Editing Infertility: Diagnosis and Evaluation (section)

=== Physical exam ===
* '''<span style="color:#ff0000">General (3)'''
*#'''<span style="color:#ff0000">Body habitus'''
*#* '''Obese men have'''
*#** '''Elevated estradiol'''
*#*** Mechanism: adipose cells have aromatase which metabolizes testosterone to estradiol
*#** '''Reduced serum testosterone and reduced SHBG''' (therefore, more bioavailable testosterone component of total testosterone)
*# '''<span style="color:#ff0000">State of virilization'''
*#'''<span style="color:#ff0000">Gynecomastia,''' may be a marker for endocrine disorders
* '''<span style="color:#ff0000">Abdomen'''
** '''Scars''' suggest previous procedures that may have involved the pelvis or impacted the urogenital system (inguinal surgery or treatment of undescended testis)
* '''<span style="color:#ff0000">Genitals'''
**'''<span style="color:#ff0000">Phallus''' 
***'''Meatal displacement''' may make it difficult for semen deposition in the vagina
*** '''Penile plaque''' as in Peyronie’s disease may make it difficult for vaginal intercourse
*** '''Penile lesions/ulcers/discharge''' may be a sign of sexually transmitted infection
**'''<span style="color:#ff0000">Scrotum (5)'''
**# '''Scars''' suggest previous scrotal surgery/trauma
**#'''<span style="color:#ff0000">Testis'''
**#*'''<span style="color:#ff0000">Size and consistency of the testis; size correlates well with sperm production'''
**#** '''<span style="color:#ff0000">Long axis length <4.6cm associated with impaired spermatogenesis</span>'''
**#** '''<span style="color:#ff0000">Volume <20mL considered low</span>'''
**#**Obstructive azoospermia is suspected if the physical examination reveals testes of normal size, fully descended into the scrotum and bilaterally indurated epididymides with or without absence of the vas deferens
**#**'''When the testes are atrophied and soft, especially in the presence of FSH greater than 7.6 IU/L, the results are suggestive of spermatogenic failure rather than obstructive azoospermia.'''
**#* Location as scrotal position of the testes is important for normal function
**#* Exam may also reveal masses consistent with a testicular cancer
**# '''<span style="color:#ff0000">Vas deferens'''
**#* Shape/consistency as normal development and contour should be confirmed to rule out agenesis as may be seen in the presence of a ''CFTR'' mutation or aberrant Wolffian duct embryogenesis
**#**'''<span style="color:#ff0000">Unilateral absence</span>'''
**#*** '''<span style="color:#ff0000">Suggests complete lack of Wolffian duct development on that side, including renal agenesis</span>'''
**#**** '''The absent vas should raise a red flag for possible ipsilateral renal agenesis because the ureteral bud and vas are both derived from the wolffian duct'''
**#**** '''Recall, male structures derived from Wolffian ducts:'''
**#****# '''Body and tail of epididymis (note efferent ductules and head of epididymis from mesonephric tubules)'''
**#****# '''Vas deferens'''
**#****# '''Seminal vesicles'''
**#****#* Distally, the wolffian ducts join the urogenital sinus by about 30 days gestation, where they develop into the seminal vesicles
**#****# '''Ejaculatory duct'''
**#****# '''Appendix epididymis'''
**#**** '''Male structures derived from Müllerian duct (2):'''
**#****#'''Appendix testis'''
**#****#'''Prostatic utricle'''
**#**** '''Male structures derived from urogenital sinus:'''
**#****# '''Prostate'''
**#****# '''Bulbourethral glands'''
**#** '''<span style="color:#ff0000">Bilateral absence</span>'''
**#*** '''<span style="color:#ff0000">Consider investigation for CF gene mutation</span>'''
**#**** '''Mutations in the ''CFTR'' gene are present in up to 80% of men with congenital bilateral absence of the vas deferens (CBAVD), 20% of men with''' '''congenital''' '''unilateral absence of the vas deferens''' and 21% of men with idiopathic epididymal obstruction[https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]
**#***** Most common CFTR mutation is ΔF508, which is severe
**#***** ≈7% of brothers of patients with CBAVD will have also vasal agenesis
**#***** No association between CBAVD and Y microdeletions.
**#**** '''If the male partner is being tested for CFTR, such is in CBAVD, both patient and female partner should be tested for CFTR to determine risk of cystic fibrosis in offspring (CUA Azoospermia Guidelines).'''
**#***** '''Only a portion of CFTR mutations are detected by routine testing.'''
**#****** '''A male with CBAVD should be assumed to be a CFTR carrier despite a negative CFTR gene test and the female partner still needs to be tested prior to any assisted reproductive techniques.'''
**#*** '''Semen is almost always of low volume and acidic in patients with CBAVD due to hypoplasia or absence of the seminal vesicles, which provide alkalinity'''
**#** '''In men with congenital bilateral or unilateral absence of the vas deferens who are not carriers of cystic fibrosis mutations, abdominal US to assess for renal agenesis is indicated since these men have a higher chance of having absence of one of their kidneys'''
**#*** '''26% of males with unilateral congenital absence of the vas deferens and 11% of males with CBAVD had an absent ipsilateral kidney''';
**#**** Most of the bilateral CAVD patients with an absent ipsilateral kidney are in patients with no identifiable CF gene mutation.
**#* Presence/location of any vasectomy defect or granuloma should also be assessed
**#'''<span style="color:#ff0000">Epididymides'''
**#* Shape/consistency as normal development should be identified to determine atresia that could be identified by the presence of a ''CFTR'' mutation.
**#* Induration/dilation could suggest obstruction.
**#* Epididymal cysts or spermatoceles may also lead to obstruction.
**#'''<span style="color:#ff0000">Varicoceles'''
**#* Potential mechanisms of varicocele contributing to infertility
**#**Hyperthermia
**#**Testicular hormonal imbalance
**#**Increased reactive oxygen species
**#**Hypoperfusion leading to hypoxia
**#*
**#*Large varicoceles are associated with greater preoperative impairment in semen quality than small varicoceles
**#* Varicocele treatment may be more cost effective than assisted-reproductive therapy or can lower the intensity of treatment'''§'''
**#* '''See [[Varicocele]] Chapter Notes'''
** '''<span style="color:#ff0000">Digital rectal exam'''
*** '''Midline prostatic cysts or dilated seminal vesicles''' may assist in the diagnosis of ejaculatory duct obstruction