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Infertility and ART Flashcards

1
Q

Define infertility

A

The inability to conceive after 1 year of unprotected intercourse

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2
Q

What is the difference between primary and secondary infertility?

A

Primary = couple has never conceived a child
Secondary = couple previously successful in conceiving but unable to achieve a subsequent pregnancy

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3
Q

When to investigate for infertility (say woman is <35 years)?

A

After 12 months of unprotected intercourse

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4
Q

Earlier investigation for infertility may be appropriate in some women. Such as: (6)

A
  1. Age 35+
  2. Menstrual abnormality
  3. Previous abd/pelvic/urogenital surgery
  4. Hx of pelvic disease
  5. Hx of STIs
  6. Abnormal genital exam
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5
Q

What are some female factors for infertility? (3)

A
  1. Increasing age
  2. Ovulatory dysfunction
    - Anovulation
    - PCOS
    - Luteal phase defect
  3. Anatomical factors
    - Tubal dysfunction
    - Cervical factors
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6
Q

Fertility declines after __ years old, with a marked decline after __ years old

A

30; 40

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7
Q

What are some contributing factors to infertility with increased age? (3)

A
  1. Increased exposure to development of dx (endometriosis, PID)
  2. Ovulation becomes more irregular
  3. Fewer eggs, lower quality eggs remain
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8
Q

What is ovulatory dysfunction?

A

Ovaries fail to produce a mature egg on a regular basis

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9
Q

What is anovulation a result of?
What are some of the potential causes (6)

A
  1. Occurs as a result of disruption of the hypothalamic-pituitary-ovarian axis
  2. Physical injury to hypothalamus or pituitary gland (i.e. neoplasm)
  3. Obesity, anorexia, bulimia
  4. Excessive exercise
  5. Stress
  6. Exposure to chemotherapy/radiation
  7. Endocrine disorders: diabetes, thyroid dysfunction, hepatic disease
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10
Q

Polycystic ovarian syndrome (PCOS) is a syndrome of ovarian dysfunction which is characterized by: (3)

A
  1. Hyperandrogenism
  2. Ovulatory dysfunction
  3. Polycystic ovaries
    (Need at least 2/3 to meet diagnostic criteria)
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11
Q

Although the cause of PCOS is unknown at the moment, what is one theory?

A

It’s thought that peripheral insulin resistance can lead to hyperinsulinemia & stimulation of excess ovarian androgen production

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12
Q

What are the signs and symptoms of PCOS? (5)

A
  1. Menstural irregularities - amenorrhea or oligomenorrhea
  2. Hyperandrogenism
    - Hirsutism
    - Acne
    - Seborrhea
    - Alopecia
  3. Overweight/obesity
  4. Infertility
  5. 20% may be asymptomatic
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13
Q

What comorbidities is PCOS often associated with? (5)

A
  1. Reproductive Challenges
    - Infertility
    - Pregnancy complications
  2. Endometrial hyperplasia or cancer
  3. Metabolic issues
    - Diabetes
    - CVD
    - Metabolic syndrome
  4. Obstructive Sleep apnea
  5. Depression
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14
Q

What are some goals of therapy for PCOS? (5)

A
  1. Decrease/get rid of hyperandrogenic features
  2. Manage underlying cardio metabolic abnormalities
  3. Prevent endometrial hyperplasia as a result of chronic anovulation
  4. Contraception for those not wanting pregnancy (as ovulation may be intermittent with oligo..and hard to predict)
  5. Ovulation induction for pregnancy
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15
Q

What is 1st, 2nd, and 3rd line treatment of PCOS for women who are overweight/obese?

A

1st line = weight loss through lifestyle modifications
- Can help improve infertility, hirsutism, BG, BP, lipids
2nd line = pharmacotherapy
3rd line = bariatric surgery
(Lifestyle modifications [diet + exercise] are the foundation for all recommendations)

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16
Q

What is the 1st line treatment of PCOS for menstrual cycle irregularities?

A

1st line = CHCs
- Regulate menstruation in those with oligomenorrhea
- Protects from endometrial hyperplasia; chronic anovulation is associated with increased risk
- Typically start with a low dose of EE and a progestin with low androgenicity

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17
Q

What are the alternative treatments of PCOS for menstrual cycle irregularities? (2)

A
  1. Progtesin-only therapy
    - Do not help with androgenic symptoms
  2. Metformin
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18
Q

What is 1st line treatment for hirsutism in PCOS?

A

CHCs
- Oral, patch, ring
- Suppress androgen

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19
Q

What is 2nd line treatment for hirsutism in PCOS? (3)

A

Add an antiandrogen (usually if suboptimal response at 6 months)
- Spironolactone (6-9 months for improvement)
- Finasteride
- Eflornithine HCl cream - topical agent to inhibit hair growth (needs to be used indefinitely to prevent the growth)

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20
Q

What is the 1st line treatment for acne in PCOS? (1)
What are the alternatives? (2)

A

1st line = CHC (particularly low androgen progestins)
2. Topical acne meds
3. Consider spironolactone

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21
Q

What are the treatment options for fertility in PCOS? (6)

A
  1. Lifestyle modification
  2. Letrozole
  3. Clomiphene citrate
  4. Metformin
  5. Gonadotropins
  6. IVF
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22
Q

What is 1st line treatment for hypothalamic pituitary failure and PCOS?

A

Ovulation induction

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23
Q

What is the first line medication for infertility treatment in PCOS?

A

Letrozole

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24
Q

What is the MOA of letrozole? (2)

A
  1. An aromatase inhibitor that is used off-label (1st line) to help with anovulation
  2. As aromatase is suppressed, so are estrogen levels, and the hypothalmus & pituitary gland increase FSH output which stimulates ovarian follicles to develop and mature in the ovary so ovulation can occur
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25
Q

What is the dosing of letrozole? How long?

A
  1. Common dose: 2.5mg/d x 5 days (Days 3-7 or 5-9)
  2. May increase to 5mg/d x 5 days (Days 3-7 or 5-9)
    On average - 3 cycles
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26
Q

What are the side effects of letrozole? (4)

A
  1. Hot flashes or night sweats
  2. Fatigue
  3. Nausea
  4. Multiple births
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27
Q

What is the contraindication of letrozole and clomiphene?

A

Pregnancy

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28
Q

What is the medication alternative to letrozole for treatment of infertility in PCOS?

A

Clomiphene citrate - compounding pharmacies only

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29
Q

What is the MOA of clomiphene?

A

It is a SERM; it blocks estradiol receptors in hypothalamus which increase gonadotropin (FSH) release. This results in growth of the ovarian follicle and in turn ovulation

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30
Q

What are some ADEs to clomiphene use? (4)

A
  1. Multiple gestations
  2. Hot flashes
  3. Abdominal discomfort
  4. Vision disturbances - blurring, spots, or flashes
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31
Q

When using clomiphene or letrozole, ovulation is expected _-__ days after the last dose

A

5-10

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32
Q

Compare efficacy of letrozole and clomiphene

A

Letrozole appears to be more effective than clomiphene citrate for achieving live birth in patients with ovulatory disorders . For unexplained infertility both clomiphene & letrozole appear to be equally effective, but less effective than gonadotropin-based treatments
(Success with ovarian stimulation declines with age)

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33
Q

What is the optimal timing and frequency of intercourse for someone trying to conceive?

A

Around ovulation (4-5 days prior to ovulation) every 24-48 hours

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34
Q

How does metformin potentially help with fertility? (3)

A
  1. Works by decreasing hepatic glucose output and improving peripheral insulin sensitivity
  2. Results in lower insulin levels and decreased androgen production
  3. Use: usually as an add-on to clomiphene
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35
Q

Name the GnRH agonist that might be used to help aid fertility

A

Gonadorelin acetate

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36
Q

Name the gonadotropins that might be used to help aid fertility (4)

A
  1. hMG
  2. hCG
  3. Urofollitropin
  4. Follitropin alpha and beta
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37
Q

What is luteal phase defect? (2)

A
  1. Insufficient progesterone levels do not allow for preparation of the endometrium for implantation –> failure to implant
  2. The uterine lining doesn’t grow properly, hence there may be difficulty with achieving or maintaining pregnancy
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38
Q

What might luteal phase defect be associated with? (6)

A
  1. Endometriosis,
  2. Anorexia
  3. Excessive exercise
  4. Hypothyroid,
  5. Hyperprolactinemia
  6. Obesity
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39
Q

What is the treatment for luteal phase defect?

A

Progesterone is used for luteal phase support to improve pregnancy rates when used with ovulation stimulators, gonadotropins (with or w/o IVF)

40
Q

True or False? You may see progesterone being used in women trying to get/maintain pregnancy

A

True

41
Q

What are some potential anatomical factors contributing to infertility? (3)

A
  1. Blocked fallopian tubes
    - Causes: endometriosis, pelvic inflammatory disease (PID), IBD, ruptured appendix, ectopic pregnancy
  2. Endometriosis:
    - Endometrial tissue outside of the uterus can cause anatomical distortion and damage the fallopian tubes
    - Prevalence much higher in infertile vs. fertile women
  3. PID:
    - A serious complication of some STIs
42
Q

What are 4 management options for infertility-associated endometriosis?

A
  1. NSAIDs for pain relief
  2. Watchful waiting
  3. Conservational surgery
    - Laparascopic tx of mild endometriosis improves pregnancy rates, however effectiveness on deeply infilitrating endometriosis is controversial
  4. Ovarian stimulation or In Vitro fertilization
43
Q

Male factor infertility overall contribution to infertility is __%

A

30

44
Q

Male factor infertility can be due to: (4)

A
  1. Obstructive/physical/genetic factors
  2. Sexual intercourse factors
  3. Endocrine factors
  4. Gonadotoxic (sperm) factors
45
Q

What are the potential obstructive/physical/genetic factors contributing to male infertility? (5)

A
  1. Trauma
  2. Surgery
    - Abdominal, prostate, others
  3. STI
  4. Cystic fibrosis
  5. Klinefelter syndrome
46
Q

What are 3 sexual intercourse factors potentially contributing to male infertility?

A
  1. Decreased libido
  2. Erectile dysfunction
  3. Impaired ejaculation
47
Q

What are 2 endocrine factors potentially contributing to male infertility?

A
  1. Obesity
  2. Hypothalamic or pituitary dysfunction alters the secretion of FSH, LH, and testosterone
48
Q

What are some environmental and lifestyle factors potentially contributing to male infertility? (6)

A
  1. Heavy alcohol use
  2. Cigarette smoking
  3. Excessive heat to scrotal area
  4. Radiation
  5. Toxin exposure: pesticides, organic solvents
  6. Electromagnetic energy?
49
Q

What are some drug-induced causes potentially contributing to male infertility? (8)

A
  1. Marijuana, cocaine
  2. Chemotherapy
  3. Anabolic steroids
  4. Cimetidine
  5. Finasteride
  6. Spironolactone
  7. Sulfasalazine
  8. Nitrofurantoin
50
Q

What are the treatment options for male factor infertility? (5)

A
  1. Correct the modifiable risk factors
  2. Surgical repair –> varicoceles; obstructive lesions
  3. Hormone therapy –> Hypogonadotrophic hypogonadism
    - Decreased testosterone, LH, and FSH
    - Tx with hormone therapy: gonadotropins or pulsatile GnRH infusion
  4. Sperm cryopreservation
  5. Assisted reproductive technologies (ART)
    - Artificial insemination with donor sperm
    - ICSI (intracytoplasmic sperm injection)
51
Q

Describe basal body temperature (BBT) (4)

A
  1. BBT is the temperature that occurs prior to rising in the am
  2. Progesterone is thermogenic (elevated levels cause an increase in temp). With ovulation, the corpus luteum releases progesterone causing an increase in temperature of approx. 0.5ºF or 0.28ºC.
  3. The rise in temperature is caused by ovulation, therefore measure temp. to find most fertile period
  4. Temperature rise occurs over a period of up to 3 days and is usually maintained until day 1 of menses.
52
Q

What are some counseling tips regarding BBT charting? (4)

A
  1. Take 1st measurement on 1st day of menstrual period.
  2. Take temperature for at least 5 minutes each morning upon awakening, before any activity or getting out of bed.
  3. Record information for 1-3 cycles in order to identify a pattern
  4. Chart temp on graph daily. Indicate on chart when intercourse occurs, illness, changes in sleeping pattern, when meds are taken…
53
Q

How do ovulation prediction kits work?

A

These kits detect the LH surge that precedes ovulation by measuring its concentration in urine

54
Q

How to use an ovulation prediction kit? (2)

A
  1. Chart menstrual cycle ahead of time so that ovulation may be predicted; it also useful to know that the most fertile period is 14 days before the next menses –> hence count backwards
  2. Begin testing 2-4 days before anticipated ovulation at same time of day (usually am)
55
Q

At what age does the definition of infertility change?

A
  1. Within 12 months in patients <35 years old
  2. Within 6 months in patients 35+ years old
56
Q

The most important factor in female infertility is ___

A

age
- as reserves decline, so do the quality of the eggs

57
Q

Why are we seeing an increase in infertility rates? (3)

A
  1. Increased maternal age
  2. Starting families later
  3. People talk about it and share more online nowadays
58
Q

What is ovulation induction (OI)? (drugs, timingx2)

A
  1. Clomiphene or letrozole
  2. Timed intercourse
  3. With or without “trigger” shot
59
Q

What is super ovulation (SO)?
What is the goal?
Often combined with?
Medications?

A
  1. Ovaries are stimulated with hormones to produce follicles
  2. Goal: to produce 2-4 eggs
  3. Often combined with intrauterine insemination (IUI)
  4. Medications used for SO & IVF are the same
    - Lower dose with SO
60
Q

What is intrauterine insemination?
How is it done (2)?

A
  1. Inserting the sperm directly into the uterus
  2. Sperm are prepped prior to insertion
    - Separated in a centrifuge
    - Evaluated
    - Washed
  3. May be done +/- superovulation
61
Q

What is intra-cytoplasmic sperm injection (ICSI)?

A

Injecting the sperm directly into the egg

62
Q

ICSI may be used for: (4)

A
  1. Low sperm count
  2. Impaired sperm penetration
  3. Anti-sperm antibodies
  4. Previous IVF failure
63
Q

What is stage 1 of IVF?

A

Controlled Ovarian Stimulation

64
Q

What is controlled ovarian stimulation?

A

Stimulation of ovaries with hormones to produce follicles

65
Q

Typical IVF stimulation lasts _-__ days

A

8-14

66
Q

With controlled ovarian stimulation in IVF, there is intense monitoring of these 3 things:

A
  1. Estrogen
  2. Progesterone
  3. Follicular development and size
67
Q

What are the FSH (3) and LH (1) drugs used in controlled ovarian stimulation

A

Follicle stimulating hormone (FSH):
- Follitropin alpha (Gonal F)
- Follitropin beta (Puregon)
- Follitropin delta (Rekovelle)
Luteinizing hormone (LH):
- e.g. lutropin alfa (Luveris)

68
Q

What are the 2 sources of hormones (thinking controlled ovarian stimulation)

A
  1. Urinary
  2. Recombinant
69
Q

How are urinary hormones collected? (2)
Limitations?
Safety?

A
  1. Post menopausal women
  2. Pregnant patients
  3. Limitations due to amount of urine able to be collected
  4. Safety - local sensitivity reactions (might see a wheal reaction, but it’s not allergic, so safe to continue)
70
Q

How are recombinant hormones collected?
How do they differ from urinary in terms of efficacy and safety?

A
  1. Synthetic/recombinant DNA technology
  2. Purity, safety, consistency is good
  3. Efficacy seems to be about the same as urinary
71
Q

During controlled ovarian stimulation there is a ‘control’ phase. What is the purpose?

A

Control to prevent premature ovulation using GnRH agonists or antagonists

72
Q

What are 3 GnRH agonists?

A
  1. Leuprolide
  2. Nafarelin acetate
  3. Buserelin
73
Q

What are 2 GnRH antagonists?

A
  1. Ganirelix
  2. Cetrorelix
74
Q

What is the MOA of GnRH agonists? (4)

A
  1. Binding to pituitary receptors
  2. Induce release of large amounts of FSH and LH (“flare-up”)
  3. Increase GnRh receptors (upregulation)
  4. Prolonged use (7-10 days of use) = decrease in GnRH receptors (down regulation) and hence a decrease in gonadotropins
75
Q

What is the MOA of GnRH antagonists? (4)

A
  1. Competitively binding GnRH receptors to prevent endogenous pulses on the pituitary
  2. Work relatively quickly (within hours of admin) and no “flare-up” occurs
  3. Discontinuation rapidly results in recovery of the pituitary-gonadal axis
  4. Highly dose dependent (remember there is endogenous and exogenous hormone)
76
Q

What are the 3 protocols for doing controlled ovarian stimulation?

A
  1. GnRH antagonist protocol
  2. GnRH agonist short protocol
  3. GnRH agonist long protocol
77
Q

What are some considerations for doing controlled ovarian stimulation? (5)

A
  1. Previous experience
  2. Good or poor responder
  3. Risk of hyperstimulation
  4. Risk of premature ovulation
  5. Number of injections
78
Q

What is a risk of ovarian stimulation?

A

Ovarian Hyperstimulation Syndrome (OHSS)

79
Q

What is ovarian hyperstimulation syndrome?
What does it result in?
(5 total)

A
  1. Ovaries are over stimulated
  2. Intensely monitored by clinic
  3. Modifications to protocol will be made
  4. Very painful
  5. Possibly detrimental
80
Q

What is the first steps of oocyte retrieval? What is the purpose? (3)

A
  1. “Trigger” shot
    - HCG
    - Choriogonadotropin alpha (Ovidrel)
  2. Matures egg
  3. Prepares for ovulation
81
Q

Oocyte retrieval occurs __-__ hours after the trigger shot

A

34-36
timing is of the utmost importance

82
Q

How many oocytes are ideally retrieved during oocyte retrieval?

A

10-12 well developed ones

83
Q

What is the luteal phase support part of oocyte retrieval?

A
  1. Progesterone to support the pregnancy
  2. Changes endometrium from follicular to luteal phase
    - Progesterone vaginal tablets or gel
    - Off-label: micronized progesterone, IM progesterone
84
Q

What is stage 3 of IVF?

A

Sperm collection/retrieval

85
Q

Why might sperm need to be be retrieved rather than collected? (4)

A
  1. Obstructive
  2. Non-obstructive
  3. Neurological such as spinal cord injury
  4. Retrograde ejaculation
86
Q

Fertilization should occur within __-__ hours after exposing oocyte to sperm

A

18-24

87
Q

Once fertilization has occurred, embryos are transfered to a growth medium, assessed, & incubated for __ hours

A

24

88
Q

Transfers of fertilized egg occurs on which days?

A

Day 2 or 3 (embryo transfer)
Day 5 (blastocyst transfer)

89
Q

How many embryos/blastocysts are usually transfered?

A

Usually 1 or 2
(3-4 may be transferred)

90
Q

Embryo/blastocyst transfer amount is dependent on factors such as? (3)

A
  1. Previous pregnancies
  2. Maternal age
  3. Medical history
91
Q

What are some side effects that may occur during the entire IVF process? (10)

A
  1. Headache
  2. Mood changes
  3. Injection site discomfort, bruising
  4. Hot flashes
  5. Breast tenderness
  6. Wheal response
  7. Bloating
  8. Constipation
  9. Nausea, cramping
  10. Fatigue and Exhaustion
92
Q

What is the success rate of IVF/infertility treatment?

A

~60-70%

93
Q

3rd party IVF variations can include: (4)

A
  1. Donor eggs
  2. Donor sperm
  3. Donor embryo
  4. Surrogate
94
Q

Cryopreservation of eggs. What are some reasons for doing this? (6)

A
  1. Donor and carrier synchronization/ timing issues
  2. Suboptimal uterine environment during start of ART protocol
  3. Issues discovered during the process
  4. Preservation of reproductive potential e.g. patient undergoing chemo/radiation
  5. Decreases future costs if lots of embryos to freeze and then do a frozen cycle
  6. Freeze to decrease damage of repeated procedures if retrieval required e.g. sperm
95
Q

What are some of the costs associated with infertility treatment? (7)

A
  1. Medications
    - Insurance?
    - Out-of-pocket?
    - Provincial coverage?
  2. Procedures
  3. Monitoring
  4. Travel
  5. Time off work
  6. Mental
  7. Physical
96
Q

What are the 3 provinces that do not cover the cost of procedures like IVF or IUI?

A
  1. AB
  2. BC
  3. SK

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