Infertility

Question 1

What is infertility?

Primary Vs secondary infertility?

Answer 1

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

Question 2

How big of an issue is infertility?

Answer 2

1 in 7 couples during the first 12 months of trying

7% of couples in the first 24 months of trying

Question 3

Who causes the infertility predominantly in couples? (males, females, both, unknown)

Answer 3

30% - male factor
30% - female factor
30% - male and female factor
Unkonwn - 10%

Question 4

What are the impacts on the couple and society?

Answer 4

No biological child 
Impact on couples well-being 
Impact on larger family 
Investigation and treatment costs 
Less births = less income tax

Question 5

What are the 3 causes of infertility in males?

Answer 5

1 Pre-testicular (hormones signalling gonads): Congenital and or acquired endocrinopathies

2. Testicular (gonads - testes): Congenital, cryptochidism, infection, STDs, immunological, vascular, trauma / surgery, toxins
3. Post-testicular (sperm on the way out have issues): congenital, erectile dysfunction, obstructive azoospermia, iatrogenic (vasectomy)

Question 6

What is Cryptochidism?

Answer 6

Undescended testes

Increased risk of testicular cancer

Question 7

What are the 6 causes of infertility in females?

What are ovarian causes of female infertility?

Answer 7

Ovarian, Tubal, Uterine, Carvical, Pelvic and unexplained causes

Most common - 40%
Insufficiency of corpus leteum
Lack of egg release (anovulation)

Question 8

What are the tubal causes of female fertility?

Answer 8

Second most common - 30%

Tubopathy due to: infection, endometriosis, trauma

Question 9

What are uterine causes of female infertility?

Answer 9

10% of cases

Unfavourable endometrium due: chronic endometritis (TB), fibroid, adhesions (Synechiae), congenital malformation

Question 10

What are cervical causes of fermale infertility?

Answer 10

10% of cases

Ineffective sperm penetration due: chronic cervicitis, immunological (antisperm Ab)

Question 11

What are the pelvic causes of female infertility?

So what percentage of cases are unexplained?

Answer 11

5% of cases
Endometriosis, adhesions

5%

Question 12

What is endometriosis and how does it cause infertility?

What are the symptoms of this?

Answer 12

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

Question 13

What are the treatments available for endometriosis?

Answer 13

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)

Question 14

What are fibroids and how do they cause infertility?

What are the symptoms of this?

Answer 14

Benign tumours of the myometrium - can block fallopian tubes, responds to oestrogen

Usually asymptomatic
Sometimes: Increased menstrual pain
Menstrual irregularities
Deep dyspareunia
Infertility

Question 15

What are the treatment options for fibroids?

Answer 15

Hormonal interventions (eg continuous OCP, prog, continuous GnRH agonists)
Hysterectomy

Question 16

What is the hypothalamic-pituitary-gonadal axis?

Answer 16

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

Question 17

What are the levels of LH, FSH, and testosterone in males with hyperprolactinaemia?

Answer 17

Hypogonadotrophic = low FSH and LH

Low testosterone due to low FSH and LH

Question 18

What are the levels of LH, FSH, and testosterone in males with Primary Testicular Failure (e.g. Klinefelters Syndrome)?

Answer 18

LH and FSH high

Low testosterone, no negative feedback results in continuous high LH / FSH

Question 19

How can hypo and hyperthyroidism cause low fertility in males?

Answer 19

Reduced bioavailable testosterone

Question 20

What are the endocrine hypothalamus causes for male fertility?

Answer 20

Congenital hypogonadotrophic hypogonadism (e.g. Kallmann Syndrome)

Acquired hypogonadotrophic hypogonadism (suppression of hypothalamus due to stress, excess exercise, low BMI etc)

Hyperprolactinaemia

Question 21

What are the endocrine pituitary causes for male infertility?

Answer 21

Hypopituitarism e.g. due to tumour, infiltration (of TB etc.), apoplexy, (haemorrhage) surgery, radiation damage

Question 22

What are the endocrine gonadal causes for male infertility?

Answer 22

Congenital primary hypogonadism (e.g. Klinefelters - XXY)

Acquired Primary Hypogonadism e.g. cryptochidrism, trauma, chemo, radiation etc.

Question 23

What is Kallmann’s Syndrome?

How does it present (reproductive features)?

Answer 23

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

Question 24

How does prolactin inhibit kisspeptin neurons?

How does hyperprolactinaemia present?

What is the treatment for this?

Answer 24

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

Question 25

What are some causes of hyperprolactinaemia?

Answer 25

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

Question 26

What is Klinefeiter's Syndrome? Symptoms / features?

Answer 26

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 ```

Question 27

What is the clinical process for male infertility investigation? [Pre-referral to infertility clinic]

Answer 27

1. Initial history - age of pubertal mile stones, previous kids, testosterone deficiency, prolactinomas, medical and surgical history, lifestyle history, family history of infertility, medicine history 2. Examination - BMI, sexual characteristics (testicular volume - 15 ml), anosmia, other endocrine signs 3. 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)

Question 28

What are the treatments for male fertility?

Answer 28

1. General lifestyle - optimise BMI, smoking cessation, alcohol reduction / cessation 2. Specific Treatment = dopamine agonist for hyperPRL Gonadotrophin treatment for fertility Testosterone to treat symptoms Surgery - micro testicular sperm extraction

Question 29

What are the levels of LH, FSH, and oestrogen in females with premature ovarian insufficiency (POI)?

Answer 29

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

Question 30

What is POI and how does it present? What are the causes?

Answer 30

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

Question 31

What are the levels of LH, FSH, and oestrogen in females with anorexia nervosa induced amenorrhoea?

Answer 31

LH, FSH and oestrogen levels are low (due to extreme weight loss, intense exercise routines and/or increased levels of stress)

Question 32

What are the endocrine hypothalamic causes for female infertility?

Answer 32

Congenital hypogonadotrophic hypogonadism - e.g. Kallmann's Syndrome Acquired hypogonadotrophic hypogonadism - low BMI, excess exercise, stress Hyperprolatinaemia

Question 33

What are the endocrine pituitary causes for female infertility?

Answer 33

Hypopituitarism - tumour, infiltration (of TB etc.), apoplexy, surgery, radiation

Question 34

What are the endocrine gonadal causes for female infertility?

Answer 34

PCOS POI Turners Syndrome (X opposed to XX)

Question 35

How can hypo and hyperthyroidism cause low fertility in females?

Answer 35

Reduced bioavailability of oestradiol

Question 36

What is PCOS?

Answer 36

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

Question 37

How is PCOS diagnosed?

Answer 37

Exclude other reproductive disorders 1. 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 2. Clinical / biochemical hyperandrogenism: acne, alopecia (spot baldness); biochemical = raised androgens 3. Polycystic ovaries = not used alone to diagnose PCOS as many people have POs

Question 38

What are the treatments for PCOS?

Answer 38

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

Question 39

What is Turner's syndrome? How does it present?

Answer 39

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 ```

Question 40

How is female infertility assessed clinically? [pre-referral to infertility clinic]

Answer 40

1. Initial History: breastfeeding, pregnancies, menstrual history and symptoms, family and social history, medication and surgical history 2. Examination = BMI, sexual characteristics, hyperandrogenism signs, pelvic examination, other endocrine signs, anosmia, syndromic features 3. 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)