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20 - infertility Flashcards

1
Q

SRY location

A

short arm of Y

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2
Q

SRY function

A

converts bipotent embryo to male

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3
Q

SRY AKA

A

testis determining factor (TDF)

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4
Q

3 events of gonadal differention that happen after transmission of y chromosome

A
  1. primordial germ cell migration, 2. mesonephric cell invasion, 3. establishment of germ cell lineage
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5
Q

at what point in gestation is urogenital ridge organized

A

4-6 wks

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6
Q

at what point in gestation are primordial germ cell migrating to UG ridge

A

6 wks

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7
Q

what controls migration

A

CAM’s - cell adhesion molecules - fibronectin and GAG’s

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8
Q

at what point in gestation are do sex cords start to develop

A

7 wks

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9
Q

what do sex cords become

A

seminiferous tubules

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10
Q

at what point in gestation do primitive germ cells develop into primitive gonocytes

A

15 wks

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11
Q

at what point in gestation do you see phenotypic male signs

A

7 wks

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12
Q

SRY - first product that steers toward male

A

steroidogenisis factor 1

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13
Q

role of SOX 9

A

critical to differentiation of gonadal cell types (sertoli/ leydig cells)

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14
Q

role of testosterone in development

A

directly induces development of epididymis, vas deferens, and SV

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15
Q

metabolism of testosterone

A

by 5 alpha reductase to dihydrotestosterone

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16
Q

DHT effect on development - 3

A

penis, scrotum, and prostate development

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17
Q

sertoli cell product in fetus

A

mullerian inhibitory substance

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18
Q

inhibin effect

A

inhibits FSH production

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19
Q

high testosterone feeds back to

A

inhibit FSH and LH

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20
Q

fetal testosterone level

A

gets to adult lefel in response to maternal gonadotropins

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21
Q

testosterone level after birth

A

drops to near zero until puberty. One small surge just after birth (?reason)

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22
Q

def of emission

A

deposition of semen into prostatic urethra due to rhythmic contraction of epididymis and vas deferens

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23
Q

neuro of emission

A

alpha adrenergic sympathetic control

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24
Q

ejaculation controlled by what nerve

A

pudendal

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25
Q

semen % breakdown

A

80% SV, 10% prostate, 10% testicular

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26
Q

ejaculate volume and vasectomy

A

stays the same

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27
Q

SV pH

A

basic

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28
Q

prostate pH

A

acidic (prostate acid phosphatase

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29
Q

time for maturation of sperm

A

64 d

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30
Q

transit time through epididymis

A

10 d

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31
Q

total transit time of sperm to ejaculation

A

3 mo

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32
Q

def of primary vs secondary infertility

A

primary - never any conception, secondary -previous conception

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33
Q

% couples concieving within a yr

A

85%

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34
Q

2010 AUA guideline caveat to eary infertility evaluation - 2

A
  1. known male or female fertility risk factors (cryptorchidism, hx chemotherapy), 2. man questions fertility potential (just has to ask)
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35
Q

if man asks for eval what do u do

A

semen analysis, reproductive history

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36
Q

% male factor infertility only

A

20%

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37
Q

% of infertile couples with an element of male factor infertility

A

30%

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38
Q

if male semen analysis are nl then?

A

eval female

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39
Q

if male and female appear initially nl

A

more in depth study of male

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40
Q

chemo agents causing damage to type a spermatogonia effect

A

high damage to type a = irreversible azoospermia, less damage = possible for recoverability

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41
Q

what determines infertility in radiation

A

dose

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42
Q

radiation dose causes temporary azoospermia

A

50 centigray, 50 rads

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43
Q

permanent azoospermia radiation dose

A

400-600 centigray

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44
Q

timeframe to recovery of germ cell production with radiation

A

1-2 yrs

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45
Q

first step in male PE for infertility

A

assessment of secondary sex characteristics

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46
Q

things to look for on DRE

A

midline prostate masses, enlarged SV

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47
Q

nl semen concentration

A

15 mil/cc

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48
Q

motility - nl%

A

40%

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49
Q

liquefy time

A

1 hr

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50
Q

ideal semen specimen - 3 factors

A

3 days of abstinence in a lab that can process within 1 hr and no lubricants

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51
Q

ddx low volume - 3

A

retrograde ejaculation, EDO, vasal agenisis (vas obstruction only lowers semen vol by 10%)

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52
Q

round sperm morphology name

A

globozoospermia

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53
Q

def globozoospermia and significance

A

absent acrosomes. Need ICSI

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54
Q

low motility ddx - 2

A

delay in processing or lubricant use

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55
Q

very low motility mgmt - 2

A

confirm with viability stain and consider immotile cillia syndrome (cartagener’s)

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56
Q

agglutination significance

A

antisperm ab’s

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57
Q

how to confirm presence of WBC

A

peroxidase stain

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58
Q

significance of WBC

A

prostatitis

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59
Q

when to get genetic testing

A

< 5 mil/cc

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60
Q

when to test endocrine axis - 3

A

[semen] < 10 mil/cc, low libido, other findings suggestive of endocrinopathy (small testis, gynecomastia)

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61
Q

what is minimum endocrine test - 2

A

early AM FSH and total testosterone

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62
Q

if low testosterone, what tests next - 3

A

prolactin, free testosterone, LH

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63
Q

what are pituitary excess vs deficiency states in infertility

A

excess - prolactinoma; deficiency - hypogonadotropic hypogonadism

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64
Q

causes of hypogonadotropic hypogonadism - 6

A

kallman’s, high prolactin, pituitary/ hypothalamic damage, prader willi, laurence moon-bardet-biedl syndrome, medications

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65
Q

prolactinoma MOA

A

prolactin inhibits GNRH release, therefore low FSH/LH

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66
Q

prolactinoma initial mgmt

A

medications

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67
Q

prolactinoma meds for tx - 2

A

cabergoline (less side effects), bromocriptine

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68
Q

most common presenting symptom for prolactimona

A

ED, decreased libido

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69
Q

meds causing elevated prolactin

A

antipsychotics, specifically phenothiazines

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70
Q

prader wili features

A

absent GNRH, obesity, small hands/feet, MR, hypotonic and short stature

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71
Q

laurence-moon-bardet-biedl pathognomonic feature

A

retinitis pigmentosa

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72
Q

laurence-moon-bardet-biedl features

A

hypogonadotripic hypogonadism, polydactyly, retinitis pigmentosa

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73
Q

idiopathic elevated prolactin mgmt

A

cabergoline

74
Q

hypogonadotripic hypogonadism definition

A

[low FSH, LH, testosterone, and low GNRH]

75
Q

kallman’s other finding - 3

A

anosmia, delayed puberty, small testis

76
Q

kallman’s inheritance

A

x linked

77
Q

kallman’s gene mutation

A

KAL-1 gene

78
Q

kallman’s treatment

A

LH/FSH analog –> specifically HCG/HMG

79
Q

kallman’s outcome w tx

A

return of spermatogenisis

80
Q

congenital version of elevated teststerone

A

CAH

81
Q

CAH mech for infertility

A

cortisol deficiency, high ACTH, increased adrenal androgens, feedsback and decreases gonadotropin release

82
Q

y chromosome microdeletion location

A

AZF (Yq11) - subclassified into a,b,c,

83
Q

which AZF have absolutely no sperm

A

AZF a,b

84
Q

which AZF have sperm

A

AZF c. has to be extracted by bx

85
Q

inheritance of AZF

A

all sons will carry mutation and potential for infertility

86
Q

what is kleinfelter’s

A

extra x chromosome (47xxy)

87
Q

kleinfelter’s physical exam findings - 4

A

small firm testis, gynecomastia, azoospermia, hypogonadism

88
Q

hormone profile on kleinfelter - T, LH, FSH, E

A

low T, high LH, high FSH, high E

89
Q

kleinfelter’s and sperm

A

2/3 have sperm on bx for ICSI

90
Q

kleinfelter’s and malignancy

A

higher risk of extragonadal (mediastinal) germ cell tumors, male breast cancer 10x risk

91
Q

CBAVD- gene

A

60% have CFTR mutation, mutation rarely found in unilateral vasal agenesis

92
Q

CFTR gene product name

A

cystic fibrosis transmembrane conductance regulator

93
Q

associated gu abnormality in CFTR

A

ipsilateral renal agenisis due to failure of development of wolffian structres

94
Q

what are wolffian structures - 3

A

vas, ureter, SV

95
Q

CBAVD presentation

A

can present like EDO due to absence of SV

96
Q

how does vas involute in pts with CBAVD

A

failure to maintain lumen of vas –> vas involutes

97
Q

kartagener’s syndrome associated with - 3

A

situs inversus, bronchiectasis, chronic sinusitis (long hx pulmonary and sinus infections)

98
Q

kartagener’s inheritance

A

AR

99
Q

kartagener’s semen analysis findings

A

abscent dinene arms on EM and low motility on semen analysis

100
Q

kartagener’s aka

A

immotile ilia syndrome

101
Q

3 genetic disorders with chronic sinusitis and infertility

A

young’s syndrome, kartagener’s, and CF

102
Q

young’s syndrome and infertility

A

thick epididymal secretions –> obstructive azoospermia

103
Q

young’s syndrome features - 3

A

bronchiectasis, sinusitis, nl vas

104
Q

low semen volume and azoospermia question to ask

A

vas present? - if abscent –> CFTR, if present –> r/o EDO

105
Q

how to r/o EDO

A

do TRUS to eval SV size

106
Q

tx EDO

A

TUR

107
Q

TRUS findings suggestive of EDO - 4

A
  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
Q

if nl TRUS and no EDO, then dx?

A

failure of emission

109
Q

how to tx failure of emission

A

sympathomymetics, electroejaculation, testiular sperm extraction

110
Q

azoospermia and nl semen volume - question to ask

A

what size are testis - if nl –> check FSH

111
Q

azoospermia and nl semen volume - interpretation of FSH

A

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
Q

antiestrogen MOA

A

block estrogen receptor at hypothalamus and pituitary. Increase LH/FSH without affecting T. Prevent negative feedback

113
Q

def of primary testicular failure (2)

A

FSH > 3x nl along with atrophic testicle on exam

114
Q

how to administer antiestrogen

A

repeat horone profile at 3 wks and titrate.

115
Q

once hormones nl on antiestrogen

A

check semen analysis at 3 mo

116
Q

2 antiestrogen drugs

A

clomiphene, tamoxiphen

117
Q

aromatase inhibitor MOA

A

blocks aromatase in fat that converts T –> E

118
Q

name of aromatase inhibitor

A

testolactone

119
Q

aromatase inhibitor good for

A

kleinfelter

120
Q

% subfertile men with varicocele

A

40%

121
Q

subclinical varicocele def

A

dx by ultrasound only

122
Q

% subfertile men with varicocele

A

40%

123
Q

subclinical varicocele def

A

dx by ultrasound only

124
Q

subclinical varicocele and infertility

A

do not cause infertility - do not repair

125
Q

time to improvement semen parameters after varicocectomy

A

3-6 mo

126
Q

recurrent varicocele after ligation - mgmt

A

embolization

127
Q

most durable repair method

A

microsurgical –> also preserve lymphatics preventing hydrocele

128
Q

preoperative factors predicting vas reversal success

A

shorter interval (<10 yrs) since vasectomy, pre-vasectomy paternity, prior conception with current partner

129
Q

intraop factors predicting successful vasectomy reversal - 5

A
  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
Q

time to sperm after VV/VE

A

6-16 mo

131
Q

time to pregnancy after vas reversal

A

12 mo

132
Q

what makes decision to do VV vs VE at time to vas reversal

A

proximal vas fluid quality

133
Q

proximal vas fluid characteristics favoring VV

A

any sperm or sperm parts, copius and clear or cloudy

134
Q

proximal vas fluid characteristics favoring VE

A

thick insuppated secretion and no sperm, or no fluid

135
Q

redo vas reversal procedure of choice

A

VE

136
Q

where to find sperm in obstructive azoospermia

A

epididymis

137
Q

quality of epididymal vs testicular sperm

A

same

138
Q

how to choose ART technique

A

total motile sperm count

139
Q

how to calculate total motile sperm count

A

volume of semen x concentration x motility

140
Q

if TMSC > 5 mil - which ART

A

IUI

141
Q

if count > 1 mil - which ART

A

IVF

142
Q

similarity by the way LH and FSH

A

share common alpha chain - beta chain is different

143
Q

where are leydig cells located in testis

A

interstitum between seminiferous tubules

144
Q

what cell type lines seminerifous tubules

A

sertoli cells

145
Q

what cell reaction happens when FSH binds sertoli cells or LH binds leydig cells

A

increase in cAMP

146
Q

3 products of sertoli cells in adult

A

androgen binding protein, inhibin, and transferrin

147
Q

what cells are responsible for blood-testis barrier

A

sertoli cells

148
Q

2 compartments created by sertoli cells in tubule

A

basal compartment has immature germ cells, adluminal compartment for germ cells undergoing differentiation and maturation.

149
Q

binding of testosterone in blood and tubule

A

blood - shbg, tubule - androgen binding protein (ABP)

150
Q

what % testosterone is bound in blood

A

85% to shbg or albumin

151
Q

what does inhibin affect

A

inhibitory effect on pituitary FSH release

152
Q

time for sperm to traverse epididymis and effect on sperm

A

12 days, become more motile and develop fertilizing capacity

153
Q

PSA function

A

serum protease in kallikrein family serves to liquefy coagulum 5-20 mins after ejaculation

154
Q

what organ secretes fructose

A

SV

155
Q

what does obstructed epididymis fee like

A

hard and enlarged

156
Q

nl testicular length

A

4 cm

157
Q

significance of low fructose

A

absence of SV and vas deferens input

158
Q

who gets a karyotype

A

all men with azoospermia and severe oligospermia (<5 mil) planning to do IVF/ICSI

159
Q

what is sperm chromatin assay

A

assesses degree of DNA fragmentation after chemically stressing sperm to eval DNA integrity. can be abnormal when nl semen analysis

160
Q

what are sperm chromatin assays called - 3

A

flow cytometry, COMET and TUNEL

161
Q

what % with NORMAL semen analysis and infertility have abnormal chromatin assay

A

5%

162
Q

what % with ABNORMAL semen analysis and infertility have ambormal chromatin assay

A

25%

165
Q

examples of causes of abnormal chromatin assay

A

causes of dan fragmentation - tobacco, medical dz, hyperthermia, air pollution, infection

166
Q

fertility significance of primary testicular failure

A

50% have testicular sperm on biopsy that can be used for IVF/ICSI

167
Q

interpretation of negative vs positive fructose test

A

positive rules out complete EDO

168
Q

ddx of negative fructose test in azoospermic male with nl hormone studies (3)

A
  1. CBAVD, 2. b/l EDO, 3. SV dysfunction (like bladder failure)
169
Q

caveat of positive fructose test

A

doesnt rule out more proximal EDO or SV dysfunction

170
Q

who gets testis biopsy

A

azoospermic male with nl testis and fructose in semen

171
Q

who gets testis biopsy

A

azoospermic male with nl testis and fructose in semen

172
Q

what % VV for azoospermia have sperm in ejaculate

A

90-95%

173
Q

fertility rate after VV for azoospermia

A

35-60%

174
Q

how long to follow patinets once environmental factors are corrected

A

3 months

175
Q

pregnancy rate after varicocelectomy in previously infertile

A

40%

176
Q

management of large ejaculate volume (>5.5cc)

A

IUI after sperm concentration (sperm may get diluted in semen)

177
Q

management of large ejaculate volume (>5.5cc)

A

IUI after sperm concentration (sperm may get diluted in semen)

178
Q

efficacy of boxers in infertility

A

not useful

179
Q

efficacy of antioxidants in infertility

A

not 100% confirmed, but cochraine study showed improved preg rate

180
Q

who responds best to clomiphine

A

low-nl testosterone and FSH levels (mild central nypogonadism)

181
Q

who is aromatase inhibitor useful for

A

oligospermic or azoospermic men with T:E ratio of <10:1 to increase sperm yield

182
Q

how many sperm are needed for IUI

A

5 mil

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