Infertility & reproductive treatments Flashcards
what is infertility?
a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12+ months of regular unprotected sexual intercourse
what is primary infertility?
infertility with no previous live birth
what is secondary infertility?
infertility with a live birth 12+ months previously
what is the prevalence of infertility?
affects 1 in 7 couples
55% seek help - positive association with socioeconomic status
what are the psychological impacts of infertility?
no biological child, impact on wellbeing, larger family, investigations and treatments (often failing)
what are the societal costs of infertility?
less births, less tax income, investigation and treatment costs
what are the male pre-testicular causes of infertility?
congenital and acquired endocrinopathies e.g Klinefelters, Y chromosome deletion, HPG, T, PRL
what are the testicular causes of male infertility?
congenital cryptorchidism infection - STDs immunological - antisperm ABs vascular - varicocoele trauma/surgery toxins - chemo, dxt, drugs, smoking
what are the post testicular causes of male infertility?
congenital - abscence of vas deferens in CF
obstructive azoospermia
erectile dysfunction - retrograde ejaculation, mechanical impairment, psychological
latrogenic - vasectomy
what is cryptorchidism?
undescended testes - 90% in inguinal canal
what are the types of causes of female infertility?
pelvic, tubal, ovarian, uterine, cervical and unexplained
what is endometriosis?
presence of functioning endometrial tissue outside the uterus
what is the prevalence of endometriosis in women?
5%
what are the symptoms of endometriosis?
menstrual pain and irregularity, deep dyspareunia, infertility
what are the treatments available for endometriosis?
hormonal (e.g continuous oral con. pill, prog)
laparascopic ablation
hysterectomy
bilateral salpingo-oophorectomy
what are fibroids?
benign tumours of the myometrium
what is the prevalence of fibroids in women?
1-20% pre-menopausal women
are fibroids or endometriosis responsive to oestrogen?
both
what are the symptoms of fibroids?
usually asymptomatic
menstrual pain, irregularities
deep dyspareunia
infertility
what are the treatments for fibroids?
hormonal (continuous OCP, prog, cont. GnRH agonists)
hysterectomy
what are the blood results for a hypothalamic cause of endocrine male infertility?
low LH/FSH
low testosterone
low GnRH (not measurable)
what are the blood results for pituitary causes of endocrine male infertility?
low LH/FSH
low testosterone
what are the blood results for gonad causes for endocrine male infertility?
high LH/FSH
low testosterone
what is Kallman’s syndrome?
failure of migration of GnRH neurons to hypothalamus from olfactory placode (during first 10wks of development)
what are the reproductive features of Kallmann’s?
cryptorchidism failure of puberty micropenis lack of testicle development primary amenorrhoea infertility
what are the blood test results for someone with Kallmann’s?
low LH/FSH
low testosterone
how is hyperprolactinemia treated?
cabergoline
or pit surgery/radiotherapy
what is a normal male/female karyotype?
46XY male
46XX female
what is the karyotype for Klinefelter syndrome?
47XXY
what is the karyotype for Turner syndrome?
45X0
what is Klinefelters syndrome?
47XXY chromosomal abnormality
male but with some female characteristics
what are the features of Klinefelters syndrome?
tall stature decreased facial/chest hair mildly impaired IQ narrow shoulders female pattern pubic hair wide hips small penis/testes low bone density slight breast development INFERTILITY
how would you approach a male history for infertility?
duration previous children pubertal milestones associated symptoms medical/surgical history medications/drugs FH/SH
how would you approach examining a male presenting with infertility?
BMI sexual characteristics testicular volume epididymis hardness presence of vas deferens syndromic features anosmia?
what are the 4 main investigations for males presenting with infertility?
semen analysis
blood tests
microbiology
imaging
what is semen analysis?
measures volume (1.5ml normal), sperm concentration and total mobility of a sperm sample
what are the main blood tests for a male presenting with infertility?
LH/FSH/PRL morning fasting testosterone sex hormone binding globulin albumin iron studies pituitary/thyroid profile karyotyping
what are the main microbiology tests for a male presenting with infertility?
urine test
chlamydia swab
what are the imaging methods used for males presenting with infertility?
scrotal ultrasound/doppler (varicocoele/obstruction, testicular volume) MRI pituitary (for low LH/FSH or high PRL)
what are the typical treatments for general male inferility?
optimise BMI
smoking cessation
alcohol cessation
what are specific treatments for male hyperPRL?
dopamine agonist - cabergoline
how is testosterone prescribed to males not desiring fertility?
daily gel
3 weekly IM injections
3 monthly IM injections
implants/oral preparations less common
what to prescribe to males desiring fertility?
hCG injections (act on LH receptors) if no response after 6mnth, add FSH injections
what treatments are used for males wanting fertility?
gonadotrophin treatment
NO TESTOSTERONE - -ve feedback on LH/FSH
when is testosterone prescribed to males presenting with infertility?
if fertility is not desired, only for symptomatic relief
what is primary amenorrhoea?
menses not started after 16 years old
what is secondary amenorrhoea?
periods start at puberty but stop for at least 3-6mnths
what is amenorrhoea?
no periods for at least 3-6mnths
or up to 3 periods/yr
what is oligomenorrhoea?
irregular/infrequent periods, >35day cycles
or 4/9 cycles/yr
what is early menopause?
menopause occurring in a female under 45
how is early menopause diagnosed?
high FSH (>25iU/L) twice at least 4wk apart
what are the odds for conception in a female with early menopause?
20%
what are the causes of early menopause?
autoimmune
genetic - fragile X, turner’s syndrome
cancer therapy - radio/chemo in past
how does hypothalamic causes of infertility in women show in a blood test?
low LH/FSH
low E2
hypogonadotrophic hypogonadism
what are the female congenital causes of hypogonadotropic hypogonadism?
anosmic (kallmann’s syndrome) or normosmic
what are the acquired female causes of hypogonadotrophic hypogonadism?
low BMI
stress
excessive exercise
hyperprolactinemia
what are the blood results for pituitary causes of female infertility?
low LH/FSH
low E2
what are the causes of female hypogonadotropic infertility? (pituitary causes)
hypopituitarism- tumour infiltration apoplexy surgery radiation
what are the acquired gonadal causes of female primary hypogonadism?
early menopause/primary ovarian insufficiency surgery trauma chemo radiation polycystic ovarian syndrome (PCOS)
what are the congenital causes of female primary hypogonadism?
turners syndrome
early menopause/premature ovarian insufficiency
what are the blood results for PCOS?
high LH/FSH
low or normal E2
what are the blood results for female primary hypogonadism?
high LH/FSH
low E2
what are other endocrine causes of female infertility outside the HPG axis?
hyper/hypothyroidism - reduced bioavailability of oestradiol
what is PCOS?
polycystic ovarian syndrome
what is PCOS’ burden of disease?
affects 5-15% women of reproductive age
most common endocrine disorder in women, most common cause of infertility
how is PCOS diagnosed?
exclude other reproductive disorders
Rotterdam criteria - 2/3
what is the Rotterdam PCOS diagnostic criteria?
oligo or anovulation
clinical+/- biochemical hyperandrogenism
polycystic ovaries on utrasound
how is oligo/anovulation assessed for the rotterdam criteria of PCOS?
by menstrual frequency - oligomenorrhoea
or proven by lack of progesterone or on ultrasound
how is clinical hyperandrogenism for the rotterdam PCOS criteria assessed?
clinical - acne, hirsutism, alopecia
how is biochemical hyperandrogenism for the rotterdam PCOS criteria assessed?
raised androgens on blood test (e.g testosterone)
how is polycystic ovaries assessed for the rotterdam PCOS criteria?
must have >20 follicles
OR
>10ml either ovary on TVUS (8MHz)
why are polycystic ovaries on ultrasound not diagnostic for PCOS?
30% of women have polycystic ovaries so isn’t confirmational
how does Clomiphene act for female fertility?
oestradiol receptor antagonist
reduces negative feedback of oestrogen on hypothalamus/pituitary gland
therefore increases LH/FSH
FSH stimulates follicle growth
what treatments for PCOS aim to restore ovulation?
weight loss
letrozole (aromatase inhibitor)
clomiphene (oestradiol receptor modulator)
FSH stimulation
how does letrozole act for female infertility?
inhibits aromatase (test-oest)
therefore reduces negative feedback of oestrogen on LH/FSH
therefore increases serum LH/FSH leading to stimulation of follicle growth
what are the treatments for PCOS?
OCP
metformin
anti-androgens
progesterone courses
what are the symptoms of PCOS?
acne hirsutism, excess facial hair oligomenorrhoea insulin resistance infertility weight gain anxiety and depression male pattern hair loss
what does metformin do for PCOS?
helps reduce BMI to help with irregular menses
helps with insulin resistance/impaired glucose homeostasis
how do anti-androgens help PCOS?
reduce hirsutism along with creams, waxing and laser hair removal
what are the physical features of Turner’s syndrome?
short stature low hairline shield chest webbed neck poor breast development, wide spaced nipples elbow deformity brown nevi short 4th metacarpal small fingernails
what are the internal features of Turner’s syndrome?
coarctation of aorta
underdeveloped reproductive tract
amenorrhoea
what are the main history points for a female presenting with infertility?
duration previous children pubertal milestones breastfeeding menstrual history associated symptoms medical/surgical history medication/DH FH/SH
what are the examinations to consider for females presenting with infertility?
BMI sexual characteristics hyperandrogenism signs pelvic examination syndromic features anosmia
what are the main types of investigations for females presenting with infertility?
blood tests
pregnancy test
microbiology
imaging
what are the blood tests for a female presenting with infertility?
LH/FSH/PRL oestradiol, androgens follicular phase 17-OHP, mid-luteal progesterone sex hormone binding globulin albumin, iron studies pit/thyroid study karyotyping
what are the microbiology tests for a female presenting with infertility?
urine test
chlamydia swab
what are the imaging methods used for a female presenting with infertility?
Ultrasound (transvaginal)
hysterosalpingogram
MRI pit
simply, what is the process of IVF?
oocyte retrieval (after high dose FSH)
fertilisation in vitro
embryo incubation
embryo transfer
what is ICSI and when is it used?
intra-cytoplasmic sperm injection
used for when sperm has mobility issues/male factor infertility
what are the steps in inducing ovulation for IVF?
FSH stimulation high dose
LH surge prevented (to prevent premature ovulation) by GnRH antagonists/agonists (short/long protocol)
what is the short protocol for preventing premature LH surge in IVF?
GnRH antagonist given around day 6 in conjunction with FSH
what is the long protocol for preventing premature LH surge in IVF?
GnRH agonist given a week before starting FSH
how are follicles matured during IVF?
exposed to LH by giving hCG or GnRH agonist
following high dose FSH, what must be done before harvesting an oocyte?
LH surge triggered
what day is the oocyte fertilised in IVF?
day 13 - immediately after LH surge ends (36hr)
when is the fertilised oocyte transferred to the endometrium in IVF?
day 18
when is the pregnancy tested by blood test in IVF?
day 30 - 11days after implantation
when is a pregnancy ultrasound done in IVF to confirm pregnancy?
day 44 - 2 weeks after blood test
what are the impermanent methods for contraception?
barriers e.g condoms/diaphragms combined OCP progesterone only pill (mini pill) long acting reversible contraception emergency contraception
what are the permanent methods for contraception?
vasectomy
female sterilisation
what are the positives for condoms?
protect against STIs
easy to obtain/no need to see healthcare professional
no contraindications
what are the negatives of condoms?
can interrupt sex
can reduce sensation
can interfere with erections
some skill needed to use
how does the combined oral contraceptive pill act for contraception?
high oest and prog negative feedback on LH/FSH
low LH/FSH cause anovulation
prog thickens cervical mucus
thinning of endometrial lining to reduce implantation
what are the positives for the combined OCP?
easy to take - one pill a day effective doesnt interrupt sex can take back to back and avoid withdrawal bleeds reduce endometrial and cervical cancer weight neutral in 90%
what are the negatives for the combined OCP?
may not remember to take it no protection against STIs P450 enzyme inducers may reduce efficacy not best choice during breastfeeding can increase appetite, weight gain
what are some possible side effects of the combined OCP?
spotting nausea sore breasts mood/libido changes hunger blood clots in legs/lungs
what are the non-contraceptive uses of the combined OCP?
makes periods lighter/less painful
regular withdrawal bleeds
help reduce LH and hyperadrogenism in PCOS
what are the positives of the mini pill?
suitable if can’t take oestrogen (blood clot risk)
easy to take
doesnt interrupt sex
periods may stop temporarily
can be used when breastfeeding
works same as OCP but a bit less reliable
what are the negatives of the mini pill?
can be hard to remember
no protection against STIs
shorter acting so needs to be taken same time each day
what are long acting reversible contraceptives? (LARC)
intra-uterine devices, coils, subdermal implants, progesterone only injections
what is an IUD?
a LARC mechanically preventing implantation, decreasing sperm egg survival
lasts 5-10 years
e.g copper coil
what is an IUS?
intra uterine system (LARC) secreting progesterone to thin endometrial lining and thicken cervical mucus
lasts 3-5 years
e.g mirena coil
what are the choices for emergency contraception?
copper coil (most effective) contraceptive pill - ulipristal acetate 30mg or levonorgestrel 1.5mg
what is the ulipristal acetate emergency contraceptive? (ellaOne)
stops progesterone working normally
prevents ovulation
must be taken within 5 days of unprotected intercourse
what is the levonorgestrel emergency contraceptive pill? (levonelle)
synthetic progesterone prevents ovulation
doesnt cause abortion
must be taken within 3 days of intercourse
what are the side effects of emergency contraceptive pills?
headache, abdo pain, nausea
what are the contraindications for combined OCP?
migraine with aura smoking(>15/day) if over 35yo stroke or CVD history current breast cancer liver cirrhosis complicated diabetes
what medications may interact with the combined OCP?
P450 liver enzyme inducing drugs (anti epileptics, antibiotics), teratogenic drugs (lithium, warfarin)
with these, would need stronger contraceptives
what are the risks for hormone replacement therapy in menopause?
venous thrombo-embolism
hormone senstive cancers
increased risk of CV disease
risk of stroke
why is venous thrombo-embolism a risk for oral oestrogen HRT?
oral oestrogens undergo first pass metabolism in liver
increases SHBG , triglycerides, CRP
transdermal oestrogens safer than oral
why are hormone sensitive cancers a risk in oestrogen HRT?
breast cancer slight increased risk if combined w prog - related to duration of treatment, reduces after stopping
ovarian cancer small increase after long term use
endometrial cancer - must have progesterone prescribed if have an endometrium
what is the cardiovascular disease risk of oestrogen HRT?
increased risk if started 10 yr after menopause
no increased risk if started before 60
what is the risk of stroke with oestrogen HRT?
small increased risk
more in oral than transdermal
more in combined than oestrogen only
what are the benefits of HRT for menopause?
symptomatic relief
less osteoporosis related fractures
which transgender gender is more common?
transgender women 3x more common than transgender men
what is the process for transgender treatment?
in prepubertal young people - GnRH agonist for pubertal suppression and then sex steroids
gender reassignment surgery after 1-2 years of hormonal treatment
what are the masculising hormones for transgender men?
testosterone
progesterone given to suppress menstrual bleeding if needed
following masculising hormones for transgender men, what effects can be seen? (1-6 months)
balding deeper voice/acne/ increased facial hair/coarser body hair change in body fat distribution enlargement of clitoris menstrual cycle stops increased muscle mass and strength
what are the feminising hormones for transgender women?
oestrogen - high dose
reduce testosterone
how is oestrogen prescribed for transgender women?
4-5mg daily to aim for estradiol levels 743pmol/L
how is testosterone reduced in transgender women?
GnRH agonists
anti-androgen medications
what should be monitored when giving testosterone ton males not desiring fertility?
haematocrit - risk of stroke/hyperviscosity
prostate specific antigen - risk of prostate cancer
first line treatment for PCOS?
metformin for weight loss
letrozole - aromatase inhibitor
inhibits test-oestr
