Kallman syndrome: generally, what is the condition?
what is the cause?
-congenital hypogonadotrophic hypogonadism
-GnRH precursor neurons do not migrate normally; cannot secrete GnRH from hypothalamus
-also: olfactory deficiency, "other midline defects"
-hormone levels: low FSH, low LH, low testosterone, failure to virilize at puberty.
Progression of cell types through process of spermatogenesis?(put these in order):
2. primary spermatocyte
3. secondary spermatocyte
4. spermatid (TID is in the MIDdle)
5. spermatozoan (Z is last)
what are a few causes of male infertility that are easily treated?
in what genetic conditions are the vas deferens completely absent?
-CBAVD (congenital bilateral absence of the vas deferens - partial mutation of the CF gene)
-absence of vas can be detected with careful palpation
what is a varicocele?
how does it impact fertility?
-an abnormal tortuosity and dilatation of the testicular veins within the spermatic cord. usually left-sided (drains into renal vein)
-most common cause of correctable male infertility.
-MoA unclear, but assoc'd with smaller testes, decr sperm motility and concentration
what is the most common hormonal finding in infertile men with low/absent sperm counts?
HIGH serum FSH
indicates significant problem with spermatogenesis
(normally, FSH secretion is regulated by inhibin, which is produced by Sertoli cells. Inadequate sertoli cell function fails to inhibit FSH --> elevated levels)
hormone lab findings in patients with hypothalamic or pituitary dysfunction?
low serum FSH, LH, testosterone
Men with azoospermia may have what genetic deletion in the Y chromosome?
what deletion allows some spermatogenesis?
Y chromo: some regions are dedicated to the spermatogenic process.
AZFa, AZFb, AZFc regions. Subject to deletion (de novo; not usually inherited for obvious reasons)
AZFc deletion (most freq) allows some spermatogenesis: the others do not
What is TESE? what should be checked before it is done?
TESE: testicular sperm extraction
should check for complete azoospermia before doing this.
(check karyotype, Y chromo microdeletion)
special issue to think about for a male about to undergo chemo or radiaton?
In postpubertal males about to undergo chemotherapy or radiotherapy, semen cryopreservation should be offered.
(Testis tissue can be harvested in those post-pubertal males not able to produce an ejaculate)
what is the ultimate goal of reproductive medicine?
birth of a healthy offspring
not just achievement of pregnancy
what does smoking do to male fertility?
-decr density, motility, quality of sperm
-decr fertilization ability
-delays natural conception
-increases risk of pediatric cancer in offspring if male is smoker at time of conception!!!
risks to male offspring if mom smokes during pregnancy?
effects in their sons:
-incr rate of testicular cancer
-sons' fertility potential is decreased
alcohol, caffeine, bicycling, running....
boxers v briefs, hot tub use, cell phone use....
-effect of these on male fertility?
alcohol, caffeine, bicycling, running -- all ok in moderation
boxers v briefs, hot tub use, cell phone use -- none matter at all
his view on supplements? multivitamins? other meds?
Does not recommend any supplements.
Doesn't recommend a multivit - just eat well.
get as healthy as possible, minimize other meds.
any foods/vitamins/additives that can boost sperm counts?
it's not like the body has all this extra sperm-producing capacity that it is underusing
how does anabolic steroid use lead to decr sperm production?
Exogenous testosterone shuts down the androgenic axis
--> Leydig cells don’t make testosterone.
Problem: Leydig cells are located where you need the testosterone to make sperm. Shuts down sperm production if no testosterone there.
You have a ton of testosterone in your body generally, but not where you need it for sperm prod'n
If a patient takes exogenous steroids, what does their hormone panel look like?
Side effects of testosterone supplementation?
CV effects, higher mortality overall (life expect for some is in the mid-50s), addiction problems
Treatment of anabolic-steroid induced azoospermia?
1. Stop all anabolics
2. Wait for pituitary to respond
-FSH and LH will increase as T decreases
-May take a few months
3. Wait for spermatogenesis to return
-May take 6-9 months if has been completely suppressed
-If longstanding use, can permanently decr the fxn of the axis
relationship between obesity and sperm density?
whatever NMS is (graph), it means sperm density
with incr obesity, sperm density goes down.
MoA: fat cells contain aromatase, converts testosterone to estrogen
how do we diagnose varicocele?
Diagnosis made by physical examination
“bag of worms”
Teenager usually has discomfort, dragging sensation
(Not dx'd by semen analysis, not by hormonal studies, not by ultrasound: this is a critical point)
can we correct varicocele? what is the result?
can correct surgically
70% improvement in semen parameters
60% -> natural preg in first year
Two types of non-obstructive azoospermia?
-Y chromosomal microdeletion (missing piece of Y-chromo)
-karyotype - Klinefelter sx
(test for these before trying to extract sperm via TESE)
AZFa, AZFb, AZFb/c, AZFc microdeletions: which of these situations can you do TESE on?
AZFc microdeletion only
if you do TESE on AZFa, AZFb, AZFb/c patients, it will not work because they are completly azoospermatogenic.
AZFc patients have spermatogenic potential
Realize that their male offspring will have this issue. (do they want to select for girl embryos? make them aware so they can decide)
Klinefelter sx: genotype?
relevance to this lecture?
Klinefelter's -> 5-10% of azoospermic men
why does Klinefelter's -> azoospermic men?
Spermatogenic axis failure:
-severe or total azoospermia
Androgenic axis failure:
-fail to virilize at puberty
-decr testosterone in adults
Klinefelter: common wrong assumptions -- and the reality...
-"Testosterone is too high to be a Klinefelter" -> in reality, T levels vary widely with this karyotype
-"too well virilized to be a Klinefelter" -> wide spectrum of pubertal development depending on Leydig cell function
-"your body doesn't look like a Klinefelter" -> not always Eunichoid habitus
-"you have a BA, you cannot be a Klinefelter" -> intellectual potential quite variable
what can be done to help Klinefelter men w fertility?
TESE can be successful
Live births have resulted with all babies of normal karyotype