Ovaries

early development of ovary

is indifferent until week 7

primordial germ cells (PGCs) appear in yolk sac, migrate to gonadal ridges, proliferate by mitosis

female development of ovary

occurs in absence of Y chromosome

3 key cells types form:

PCGs —> oogonia

granulosa cells

theca cells

adult ovary functions

produce oocytes (eggs)

hormones (oestrogen, progesterone, androgens)

oogenesis

formation of female gametes (oocytes)

stages of oogenesis

primordial germ cell - oogonium - primary oocyte - secondary oocyte - mature oocyte

when does oogenesis begin

before birth

primary oocytes enter meiosis 1 in fetal life

what are the 2 meiotic arrests

prophase 1 (until puberty)

metaphase 2 (until fertilisation)

what is asymmetrical division

ensures oocyte has maximum cytoplasm

produces 1 large oocyte, polar bodies (waste DNA)

stages of folliculogenesis

primordial - primary - secondary - tertiary

ensures continuous release of fertilisable oocyte

what does zona pellucida do

sperm binding and prevents polyspermy

regulation of oogenesis

hypothalamus —> GnRH

pituitary —> FSH and LH

ovary —> oestrogen and progesterone

GnRH

released in pulses

acts on GPCRs in pituitary

continuous GnRH = decreased receptor sensitivity

FSH

stimulates follicle development

activates granulosa cells

LH

triggers ovulation, stimulates theca cells, forms corpus luteum

2-cell hypothesis

explains oestrogen production

theca cells (LH): produce testosterone

granulosa cells (FSH): convert to oestrogen

puberty trigger

kisspeptin (KISS1): activates GnRH neurons

leptin (body fat): required for puberty onset

GnRH becomes pulsatile —> activates HPG axis

menstrual cycle

follicular phase

ovulation

luteal phase

follicular phase

increase FSH —> follicle growth

granulosa cells increase oestrogen

effects: endometrium thickens, cervical mucus thins

oestrogen inhibits FSH

ovulation

high oestrogen —> LH surge

results: completion of meiosis 1, release of secondary oocyte

luteal phase

corpus luteum forms

produces: progesterone, some oestrogen

function: maintains endometrium

if no fertilisation:

corpus luteum degenerates

low progesterone —> menstruation

if fertilisation occurs;

embryo produces hCG

maintains corpus luteum

sustains progesterone

when does implantation occur

luteal phase (progesterone dominant)

progesterone: maintains endometrium, essential throughout pregnancy

hCG

secreted 1 week post fertilisation

maintains corpus luteum

placenta takes over progesterone production at 6 weeks

key hormones in pregnancy

oestrogen, progesterone, hPL, prolactin

progesterone in pregnancy

maintains pregnancy

inhibits uterine contractions

oestrogen in pregnancy

increases throughout pregnancy

produced by placenta + fetus

hPL (human placental lactogen)

anti-insulin effects; decreases insulin sensitivity, increases blood glucose for fetus

increases lipolysis: ensures fetal nutrient supply

prolactin

gradually increases

prepares breast for lactation

triggers of parturition

increased oestrogen: progesterone ratio

increased oxytocin receptors

increased prostaglandins

oxytocin

causes uterine contractions

released from posterior pituitary

Ferguson reflex (positive feedback)

cervical stretch —> oxytocin —> increased contractions

fetal HPA axis activates:

increased fetal cortisol —> lung maturation, increased prostaglandins

fetus helps trigger labour

lactation before birth

high oestrogen & progesterone

inhibit milk secretion

lactation after birth:

lower oestrogen & progesterone

prolactin —> milk production

milk ejection (let-down reflex)

suckling —> oxytocin release

causes: contraction of myoepithelial cells, milk ejection

positive feedback of lactation

sucking = high prolactin + oxytocin

what is lactational amenorrhea

temporary form of natural postpartum contraception

high prolactin —> decreases GnRH —> decreases FSH/LH

menopause

permanent cessation of menstruation

diagnosed after 12 months of no periods (over 50)

cause of menopause

depletion of ovarian follicles

decreased oestrogen

increased FSH & LH

symptoms of menopause

hot flushes

mood changes

vaginal dryness

loss of libido

long-term effects of menopause

osteoporosis

increased cardiovascular risk

hormone replacement therapy

oestrogen and/or progesterone

for symptom relief

risks: breast cancer, thromboembolism

contraception

methods to prevent pregnancy

hormonal methods

emergency contraception

barrier methods

IUDs or permanent methods

hormonal methods

suppress ovulation, thicken cervical mucus, thin endometrium

e.g. combined pill, progesterone-only pill, implant

emergency contraception

delay ovulation

barrier methods

condoms, diaphragm, prevent sperm reaching egg

IUDs

copper: toxic to sperm, prevent fertilisation

hormone: releases progesterone, suppress ovulation

permanent methods

tubal ligation

vasectomy

natural methods

fertility awareness

lactational amenorrhoea

puberty disorders

precocious puberty

delayed puberty

precocious puberty

secondary sexual characteristics before 8

period before 10

usually constitutional, sometimes tumours

delayed puberty

no menstruation by 14,16 (without secondary sexual characteristics)

causes: hypothalamic-pituitary dysfunction, genetic conditions

amenorrhoea

= no periods

primary - never started

secondary - stopped for more than 6 months

oligomenorrhoea

infrequent cycles (less than 9 per year)

symptoms of menstrual disorders

infertility

oestrogen deficiency —> hot flushes

androgen excess

primary ovarian insufficiency

menopause-like state (under 40)

features: amenorrhoea, low oestrogen, high FSH/LH

causes: turner syndrome, autoimmune, chemotherapy

hyperprolactinaemia

high prolactin —> low GnRH —> low FSH/LH

causes: pituitary tumour, low dopamine

Kallmann syndrome

GnRH deficiency

lifestyle causes of ovarian function disorders

stress, excess exercise, anorexia, obesity

polycystic ovarian syndrome (PCOS)

features: oligomenorrhoea, obesity, infertility

cause: increased androgens, high LH/FSH ratio, possible insulin resistance

diagnosis of PCOS (Rotterdam criteria)

need 2 out of 3

1. oligo/anovulation

2. hyperandrogenism

3. polycystic ovaries on ultrasound

female infertility causes

ovulatory disorders

tubal damage

endometriosis

infertility

failure to conceive after 2 years

can be unexplained causes

diagnosis of ovarian dysfunction

1. pregnancy test (rule out pregnancy)

2. hormone tests (progesterone day 21 confirms ovulation)

3. progesterone challenge test (withdrawal bleed after given progesterone?)

bleed= normal oestrogen

no bleed = problem with oestrogen or uterus

male infertility

sperm abnormalities

fertility treatment options

ovulation induction

intrauterine insemination

in vitro fertilisation

intracytoplasmic sperm injection

ovulation induction

anti-oestrogen

removes negative feedback —> increases FSH

stimulates ovulation

IUI

sperm placed directly into uterus

simple, less invasive

lower success rate

ICSI

single sperm injected into egg

used for severe male infertiltiy

IVF

1. pituitary suppression (GnRH agonist)

2. ovarian stimulation (FSH)

3. monitor follicles

4. hCG trigger (mimics LH surge)

5. egg collection

6. embryo transfer

7. luteal support

IVF risks

multiple pregnancy

ovarian hyperstimulation syndrome

invasive procedures