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Stage 2: Human Deveopment > Infertility > Flashcards

Infertility Flashcards

1
Q

At what 3 steps of the HPG axis can problems occur leading to gonadal dysfunction?

A

1) Problem with driver - hypothalamic, pituitary
2) Problem with the functional units (follicles) - none, limited, insensitive
3) Problem with the receiver - absent, insensitive, obstructed

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2
Q

What 4 things can go wrong in a female?

A

1) Puberty sequence
2) Oestrogen dominance
3) Effect of hypoestrogenic status
4) Effect of hyperandrogenic status

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3
Q

What are 5 causes of anovulation?

A

1) Hypothalamic dysfunction
2) Pituitary dysfunction
3) Thyroid dysfunction
4) Ovarian failure
5) PCOS

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4
Q

Describe PCOS

A
  • In polycystic ovaries, the follicles are not competing, one dominant follicle will present itself (why the cycle is not consistent)
  • Need lifestyle interventions (weight loss) which restores ovulation and achieves spontaneous pregnancy
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5
Q

What are the most common causes of ovulatory dysfunction?

A

1) PCOS (70%)
2) Hypothalamic amenorrhea (10%)
3) Hyperprolactinaemia (10%)
4) Premature ovarian failure (10%)

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6
Q

How does obesity affect fertility?

A

Obese woman are less fertile, have higher rates of miscarriage and require higher doses of ovulation-inducing agents

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7
Q

How can weight loss be used to treat infertility?

A
  • Weight loss restores ovulation and achieves spontaneous pregnancy
  • It is effective and cheap with no side effects and should be the first line of treatment in obese women with anovulatory infertility
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8
Q

What are central obesity and BMI major determinants of?

A

1) Insulin resistance
2) Hyperinsulinaemia
3) Hyperandrogenaemia

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9
Q

What are problems with ovulation related to the 2 phases of the menstrual cycle?

A

1) Follicular phase → no egg

2) Luteal phase → transport in tubes, tubal factor - absence/non-functioning of tubes

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10
Q

What medication is used to treat anovulation/infertility?

A

Clomiphene citrate

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11
Q

How does clomiphene citrate work?

A
  • FSH stimulates ovulation

- Clomiphene citrate stimulates endogenous FSH production

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12
Q

When is clomiphene citrate used?

A

It is the first line of treatment for those with absent or irregular ovulation but who have normal basal levels of endogenous estradiol

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13
Q

What is laparoscopic ovarian drilling used for?

A

To treat infertility - drill in 4 places to a depth of 4-10mm on each ovary
- this destroys the stroma and brings down LH

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14
Q

How successful is laparoscopic ovarian drilling?

A

82% ovulation, 63% conception rate

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15
Q

What are factors/causes of hypogonadotropic hypogonadism?

A

1) Damage to pituitary gland or hypothalamus from surgery, injury, tumour, infection or radiation
2) Low BMI (<20) - reversible
3) High intensity exercise
4) Certain dietary patterns incl. high fibre, low fat diets
5) Excessive stress

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16
Q

How effective is ovulation induction with gonadotropins?

A

Cumulative conception rates of 90% for gonadotropin-deficient patients are 6 months of treatment with hMG (human menopausal gonadotropin)

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17
Q

What are complications of gonadotropin therapy (IVF?)?

A

1) OHSS (ovarian hyper stimulation syndrome) and multiple pregnancies - both caused by multiple follicular development (which can all rupture at once)
2) Anovulatory women with PCOS are particularly prone to multiple follicular development when receiving gonadotropins - so monitor dose using transvaginal scan as need to make sure there is only one dominant follicle (don’t want triplets)

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18
Q

When is ovulation induced with pulsatile GnRH used?

A

Tailor made for patients who have an intact pituitary gland

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19
Q

Describe ovulation induced with pulsatile GnRH

A
  • An infusion pump, either SC or IV once every 60-90min
  • Safe, simple and effective
  • Compared with gonadotropin treatment, needs little or no monitoring and low multiple pregnancy and OHSS rate
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20
Q

What are the 2 main causes of hyperprolactinaemia?

A

1) Prolactin-secreting pituitary gland tumour

2) Use of psychiatric medications

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21
Q

What should all women with hyperprolactinaemia be tested for?

A

1) Hypothyroidism (TSH and/or thyroid hormones)

2) Pregnancy

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22
Q

What is the choice treatment for ovulation induction in women with hyperprolactinaemia and why?

A

Dopamine-agonist drugs → Dopamine is the main hormone that controls PRL
→ They directly suppress prolactin production by the tumour and cause an increase in endogenous GnRH secretion, which stimulates the pituitary gland secretion of LH and FSH → induces follicle development and ovulation

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23
Q

How does age affect fertility?

A

1) Age reduction in fecundity → decrease pregnancy rate, increase miscarriage rate
2) Age-related increase in aneuploidy due to non-disjunction

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24
Q

What is ovarian reserve (OR)?

A

The number (and quality?) of the follicles left in the ovary at any given time

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25
Q

Why is there declined fertility with age?

A

1) Germ cells in the female are not replenished during life
2) Attrition and utilisation of follicles leads to a decline in the number of oocytes from birth to menopause
3) The quality of existing oocytes diminishes with age
4) On average, intercourse frequency declines with age

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26
Q

Describe age-related ovulation dysfunction and premature ovarian failure

A

1) The ovarian follicular pool depletes with age
2) The remaining follicles appear to be less capable of fertilisation and establishing a successful pregnancy
3) Inhibin B production by the small follicles decreases with age, so the inhibin suppression of FSH secretion decreases and pituitary gland secretion of FSH increases

27
Q

What is an elevated day 3 FSH level in women with menses is highly sensitive and specific for what?

A

For identifying women with a depleted ovarian follicular pool

28
Q

What physiological events are required for conception?

A

1) Ovulation
2) Spermatogenesis
3) Intercourse
4) Ejaculation
5) Fertilisation
6) Implantation

29
Q

What is defined as infertility in a woman?

A

A woman of reproductive age who has not conceived after 1 year of unprotected sexual intercourse

30
Q

Describe the incidence of infertilty

A
  • Affects 1 in 7 couples
  • Slight increase in prevalence in recent years
  • Figures may rise with delayed parenthood
31
Q

After how many years of trying are you very unlikely to get pregnant?

A

3

32
Q

What is the most significant predictor of successful outcome after infertility and chances of a live birth after IVF?

A

Women’s age

33
Q

What is sub-fertility?

A

Reduced chance of getting pregnant

34
Q

What causes sub-fertility

A

1) Male factor (sperm)
2) Anovulation
3) Tubal factor (fallopian tubes)
4) Subtle factors (unexplained) that are not detectable on routine investigations

35
Q

What is primary infertility?

A

When the woman has never been pregnant

36
Q

What is secondary infertility?

A

When the woman has been pregnant before

37
Q

What could pregnancy be a risk factor for?

A

Tubule disease so want to assess fallopian tubes

38
Q

What guidance and advice is provided for infertility?

A

1) Timed intercourse causes stress and is not recommended
2) Smoking reduces women’s fertility and reduces semen quality
3) Excessive alcohol is detrimental to semen quality
4) BMI > 25 - reduced fertility in both men and women

39
Q

What information would you want to know when taking an infertility history from a couple?

A

1) How long together
2) How long trying to conceive
3) Pregnancies together and outcomes
4) Pregnancies with previous partners
5) Smoking, alcohol
6) Coital frequency, timing and problems

40
Q

What information would you want to know when taking an infertility history from the female?

A

1) Age
2) Cycle - regular cycle = normal ovulation
3) Weight/change in weight
4) Drugs
5) Risk of tubal disease - STI, ectopic, surgery - if no, then most likely that fallopian tubes are fine
6) History of endometriosis

41
Q

What information would you want to know when taking an infertility history from the male?

A

1) Occupation
2) Testicular maldescent - if left late (age 8/9) could have effect
3) Trauma
4) Infections - STI, mumps orchitis (damage in testes and sperm production)
5) Surgery
6) Drugs - therapeutic, recreational

42
Q

What are basic investigations that can be done to investigate infertility?

A

1) Assessment of ovulation
2) Semen fluid analysis
3) Pelvic anatomy and tubal patency
4) Ovarian reserve

43
Q

Describe assessment of ovulation

A
  • Over 95% of women with regular menstrual cycles are likely to be ovulating
  • Midluteal progesterone, 7 days before the next expected period (D21) - want it in ovulatory range
  • Basal body temperature and urinary LH (no beneficial effect)
44
Q

Describe semen analysis

A

1) Concentration → volume > 1.5ml, density > 15 x 10^6/ml
2) Motility → need to be able to get to the egg - >40% progressively motile
3) Morphology - need to have a structure to allow fertilisation > 4% normal (but if motility and concentration is ok is probably fine)

45
Q

Describe assessment of pelvic anatomy and fallopian tubes patency

A

In all 3 are passing fluid through fallopian tubes and exit into cervix - shows tubes aren’t blocked

1) Laparoscopy and dye - gold standard in tubal patency evaluation bc also looking at anatomy, no scar tissue or adhesions (normally done more therapeutically)
2) Hysterosalpingogram (HSG) - contrast and X ray
3) Hystero contrast sonogram (hycosy)

46
Q

Describe ovarian reserve

A
  • Number and quality of oocytes decline with a woman’s age as does her overall fertility
  • Measures to assess ovarian reserve used to predict the likelihood of a successful response to ovarian stimulation with assisted reproduction treatment, although seem to have poor correlation with pregnancy outcomes
  • Testing for ovarian reserve is mainly a measure of quantity but also reflects the quality of the oocytes
  • A woman’s age at the time of treatment remains the best predictor for oocyte quality
47
Q

What is used to measure ovarian reserve?

A

1) Early follicular FSH (not v accurate)
2) Antral follicle count (AFC)
3) AMH (anti-mullerian hormone) - most commonly used

48
Q

Describe the early follicular FSH test for ovarian reserve

A
  • Traditional test for ovarian reserve
  • Inter-cycle variability - so not very reliable e.g. can be v low one month
  • An elevated early follicular FSH level is highly sensitive for identifying women with a depleted ovarian follicular pool
49
Q

Describe AFC to test for ovarian reserve

A
  • The count of antral follicles → 8 follicles is normal (unlikely to vary e.g. 7-9)
  • Correlates well with ovarian response
  • Variability between observers can occur
  • Best checked in the early follicular phase (via US)
50
Q

Describe AMH to test for ovarian reserve

A
  • AMH is produced by granulosa cells, from the pre-antral and antral follicles
  • Can be measured anytime in the cycle and inter-cycle variability is low
  • Can be accurately measured in women receiving hormonal contraception
  • AMH equally effective to AFC bc granulosa cells are produced by follicles (?)
  • Adequate accuracy for predicting poor response in regularly cycling women
  • Has hardly any clinical value for pregnancy prediction
  • May well be used as a screening test for possible poor responders
51
Q

What else may well be the best predictor of ovarian reserve?

A

Response achieved during an ART (assistive reproductive technology) cycle

52
Q

What is the normal size of a follicle?

A

2-9mm

53
Q

What other investigations can be carried out for infertility?

A

1) D2-4 hormone profile - FSH, LH, PRL, TSH, testosterone
2) Rubella
3) Cervical smear
4) Chlamydia swabs
5) Viral serology (Hep B, Hep C, HIV)
6) US looking at anatomy as well

54
Q

What characteristics would warrant early referral?

A

1) Female age >35
2) Low ovarian reserve
3) Amenorrhoea or oligomenorrhoea
4) Suspected tubal factor - surgery, infection
5) Suspected male factor

55
Q

What are common causes of tubal damage e.g. adhesions?

A

1) Infection - PID (pelvic inflammatory disease), STI
2) Surgery e.g. ruptured appendix
3) Ectopic pregnancy
4) Endometriosis

56
Q

When is IVF (assisted conception) used and how?

A

When there is tubal disease

  • Bypass fallopian tubes
  • FSH injections to stimulate eggs to grow (no negative feedback)
  • Multiple follicles
  • Mix egg and sperm
57
Q

What is ICSI?

A

Intracytoplasmic sperm injection → injecting sperm into egg (if problem with sperm)

58
Q

What are the 3 classifications of ovulatory disorders?

A

1) Group 1 → hypothalamic pituitary failure - hypothalamic amenorrhoea or hypogonadotrophic hypogonadism
2) Group 2 - hypothalamic pituitary ovarian dysfunctions (mainly PCOS)
3) Group 3 - ovarian failure

59
Q

What are the treatment options for anovulation?

A

Both are for ovulation induction

1) Clomiphene citrate
2) Gonadotrophins - FSH in small doses

60
Q

What are causes of male sub-fertility?

A

Damaged/absent spermatogenesis, blocked/absent genital tracts

1) Infection - mumps, STIs
2) Truma
3) Drugs
4) Radiotherapy
5) Varicocele - enlargement of the veins within the scrotum
6) Congenital

61
Q

What is azoospermia?

A

When the semen doesn’t contain any sperm

62
Q

Describe the 2 types of azoospermia

A

1) Obstructive azoospermia (normal spermatogenesis) → normal sized testes and FSH level - post infection, post vasectomy, congenital absence of vas deferens
2) Non-obstructive azoospermia (impaired spermatogenesis) → small testes, raised FSH - testicular failure, 50% have evidence of spermatogenesis on testicular biopsy

63
Q

Describe sperm retrieval for ICSI

A
  • Local anaesthetic
  • Outpatient procedure
  • Samples may be stored for future cycles
64
Q

What two techniques are used to retrieve sperm for ICSI?

A

1) Percutaneous epididymal sperm aspiration (PESA)

2) Testicular sperm extraction (TESE)

Stage 2: Human Deveopment (34 decks)

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