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Year 2 - BRS > 3.12 - Infertility > Flashcards

3.12 - Infertility Flashcards

1
Q

What is infertility?

A
  • a disease of the reproductive system defined by failure to achieve a clinical pregnancy after >12 months of regular unprotected sexual intercourse
  • regular intercourse = every 2-3 days
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2
Q

What is primary infertility?

A

When a couple have not had a live birth previously

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3
Q

What is secondary infertility?

A

When a couple has had a live birth >12 months previously

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4
Q

What are some stats about the epidemiology of infertility?

A
  • affects 1 in 7 couples - but half of these will then conceive in the next 12 months (i.e. at 24 months, 1 in 14 couples affected)
  • 55% will seek help and there is a positive correlation with socioeconomic status
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5
Q

What are the four most common causes of infertility in a couple?

A
  • male factor (30%)
  • female factor (30%)
  • combined male and female factor (30%)
  • unknown factor (10%)
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6
Q

How can infertility cause psychological distress to a couple? (5)

A
  • no biological child
  • impact on couple’s wellbeing
  • impact on larger family
  • investigations
  • treatments (often fail)
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7
Q

What is the impact of infertility on society?

A
  • less births
  • less tax income
  • investigation costs
  • treatment costs
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8
Q

What can the causes of infertility in males be divided into?

A
  • pre-testicular (before sperm production)
  • testicular (during sperm production)
  • post-testicular (after sperm production)
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9
Q

What are the pre-testicular causes of male infertility?

A
  • congenital and acquired endocrinopathies:
  • Klinefelters 47XXY
  • Y chromosome deletions
  • HPG axis issues, testosterone and prolactin issues
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10
Q

What are the testicular causes of male infertility?

A
  • congenital
  • cryptorchidism
  • infection (STDs)
  • immunological (antisperm antibodies)
  • vascular (varicocoele)
  • trauma/surgery
  • toxins (chemo/radiotherapy/drugs/smoking)
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11
Q

What is cryptorchidism?

A
  • normal pathway for testis descent during embryo development is through inguinal canal from abdomen
  • in cryptorchidism, the testes do not descend (90% stuck in inguinal canal)
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12
Q

What are the post-testicular causes of male infertility?

A
  • congenital (absence of vas deferens in cystic fibrosis)
  • obstructive azoospermia (obstruction of sperm leaving testicles)
  • erectile dysfunction (retrograde ejaculation, mechanical impairment, psychological)
  • iatrogenic (vasectomy)
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13
Q

What pattern of LH, FSH and T would you see in hyperprolactinaemia?

A
  • LH down
  • FSH down
  • T down
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14
Q

What pattern of LH, FSH and T would you see in primary testicular failure (e.g. in Klinefelter’s)?

A
  • LH up
  • FSH up
  • T down
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15
Q

What diseases are there that affect the hypothalamus to cause hypogonadism in males?

A
  • congenital hypogonadotrophic hypogonadism e.g. anosmic (Kallmann Syndrome) or normosmic
  • acquired hypogonadotrophic hypogonadism e.g. low BMI, excess exercise, stress, anorexia nervosa
  • hyperprolactinaemia
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16
Q

What do diseases affecting the hypothalamus to cause hypogonadism do to GnRH, LH+FSH and T?

A
  • GnRH down (not measurable)
  • LH and FSH down (hypogonadotrophic)
  • T down (hypopgonadism)
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17
Q

What diseases are there that affect the pituitary to cause hypogonadism in males?

A
  • tumour
  • infiltration (e.g. of sarcoid/TB)
  • apoplexy (sudden loss of blood supply)
  • surgery
  • radiation
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18
Q

What do diseases affecting the pituitary to cause hypogonadism do to LH, FSH and T?

A
  • LH and FSH down (hypogonadotrophic)
  • T down (hypogonadism)
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19
Q

What diseases are there that affect the gonads to cause hypogonadism in males?

A
  • congenital primary hypogonadism e.g. Klinefelter’s 47XXY
  • acquired primary hypogonadism e.g. cryptorchidism, trauma, chemo, radiation
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20
Q

What do diseases affecting the gonads to cause hypogonadism do to LH, FSH and T?

A
  • LH and FSH up (hypergonadotrophic)
  • T down (hypogonadism)
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21
Q

What causes Kallmann’s syndrome?

A
  • within first 10 weeks of conception, GnRH neurones migrate from olfactory placode in the primitive nose to the hypothalamus along with olfactory fibres
  • failure of migration of GnRH neurons with olfactory fibres causes Kallmann’s
  • low LH and FSH and T
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22
Q

What are the symptoms of Kallmann’s syndrome?

A
  • anosmia - inability to smell
  • failure of puberty - lack testicle development, micropenis, primary amenorrhoea
  • infertility
  • cryptorchidism
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23
Q

How does hyperprolactinaemia inhibit the HPG axis?

A
  • prolactin binds to prolactin receptors on kisspeptin neurons in hypothalamus
  • inhibits kisspeptin release
  • decreases downstream GnRH/LH/FSH/oest
  • oligo/amenorrhoea, low libido, infertility, osteoporosis etc
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24
Q

What is Klinefelter’s syndrome?

A
  • where males have XXY
  • 1-2/1000 births (fairly common)
  • high LH&FSH, low T (hypergonadotrophic hypogonadism)
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25
What are the symptoms of Klinefelter's syndrome? (11)
- tall stature - mildly impaired IQ - reduced facial hair - narrow shoulders - breast development - reduced chest hair - wide hips - female-type pubic hair pattern - low bone density - small penis and testes - infertility (accounts for up to 3% of cases)
26
What do we assess about a patient's history to diagnose male infertility?
- duration - previous children - pubertal milestones - associated symptoms (e.g. T deficiency, PRL symptoms, congenital hypogonadotrophic hypogonadism) - medications/drugs - medical, family and social history - (symptoms: loss of libido, osteoporosis, small testes, impotence/ED, decreased muscle bulk = LOSID)
27
What do we assess as part of a patient examination to diagnose male infertility?
- BMI - sexual characteristics - testicular volume - anosmia (lack of smell)
28
What are the key investigations to diagnose male infertility?
- semen analysis (repeat after 3 months) - blood tests - imaging
29
What semen analysis do we carry out to diagnose male infertility?
- volume 1.5ml - sperm concentration 15 million/ml - total motility 40% - azospermia - no sperm - oligospermia - reduced sperm
30
What blood tests do we do to diagnose male infertility?
- LH, FSH, PRL - morning fasting testosterone - karyotyping
31
What imaging techniques are used to diagnose male infertility?
- scrotal ultrasound/doppler (for varicocoele/obstruction, testicular volume) - MRI pituitary (if low LH/FSH or high PRL)
32
What are some general lifestyle treatments for male infertility? (3)
- optimise BMI - smoking cessation - alcohol reduction/cessation
33
How do you treat hyperprolactinaemia?
Dopamine agonist e.g. cabergoline (increased dopamine inhibits prolactin secretion)
34
How do you treat male infertility (for fertility)?
Gonadotrophin treatment (will also increase testosterone) - subcutaneous gonadotropin injections for sperm induction (hCG injections which act on LH receptors, if no response after 6 months add FSH injections)
35
How do you treat male infertility symptoms if no fertility required?
Testosterone (T alone will not stimulate sperm production as LH&FSH needed, will in fact suppress LH&FSH)
36
What is a surgical method to treat male infertility?
Surgery - micro testicular sperm extraction (micro TESE)
37
What can the causes of female infertility be divided into?
- ovarian (40%) - tubal (30%) - uterine (10%) - cervical (5%) - pelvic (5%) - unexplained (10%)
38
What are the ovarian causes of female infertility?
- anovulation - corpus luteum insufficiency (not enough progesterone to support early pregnancy)
39
What are the tubal causes of female infertility?
- infection - endometriosis - trauma
40
What are the uterine causes of female infertility (unfavourable endometrium)?
- congenital malformations - infection/inflammation/scarring (adhesions) - fibroids
41
What are the cervical causes of female infertility?
Ineffective sperm penetration due to: - infection/inflammation - immunological (antisperm antibodies)
42
What are the pelvic causes of female infertility?
- endometriosis - adhesions
43
What is endometriosis?
- presence of functioning endometrial tissue outside the uterus - 5% of women - responds to oestrogen
44
What are the symptoms of endometriosis?
- increased menstrual pain - menstrual irregularities - deep dyspareunia (pain during sex) - infertility
45
What are fibroids?
- benign tumours of the myometrium - 1-20% of pre-menopausal women (increases with age) - responds to oestrogen
46
What are the symptoms of fibroids? (5)
- usually asymptomatic (if small) - increased menstrual pain - menstrual irregularities - deep dyspareunia - infertility
47
What pattern of LH, FSH and oestradiol would you see in premature ovarian insufficiency?
- LH and FSH high - E2 low
48
What is premature ovarian insufficiency (POI)?
- same symptoms as menopause - previously called premature ovarian failure (POF) - conception can happen in 20% of cases - diagnosis: high FSH > 25 iU/L (x2 at least 4wks apart)
49
What are the causes of premature ovarian insufficiency (POI)?
- autoimmune - genetic e.g. Turner's syndrome - cancer therapy (previous radio/chemotherapy)
50
What pattern of LH, FSH and oestradiol would you see in anorexia nervosa-induced amenorrhoea?
- LH and FSH low - E2 low - as reduced leptin inhibits kisspeptin
51
What diseases are there that affect the hypothalamus to cause hypogonadism in females?
- congenital hypogonadotrophic hypogonadism e.g. anosmic (Kallmann Syndrome) or normosmic - acquired hypogonadotrophic hypogonadism e.g. low BMI, excess exercise, stress, anorexia nervosa - hyperprolactinaemia
52
What do diseases affecting the hypothalamus to cause hypogonadism do to GnRH, LH+FSH and E2?
- GnRH down (not measurable) - LH and FSH down (hypogonadotrophic) - E2 down (hypopgonadism)
53
What diseases are there that affect the pituitary to cause hypogonadism in females? (5)
- tumour - infiltration (e.g. of sarcoid/TB) - apoplexy (sudden loss of blood supply) - surgery - radiation
54
What do diseases affecting the pituitary to cause hypogonadism do to LH, FSH and E2?
- LH and FSH down (hypogonadotrophic) - E2 down (hypogonadism)
55
What diseases are there that affect the gonads to cause hypogonadism in females?
- polycystic ovarian syndrome (PCOS) - congenital primary hypogonadism e.g. Turners (45X0), POI - acquired primary hypogonadism e.g. POI, surgery, trauma, chemo, radiation
56
What do diseases affecting the gonads to cause hypogonadism do to LH, FSH and E2?
- LH and FSH up (hypergonadotrophic) - E2 down (hypogonadism)
57
What is the epidemiology of PCOS?
- affects 5-15% of women of reproductive age - frequent family history - most common endocrine disorder in women - most common cause of infertility in women
58
How do we diagnose PCOS?
- exclude other reproductive disorders then use **Rotterdam PCOS Diagnostic Criteria** (need 2/3): - oligo/anovulation - clinical +/- biochemical hyperandrogenism - polycystic ovaries (US)
59
What is the specific pattern of LH, FSH and E2 seen in PCOS?
- LH:FSH ratio increased - normal/low E2
60
How do you assess oligo/anovulation?
Normally assessed by menstrual frequency as oligomenorrhoea: <8/9 cycles/year (>35 day cycles)
61
How do you assess clinical +/- biochemical hyperandrogenism?
- clinical - acne, hirsutism (excess hair growth), alopecia - biochemical - raised androgens (e.g. testosterone)
62
How do we treat irregular menses/amenorrhoea in PCOS?
- oral contraceptive pill (but not if they want child) - metformin
63
How do we treat infertility in PCOS?
Ovulation induction e.g. IVF (or clomiphene, letrozole) ## Footnote Clomiphene = oestradiol receptor modulator Letrozole = aromatase inhibitor
64
How do we treat increased insulin resistance in PCOS?
- diet and lifestyle - metformin
65
How do we treat hirsutism in PCOS?
- anti-androgens e.g. spironolactone - creams, waxing, laser
66
How do we treat for increased risk of endometrial cancer in PCOS?
Progesterone courses
67
What is Turner's syndrome (45X0)?
- 1 in 2500 live female births - increased FSH and LH but lower E2 (hypergonadotrophic hypogonadism)
68
What are the symptoms of Turner's syndrome?
- short stature - characteristic facies - low hairline - webbed neck - **coarctation of aorta** - shield chest - poor breast development - wide spaced nipples - elbow deformity - short 4th metacarpal - small fingernails - underdeveloped reproductive tract - amenorrhoea - brown nevi
69
What things do we assess about a patient's history to diagnose female infertility?
- duration - previous children - pubertal milestones - breastfeeding? - menstrual history - medications/drugs - medical, family, social history
70
What things do we assess as part of a patient examination to diagnose female inferility?
- BMI - sexual characteristics - hyperandrogenism signs - anosmia
71
What are the key investigations to diagnose female infertility?
- pregnancy test (urine/serum hCG) - blood tests - imaging
72
What blood tests are carried out to diagnose female infertility?
- LH, FSH, PRL - oestradiol, androgens - mid-luteal progesterone (follicular phase 17-OHP) - karyotyping
73
What imaging techniques are used to diagnose female infertility?
- transvaginal ultrasound - hysterosalpingogram - MRI pituitary (if low LH/FSH or high PRL)

Year 2 - BRS (84 decks)

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