(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)
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)
3
Q
define secondary infertility
A
infertility in a couple that has previously had a live birth >12 months ago
4
Q
what is the most common cause of infertility in couples?
A
male factor, female factor or combined
5
Q
what are the main causes of infertility in males?
A
1) pre-testicular
2) testicular
3) post-testicular
6
Q
what are the pre-testicular causes of infertility?
A
congenital + acquired endocrinopathies
- Klienfelter’s 47XXY, Y chromosome deletion, HPG, T, PRL
7
Q
what are the testicular causes of infertility?
A
- cryptorchidism
- infection (STDs)
- trauma/surgery
- immunological (antisperm Abs)
- toxins (chemo, drugs smoking)
- vascular (varicocele)
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)
9
Q
what is obstructive azoospermia?
A
obstruction to sperm leaving the testicels
10
Q
what is retrograde ejaculation?
A
when semen enters the bladder instead of emerging through the penis
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)
12
Q
what is the normal path for testicular descent?
A
through the inguinal canal
13
Q
where are the majority of undescended testes usually found?
A
inguinal canal
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
15
Q
what are possible ovarian causes of infertility in females?
A
- anovulation
- corpus luteum insifficiency
16
Q
what are possible tubal causes of infertility in females?
A
- infection
- endometriosis
- trauma
17
Q
what are possible uterine causes of infertility in females?
A
unfavourable endometrium:
- chronic endometriosis (TB)
- fibroids
- adhesions (synechiae)
- congenital malformation
18
Q
what are possible cervical causes of infertility in females?
A
- chronic cervicitis
- immunological (antisperm antibodies)
19
Q
what are possible pelvic causes of infertility in females?
A
- endometriosis
- adhesions
20
Q
how is anovulation a cause of infertility?
A
(ovarian cause)
the HPG axis controlling ovarian hormones and ovulation is ineffective
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
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
23
Q
what can cause chronic endometriosis?
A
(uterine causes)
can be caused due to TB
24
Q
what is chronic cervicitis?
A
(cervical causes)
chronic inflammation of the cervix
= ineffective sperm penetration
25
what is endometriosis?
presence of functioning endometrial tissue outside the uterus
26
what does endometrial tissue respond to and why is this a problem?
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
27
what are the symptoms of endometriosis?
- increased menstrual pain
- menstrual irregularities
- deep dyspareunia (painful intercourse)
- infertility
28
why do patients with endometriosis experience more menstrual pain?
there is more endometrial tissue that responds to oestrogen
| = more pain overall
29
how is endometriosis treated?
1) hormonal (continuous, OCP, progesterone)
2) laparoscopic ablation
3) hysterectomy
4) bilateral salpingo-oopherectomy (removal of both ovaries and fallopian tubes)
30
what are fibroids?
benign tumours of the myometrium
31
how common is endometriosis?
experienced by 5% of women
32
how common are fibroids?
experienced by 1-20% of pre-menopausal women
(more common
33
what do fibroids respond to?
respond to oestrogen
| similar to endometriosis
34
what are the symptoms of fibroids?
usually asymptomatic BUT can experience
- increased menstrual pain
- menstrual irregularities
- deep dyspareunia
- infertility
35
how are fibroids treated?
1) hormonal (continuous, OCP, progesterone, continuous GnRH agonists)
2) hysterectomy
36
where are fibroids usually found?
1) subserosal
2) intramural
3) submucosal
4) pedunculated subserosal
37
which hormone is mainly involved in the negative feedback loop of the HPG axis?
oestrogen, testosterone and progesterone
BUT mainly oestrogen in both women and men (aromatised from testosterone)
38
which blood test results are expected in patients with hyperprolactinaemia?
```
LH = low
FSH = low
testosterone = low
```
39
which blood test results are expected in patients with primary testicular failure?
```
LH = high
FSH = high
testosterone = low
```
*hypergonadotrophic hypogonadism*
40
what is primary testicular failure also known as?
hypergonadotropic hypogonadism
41
what blood test results are expected in hypergonadotrophic hypogonadism?
LH + FSH = high
| testosterone = low
42
give examples of hypergonadotrophic hypogonadism
1) congenital = Klinefelter's 47XXY
| 2) acquired = cryptorchidism, trauma, surgery, infection, immunological, chemo, radiation
43
what blood test results are expected in hypogonadotrophic hypogonadism?
either
1) high GnRH; low LH + FSH; low T
2) low GnRH; low LH + FSH; low T
44
what are the possible causes of the following:
- high GnRH
- low LH + FSH
- low T
pituitary problems (e.g. surgery, radiotherapy, apoplexy, infection, tumour)
= hypopituitarism
45
what are the possible causes of the following:
- low GnRH
- low LH + FSH
- low T
1) congenital = anosmic (Kallmann syndrome) or normosmic
2) acquired = low BMI, excess exercise, stress
3) hyperprolactinaemia
46
what are the non-HPG axis related causes of male infertility?
1) androgen receptor deficiency
| 2) hyper/hypothyroidism
47
how can hyper/hypothyroidism lead to male infertility?
hyperthyroidism = increases SHBG so reduced free testosterone
hypothyroidism = decreased testosterone secretion
48
what is Kallmann syndrome?
a disorder which combines an impaired ability to smell with hormonal and endocrine imbalances that prevent puberty
49
explain the pathophysiology of Kallmann syndrome
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
why do patients with Kallmann syndrome experience anosmia?
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
what are the main symptoms of Kallmann syndrome?
1) anosmia
2) cryptorchidism
3) failure/delayed puberty (micropenis, primary amenorrhoea, lack of testicular development)
4) infertility
52
what are the expected blood test results of a patient with Kallmann syndrome?
low GnRH (cannot measure)
low LH/FSH
low testosterone/oestrogen/progesterone
53
what are the symptoms of hyperprolactinaemia?
- low libido
- erectile dysfunction
- amenorrhoea/oligomenorrhoea
- osteoporosis
- infertility
54
how is hyperprolactinaemia treated?
1) dopamine agonist (cabergoline)
| 2) surgery/DXT
55
how does a dopamine agonist treat hyperprolactinaemia?
bind to the dopamine receptor and mimics the actions of dopamine to inhibit prolactin release from lactotrophs of the APG
56
name common sex chromosome disorders in males
(normal males = 46XY)
1) Klinefelter syndrome (47XXY)
2) XYY syndrome
57
name common sex chromosome disorders in females
(normal females = 46XX)
1) triple X syndrome (47XXX)
2) Turner's syndrome (45X0)
3) fragile X syndrome
58
what are the chromosomes like in Klinefelter's syndrome?
47XXY
| when it should be 46XY
59
what are the chromosomes like in Turner's syndrome?
45X0
| when it should be 46XX
60
what are the symptoms of Klinefelter's syndrome?
- 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
how does Klinefelter's compare to Turner's?
Klinefelter's = 47XXY (trisomy)
Turner's = 45X0 (monosomy)
62
which symptoms of Klinefelter's syndrome are female-type?
- narrow shoulders
- breast development
- reduced chest hair
- femal-type pubic hair pattern
- wide hips
- low bone density
63
what blood test is expected for a patient with Klinefelter's?
```
LH/FSH = elevated
testosterone = low
```
*hypergonadotrophic hypogonadism*
64
what is the expected volume of semen in a sample?
1.5ml
65
what is the expected concentration of semen in a sample?
15 million/ml
66
what is the expected motility of semen in a sample?
approx 40%
67
define azospermia
no sperm
68
define oligospermia
reduced sperm
69
in order to assess male infertilty, which tests are done?
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
in order to assess male infertilty, what must be asked in the history?
- previous children
- pubertal milestones
- associated symptoms
71
what lifestyle advice is given to treat male infertility?
1) optimise BMI
2) smoking cessation
3) alcohol reduction/cessation
72
what specific medical treatment is given to treat male infertility?
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
if fertility is required, why can pure testosterone not be given to a patient?
administration of T will cause reduced LH + FSH secretion via the negative feedback loop
= gonadotrophins are required for fertility (!!)
74
what are the expected blood results for a patient with premature ovarian insufficiency?
high LH + FSH
| low oestrogen
75
what are the expected blood results for a patient with anorexia-induced amenorrhoea?
low GnRH (non-measurable)
low LH + FSH
low oestrogen
76
what are the causes of hypergonadotrophic hypogonadism in females?
1) congenital = Turner's 45X0, premature ovarian insufficiency
2) acquired = premature ovarian insufficiency, trauma, surgery, infection
3) PCOS (polycystic ovarian syndrome)
77
what are the causes of hypogonadotrophic hypogonadism in females?
1) pituitary problems
| 2) hypothalamic problems
78
which pituitary problems can cause infertility in females?
hypogonadotrophic hypogonadism
= HYPOPITUITARISM
(low LH/FSH, low O)
e.g. infection, apoplexy, tumour, chemo, radiation
79
which hypothalamic problems can cause infertility in females?
hypogonadotrophic hypogonadism
= low GnRH, low LH/FSH, low O
1) congenital = Kallmann syndrome
2) acquired = low BMI, excess exercise, stress
3) hyperprolactinaemia
80
why are hypothalamic-infertility problems alternatively known as in women?
hypothalamic amenorrhoea
81
what are the non-HPG axis related causes of female infertility?
1) hypo/hyperthyroidism = reduce bioavailabel oestradiol
82
what is the most common cause of infertility in women?
polycystic ovarian syndrome
| affects 5-15% of women of reproductive age
83
how is PCOS diagnosed?
Rotterdam PCOS Diagnostic Criteria
| need to fulfil 2 out of 3 criteria
84
what is the Rotterdam PCOS diagnostic criteria?
1) oligo OR anovulation
2) clinical +/- biochemical hyperandrogenism
3) polycystic ovaries (US)
85
how is oligomenorrhoea/anovulation assessed as part of the Rotterdam PCOS scale?
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
how is hyperandrogenism assessed as part of the Rotterdam PCOS scale?
1) clinical = acne, hirsutism (Ferriman-Galleway score), alopecia (Ludwig score)
2) biochemical = raised androgens (e.g. testosterone)
87
how are polycystic ovaries assessed as part of the Rotterdam PCOS scale?
>= 20 follicles OR >= 10ml either ovary
| don't use US until 8y post-menarche
88
when is the Rotterdam PCOS diagnostic criteria used?
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
what confers the worst metabolic risk in terms of PCOS?
if the 2/3 criteria fulfilled are:
1) oligomenorrhoea/anovulation
2) clinical/biocehmical hyperandrogenism
90
what treatments are available for PCOS?
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
what is normally given to PCOS patients to treat their infertility?
IVF, clomiphene, letrozole
92
what is normally given to PCOS patients to treat their irregular menses?
oral contraceptive pill
93
what is normally given to PCOS patients to treat their T2DM/impaired glucose tolerance?
diet + lifestyle changes
metformin
94
what is normally given to PCOS patients to treat their hirsutism?
1) anti-androgens (e.g. spironolactone)
| 2) creams, waxing, laser
95
what is normally given to PCOS patients to treat their risk of endometrial cancer?
progesterone courses
96
what is Turner's syndrome?
a genetic condition in which the patient is 45X0
| = a form of hypergonadotrophic hypogonadism (high LH/FSH, low O)
97
what are the symptoms of Turner's syndrome?
- 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
in order to assess female infertilty, what must be asked in the history?
- previous children
- pubertal milestones
- breastfeeding
- menstrual history
99
in order to assess female infertilty, what tests must be done?
(! 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
why is follicular phase 17-OH tested when assessing female infertility?
indicates whether congenital adrenal hyperplasia is present
| as 17-OH prog can build-up if CAH is present
101
why is mid-luteal progesterone tested when assessing female infertility?
to assess whether ovulation has occurred
