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12
Q

PCOS:

A

common disorders, often chronic, anovulatory infertility and hyperandrogenism with clinical manifestation of oligomenorrhoea, hirstuitism and acne

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13
Q

PCOS: Causes:

A
  • hyperinsulinaemia due to
    insulin resistance, which in
    turn stimulates excess
    ovarian androgens to be
    produced
  • genetic and epigenetic
    factors
  • environmental factors
14
Q

PCOS Signs and Symptoms:

A
  • oligomenorrhoea
  • hisuitism
  • acne
  • weight control issue
  • impaired glucose tolerance
  • diabetes mellitus
  • sleep apnoea
15
Q

PCOS: Diagnosis and Investigations:

A
  • total testosterone is elevated
  • SHBG low
  • rule out amenorrhoea through
    blood tests: FSH/LH, prolactin,
    TSH
  • rule out other causes of
    hyperandrogenism like cushings,
    congenital adrenal hyperplasia
  • Imaging: USS, 12 or more
    follicles in at least one ovary or
    increased ovarian volume,
    presence of polycystic ovaries on
    ultrasound is not alone, enough
    for diagnosis
16
Q

PCOS: Management:

A
  • life style modification
  • management of CVD risk
  • hisutism (anti-androgens, hair
    removal)
  • infertility: ovulation induction, IVF
17
Q

Congenital Adrenal Hyperplasia:
- inheritance pattern
- defect in
- results
- pathophysiology

A
  • autosomal recessive inheritance
  • enzyme defects in steroid
    synthesis: 21 alpha hydroxylase
  • low cortisol and aldosterone
  • failure to produce cortisol leads
    to increased ACTH release from
    anterior pituitary and hence
    adrenal cortex is overstimulated
    leading to hyperplasia, which in
    turns produces excess
    androgens
18
Q

Congenital Adrenal Hyperplasia:
- clinical features

A
  • cortisol deficiency:
    • hypoglycaemia
    • cardiovascular failure
    • adrenal crisis
  • androgen excess:
    • virilization of female infants
      (ambiguous genitalia at birth,
      amenorrhoea later,
      precocious puberty in males)
  • aldosterone deficiency:
    • salt wasting: low aldosterone
      results in poor re-absorption
      of Na+
    • hyponatraemia,
      hyperkalaemia,
      hypoglycaemia
19
Q

Congenital Adrenal Hyperplasia:
- Diagnosis and Investigations

A
  • difficult to diagnose male infants
    because few clinical
    manifestations at birth
  • men more likely to present with
    salt-wasting and adrenal crisis
  • diagnosis relies on elevated
    levels of 17 alpha
    hydroxyprogesterone in serum
    and assessment of urine steroid
    profile
  • screening involves a high rate of
    false positives
20
Q

Congenital Adrenal Hyperplasia:
- management

A
  • initial management of salt-losing
    crisis:
    - volume replacement with
    saline and systemic steroids
    - cortisol replacement with
    hydro and fludrocortisone to
    replace deficiency and
    suppress ACTH
  • growth is used to measure
    sufficiency of treatment
21
Q

A 2‐day old female neonate called Aiysha Baptiste presents to A+E with profound hypotension and circulatory shock. There were no problems antenatally, however Aiysha has not fed well since birth and became increasingly distressed overnight so her parents bought her in to hospital for urgent review. She is found to have signs of virilised genitalia on examination.

What is the likely diagnosis?

A
  • likely diagnosis = CAH
    consider sepsis, trauma
22
Q

A 2‐day old female neonate called Aiysha Baptiste presents to A+E with profound hypotension and circulatory shock. There were no problems antenatally, however Aiysha has not fed well since birth and became increasingly distressed overnight so her parents bought her in to hospital for urgent review. She is found to have signs of virilised genitalia on examination.

  • diagnosis: CAH

What is initial management?

A
  • salt losing will present with low
    Na+, Cl- and high K+
  • give saline and systemic steroids
  • long term cortisol replacement
    with hydro and fludrocortisone to
    suppress ACTH
  • definitive diagnosis needs high
    levels of 17 alpha
    hydroxyprogesterone