Repro Pathophys: Puberty and Repro-age Flashcards
SRY
male gonadal development master regulator
Y chromosome
SOX9
male gonadal development TF
interacts with SRY
suppressed by genes of X chromosome when SRY is absent
Wolffian ducts
male repro embryology
forms male duct system (epididymis, vas deferens, seminal vesicles)
testosterone production by leydig cells contributes to Wolffian duct formation
sertoli cells
male repro
produce antimullerian hormone (AMH) to prevent formation of female mullerian duct system
Mullerian ducts
female repro embryology
forms Fallopian tubes, uterus, cervix, and upper vagina
default, in absence of AMH or androgens
5-alpha-reductase
male development & embryo
converts testosterone to more potent dihydrotestosterone
essential for complete masculinization of male external genitalia
anosmia and delayed puberty
absence of smell
points to GnRH issue
GnRH neurons migrate from olfactory placed during development
therefore abnormal migration of GnRH neurons also tends to accompany abnormal olfactory development
puberty of infancy
normal “mini-puberty” due to reduction in placental inhibition of GnRH
females: estradiol monthly cycling + gradual (non-cyclic) decline in FSH and LH after initial spike ~1 mo
males: breast development and genital enlargement, testosterone curve peaks around 6 weeks and then gradually declines to very low levels by about 6 mo
FSH and LH targets in male
LH - leydig cells - testosterone production
FSH - Sertoli cells - AMH production and nutritional etc. support of sperm development
timing of lab workup for abnormal puberty
morning ~8am
LH is released overnight
initiation of puberty male
release of inhibition of hypothalamic GnRH pulse generator
(constant low-level GnRH suppresses FSH and LH, while pulsatile GnRH activates)
following increase in pulsatile GnRH production, pituitary and gonadal sensitivity also increases creating acceleration
testicular enlargement is the first observed sign
normal pubertal window male
9-14 y/o onset (testes stage G2, ~4cc)
14-18 y/o testes reach full size (G5, 15-25cc)
timing mainly genetic
height: 10.5-16 onset, 13-17.5 end
penis: 11-14.5 onset, 13.5-17 end
pubic hair coincides with testes usually
strength: ~15-16
very rare to see any changes past age 20
tanner stages male
G(gonadal)1 - prepubertal
G2
- testicular enlargement (~4cc)
- sparse, fine, straight pubic hair
- no penile enlargement
G3
- continued testicular enlargement
- long, dark, curly pubes around mons only
- penile length, no girth change
G4
- continued testicular and penile enlargement (length and girth)
- pubic hair thick but not yet spread to thighs
G5- mature (
- testes ~15-25cc
- flaccid penis ~3.5 in (2-6, 2.5-97.5 percentile)
- stretched penis ~5 in (4.3-6.5)
- erect penis ~6 in (4.5-7.5)
- pubic hair thick, inverted triangle distribution with spread to thighs
note that right testis is generally slightly bigger than left
orchidometer
measures testicular size (approx)
pubarche
appearance of body hair and odor
d/t adrenarche - androgen precursors from *adrenal gland
separate process from puberty but normally occurs around same time
epithelia of endocervix
simple columnar
mucus producing
mucus is responsive to estrogen and changes throughout cycle
epithelia of ectocervix
stratified squamous
SCJ (transitional zone)
squamous-to-columnar junction of cervix
prone to metaplasia
important to sample during PAP
layers of uterus
endometrium - functional layer sheds during menstruation - basal layer myometrium perimetrium
cells of inner mucosal lining of fallopian tube
ciliated and nonciliated secretory epithelial cells
4 segments of fallopian tube
interstitial
- junction w/ uterus
isthmus
- straight segment close to uterus
ampula
- most of tube, after isthmus)
infundibulum
- with fimbriae
layers of fallopian tube
mucosa (inner)
muscular
serosa (outer)
epithelia of vagina
stratified squamous
significance of glycogen in vagina
supports lactobacillus in microbiota
pre-puberty and post-menopause there is less glycogen and therefore less colonization
granulosa cell
aka follicular cell
proliferate and hypertrophy to surround developing oocyte
secrete progesterone after ovulation
respond to FSH
theca cell
secrete androgens in ovary, which are later converted to estrogens in the granulosa cell
crosstalk with granulose cell
squamous, surround granulosa cells
respond to LH
primordial follicle
single layer of granulosa cells
primary follicle
several layers of granulosa cells
compact around oocyte
no liquid filled regions
secondary follicle
more layers of granulosa cells than primary
liquid filled regions begin to appear
first meiotic division completed
arrest at this stage
graffian follicle
aka tertiary
mature, liquid filled
rupture to release egg
second meiotic division starts
atretic follicle
degenerated follicle
apoptosis prior to follicle maturity
common pre-puberty and repro age (the oocytes that do not continue to develop each cycle)
in excess can be sign of pathology
atresia occurs when follicles are not stimulate by FSH
thelarche
breast development in female
tanner stages female
1- prepubertal
2
- breast budding
- areolar enlargement
- some coarse, pigmented hair along labia majora
3
- breast and areola enlargement
- spread of pubes over mons pubis
4
- continued breast enlargement
- secondary mound of areola
- near adult pubes
5
- mature breast contour
- adult pube distribution
normal pubertal window female
first sign usually breast development
average age 10.5, range 8-12 onset
stops 14.5 (11.5-18)
menarche 12.5 (10-16.5)
0.5 yr after peak growth spurt
2-2.5 yr after thelarche
height and pubic hair (usually) lags slightly behind breast development
pubarche first sign in ~15%
thelarche age black (~9.5) < Mexican < white (~10.5)
early menarche pattern
irregular cycles for 3-5 years (90% have >10 periods/yr after 3 years)
initially irregular, anovulatory q21-45 days
onset of puberty mechanism
similar in male and female
release of brake on pulsatile hypothalamic GnRH
primary signal is unknown other than genetic influence
- kisspeptin and neurokinin B activation are involved
- leptin, sufficient adipose needed (and obesity is associated with early puberty)
- CNS pubertal clock
- trending earlier
FSH and LH targets female
FSH
- granulosa cell
- makes estrogens (which support endometrium proliferation)
- granulosa cell proliferation
- otherwise atresia
LH
- theca cell
- makes androgens
- stimulates estrogen/progesterone production in granulosa cell
- LH spike (due to estrogen levels crossing a threshold from negative to positive feedback) induces ovulation
estradiol in menstrual cycle
produced by pre-ovulatory follicle peaks ~24 h prior to ovulation when estradiol levels reach critical concentration, there is a switch from negative to positive feedback on LH causes LH surge that causes ovulation ovulation ~24-36 h after LH surge
ovulation induction
estradiol produced by pre-ovulatory follicle reaches critical concentration, switches from negative to positive feedback on LH
~24 h later, LH surge occurs
~24-36 h after that, ovulation occurs (caused by LH)
LH surge
- resumption of meiosis 1 of primary oocyte
- synthesis of prostaglandins –> follicle rupture
- luteinization of granulosa cells –> progesterone production
luteal phase
- after LH surge/ovulation
- granulosa and theca cells luteinize to form corpus luteum
- corpus luteum produces estrogen and progesterone
- – negative feedback on LH/FSH –> no new follicular growth
- – secretory changes of functional endometrium in support of pregnancy (arteries, glycoproteins, edema)
- corpus luteum loses function after 9-11 days if not rescued by hCG
normal menstrual cycle duration and ovulation
q21-35 days (60% 25-28 days)
if regular, almost always ovulatory (except PCOS)
anovolation common in setting of irregular menses
timing of luteal phase (~14 days) is more consistent than follicular phase (where most of variability in cycle length comes from)
- period will almost always occur ~14 days after ovulation
normal menopause window
average 51.5
considered premature if <40
dx if no menses for 1 year
ovulation predictors
- basal body temp (rough)
- kits: LH surge, ± estrogen
- luteal phase progesterone
- cervical mucous changes
when to investigate primary amenorrhea
- age 15-16 if normal growth and secondary characteristics
- age 13 in absence of secondary characteristics or height <3%ile
- age 12-13 if + breast dev and + cyclic pelvic pain
- within 2 years of breast development
when to investigate secondary amenorrhea
- 3 months if previously regular periods
- 6 months if previously irregular periods
- likelihood of pregnancy
- hx of intermenstrual intervals >35 days
Asherman’s syndrome
partial or complete blockage of uterine outflow tract d/t adhesions
can cause primary or secondary amenorrhea
usually d/t hx of D&C
genital TB also common cause in endemic areas
5-alpha-reductase deficiency
primary amenorrhea of person with female genitalia
develops male secondary characteristics at puberty
XY chromosome, but inability to convert testosterone to more potent form prevents formation of male external genitalia
androgen insensitivity syndrome
primary amenorrhea of person with female genitalia
no male secondary characteristics at puberty
XY chromosome, but does not respond to testosterone
testosterone in male range
uterine outflow tract obstruction in primary amenorrhea
- imperforate hymen, transverse vaginal septum, mullein agenesis, Asherman’s syndrome, tumor/mass/polyp/fibroid
- often presents with cyclic pelvic pain
- surgical - risk of endometriosis with retrograde menstrual flow
initial labs amenorrhea
pregnancy test
FSH
- ovarian or central
- increased in primary ovarian insufficiency (POI)
- normal to low in hypothalamic amenorrhea, neuroanatomic abnormality
- low in idiopathic hypogonadotropic hypogonadism
hyperandrogegism
- PCOS
prolactin
- increased in neuroanatomic abnormality, idiopathic hypogonadotropic hypogonadism, certain drugs
AMH (antimullerian hormone)
- androgen insensitivity
- low in POI
all of the above may be normal in functional hypothalamic amenorrhea (FSH may also be low), eating disorder, excess exercise, chronic disease
functional hypothalamic amenorrhea
dx of exclusion
r/o:
- chronic disease (T1DM, celiac, hypERthyroid, Cushing)
- opioids, glucocorticoids, psychotropes that increase prolactin
- eating disorders
- typically energy intake:expenditure mismatch
- stress may also cause
- certain genes are linked
- some features of PCOS may also be present
low gonatotropins, normal prolactin
get an MRI if these red flags are present:
- atypical hx
- headache
- signs of other hypothalamic disfunction
- hyperprolactinemia
hypergonadotropic hypogonadism (female)
primary ovarian insufficiency
aka premature menopause
~10% of secondary amenorrhea
high FSH
low AMH
low estrogen
d/t:
- unknown (most)
- turner’s
- autoimmune polyglandular failure
- other rare disorders
- radiotherapy/chemo
f/u test:
- karyotype
- serum anti-cortical Ab
- serum 21-hydroxylase Ab
- T3/T4
- TPO
- FMR1 permutation screening
- bone mineral density assessment
estrogen and amenorrhea
almost always low
PCOS
- amenorrhea or oligomenorrhea
- hirsutism
- acne
- dark patches of skin
- insulin resistance
- ~50% obese
- sx onset shortly after menarche, slowly progressive
- high androgens
- low estrogen
- cysts on US (not in all cases)
tx:
- OCPs
- spironolactone
- clomiphene citrate
- letrozole
- metformin
cyclic pelvic pain ddx
- dysmenorrhea
- endometriosis
- Mittelschmerz (painful ovulation)
acute noncyclic pelvic pain ddx
PID ruptured or hemorrhagic ovarian cyst ectopic spontaneous abortion ovarian torsion endometrioma endometriosis acute growth or degeneration of uterine myoma/leioma (fibroid)
non-pelvic:
- appendicitis
- cholecystitis
- diverticulitis
- SBO
- IBD
- GI infection
chronic noncyclic pelvic pain ddx
pelvic congestion syndrome (pelvic vein incompetence) adhesions of uterus retroversion of uterus vulvodynia (vulva pain) chronic PID tuberculosis salpingitis hx of traumatic intercourse
PID
pelvic inflammatory disease bilateral lower abd pain exacerbated by intercourse or jarring movements recent onset fever ~50% abnormal uterine bleeding ~30% ± discharge, urethritis, chills
risk of infertility and ectopic
d/t:
- STI
- trachomatis
ectopic pregnancy
generally unilateral pelvic pain clinical signs 6-8 wk post LMP bleeding ~50% ± orthostatic, fever life threatening fallopian rupture ~20%
d/t:
- hx tubal disease
- hx ectopics
- hx infertility
- hx DES exposure of mother in utero
- hx PID
unruptured can be treated w/ methotrexate ~90%
primary amenorrhea with athelarche
- absence of estrogen
low FSH:
- hypogonadotropic - pituitary or ht problems
- MRI recommended to r/o neuroanatomical causes
- may also be (normal-ish) congenital delay of puberty (genetic; dx of exclusion)
high FSH:
- gonadal dysgenesis
- 46XY (e.g. 5-alpha-reductase deficiency; note androgen insensitivity usually has thelarche)
- 45XO (Turner’s)
- estrogen production defect
mullerian agenesis
congenital absence of uterus primary amenorrhea –cyclic pain \+thelarche as with all abnormalities of vagina/uterus, often accompanies renal abnormalities e.g. unitary kidney or double collecting system
premature pubarche/adrenarche (male)
- <9 y/o
- isolated body hair/odor/acne (not full precocious puberty)
- no genital changes
- no growth spurt or advancement of bone age
d/t:
- prematurity
- small for gestational age
- excess weight gain
- elevated DHEA
precocious thelarche
- <8 y/o breast budding
- isolated, no growth spurt, no advancement of bone age
- ≠ precocious puberty
d/t:
- over function of pituitary-ovarian axis
- FSH high-normal but increases more than usual on stim testing
- LH normal
- elevated estradiol
- ovarian microcysts
- also associated with obesity
precocious puberty workup male
- note 5-10x F>M
clinical:
- growth spurt
- accelerated bone age
- testicular enlargement
- possible pubarche/adrenarche
male:
- testicular ultrasound - asymmetric testicular enlargement
- 8am labs:
- peds LH
- peds FSH
- testosterone
- 17OHP/DHEAS (for signs of pubarche/adrenarche)
- TSH, free T4
- HCG/AFT (for germ cell tumors, hepatoblastoma)
precocious puberty causes (male)
central:
- gonadotropin dependent, i.e. increased LH/FSH
- note symmetric testicular enlargement
- idiopathic
- congenital anomaly
- CNS insult (infection, trauma, radiation)
- tumors
- sturge-weber
- tuberous sclerosis
- neurofibromatosis-1
peripheral:
- gonatotropin independent, decreased LH/FSH
- exogenous testosterone
adrenal tumor
- CAH (note penis enlargement > testicular enlargement)
- familial testotoxicosis (note penis enlargement > testicular enlargement)
- hCG testicular tumor (note penis enlargement > testicular enlargement)
- testosterone/leydig cell testicular tumor (note asymmetric testes)
- primary hypothyroidism
- McCune-Albright
delayed puberty (male)
> 14 y/o
d/t:
- constitutional delay of growth ~65%
- functional hypogonadotropic (central) hypogonadism ~20%
- permanent hypogonadotropic (central) hypogonadism ~10%
- gonadal failure 5-10%
constitutional delay of growth and puberty (male)
CDGP
- slow growth in childhood
- growth deviates at puberty
- eventual catch-up
- delayed bone age
- family hx of delay
- short stature for family (current height < mid parental target = avg(mom+5,dad))
- negative ROS (chronic illness)
- evidence of appropriate nutrition
isolated hypogonadotropic hypogonadism (male)
IHH
- presents similarly to CDGP
- anosmia ~50%
- normal bone age
- micropenis
- cryptorchidism (failure to descend)
- testicular volume 1 ml
delayed puberty (male) workup
- bone age XR
- 8 am labs:
- systemic: CBC, CMP, ESR…
- karyotype if gynecomastia, pectus, small testes
- peds LH
- peds FSH
- estradiol/testosterone
- TSH, free T4
- prolactin
kleinfelter syndrome
XXY
signs:
- male phenotype
- delayed puberty
- pectus
- gynecomastia
- firm, small testicles
- above average height
- low testosterone
- elevated LH/FSH (hypergonadotropic hypothyroidism)
ddx abnormal uterine bleeding
PALM-COEIN
local: polyps adenomyosis leiomyomas (fibroids) metaplasia (endometrial hyperplasia or carcinoma)
systemic: coagulopathies ~20% ovulatory dysfunction endometriosis iatrogenic not yet classified
some specifics:
- vWF disease (AUB at onset of menses is often first sign)
- hypO AND hypERthyroid
- chlamydia
dx AUB
labs: CBC (anemia, thrombocytosis) TSH/T4 PAP gonharrhea/chlamydia
exam:
- pelvic w/ speculum and bimanual
imaging:
- transvaginal US
- in adolescents, trans abdominal US may be preferred
- if inconclusive, sonohysterography or hysteroscopy
- if further workup needed, MRI
biopsy if needed
tx AUB
NSAIDs progestins OCPs levonorgestrel IUD tranexamic acid
surgery if structural (e.g., myxomas, polyps)
post-childbearing or no kids desired:
- endometrial ablation
- hysterectomy
fibroids/leiomyomas
- most common solid and symptomatic neoplasm in women
- most common indication for hysterectomy
- incidence increases w/ age thru menopause
- racial disparity black>white
sx:
- ~25% symptomatic
- AUB (heavy or prolonged)
- ± anemia
- fertility issues
- pain
- bulk symptoms (pressure, constipation, urinary frequency)
dx:
- transvaginal US
- pelvic exam
- PAP
- r/o cancer
tx:
- watch and wait
- oral GnRH antagonist for up to 2 years (elagolix) - reduces uterine size and reduces bleeding
- OCPs (does not help bulk symptoms)
- LNG-IUD
- trainexamic acid (antifibrinolytic)
- myomectomy (fertility-preserving)
- uterine artery embolization
- hysterectomy
endometriosis etiology
- ~10% incidence, most common disorder in repro-aged women
- endometrial tissue outside uterus
mx:
- estrogen-dependent
- implantation s/p retrograde menstrual flow thru fallopian tube
- metaplasia to embryonic mesothelium
- induction of undifferentiated peritoneal cells –> endometrium
- metastatic (outside pelvis): lymphatic or vascular dissemination of endometrial cells
- reduced NK cell or mq clearance of peritoneal cells
sites:
- ovary (most common)
- cul-de-sac
- broad ligament
- bladder peritoneum
- bowel peritoneum
- post surgical:
- - umbilicus (laparotomy)
- - tubal stumps (tubectomy)
- - amputated stumps of cervix
pathology:
- dark red, blue-ish, or black cyst
- scarring –> puckered appearance
- “powder burnt” areas = inactive lesions
- small risk of conversion to metaplasia
endometriosis dx
clinical:
- dysmenorrhea (pain during periods)
- dyspareunia (pain during sex)
- dyschezia (constipation)
- infertility
- chronic pelvic pain
exam:
- fixed pelvic mass
- puckered regions in posterior fornix
- cervical shift to one side
- fixed uterus
imaging:
- US
- laparoscopy w/ biopsy
histology:
- biopsy essential
- endometrial glands
- endometrial stroma
classification:
- minimal to severe
- describes fertility outcome, not symptoms
- baed on size and location of lesion
ddx:
- PID
- fibroid/leiomyoma
- adenomyosis
- cervical cancer
- rectal cancer
- ovarian cancer
endometriosis tx
- fulguration (thermal destruction)
- cystectomy
symptomatic:
- combined OCPs
- progestin
- GnRH agonist
- GnRH antagonist
hysterectomy + oophorectomy not definitive (~15% reemergence)
reemergence common with all tx
gonorrhea name, structure, dx, tx
neisseria gonorrheae
gram negative diplococci
dx: NAAT (PCR)
tx: ceftriaxone 500mg IM x1
chlamydia name, structure, dx, tx
chlamydia trachomatis
gram negative
intracellular
no peptidoglycan wall
dx: NAAT (PCR)
tx: doxycycline 100mg po BID x7 days
specific infections caused by chlamydia
asymptomatic >80% cervicitis urethritis PID ectopic pregnancy/infertility
baby:
ophthalmia neonatorum
infant pneumonia
PID
infection/inflammation of upper female repro tract
- endometritis
- salpingitis
- tubo-overian abscess
- peritonitis
usually gonorrhea or chlamydia
potential long-term problems
- e.g. perihepatitis (rare)
- ectopics
sx:
- acute
- lower abd/pelvic pain
- cervical motion tenderness
- various
trichomoniasis
thrichomonas vaginalis
single-celled protozoan parasite (only protozoal infection of genital tract)
anaerobic, flagellated
clinical:
- mainly sx in women (hence vaginalis)
- cervicitis, discharge, pain, itching, burning
- rarely urethritis in males
dx:
- NAAT
- Ag
- wet mount
tx: metronidazole or tinidazole
syphilis name, structure, dx, tx
treponema pallidum pallidum
spirochete
gram negative
dx:
- RPR (rapid plasma reagin)
- treponemal Ag or Ab (TPPA/FTA Ab)
- dark field microscopy, if ulcerated
tx:
- primary/secondary: benzathine penicillin x1
- late latent: benzathine penicillin x3
- neurosyphilis, otic, ocular: penicillin G
stages of syphilis
primary
- chancre (ulcer)
secondary
- body rash
- alopecia (“moth-eaten” hair)
- mucous patch
early latent
- <1 yr
- asymptomatic
late latent
- > 1 yr
- asymptomatic
tertiary
- gumma
- aortitis
- tabes dorsalis
- paresis
- neurosyphilis
- otic
- ocular
genital herpes
HSV type 1 and 2 (usually 2)
dsDNA virus
clinical:
- vesicles
- then ulceration
- then healing
dx:
- HSV PCR of lesion swab
transmission:
- mucosal or epithelia surface
- genital/oral secretions
tx:
- acyclovir or valacyclovir (decoy nucleotide, chain termination)
mucosal HPV risk stratification by strain
low oncogenic potential:
- most common
- 6, 11, 42, 43, 44
- types 6 and 11 cause respiratory sx
high oncogenic potential::
- HPV 16 and 18 >70% cervical
- HPV 16 is most common in penile carcinoma
- most of 30’s and 50’s, 66, 68
infectious diseases in pregnancy
TORCH
- toxoplasmosis
- “other”: HIV, syphilis
- rubella (blueberry muffin rash)
- CMV (microcephaly)
- HSV/VZV
parvovirus (fetal hydrops)
listeriosis (neuro; stillbirth)
congenital toxoplasmosis
- cat feces and cow meat
- 1st trimester: spontaneous abortion
- 2nd/3rd: chorioretinitis, hydrocephalus
congenital syphilis
- miscarriage/stillbirth/prematurity
- deformed bones
- anemia
- hepatosplenomegaly
- jaundice
- meningitis
- skin rash
900% increased incidence in CA since 2012
congenital CMV
- most common maternal-fetal infection in US
- saliva/urine exposure has highest risk
- 1 in 200 affected, 1 in 5 of those sx
clinical:
- microcephaly
- seizures
- retinitis
- rash
- IUGR
- hepatosplenomegaly
- jaundice
sequelae:
- hearing loss
- dev/motor delay
- vision loss
- microcephaly
- seizures
dx:
- IgG avidity (maternal)
- amniocentesis w/ culture and PCR
congenital HSV
skin eyes mucosa ~45% CNS ~30% - lethargy - seizures - poor feed - dev delay - blindness sepsis, visceral involvement common
prevention:
- C section
- avoid fetal scalp monitors
- ARVs near term if lesions present or recent acquisition
tx (infant)
- IV ACV
consequences of untreated STI
- PID
- infertility
- spread
- disease progression w/ some
genital ulcers ddx
- syphilis
- HSV
urethritis and cervicitis ddx
- GC
- chlamydia
- trichomonas
dx infertility (time)
> 1 year properly timed unprotected intercourse
>6 mo in female >35 y/o
male factor infertility (stats)
approx 15% couples infertile
male solely responsible 20% infertility
contributes in additional 30-40%
i.e. male factor infertility involved 50-60%
ddx male factor infertility
ejaculate:
- azoospermia (no sperm) d/t anatomy or testicular failure
- oligozoospermia (low sperm count)
- retrograde ejaculation (semen –> bladder)
- anejaculation s/p surgery, spinal cord injury (sperm made but not ejaculated)
sperm:
- infection
- inflammation
- DNA damage d/t oxidative stress
testes:
- varicoceles (enlarged scrotal veins)
- hypogonadism
- trauma, surgery, etc.
central:
- pituitary tumor
- genetic abnormalities
organs of male repro tract
production: testes
storage, maturation: epididymis
pathway: epididymis –> vas deferens –> ejaculatory duct via accessory –> urethra
accessory:
- seminal vesicles produce and store seminal fluid
- prostate and bulbourethral glands contribute to volume and composition of semen
achieving pregnancy male factor infertility
- sometimes continued sexual intercourse
- intrauterine insemination of concentrated sperm (esp for oligozoospermia)
- sometimes IVF
- IVF w/ intracytoplapmic sperm injection
hx questions male infertility
- ages M&F
- how long trying to conceive
- “how”?
- ovulation tracking
- intercourse timing
- stopping contraception
- prior pregnancy details
- prior infertility tx
- ED
- libido
- orgasm
- pain w/ sex
- urinary changes
- hormone use/steroids
- fever
- heat exposure (hot tub, sauna, occupational)
- recent virus
- olfactory changes
- vision changes
- change in testicular size
hx:
- GU surgery
- trauma
- torsion
- hernia
- undescended or atrophic testis
- mumps
- diabetes
- htn
- neurological
- cancer
- overall fitness and diet
fhx:
- infertility, GU, endocrine conditions
shx:
- heavy lifting, desk work
- drugs
meds that affect male fertility
erythromycin, tetracycline, gentamicin
chemo - alkylating
exogenous testosterone, anabolic steroids
androgen blockers e.g. spironolactone
5-alpha reductase inhibitors
antidepressants (affects ejaculatory latency, ED, libido)
sulfasalazine (affects sperm count)
cimetidine (affects LH secretion)
alpha blockers e.g. tamsulosin (retrograde ejacualtion)
varicoceles
enlargement of pampiniform plexus
15-20% of all men
sx:
- often asymptomatic
- heaviness
- aching or throbbing discomfort
- impaired sperm count and motility
- may cause DNA damage to sperm d/t hypoxic stress
exam:
- visible enlargement/gnarling of spermatic vein
- more common on left d/t angle of insertion of gonadal vein to renal vein
- isolated right varicocele: imaging to look for tumor
tx:
- surgery or embolization may improve chances of spontaneous pregnancy
CUAVD/CBAVD
congenital unilateral or bilateral absence of vas deferens
associated w/ CFTR mutations including carrier (CBAVD ~80%)
tx:
- testicular sperm extraction
labs and imaging male infertility
always:
- semen analysis x2 (4 weeks apart, each following 48-72 h of abstinence from ejaculation)
- testosterone
- FSH
- testicular, transrectal (prostate + seminal vesicles) US
optional, useful:
- LH
- estradiol
- prolactin
special cases:
- post-ejaculatory urinalysis
- karyotype
- Y chromosome microdeletion
- CFTR mutations
- sperm DNA fragmentation
- abd/pelvic imaging
- pituitary MRI
- vasography or seminal vesiculography
hypospermia or aspermia ddx
low or no semen volume
- retrograde ejaculation
- post-ejaculatory UA
- tx pseudoephedrine or TCA (imipramine) ~65% effective
- alt tx sperm harvesting from PEU
obstructive azoospermia
- no sperm
- negative PEU
other rare causes
azoospermia ddx
no sperm count
obstructive - obstruction of seminal tract preventing passage of sperm
- hypospermia w/ negative PEU
- transrectal US
- aspirate seminal fluid to check for sperm
- if yes, ejaculatory duct obstruction
- tx w/ transurethral resection of ejaculatory duct
- if vas deferens obstruction, vasography + nasal reconstruction
non-obstructive - failure to manufacture
- measure pituitary and testicular hormones
- karyotype for klinefelter esp if other clinical signs ~11%
- – atrophic testes
- – tall
- – hypergonadotropic hypogonadism
- Y chromosome micro deletion testing
- same ddx as abnormal male puberty
anejaculation
most often s/p spinal cord injury
inability to climax
tx:
- penile vibratory stimulation to glans
- electroejaculation - electrical probe in rectum against prostate (often –> retrograde ejaculation; alkalinize urine with oral meds to improve sperm viability)
seminiferous tubules
long, coiled tubules comprising testes
make sperm
interstitial tissue of testes
Leydig cells (LH responsive, produce testosterone)
- large
- eosinophilic
- crystals of Reinke
neurovasculature
Sertoli cell fx
“mother cell”
structural and nutritional support
androgen-binding protein aids w/ DHT and T transport
AMH secretion (prevents formation of mullein ducts)
stages of spermatogenesis
spermatogonia A –> B (most basal)
spermatocyte I –> II
spermatid - no tail yet (most luminal)
sperm (in epididymis)
epithelium of epididymis
pseudo stratified columnar w/ microvilli
previously thought to be cilia but actually seem to fx in resorption of excess testicular fluid
vas deferens histology
3 thick layers of smooth muscle
innervated
pseudo stratified columnar epithelium
seminal vesical histology
glandular sacs
zones of prostate
peripheral zone
- most prone to malignancy, inflammation
- bulk of prostate
- outer parenchyma
- glandular
central zone
- least prone to inflammation, hyperplasia
- surrounds ejaculatory duct and utricle (mullerian remnant)
transitional zone
- hyperplasia –> BPH
- surrounds prostatic urethra (large central “U” or V shape)
- fibrous mucosa, submucosal glands
glands are histologically similar throughout but vary in density
features of dysplastic cervical cells on PAP
larger, hyper chromatic (purple to brown), darker, irregular shape
