REI Flashcards
What is the scoring system for hirsutism?
Ferriman-Gallway score >=8 excessive hair growth 8-15 mild hirsutism 16-25 moderate hirsutism >25 severe hirsutism
SOGC 350
What is the incidence of women of reproductive-age who are diagnosed with hirsutism?
5-10%
SOGC 350
What is non-classical congenital adrenal hyperplasia? What test would we order if we suspect it in a patient with hyperandrogenism hirsutism?
It is a partial deficiency of the 21-dehydroxylase enzyme
We would need to order 17-hydroxyprogesterone if we suspect it
SOGC 350
What are the incidences of moderate and severe OHSS after superovulation for IVF?
3-6% for moderate OHSS
0.1-2% for severe OHSS
Mild OHSS occurs in 20-33% of IVF cycles
SOGC 268
What is the mechanism by which OHSS occurs?
Systemic condition thought to result from vasoactive peptides released from granulosa cells in hyperstimulated ovaries
• Increase in vascular permeability resulting in fluid shift from intravascular to third space compartments (peritoneum or thoracic cavities)
• HCG shown to increase VEGF expression in human granulosa cells -> raises serum VEGF concentration
SOGC 268
Name the 8 risk factors for the development of OHSS.
Risk factors of OHSS
• Age <30 years old
• PCOS of high basal antral follicle count on US
• Rapidly rising or high serum estradiol
• Previous history of OHSS
• Large number of small follicles (8-12mm) seen on US during ovarian stimulation
• Use of hCG as opposed to progesterone for luteal phase support after IVF
• Large number of oocytes retrieved (>20)
• Early pregnancy
SOGC 268
What is the first sign of impending severe OHSS?
Abdominal bloating
SOGC 268
What are the criteria for critical OHSS?
1) tense ascites or pleura effusion
2) oliguria/anuria
3) hematocrit >55%
4) acute respiratory distress
5) thromboembolism
6) WBC>25
SOGC 268
What medications should be avoided in women with OHSS?
NSAIDS and diuretics
SOGC 268
Natural female fertility declines at what age
mid-30s
SOGC 346
Negative aspects of ART (4)
- Will not compensate for decline in natural fertility due to delayed child-bearing
- Invasive
- Expenseive
- Increased pregnancy complications for both mother + fetus with advancing maternal age
SOGC 346
How many oocytes in:
- a 20wk fetus
- a neonate
- a pubertal girl
- a woman at menopause
20wk: 6-7 million
birth: 1-2 million
puberty: 3-500 thousand
menopause: a few hundred
SOGC 346
How many ovulations in a reproductive lifetime
4-500; majority of the rest are lost through apoptosis
SOGC 346
Natural course of reproductive life as ovarian follicular pool decreases (5 steps)
- Infertility
- Sterility
- Cycle shortening
- Menstrual irregularity
- Menopause
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Optimal fertility age range
20-30
SOGC 346
Average age (and range) of menopause in Western countries
51 (40-60)
SOGC 346
Rate of premature ovarian failure (menopause < 40)
1%
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True/false: earlier loss of fertility is associated with earlier menopause
True
SOGC 346
How many years before menopause does child-bearing usually end?
10 years
SOGC 346
What cell makes inhibin-B, and in which phase of menstrual cycle
Granulosa cell in early follicular phase
SOGC 346
Describe physiology of transitioning to menopause
Decreasing # of follicles → decreasing inhibin-B → increasing FSH from loss of negative feedback
SOGC 346
Earliest sign of ovarian aging (lab test)
Rise in FSH
SOGC 346
Earliest sign of ovarian aging (clinical)
Cycle shortening (shorter follicular phase) due to earlier recruitment of a dominant follicle
SOGC 346
After cycle shortening, why do cycles get longer closer to menopause?
Ovulation is less consistent, leading to longer and more irregular cycles
SOGC 346
Women whom are sterile at age 35 already have lower fecundity by what age
30
SOGC 346
How long after menopause is there still ovarian activity and estrogen production
At least 1 year after menopause
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Impact of smoking on reproductive potential (2)
- Decreases follicular pool
- Leads to earlier menopause
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Rate of aneuploidy in oocytes in stimulated cycles
- age < 35
- age 40
- age 43
- age > 45
- < 35 = 10%
- 40 = 30%
- 43 = 40%
- > 45 = 100%
SOGC 346
At the cellular level, why do rates of aneuploidy in oocytes increase with age?
More diffuse formation and function of spindles → chromosomes less tightly arranged → meiotic errors
Reasons for poorer oocyte quality with increasing age (5)
- Meiotic errors from poor spindle formation/function
- Oocyte selection process diminishes with age
- Less discrimination of dominant follicle selection (dominant follicle allowed to mature instead of undergo atresia)
- Cumulative damage to oocyte with age
- Decreasing quality of granulose cells
SOGC 346
Natural decline in birth rate begins at what age
35
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Average age of last child (and range)
41 (23-51)
SOGC 346
Factors leading to decreased live birth rate later in life (5)
SOGC 346
- Desire to prevent pregnancy
- Coital frequency decreases
- Aging partners
- Medical conditions that affect live birth rate
- Fibroids and endometriosis more common in later reproductive years
Definition of fecundity rate
Rate at which a woman is able to conceive (how long it takes to get pregnant)
SOGC 346
True/false: fecundity rate decreases with age
True: younger women have a higher fecundity rate than older women
SOGC 346
% of women married in early 20s (vs. married in 40s) who remain childless
6% vs. 64%
SOGC 346
True/false: current ART success rates are able to compensate for loss in natural fertility that occurs with aging (e.g. 30 to 35)
False
SOGC 346
Cumulative pregnancy rates after 12 IUI cycles by age:
- < 30
- 30+
< 30 → 62%
30+ → 44%
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Live birth rate with IVF by age:
- < 35
- 35-39
- 40+
< 35 → 41%
35-39 → 30.9%
40+ → 12.3%
SOGC 346
True/false: age is the most significant prognostic factor for IVF success
True
SOGC 346
True/false: age affects the endometrium’s response to hormonal stimulation
False: the age of recipient does not affect pregnancy rates in donor egg cycles
SOGC 346
How soon after attempting to conceive should women > 35 be referred for infertility workup?
6 months (as opposed to 12 months in younger women)
SOGC 346
True/false: ovarian reserve testing can predict infertility and/or time to infertility
False: it cannot do either of those
SOGC 346
Ovarian reserve testing values correlate with what 2 things
- Egg quantity
- Response to ovarian stimulation
SOGC 346
True/false: ovarian reserve testing values correlate well with oocyte quality
False
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True/false: ovarian reserve testing values correlate well with pregnancy achieved with ART
False; however, very abnormal results (3% of women) are associated with lower pregnancy rates (<5%)
SOGC 346
How should interpretation of ovarian reserve testing be used in clinical practice?
It should be used to counsel patients (offer oocyte donation to increase pregnancy rates), but it should not be used to exclude women from ART, as some women with abnormal tests still get pregnant
SOGC 346
What are risk factors for decreased ovarian reserve, that would prompt you to do testing in women < 35 (5)
- Single ovary
- Previous ovarian surgery
- Poor response to FSH
- Previous chemo/radiation
- Unexplained infertility
SOGC 346
List markers of ovarian reserve (6)
- Day 3 (basal) FSH
- Ovarian antral follicle count (early in cycle)
- Antimullerian hormone
- Clomiphene citrate challenge
- Inhibin-B
- Basal estradiol
SOGC 346
Above what level of FSH denotes ovarian aging, and at what age does this usually happen
FSH > 14 IU/L
Usually age 35-40
SOGC 346
Why does FSH rise with ovarian aging?
It goes up in response to loss of negative feedback from inhibin A and B
SOGC 346
FSH as a marker of ovarian reserve is predictive of what 2 things
- Predictive of poor response to ovarian stimulation
- At extremely elevated levels, it is predictive of non-pregnancy
SOGC 346
In what population does FSH have less predictive power as a marker of ovarian reserve
Women < 35
SOGC 346
When should an ovarian antral follicle count be performed
Early in the menstrual cycle
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What size are antral follicles
2-10 mm
SOGC 346
Why is antral follicle count used as a marker of ovarian reserve
Antral follicles are sensitive to FSH, and are considered representative of the available follicular pool; they correlate with # of primordial follicles in the ovary
SOGC 346
What makes antral follicle count less valuable as a marker of ovarian reserve
The proportion of antral follicles : total follicles may increase later in reproductive years, as the ovary allows a higher proportion of follicles to be selected
SOGC 346
Antral follicle count as makers of ovarian reserve is predictive of what 2 things
- Predictor of menopause transition
- Predictor of ovarian response to stimulation
(However, it is not a good predictor of pregnancy)
SOGC 346
Where is antimullerian hormone made?
Produced by granulose cells of preantral and small antral follicles, but not by dominant follicles
SOGC 346
When in the menstrual cycle should AMH be measured
At any point! Levels are consistent throughout the cycle
SOGC 346
As a marker of ovarian reserve, what 1 thing does AMH level predict
- Provides moderate value in prediction of ovarian response in IVF
(However, it is a poor predictor of pregnancy)
SOGC 346
How do AMH levels correlate with AFC levels
AMH levels decrease with decreasing AFC
SOGC 346
Describe clomiphene citrate challenge test
100 mg PO daily from days 5-9
Measure FSH level days 3 and 10
An adequate response is noted if the rise in FSH is suppressed by the release of estradiol and inhibin-B by developing follicles
SOGC 346
How is clomiphene citrate challenge test more beneficial than other markers of ovarian reserve
There is no benefit to this test over basal FSH or AFC
SOGC 346
How are inhibin-B and basal estradiol more beneficial than other markers of ovarian reserve
These tests are not more useful predictors of poor response or pregnancy than basal FSH
SOGC 346
List 1 way estradiol works WITH FSH and 1 way it works AGAINST FSH as a marker of ovarian reserve
with: basal estradiol levels, when analyzed with FSH, can confirm correct timing in the menstrual cycle
against: elevated estradiol level may falsely suppress FSH levels
SOGC 346
What are 2 distinct populations in which ovarian reserve testing may be considered
- Age 35+
- Age < 35 with risk factors for decreased ovarian reserve
SOGC 346
What is the goal of treatment of age-related infertility
To decrease time to conception
SOGC 346
What is the best treatment for age-related infertility
Oocyte donation
SOGC 346
What are the success (pregnancy rates) of clomiphene citrate + IUI based on age
- 38-40
- 41-42
- > 42
- 38-40 → 7%
- 41-42 → 4%
- > 42 → 1%
SOGC 346
What are the success (live birth rates) of gonadotropins + IUI based on age
- 38-39
- > 40
- 38-39 → 6%
- > 40 → 2%
SOGC 346
What are live birth rates per cycle of IVF based on age
- > 40
- 42+
- 45+
- > 40 → 12.3%
- 42+ → < 5%
- 45+ → 0%
SOGC 346
What are miscarriage rates with IVF based on age
- 40-42
- > 42
- 40-42 → 43.1%
- > 42 → 65.2%
SOGC 346
What should be the threshold to transition from controlled ovarian hyperstimulation (COH) to IVF in patients > 40
May consider 1-2 cycles of COH, but should move on to IVF quickly if unsuccessful
SOGC 346
True/false: oocyte donation may help achieve pregnancy in women who have already gone through menopause
True!
SOGC 346
Outline the rules of the 2004 Assisted Human Reproduction Act
- It regulates all reproductive technologies
- It prohibits sale of eggs, sperm, or surrogacy services
- Compensation to donors for receptacle expenses (e.g. prescriptions, parking) is allowable
- Must rely on altruistic egg donors
- May access donor banks in USA for frozen oocytes from anonymous donors
SOGC 346
Between oocyte donor and oocyte recipient, whose age is more predictive of pregnancy rate
The age of the oocyte donor
SOGC 346
What complications make oocyte donation to women > 50 controversial (5)
- Maternal death
- Hypertension
- Prematurity
- Fetal and neonatal death
- Operative delivery
SOGC 346
What is the age limit for ART?
There is no age limit in Canada; however, guidelines recommend women > 45 have medical assessment and obstetrical consultation prior to treatment
SOGC 346
What early pregnancy complications increase with age (3) (see text for rates)
- SAB (whether with or without ART)
- Rates of chromosomal anomalies
- Rates of Down syndrome
SOGC 346
What later pregnancy complications increase with age (5) (see text for rates)
- Surgical delivery
- Gestational diabetes
- Preeclampsia
- IUGR
- Low birth weight
SOGC 346
What preconceptional counselling/screening should be considered in women > 40 (3)
- Promotion of optimal health and weight
- Screen for hypertension
- Screen for diabetes
SOGC 346
What physiologic parameter changes lead to paternal age-related fertility decline (4)
- Decline in testicular function, including testosterone levels
- Lower semen volume
- Lower sperm motility
- More abnormal sperm morphology
SOGC 346
Does paternal age affect natural fertility?
1 study suggests that odds of conception decrease by 3% per year; other studies show only a small effect
SOGC 346
Does paternal age affect IUI or IVF success?
1 study suggests paternal age > 35 may have an effect on IUI
Most studies suggest paternal age has no effect on IVF/ICSI. However, there is a significant decrease in rate of blastocyst embryo formation on day 5 and in # of cry–reservable embryos
SOGC 346
What 3 autosomal dominant syndromes are associated with increasing paternal age
- Alport syndrome
- Achondroplasia
- Neurofibromatosis
(However, absolute risk < 0.5%)
SOGC 346
True/false: increasing paternal age impacts rates of preterm birth and low birth weight
Conflicting evidence
SOGC 346
True/false; increasing paternal age is associated with greater risk of miscarriage
True: even when controlling for maternal age
SOGC 346
What 2 neuropsychiatric disorders are associated with increasing paternal age (see text for rates)
- Autism spectrum disorder
- Schizophrenia
SOGC 346
Should additional prenatal testing take place due to increased paternal age?
SOGC 346
No; however, men > 40 and their partners should be counselled about these potential risks when they are seeking pregnancy, although the risks remain small