REI Flashcards
(123 cards)
0
Q
Define fecundability
A
Ability to conceive during one menstrual cycle
1
Q
What is the avg cycle fecundability?
A
20%
2
Q
Define fecundity
A
Probability that a cycle will result in a live birth
3
Q
What % of couples are infertile?
A
10-15%
4
Q
Normally what % of couples conceive within 6 months of trying? One year?
A
75% in 6 months
85% within 1 year
5
Q
List four main groups of etiologies of infertility and what % of causes they represent
A
20-40% ovulatory dysfct
30-40% tubal and peritoneal pathology
30-40% male factor
10-30% Unexplained infertility
6
Q
What are the WHO’s 4 groups of ovulatory dysfct? Name an example of each and what % of anovulation each group represents.
A
Group 1 hypo gonadotropin hypogonadism (5-10%, ex female athlete syndrome)
Grp 2 eugonadotropic eustrogenic anovulation (75-85%, PCOS)
Grp 3 hypergonadotropic anovulation (10-20%, usually POF)
HyperPRL (5-10%)
Hyp
7
Q
Incidence of tubal infertility after 1, 2 or 3 episodes of PID?
A
10-12% after 1 episode
23-35% after 2 episodes
54-75% after 3 episodes
8
Q
List the 4 main groups of etiologies of male infertility, an example of each and what percentage of male infertility each represents.
A
1-2% hypothalamic-pituitary (ex: Kallman syndrome)
30-40% primary gonadal disorders (ex Klinefelter syndrome)
10-20% disorders of sperm transport (congenital bilateral absence of vas deferens)
40-50% idiopathic
9
Q
What criteria must be met in order to have dx unexplained infertility?
A
Normal semen analysis Normal ovulatory fct Normal uterine cavity Bilateral tubal patency Normal TVUS (no ovarian pathology)
10
Q
What is the avg cycle fecundability of a couple with unexplained infertility?
A
2-4%
11
Q
What is the most effective tx for couples w/ unexplained infertility?
A
IVF
12
Q
Can uterine fibroids cause infertility?
A
Sub mucous ones yes (and they decrease IVF success rates by 70%)
13
Q
What are the 5 criteria for a normal semen analysis?
A
Volume >1.5mL Count >15 million/mL Motility >50% forward progression Morphology >30% normal Absence of pyospermia, hyperviscosity, or agglutination
14
Q
Name several ways to confirm ovulation.
A
Menstrual hx, BBT rises 0.4-0.8 F, serum progesterone 1 week prior to expected menses, urinary LH kit, TVUS
15
Q
When does ovulation occur after LH surge?
A
14-26h
16
Q
What level of progesterone is indicative of ovulation?
A
> 4-6 ng/mL
17
Q
What is the gold standard test for evaluating the uterine cavity? Testing for tubal patency?
A
Uterine cavity = hysteroscopy
Tubes. = laparoscopy
18
Q
What is the risk of infection after HSG? Who should receive Abx with an HSG?
A
1-3% risk but doxycycline 100mg po BID x 5 days starting 1-2 days prior should be given to pts when tubal dz is highly suspected or when HSG reveals distal tubal obstruction (risk infection 10% in these pts)
19
Q
Who should be tested for ovarian reserve?
A
Age >/= 35 or <35 but with risk factors for DOR:
Single ovary, prev ovarian surgery, poor response to FSH, prev chemo or radiation, unexplained infertility
20
Q
Name 4 tests of ovarian reserve
A
Day 3 FSH, anti mullerian hormone, antral follicle count, clomiphene challenge test
21
Q
What level of FSH is considered abnormal when testing ovarian reserve?
A
> 14 IU/L (SOGC)
22
Q
What level of AMH is abnormal when testing for ovarian reserve?
A
<0.7 ng/mL
23
Q
What is the usefulness of AMH in testing ovarian reserve? What is its weakness?
A
Can predict ovarian response in IVF but is a poor predictor of pregnancy
24
How many antral follicles indicate DOR?
<4
25
What is the only effective tx for DOR?
Oocyte donation
26
What are some general tx recommendations for infertile couples?
Quit smoking (improves pregnancy rates by 50%), lose weight, decrease EtOH to <250mg/day, stop drugs, avoid toxic chemicals , timed intercourse
27
What is the conception rate after tubal reversal? What is their risk of ectopic pregnancy?
45-82% (best px is young women w/ filche clips) conception rates; 1-7% chance ectopic
28
HSG shows tubal obstruction. What is the chance that this is false?
60%
29
Name 3 indications for gonadotropin tx.
Hypogonadotropic hypogonadism
Clomiphene resistant anovulation
Unexplained infertility
30
What type of gonadotropin tx regimen is most effective? (Ie daily set dose? Weekly dose? Frequent changes?)
Daily tx with frequent adjustments according to clinical response is best
31
Which IVF tx protocol is preferred and why?
The Long Protocol (GnRH agonist down-regulation gonadotropin stimulation) because the down regulating prevents a premature LH Surge during exogenous gonadotropin stimulation and b/c there is evidence of better egg yields and pregnancy rates this way
32
Describe a typical IVF long protocol
Start GnRH agonist day 21 +/- ASA
15 days later have TVUS and estradiol level
If successfully down regulated:
Decrease GnRH dose
Start Menopur and Bravelle (urofollitropin) on 1st Thurs after U/S
+/- Abx for both partners on Friday
Bloodwork and scans prn
Once at least two follicles reach 17-18mm, give hCG injection
36h later egg retrieval
Start prometrium 200mg Pv TID and Estrace 2ng BID until 11 wks pregnant
Embryo transfer 3-5 days later
33
What is the significance of ovarian cysts in IVF following GnRH agonist tx?
Evidence suggests that these women are more likely to respond poorly to gonadotropin stimulation and are less likely to achieve a pregnancy
34
Why do some IVF clinics give LH or add hMG to FSH stimulation?
Use of hMG may increase live birth rates and to help a subgroup of women who have markedly suppressed LH levels that can't maintain steroidogrnesis (which may adversely affect fertilization, implantation and preg rates)
35
What is the avg cycle fecundability in spontaneous and clomiphene- stimulated donor insemination cycles?
6-13% (ie no significant benefit to clomiphene)
36
What is the cycle fecundability in exogenous gonadotropin stimulated cycles with donor insemination?
14-24%
37
When should IUI be performed?
In natural cycles: the day following LH surge
| In ovulation induction: 34-40h after hCG injection
38
Define amenorrhea
No menses or sec sexual charc by age 14, no menses by age 16 in presence of sec sexual charc or no menses x at least 3 cycles or 6 months
39
Name one reliable clinical sign that demonstrates exposure to estrogens (esp in young women)
Breast development (urogenital atrophy doesn't always appear in young women)
40
Name one clinical sign that reliably demonstrates androgen exposure
Pubic hair
41
A teenage girl with amenorrhea has a patent vsgina and cx. Name three causes of amenorrhea that you have now eliminated.
Mullerian agenesis, vsginal agenesis and androgen insensitivity syndrome, imperforate hymen..
42
Are Müllerian ducts from the paramesonephric ducts or the meson euphoric ducts?
Paramesonephric ducts
43
Amenorrhea + blind vaginal pouch. Name two dx possibilities. How will you clinically differentiate between the two?
Mullerian agenesis (they have pubic hair) and androgen insensitivity syndrome (they don't have pubic hair)
44
What are the top 4 causes of primary amenorrhea?
Turner syndrome 27%, Mullerian agenesis 15%, hypergonadotropic hypogonadism but normal 46XX karyotype 14%, constitutional delay 14%
45
What are the four most common causes of secondary amenorrhea excluding pregnancy?
PCOS 28%, nonspecific hypothalamic cause (low or normal FSH) 18%, functional hypothalamic amenorrhea 15.5% and POI with normal chromosomes 10% (table in Williams Gyne)
46
What initial investigations should be ordered for a woman with amenorrhea?
Pregnancy test, TSH, PRL, estradiol and FSH, progestin challenge once labs done
47
Name the 3 phases of hair growth.
Telogen (resting phase)
Anagen (growing)
Catagen (involution)
48
What is telogen effluvium and why does it occur?
Large proportion of hair growth becomes synchronous and enters telogen simultaneously, causing noticeable shedding. May occur during pregnancy, with a febrile illness or with some rx
49
What is hypertrichosis and what can cause it?
Generalized increase in vellus (fine) body hair. May be assoc with:
- Rx (phenytoin, cyclosporin)
- systemic illness (hypoT4, anorexia, malnutrition, dermatomyositis)
- cancer (paraneoplastic syndrome)
50
Why is it important to tx female hirsutism ASAP?
Once hair follicles have responded to androgen stimulation, they will only grow thick dark hair from then on, even if androgen levels normalize afterwards
51
What is the most bio active androgen? Where is it produced?
Dihydroxytestosterone - produced in the periphery from intracellular conversion of testosterone by 5 alpha reductase
52
What kind of biological activity do DHEA, DHEA-S and androstenedione have?
Minimal or no biological activity - they must be converted to testosterone in order to be active
53
Where is DHEA-S produced?
Adrenal glands
54
Where is DHEA produced?
50% adrenals, 20% ovaries, 30% from peripheral conversion of DHEA-S
55
Where is androstenedione produced?
50% adrenals, 50% ovaries
56
Where is testosterone produced in women? What % of circulating testosterone is usually bound to SHBG?
25% adrenals, 25% ovaries, 50% from peripheral conversion of androstenedione
80% usually bound to SHBG, 19% bound to albumin, 1% free
57
Name 2 things that decrease SHBG levels and two things that increase their production
Decreased by insulin and glucocorticoids, increased by estrogens and thyroid hormone
58
In the post menopausal ovary, which is that main hormone produced?
Androgens
59
What is the dx for female hirsutism?
```
80% PCOS
7% hyperandrogenemia but normal ovulation
4.5% idiopathic hirsutism
4% HAIR-AN syndrome
2% non classical CAH
0.7% classical CAH
0.2% androgen secreting neoplasm
```
60
What is the HAIR-AN syndrome?
Hyperandrogenic insulin-resistant acanthosis nigricans
Same clinical features as PCOS but in the extreme; primary underlying pathology is severe insulin resistance, which stimulates ovarian androgen production
61
How does hyperinsulinemia stimulate androgen production?
Via theca cell receptors for insulin and IGF-1
62
What is the most common enzyme defect in CAH? What hormones then accumulates?
21-hydroxylase
Accumulate 17-OH progesterone
63
Name three types of ovarian tumors that can produce androgens
Sertoli-Leydig tumors
Theca-cell tumors
Hilus-cell tumors
64
How come some pts w/ hyperPRL have hirsutism?
Elevated PRL can be assoc w/ increased DHEA-S, which is then converted to testosterone
65
Woman is 26 wks weeks pregnant and presents w/ new onset hirsutism and clitoromegaly. What dx should you suspect?
Pregnancy luteoma (not a true tumor - it's a hyper plastic mass of luteinized ovarian cells); 1/3 are assoc w/ hirsutism or virilization
Solid tumor, 6-10cm, 50% are bilateral
66
What functional ovarian cyst can produce androgens? When do they develop?
Theca-lutein cysts
| Multiple gestation, isoimmunization, DM in pregnancy, GTN
67
Name the 9 areas evaluated in the modified Ferriman-Gallway scoring system for hirsutism
Upper lip, chin, chest, upper abdo, lower abdo, upper arm, thighs, upper back, lower back
68
On the Modifued Ferriman-Gallway system, what score is considered abnormal?
3 or higher
69
What is ovarian stromal hyperthecosis and how does it present?
Histologic dx (clusters of luteinized thecal cells scattered throughout ovarian stroma).
Present w/ obesity, severe hirsutism, virilization, severe insulin resistance, hyperinsulinemia
Most women w/ HAIR-AN have ovarian stromal hyperthecosis, but you can have hyperthecosis without HAIR-AN in post menopausal women
70
What % of women w/ PCOS have IGT or type 2 DM?
35% IGT
| 10% type 2 DM
71
Which women with hirsutism should be investigated? What tests should be ordered?
Should be investigated if pre or peri-menarchal onset or onset after age 25, sudden and severe, family hx CAH, high risk ethnic groups (Hispanic, Mediterranean, Slavic, Ashkenazi Jewish), accompanied by signs of Cushings or virilization or with menstrual disturbances.
If AUB: do TSH and PRL
To R/O other potentially serious endocrine disorders:
Total testosterone
17-OH Progesterone
Only do DHEA-S if you highly suspect adrenal tumor
TVUS if you suspect ovarian tumor
Consider 2h 75g OGTT with fasting and 2h insulin
72
What happens to insulin sensitivity when androgen levels are high?
Causes decreased sensitivity to insulin
73
Name 5 medical tx options for hirsutism
OCP (Diane-35 contains cyproterone)
Spironolactone 50-100mg BID
Cyproterone acetate 12.5-100mg/d
Flutamide 62.5mg die, eflornithine cream
74
Name two progestins that have anti-androgen properties. Which OCPs are they in?
```
Cyproterone acetate (Diane-35)
Drospirenone (Yaz and Yasmin)
```
75
In chronic anovulation, what happens to gonadotropin and sex steroid hormone levels?
They are in a steady state (compared to normal cyclic pattern)
76
What happens to LH and FSH levels in PCOS pts?
Increased LH (via increased pulse frequency and amplitude)
Low-normal FSH (via increased GnRH pulse frequency, negative feedback from chronically elevated estrone levels and normal or elevated inhibit B levels from small antral follicles)
77
What is the prevalence of insulin resistance in PCOS pts?
50-75% (less in lean women)
78
What is the prevalence of IGT and DM in PCOS pts?
35% IGT
| 7-10% type 2 DM
79
How do increased circulating insulin levels contribute to hyperandrogenism in women with PCOS?
1. Stimulate increased ovarian androgen production
2. Inhibit hepatic SHBG production
3. Potentiates the action of LH
80
What % of PCOS pts are obese (USA)?
60%
81
Where does the excess androgen come from in pts w PCOS?
Ovaries
| 60% androstenedione and testosterone
82
What are the primary mechanisms driving increased ovarian androgen production in pts w PCOS?
Increased LH stimulation from abnormal LH secretion dynamics and increased LH bio activity
And hyperinsulinemia (due to insulin resistance) which potentiates the action of LH and is worsened by obesity
83
What causes polycystic ovaries?
they are the end result of a functional derangement in follicular develop induced or sustained by increased intraovarian androgen levels as a consequence of chronic anovulation
84
Women with PCOS are at an increased risk of which problems?
DUB, infertility, endometrial cancer, obesity, type 2 DM, DLPD, HTN, cardiovasc dz
85
What are the dx criteria for PCOS?
Rotterdam criteria:
2/3 of:
1) oligo/anovulation
2) hyperandrogenism (clinical or biochemical)
3) polycystic ovaries
After excluding other androgen excess disorders
86
What is the avg cycle fecundability after age 40?
7% age 40-42
| 5% and falling after age 42
87
What is the risk of miscarriage after age 40?
50-60%
88
What is the chance of success (live birth) after age 40 with 1) clomiphene and IUI 2) COH 3) IVF 4) donor oocyte
1) 1% clomiphene + IUI
2) 2% COH
3) 5-10% IVF
4) 30-50% donor oocyte
89
What are the ultrasound criteria to dx polycystic ovaries?
>/= 12 follicles 2-9mm in diameter in at least one ovary and/or increased ovarian volume >10mL
90
You suspect someone has PCOS. What investigations should you order?
Pelvic ultrasound (not first line in teens)
Serum total testosterone
(Controversial whether or not to order other androgens or to work up for other causes of hyperandrogenism unless you are highly suspicious)
--> consider 17-OH progesterone
2h 75g GTT with fasting and 2h insulin levels
HDL, LDL, triglycerides
TSH, PRL
91
What % of PCOS pts have AUB?
60-85% (usually oligo or amenorrhea)
| 15-40% are eumenorrheic despite evidence of oligo-anovulation
92
What % of normal women meet the ultrasound criteria for polycystic ovaries?
8-25%
93
You measure 17-OH progesterone in a woman with hirsutism. What are you looking for?
CAH (usually late-onset)
94
Which women with hirsutism should absolutely be tested for late onset CAH?
2 theories: test universally it test only the following women:
Pre- or peri menarchal onset or hirsutism, women w/ family hx CAH, Hispanic, Mediterranean, Slavic, Askenazi Jews, Eskimos
95
When managing pts w/ PCOS, what immediate and long-term consequences need to be addressed?
```
Menstrual abnormalities
Increased risk for hyperplasia and endo ca
Hyperandrogenism
Infertility
Increased risk type2 DM
increased risk cardiovasc dz
```
96
What is the first best tx of PCOS for obese women?
Weight loss
97
What is the first-line tx for women with PCOS and infertility who want to conceive?
Clomiphene
98
In women with PCOS, what is the cumulative pregnancy rate with clomiphene after 3 cycles? 6-9 cycles?
50% within 3 cycles
| 75% within 6-9 cycles
99
Which PCOS pts are less likely to respond to clomiphene for infertility?
Those with obesity or severe hyperandrogenism
100
What are the dx criteria for POI?
Younger than age 40
Oligo/amenorrhea x >/= 4 months
Two FSH levels > 25 IU obtained at least 1 month apart
(NEJM 2009)
101
What % of women w/ POI ovulate irregularly despite dx POI?
50%
102
What % of women w/ POI conceive after dx POI?
5-10%
103
What % of POI pts have no identifiable cause?
90%
104
What are the two major mechanisms for POI?
Follicle dysfct and follicle depletion
105
What is the incidence of POI by the age of 40?
1/100 women
106
List possible causes of POI
fragile x premutation, autoimmune polyendocrine syndrome type 1 or 2, CAH, galactosemia, ataxia-telangiectasia, numerical and structural chromosomal anomalies, radiation, chemo, other autoimmune dz
107
How do you dx APAS?
One clinical and one lab criteria:
Clinical: vascular thrombosis or pregnancy morbidity
SA>10 wks normal fetus
PTB /=3 consecutive SA 1 at least 12 wks apart
108
What % of pregnancies end in SA?
15-25% (ASRM 2012)
109
What is the most common cause of T1 losses <10 wks?
Random chromosomal errors (trisomy, monosomy and polyploidy)
110
How is recurrent preg loss (RPL) defined?
>/= 2 SA
111
What % of women will have 2 consecutive SA? 3?
```
2SA = <5%
3SA= 1%
```
112
What % of pts with RPL have unexplained RPL?
50-75%
113
What are the possible causes of RPL?
```
Cytogenetic (balanced reciprocal trans locations)
APAS
Anatomical probs
Hormonal or metabolic probs
Psychological factors
Infections
Alloimmune
```
114
What investigations should be offered to women w/ RPL?
Parental karyotyping
Test for APAS only if meets criteria and if other causes have been ruled out
Check uterine cavity
TSH, PRL
HbA1c if diabetic or at risk
Test for Thrombophilias only if pt has hx unprovoked DVT or family hx +
Consider autopsy with karyotype of fetus
115
If a pt has RPL and a structural genetic anomaly, does IVF with PIGD improve live birth rates?
No ( 33% IVF vs 55-74% natural conception)
116
What is the tx for APAS with RPL?
Low dose ASA plus UFH BID (comparable efficacy of LMWH has not been established)
117
What % of general fertile population have congenital uterine anomalies? Pts w/ RPL?
4% general pop
| 12% pts w/ RPL
118
Which congenital uterine anomalies increase the risk of SA?
Septate 44% rate of SA
Bicornuate 36%
Arcyate 25.7% loss
119
What impact does correction of uterine septum have on live birth rate?
83% live birth rate after septum removal
120
In a pt w/ RPL, what impact does tx her hyperPRL have on live birth rates?
Live birth rates 52% if untx
| And 86% if tx
121
What is the role of Progesterone in tx RPL?
May be useful in women w/ 3 or more consecutive SA preceding this pregnancy
122
In pts w/ unexplained RPL, what is the chance for a future successful pregnancy even without tx?
50-60%
