Infertility Flashcards
What is infertility?
Primary Vs secondary infertility?
A disease of the reproductive system defined by the failure to achieve clinical prenancy after 12 months of regular unprotected sexual intercourse
Primary = no live births previously Secondary = had a live birth previously
How big of an issue is infertility?
1 in 7 couples during the first 12 months of trying
7% of couples in the first 24 months of trying
Who causes the infertility predominantly in couples? (males, females, both, unknown)
30% - male factor
30% - female factor
30% - male and female factor
Unkonwn - 10%
What are the impacts on the couple and society?
No biological child Impact on couples well-being Impact on larger family Investigation and treatment costs Less births = less income tax
What are the 3 causes of infertility in males?
1 Pre-testicular (hormones signalling gonads): Congenital and or acquired endocrinopathies
- Testicular (gonads - testes): Congenital, cryptochidism, infection, STDs, immunological, vascular, trauma / surgery, toxins
- Post-testicular (sperm on the way out have issues): congenital, erectile dysfunction, obstructive azoospermia, iatrogenic (vasectomy)
What is Cryptochidism?
Undescended testes
Increased risk of testicular cancer
What are the 6 causes of infertility in females?
What are ovarian causes of female infertility?
Ovarian, Tubal, Uterine, Carvical, Pelvic and unexplained causes
Most common - 40%
Insufficiency of corpus leteum
Lack of egg release (anovulation)
What are the tubal causes of female fertility?
Second most common - 30%
Tubopathy due to: infection, endometriosis, trauma
What are uterine causes of female infertility?
10% of cases
Unfavourable endometrium due: chronic endometritis (TB), fibroid, adhesions (Synechiae), congenital malformation
What are cervical causes of fermale infertility?
10% of cases
Ineffective sperm penetration due: chronic cervicitis, immunological (antisperm Ab)
What are the pelvic causes of female infertility?
So what percentage of cases are unexplained?
5% of cases
Endometriosis, adhesions
5%
What is endometriosis and how does it cause infertility?
What are the symptoms of this?
Presence of functioning endometrial tissue outside of the uterus - responds to oestrogen so can distort anatomy, cause scarring of fallopian tubes, inflame pelvic structures, etc.
Increased menstrual pain
Menstrual irregularities
Deep dyspareunia (recurring pain the genitals during intercourse)
Infertility
What are the treatments available for endometriosis?
Hormonal (eg continuous OCP, prog)
Laparascopic ablation (excision of endometriosis visible in the pelvis)
Hysterectomy (surgical removal of the womb)
Bilateral Salpingo-oophorectomy (surgical removal of the womb and fallopian tubes)
What are fibroids and how do they cause infertility?
What are the symptoms of this?
Benign tumours of the myometrium - can block fallopian tubes, responds to oestrogen
Usually asymptomatic Sometimes: Increased menstrual pain Menstrual irregularities Deep dyspareunia Infertility
What are the treatment options for fibroids?
Hormonal interventions (eg continuous OCP, prog, continuous GnRH agonists) Hysterectomy
What is the hypothalamic-pituitary-gonadal axis?
Hypothalamus contains kisspeptin neurons, which release kisspeptin to trigger GnRH release into the hypophyseal portal circulation
GnRH travels to the pituitary and stimulates gonadotrophs to release LH and FSH
LH and FSH reach the gonads = oestrogen release in females, and testosterone in males
Oestrogen = negative feedback on GnRH Progesterone = negative feedback on the kisspeptin neurons
What are the levels of LH, FSH, and testosterone in males with hyperprolactinaemia?
Hypogonadotrophic = low FSH and LH
Low testosterone due to low FSH and LH
What are the levels of LH, FSH, and testosterone in males with Primary Testicular Failure (e.g. Klinefelters Syndrome)?
LH and FSH high
Low testosterone, no negative feedback results in continuous high LH / FSH
How can hypo and hyperthyroidism cause low fertility in males?
Reduced bioavailable testosterone
What are the endocrine hypothalamus causes for male fertility?
Congenital hypogonadotrophic hypogonadism (e.g. Kallmann Syndrome)
Acquired hypogonadotrophic hypogonadism (suppression of hypothalamus due to stress, excess exercise, low BMI etc)
Hyperprolactinaemia
What are the endocrine pituitary causes for male infertility?
Hypopituitarism e.g. due to tumour, infiltration (of TB etc.), apoplexy, (haemorrhage) surgery, radiation damage
What are the endocrine gonadal causes for male infertility?
Congenital primary hypogonadism (e.g. Klinefelters - XXY)
Acquired Primary Hypogonadism e.g. cryptochidrism, trauma, chemo, radiation etc.
What is Kallmann’s Syndrome?
How does it present (reproductive features)?
Congenital defect in the hypothalamic travelling of GnRH
Low GnRH = low LH/FSH = low T
Micropenis No pubic hair Cryptorchidism (undescended testes) In females - primary amenorrhoea Ultimately - infertility
How does prolactin inhibit kisspeptin neurons?
How does hyperprolactinaemia present?
What is the treatment for this?
Prolactin binds to kisspeptin neurons in the hypothalamus
Inhibits kisspeptin release
Decreased GnRH production downstream - low LH/FSH = low testosterone
Presents = Lack of shaving, lack of public hair, osteoporosis, infertility
Treatment = Dopamine agonist, or surgery
What are some causes of hyperprolactinaemia?
Prolactinoma (macro / micro depending on size)
Pituitary stalk compression
Pregnancy / breast feeding
Medications (OCP, anti-emetics, dop antagonists, anti-psychotics)
Smaller rises in PCOS and hypothyroidism
What is Klinefeiter’s Syndrome?
Symptoms / features?
XXY abnormality (as opposed to XY)
Tall stature Reduced chest and facial hair Breast development Wide hips Low bone density Small penis and testes Infertility Mildly impaired IQ Narrow shoulders
What is the clinical process for male infertility investigation?
[Pre-referral to infertility clinic]
- Initial history - age of pubertal mile stones, previous kids, testosterone deficiency, prolactinomas, medical and surgical history, lifestyle history, family history of infertility, medicine history
- Examination - BMI, sexual characteristics (testicular volume - 15 ml), anosmia, other endocrine signs
- Investigations = semen analysis 1.5ml or greater and 40% motility. Blood test: look at LH and FSH (look for hyper/hypo-gonadism), SHBG and albumin= most testosterone bound to that, morning fasting testosterone levels, iron levels, thyroid function, karyotyping. Microbiology (urine test and chlamydia swab). Imaging (scrotal US, MRI pituitary to look for issues with the gland)
What are the treatments for male fertility?
- General lifestyle - optimise BMI, smoking cessation, alcohol reduction / cessation
- Specific Treatment = dopamine agonist for hyperPRL
Gonadotrophin treatment for fertility
Testosterone to treat symptoms
Surgery - micro testicular sperm extraction
What are the levels of LH, FSH, and oestrogen in females with premature ovarian insufficiency (POI)?
High LH and FSH
Low oestrogen as the ovaries stop working, so stop producing oestrogen - lack of negative feedback leads to high LH and FSH
What is POI and how does it present?
What are the causes?
Ovaries stop working before the age of 40, similar symptoms to menopause
Conception can happen in 20%
Autoimmune
Genetic - e.g. Turner’s Syndrome
Cancer therapy
What are the levels of LH, FSH, and oestrogen in females with anorexia nervosa induced amenorrhoea?
LH, FSH and oestrogen levels are low (due to extreme weight loss, intense exercise routines and/or increased levels of stress)
What are the endocrine hypothalamic causes for female infertility?
Congenital hypogonadotrophic hypogonadism - e.g. Kallmann’s Syndrome
Acquired hypogonadotrophic hypogonadism - low BMI, excess exercise, stress
Hyperprolatinaemia
What are the endocrine pituitary causes for female infertility?
Hypopituitarism - tumour, infiltration (of TB etc.), apoplexy, surgery, radiation
What are the endocrine gonadal causes for female infertility?
PCOS
POI
Turners Syndrome (X opposed to XX)
How can hypo and hyperthyroidism cause low fertility in females?
Reduced bioavailability of oestradiol
What is PCOS?
V. common condition affecting how a woman’s ovaries work
5-15% of women of reproductive age affected - esp. in patient with freq. family history of PCOS
How is PCOS diagnosed?
Exclude other reproductive disorders
- Oligo/anovulation: measured by menstrual cycle lengths and freq., ultrasound to see corpus luteum, or if necessary anovulation can be proven by lack of progesterone rise
- Clinical / biochemical hyperandrogenism: acne, alopecia (spot baldness); biochemical = raised androgens
- Polycystic ovaries = not used alone to diagnose PCOS as many people have POs
What are the treatments for PCOS?
Irregular menses = infertility = oral contraceptive pill or metformin
Increased insulin resistance = metformin
Hirustism (male-like hair growth) = anti-androgens, creams, waxing
Increased risk of endometrial cancer = progesterone courses
What is Turner’s syndrome?
How does it present?
X (opposed to XX)
Short stature Low hairline Shield chest Webbed neck Poor breast development Wide spaced nipples Small fingernails Short 4th metacarpal Small breasts Amenorrhoea Elbow deformity
How is female infertility assessed clinically?
[pre-referral to infertility clinic]
- Initial History: breastfeeding, pregnancies, menstrual history and symptoms, family and social history, medication and surgical history
- Examination = BMI, sexual characteristics, hyperandrogenism signs, pelvic examination, other endocrine signs, anosmia, syndromic features
- Investigations = Blood test: look at mid-luteal prog = previous release of egg, LH and FSH and PRL (look for hyper/hypo-gonadism), SHBG and albumin = most oestrogen bound to that, oestradiol and androgen levels, iron levels, thyroid function, karyotyping. Microbiology (urine test and chlamydia swab). Pregnancy test (urine or serum HCG), Imaging (transvaginal US, pituitary MRI if low LH/FSH or high PRL)
