20 - infertility Flashcards
(180 cards)
1
Q
SRY location
A
short arm of Y
2
Q
SRY function
A
converts bipotent embryo to male
3
Q
SRY AKA
A
testis determining factor (TDF)
4
Q
3 events of gonadal differention that happen after transmission of y chromosome
A
- primordial germ cell migration, 2. mesonephric cell invasion, 3. establishment of germ cell lineage
5
Q
at what point in gestation is urogenital ridge organized
A
4-6 wks
6
Q
at what point in gestation are primordial germ cell migrating to UG ridge
A
6 wks
7
Q
what controls migration
A
CAM’s - cell adhesion molecules - fibronectin and GAG’s
8
Q
at what point in gestation are do sex cords start to develop
A
7 wks
9
Q
what do sex cords become
A
seminiferous tubules
10
Q
at what point in gestation do primitive germ cells develop into primitive gonocytes
A
15 wks
11
Q
at what point in gestation do you see phenotypic male signs
A
7 wks
12
Q
SRY - first product that steers toward male
A
steroidogenisis factor 1
13
Q
role of SOX 9
A
critical to differentiation of gonadal cell types (sertoli/ leydig cells)
14
Q
role of testosterone in development
A
directly induces development of epididymis, vas deferens, and SV
15
Q
metabolism of testosterone
A
by 5 alpha reductase to dihydrotestosterone
16
Q
DHT effect on development - 3
A
penis, scrotum, and prostate development
17
Q
sertoli cell product in fetus
A
mullerian inhibitory substance
18
Q
inhibin effect
A
inhibits FSH production
19
Q
high testosterone feeds back to
A
inhibit FSH and LH
20
Q
fetal testosterone level
A
gets to adult lefel in response to maternal gonadotropins
21
Q
testosterone level after birth
A
drops to near zero until puberty. One small surge just after birth (?reason)
22
Q
def of emission
A
deposition of semen into prostatic urethra due to rhythmic contraction of epididymis and vas deferens
23
Q
neuro of emission
A
alpha adrenergic sympathetic control
24
Q
ejaculation controlled by what nerve
A
pudendal
25
semen % breakdown
80% SV, 10% prostate, 10% testicular
26
ejaculate volume and vasectomy
stays the same
27
SV pH
basic
28
prostate pH
acidic (prostate acid phosphatase
29
time for maturation of sperm
64 d
30
transit time through epididymis
10 d
31
total transit time of sperm to ejaculation
3 mo
32
def of primary vs secondary infertility
primary - never any conception, secondary -previous conception
33
% couples concieving within a yr
85%
34
2010 AUA guideline caveat to eary infertility evaluation - 2
1. known male or female fertility risk factors (cryptorchidism, hx chemotherapy), 2. man questions fertility potential (just has to ask)
35
if man asks for eval what do u do
semen analysis, reproductive history
36
% male factor infertility only
20%
37
% of infertile couples with an element of male factor infertility
30%
38
if male semen analysis are nl then?
eval female
39
if male and female appear initially nl
more in depth study of male
40
chemo agents causing damage to type a spermatogonia effect
high damage to type a = irreversible azoospermia, less damage = possible for recoverability
41
what determines infertility in radiation
dose
42
radiation dose causes temporary azoospermia
50 centigray, 50 rads
43
permanent azoospermia radiation dose
400-600 centigray
44
timeframe to recovery of germ cell production with radiation
1-2 yrs
45
first step in male PE for infertility
assessment of secondary sex characteristics
46
things to look for on DRE
midline prostate masses, enlarged SV
47
nl semen concentration
15 mil/cc
48
motility - nl%
40%
49
liquefy time
1 hr
50
ideal semen specimen - 3 factors
3 days of abstinence in a lab that can process within 1 hr and no lubricants
51
ddx low volume - 3
retrograde ejaculation, EDO, vasal agenisis (vas obstruction only lowers semen vol by 10%)
52
round sperm morphology name
globozoospermia
53
def globozoospermia and significance
absent acrosomes. Need ICSI
54
low motility ddx - 2
delay in processing or lubricant use
55
very low motility mgmt - 2
confirm with viability stain and consider immotile cillia syndrome (cartagener's)
56
agglutination significance
antisperm ab's
57
how to confirm presence of WBC
peroxidase stain
58
significance of WBC
prostatitis
59
when to get genetic testing
< 5 mil/cc
60
when to test endocrine axis - 3
[semen] < 10 mil/cc, low libido, other findings suggestive of endocrinopathy (small testis, gynecomastia)
61
what is minimum endocrine test - 2
early AM FSH and total testosterone
62
if low testosterone, what tests next - 3
prolactin, free testosterone, LH
63
what are pituitary excess vs deficiency states in infertility
excess - prolactinoma; deficiency - hypogonadotropic hypogonadism
64
causes of hypogonadotropic hypogonadism - 6
kallman's, high prolactin, pituitary/ hypothalamic damage, prader willi, laurence moon-bardet-biedl syndrome, medications
65
prolactinoma MOA
prolactin inhibits GNRH release, therefore low FSH/LH
66
prolactinoma initial mgmt
medications
67
prolactinoma meds for tx - 2
cabergoline (less side effects), bromocriptine
68
most common presenting symptom for prolactimona
ED, decreased libido
69
meds causing elevated prolactin
antipsychotics, specifically phenothiazines
70
prader wili features
absent GNRH, obesity, small hands/feet, MR, hypotonic and short stature
71
laurence-moon-bardet-biedl pathognomonic feature
retinitis pigmentosa
72
laurence-moon-bardet-biedl features
hypogonadotripic hypogonadism, polydactyly, retinitis pigmentosa
73
idiopathic elevated prolactin mgmt
cabergoline
74
hypogonadotripic hypogonadism definition
[low FSH, LH, testosterone, and low GNRH]
75
kallman's other finding - 3
anosmia, delayed puberty, small testis
76
kallman's inheritance
x linked
77
kallman's gene mutation
KAL-1 gene
78
kallman's treatment
LH/FSH analog --> specifically HCG/HMG
79
kallman's outcome w tx
return of spermatogenisis
80
congenital version of elevated teststerone
CAH
81
CAH mech for infertility
cortisol deficiency, high ACTH, increased adrenal androgens, feedsback and decreases gonadotropin release
82
y chromosome microdeletion location
AZF (Yq11) - subclassified into a,b,c,
83
which AZF have absolutely no sperm
AZF a,b
84
which AZF have sperm
AZF c. has to be extracted by bx
85
inheritance of AZF
all sons will carry mutation and potential for infertility
86
what is kleinfelter's
extra x chromosome (47xxy)
87
kleinfelter's physical exam findings - 4
small firm testis, gynecomastia, azoospermia, hypogonadism
88
hormone profile on kleinfelter - T, LH, FSH, E
low T, high LH, high FSH, high E
89
kleinfelter's and sperm
2/3 have sperm on bx for ICSI
90
kleinfelter's and malignancy
higher risk of extragonadal (mediastinal) germ cell tumors, male breast cancer 10x risk
91
CBAVD- gene
60% have CFTR mutation, mutation rarely found in unilateral vasal agenesis
92
CFTR gene product name
cystic fibrosis transmembrane conductance regulator
93
associated gu abnormality in CFTR
ipsilateral renal agenisis due to failure of development of wolffian structres
94
what are wolffian structures - 3
vas, ureter, SV
95
CBAVD presentation
can present like EDO due to absence of SV
96
how does vas involute in pts with CBAVD
failure to maintain lumen of vas --> vas involutes
97
kartagener's syndrome associated with - 3
situs inversus, bronchiectasis, chronic sinusitis (long hx pulmonary and sinus infections)
98
kartagener's inheritance
AR
99
kartagener's semen analysis findings
abscent dinene arms on EM and low motility on semen analysis
100
kartagener's aka
immotile ilia syndrome
101
3 genetic disorders with chronic sinusitis and infertility
young's syndrome, kartagener's, and CF
102
young's syndrome and infertility
thick epididymal secretions --> obstructive azoospermia
103
young's syndrome features - 3
bronchiectasis, sinusitis, nl vas
104
low semen volume and azoospermia question to ask
vas present? - if abscent --> CFTR, if present --> r/o EDO
105
how to r/o EDO
do TRUS to eval SV size
106
tx EDO
TUR
107
TRUS findings suggestive of EDO - 4
1. SV > 15 mm AP diameter, 2. ejaculatory ducts > 2.3 mm diameter, 3. calcifications in ejaculatory duct, 4. midline cystic structure in prostate
108
if nl TRUS and no EDO, then dx?
failure of emission
109
how to tx failure of emission
sympathomymetics, electroejaculation, testiular sperm extraction
110
azoospermia and nl semen volume - question to ask
what size are testis - if nl --> check FSH
111
azoospermia and nl semen volume - interpretation of FSH
NL FSH - testis bx to r/o obstruction with VV or EV eventually. High FSH - primary testicular failure (testicular sperm extraction). Low FSH - hypogonadotropic hypogonadism
112
antiestrogen MOA
block estrogen receptor at hypothalamus and pituitary. Increase LH/FSH without affecting T. Prevent negative feedback
113
def of primary testicular failure (2)
FSH > 3x nl along with atrophic testicle on exam
114
how to administer antiestrogen
repeat horone profile at 3 wks and titrate.
115
once hormones nl on antiestrogen
check semen analysis at 3 mo
116
2 antiestrogen drugs
clomiphene, tamoxiphen
117
aromatase inhibitor MOA
blocks aromatase in fat that converts T --> E
118
name of aromatase inhibitor
testolactone
119
aromatase inhibitor good for
kleinfelter
120
% subfertile men with varicocele
40%
121
subclinical varicocele def
dx by ultrasound only
122
% subfertile men with varicocele
40%
123
subclinical varicocele def
dx by ultrasound only
124
subclinical varicocele and infertility
do not cause infertility - do not repair
125
time to improvement semen parameters after varicocectomy
3-6 mo
126
recurrent varicocele after ligation - mgmt
embolization
127
most durable repair method
microsurgical --> also preserve lymphatics preventing hydrocele
128
preoperative factors predicting vas reversal success
shorter interval (<10 yrs) since vasectomy, pre-vasectomy paternity, prior conception with current partner
129
intraop factors predicting successful vasectomy reversal - 5
1. sperm in vasal fluid, 2. high sperm quality in vasal fluid, 3. clear vasal fluid, 4. sperm granuloma at vasectomy site, 5. >2.7 cm from epididymis to vasectomy site
130
time to sperm after VV/VE
6-16 mo
131
time to pregnancy after vas reversal
12 mo
132
what makes decision to do VV vs VE at time to vas reversal
proximal vas fluid quality
133
proximal vas fluid characteristics favoring VV
any sperm or sperm parts, copius and clear or cloudy
134
proximal vas fluid characteristics favoring VE
thick insuppated secretion and no sperm, or no fluid
135
redo vas reversal procedure of choice
VE
136
where to find sperm in obstructive azoospermia
epididymis
137
quality of epididymal vs testicular sperm
same
138
how to choose ART technique
total motile sperm count
139
how to calculate total motile sperm count
volume of semen x concentration x motility
140
if TMSC > 5 mil - which ART
IUI
141
if count > 1 mil - which ART
IVF
142
similarity by the way LH and FSH
share common alpha chain - beta chain is different
143
where are leydig cells located in testis
interstitum between seminiferous tubules
144
what cell type lines seminerifous tubules
sertoli cells
145
what cell reaction happens when FSH binds sertoli cells or LH binds leydig cells
increase in cAMP
146
3 products of sertoli cells in adult
androgen binding protein, inhibin, and transferrin
147
what cells are responsible for blood-testis barrier
sertoli cells
148
2 compartments created by sertoli cells in tubule
basal compartment has immature germ cells, adluminal compartment for germ cells undergoing differentiation and maturation.
149
binding of testosterone in blood and tubule
blood - shbg, tubule - androgen binding protein (ABP)
150
what % testosterone is bound in blood
85% to shbg or albumin
151
what does inhibin affect
inhibitory effect on pituitary FSH release
152
time for sperm to traverse epididymis and effect on sperm
12 days, become more motile and develop fertilizing capacity
153
PSA function
serum protease in kallikrein family serves to liquefy coagulum 5-20 mins after ejaculation
154
what organ secretes fructose
SV
155
what does obstructed epididymis fee like
hard and enlarged
156
nl testicular length
4 cm
157
significance of low fructose
absence of SV and vas deferens input
158
who gets a karyotype
all men with azoospermia and severe oligospermia (<5 mil) planning to do IVF/ICSI
159
what is sperm chromatin assay
assesses degree of DNA fragmentation after chemically stressing sperm to eval DNA integrity. can be abnormal when nl semen analysis
160
what are sperm chromatin assays called - 3
flow cytometry, COMET and TUNEL
161
what % with NORMAL semen analysis and infertility have abnormal chromatin assay
5%
162
what % with ABNORMAL semen analysis and infertility have ambormal chromatin assay
25%
165
examples of causes of abnormal chromatin assay
causes of dan fragmentation - tobacco, medical dz, hyperthermia, air pollution, infection
166
fertility significance of primary testicular failure
50% have testicular sperm on biopsy that can be used for IVF/ICSI
167
interpretation of negative vs positive fructose test
positive rules out complete EDO
168
ddx of negative fructose test in azoospermic male with nl hormone studies (3)
1. CBAVD, 2. b/l EDO, 3. SV dysfunction (like bladder failure)
169
caveat of positive fructose test
doesnt rule out more proximal EDO or SV dysfunction
170
who gets testis biopsy
azoospermic male with nl testis and fructose in semen
171
who gets testis biopsy
azoospermic male with nl testis and fructose in semen
172
what % VV for azoospermia have sperm in ejaculate
90-95%
173
fertility rate after VV for azoospermia
35-60%
174
how long to follow patinets once environmental factors are corrected
3 months
175
pregnancy rate after varicocelectomy in previously infertile
40%
176
management of large ejaculate volume (>5.5cc)
IUI after sperm concentration (sperm may get diluted in semen)
177
management of large ejaculate volume (>5.5cc)
IUI after sperm concentration (sperm may get diluted in semen)
178
efficacy of boxers in infertility
not useful
179
efficacy of antioxidants in infertility
not 100% confirmed, but cochraine study showed improved preg rate
180
who responds best to clomiphine
low-nl testosterone and FSH levels (mild central nypogonadism)
181
who is aromatase inhibitor useful for
oligospermic or azoospermic men with T:E ratio of <10:1 to increase sperm yield
182
how many sperm are needed for IUI
5 mil
