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brs (phase 1b) > (endo) infertility > Flashcards

(endo) infertility Flashcards

1
Q

define 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

(regular sexual intercourse = every 2-3 days)

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2
Q

define primary infertility

A

infertility in a couple that has previously not had a LIVE birth

(i.e. miscarriage/stillborns would still qualify as infertility)

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3
Q

define secondary infertility

A

infertility in a couple that has previously had a live birth >12 months ago

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4
Q

what is the most common cause of infertility in couples?

A

male factor, female factor or combined

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5
Q

what are the main causes of infertility in males?

A

1) pre-testicular
2) testicular
3) post-testicular

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6
Q

what are the pre-testicular causes of infertility?

A

congenital + acquired endocrinopathies

  • Klienfelter’s 47XXY, Y chromosome deletion, HPG, T, PRL
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7
Q

what are the testicular causes of infertility?

A
  • cryptorchidism
  • infection (STDs)
  • trauma/surgery
  • immunological (antisperm Abs)
  • toxins (chemo, drugs smoking)
  • vascular (varicocele)
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8
Q

what are the post-testicular causes of infertility?

A

1) congenital (absence of vas deferens)
2) obstructive azoospermia
3) erectile dysfunction (retrograde ejaculation, mechanical impairment, psychological)
4) iatrogenic (vasectomy)

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9
Q

what is obstructive azoospermia?

A

obstruction to sperm leaving the testicels

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10
Q

what is retrograde ejaculation?

A

when semen enters the bladder instead of emerging through the penis

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11
Q

what is cryptorchidism?

A

a condition wherein one/both testicles fail to move from the abdomen, where they develop, into the scrotum

(i.e. undescended testes)

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12
Q

what is the normal path for testicular descent?

A

through the inguinal canal

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13
Q

where are the majority of undescended testes usually found?

A

inguinal canal

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14
Q

what are the main causes of infertility in females?

A

1) ovarian causes
2) tubal causes
3) uterine causes
4) cervical causes
5) pelvic causes
6) unexplained

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15
Q

what are possible ovarian causes of infertility in females?

A
  • anovulation

- corpus luteum insifficiency

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16
Q

what are possible tubal causes of infertility in females?

A
  • infection
  • endometriosis
  • trauma
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17
Q

what are possible uterine causes of infertility in females?

A

unfavourable endometrium:

  • chronic endometriosis (TB)
  • fibroids
  • adhesions (synechiae)
  • congenital malformation
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18
Q

what are possible cervical causes of infertility in females?

A
  • chronic cervicitis

- immunological (antisperm antibodies)

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19
Q

what are possible pelvic causes of infertility in females?

A
  • endometriosis

- adhesions

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20
Q

how is anovulation a cause of infertility?

A

(ovarian cause)

the HPG axis controlling ovarian hormones and ovulation is ineffective

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21
Q

how is corpus luteum insufficiency a cause of infertility?

A

the corpus luteum may not secrete sufficient amounts of progesterone to maintain an early pregnancy

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22
Q

what is the role of progesterone in terms of the endometrium?

A

transforms the endometrium into a receptive state to enable blastocyst implantation

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23
Q

what can cause chronic endometriosis?

A

(uterine causes)

can be caused due to TB

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24
Q

what is chronic cervicitis?

A

(cervical causes)
chronic inflammation of the cervix

= ineffective sperm penetration

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25
Q

what is endometriosis?

A

presence of functioning endometrial tissue outside the uterus

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26
Q

what does endometrial tissue respond to and why is this a problem?

A

endometrial tissue responds to oestrogen

= and so if it is present where it should not be (i.e. in endometriosis), can proliferate + bleed in response to oestrogen

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27
Q

what are the symptoms of endometriosis?

A
  • increased menstrual pain
  • menstrual irregularities
  • deep dyspareunia (painful intercourse)
  • infertility
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28
Q

why do patients with endometriosis experience more menstrual pain?

A

there is more endometrial tissue that responds to oestrogen

= more pain overall

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29
Q

how is endometriosis treated?

A

1) hormonal (continuous, OCP, progesterone)
2) laparoscopic ablation
3) hysterectomy
4) bilateral salpingo-oopherectomy (removal of both ovaries and fallopian tubes)

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30
Q

what are fibroids?

A

benign tumours of the myometrium

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31
Q

how common is endometriosis?

A

experienced by 5% of women

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32
Q

how common are fibroids?

A

experienced by 1-20% of pre-menopausal women

(more common

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33
Q

what do fibroids respond to?

A

respond to oestrogen

similar to endometriosis

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34
Q

what are the symptoms of fibroids?

A

usually asymptomatic BUT can experience

  • increased menstrual pain
  • menstrual irregularities
  • deep dyspareunia
  • infertility
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35
Q

how are fibroids treated?

A

1) hormonal (continuous, OCP, progesterone, continuous GnRH agonists)
2) hysterectomy

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36
Q

where are fibroids usually found?

A

1) subserosal
2) intramural
3) submucosal
4) pedunculated subserosal

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37
Q

which hormone is mainly involved in the negative feedback loop of the HPG axis?

A

oestrogen, testosterone and progesterone

BUT mainly oestrogen in both women and men (aromatised from testosterone)

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38
Q

which blood test results are expected in patients with hyperprolactinaemia?

A 
LH = low
FSH = low
testosterone = low
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39
Q

which blood test results are expected in patients with primary testicular failure?

A 
LH = high
FSH = high
testosterone = low

hypergonadotrophic hypogonadism

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40
Q

what is primary testicular failure also known as?

A

hypergonadotropic hypogonadism

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41
Q

what blood test results are expected in hypergonadotrophic hypogonadism?

A

LH + FSH = high

testosterone = low

42
Q

give examples of hypergonadotrophic hypogonadism

A

1) congenital = Klinefelter’s 47XXY

2) acquired = cryptorchidism, trauma, surgery, infection, immunological, chemo, radiation

43
Q

what blood test results are expected in hypogonadotrophic hypogonadism?

A

either
1) high GnRH; low LH + FSH; low T

2) low GnRH; low LH + FSH; low T

44
Q

what are the possible causes of the following:

  • high GnRH
  • low LH + FSH
  • low T
A

pituitary problems (e.g. surgery, radiotherapy, apoplexy, infection, tumour)

= hypopituitarism

45
Q

what are the possible causes of the following:

  • low GnRH
  • low LH + FSH
  • low T
A

1) congenital = anosmic (Kallmann syndrome) or normosmic
2) acquired = low BMI, excess exercise, stress
3) hyperprolactinaemia

46
Q

what are the non-HPG axis related causes of male infertility?

A

1) androgen receptor deficiency

2) hyper/hypothyroidism

47
Q

how can hyper/hypothyroidism lead to male infertility?

A

hyperthyroidism = increases SHBG so reduced free testosterone

hypothyroidism = decreased testosterone secretion

48
Q

what is Kallmann syndrome?

A

a disorder which combines an impaired ability to smell with hormonal and endocrine imbalances that prevent puberty

49
Q

explain the pathophysiology of Kallmann syndrome

A

1) olfactory neurones are found alongside GnRH-producing neurones in the olfactory placode
2) failure of migration of GnRH neurones to hypothalamus and olfactory neurones to cribiform plate
3) no GnRH-producign neurones = no LH/FSH = no oestrogen/testosterone/progesterone = delayed puberty/infertility
4) no olfactory neurones embedded into cribiform plate = anosmia

50
Q

why do patients with Kallmann syndrome experience anosmia?

A

the GnRH-producing neurones are found alongside the olfactory neurones in the olfactory placode

so if GnRH neurones do not migrate (to hypothalamus), neither do the olfactory neurones (to cribiform plate)

= both reproductive problems + anosmia

51
Q

what are the main symptoms of Kallmann syndrome?

A

1) anosmia
2) cryptorchidism
3) failure/delayed puberty (micropenis, primary amenorrhoea, lack of testicular development)
4) infertility

52
Q

what are the expected blood test results of a patient with Kallmann syndrome?

A

low GnRH (cannot measure)
low LH/FSH
low testosterone/oestrogen/progesterone

53
Q

what are the symptoms of hyperprolactinaemia?

A
  • low libido
  • erectile dysfunction
  • amenorrhoea/oligomenorrhoea
  • osteoporosis
  • infertility
54
Q

how is hyperprolactinaemia treated?

A

1) dopamine agonist (cabergoline)

2) surgery/DXT

55
Q

how does a dopamine agonist treat hyperprolactinaemia?

A

bind to the dopamine receptor and mimics the actions of dopamine to inhibit prolactin release from lactotrophs of the APG

56
Q

name common sex chromosome disorders in males

A

(normal males = 46XY)

1) Klinefelter syndrome (47XXY)
2) XYY syndrome

57
Q

name common sex chromosome disorders in females

A

(normal females = 46XX)

1) triple X syndrome (47XXX)
2) Turner’s syndrome (45X0)
3) fragile X syndrome

58
Q

what are the chromosomes like in Klinefelter’s syndrome?

A

47XXY

when it should be 46XY

59
Q

what are the chromosomes like in Turner’s syndrome?

A

45X0

when it should be 46XX

60
Q

what are the symptoms of Klinefelter’s syndrome?

A
  • tall stature
  • less facial hair
  • mildly impaired IQ
  • small penis & testes
  • infertility

(breast development, narrow shoulders, reduced chest hair, wide hips, low bone density)

61
Q

how does Klinefelter’s compare to Turner’s?

A

Klinefelter’s = 47XXY (trisomy)

Turner’s = 45X0 (monosomy)

62
Q

which symptoms of Klinefelter’s syndrome are female-type?

A
  • narrow shoulders
  • breast development
  • reduced chest hair
  • femal-type pubic hair pattern
  • wide hips
  • low bone density
63
Q

what blood test is expected for a patient with Klinefelter’s?

A 
LH/FSH = elevated
testosterone = low

hypergonadotrophic hypogonadism

64
Q

what is the expected volume of semen in a sample?

A

1.5ml

65
Q

what is the expected concentration of semen in a sample?

A

15 million/ml

66
Q

what is the expected motility of semen in a sample?

A

approx 40%

67
Q

define azospermia

A

no sperm

68
Q

define oligospermia

A

reduced sperm

69
Q

in order to assess male infertilty, which tests are done?

A

1) morning fasting testosterone, LH, FSH
2) PRL
3) pituitary MRI scan & pituitary exam
4) karyotyping
5) thyroid studies, SHBG
6) iron studies, albumin

70
Q

in order to assess male infertilty, what must be asked in the history?

A
  • previous children
  • pubertal milestones
  • associated symptoms
71
Q

what lifestyle advice is given to treat male infertility?

A

1) optimise BMI
2) smoking cessation
3) alcohol reduction/cessation

72
Q

what specific medical treatment is given to treat male infertility?

A

1) dopamine agonist (for hyperprolactinaemia)
2) if fertility required = gonadotrophin injections (will stimulate T production)
3) if fertility NOT desired = testosterone
4) surgery (micro TESE)

73
Q

if fertility is required, why can pure testosterone not be given to a patient?

A

administration of T will cause reduced LH + FSH secretion via the negative feedback loop

= gonadotrophins are required for fertility (!!)

74
Q

what are the expected blood results for a patient with premature ovarian insufficiency?

A

high LH + FSH

low oestrogen

75
Q

what are the expected blood results for a patient with anorexia-induced amenorrhoea?

A

low GnRH (non-measurable)
low LH + FSH
low oestrogen

76
Q

what are the causes of hypergonadotrophic hypogonadism in females?

A

1) congenital = Turner’s 45X0, premature ovarian insufficiency
2) acquired = premature ovarian insufficiency, trauma, surgery, infection
3) PCOS (polycystic ovarian syndrome)

77
Q

what are the causes of hypogonadotrophic hypogonadism in females?

A

1) pituitary problems

2) hypothalamic problems

78
Q

which pituitary problems can cause infertility in females?

A

hypogonadotrophic hypogonadism
= HYPOPITUITARISM

(low LH/FSH, low O)

e.g. infection, apoplexy, tumour, chemo, radiation

79
Q

which hypothalamic problems can cause infertility in females?

A

hypogonadotrophic hypogonadism
= low GnRH, low LH/FSH, low O

1) congenital = Kallmann syndrome
2) acquired = low BMI, excess exercise, stress
3) hyperprolactinaemia

80
Q

why are hypothalamic-infertility problems alternatively known as in women?

A

hypothalamic amenorrhoea

81
Q

what are the non-HPG axis related causes of female infertility?

A

1) hypo/hyperthyroidism = reduce bioavailabel oestradiol

82
Q

what is the most common cause of infertility in women?

A

polycystic ovarian syndrome

affects 5-15% of women of reproductive age

83
Q

how is PCOS diagnosed?

A

Rotterdam PCOS Diagnostic Criteria

need to fulfil 2 out of 3 criteria

84
Q

what is the Rotterdam PCOS diagnostic criteria?

A

1) oligo OR anovulation
2) clinical +/- biochemical hyperandrogenism
3) polycystic ovaries (US)

85
Q

how is oligomenorrhoea/anovulation assessed as part of the Rotterdam PCOS scale?

A

1) oligomenorrhoea = 4-9 cycles a year // 35+ day cycles

2) anovulation = test midluteal/d21 progesterone (show there is a lack of progesterone rise) or ultrasound

86
Q

how is hyperandrogenism assessed as part of the Rotterdam PCOS scale?

A

1) clinical = acne, hirsutism (Ferriman-Galleway score), alopecia (Ludwig score)
2) biochemical = raised androgens (e.g. testosterone)

87
Q

how are polycystic ovaries assessed as part of the Rotterdam PCOS scale?

A

> = 20 follicles OR >= 10ml either ovary

don’t use US until 8y post-menarche

88
Q

when is the Rotterdam PCOS diagnostic criteria used?

A

exclude all other possible causes of infertility
e.g. Kallmann, hypopotuitarism, Turner’s, hyperPRL

use Rotterdam and ensure at least 2/3 criteria are fulfilled

89
Q

what confers the worst metabolic risk in terms of PCOS?

A

if the 2/3 criteria fulfilled are:

1) oligomenorrhoea/anovulation
2) clinical/biocehmical hyperandrogenism

90
Q

what treatments are available for PCOS?

A

depends on which aspect/symptom the patients wants to address

1) irregular menses = OCP
2) increased insulin resistance/T2DM/impaired glucose homeostasis = METFORMIN + diet/lifestyle
3) hirsutism = ANTI-ANDROGENS/LASER/CREAMS/WAXING
4) increased risk of endometrial cancer = progesterone courses
5) infertility = IVF, letrozole, clomiphene

91
Q

what is normally given to PCOS patients to treat their infertility?

A

IVF, clomiphene, letrozole

92
Q

what is normally given to PCOS patients to treat their irregular menses?

A

oral contraceptive pill

93
Q

what is normally given to PCOS patients to treat their T2DM/impaired glucose tolerance?

A

diet + lifestyle changes

metformin

94
Q

what is normally given to PCOS patients to treat their hirsutism?

A

1) anti-androgens (e.g. spironolactone)

2) creams, waxing, laser

95
Q

what is normally given to PCOS patients to treat their risk of endometrial cancer?

A

progesterone courses

96
Q

what is Turner’s syndrome?

A

a genetic condition in which the patient is 45X0

= a form of hypergonadotrophic hypogonadism (high LH/FSH, low O)

97
Q

what are the symptoms of Turner’s syndrome?

A
  • short stature
  • low hairline
  • wide-spaced nipples
  • short 4th metacarpal
  • small fingernails
  • brown nevi
  • webbed neck
  • coarctation of the aorta
  • poor breast development
  • elbow deformity
  • underdeveloped reproductive tract
  • amenorrhoea
98
Q

in order to assess female infertilty, what must be asked in the history?

A
  • previous children
  • pubertal milestones
  • breastfeeding
  • menstrual history
99
Q

in order to assess female infertilty, what tests must be done?

A

(! must do a pregnancy test !)

1) LH, FSH, oestradiol, PRL, androgens
2) karyotyping
3) thyroid tests, SHBG
4) pituitary scan MRI
5) albumin, iron studies

special = follicular phase 17-OHP, midluteal phase progesterone

100
Q

why is follicular phase 17-OH tested when assessing female infertility?

A

indicates whether congenital adrenal hyperplasia is present

as 17-OH prog can build-up if CAH is present

101
Q

why is mid-luteal progesterone tested when assessing female infertility?

A

to assess whether ovulation has occurred

brs (phase 1b) (71 decks)

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