Disorders of Ovulation Flashcards
Ovarian Microanatomy:
- Hilum
- Medulla
- Outer Cortex
- 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
Ovarian Microanatomy:
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Gamete Production and Maturation:
- 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)
HPG Axis:
- 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
What occurs during ovulation?
- 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
The menstrual cycle related to ovarian cells and hormones:
- 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
Ovulation Refresher:
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Amenorrhoea: Definition:
Absence of periods at expected time
primary = have not begun by 16
secondary = stopped for more than 6 months in the absence of pregnancy
Primary Amenorrhea Causes:
- 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
Investigations for Primary Amenorrhea:
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
Secondary Amenorrhea: Causes:
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).
Oligomenorrhoea:
- irregular/inconsistent
menstruation outside of
normal - cycle lasting >35 days
Primary Oligomenorrhoea: Causes:
- low body weight/excessive
exercise - congenital absence of
uterus/ anatomical
abnormalities - other causes: brain
tumours, chemo
Causes of Secondary Oligomenorrhoea:
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.
PCOS:
common disorders, often chronic, anovulatory infertility and hyperandrogenism with clinical manifestation of oligomenorrhoea, hirstuitism and acne
PCOS: Causes:
- hyperinsulinaemia due to
insulin resistance, which in
turn stimulates excess
ovarian androgens to be
produced - genetic and epigenetic
factors - environmental factors
PCOS Signs and Symptoms:
- oligomenorrhoea
- hisuitism
- acne
- weight control issue
- impaired glucose tolerance
- diabetes mellitus
- sleep apnoea
PCOS: Diagnosis and Investigations:
- 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
PCOS: Management:
- life style modification
- management of CVD risk
- hisutism (anti-androgens, hair
removal) - infertility: ovulation induction, IVF
Congenital Adrenal Hyperplasia:
- inheritance pattern
- defect in
- results
- pathophysiology
- 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
Congenital Adrenal Hyperplasia:
- clinical features
- cortisol deficiency:
- hypoglycaemia
- cardiovascular failure
- adrenal crisis
- androgen excess:
- virilization of female infants
(ambiguous genitalia at birth,
amenorrhoea later,
precocious puberty in males)
- virilization of female infants
- aldosterone deficiency:
- salt wasting: low aldosterone
results in poor re-absorption
of Na+ - hyponatraemia,
hyperkalaemia,
hypoglycaemia
- salt wasting: low aldosterone
Congenital Adrenal Hyperplasia:
- Diagnosis and Investigations
- 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
Congenital Adrenal Hyperplasia:
- management
- 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
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?
- likely diagnosis = CAH
consider sepsis, trauma
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?
- 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
