reproduction/gondal Flashcards
where does HCG come from?
the implanted embryo releases HCG
HCG causes hyperemesis = N+V during pregnancy
what use is HCG in practice?
hormone used in pregnancy test
Human Placental Lactogen (HPL) is secreted from where?
the placenta
also secretes placental progesterone + placental oestrogen
what does HPL do apart from breast development?
causes insulin resistance in mother
along with placental progesterones
what hormone does the follicle secrete?
ostradiol
what hormone does the corpus luteum (fertilised ovum) secrete?
progesterone
what week of pregnancy does organogenesis start?
week 5 probs earlier
what increases thyroxine in pregnancy?
HCG - excessive hCG mimics hyperthyroidism
increased thyroxine suppresses TSH
function of follicle stimulating hormone in males + females
male - causees testes to produce sperm (spermatogenesis)
female - causes growth of ovarian follicles (oogenesis) + ovary to secrete oestrogen
luteinizing hormone effect in males + females
male - causes testes to secrete testosterone
female - causes ovulation + causes progesterone production by corpus luteum
how does the pulsatile manner of GnRH release differ between males and females?
males - pulses at constant frequency
females - frequency of pulses varies during menstrual cycle
follicular = high frequency luteal = low
does a high frequency of GnRH pules favour LH release or FSH?
LH pulses
low frequency = FSH pulses
effect of oestrogen + progesterone on GnRH pulses?
high oestrogen increases GnRH pulses - increasing LH release
high progesterone reduces GnRH pulses
where are oestrogen and progesterone receptors that influence GnRH pulses found?
kisspeptin neurones - these indirectly influence GnRH neurones
where is oestrogen secreted from?
primarily by ovaries (follicles) + adrenal cortex
and placenta in pregnancy
functions of oestrogen (4)
increase thickness of vaginal wall
regulate LH surge
reduce vaginal pH through increase in lactic acid production
decrease viscosity of cervical mucus to facilitate sperm penetration –> FERTILE mucus
where is progesterone secreted from?
corpus luteum + placenta during pregnancy
function of progesterone (5)
“pro-gestation” (maintain pregnancy)
- responsible for INFERTILE thick mucus - prevents sperm transport + infection
- maintain thickness of endometrium
- relaxes myometrium (smooth muscle)
- inhibits secretion of LH
- increase basal body temp
what does the LH surge lead to?
ovulation
regulates formation of corpus luteum
regulates progesterone production + secretion
–> increasing progesterone decreases LH secretion by influecing GnRH pulses
LH surge
preceds ovulation by approx 34-36hrs
thershold of oestrogen (200pg/ml) is required for LH surge - via increase GnRH pulses
increase LH levels -> progesterone levels begin to increase
which follicular cell expresses LH receptors?
theca cells - release androgens in response to LH
which follicular cell expresses FSH receptors?
granulosa cella
folliculogenesis
early stages occur independently of gonadotrophins, once follicle is certain size becomes gandotrophin dependent (MUST coincide with rise in FSH during early follicular phase
describe the formation of corpus luteum
occurs under influence of LH
granulosa + theca cells transform to luteal cells
increase in progesterone production (via increased cholesterol - substrate for progesterone synthesis)
histology and function of the cells in the cervix
epithelium = columnar epithelium cells = site of mucus production
stroma(behind epithelium) = collagen matrix + fibroblasts = regulates rigidity of cervical wall
what regulates sperms ability to penetrate cervical mucus?
thickness of mucus - based on hormonal control
motility of sperm
interaction of oxygen species - produced by WBCs that have infiltrated mucu
interactions with mucins
what is the optimum route for sperm throught the cervix?
through primary + secondary grooves avoiding mucucs and imune cells
is cervical mucus thicker in the cervical canal or secondary grooves?
thicker in cervical canal
where are the immune cells of the cervix most concentrated?
cervical canal
histology of seminiferous tubules
inside contains Sertoli cells - protect germ cells
outside surrounded by interstitial tissue, blood vessels, WBCs, fibroblasts
testosterones role during spermatogenesis
maintains integrity of blood-testes barrier
release of mature spermatozoa from Sertoli cells - by influencing peritubular myoid cells
pathway of FSH action in males
FSH stimulates Sertoli cells
Sertoli cells secretes androgen binding globulin (ABG) (which testosterone binds to) and inhibin
- inhibin decreases secretion of FSH (via neg feedback)
pathway of LH action in males
LH stimulates interstitial Leydig cells to secrete testosterone
- testoterone inhibits GnRH + LH secretion (via neg feedback)
of the testosterone secrete by interstitial Leydig cells - how much of this is taken up by Sertoli cells?
90%
define ooligomenorrhea
cycles >42days / <8 periods per year
causes of infertility
tubal disease fibroids endometriosis sperm problems weight related unexplained combination of male + female probs
what is the WHO classification if anovulation?
group I = hypothalamic pituitary FAILURE (hypogonadotrophic hypogonadism)
group II = hypothalamic pituitary DYSFUNCTION - commonest
group III = OVARIAN FAILURE (hypergonadotrophic hypogonadism)
gonadal hormone levels in group I anovulation
hypogonadotrophic hypogonadism
low FSH +LH
low oestrogen
investigation for hypogonadotrophic hypogonadism
progesterone challenge test
= admin of progesterone to induce a period
–> if no bleeding after 7-10days = oestrogen low
causes of hypogonadotrophic hypogonadism
stress excessive exercise anorexia / low BMI brain / pituitary tumours head trauma Kallman's syndrome drugs - steroids, opiates
management of hypogonadotrophic hypogonadism
stabilie weight / lifestyle advice (reduce caffience etc)
- pulsatile GnRH - SC/IV pump worn continuously - pulsatile admin every 90mins
- gonadotrophin (LH+FSH) daily injections - higher multiple pregnancy rates
–> both need US monitoring of response (follicle tracking)
gonadal hormone levels in group II anovulation
all normal
85% of ovulatory disorders
includes PCOS, hyperprolactinemic
management of group II anovulation
clomifene citrate (anti-oestrogen) - stimulates ovulation --> alternatives: letrozole, tamoxifen (aromatase inhibitor)
gonadotrophin daily injections - risk of overstimulation + multiple pregnancy
laparoscopic ovarian diathermy induce ovulation
IVF
what is laparocopic ovarian diathermy induced ovulation?
key hole surgery delivering heat
disrupts ovarian cortex + stoma
rule of 4: 40W current, 4 seconds, 4 punctures
risks = ovarian destruction/adhesions
gonadotrophin levels in group II anovulation
hypergonadotophic hypogonadism
high gonadotrphins
group III anovulation conditions + management
menopausal
5% ovulatory disorders
premature ovarian failure
management = oocyte donation
infertility lifestyle advice
400mcg folic acid daily healthy BMI no smoking + excessive alcohol reduce stress reduce caffiene aim for sex every 2-3 days - stop planning, can add stress
initial primary care tests for infertility
BMI - low could indicate anovulation, high - PCOS
chlamydia screening
semen analysis
rubella immunity in mother
fermale hormone testing
pregnancy test !!
what female hormone tests can be done in infertility?
serum progesterone on day 21 of cycle - or 7 days before end
day 2-5 of cycle -
- serum LH + FSH, estradiol
- prolactin - when symptoms of glactorrhoea or amenorrhoea
- testosterone / SHBG (free androgen index)
progesterone challenge test - bleed indicates normal oestrogen levels
anti-MUllerian hormone, thyroid function tests
what does a high FSH indicate?
poor ovarian reserve (number of follicles women have left in her ovaries)
pituitary gland is producing extra FSH in an attempt to stimulate follicular development
what does a high LH indicate?
PCOS
what does a low anti-mullerian hormone indicate?
= accurate marker of ovarian reserve - released by granulosa cells in follicles
levels fall when eggs are depleted
what does a progesterone rise on day 21 indicate?
ovulation has occured + corpus luteum has formed + started secreting progesterone
secondary care investigations of infertility
ultrasound of pelvis - PCOS, structural
hysterosalpinogram - patency of fallopian tubes
laparoscopy + dye test - endometriosis, treat adhesions
what conditions causing infertility is surgery the primary treatment?
(laparoscopy/hysteroscopy)
pelvic adhesions
grade 2 endometriosis
chocolate cysts in ovary
tubal block
mode of action of clomifene
anti-oestrogen (a selective oestrogen receptor modulator)
stops neg feedback of oestrogen on hypothalamus - results in greater release of GnRH + subsequently LH + FSH
given on days 2-6 of menstrual cycle
risk of ovulation induction
ovarian hyperstimulation
multiple pregnancy - hypertension, low birth weight, prematurity
theoretical risk ovarian cancer
management of submucosal, intramural and subserosal respectively
submucosal = hysteroscopy
intramural = individualised on a case to case basis
subserosal = conservative, unlikely to impact fertility
PCOS presentation (triad)
triad = anovulation, hyperandrogenism, polycystic ovaries on US
obesity, hirsutism, acne
insulin resistance
high LH
impaired glucose tolerance
how can insulin resistance cause hyperandrogenism?
insulin lowers SHBG
–> increased free testosterone = hyperandrogenism
diagnostic criteria of PCOS
rotterdam criteria, 2 or 3 of -
- ooligoovulation or annovulation
- hyperandrogenism - characterised by hirsutism + acne
- polycystic ovaries on ultrasound
PCOS investigations
raised LH
raised LH:FSH ratio - high LH compared with FSH
raised free testosterone
raised insulin
transvaginal US = gold standard
– follicles around ovary periphery, 12+
causes of premature ovarian failure
Turner's syndrome chemo, radio oophorectomy autoimmune - coeliac, adrenal insufficiency, T1DM infections - mumps, TB
diagnosis of premature ovarian syndrome
younger than 40
menopausal symptoms
elevated FSH - persistently on 2 consecutive samples separated by 4 weeks
causes of tubal disease
infective
- pelvic inflammatory disease (PID) - chlamydia, gonorrhoea, TB, syphilis
- transperitoneal spread - appendicitis
- iatrogenic - coil insertion
non-infective
- endometriosis
- fibroids
- polyps
- congenital
what is a hydrosalpinx and how does it present?
fluid filled fallopian tube - can be due to pelvic inflam disease
abdo/pelvic pain discharge pain during sex (dyspareunia) heavy/long periods severe cramps infertility ectopic pregnancy
what is endometriosis?
presence of endometrial glands outside uterine cavity
20-30% of infertile women
causes of endometriosis
retrograde menstruation - blood flows backwards into pelvis
altered immune function
abnormal cellular adhesion
genetic
endometriosis presentation
severe cramps before menstruation pain during sex (dyspareunia) heavy periods (menorrhagia) painful defaecation chronic pelvic pain infertility
chocolate cysts
gunpowder appearance on laparoscopy
causes of male infertility
non-obstructive - hypogonadism - hypothyroidism - hyperprolactinaemia - diabetes - Klinefelter - undescended testes Y deletions heat, radiation, chemo torsion/variocele
obstructive - congenital, infection, vasectomy
drugs causing male infertility
marijuana anabolic steroids SSRI antidepressants cocaine alcohol, tobacco
treatment of male infertility
surgery to obstructed vasdeferens intrauterine insemination intracytoplasmic sperm injection (ICSI) surgical sperm aspiration from epididymis or testicle combined with ICSI donor sperm insemination
male hypogonadism presentation
gynaecomastia
decreased body hair, high pitch voice, low libido
decreased testicular volume
decreased bone + muscle mass
pre-pubertal = eunuchoidal habitus (tall, slim, long arms + legs)
++ symptoms associated with cause
male hypogonadism investigation
measure AM testosterone twice - peaks in morning
total testosterone can be misleading - only free portion is biologically active
if LH/FSH were high in suspected male hypogonadism, what further investigation would you do?
primary (hypergonadotrophic hypogonadism)
karyotyping, iron studies
if LH/FSH were low in suspected male hypogonadism, what further investigation would you do?
seconday (hypogonadotropic hypogonadism)
exclude medications
iron studies
MRI, prolactin + pituitary hormones
management of male hypogonadism
testosterone replacement
-> transdermal, oral, IM
requires monitoring
- 3-6 monthly when starting then annually after that
- DRE + PSA, haematocrit, sleep apnoea, general health
different types of testosterone replacement
transdermal - applied daily, mimics circadian rhythm, skin irritation, compliance issues
undecanoate
- oral - daily, nauses, variable testosterone levels, compliance
- IM - every 10-14weeks, improved compliance, steady testosterone levels, hard to withdraw
sustanon (IM) - every 2-3 weeks, easy to withdraw, sekf admin, variable testosterone levels
disadvantages of IM testosterone replacement treatment
contraindicated in bleeding disorders
local pain at injection sight
coughing following injection
testosterone replacement therapy contraindications
hormone responsive cancer - prostate/breast
possible prostate cancer - raised PSA, sus DRE
haematocrit >50%
severe sleep apnoea / heart failure
causes of primary hypogonadism
congenital
- Klinefelters
- cryptorchidism (testicles not descending)
- Y chromosome microdeletions
acquired
- testicle trauma / torsion
- chemo/radio
- variocele
- orchitis (mups infection)
- infiltrative disease - sarcoidosis, haemochromatosis
- medications - glucocorticoids, ketoconazole
medications that can cause primary hypogonadism?
glucocorticoids
ketoconazole
Klinefelters syndrome
not inherited, caused by nondisjunction
usually 47XXY but varies - variations mean late/misdiagnosis
1/550 birth
Klinefelters presentation
infertile - due to tubage damage
small firm testes
cryptorchidism
learning siability, psychosocial issues
diagnosis of Klinefelters
karyotyping
Klinefelters associated risks
increased risk of breast cancer + non-hodgkin lymphoma
how are spermatogenesis + testosterone production affected in primary vs secondary hypogonadism?
primary - spermatogenesis is affected more than testosterone production
secondary - both are affected equally
causes of secondary hypogonadism
congenital
- Kallmann’s
- Prader-Wili syndrome
acquired
- pituitary damage - tumours, sarcoidosis, infection, trauma
- obesity, diabetes
- hyperprolactinaemia
- medications - steroid, opiods
- acute systemic illnes
- eating disorders, excessive exercises
medications that cause secondary hypogonadism
steroids
opiods
Kallmans syndrome
isolated GnRH deficiency + loss/change in smell (hyposmia/anosmia)
Kallman’s presentation
unilateral renal angenesis (lack of organ)
red-green colour blindness
cleft lip
bilateral synkinesis (face muscle twitches)
+ symptoms associated with hypogonadism
