Editing Infertility: Diagnosis and Evaluation (section)

== Genetic Testing ==

=== Options ===

# '''<span style="color:#ff0000">Karyotype</span>'''
# '''<span style="color:#ff0000">Y Chromosome Microdeletion</span>'''
#'''<span style="color:#ff0000">Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutation carrier testing</span>'''

=== Indications ===

* '''<span style="color:#ff0000">Karyotype and Y chromosome microdeletion</span>'''
**'''<span style="color:#ff0000">Primary infertility and (3):</span>'''
**#'''<span style="color:#ff0000">Azoospermia or severe oligozoospermia (<5 million sperm/mL) with elevated FSH OR</span>'''
**#'''<span style="color:#ff0000">Testicular atrophy OR</span>'''
**#'''<span style="color:#ff0000">Presumed diagnosis of impaired sperm production as the cause of azoospermia</span>'''
*'''<span style="color:#ff0000">Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutation carrier testing (3):</span>'''
*#'''<span style="color:#ff0000">Vasal agenesis/abnormalities OR</span>'''
*#'''<span style="color:#ff0000">Idiopathic obstructive azoospermia OR</span>'''
*#'''<span style="color:#ff0000">If the female partner is a carrier (to consider for preimplantation diagnosis)</span>'''

=== Karyotype ===
* Evaluates the number and structure of chromosomes in order to detect abnormalities
*'''<span style="color:#ff0000">Karyotype abnormalities (e.g. Klinefelter syndrome) are the most common known genetic abnormalities that cause male infertility.</span>'''
**An abnormal karyotype is present in about 6% of all infertile men[https://pubmed.ncbi.nlm.nih.gov/33295257/]

=== Y Chromosome Microdeletion Analysis ===
* '''<span style="color:#ff0000">Y chromosome microdeletions are the second most common known genetic cause of infertility in the male</span>'''
*'''<span style="color:#ff0000">Should be done in azoospermia before surgical sperm extraction to counsel likelihood of retrieval</span>'''
**'''<span style="color:#ff0000">Men with complete deletions of AZFa and/or AZFb should not undergo TESE for ART.</span> [https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]'''
**'''Men with deletions of AZFc and smaller partial deletions of AZFa and/or AZFb should be counseled that sperm may or may not be found with TESE.[https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]'''

=== Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutation carrier testing ===

* '''Including assessment of the 5T allele'''
** In addition to classic mutations, the 5-thymidine (5T) variant of the polythymidine tract in the splice site of intron 8 (which regulates exon 9 splicing efficiency) is also commonly found in men with obstructive azoospermia due to ''CFTR'' abnormalities. 
*'''For men who harbor a ''CFTR'' mutation, genetic evaluation of the female partner should be recommended.'''
** In cases where the male patient has a mutation in the ''CFTR'' gene and the partner is also a carrier, then there is a risk of an affected offspring (25% if both partners are carriers, and up to 50% if the male has mutations in both alleles with a female partner who is a carrier)

*