Menopause, PCOS and infertility Flashcards
Define perimenopause
the period when ovarian function declines and menopausal symptoms appear
describe what happens during perimenopause on a hormonal level?
gradual rise in FSH
fluctuations in E2 and progesterone
decreased ovarian inhibin
gradually E2 becomes very low
what FSH levels define non-menopause, perimenopause and post menopause?
non-menopause i.e. still cycling= FSH less than 10u/L
perimenopause= FSH > 20u/L
post menopause= FSH > 40u/L
what are the short-term effects of menopause?
Vasomotor symptoms- hot flashes, night sweats, formication
Vaginal dryness–> dyspareunia, dysuria, urgency
Sleep disturbance
what are the long term effects of menopause?
reduced bone density
what lifestyle advice might we give to a post menopausal woman to help reduce her risk of osteoporosis?
weight bearing exercise > 3 times per week
calcium intake 1200mg/day
adequate vitamin D
avoid excess alcohol and smoking
what are the causes of premature menopause?
primary ovarian insufficiency
iatrogenic causes- e.g. surgical/chemo/radiotherapy
Genetic causes- turner’s, fragile x
autoimmune causes
what is the criteria diagnosis for premature menopause?
at least 4 months of amenorrhea prior to age 40yrs
+
FSH > 40 U/L on 2 occasions at least 1 month apart
+
exclusion of secondary amenorrhoea causes
what are the risks of oestrogen alone HRT?
increased risk of stroke, VTE, PE, DVT
increased risk of cholecystitis
unopposed E2 in presence of uterus can cause endometrial hyperplasia
what are the risks of oestrogen +progesterone HRT?
increased risk of stroke, VTE, PE, DVT
increased risk of cholecystitis
increased risk of breast cancer if used for > 5 yrs
if a perimenopausal women complains of vaginal dryness but has a significant hx of IHD, would you commence HRT?
more consideration is indicated
generally caution AGAINST using HRT
but if must, transdermal route may be preferable
what drug is Livial?
tibolone, a synthetic steroid with weak oestrogen, progesterone and anti-androgenic action
what is the difference between vagifem and ovestin cream?
vagifem= estradiol
ovestin= estriol
what are some ix you need to order in a 38 yr old woman who you suspect is going through premature menopause?
- Check FSH > 40 on two occasions
- Exclude secondary causes of amenorrhoea such as PRL, TFTs, bHCG
- Establish any genetic abnormalities such as Fragile X, Turner’s syndrome–> do a karyotype
Do an autoimmune screen including thyroid antibodies, gastric parietal cell autoantibodies
what are the long term consequences of premature menopause?
increased risk of CV disease
increased risk of osteoporosis
infertility
what FSH level (low or high) do we expect in a woman with ovarian failure or HPG axis dysfunction causing anovulation?
what if the FSH level was normal but the woman is still anovulating? what must we consider?
FSH= high if Ovarian failure
FSH= low if HPG axis dysfunction
FSH= normal if PCOS/obesity
What biomarker indicates ovarian reserve? How else can we test for ovarian reserve?
anti-mullerian hormone- low AMH may indicate low ovarian reserve
more common test for ovarian function or reserve- is the day 3 FSH and LH. High FSH > 10 may indicate poor ovarian reserve
what are some things we should ask about the male partner when consulting about infertility?
Has he fathered any children from previous relationships?
Smoking, drug and alcohol intake, anabolic steroid use
Past STI history
Ability to sustain erection and ejaculation during intercourse
Past history of mumps, undescended testes, genital trauma or surgery including vasectomy
what are some key things to examine for in a male partner if a couple come in with the issue of infertility?
Body habitus, height, weight, BMI, muscle mass and strength, fat distribution
Secondary sexual characteristics: hair thickness and distribution
Breasts (gynaecomastia), signs of endocrinopathy
Blood pressure lying and standing
Inguinal canals
As indicated, testicular examination: determine size (with aid of orchidometer), consistency, masses, hydrocoele, varicocele
a woman comes in to see you because she has been having difficulty conceiving over the past year. what on general history do you want to know?
Maternal Age
Past reproductive history and previous pregnancy outcomes
Past gynaecological history
Menstrual history, including frequency and regularity, symptoms of ovulation
Sexual history: frequency, problems, lubricant use, timing in fertile window
- Weight gain, acne, hirsutism
- Dyspareunia, dysmenorrhoea
- Galactorrhoea, visual disturbance
- Contraceptive history: type and duration
- Past STI history, previous PID
- Medical, surgical, psychiatric, general health
- Family history, genetic illness
- Medications, smoking, drug and alcohol intake
how might we determine whether a woman is ovulatory or anovulatory as an ix for cause of infertility?
Mid-luteal progesterone (day 21) if high then indicates that ovulation has occured
how might we assess tubal patency as a possible cause of infertility?
hysterosalpingogram or saline sonohysterography
what are some associated female conditions to screen for in a woman who is presenting with difficulty conceiving?
PCOS-acne, hirsutism, weight gain
endometriosis- dysmenorrhoea, dyspareunia
why is anabolic steroid use in males associated with infertility?
Anabolic steroid abuse results in hypogonadotrophic hypogonadism due to the negative feedback of high androgen levels
what exactly is the mechanism of infertility in kallman’s disease?
absence of GnRH releasing neurons at the hypothalamus
what are some causes of testicular failure leading to infertility?
congenital genetic causes e.g. kleinfelter’s
acquired causes: mumps, trauma, torsion, chemotherapy/radiotherapy
if a man had testicular failure causing infertility, what would show up on his LH/FSH blood test?
raised LH/FSH often with normal T levels
what is the relationship between CF carrier state and infertility in males?
Congenital bilateral absence of the vas deferens can occur and is associated with the cystic fibrosis carrier state.
what progesterone level in the mid-luteal phase is indicative of ovulation?
A progesterone level over 20 nmol/L in the mid-luteal phase is a reliable indicator that ovulation has occurred.
what are the three main causes of anovulation in women?
- hypothalamic dysfunction
- pituitary dysfunction
- ovarian failure (raised FSH/LH).
why are TSH levels important to evaluate in a woman who is having trouble conceiving?
Chronically high TSH seen in hypothyroidism may alter the dopamine-mediated control of prolactin secretion, resulting in hyperprolactinaemia that will resolve with thyroxine replacement therapy.
what is the hormonal pattern characteristic for PCOS we should look for in assessing causes of infertility for a female patient?
In PCOS there are normal serum levels of FSH and LH; however, the ratio of FSH to LH on day 3 of the menstrual cycle is often reversed, meaning that LH exceeds FSH, usually by a factor of at least 2:1.
Androgen levels are raised, and there is a fall in sex hormone-binding globulin (SHBG) that results in a raised free androgen index (FAI)
what is ovarian failure?
there is a complete cessation of ovarian follicular activity even in the setting of high levels of FSH/LH
what are some causes of premature ovarian failure?
There are a number of possible causes for premature ovarian failure including genetic abnormalities such as Turner’s syndrome (45XO), Turner’s mosaicism (45XO/46XX) and fragile X carrier states.
Other causes of ovarian failure include autoimmune disease, especially co-existent with autoimmune adrenal disease, radiation therapy, chemotherapy and galactosaemia.
when do we give clomiphene during the menstrual cycle?
clomiphene can be given in doses from 25 to 150 mg for cycle days 2 through 6 with ovulation expected at about day 14 of a 28-day cycle.
i.e. given during the follicular phase of the menstrual cycle
what is the main long term risk of untreated PCOS?
endometrial hyperplasia due to unopposed E2 as a result of anovulation
what female/male conditions would make you think that intrauterine insemination is NOT the best option as an artificial reproductive techniques?
any technique using IUI relies on normal patent fallopian tubes and a sufficient number of sperm being available for fertilisation. It is therefore not suitable for tubal disease or moderate to severe male factor infertility.
what is the difference between hysterosalpingogram and saline sonohysterography?
both assess fallopian tube patency
Hysterosalpingography involves the introduction
of radio-opaque material through the cervix
into the uterus and the fallopian tubes. An abdominal
X-ray is then taken.
Sonohysterography, utilises contrast
material introduced through the cervix and ultrasound
visualisation of fill and spill of the material
through the fallopian tubes, into the pelvis and
around the ovaries
what is the risk of gonadotrophin induction of ovulation for infertility?
multiple pregnancy and ovarian hyperstimulation syndrome
describe the general process of IVF
IVF involves induction of multiple follicles with subcutaneous FSH injections and the collection of multiple oocytes under ultrasound control. Fertilisation with the partner’s sperm then occurs in the laboratory. One or two embryos are replaced transcervically into the uterine cavity after 48–72 hours.
what is the main thing that occurs in ovarian hyperstimulation syndrome?
OHSS-vascular hyperpermeability resulting in shift of fluids into the third space e.g. ascites, pleural effusions etc
which types of fibroids can cause issues with fertility?
submucosal fibroids as they disrupt the endometrium
how does a woman take clomiphene for induction of ovulation?
The woman should be given 50 mg to take on day 2–6 of the menstrual cycle, with day 21 progesterone checked to confirm ovulation. If ovulation occurs, then the clomiphene is continued for up to six cycles unless pregnancy occurs. If ovulation is not confirmed then the dose is increased to 100 mg.
what are some ddx for hirsutism?
PCOS
non-classical CAH
idiopathic
androgen hormone secreting tumour
what are two anti-androgenic agents often used for refractive PCOS?
spironolactone and cyproterone acetate
what is the mainstay treatment of idiopathic hirsutism
COCP
what is the medical long term risk of anovulation with PCOS?
unopposed E2 –> endometrial hyperplasia
what is the diagnostic criteria for PCOS?
For PCOS to be diagnosed, the Rotterdam criteria require the presence of at least two of the following:
- polycystic ovary morphology on ultrasound
- oligomenorrhoea or anovulation
- hyperandrogenism, either clinical or biochemical.
or
The ultrasound diagnosis of PCOS requires either: the presence of 12 or more follicles, on either ovary, measuring between 2 and 9 mm; or ovarian volume greater than 10 mL on transvaginal scanning
what is a common cause of male infertility that you must rule out?
varicocoele
what are some lifestyle advice you would advise to a couple who wish to become pregnant?
• Reduce alcohol intake
• Stop smoking both male and female partner
• Folic acid for female partner
• Avoid strenous exercise
• Avoid hot baths/saunas for men
• Weight loss
• Review of medications
• Optimal timing of unprotected sexual intercourse around day of ovulation
• Rhythm method- subtract 14 days from end of cycle to get ovulation day. Have sex 3-4 days leading up to and on ovulation day
• Use home kits to help identify LH surge (urine test usually). LH surge associated with ovulation
• Monitor basal body temperature
Monitor changes in cervical mucus- stretchy egg white cervical mucus= time of ovulation
if clomiphene citrate does not work for infertility, what is your next line of treatment?
Gonadotrophins FSH/LH
• Subcutaneous injections of FSH- treatment course depends on individual basis
Requires blood tests and transvaginal u/s to determine maturity of follicles then an injection of HCG to help ovulate or release this mature oocyte
Describe intracytoplasmic sperm injection
Injecting a single sperm into an egg
Used when the sperm is unable to penetrate the egg wall
Fertilised egg is transferred back to uterus for implantation, same way as IVF
describe in-vitro fertilisation?
- Eggs and sperm are collected and placed into a petri dish for fertilisation
- Often female partner uses clomiphene to induce ovulation of many eggs
- Fertilised egg is then transferred back to uterine cavity for implantation
Stage 1
Ovarian stimulation and triggering of ovulation
Stage 2
Egg retrieval under light sedation, local and GA with suction
Stage 3
Fertilisation in the laboratory
Stage 4
Embryo transfer to uterus
describe intrauterine insemination?
type of artificial insemination
- Injection of sperm directly into the uterus around the time of ovulation
- Commonly used with clomiphene or gonadotrophins
- Used for when there is problems with semen volume or sperm motility or problems with cervical mucus
Sperm donor can be used
what are some signs and symptoms of ovarian hyperstimulation syndrome?
bloating
pain in the abdomen
problems with urination
difficulty breathing
what does ART stand for?
assisted reproductive technology
what are some key questions you should ask in a postmenopausal history?
Check for postmenopausal bleeding
• Have they had a hysterectomy?
• What are their risk factors e.g. breast cancer in the past, smoking, BMI, have they had clots?
• Did they ever take the COCP in the past and did they have any adverse reactions e.g. headaches from it?
• Ascertain risk of osteoporosis
• Enquire about mood, libido, vaginal dryness, vasomotor symptoms
• Enquire about their triggers/relieving factors for symptoms
Ask about impact on QOL
what is your management of premature menopausal women?
BONE DEXA SCAN every 2 yrs; treat osteoporosis if needed
Gold standard treatment is HRT therapy (high dose) till age 51 as we need to protect their bones–> if premature menopause
Manage symptoms as appropriate with other non-hormonal means if HRT is contraindicated due to breast cancer or other CI
Multidisciplinary approach: e.g. Provide psychosocial support as these women are prone to poor body image etc
what are some lifestyle modifications we can suggest for managing menopausal symptoms?
Lose weight if appropriate Exercise 30 mins per day Avoid triggers e.g. spicy foods Fans, cold drink, wet towels for hot flushes Smoking cessation Reduce alcohol intake Avoid caffeine
prior to prescribing HRT for menopausal women, what are some things you must consider first?
First, establish contraindications:
Absolute= previous cardiovascular/cerebrovascular disease, previous venous thromboembolism, smoking, otherwise high CV risk, hx of breast cancer or other hormone dependent cancer
Relative= SLE, diabetes mellitus, abnormal LFTs
Second, consider the following:
• Have they still got a uterus?
• Lowest dose for the shortest time
• HRT is NOT first line for osteoporosis
IF the above is heeded, then can begin HRT
what are some non-HRT ways we can treat vasomotor symptoms and or vaginal dryness?
To treat vasomotor symptoms
1. Gabapentin 2. SSRI/SNRI such as venlafaxine/escitalopram 3. Clonidine
To treat vaginal dryness
• Topical oestrogen- Vagifem cream or Ovestin cream
• Tibolone
what are some options for HRT in a postmenopausal women who still has her uterus?
E2 + constant P- oral
Or Mirena + E2
how long should we use HRT for in a menopausal women post 50 yrs?
trial of HRT should not exceed more than 5 yrs
what is the main difference between HRT prescribed for premature menopausal women and those prescribed for post-menopausal women?
high dose of HRT for premature menopausal women if no contraindications
low dose of HRT for postmenopausal women if no contraindications
alongside managing their symptoms of menopause, what are some other management considerations for a postmenopausal woman?
Are they up to date with pap smears/ mammograms?
Multidisciplinary care for psychosocial/QOL symptoms
Assessment of ongoing CVD and osteoporotic risk
what are some structural anatomic abnormalities that can cause amenorrhoea?
Androgen insensitivity syndrome XY- no uterus
MRKH syndrome- no uterus
Imperforate hymen
what is the hormonal profile for premature ovarian insufficiency?
high FSH, low E2
low AMH
what are your ix for PCOS?
FSH, LH, E2, FBE (look at Day 2-3 LH vs FSH ratio)
T, SHBG–> to calculate free androgen index
If T> 5=look for a T releasing tumour
Transvaginal ultrasound
+/- OGTT
if FSH > 10 in early follicular phase of the cycle, what does this indicate?
ovarian failure
other than a prolactinoma, what could be another cause of hyperprolactinaemia causing infertility?
use of dopamine antagonists such as metoclopramide
so do a thorough medication review
what is your ddx for PCOS?
androgen secreting tumour
what are some ways we can manage PCOS?
COCP containing cyproterone acetate
Mirena for protection of endometrial lining as unopposed E2 –> hyperplasia
Sequential progesterone withdrawal regime in the case patient wants to have children (maintains safe endometrial lining)
Weight loss
Metformin for insulin resistance
Hair removal for hirsutism
a post menopausal 52 yr old woman was commenced on HRT 2 months ago. she comes to see you bc she has noticed some post menopausal bleeding. what do you think is happening?
HRT therapy can cause vaginal bleeding as a side effect
if it persists > 6 months post commencement of HRT, then it warrants further ix
