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BRS - Year 2 > 🧪Endocrinology🧪 - Infertility > Flashcards

🧪Endocrinology🧪 - Infertility Flashcards

1
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.’

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2
Q

What is primary vs secondary infertility?

A

Primary infertility - not had a live birth previously
Secondary infertility - have had a live birth >12 months previously

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3
Q

Give some statistics about infertility?

A

Affects 1 in 7 couples, but half of these will then conceive in the next 12 months (i.e. after 24months, 1in14/7% of couples)
55% of couples will seek help - positive/neutral association with socioeconomic status

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4
Q

What are the most common causes of infertility in a couple?

A
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5
Q

What are the impacts of infertility on a couple?

A

Psychological distress to couple
No biological child
Impact on couple’s wellbeing
Impact on larger family
Investigations and treatments (often fail)

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6
Q

What are the impacts of infertility on society?

A

Less births
Less tax income (lower population)
Increased investigation costs
Increased treatment costs

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7
Q

What are the 3 categories of infertility causes in males?

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
Klinefelter’s syndrome, 47XXY
HPG axis issues, testosterone issues, hyperprolactinaemia issues

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9
Q

What are some testicular causes of infertility?

A

Congenital
Cryptorchidism
Infection (STDs, Mumps etc…)
Immunological (antisperm antibodies)
Vascular (varicocoele)
Trauma/surgery
Toxins (chemo/drugs/smoking)

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10
Q

What is cryptorchidism?

A

An undescended testicle

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11
Q

Why can chemotherapy cause infertility?

A

Chemotherapy targets rapidly dividing cells (usually tumours)
Testes also contain rapidly dividing cells, part of spermatogenesis, therefore leading to affects/damage by chemotherapy

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12
Q

What are some post-testicular causes of infertility?

A

Congenital (absence of vas deferens in CF)
Obstructive Azoospermia
Erectile dysfunction (retrograde ejaculation, mechanical impairment, psychological)
Iatrogenic (vasectomy) (note IAtrogenic, not LAatrogenic)

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13
Q

What is obstructive azoospermia?

A

Obstructive azoospermia is a condition in which a man’s sperm production is normal, but a blockage in the reproductive tract prevents sperm from being present in the ejaculate.

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14
Q

What does iatrogenic mean?

A

As a result of medical intervention

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15
Q

What are the causes of infertility in women?

A

Ovarian causes (40%)
Tubal causes (30%)
Uterine causes (10%)
Cervical causes (5%)
Pelvic causes (5%)
Unexplained (10%)

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16
Q

What are the ovarian causes of infertility?

A

Anovulation (usually endocrine)
Corpus luteum insufficiency

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17
Q

What are the tubal causes of infertility?

A

Tubopathy due to:
Infection
Endometriosis
Trauma

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18
Q

What are the uterine causes of infertility?

A

Unfavourable endometriosis due to:
Congenital malformations
Infection/inflammation/scarring(adhesions)
Fibroids

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19
Q

What are the cervical causes of infertility?

A

Ineffective sperm penetration due to:
Infection/inflammation
Immunological (antisperm antibodies)

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20
Q

What are the pelvic causes of infertility?

A

Endometriosis
Adhesions

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21
Q

What is endometriosis?

A

Presence of functioning endometrial tissue outside of the uterus
5% of women
Responds to oestrogen

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22
Q

What are the symptoms of endometriosis?

A

Greatly increased menstrual pain
Menstrual irregularities
Deep dyspareunia
Infertility

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23
Q

What is dyspareunia?

A

Pain during intercourse

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24
Q

How can ovulation be tested?

A

A day 21 progesterone test
Corpus luteum secretes progesterone - presence of corpus luteum means ovulation has occurred
Above 10 = ovulation

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25
Q

What are fibroids?

A

Benign tumours of the myometrium
1-20% of pre-menopausal women (increases with age)
Responds to oestrogen

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26
Q

What are the symptoms of fibroids?

A

Usually asymptomatic but can cause:
Increased menstrual pain
Menstrual irregularities
Deep dyspareunia
Infertility

27
Q

Name the following hormones/structures

A

A - kisspeptin neurons
B - GnRH neurons
C - Gonadotroph
D - LH and FSH
E - Testosterone/oestrogen
F - oestrogen and progesterone

28
Q

What is the effect of prolactin on the HPG axis?

A

Completely shuts it down
Acts on kisspeptin neurons, blocking them

29
Q

What hormone levels would you expect to see in hyperprolactinaemia

A

Low LH+FSH
Low testosterone

30
Q

What hormone levels would you expect to see in Klinefelter’s syndrome?

A

High LH+FSH
Low testosterone

31
Q

Explain the difference in hormone levels between hyperprolactinaemia and Klinefelter’s?

A

In hyperprolactinaemia, the whole axis is down so nothing is being made anywhere, as kisspeptin neurons are blocked
In Klinefelter’s, there is testicular failure, so testosterone cannot be made, but the rest of the axis is functional, so the lack of testosterone stimulates large quantities of FSH+LH to be released (negative feedback system still intact)

32
Q

What are the 3 types of endocrine male infertility?

A

Hypogonadotrophic hypogonadism (problem in the hypothalamus)
Hypogonadotrophic hypogonadism (problem in the pituitary)
Hypergonadotrophic hypogonadism (problem in the gonads)

33
Q

What hormone levels would be found in Hypogonadotrophic hypogonadism (problem in the hypothalamus) and why?

A

Low GnRH
Low FSH+LH
Low testosterone
Problem in hypothalamus means no stimulus for GnRH neurons to release GnRH, entire axis can’t start

34
Q

What hormone levels would be found in Hypogonadotrophic hypogonadism (problem in the pituitary) and why?

A

Normal/elevated GnRH
Low LH+FSH
Low testosterone
Hypopituitarism, GnRH is fine as hypothalamus is functional (and possibly raised to due no negative feedback from testosterone), however gonadotrophs are not responding and producing enough FSH+LH, so less testosterone produced as well

35
Q

What hormone levels would be found in Hypergonadotrophic hypogonadism (problem in the gonads) and why?

A

High LH +FSH
Low testosterone
Primary testicular failure, no testosterone
Rest of axis is intact, so lack of testosterone means no negative feedback, so increased FSH+LH but no response from testes

36
Q

What are some causes of Hypogonadotrophic hypogonadism (problem in the hypothalamus)?

A

Can be congenital
If anosmic - Kallmann syndrom
Otherwise normosmic
Acquired from Low BMI, excess exercise, stress
Hyperprolactinaemia (prolactin’s effect on kisspeptin neurons)

37
Q

What are some causes of Hypogonadotrophic hypogonadism (problem in the pituitary) ?

A

Hypopituitarism
Tumour, infiltration, apoplexy, surgery, radiation

38
Q

What are some causes of Hypergonadotrophic hypogonadism (problem in the gonads)?

A

Congenital primary hypogonadism - Klinefelter’s
Acquired primary hypogonadism - Cryptorchidism, trauma, chemo, radiation

39
Q

What is Kallmann Syndrome?

A

A failure of migration of GnRH neurons from the olfactory bulb to the hypothalamus during embryological development
Features include:
Anosmia (lack of smell)
Failure of puberty
Infertitlity

40
Q

What are the symptoms of hyperprolactinaemia?

A

Binds to prolactin receptors on kisspeptin neurons, stopping kisspeptin and therefore GnRH release
Oligo/amenorrhoea
Low libido(and other hypogonadal symptoms)
Infertility
Osteoporosis

41
Q

What are the treatments for hyperprolactinaemia?

A

Dopamine agonist (cabergoline)
Surgery/DXT

42
Q

What type of condition is Klinefelter’s?

A

Hypergonadotrophic hypogonadism

43
Q

What are the features of Klinefelter’s?

A

Trisomy of sex chromosomes (47XXY)
Can be more (e.g. 48XXXY, 49XXXXY etc…) and more chromosomes means more severe symptoms
Tall stature, narrow shoulders, wide hips
Low facial and chest hair
female-type pubic hair pattern, breast development
mildly impaired IQ (down 15points on average)
Small penis and tests
Infertility

44
Q

How does Klinefelter’s cause tall stature?

A

Sex hormones are needed to fuse the epiphyseal plates at the end of long bones

45
Q

How should you approach a history on male infertility?

A

Duration
Previous children
Pubertal milestones
Associated symptoms
Medications/drugs

46
Q

What are the key characteristics that should be observed in a male presenting with infertility?

A

BMI
Sexual characteristics
Testicular volume
Anosmia

47
Q

What are the key investigations for a male presenting with infertility?

A

Semen analysis
Blood tests:
LH+FSH
Morning fasting testosterone
Karyotyping
Imaging:
Scrotal ultrasound/doppler
pituitary MRI (if low LH/FSH or high prolactin)

48
Q

What are the 2 different types of treatment for male infertility?

A

General lifestyle
Specific treatment

49
Q

What are the general lifestyle treatments for male infertility?

A

Optimise BMI
Smoking cessation
Alcohol reduction/cessation

50
Q

What are the specific treatments available for male infertility?

A

Dopamine agonist for hyperprolactinaemia
GnRH treatment for fertility (will also increase testosterone)
Testosterone (for symptoms if no fertility is required - fertility requires gonadotrophins for spermatogenesis)
Surgery (e.g. micro testicular sperm extraction (micro TESE))

51
Q

What is premature ovarian insufficiency?

A

Premature ovarian insufficiency (POI), also known as premature ovarian failure (POF), is a condition where the ovaries stop functioning properly before the age of 40. It results in the loss of normal ovarian function, leading to reduced production of oestrogen and other reproductive hormones, irregular or absent menstrual periods, and often, infertility

52
Q

What pattern of hormones would you expect to see in POI?

A

High FSH+LH
Low Oestradiol

53
Q

Outline the symptoms and causes of POI?

A

Same symptoms as menopause
Previously called Premature Ovarian Failure (POF)
Conception can happen in 20%
Diagnosis is high FSH (>25iU/L) at least twice, and at least 4 weeks apart
Causes:
Autoimmune
Genetic (e.g. Turner’s syndrom)
Cancer therapy (e.g. radio/chemotherapy in the past)

54
Q

What pattern of hormones would you expect to so in anorexia nervosa-induced amenorrhoea?

A

Low LH+FSH
Low oetradiol
Need leptin from fat cells for kisspeptin neurons, anorexia = low BMI so no fat cells
No kisspeptin = no HPG axis so all hormones are low

55
Q

Outline the causes for female infertility?

A

Hypothalamic and pituitary-related causes are same as men
Hypergonadotrophic hypogonadism caused by PCOS (acquired)
Congenital is Turners (45X0) or POI
These feature high LH+FSH and low oestradiol

56
Q

Outline the epidemiology of PCOS

A

Affects 5-15% of women of reproductive age
Frequent family history
Most common endocrine disorder in women
Most common cause of infertility in women

57
Q

How is PCOS diagnoses?

A

Using the Rotterdam PCOS diagnostic criteria (2/3 needed for diagnosis)
1. Oligo/anovulation
2. Clinical +/- biochemical hyperandrogenism
Clincal = acne, hirsutism, alopecia
Biochemical = raised androgen levels (e.g. testosterone)
3. Polycstic ovaries (utrasound)

58
Q

What are the complications and consequences of PCOS?

A

Irregular menses/amenorrhoea - infertility
Increased insulin resistance - impaired glucose homeostasis
Hirsutism
Increased endometrial cancer risk

59
Q

What are the associated treatments for the consequences of PCOS?

A
60
Q

What are the symptoms of Turner’s syndrome (45X0)?

A

Short stature
Low hairline
Shield chest
Wide-spaced nipples
Short 4th metacarpal
Small fingernails
Brown nevi
Amenorrhoea
Characteristic facies, webbed neck
Poor breast development, underdeveloped reproductive tract
Coarctation of the aorta

61
Q

What is the key history for a female presenting with infertility?

A

Duration
Previous children
Pubertal milestones
Menstrual history
Medications/drugs

62
Q

What key examinations should be undertaken for a female presenting with infertility?

A

BMI
Sexual characteristics
Hyperandrogenism signs
Ansomia

63
Q

What key investigations should be undertaken for a female presenting with infertility?

A

Blood tests:
LH, FSH, prolactin
Oestradiol, androgens
Mid-luteal progesterone (day21)
Karyotyping
Pregnancy test (urine or serum HCG)
Imaging:
Transvaginal ultrasound
Hysterosalpingogram
Pituitary MRI (if low LH/FSH or high prolactin)

BRS - Year 2 (46 decks)

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