Repro Flashcards
subfertility and infertility definitions
inability to conceive after 6months or 1year of unprotected sex
sperm and egg fertility comparison
sperm- constant fertility from puberty, gradual decline with age
egg- cyclical fertility, 7M follicles in utero declines to 0 at menopause
formation of ovarian reserve of follicles
- primordial germ cells colonise the gonad and numbers expand by meiosis
- germ cells enter and then arrest in, meiosis which begins again at ovulation
- primordial follicles form
- folliculogenesis
stages of follicle development
- primordial follicle- oocyte with squamous granulosa cells
- primary follicle- oocyte with stratified cuboidal granulosa cells
- secondary follicle- stroma and theca cells
- early antral follicle- theca external and interna with blood vessels
- graafian follicle ready to be ovulated
feedback loop of FSH LH
- hypothalamus secretes GnRH
- stimulates anterior pituitary to secrete FSH and LH
- oestrogen, progesterones negatively feedback from follicle to inhibit AP and hypothalamus
inhibins negatively feedback on FSH only
oxytocin effects
smooth muscle contraction:
- milk ejection
- contraction of uterus during childbirth: used to induce labour
- during orgasm
Secretion stimulated in response to stimulation of nipples or uterine distension
why does GnRH have a pulsatile release?
prevent receptor desensitisation and downregulation
kisspeptin
neuropeptide that feeds back on GnRH neurons and regulate secretion
water soluble hormones
GnRH, FSH, LH
travel through blood freely and bind to cell surface receptor
lipid soluble hormones
oestrogen, progesterone
travel attached to transport protein and freely diffuse into cell
gonadotrophin regulated growth phase
from preantral follicle to preovulatory follicle
FSH- astral granulosa cell differentiation, proliferation & function, can make oestrogen
LH- theca cell androgen production, ovulation
AMH
anti-mullerian hormone
made by granulosa cells, absent in primordial follicle but present at later stages
has an inhibitory effect on follicle development- neg feedback on small follicles from more developed follicle
unaffected by GnRH/steroid hormones
reliable reflection of growing follicles- decreases over age
which follicles are selected to be ovulated?
estrogen and LH induce expression of LH receptor on theca cells
↳ follicle with largest #of LH receptors is ovulated and others die
hormones when follicle begins growth
FSH increase, oestrogen increase
When do FSH levels drop during follicle growth?
when oestrogen levels are high due to negative feedback causing endometrial thickening
what does the oestrogen peak cause?
LH release from the pituitary and suddenly has stimulatory effect on FSH secretion
oestrogen and FSH stimulate LH binding sites on granulosa cells
LH surge on day 14
ovulation
oestrogen drops as follicle is gone, corpus luteum produces some
hormones in luteal phase of menstruation
drop on FSH/LH as progesterone levels rise completing the endometrium
corpus luteum
made fo granulosa and theca cells, lutein cells contain lipid droplets and pigment lutein which give yellow colour, secrete progesterone
hormones when no pregnancy is detected in menstrual cycle
CL regresses, FSH rise, progesterone and oestrogen drop as endometrium shed
hCG
produced by blastocysts which bind to LH receptors and maintain progesterone if preggo and surpasses maternal immune rejection of placenta
how does hormonal contraception work?
suppresses ovulation via negative feedback of progesterone- secondary effects on female genital tract
HPG axis can be awakened in off period
combined pill mechanism
oestrogen provides additional feedback and promotes progesterone receptor expression
when can the breast produce milk?
once the placenta is delivered
myoepithelial cells in breast
contract on signal from oxytocin and expel milk from ducts
milk ejection reflex
suckling breast stimualtes prolactin release and oxytocin synthesis and secretion
myoepithelial cell contraction -> milk expulsion
why is fertility reducing during lactation?
negative feedback fo prolactin on FSH/LH
difference between early and premature menopause
early- <45
premature- <40 (premature ovarian insufficiency)
causes of premature menopause
- idiopathic
- autoimmune- Addisons, thyroid
- surgery/ chemo/ radiotherapy
- chromosomal/infecitons/ metabolic
management of early menopause
treat with oestrogen replacement
Biochemical profile of post-menopausal women
low estradiol
high FSH (main marker)
high LH
predictors of menopause
FSH – day 3 raised level
•AMH – anti-Mullerian hormone: declines with age and useful marker of ovarian reserve
•Inhibin B - declines with age and protein hormone marker of ovarian reserve
•Ovarian antral follicle count by ultrasound
vasomotor symptoms of lack of oestrogen
Hot flushes and night sweats • Palpitations, faintness
• Severe sleep deprivation
Urogenital ageing
Vaginal dryness and dyspareunia
• Bladder neck symptoms: urgency, urge incontinence, nocturia, recurrent urinary infections
HRT hormones that can be given
• Estrogen- improve symptoms but don’t restore fertility
• Progestogen - for endometrial protection
• Testosterone
oral, skin (transdermal) patches and gels, subdermal
implant, intra-uterine progestogen
Prescribed for menopausal symptom
benefits of HRT
improve QOL, protection against osteoporosis (provided HRT is taken long enough) and bowel cancer
risks of HRT
• Small extra risk of breast cancer with prolonged duration of use
• Increased risk of venous thromboembolism: x2 fold increase
• Small excess risk of stroke
(last 2 for tablets not transdermal patches)
erectile dysfunction marker of cardiovascular disease
especially predictive of CV in men younger than 60 and in those with diabetes
Testicular dysgenesis syndrome
condition characterised by:
- cryptorchism, hypospadias
- testis GC cancer, low sperm count, low-norm testosterone levels
(penis may be reduced in size)
what can cause cryptoorchism and hypospadias?
deficiencies in fetal androgens
what is cryptorchidism
A congenital undescended testis is one that has failed to reach the bottom of the scrotum by 3 months of age- dependant on there being enough androgens
Reasons for correction of cryptorchidism
Reduce risk of infertility
Allows the testes to be examined for testicular cancer
Avoid testicular torsion
Cosmetic appearance
cryptorchidism link to cancer
Males with undescended testis are 40 times as likely to develop testicular cancer (seminoma) as males without undescended testis
After the age of 2 years in untreated individuals the Sertoli cells will degrade
assisted reproduction effectiveness with age
increasingly ineffective with age
why do Sertoli cells have an impact on sperm count?
each Sertoli cell can only support a fixed number of germ cells during their 10 week development into sperm, mainly determined during fetal/early postnatal life
AGD
anogenital distance, between anal opening and base of penis/vaginal opening
determined by fetal androgen exposure
male AGD is
twice that of female
masculinisation programming window
male- female difference in AGD was induced by androgen exposure specifically in the MPW, TDS orginate in 1st trimester MPW (8-12w)
factors via mother in TDS
smoking, medications, lifestyle, diet
hypospadias is characterised by:
Hypospadias is characterised by
- a ventral urethral meatus
- a hooded prepuce
- chordee (ventral curvature of the penis) in more severe forms
- the urethral meatus may open more proximally in the more severe variants. However, 75% of the openings are distally located.
Turner’s syndrome (45 XO)
Women with Turner’s syndrome run out of eggs as a neonate and therefore have streak ovaries in adult life.
cannot produce ovarian oestrogen in response to the increasing LH and FSH during puberty- puberty induced at appropriate time
hypogonadotropic hypogonadal anovulation
LH and FSH are low because there is not enough GnRH being secreted from the hypothalamus- low test and oestrogen
notably hypothalamic amenorrhoea- excessive exercise, anorexia
hyperprolactinemia
Prolactin inbibits gonadotrophin secretin locally. This results in low LH, low FSH and low oestradiol
symptoms: galactorrhea
visual defect caused by pituitary tumour
bitemporal hemianopia
oligomenorrhoea
fewer than six to eight periods per year
hypergonadotropic hypoestrogenic anovulation
hypogonadism due to an impaired response of the gonads to the GnRH, FSH and LH, and in turn a lack of sex steroid hormone production
normogonadotropic normoestrogenic anovulation
PCOS- high LH and androgens with normal/low FSH and estradiol
hyperinsulinaemia also seen
PCOS symptoms
hisuitism, acne, oily skin, menstrual disturbances: oligomenorrhea and amenorrhoea, obesity, acanthosis nigricans (due to insulin resistance)
PCOS physiology
normal FSH and oestrogen stimulates growth of follicles but high androgens pause growth and inability to ovulate
high LH stimulates androgen production- ovary has many arrested follicles looking polycystic
overlap with metabolic syndrome
treatment of PCOS
COCP- suppresses hormones
weight control
additional testosterone blocking drugs- cyproterone acetate
diagnosis of PCOS
transvaginal USS
finding on examination of premature menopause
atrophic vaginitis
Which hormone is required to maintain progesterone production during the menstrual cycle?
LH
What problem limited the development of IVF as we know it now?
premature LH surge
_ increase bleeding at menstruation
prostaglandins
When is the best time in an average 28-day menstrual cycle to do a blood test for ovulation?
Day 21- progesterone from CL is measured to confirm ovulation
estrogen agonists uses
- HRT: treat post-menopausal atrophic vaginitis, after hysterectomy or induction of puberty
- COCP
Continuous combined HRT
estrogen and progestagen are taken continually. It is used two years after the menopause and does not cause vaginal bleeding.
sequential HRT
estrogen is given followed by two weeks of progestogen. This causes regular periods (after progestogen withdrawal).
- used for younger women with hypogonadotrophic hypogonadism or in the climacteric.
- not contraceptive but will have less side effects than the oral contraceptive pill
oestrogen side effects
nausea, headaches and breast tenderness
COCP side effects
headaches, nausea, weight gain, reduce libido, prevent lactation, associated with thromboembolism
why can’t women with a uterus be given oestrogen alone?
cause continued proliferation of the endometrium and this can cause heavy irregular bleeding or pathologies such as endometrial hyperplasia and endometrial cancer
oestrogen antagonist
- ovulation induction (clomifene)- Anti-estrogens for ovulation induction in PCOS are only used for 5 days each month at the beginning of the cycle to allow the endometrium and potential for the LH surge to recover.
- breast cancer (tamoxifen)
progesterone agonist
- menstrual induction- PCOS
- heavy menstrual bleeding- reduce endometrial thickness
- progesterone replacement in IVF
types of progesterone contraception
- progestagen only contraception
- depo contraception- IM, inhibits gonadotrophins
- implant contraception
- intrauterine system- coil causes endometrial atrophy
- post coital contraception- makes endometrium less receptive
progesterone vs oestrogen contraception
most of the serious side effect of the combined contraceptive pill are because of the estrogen, progesterone alone is a safer contraceptive and used in higher risk women. However, unlike the combined pill which gives a regular cycle, progesterone only contraception causes irregular bleeding which can be frequent
progesterone antagonist
- termination of pregnancy
- post coital contraception
- shrink fibroid growth
androgen agonist
HRT- increase energy & libido
androgen antagonist
treatment of hirsuitism (cyproterone acetate, finasteride)- need effective contraception also
cyproterone acetate
androgen antagonist and progesterone agonist
which 2 drugs are used for termination of pregnancy?
progesterone antagonist (mifepristone) and second stage prostaglandin E (agonist)
FSH agonist
- ovulation induction
- superovulation- collect multiple eggs in IVF treatment
FSH antagonist
gonadotrophin suppression
LH agonist
- superovulation
- ovulation
LH antagonist
- IVF- prevent a premature LH surge
oxytocin antagonist
prevention fo preterm labour (atosiban)- stop uterine contractions
oxytocin agonist
- augmentation fo labour
- post-partum haemorrhage- solve uterine atony
prostaglandin agonist in inducing labour
Vaginal prostaglandin E2 gel- cervical ripening and myometrium contractions
prostaglandin antagonist
- treatment of heavy menstrual bleeding (mefenamic acid)
- premature labour (indomethacin)- SE: premature closure of the fetal ductus
Which peptide hormones are produced from: arcuate nucleus preoptic nucleus supraoptic nucleus paraventricular nucleus periventricular nucleus
GHRH, dopamine GnRH AVP, oxytocin AVP, oxytocin, CRH, TRH somatostatin
Kallman syndrome
50% of hypogonadotropic hypogonadism cases defined by a delay or absence in onset of puberty and an impaired or absent sense of smell
presentation in males is characterised by low gonadotrophins & testosterone and small external genitalia, with small or undescended testis
