3.12 Infertility Flashcards

1
Q

What are 2 other endocrine causes (rare) that aren’t related to the hypothalamic-pituitary gonadotrophic axis?

A

androgen receptor deficiency (rare)

hyper/hypothyroidism (reduced bioavailable testosterone)

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2
Q

What is infertility?

A

A disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months of regular unprotected sexual intercourse.
(every 2-3 days)

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3
Q

What is primary infertility?

A

Couple have not had a live birth previously (doesn’t count miscarriages)

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4
Q

What is secondary infertility?

A

when have had a liver birth more than >12 moths previously

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5
Q

How common is infertility?

A

~14% of couples (1 in7)

BUT half of these will conceive in next 12 months (at 24 months, 7%)

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6
Q

What is the most common cause of infertility in a couple?

A
combined male and female factor (30%)
female factor (30%)
male factor (30%)
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7
Q

How can we divide male factor infertility into 3 categories?

A

pre-testicular
testicular
post-testicular

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8
Q

What are some pre-testicular causes of infertility?

A
congenital and acquired endocrinopathies:
Klinefelters Syndrome 47XXY
Y chromosome deletion
Hypothalamic-pituitary-gonadal axis
Testosterone
Prolactin
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9
Q

What are some testicular causes of infertility?

A
congenital - cryptorchidism
infection (STDs)
immunological (anti-sperm)
vascular
trauma/surgery
toxins (chemo, drugs, smoking)
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10
Q

What are some post-testicular causes of infertility?

A
congenital (absence of vas deference is CF)
obstructive azoospermia
iatrogenic (vasectomy)
ED caused by:
- retrograde ejaculations
- mechanical impairment
- psychological
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11
Q

What is cryptorchidism?

A

undescended tested

90% in inguinal canal

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12
Q

How can we categorise infertility in females? (5)

A
Ovarian causes (40%)
Tubal causes (30%)
Uterine causes (10%)
Cervical causes (5%)
Pelvic causes (5%)
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13
Q

What are some ovarian causes of female infertility? (2)

A

anovulation

corpus luteum insufficiency

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14
Q

What are some tubual causes of female infertility? (3)

A

tubopathy due to :

  • infection
  • endometriosis
  • trauma
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15
Q

What are some uterine causes of female infertility? (4)

A

Unfavourable endometrium due to:

  • chronic endometritis (TB)
  • fibroid
  • adhesions
  • congenital malformation
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16
Q

What are some cervical causes of female infertility? (2)

A

ineffective sperm penetration due to:

  • chronic cervicitis
  • immunological (antisperm Ab)
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17
Q

What are some pelvic causes of female infertility? (2)

A

endometriosis

adhesions

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18
Q

What is endometriosis?

A

presence of functioning endometrial tissue outside of the uterus 5% of women

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19
Q

Why does endometriosis cause problems?

A

endometrial tissue continues to respond to oestrogen as normal

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20
Q

What are some symptoms of endometriosis? (4)

A

inc. menstrual pain
menstrual irregularities
deep dyspareunia (pain during sexual intercourse)
infertility

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21
Q

What are some treatments for endometriosis? (4)

A

hormonal
laparoscopic ablation (destroy endometrial tissue outside of uterus)
hysterectomy
bilateral salpingo-oopherectomy (remove both ovaries and fallopian tubes)

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22
Q

What are fibroids?

A

benign tumours of myometrium (also causes problems as respond to oestrogen)

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23
Q

What is the incidence of fibroids in pre-menopausal women?

A

1-20%, incidence increases with age

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24
Q

What are some symptoms of fibroids? (5)

A
usually asymptomatic
inc. menstrual pain
menstrual irregularities
deep dyspareunia
infertility
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25
Q

What is the treatment for fibroids? (2)

A

hormonal (to reduce proliferation)

hysterectomy

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26
Q

What are two main non-endocrine causes of female infertility?

A

endometriosis

fibroids

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27
Q

Explain the hypothalamuic-pituitary-gonadal axis

A

In hypothalamus, kisspeptin neurones activate kisspeptin receptors on GnRH neurones.
GnRH neurones then secrete GnRH into hypophyseal-portal circulation.
GnRH acts on gonadotrophs in anterior pituitary causing them to secrete LH & FSH into the blood.
LH & FSH act on gonads to produce (testosterone and oestrogen)
Oestrogen (aromatised in men) and progesterone provide negative feedback to hypothalamus and anterior pituitary

28
Q

What is the release pattern of GnRH?

A

Pulsatile

29
Q

What is the release pattern of LH & FSH?

A

pulsatile (cyclical in women)

30
Q

What is the release pattern of testosterone?

A

diurnal

31
Q

What would LH, FSH, and testosterone be in hyperprolactinemia?

A
LH = low
FSH = low
Testosterone = low
32
Q

What would LH, FSH, and testosterone be in primary testicular failure (e.g. Klinefelters syndrome)?

A
LH = high
FSH = high
Testosterone = low
33
Q

What is Klinefelters syndrome an example of?

A

primary hypogonadism

34
Q

What are causes of male infertility that affect the hypothalamus?

A

Congenital hypogonadotrophic hypogonadism (asnomic (Kallmann Syndrome), or normosmic)

Acquired hypogonadotrophic hypogonadism (low BMI, excess exercise, stress, anorexia)
Hyperprolactinaemia

35
Q

What are causes of male infertility that affect the anterior pituitary?

A

hypopituitarism

  • remember causes of hypopituitarism
36
Q

What does male infertility affecting the hypothalamus and pituitary have in common?

A

Both known as hypogonadotrophic hypogonadism,

Male fertility problems in pituitary just hypogonadism

37
Q

What are causes of male infertility that affect the gonads?

A

congenital primary hypogonadism (Klinefelters 47 XXY)

acquired primary hypogonadism (cryptorchidism, trauma, chemo, radiation)

38
Q

What is Kalmann’s syndrome caused by?

A

failure of embryological migration of GnRh neurones with olfactory fibers

39
Q

What are the symptoms of Kalmann’s syndrome?

A

anosmia
cryptorchidism
failure of puberty (lack of testicle development, micropenis, primary amenorrhea)
infertility

40
Q

What would tests for Kalmann’s syndrome look like?

A

low GnRH (not measureable)
low FSH and LH
low T

41
Q

How does hyperprolactinaemia cause infertility?

A

prolactin binds to prolactin receptors on kisspeptin neurones in hypothalamus
inhibits kisspeptin release
decreases downstream FSH LH , then T/O
=oligomenorrhorea, amenorrhea, low libido, infertility, osteoporosis

42
Q

What is the treatment for hyperprolacinaemia

A

dopamine agonist (cabergoline)

43
Q

What is Klinefelter’s?

A

XXY

44
Q

What would test results of Klinefelter’s be?

A
high LSH, FH
low T (as problem in the testicles)
45
Q

What are the symptoms of Klinefelter’s?

A
tall stature
decreased facial hair
breast developemnt
mildly impaired IQ
narrow shoulders
reduced chest hair
female type pubic hair pattern
wide hips
low bone density
small penis and testes
infertility
46
Q

What are the main investigations for male infertlity?

A
semen analysis
blood test: morning fasting T, LH, FSH, PRL, Karyotyping
scrotal US/doppler
MRI pituitary
Chlamydia swab
47
Q

What to look for in semen analysis?

A

sperm conc: 15 million/ml

total motility: 40%

48
Q

What are the general lifestyle treatments for male infertility?

A

optimise BMI
smoking cessation
alcohol reduction/cessation

49
Q

What would we see in premature ovarian insufficiency?

A

LH& FSH: high

Oestrogen: low

50
Q

What would we see anorexia induced amenorrhoea?

A

all down (LH FSH Oestodiol)

51
Q

What is premature ovarian insufficiency?

A

same symptoms as menopause
conception still in 20%
high FSH

52
Q

What are some causes of premature ovarian insufficency?

A

autoimmune
genetic - fragile X/Turners syndrome
cancer therapy in past

53
Q

What are some causes of hypergonadotropic hypogonadism in women?

A

premature ovarian insufficiency (aquired and congenital)

Turners (45X0) (congenital)

54
Q

What is the most common endocrine disorder in women?

A

PCOS

55
Q

What is the most common cause of infertility in women?

A

PCOS

56
Q

How do we diagnose PCOS?

A

Rotterdam PCOS criteria (2 out of 3
Oligo or anovulation
Clinical +/- biochemical hyperandrogenism
polycystic ovaries (on ultrasound)

57
Q

How is oligo or anovulation measured?

A

<21 or >35 day cycles
<8 or 9 cycles a year
>90 days for any cycle

58
Q

How is clinical hyperandrogenism measured?

A

acne
hirsutism
alopecia

59
Q

How is biochemical hyperandrogenism measured?

A

raised androgens (testosterone)

60
Q

How is polycystic ovaries measured?

A

> 20 follicles or >10 per ovary

do not use US until 8 years post-menarche due to high incidence of multi-follicular ovaries at this stage

61
Q

Which 2 factors of the Rotterdam PCOS gives the highest risk for impaired metabolism?

A

oligo or anovulation
and
clinical/biochemical hyperandrogenism

62
Q

What are the treatments for PCOS?

A

what is being treated?
irregular menses - oral contraceptive pill
increased endometrial cancer risk - progesterone courses
amenorrhoea and T2D - metformin
infertility - clomiphene, letrozole

63
Q

What is Turners syndrome?

A

45X0

64
Q

What are the symptoms of Turners syndrome?

A
short stature
low hairlines
shield chest
wide spaced nipples
short 4th metacarpal
small fingernails
characteristic faces
webbed neck
coarctation of aorta
poor breast development
elbow deformity
underdeveloped reproductive tract
amenorrhoea
65
Q

What are some tests for female fertility?

A

follicular phase 17-OHP

mid-luteal progesterone = successful ovulation