Editing Infertility: Epidemiology and Etiology (section)

==== <span style="color:#ff0000">Congenital</span> ====
*<span style="color:#ff0000">'''Causes of primary hypogonadism'''</span>
**'''<span style="color:#0000ff">DUNKY XX</span><span style="color:#ff0000">:</span>'''
**#'''<span style="color:#0000ff">D</span><span style="color:#ff0000">own syndrone</span>'''
**#'''<span style="color:#0000ff">U</span><span style="color:#ff0000">ndescended testis/cryptorchidism</span>'''
**#'''<span style="color:#0000ff">N</span><span style="color:#ff0000">oonan’s Syndrome</span>'''
**#'''<span style="color:#0000ff">K</span><span style="color:#ff0000">linefelter Syndrome</span>'''
**#'''<span style="color:#0000ff">Y</span> <span style="color:#ff0000">chromosome micro deletions</span>'''
**#'''<span style="color:#0000ff">XX<span style="color:#ff0000">-male</span>'''

* '''<span style="color:#ff0000">Klinefelter Syndrome</span>'''
** '''<span style="color:#ff0000">Most common known genetic cause of male infertility</span>'''
**'''Most common major abnormality of sexual differentiation'''
** '''See [https://test.urologyschool.com/index.php/Disorders_of_Sexual_Differentiation#Klinefelter_syndrome Klinefelter Syndrome Section] in [[Disorders of Sexual Differentiation]] Chapter Notes'''
** Males with Klinefelter syndrome should be counseled that few non-mosaic XXY men will have sperm in the ejaculate and medically-unassisted paternity is rare.[https://pubmed.ncbi.nlm.nih.gov/33295257/ §]
* '''<span style="color:#ff0000">Y chromosome microdeletion</span>'''
** '''<span style="color:#ff0000">Second most common known genetic cause of infertility in the male</span>'''
**Can result from errors that occur during homologous recombination during meiosis due to the palindromic structure of the chromosome
**Majority of (but not all) genes on the Y chromosome encode proteins involved in testis determination or spermatogenesis
**'''<span style="color:#ff0000">Azoospermia Factor (AZF) region[https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]'''
***'''In the long arm of the Y chromosome''' 
***'''Critical to formation of sperm'''
***'''<span style="color:#ff0000">Consists of three areas encoding genes involved in spermatogenesis (AZFa, AZFb, AZFc)</span>'''
****'''<span style="color:#ff0000">AZFa (also known as AZF1) or AZFb complete microdeletion: generally result in absence of spermatogenesis.</span>'''
*****Common phenotypic manifestations of deletions in AZFa region are azoospermia and Sertoli cell-only syndrome
*****Genes in the AZFb region have been found to support the growth and maturity of sperm and are critical for efficient progression of spermatogenesis. Common phenotypic manifestations of deletions in this region are spermatogenic arrest and azoospermia
****'''<span style="color:#ff0000">AZFc microdeletion: may result in spermatogenic impairment but not necessarily absence of spermatogenesis</span>'''
*****Genes in the AZFc region have a diverse role, but overall, they are essential to complete spermatogenesis. AZFc deletions have been associated with drastic reduction in sperm count, and there are subsets of men with AZFc microdeletions that experience progressive declines in their sperm count.
****'''Originally, the AZFb and AZFc genes were identified and thought to be separate regions. They were later found to be overlapping and are now referred to as AZF2.'''
*'''<span style="color:#ff0000">Cryptorchidism</span>'''
** If underwent orchidopexy and had unilateral cryptorchidism, 96% paternity rate; 70% if bilateral.
** The sooner orchidopexy the better, but age unknown. Better if done prior to age 10.

* '''<span style="color:#ff0000">Sertoli Cell Only syndrome</span>'''
** '''Patients present with normal levels of LH and testosterone. The low level of inhibin-B leads to elevated levels of follicle-stimulating hormone FSH.[https://www.ncbi.nlm.nih.gov/books/NBK534293/ §]'''
* '''<span style="color:#ff0000">Leydig cell insufficiency</span>'''
** '''Exogenous testosterone not indicated since insufficient testicular testosterone concentrations are achieved for spermatogenesis'''
** If azoospermia, low testosterone, and elevated LH, perform surgical sperm extraction
* '''<span style="color:#ff0000">Androgen-receptor (AR) resistance</span>'''
** '''See [[Disorders of Sexual Differentiation]] Chapter Notes'''
** Diagnosis and Evaluation: significantly elevated testosterone associated with impaired male fertility. LH is mildly elevated, FSH is normal