Ovulation Disorders and Infertility Flashcards
1
Q
what is oligomenorrhea
A
reduction in frequency of periods to less than 9/year
2
Q
what is primary amenorrhea
A
failure of menarche (first menstrual cycle, or first menstrual bleeding) by the age of 16 years
3
Q
what is secondary amenorrhea
A
cessation of periods for >6 months in an individual who has previously menstruated
4
Q
causes of primary amenorrhea
A
congenital
- Turner’s syndrome, Kallman’s syndrome
5
Q
causes of secondary amenorrhea
A
Ovarian problem: PCOS, Premature Ovarian Failure
Uterine problem: uterine adhesions
Hypothalamic Dysfunction: weight loss, over exercise, stress, infiltrative
Pituitary: high PRL, hypopituitarism
6
Q
physiological causes of amenorrhea
A
pregnancy
post-menopause
7
Q
Hx of amenorrhea
A
Sx of oestrogen deficiency
- flushing, libido, dyspareunia (difficult, painful intercourse)
Hypothalamic problem
- exercise, weight loss, stress
Features of PCOS/androgen excess: hirsutism/acne
Anosmia - in Kallman’s, loose ability to smell
Symptoms of hypopituitarism/pituitary tumour including galactorrhea
8
Q
Ix of amenorrhea
A
First line:
LH, FSH, Oestradiol
Thyroid function, Prolactin
Second line:
Ovarian ultrasound +/- endometrial thickness
Testosterone if hirsutism
Pituitary function tests + MRI pituitary if hypothalamic pituitary probems suspected
9
Q
what should be considered in amenorrhea
A
hypogonadism
10
Q
how does hypogonadism present in females
A
low levels of oestrogen
11
Q
what is cause of primary hypogonadism
A
Problem with the ovaries
High LH/FSH – hypergonadotrophic hypogonadism
e.g. premature ovarian failure
12
Q
what is cause of secondary hypogonadism
A
Problem with hypothalamus or pituitary
Low LH/FSH – hypogonadotrophic hypogonadism
e.g. high PRL, hypopituitarism
13
Q
what is classified as premature ovarian failure (POF)
A
Amenorrhea
Oestrogen deficiency
Elevated gonadotrophins occuring
14
Q
what is diagnostic of POF
A
FSH 430 on 2 separate occasions > 1 month apart
15
Q
causes of POF
A
Chromosomal abnormalities
e.g. Turner’s, Fragile X
Gene mutations e.g. FSH/LF receptor
Autoimmune disease e.g. association with Addison’s
Iatrogenic
- radio/chemotherapy
16
Q
what is secondary hypogonadism and how is it characterised
A
Hypogonadism as a result of hypothalamic or pituitary disease
Characterised by low oestradiol with low/normal LH/FSH
17
Q
causes of secondary hypogonadism
A
Hypothalamic problem:
- functional hypothalamic disorder
- Kallman’s syndrome
- Idiopathic hypogonadotrophic hypogonadism (IHH)
Pituitary problem
18
Q
what can cause functional hypothalamic disorder
A
weight change stress exercise anabolic steroids systemic illness iatrogenic Kallman's syndrome recreational drugs head trauma infiltrative disorder e.g. sarcoidosis
19
Q
what is pathway of hypothalamic dysfunction
A
Low GnRH Loss of pulsatile secretion >> Low or low normal LH/FSH >> Low oestradiol
20
Q
what is Kallman’s syndrome
A
genetic disorder characterised by a loss of GnRH secretion +/- anosmia
M > F
21
Q
how can pituitary dysfunction cause amenorrhea
A
Loss of LH/FSH stimulation due to: - Non-functioning pituitary macroadenoma (pressure effects lead to hypopituitarism) - Empty Sella - Pituitary infarction
Hyperprolactinemia
due to:
- Micro- or macro-prolactinoma
- Drugs (e.g. dopamine antagonists)
22
Q
what is empty sella
A
pituitary gland shrinks or becomes flattened, filling the sella turcica, or “Turkish Saddle”
23
Q
what are ovarian causes of Amenorrhea
A
PCOS Ovarian failure (high gonadotrophin) Congenital problem with ovarian development
24
Q
what is hirsutism
A
excess hair growth in a male distribution in females
25
what causes hirsutism
caused by androgen excess at the hair follicle
| - due to excess circulating androgen
26
what causes the excess production of androgen
ACTH
27
what is the best way to investigate adrenal and ovarian tumour
MRI
28
Tx of amenorrhea
Depends on cause
PCOS
- Oral contraceptive pill
- Anti-androgens
- local anti-androgens
Late onset CAH
- Low dose glucocorticoid to suppress ACTH drive
29
what is Turner Syndrome
when there is only 1 X chromosome
30
clinical features of Turner's
```
short stature
webbed neck
shield chest with wide spaced nipples
cubitus valgus (deformity of the elbow resulting in an increased carrying angle)
lymphoedema
```
31
presentation of Turner's in children
Short Stature
| Failure to progress through puberty
32
presentation of Turner's in adults
Primary or secondary amenorrhea
| Infertility
33
risk factors for infertility
```
older women >35 y/o
previous chlamydia infections
obesity
smoking
high caffeine intake
excessive alcohol
Woman's BMI 30
Regular use of recreational drugs
```
34
definition of infertility
failure to achieve a clinical pregnancy after 12 months of more of regular unprotected sexual intercourse (in absence of known reason) in a couple who have never had a child
35
what is the difference between primary and secondary infertility
primary - couple has never conceived
secondary - couple previously conceived. Pregnancy may not have been successful e.g. miscarriage or ectopic pregnancy)
36
female causes of infertility
ovulation failure - 50%
tubal damage - 25%
endometriosis - 10%
miscellaneous - 15%
37
what is a Anovulatory cycle
a menstrual cycle where an egg is not release
38
physiological causes of Anovulatory cycle
before puberty, pregnancy, lactation, menopause
39
gynaecological causes of Anovulatory cycle
Hypothalmic: anorexia/bulimia, excessive exercise,
Pituitary: hyperprolactinaemia, tumours, Sheehan syndrome
Ovarian: PCOS, premature ovarian failure
40
other causes of Anovulatory cycle
Chronic renal failure
CAH
Hypo/Hyperthyroidism
41
what is clinical features of anorexia nervosa
low BMI (below 18.5),
loss of hair, increased lanugo,
low pulse and BP,
anaemia
42
endocrine features of anorexia nervosa
low FSH, LH and oestradiol
43
what is the triad of PCOS
chronic Oligo/Amenorrhoea
polycystic ovaries
hyperandrogenism (clinical or biochemical) e.g. acne, hirsutism, male pattern baldness
need 2 out of 3 for diagnosis
44
clinical features of PCOS
obesity
hirsutism or acne
cycle abnormalities and infertility
45
endocrine features of PCOS
high free androgens,
high LH,
impaired glucose tolerance
46
what is premature ovarian failure
when a woman's ovaries stop working before she is 40
47
causes of POF
idiopathic
genetic - Turner's, fragile X
Chemo/radiotherapy
48
features of POF
clinical
- hot flushes, night sweats
- atrophic vaginitis
endocrine
- high FSH
- high LH
- low oestradiol
49
infective tubal disease causes
Pelvic inflammatory disease
| - chlamydia, gonorrhoea, TB, syphilis
50
non-infective tubal disease cause
```
endometriosis
surgical - sterilisation
fibroids
polyps
congenital
```
51
what is a Hydrosalpinx and what can cause it
fallopian tube dilated with fluid
| pelvic inflammatory disease
52
features of a hydrosalpinx
```
abdominal/pelvic pain febrile
vaginal discharge
dyspareunia
cervical excitation
menorrhagia
dysmenorrhoea
infertility
ectopic pregnancy
```
53
what is endometriosis
presence of endometrial glands outside uterine cavity
54
clinical features of endometriosis
```
dysmenorrhoea (classically before menstruation), dysparenuia,
menorrhagia,
painful defaecation,
chronic pelvic pain
infertility
```
55
what is a characteristic sign seen on a scan of the ovary in endometriosis
'chocolate' cysts
Laparoscopic view
56
Ix for endometriosis
transvaginal ultrasound (TVUS)
57
male causes of infertility
```
idiopathic - 25%
varicocele - 37%
chryptorchisism - 6%
obstruction - 6%
testicular failure - 9%
semen disorders - 10%
other - 7%
```
58
what can cause erectile dysfunction in males
diabetes
| spinal cord injury
59
congenital disease that can cause absence of vas defers and therefore infertility
Cystic fibrosis
60
endocrine causes of male infertility
hypogonadotropic hypogonadism (e.g. Kallmann syndrome, anorexia)
testicular failure
hyperprolactinaemia (macro or microadenoma)
acromegaly
Cushing’s disease
hyper or hypothyroidism
61
obstructive clinical features of male infertility
normal testicular volume (over 8cm - less 5cm fertility decreases)
normal secondary sexual characteristics
vas deferens may be absent
normal LH, FSH and testosterone
62
clinical and endocrine features of non-obstructive male infertility
low testicular volume
reduced secondary sexual characteristics
vas deferens present
High LH, FSH and low testosterone
63
Ex of infertility - male
BMI
General examination
Genital examination, assessing size/position testes, penile abnormalities, presence vas deferens, presence varicoceles
64
what is varicoceles
a mass of varicose veins in the spermatic cord.
65
Ex of infertility - female
BMI
General examination, assessing body hair distribution, galactorrhoea
Pelvic examination, assessing for uterine and ovarian abnormalities/tenderness/mobility
66
Ix of infertility - female
```
endocervical swab for chlamydia
cervical smear if due
blood for rubella immunity
midluteal progesterone level (day 21 of 28 day cycle)
test of tubal patency
```
67
what suggests ovulation
day 21 progesterone > 30 mol/l
68
how can tubal patency be tested
Hysterosalpingiogram
| Laparoscopy
69
when would a hysteroscopy be preformed in suspected infertility
suspected or known endometrial pathology: i.e. uterine septum, adhesions, polyp
70
what test can be done if there is an abnormality on pelvic examination
pelvic ultrasound
71
Ix for male infertility
semen analysis - twice over 6 weeks apart
72
what are the two phases of the menstrual cycle
follicular
| luteal
73
what is oligomenorrhea
light or infrequent menstrual periods
74
what is GnRH and where it is synthesised
```
Pulsatile release
Stimulates FSH (low frequency pulses) and LH (high frequency pulses) synthesis / release
```
Synthesised in hypothalamus
75
what does FSH do and where is it produced
Stimulates follicular development
Thickens endometrium
secreted by anterior pituitary
76
what does LH do and where is it produced
Peak stimulates ovulation
Stimulates corpus luteum development
Thickens endometrium
secreted by anterior pituitary
77
what triggers ovulations
LH surge roughly 36 hours before ovulation begins
78
what peaks before ovulation
LH
| Estradiol
79
when does progesterone peak and what makes it
following ovulation in luteal phase
| produced by corpus luteum
80
what secretes oestrogen
primarily by the ovaries (follicles) and adrenal cortex
81
what also secretes oestrogen during pregnancy
placenta
82
what is function of oestrogen
thickening of the endometrium
responsible for fertile cervical mucus
83
what does high oestrogen concentration cause
inhibits secretion of FSH and prolactin (-ve feedback)
stimulates secretion of LH (+ve feedback)
84
why does the corpus luteum secrete progesterone and what takes over secreting it during pregnancy
maintain early pregnancy
the placenta takes over
85
other function of progesterone
Inhibits secretion of LH
Responsible for infertile (thick) cervical mucus
Maintain thickness of endometrium
Has thermogenic effect (increases basal body temperature)
Relaxes smooth muscles
86
how is ovulation confirmed
confirm by midluteal (D21) serum progesterone (>30 nmol/L) X 2 samples
87
what are the 3 WHO classifications for cause of infertile couples
Group I Hypothalamic pituitary failure
Group II Hypothalamic pituitary dysfunction
Group III Ovarian failure
88
what is seen in Hypogonadotrophic hypogonadism
```
Low levels FSH / LH
Oestrogen deficiency
- Negative progesterone challenge test
Normal prolactin
Amenorrhoea
```
89
Mx of hypothalamic anovulation
```
Stabilise weight (BMI >18.5)
Pulsatile GnRH if hypog hypog
Gonadotrophin (FSH+LH) daily injections
```
90
what is suggestive of hypothalamic pituitary dysfunction
Normal gonadotrophins / excess LH
Normal oestrogen levels
Oligo/amenorrhoea
91
what is commonly associated with PCOS and what does this cause
insulin resistance
Insulin acts as co-gonadotrophin to LH >> elevated LH
Insulin lowers sex hormone binding globulin >> increased free testosterone >> hyperandrogenism
92
Tx of PCOS
Weight loss
No smoking + alcohol
Folic Acid 5mg
Clomifene citrate
can add Metformin for insulin resistance
93
what treatments can be used for ovulation induction
Clomifene citrate
Gonadotrophin therapy: daily injections
Laparoscopic ovarian diathermy:
94
what are potential risks of ovulation induction
ovarian hyperstimulation
multiple pregnancy
risk ovarian cancer
95
what are the risks of multiple pregnancy
increased maternal pregnancy complications e.g. morning sickness, anaemia, postnatal depression
Twin-twin transfusion syndrome
increased risk of miscarriage
increased risk of low birth weight
increased risk prematurity and disability
increased risk of still birth
96
what are monochorionic and dichorionic twins
mono - identical twins/triplets
| di - non-identical twins/triplets
97
what are the scan findings that can help identify mono or di-chornic twins
Lambda sign - dichorionic
T sign - monochorionic
98
what is twin-twin transfusion syndrome
unbalanced vascular communications/connection within placental bed
- Recipient develops polyhydramnios
- Donor develops oliguria, oligohydramnios and growth restriction
99
prematurity problems
early - respiratory distress syndrome
long term - Cerebral palsy, impaired sight, congenital heart disease
- lower IQ, ADHD
100
what is suggestive of ovarian failure
```
High levels gonadotrophins
Raised FSH>30IU/L x 2 samples
Low oestrogen levels
Amenorrhea
Menopausal symptoms; flushing, sweats
```
101
what is the difference between oogenesis and spermatogenesis
oogenesis - takes many years to complete, ceases at menopause (50/55 y/o), begins in utero, suspended for many years and then begins again a puberty
spermatogenesis- takes much less time; around 72 days, no sperm production before puberty, men keep producing sperm for the majority of their life
102
what are the female germ cells
Primordial germ cell
| Oogonia
103
what are the earliest recognisable germinal cell and what are features of it
Primordial germ cell
Capable of mitosis
Migrate to genital ridge by week 6 of embryo development
104
what is a oogonia called when it completes its last pre-meiotic division
oocytes
105
what happens after oocytes enter meiosis
1st meiotic division - Primary oocytes -
2nd meiotic division - Secondary oocytes
106
what signifies sperm enter and completion of 2nd meiotic division
presence of two polar bodies
107
what is the follicular phase of the ovarian cycle
1st half of cycle
Maturation of egg, ready for ovulation at midcycle – ovulation signals end of follicular phase
108
what is the luteal phase of the ovarian cycle
2nd half of cycle
Development of corpus luteum.
Induces preparation of reproductive tract for pregnancy (if fertilisation occurs)
109
what signals start of new follicular phase
degeneration of corpus luteum
110
what hormone is most dominant in follicular phase
FSH
| little LH
111
Tx of male infertility
Surgery to obstructed vas deferens (50% success following vasectomy)
Intrauterine insemination in mild disease
Intracytoplasmic sperm injection (ICSI)
ICSI combined with surgical sperm aspiration from epididymis or testicle
Donor insemination.
112
Mx of infertility - general factors
```
Sexual intercourse: 2-3 times per week
Alcohol: females limit to 4 units per week
Weight loss
Stop Smoking
Folic acid
Rubella immunity
Cervical smears
Occupational factors
Drugs: prescribed, over-the-counter and recreational
```
