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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
Q

What are the symptoms of Klinefelter’s syndrome? (11)

A
  • 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)
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26
Q

What do we assess about a patient’s history to diagnose male infertility?

A
  • 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)
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27
Q

What do we assess as part of a patient examination to diagnose male infertility?

A
  • BMI
  • sexual characteristics
  • testicular volume
  • anosmia (lack of smell)
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28
Q

What are the key investigations to diagnose male infertility?

A
  • semen analysis (repeat after 3 months)
  • blood tests
  • imaging
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29
Q

What semen analysis do we carry out to diagnose male infertility?

A
  • volume 1.5ml
  • sperm concentration 15 million/ml
  • total motility 40%
  • azospermia - no sperm
  • oligospermia - reduced sperm
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30
Q

What blood tests do we do to diagnose male infertility?

A
  • LH, FSH, PRL
  • morning fasting testosterone
  • karyotyping
31
Q

What imaging techniques are used to diagnose male infertility?

A
  • scrotal ultrasound/doppler (for varicocoele/obstruction, testicular volume)
  • MRI pituitary (if low LH/FSH or high PRL)
32
Q

What are some general lifestyle treatments for male infertility? (3)

A
  • optimise BMI
  • smoking cessation
  • alcohol reduction/cessation
33
Q

How do you treat hyperprolactinaemia?

A

Dopamine agonist e.g. cabergoline (increased dopamine inhibits prolactin secretion)

34
Q

How do you treat male infertility (for fertility)?

A

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
Q

How do you treat male infertility symptoms if no fertility required?

A

Testosterone (T alone will not stimulate sperm production as LH&FSH needed, will in fact suppress LH&FSH)

36
Q

What is a surgical method to treat male infertility?

A

Surgery - micro testicular sperm extraction (micro TESE)

37
Q

What can the causes of female infertility be divided into?

A
  • ovarian (40%)
  • tubal (30%)
  • uterine (10%)
  • cervical (5%)
  • pelvic (5%)
  • unexplained (10%)
38
Q

What are the ovarian causes of female infertility?

A
  • anovulation
  • corpus luteum insufficiency (not enough progesterone to support early pregnancy)
39
Q

What are the tubal causes of female infertility?

A
  • infection
  • endometriosis
  • trauma
40
Q

What are the uterine causes of female infertility (unfavourable endometrium)?

A
  • congenital malformations
  • infection/inflammation/scarring (adhesions)
  • fibroids
41
Q

What are the cervical causes of female infertility?

A

Ineffective sperm penetration due to:

  • infection/inflammation
  • immunological (antisperm antibodies)
42
Q

What are the pelvic causes of female infertility?

A
  • endometriosis
  • adhesions
43
Q

What is endometriosis?

A
  • presence of functioning endometrial tissue outside the uterus
  • 5% of women
  • responds to oestrogen
44
Q

What are the symptoms of endometriosis?

A
  • increased menstrual pain
  • menstrual irregularities
  • deep dyspareunia (pain during sex)
  • infertility
45
Q

What are fibroids?

A
  • benign tumours of the myometrium
  • 1-20% of pre-menopausal women (increases with age)
  • responds to oestrogen
46
Q

What are the symptoms of fibroids? (5)

A
  • usually asymptomatic (if small)
  • increased menstrual pain
  • menstrual irregularities
  • deep dyspareunia
  • infertility
47
Q

What pattern of LH, FSH and oestradiol would you see in premature ovarian insufficiency?

A
  • LH and FSH high
  • E2 low
48
Q

What is premature ovarian insufficiency (POI)?

A
  • 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
Q

What are the causes of premature ovarian insufficiency (POI)?

A
  • autoimmune
  • genetic e.g. Turner’s syndrome
  • cancer therapy (previous radio/chemotherapy)
50
Q

What pattern of LH, FSH and oestradiol would you see in anorexia nervosa-induced amenorrhoea?

A
  • LH and FSH low
  • E2 low
  • as reduced leptin inhibits kisspeptin
51
Q

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

A
  • congenital hypogonadotrophic hypogonadism e.g. anosmic (Kallmann Syndrome) or normosmic
  • acquired hypogonadotrophic hypogonadism e.g. low BMI, excess exercise, stress, anorexia nervosa
  • hyperprolactinaemia
52
Q

What do diseases affecting the hypothalamus to cause hypogonadism do to GnRH, LH+FSH and E2?

A
  • GnRH down (not measurable)
  • LH and FSH down (hypogonadotrophic)
  • E2 down (hypopgonadism)
53
Q

What diseases are there that affect the pituitary to cause hypogonadism in females? (5)

A
  • tumour
  • infiltration (e.g. of sarcoid/TB)
  • apoplexy (sudden loss of blood supply)
  • surgery
  • radiation
54
Q

What do diseases affecting the pituitary to cause hypogonadism do to LH, FSH and E2?

A
  • LH and FSH down (hypogonadotrophic)
  • E2 down (hypogonadism)
55
Q

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

A
  • polycystic ovarian syndrome (PCOS)
  • congenital primary hypogonadism e.g. Turners (45X0), POI
  • acquired primary hypogonadism e.g. POI, surgery, trauma, chemo, radiation
56
Q

What do diseases affecting the gonads to cause hypogonadism do to LH, FSH and E2?

A
  • LH and FSH up (hypergonadotrophic)
  • E2 down (hypogonadism)
57
Q

What is the epidemiology of PCOS?

A
  • 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
Q

How do we diagnose PCOS?

A
  • exclude other reproductive disorders then use Rotterdam PCOS Diagnostic Criteria (need 2/3):
  • oligo/anovulation
  • clinical +/- biochemical hyperandrogenism
  • polycystic ovaries (US)
59
Q

What is the specific pattern of LH, FSH and E2 seen in PCOS?

A
  • LH:FSH ratio increased
  • normal/low E2
60
Q

How do you assess oligo/anovulation?

A

Normally assessed by menstrual frequency as oligomenorrhoea: <8/9 cycles/year (>35 day cycles)

61
Q

How do you assess clinical +/- biochemical hyperandrogenism?

A
  • clinical - acne, hirsutism (excess hair growth), alopecia
  • biochemical - raised androgens (e.g. testosterone)
62
Q

How do we treat irregular menses/amenorrhoea in PCOS?

A
  • oral contraceptive pill (but not if they want child)
  • metformin
63
Q

How do we treat infertility in PCOS?

A

Ovulation induction e.g. IVF (or clomiphene, letrozole)

Clomiphene = oestradiol receptor modulator
Letrozole = aromatase inhibitor

64
Q

How do we treat increased insulin resistance in PCOS?

A
  • diet and lifestyle
  • metformin
65
Q

How do we treat hirsutism in PCOS?

A
  • anti-androgens e.g. spironolactone
  • creams, waxing, laser
66
Q

How do we treat for increased risk of endometrial cancer in PCOS?

A

Progesterone courses

67
Q

What is Turner’s syndrome (45X0)?

A
  • 1 in 2500 live female births
  • increased FSH and LH but lower E2 (hypergonadotrophic hypogonadism)
68
Q

What are the symptoms of Turner’s syndrome?

A
  • 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
Q

What things do we assess about a patient’s history to diagnose female infertility?

A
  • duration
  • previous children
  • pubertal milestones
  • breastfeeding?
  • menstrual history
  • medications/drugs
  • medical, family, social history
70
Q

What things do we assess as part of a patient examination to diagnose female inferility?

A
  • BMI
  • sexual characteristics
  • hyperandrogenism signs
  • anosmia
71
Q

What are the key investigations to diagnose female infertility?

A
  • pregnancy test (urine/serum hCG)
  • blood tests
  • imaging
72
Q

What blood tests are carried out to diagnose female infertility?

A
  • LH, FSH, PRL
  • oestradiol, androgens
  • mid-luteal progesterone (follicular phase 17-OHP)
  • karyotyping
73
Q

What imaging techniques are used to diagnose female infertility?

A
  • transvaginal ultrasound
  • hysterosalpingogram
  • MRI pituitary (if low LH/FSH or high PRL)

Year 2 - BRS (84 decks)

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