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PHAR 359 > Infertility > Flashcards

Infertility Flashcards

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1
Q

What is infertility?

A

The inability to conceive after 1 year of unprotected intercourse

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2
Q

What are the two types of infertility?

A

Primary infertility: couple has never conceived a child

Secondary infertility: couple is previously successful in conceiving but unable to acheive a subsequent pregnancy

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3
Q

What is the impact of infertility on couples?

A

Emotionally and psychologically difficult (anger, sadness, jealousy, guilt)

Impacts relationships

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4
Q

When should infertillity be investigated?

A

Woman under 35, and after 12 months of unprotected intercourse

Earlier investigation is appropriate in the following groups:
- Age over 35
- Menstrual abnormality
- Previous urogenital surgery
- History of pelvic disease and STIs
- Abnormal genital exam

Initial male infertility evaluation is non-invasive

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5
Q

What are some risk factors for female factor infertility?

A

Increasing age

Ovulatory dysfunction
- Anovulation
- PCOS
- Luteal phase defect

Anatomical factors
- Tubal dysfunction
- Cervical factors

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6
Q

Why is increased age a risk factor for infertility?

A

Increased exposure to development of disease (ex. endometriosis, PID)

Ovulation becomes more irregular

Fewer eggs, lower quality eggs remain

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7
Q

What causes anovulation?

A

Occurs as a result of disruption of the hypothalamic-pituitary-ovarian (HPO) axis
- Physical injury to hypothalamus or pituitary
- Obesity, anorexia, bulimia
- Excessive exercise
- Stress
- Exposure to chemo/rad
- Endocrine disorders (diabetes, thyroid, hepatic disease)

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8
Q

What are some diagnostic criteria PCOS?

A
  1. Hypogonadism
  2. Ovulatory dysfunction
  3. Polycystic Ovaries

Need 2-3 symptoms to diagnose

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9
Q

What causes PCOS to develop?

A

Peripheral insulin resistance leads to hyperinsulinemia and stimulation of excess ovarian androgen production

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10
Q

What are some signs of PCOS?

A

Menstrual irregularities (amenorrhea or oligomenorrhea)

Hyperandrogenism (hirsutism, acne, alopecia)

Overweight/Obesity (60-70%)

Infertility (70%)

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11
Q

What are some conditions that are associated with PCOS?

A

Reproductive challenges
- Infertility
- Pregnancy complications

Endometrial hyperplasia or cancer

Metabolic issues
- DM
- CVD
- Metabolic Syndrome

Obstructive Sleep Apnea

Depression

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12
Q

What are the goals of treatment for PCOS?

A
  • Reduce or eliminate hyperandrogenic features
  • Manage underlying cardio metabolic abnormalities
  • Prevent endometrial hyperplasia due to chronic anovulation
  • Contraception for those not wanting pregnancy
  • Ovulation induction for pregnancy
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13
Q

What are the treatment options for PCOS?

A

1st line: weight loss for overweight women
- Improve fertility, help with hirsutism, can help with BG, BP. lipids

2nd line: pharmacotherapy
3rd line: bariatric surgery

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14
Q

What are some treatment options for menstrual cycle irregularities with PCOS?

A

1st line: CHCs (oral route preferred, start with low dose estrogen and progestin with low androgenicity, assess for VTE risk)
- Regulate menstruation
- Protects against endometrial hyperplasia
- Helps androgenic symptoms

Alternatives:
- Progestin-only therapy (LNG IUS, cyclic progestins, progestin-only pill)
- Metformin (off-label use, improves glucose tolerance, reduced androgen production in ovaries)

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15
Q

What are some treatment options for hirsutism in PCOS?

A

1st line: CHC (oral preferred, try for 6 months before moving on)

2nd line: antiandrogen (spironolactone & finasteride)

3rd line: Eflornithine cream (directly inhibits hair growth)

Non-drug: laser treatment, electrolysis, waxing

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16
Q

What are some treatment options for acne in PCOS?

A

1st line: CHCs (particularly low androgen progestins)

Topical acne medications
Consider spironolactone

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17
Q

What are some pharmacological treatment options for improving fertility in women with PCOS?

A
  • Letrozole (1st line drug option)
  • Clomiphene citrate
  • Metformin
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18
Q

What is the MOA of letrozole in treatment of infertility in women with PCOS?

A

Aromatase inhibitor (off-label use to help with anovulation)

By supressing aromatase, estrogen also falls. Lower estrogen levels promote production of FSH, which stimulates ovarian follicles to develop and mature

70-80% of patients will ovulate and a pregnancy rate of 30%

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19
Q

What is the dosing for letrozole?

A

Take 2.5mg for 5 days during either days 3-7 or days 5-9 of the menstrual cycle

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20
Q

What are some side effects associated with letrozole?

A

Hot flashes
Fatigue
Nausea
Multiple births (twins)

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21
Q

What is the MOA of clomiphene citrate for treatment of infertility among women with PCOD?

A

It is a SERM and blocks estradiol receptors in the hypothalamus which allows for FSH release and subsequent follicular stimulation and ovulation

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22
Q

How is clomiphene citrate dosed to induce ovulation in women with infertility due to PCOS?

A

take 50mg daily for 5 days staring on day 5 of the menstrual cycle or at any time if amenorrheic

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23
Q

What are some adverse effects associated with clomiphene citrate?

A

Multiple gestations (higher risk vs. letrozole)
Hot flashes
Abdominal discomfort
Vision disturbances

CI in pregnancy just like letrozole

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24
Q

When are letrozole and clomiphene expected to induce ovulation?

A

5-10 days after the last dose

Letrozole is more effective for acheiving live birth in patients with ovulatory disorders

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25
What is the optimal timing for intercourse to maximize chances of becoming pregnant?
4-5 days prior to ovulation and every 24-48 hours (ensure ejaculate volume and healthy sperm)
26
What is the utility of metformin on treating infertility in women with PCOS?
Works by helping reduce weight and improves cycles by regulating the insulin component of PCOS
27
27
What is the dosing for metformin for treatment of infertility in women with PCOS?
Start with 250-500mg, and gradually increase Can d/c once pregnancy acheived in women with no history of T2DM
28
What is luteal phase defect?
Insufficient progesterone levels do not allow for the preparation of the endometrium for implantation Difficulty acheiving or maintaining pregnancy
29
How is luteal phase defect treated?
Progesterone is used for luteal phase support
30
What are some causes for blocked fallopian tubes resulting in infertility?
Endometriosis Pelvic inflammatory disease (PID is a serious complication of some STDs)
31
What are some treatment options for infertility-associated endometriosis?
1. NSAIDs for pain relief 2. Watchful waiting 3. Conservational surgery (remove surface endometriosis) 4. Ovarian stimulation or in-vitro fertilization
32
What are some causes of male factor infertility?
Unknown (40-60%) Obstructive/physical/genetic factors Sexual intercourse factors Endocrine factors Gonadotoxic (sperm) factors
33
What are some obstructive factors that can cause male factor infertility?
- Trauma - Surgery (abdominal, prostate, others) - STIs - Cystic fibrosis - Klinefelter syndrome
34
What are some sexual intercourse factors that are linked with male factor infertility?
Decreased libido Erectile dysfunction Impaired ejaculation (retrograde)
35
What are some endocrine factors associated with male factor infertility?
Obesity Hypothalamic or pituitary dysfunction alters the secretion of FSH, LH, and testosterone
36
What are some sperm factors that can affect male fertility?
Environmental: - Alcohol, cigarette, excessive heat, radiation, toxin exposure Drug-induced: - Marijuana, cocaine, chemo, steroids, finasteride, spironolactone, nitrofurantoin
37
What are some treatment options for male factor infertility?
Correct modifiable risk factors Surgical repairs (varicoceles, obstructive lesions) Hormone therapy (gonadotropins or pulsatile GnRH) Sperm cryopreservation (done before cancer therapies) Assisted reproductive technologies
38
What are some devices used to aid fertility?
Basal Body Temperature (BBT) charting Ovulation prediction kits
39
How does maternal age affect IVF success?
Steady decline after the age of 35
40
Why is infertility becoming more common?
Increased maternal age Starting families later (higher education, costs associated with child-rearing) People talk about it and share (less taboo now)
41
What is involved in ovulation induction (OI)?
Letrozole or clomiphene therapy Timed intercourse With or without trigger shot (to help with oocyte retrieval)
42
What is superovulation (SO)?
Ovaries are stimulated with hormones to produce follicles Goal is to produce 2-4 eggs Combined with IUI Medications used for SO and IVF are the same, but doses are lower in SO
43
What is intrauterine insemination (IUI)?
Insert sperm directly into the uterus Sperm is prepped (separated in centrifuge, evaluated and washed) Can be done +/- superovulation
44
What is intra-cytoplasmic sperm injection (ICSI)?
Inject the sperm directly into the egg (done in a lab) May be used for low sperm count, impaired sperm penetration, anti-sperm antibodies, previous IVF failure)
45
List the steps involved in in-vitro fertilization (IVF)?
Tests & Diagnosis Ovarian Stimulation & Control Egg Retrieval Sperm Collection/Retrieval Fertilization Transfer Pregnancy Test
46
Review slides 70 and 71 for an overview of hormones in IVF
47
How are ovaries stimulated in IVF?
Estrogen and progesterone are monitored for 8-14 days FSH and LH analogues are administered (urinary or recombinant sources)
48
Review slide 74 for comparing urinary and recombinant analogues of FSH and LH
49
How is premature ovulation prevented to ensure multiple follicles mature at the same time?
GnRH agonists (leuprolide) - Induce release of large amounts of FSH and LH - Used for 7-10 days to see downregulation of GnRH receptors OR GnRH antagonists (ganirelix) - prevent endogenous pulses of FSH and LH
50
Review slide 79 for GnRH anatagonist protocol for IVF
51
What are some risks associated with ovarian stimulation?
Ovarian Hyperstimulation Syndrome (OHSS) Ovaries can enlarge, and is very painful and can result in permanent damage to ovary Need to monitor patient Can be avoided by limiting the amount of stimulation and expected number of eggs to be harvested
52
What is involved in oocyte retreival in IVF?
A trigger shot (HCG) is given to mature oocytes to encourage ovulation of mature oocytes Retrieval occurs 34-26h after trigger shot (timing is of the utmost importance) Transvaginal ultrasound guided needle aspiration to extract eggs Ideally retrieve several (10-12) well developed oocytes Progesterone is given for luteal phase support. This promotes the endometrium to become more hospitable to embryo implantation
53
What is involved in sperm collection/retrieval in IVF?
Collect fresh sperm (ideally obtained on day of oocyte retrieval) Retrieval may be considered if pt has obstructive issues, non-obstructive issues, neurological injury, retrograde ejaculation
54
What is involved in the fertilization & culture step of IVF?
Fertilization occurs within 18-24h of exposing oocyte to sperm Oocytes and sperm are assesed and evaluated Once fertilization has occurred, embryos are transferred to a growth medium and incubated
55
What is involved in the transfer step in IVF?
Transfers occur on Day 2 (embryo transfer) or Day 5 (blastocyst transfer) Usually 1-2 embryos/blastocysts are transferred Number of embryo/blastocysts transferred depends on previous pregnancies, maternal age, and medical history
56
Review slide 89 for overview of IVF process
57
What are some side effects associated with IVF?
Headache Mood changes Injection site discomfort Hot flashes Breast tenderness See slide 91
58
What are the success rates for infertility treatments?
60-70% of couples treated for infertility end up with a healthy child
59

PHAR 359 (17 decks)

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