Ovulation Disorders and Infertility Flashcards

1
Q

what is oligomenorrhea

A

reduction in frequency of periods to less than 9/year

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2
Q

what is primary amenorrhea

A

failure of menarche (first menstrual cycle, or first menstrual bleeding) by the age of 16 years

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3
Q

what is secondary amenorrhea

A

cessation of periods for >6 months in an individual who has previously menstruated

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4
Q

causes of primary amenorrhea

A

congenital

- Turner’s syndrome, Kallman’s syndrome

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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

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6
Q

physiological causes of amenorrhea

A

pregnancy

post-menopause

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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

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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

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9
Q

what should be considered in amenorrhea

A

hypogonadism

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10
Q

how does hypogonadism present in females

A

low levels of oestrogen

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11
Q

what is cause of primary hypogonadism

A

Problem with the ovaries

High LH/FSH – hypergonadotrophic hypogonadism
e.g. premature ovarian failure

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12
Q

what is cause of secondary hypogonadism

A

Problem with hypothalamus or pituitary

Low LH/FSH – hypogonadotrophic hypogonadism
e.g. high PRL, hypopituitarism

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13
Q

what is classified as premature ovarian failure (POF)

A

Amenorrhea
Oestrogen deficiency
Elevated gonadotrophins occuring

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14
Q

what is diagnostic of POF

A

FSH 430 on 2 separate occasions > 1 month apart

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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

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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

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17
Q

causes of secondary hypogonadism

A

Hypothalamic problem:

  • functional hypothalamic disorder
  • Kallman’s syndrome
  • Idiopathic hypogonadotrophic hypogonadism (IHH)

Pituitary problem

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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
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19
Q

what is pathway of hypothalamic dysfunction

A
Low GnRH
Loss of pulsatile secretion
>>
Low or low normal LH/FSH
>>
Low oestradiol
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20
Q

what is Kallman’s syndrome

A

genetic disorder characterised by a loss of GnRH secretion +/- anosmia

M > F

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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)

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22
Q

what is empty sella

A

pituitary gland shrinks or becomes flattened, filling the sella turcica, or “Turkish Saddle”

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23
Q

what are ovarian causes of Amenorrhea

A
PCOS
Ovarian failure (high gonadotrophin)
Congenital problem with ovarian development
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24
Q

what is hirsutism

A

excess hair growth in a male distribution in females

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25
Q

what causes hirsutism

A

caused by androgen excess at the hair follicle

- due to excess circulating androgen

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26
Q

what causes the excess production of androgen

A

ACTH

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27
Q

what is the best way to investigate adrenal and ovarian tumour

A

MRI

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28
Q

Tx of amenorrhea

A

Depends on cause

PCOS

  • Oral contraceptive pill
  • Anti-androgens
  • local anti-androgens

Late onset CAH
- Low dose glucocorticoid to suppress ACTH drive

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29
Q

what is Turner Syndrome

A

when there is only 1 X chromosome

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30
Q

clinical features of Turner’s

A
short stature
webbed neck
shield chest with wide spaced nipples
cubitus valgus (deformity of the elbow resulting in an increased carrying angle)
lymphoedema
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31
Q

presentation of Turner’s in children

A

Short Stature

Failure to progress through puberty

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32
Q

presentation of Turner’s in adults

A

Primary or secondary amenorrhea

Infertility

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33
Q

risk factors for infertility

A
older women >35 y/o
previous chlamydia infections
obesity
smoking 
high caffeine intake 
excessive alcohol
Woman's BMI  30
Regular use of recreational drugs
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34
Q

definition of infertility

A

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

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35
Q

what is the difference between primary and secondary infertility

A

primary - couple has never conceived

secondary - couple previously conceived. Pregnancy may not have been successful e.g. miscarriage or ectopic pregnancy)

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36
Q

female causes of infertility

A

ovulation failure - 50%
tubal damage - 25%
endometriosis - 10%
miscellaneous - 15%

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37
Q

what is a Anovulatory cycle

A

a menstrual cycle where an egg is not release

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38
Q

physiological causes of Anovulatory cycle

A

before puberty, pregnancy, lactation, menopause

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39
Q

gynaecological causes of Anovulatory cycle

A

Hypothalmic: anorexia/bulimia, excessive exercise,

Pituitary: hyperprolactinaemia, tumours, Sheehan syndrome

Ovarian: PCOS, premature ovarian failure

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40
Q

other causes of Anovulatory cycle

A

Chronic renal failure
CAH
Hypo/Hyperthyroidism

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41
Q

what is clinical features of anorexia nervosa

A

low BMI (below 18.5),
loss of hair, increased lanugo,
low pulse and BP,
anaemia

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42
Q

endocrine features of anorexia nervosa

A

low FSH, LH and oestradiol

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43
Q

what is the triad of PCOS

A

chronic Oligo/Amenorrhoea
polycystic ovaries
hyperandrogenism (clinical or biochemical) e.g. acne, hirsutism, male pattern baldness

need 2 out of 3 for diagnosis

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44
Q

clinical features of PCOS

A

obesity
hirsutism or acne
cycle abnormalities and infertility

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45
Q

endocrine features of PCOS

A

high free androgens,
high LH,
impaired glucose tolerance

46
Q

what is premature ovarian failure

A

when a woman’s ovaries stop working before she is 40

47
Q

causes of POF

A

idiopathic
genetic - Turner’s, fragile X
Chemo/radiotherapy

48
Q

features of POF

A

clinical

  • hot flushes, night sweats
  • atrophic vaginitis

endocrine

  • high FSH
  • high LH
  • low oestradiol
49
Q

infective tubal disease causes

A

Pelvic inflammatory disease

- chlamydia, gonorrhoea, TB, syphilis

50
Q

non-infective tubal disease cause

A
endometriosis 
surgical - sterilisation
fibroids
polyps
congenital
51
Q

what is a Hydrosalpinx and what can cause it

A

fallopian tube dilated with fluid

pelvic inflammatory disease

52
Q

features of a hydrosalpinx

A
abdominal/pelvic pain febrile
vaginal discharge 
dyspareunia
cervical excitation 
menorrhagia
dysmenorrhoea
infertility
ectopic pregnancy
53
Q

what is endometriosis

A

presence of endometrial glands outside uterine cavity

54
Q

clinical features of endometriosis

A
dysmenorrhoea (classically before menstruation), dysparenuia, 
menorrhagia, 
painful defaecation, 
chronic pelvic pain
infertility
55
Q

what is a characteristic sign seen on a scan of the ovary in endometriosis

A

‘chocolate’ cysts

Laparoscopic view

56
Q

Ix for endometriosis

A

transvaginal ultrasound (TVUS)

57
Q

male causes of infertility

A
idiopathic - 25%
varicocele - 37%
chryptorchisism - 6%
obstruction - 6%
testicular failure - 9%
semen disorders - 10%
other - 7%
58
Q

what can cause erectile dysfunction in males

A

diabetes

spinal cord injury

59
Q

congenital disease that can cause absence of vas defers and therefore infertility

A

Cystic fibrosis

60
Q

endocrine causes of male infertility

A

hypogonadotropic hypogonadism (e.g. Kallmann syndrome, anorexia)

testicular failure

hyperprolactinaemia (macro or microadenoma)

acromegaly

Cushing’s disease

hyper or hypothyroidism

61
Q

obstructive clinical features of male infertility

A

normal testicular volume (over 8cm - less 5cm fertility decreases)
normal secondary sexual characteristics
vas deferens may be absent

normal LH, FSH and testosterone

62
Q

clinical and endocrine features of non-obstructive male infertility

A

low testicular volume
reduced secondary sexual characteristics
vas deferens present

High LH, FSH and low testosterone

63
Q

Ex of infertility - male

A

BMI
General examination
Genital examination, assessing size/position testes, penile abnormalities, presence vas deferens, presence varicoceles

64
Q

what is varicoceles

A

a mass of varicose veins in the spermatic cord.

65
Q

Ex of infertility - female

A

BMI
General examination, assessing body hair distribution, galactorrhoea
Pelvic examination, assessing for uterine and ovarian abnormalities/tenderness/mobility

66
Q

Ix of infertility - female

A
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
Q

what suggests ovulation

A

day 21 progesterone > 30 mol/l

68
Q

how can tubal patency be tested

A

Hysterosalpingiogram

Laparoscopy

69
Q

when would a hysteroscopy be preformed in suspected infertility

A

suspected or known endometrial pathology: i.e. uterine septum, adhesions, polyp

70
Q

what test can be done if there is an abnormality on pelvic examination

A

pelvic ultrasound

71
Q

Ix for male infertility

A

semen analysis - twice over 6 weeks apart

72
Q

what are the two phases of the menstrual cycle

A

follicular

luteal

73
Q

what is oligomenorrhea

A

light or infrequent menstrual periods

74
Q

what is GnRH and where it is synthesised

A
Pulsatile release
Stimulates FSH (low frequency pulses) and LH (high frequency pulses) synthesis / release

Synthesised in hypothalamus

75
Q

what does FSH do and where is it produced

A

Stimulates follicular development
Thickens endometrium

secreted by anterior pituitary

76
Q

what does LH do and where is it produced

A

Peak stimulates ovulation
Stimulates corpus luteum development
Thickens endometrium

secreted by anterior pituitary

77
Q

what triggers ovulations

A

LH surge roughly 36 hours before ovulation begins

78
Q

what peaks before ovulation

A

LH

Estradiol

79
Q

when does progesterone peak and what makes it

A

following ovulation in luteal phase

produced by corpus luteum

80
Q

what secretes oestrogen

A

primarily by the ovaries (follicles) and adrenal cortex

81
Q

what also secretes oestrogen during pregnancy

A

placenta

82
Q

what is function of oestrogen

A

thickening of the endometrium

responsible for fertile cervical mucus

83
Q

what does high oestrogen concentration cause

A

inhibits secretion of FSH and prolactin (-ve feedback)

stimulates secretion of LH (+ve feedback)

84
Q

why does the corpus luteum secrete progesterone and what takes over secreting it during pregnancy

A

maintain early pregnancy

the placenta takes over

85
Q

other function of progesterone

A

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
Q

how is ovulation confirmed

A

confirm by midluteal (D21) serum progesterone (>30 nmol/L) X 2 samples

87
Q

what are the 3 WHO classifications for cause of infertile couples

A

Group I Hypothalamic pituitary failure
Group II Hypothalamic pituitary dysfunction
Group III Ovarian failure

88
Q

what is seen in Hypogonadotrophic hypogonadism

A
Low levels FSH / LH
Oestrogen deficiency
- Negative progesterone challenge test
Normal prolactin
Amenorrhoea
89
Q

Mx of hypothalamic anovulation

A
Stabilise weight (BMI >18.5)
Pulsatile GnRH if hypog hypog
Gonadotrophin (FSH+LH) daily injections
90
Q

what is suggestive of hypothalamic pituitary dysfunction

A

Normal gonadotrophins / excess LH
Normal oestrogen levels
Oligo/amenorrhoea

91
Q

what is commonly associated with PCOS and what does this cause

A

insulin resistance

Insulin acts as co-gonadotrophin to LH&raquo_space; elevated LH
Insulin lowers sex hormone binding globulin&raquo_space; increased free testosterone&raquo_space; hyperandrogenism

92
Q

Tx of PCOS

A

Weight loss
No smoking + alcohol
Folic Acid 5mg

Clomifene citrate
can add Metformin for insulin resistance

93
Q

what treatments can be used for ovulation induction

A

Clomifene citrate
Gonadotrophin therapy: daily injections
Laparoscopic ovarian diathermy:

94
Q

what are potential risks of ovulation induction

A

ovarian hyperstimulation
multiple pregnancy
risk ovarian cancer

95
Q

what are the risks of multiple pregnancy

A

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
Q

what are monochorionic and dichorionic twins

A

mono - identical twins/triplets

di - non-identical twins/triplets

97
Q

what are the scan findings that can help identify mono or di-chornic twins

A

Lambda sign - dichorionic

T sign - monochorionic

98
Q

what is twin-twin transfusion syndrome

A

unbalanced vascular communications/connection within placental bed

  • Recipient develops polyhydramnios
  • Donor develops oliguria, oligohydramnios and growth restriction
99
Q

prematurity problems

A

early - respiratory distress syndrome

long term - Cerebral palsy, impaired sight, congenital heart disease
- lower IQ, ADHD

100
Q

what is suggestive of ovarian failure

A
High levels gonadotrophins
Raised FSH>30IU/L x 2 samples
Low oestrogen levels
Amenorrhea
Menopausal symptoms; flushing, sweats
101
Q

what is the difference between oogenesis and spermatogenesis

A

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
Q

what are the female germ cells

A

Primordial germ cell

Oogonia

103
Q

what are the earliest recognisable germinal cell and what are features of it

A

Primordial germ cell

Capable of mitosis
Migrate to genital ridge by week 6 of embryo development

104
Q

what is a oogonia called when it completes its last pre-meiotic division

A

oocytes

105
Q

what happens after oocytes enter meiosis

A

1st meiotic division - Primary oocytes -

2nd meiotic division - Secondary oocytes

106
Q

what signifies sperm enter and completion of 2nd meiotic division

A

presence of two polar bodies

107
Q

what is the follicular phase of the ovarian cycle

A

1st half of cycle

Maturation of egg, ready for ovulation at midcycle – ovulation signals end of follicular phase

108
Q

what is the luteal phase of the ovarian cycle

A

2nd half of cycle

Development of corpus luteum.
Induces preparation of reproductive tract for pregnancy (if fertilisation occurs)

109
Q

what signals start of new follicular phase

A

degeneration of corpus luteum

110
Q

what hormone is most dominant in follicular phase

A

FSH

little LH

111
Q

Tx of male infertility

A

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
Q

Mx of infertility - general factors

A
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