https://embryology.med.unsw.edu.au/embryology/api.php?action=feedcontributions&feedformat=atom&user=Z3462833Embryology - User contributions [en-gb]2026-08-13T21:56:06ZUser contributionsMediaWiki 1.39.10https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=209845User:Z34628332015-10-30T01:08:27Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
[[Image:Proteomics Technologies PMID- 26471863.jpeg]]<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:46, 23 October 2015 (AEDT)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 30 October 2015 (AEDT)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=209843User:Z34628332015-10-30T01:07:51Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
[[Image:Proteomics Technologies PMID- 26471863.jpeg|thumb]]<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:46, 23 October 2015 (AEDT)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 30 October 2015 (AEDT)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=208311User:Z34628332015-10-23T06:32:12Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
[[Image:Proteomics Technologies PMID- 26471863.jpeg|thumb]]<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:46, 23 October 2015 (AEDT)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=208309User:Z34628332015-10-23T06:31:59Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
[[Image:Proteomics Technologies PMID- 26471863.jpeg]]<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:46, 23 October 2015 (AEDT)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=208307User:Z34628332015-10-23T06:31:41Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
[[Image:Proteomics Technologies PMID- 26471863.jpeg|thumb|alignmentleft]]<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:46, 23 October 2015 (AEDT)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=208303User:Z34628332015-10-23T06:30:43Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
[[Image:Proteomics Technologies PMID- 26471863.jpeg|thumb]]<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:46, 23 October 2015 (AEDT)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=208301User:Z34628332015-10-23T06:30:34Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:46, 23 October 2015 (AEDT)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=208299User:Z34628332015-10-23T06:30:22Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
[[Image:Proteomics Technologies PMID- 26471863.jpeg|thumb]]<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:46, 23 October 2015 (AEDT)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=208297User:Z34628332015-10-23T06:30:10Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
[[Image:Proteomics Technologies PMID- 26471863.jpeg|thumb]]<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:46, 23 October 2015 (AEDT)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=208295User:Z34628332015-10-23T06:29:52Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
[[Image:Proteomics Technologies PMID- 26471863.jpeg|thumb|alignment]]<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
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Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:46, 23 October 2015 (AEDT)<br />
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{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=208293User:Z34628332015-10-23T06:28:20Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
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<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
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==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
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[[Image:Proteomics Technologies PMID- 26471863.jpeg]]<br />
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==References==<br />
PMID 26244658<br />
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look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:46, 23 October 2015 (AEDT)<br />
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{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Proteomics_Technologies_PMID-_26471863.jpeg&diff=208099File:Proteomics Technologies PMID- 26471863.jpeg2015-10-23T02:34:04Z<p>Z3462833: </p>
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<div>PMID: 26471863<br />
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Application of state‐of‐the‐art proteomics technologies to clinical embryology, identifying and quantifying proteins secreted by the early human embryo in the hours before implantation.<br />
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<pubmed>26471863</pubmed><br />
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This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.<br />
<br />
{{Template:Student Image}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Proteomics_Technologies_PMID-_26471863.jpeg&diff=207991File:Proteomics Technologies PMID- 26471863.jpeg2015-10-23T02:07:12Z<p>Z3462833: PMID: 26471863</p>
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<div>PMID: 26471863</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=207959User:Z34628332015-10-23T01:46:36Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:46, 23 October 2015 (AEDT)<br />
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{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=2015_Group_Project_4&diff=2076412015 Group Project 42015-10-22T13:00:00Z<p>Z3462833: /* Intracytoplasmic Sperm Injection (ICSI) */</p>
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<div>{{ANAT2341Project2015header}}<br />
<br />
=Male Infertility=<br />
<br />
Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male. <br />
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Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails. <br />
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<br />
<br />
==Spermatogenesis and Fertility==<br />
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]<br />
===Structure of spermatozoa===<br />
The shape of spermatozoa are suitable for its transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion <ref><pubmed>14617369</pubmed></ref>. Spermatozoa also consist of a flagellum for progressive motility during its movement through the epididymal ducts and within the female reproductive organ. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref><br />
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<br />
[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]<br />
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===Spermatogenesis===<br />
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis: <br />
<br />
1. Spermatogoniogenesis <br />
<br />
2. Maturation of spermatocytes <br />
<br />
3. Spermiogenesis (which is the cytodifferentiation of spermatids)<br />
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<b>Spermatogoniogenesis</b> is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of <b>meiosis</b> is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During <b>spermiogenesis</b> three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref><br />
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<br />
===Physiology of fertility in Males===<br />
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref><br />
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==Male infertility disorders==<br />
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Although infertility refers to the inability to conceive, there are numerous disorders that address particular reasons as to why this is the case. For males, the causes of infertility are endless and the most common factors have been discussed previously. Due to the range of aetiological factors, each one may effect a different aspect of the male's sperm including sperm count, morphology and motility rates. <br />
A fertile male is suggested have normospermia <ref><pubmed>PMC4156950</pubmed></ref> , in which the male's ejaculate contains normal sperm quality and quantity which are (based on the World Health Organisation (WHO)):<br />
*Ejaculate volume of approximately 1.5 to 5 mL <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Count of approximately 15 million to over 200 million spermatozoa per mL of ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Progressive motility of 32% or more spermatozoa <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Normal morphology present in 4% of the ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>, in which normal form refers to the spermatozoa containing the 3 fundamental parts; a head, midpiece and tail. <br />
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Based on WHO's normal semen analysis, the specific types of male infertility disorders have been categorised accordingly. <br />
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<span style="font-size:100%">'''Types of Male Infertility'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Type'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count of less than 15 million sperm/mL of ejaculate <ref><pubmed>23757979</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''<br />
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen with a progressive motility of less than 20% <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| More than 95% of spermatozoa in the ejaculate has abnormal morphology <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''<br />
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia) (referring to the statistics mentioned for each condition)<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa, despite normal spermatogenesis within the semen due to a blockage in the genital tract, obstructing the pathway for sperm to enter the penis from the testes <ref><pubmed>PMC3583161</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''<br />
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to the abnormal process or failure of spermatogenesis occurring, whereby sperm producing cells being damaged or destroyed <ref><pubmed>PMC3583162</pubmed></ref><br />
|}<br />
<br />
==Causes of Infertility== <br />
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.<br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media><br />
<br />
Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref><br />
<br />
===Major Causes of Male Infertility===<br />
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]<br />
<br />
====Varicocele====<br />
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).<br />
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<br />
<br />
====Male Reproductive Cancers====<br />
<br />
Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref><br />
<br />
====Chromosomal Abnormalities====<br />
<br />
Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref><br />
<br />
====Damage to DNA====<br />
<br />
[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]<br />
<br />
DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref><br />
<br />
====Lifestyle Factors====<br />
<br />
[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]<br />
<br />
There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref><br />
<br />
====Immunological Infertility====<br />
<br />
Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref><br />
<br />
==Diagnosis== <br />
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.<br />
<br />
[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]<br />
<br />
===Physical examination===<br />
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref><br />
<br />
Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
<br />
<span style="font-size:100%">'''Classifications of Valsalva manoeuvre'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Grade'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Grade 1''' <br />
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam<br />
* No dilationed instrascrotal veins<br />
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre<br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''<br />
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre<br />
* No major dilation in supine position <br />
* Dilated veins up to lower pole of testis seen only in standing position <br />
* Reflux at lower pole veins during Valsalva manoeuvre<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Grade 3''' <br />
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre<br />
* Dilated veins<br />
* Reflex without Valsalva manoeuvre<br />
|}<br />
<br />
===Semen Analysis===<br />
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.<br />
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]<br />
<br />
===Testicular Colour Doppler Ultrasound===<br />
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref><br />
<br />
<br />
<br />
==Risk Factors and Prevention==<br />
<br />
<span style="font-size:100%">'''Risk Factors of Male Infertility'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Risk Factors'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Smoking''' <br />
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''<br />
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity''' <br />
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''<br />
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma''' <br />
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref><br />
|}<br />
<br />
If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse. <br />
<br />
==Treatments==<br />
<br />
Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.<br />
<br />
===Non-surgical Treatments===<br />
<br />
In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available. <br />
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]<br />
<br />
====Injectable Hormones & Fertility Drugs====<br />
<br />
Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. The associated image demonstrates the development and availability of gonadotropins for commercial use. <br />
<br />
Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.<br />
<br />
====Antioxidants====<br />
<br />
There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. <br />
<br />
The following are a few antioxidants that have been proven to treat oxidative stress, and hence improves male fertility. <br />
<br />
=====1. Carotenoids===== <br />
*Naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. <br />
*Subtypes are divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref><br />
*Main source of carotenoids in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. <br />
*Have been suggested as daily supplements for the human body, and act as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. <br />
*Their antioxidant activity of is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.<br />
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]<br />
<br />
Two common carotenoids that have been strongly advised as treatments for male infertility include lycopenes and Astaxanthin, described below. <br />
<br />
======Lycopenes====== <br />
*Type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. <br />
*Possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. <br />
*Have a role in neutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. <br />
*Inhibit lipid peroxidation allowing for spermatozoal membranes to be retained and protected from further damage. <br />
*Suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents. <br />
<br />
======Astaxanthin======<br />
*Keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. it has been <br />
*Suggested as an effective treatment and supplement for male factor infertility due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine. <br />
*An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for increased motility concentration, improved sperm morphology and motility, and a decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels. <br />
<br />
<br />
<br />
[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]] <br />
=====2. Cerium dioxide nanoparticles (CNPs)=====<br />
*Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility.<br />
*They are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. <br />
*CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. <br />
*A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress. <br />
<br />
=====3. Vitamin E=====<br />
*A fat – soluble antioxidant that exists in 8 chemical forms of different biological activity.<br />
*The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>, found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. <br />
*The recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. <br />
*Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. <br />
*From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility . <br />
<br />
=====4. Vitamin C=====<br />
*A water-soluble antioxidant that neutralizes free radicals and also prevents ROS synthesis<ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. <br />
*The human body does not produce or store vitamin C, so daily intakes of vitamin C – containing foods are required to maintain its levels internally.The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.<br />
*Foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. <br />
*A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.<br />
<br />
====Traditional Chinese Medicine====<br />
<br />
More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. <br />
<br />
Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.<br />
<br />
<span style="font-size:100%">'''Examples of Chinese Herbal Therapies'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Herb'''<br />
! scope="col" width="500px"| '''Evidence'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction''' <br />
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''<br />
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang''' <br />
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref><br />
|}<br />
<br />
===Surgical Treatments===<br />
<br />
====Varicocelectomy====<br />
<br />
Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur. <br />
<br />
Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. <br />
<br />
As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus. <br />
<br />
<span style="font-size:100%">'''Surgical Approach to Varicocele Repair'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery ''' <br />
|style="height: 50px; background: #CCEEEE;"| <br />
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
*Allows preservation of lymphatic vessels<br />
*Takes longer to heal <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''<br />
|style="height: 50px; background: #EEEEEE;"| <br />
*Incision below external inguinal ring<br />
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery''' <br />
|style="height: 50px; background: #CCEEEE;"| <br />
*Ligation of the internal spermatic vein <br />
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''<br />
|style="height: 50px; background: #EEEEEE;"| <br />
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref><br />
*Allows for a more accurate identification of vessels within the area <br />
|}<br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media><br />
<br />
Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref><br />
<br />
====Ejaculatory Duct Resection====<br />
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]<br />
<br />
Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.<br />
<br />
===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===<br />
<br />
It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm. <br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media><br />
<br />
Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref><br />
<br />
<br />
====Intrauterine Insemination (IUI)====<br />
<br />
Intrauterine insemination (IUI) is a simple procedure performed by a medical practitioner where washed sperm is injected directly into the uterus with a catheter. This allows the sperm to get as close to the egg as possible, increasing the chances of reaching it. This method is known as in vivo fertilisation as it is performed within the body of the female. <br />
It has been shown that if the woman rests for up to 15 minutes after insemination the chance of pregnancy is greater than if they are mobilised immediately after the procedure.<ref><pubmed>19875843</pubmed></ref><br />
The optimal conditions for an IUI include; the female being less than age 30, the male having a total motile sperm count of more than 5 million per mL. A likely pregnancy will result from a cycle that produces two eggs of 16 mm or more and an oestrogen concentration of 500 pg/mL at the time of the procedure.<ref><pubmed>18996517</pubmed></ref><br />
<br />
====In Vitro Fertilisation (IVF)====<br />
<br />
Theoretically, all that is required for in vitro fertilisation is to combine the contents of a woman’s fallopian tubes and sperm, followed by re-inserting this mixture into the uterus. In practice, however, this process would be an oversimplification and not particularly successful. There are several major steps in the procedure that are necessary for pregnancy. <br />
The first step is hyperstimulation of the ovaries. The purpose of this step is to produce several oocytes to make sure there are enough suitable candidates for the procedure. This is achieved by injecting a GnRH antagonist and gonadotropins into the female. Careful monitoring of the concentrations of these hormones is essential for the safety and well-being of the patient and for the successful removal of adequate follicles. <br />
Next, after the follicles have reached an appropriate level of development, final maturation induction is performed, typically by injection of hCG and GnRH agonist. This step is to replace the natural surge of LH that would normally mature the ovarian follicles.<br />
Once the follicles have matured, they are retrieved from the ovaries by a process known as transvaginal oocyte retrieval. This involves a needle guided by ultra-sound to pierce the vaginal walls, reaching the ovaries and finally aspiration of the mature oocytes and follicular fluid. Typically, 10-30 oocytes are removed under general anaesthesia. <br />
The oocytes are then inspected and only those with the highest chance of successful pregnancy are chosen and the surrounding layer of cells is removed from the eggs. Semen is washed simultaneously by removing any seminal fluid and other proteins. <br />
The next step is for the oocytes and semen to undergo co-incubation. The sperm cells and oocytes are incubated in culture media at a ratio of 75 000:1. It is at this point that another ART may be used (ICSI) if the sperm count or motility is not optimal. Once fertilisation takes place, the egg is placed in special growth medium and left for approximately 2 days until the cell mass is around 6-8 cells.<br />
Following this the best 2-3 embryos are selected based on a morphokinetic scoring system to increase the chances of a successful pregnancy. Characteristics tested include the if the growth of the cells is even, the number of cells and the level of fragmentation. <br />
The best embryos are transferred to the patient with a plastic catheter to the uterus. More than one may be transferred to increase the chances of a successful pregnancy in older women or women who have infertility issues. <br />
In order to ensure the embryo grows normally and implants properly, the patient is given adjunctive medication. This involves injection of specific concentrations of progesterone and GnRH agonists which is performed to support the corpus luteum.<br />
<br />
====Intracytoplasmic Sperm Injection (ICSI)====<br />
<br />
ICSI is typically performed during the co-incubation stage of IVF to make sure an oocyte is properly fertilised if the sperm is immobile. <br />
The process involves several devices under a microscope, namely; micromanipulator, microinjectors and micropipettes), and is fully outlined below:<br />
<br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=h7uucZ7xpYs</html5media><br />
<br />
ICSI Procedure <ref>Mothercare Hosp. (2014, July 7) 3D Animation of how ICSI works. Retrieved from https://www.youtube.com/watch?v=h7uucZ7xpYs</ref><br />
<br />
<br />
Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.<br />
<br />
==Glossary==<br />
<br />
ARTs - Assisted Reproductive Technologies<br />
<br />
Aetiological factors - causative agents <br />
<br />
Aneuploidy - the presence of an abnormal number of chromosomes in a cell<br />
<br />
Cadmium - a soft, insoluble transition metal that is a byproduct of zinc production <br />
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Clomiphene citrate - a non-steroidal medication that induces infertility by increasing the release of GnRH, LH and FSH required for spermatogenesis<br />
<br />
CNPs - Cerium dioxide nanoparticles<br />
<br />
FSH - Follicle stimulating hormone<br />
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Gametogenesis - a biological process resulting in the formation of mature haploid male (spermatogenesis) and female (oogenesis) germ cells <br />
<br />
GnRH - Gonadotropin releasing hormone<br />
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hCG - Human chorionic gonadotropin<br />
<br />
hMG - Human menopausal gonadotropin<br />
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Hypogonadatropic hypogonadism - a condition characterised by a decrease in functional activity of the gonadH<br />
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ICSI - Intracytoplasmic Sperm Injection<br />
<br />
IUI - Intrauterine Insemination<br />
<br />
IVF - In Vitro Fertilisation<br />
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Kiss1 - KiSS-1 Metastasis-Suppressor; a gene that codes for Kisspeptin, a G protein coupled receptor associated with hypogonadotropic hypogonadism <br />
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Klinefelter syndrome - genetic disorder whereby a male has an extra X chromosome <br />
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LH - Luteinizing hormone<br />
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Lipid peroxidation - the oxidation of lipids causing its degradation, usually caused by ROS <br />
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Progressive motility - the swimming of sperm from one place to another rather than in circles or twitching <br />
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Quenching - the deactivation of reactive oxygen forms <br />
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RDA - Recommended dietary allowance<br />
<br />
ROS - Reactive oxygen species<br />
<br />
Spermatogenesis - the production of development of new sperm <br />
<br />
Sperm-reactive antibodies (SpAb) - antibodies present on the membrane of spermatozoa that result in adverse affects to reproduction and often infertility. <ref><pubmed>8194608</pubmed></ref><br />
<br />
TCM - Traditional Chinese medicine<br />
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Testicular Dysgenesis Syndrome (TDS) - a syndrome resultant of the disruption of embryonal programming and gonadal development during fetal life that is related to poor semen quality and testicular cancer, <ref><pubmed>11331648 </pubmed></ref><br />
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TMS - Total Motile Sperm<br />
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TURED - Transurethral resection of ejaculatory ducts<br />
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Varicocele - Abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood<br />
<br />
==References==<br />
<br />
<references/><br />
<br />
==External Resources==</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2015_Group_Project_4&diff=207637Talk:2015 Group Project 42015-10-22T12:59:07Z<p>Z3462833: /* Discussion */</p>
<hr />
<div>{{ANAT2341Project2015discussionheader}}<br />
<br />
==Discussion==<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 23:59, 22 October 2015 (AEDT)<br />
Hey guys, <br />
Have added my final bits of info for the ARTS, just need to fill in the references tomorrow morning. <br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:20, 25 September 2015 (AEST) OK I discussed this with your group in last week's lab. you have not shown animal models, graphics, histology, media etc to really build your project page. The introduction does not give me a clear idea of the scope of the project. Not ready for peer review.<br />
<br />
<br />
Hey guys, I have just had a really quick look on PubMed and I found a good starting article. Its a review article (I'm pretty sure) so I'm not sure if we can use it, but it discusses some interesting genetic causes of male infertility and also references a lot of primary articles. <br />
<br />
PMID 26178295 <br />
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--[[User:Z3462124|Z3462124]] ([[User talk:Z3462124|talk]]) 13:38, 25 August 2015 (AEST)<br />
<br />
<br />
I can't seem to view anything but the first page of the article but the introduction gives a good idea on what male infertility is and how it arises. At the moment I have found 2 research articles that address factors that can increase male fertility. Although they do not address male infertility conditions specifically, in the discussion they imply that these methods can be applied to men who have them such as oligospermia and azoospermia. I feel as though we can use these articles when discussing alternative therapies for successful conception. Please have a read and share your opinions! <br />
<br />
PMID 22958644 - note that you can only view the condensed version of this article<br />
<br />
PMID 26097523 - you can view the whole article on biomed (subheadings in the discussion particularly addresses male infertility)<br />
<br />
--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 14:17, 25 August 2015 (AEST)<br />
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<br />
<br />
Hey guys, it was pretty hard finding research articles from Pubmed regarding the epidemiology of male infertility. For now, I have found an article about sperm extraction which I thought could be an alternative for treatments. However I can't view the full article without paying, but the abstract from Pubmed seems to sum it up.<br />
So, I came across a research article addressing the epidemiology and aetiology of male infertility, through Pubmed it doesn't have a direct link to the full PDF article however I linked it you guys on Facebook so have a read!<br />
<br />
PMID 22128297<br />
<br />
PMID 9663768<br />
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--[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 11:59, 26 August 2015 (AEST)<br />
<br />
<br />
Hello everyone! To get started, I just added a few headings on the page where you can add your research/review articles. Feel free to add more subheadings or change the wording of the titles - I'm sure we will need to as we research more. From looking at other groups' pages, I think it is also important we add a bit of 'Background Information" regarding the process of spermatogenesis and how any abnormalities can cause infertility so we can all look for articles as we go. Remember we are targeting this towards students like us, so a bit of key background info is essential. <br />
<br />
--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 00:06, 27 August 2015 (AEST)<br />
<br />
<br />
I just posted the articles that I found on male infertility. It was kind of hard to find ones because I stuck to studies in humans- but i found some good ones that were studies on rats (not sure if we can use them) and also some good secondary or review articles that we could use as background information maybe? So I'll just post the PMID's here..<br />
* PMID 26303086<br />
* PMID 23725463 <br />
* PMID 25160621<br />
* PMID 25142466<br />
--[[User:Z3462124|Z3462124]] ([[User talk:Z3462124|talk]]) 09:59, 27 August 2015 (AEST)<br />
<br />
<br />
Not sure if we are review articles are any good, but I thought that it's also important to talk about "detecting abnormalities". I came across this review article which talks about the "male genital tract - colour dopple ultrasound" is a useful tool to detect impaired reproductive health.<br />
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PMID 25038770 <br />
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--[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 19:59, 27 August 2015 (AEST)<br />
<br />
<br />
Good thinking! If anyone comes across more articles regarding this, please post them up! I'll add a 'diagnosis' sub-heading to the page <br />
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--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 22:23, 27 August 2015 (AEST)<br />
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<br />
Hey guys, found a couple of articles describing different methods of ARTs for male infertility:<br />
<br />
These 2 talk about Intrauterine Insemination (IUI)<br />
PMID 26294874<br />
PMID 26288981<br />
<br />
Also, another potential sub-heading to research might be the risks involved different ARTs<br />
E.g. the following article about the prevalence of birth defects after a number of different male-related ARTs<br />
PMID 26265143<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 23:38, 27 August 2015 (AEST)<br />
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<br />
That sounds good. I think mentioning risks are important to show what is successful and what isnt. Feel free to add it under the "ART" heading (as a sub-heading)<br />
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--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 23:06, 31 August 2015 (AEST)<br />
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<br />
Hey I found this article that discusses some ARTs for infertile men. Its not a bad read and has info on two different methods, Intracytoplasmic morphologically selected sperm injection (IMSI) and conventional intracytoplasmic sperm injection (cICSI). You can read the full text on biomod <br />
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PMID 26307050<br />
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--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 17:27, 1 September 2015 (AEST)<br />
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<br />
LOOK! <br />
This is a really good review article that talks about causes, diagnosis AND treatments. I recommend everyone to read it! <br />
<br />
PMID 21243017 <br />
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--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 11:09, 2 September 2015 (AEST)<br />
<br />
==Peer Assessment==<br />
<br />
===1===<br />
<br />
To start, I think some of your subheadings are a bit unnecessary, for example, you could get away without having the subheading “background information” and just having the sub-subheadings as subheadings below your intro. Whilst some subheadings are good as it helps break down the info in the table of contents, it makes the actual page difficult to read and follow. <br />
<br />
Great use of images on the page. There are many, without it cluttering the page and they are simple and relevant. However, the pictures you have used under “background information” appear to be a bit lifeless and complex. Perhaps using more simplified images with some colours would help liven up the section as well as allow people who use this page, with less scientific knowledge than you, to understand what they are seeing. They are important images as they set the basis for the rest of the page. It would also be good to see a hand-drawn image on the page. <br />
<br />
Your use of tables is also great, it really helps to break down the information. I would suggest however, you include a little more information and references under the section “male infertility disorders”. It is a big vague and there are no citations. Your list of references is incredible and you should be commended on that. It shows a great deal of research has gone into this page. Your citations appear to be correctly done throughout the page. Your “Causes of fertility” section is done really well and is very thorough. The video accompanying it is good to as it is easy to understand and explanatory. Your “risk factors and prevention” heading could use more work. I would suggest actually splitting them up into two separate headings and really delving more into prevention and how to handle infertility. <br />
<br />
Your “treatment” section is really well done and thorough. I would suggest however, to make it easier to read, that you simplify some of your paragraphs into bullet points. A glossary section may also be useful for people reading this page with a lesser degree of embryology knowledge than you or I. I will say, this page has covered its chosen topic well and has attacked it from an embryologically focused angle. Lastly I would suggest including a section on animal models and the literature for the more advanced student.<br />
<br />
----<br />
Very impressive work so far guys! Your page covers a comprehensive topic very well, without focussing too much on certain subheadings at the expense of others. Your use of both tables and images is excellent so far. All necessary copyright information seems to be present for the images that you have uploaded. It's good to see that you have also included a video to give some variety to the media on your page. The 'background information' gives context to the issues which you discuss and though it might not be of great use for someone familiar with embryology, it would be a great help to those with no experience in this field and is therefore useful in establishing the topic of male infertility.<br />
<br />
The only things that could be changed to improve your wiki page is perhaps altering the location of tables and pictures on your page. For example all pictures are located on the right side of the page, although not a significant issue, becomes slightly monotonous as one progresses through the page. It may be worth alternating pictures between left and right to mix things up a little bit and improve the overall flow of the page. <br />
It might also be worth including a short video underneath the 'surgical treatments' subheading to give a visual example of some of the techniques discussed.<br />
<br />
Furthermore a subheading on future research could possibly be included under the 'treatments' subheading to give the reader information on techniques and therapies which may come to prominence in the near future.<br />
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Your wiki page thus far is very impressive! Excellent work so far.<br />
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<br />
===3===<br />
<br />
Probably the most enjoyable page to read, thus far.<br />
<br />
'''COMMENDATIONS'''<br />
<br />
• Great introduction; straight to the point and easy to understand. <br />
<br />
• Your information is organised under appropriate subheadings, making your page easy to read and follow. <br />
<br />
• Your “Types of Male Infertility” table is great! You have provided clear definitions of each condition and the use of colour makes the information stand out. <br />
<br />
• Appropriate referencing throughout.<br />
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• Great audio-visual sources, especially the video. <br />
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• Your page looks even better than a Wikipedia page! A lot of time and effort has gone into it.<br />
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<br />
'''RECOMMENDATIONS'''<br />
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• A glossary at the end of the page would be great, even though you have explained a lot of the concepts in your text. This way the reader does not have to skim through your page to find a term and they can go straight to the glossary.<br />
<br />
• Information under IVF and IUI is absent in “Male Infertility Treatments.” I am not sure if these were meant to be deleted or text will be added later.<br />
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It is evident that you have worked fantastically as a team and you have done a lot of research. Each topic is covered comprehensively and aided by a table, image or diagram, making the topic more appealing to the reader. Well done!<br />
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----<br />
<br />
===4===<br />
<br />
The wikipage is very well organised and the headings, subheadings and tables made everything easy to follow. I particularly liked the blue theme you kept with all the tables, it is very aesthetically pleasing. In terms of content the background information provided a clear overview of the subject especially the information about the physiology of fertility in males which laid down the foundation some basic knowledge surrounding male fertility under normal circumstances which I found useful in grasping other concepts throughout the page. The page is filled with an extensive amount of content and along with the long list of references I was given the impression of good understanding of the topic and commendable effort placed into the research.<br />
<br />
One thing I found that wasn’t quite compatible with your page was the inclusion of the video in the ‘Causes of infertility section’. Although I do agree that it is a very good video, it had little information surrounding male infertility and was more about infertility in general. Perhaps a video exclusively about male infertility would be more suitable for your page. <br />
<br />
As for some additional improvements, it would be beneficial to include a glossary to explain some difficult terms that would help the audience gain a better understanding of the content. Also, the addition of a hand-drawn image would also be nice. A suggestion would be to exchange your existing ‘components and structure of spermatozoa’ image with a more simplified and schematic diagram of the structure of sperm. <br />
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Overall, I enjoyed reading about male infertility and the page is coming together very nicely.<br />
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===5===<br />
<br />
The introduction is a really important part of the project so it’s important that you get that down. The introduction is well written but it is not done yet as it does not give me a clear idea of the scope of the project. You need to explain the topic in more depth to give readers overall understanding of the male infertility. Maybe think about adding an image to make it a bit more appealing.<br />
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Overall this is a well-produced project so far, very impressed. First thing noticeable on the page is the amount of information you have which is great. Only minor changes to polish up some sections are needed which I will explain as we go on. The project as a whole is not text heavy with some good images, tables, diagrams and a short video included which again are helpful in guiding the information. The table in “Diagnosis” section is great and really well done. One thing you could maybe do here is add a few diagrams or images related. I know you have added 2 images down below but I think it’s something that might make it even easier to follow. Try to add more related images to the content of the table. For the “Male infertility disorders”, I believe you can find more information and add to the table as this topic is a big vague and broad. Most of the sections have great amount of detail with a number of in text citations and this is great to see except for the table used in “Male infertility disorders”. Try to fix this up as citations should be carried through the entire page. Other than that, all the citations formatted correctly and it is good that all the references appear in one long list at the end of the page. Well done!<br />
<br />
Some sections like “Intrauterine Insemination (IUI)” or “IVF” seems to be untouched. I’m assuming you are still in the process of adding content. However, the “Treatments” section is extensive and well researched. Good job. <br />
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To sum up, in terms of improvement, my suggestions are: <br />
<br />
• There is no hand drawn image yet .You may only have 1-2 weeks to complete this project so don’t leave it until last minute.<br />
<br />
• Add more related videos to create the balance.<br />
<br />
• The project could benefit from having a ‘Glossary’ list so that viewers can understand some uncommon words.<br />
<br />
• You have not shown animal model so this can be a potential subheading as well as “future research” or “current research”. Just some tips, when researching on pubmed, there's an option to look at recent articles by customising dates to say 2012-onwards<br />
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• In text-citation <br />
<br />
• Simplify some of your paragraphs into bullet points. This can be done for “Causes of Infertility” or “Treatments”.<br />
<br />
• Finish those untouched topics<br />
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<br />
Overall, the project page is interesting, easy to comprehend and follow, however certain changes should be addressed and more information added.<br />
<br />
===6===<br />
<br />
I’ll begin by commending you on a well contructed wikipage with a great balance of texts and figures. You have used a great variety of supporting resources which complement your text well and aid in the teaching and the understanding of your key points which you have chosen well and mostly covered sufficiently. I particularly liked that you included a graph, (since you are the first project I see with one) and your widespread use of tables which breaks up the text whilst teaching your content well. Good job on being consistent in using the same colour and formatting in your tables. Your explanations are clear and extensive with the main points covered well. Your topic appears to be well research with a thorough list of references and your citations are correct. <br />
<br />
While you have included a great table on the types of infertility in males with a brief explanation of each, I feel like this should be elaborated on further. Also, your background information is well written however I feel it is too abrupt. You can include an introductory sentence or paragraph to your subheadings. While it is great that you included a video, I don’t feel like it is relevant to where you have placed it under the causes heading. Since it is more of an overview of infertility in general you can move it to the beginning of the page if you would like to keep it or choose a different video. <br />
<br />
While I did say your explanations in general are well written, some areas need more focus, such as your explanation of Varicocele, while you have said that varicocele leads to infertility and explained what is was, it wasn’t clear to me why it causes infertility. Also you should add more significant research beyond the teaching aspect by including some studies conducted and animal models. You can contribute further to the teaching and understanding of your topic by adding your own innovative, drawn diagrams to your great selection of files already added. Just a final formatting point, your images need a higher resolution, most of them are unclear and the words are not very readable. You can edit this by increasing the current 300px resolution to the appropriate pixels. <br />
<br />
Great progress overall, good luck with the rest!<br />
<br />
===7===<br />
The topic is well investigated in this project wiki. It is excellent that you also include some background information on the structure and development of spermatozoa, which would help readers without knowledge in this field.<br />
<br />
Images are properly cited and referenced. They make the page looked refreshing. Tables are used wisely to summarize information on ‘male infertility disorders’, but will need some more in-text referencing with the table contents.<br />
<br />
Paragraphs are written very well. There are great efforts in rewriting and summarizing. It will be better if the texts can be simplified by some diagrams or lists, which will be easier for readers to get through. Overall, this project wiki is an excellent work.<br />
<br />
===8===<br />
The website is very well organized and contains a lot of researched information and content. The introduction gives a short and precise definition of male infertility and let’s the reader know what to expect from the website. Overall the order of the headings and subheadings is very logical. To start off with explaining the healthy male physiology is a smart way to allow readers with less knowledge about the topic to understand the website. The blue theme of the tables is very coherent and the recurrent incorporation of the tables is alternative to plain text. The “treatment” heading has a lot of information ranging from traditional to Western medicine, which shows that the topic was very well researched. <br />
<br />
In addition, it is good to see that at the end of the treatment section (upon completion) the page will give a direct link to ART. The referencing of the website and the images is correct. Here and there are some paragraphs or tables that are not referenced yet (Classifications of Valsalva manoeuvre, Intro. of “Diagnosis”). The amount of references is extensive showing again that the topic has been researched quite well. The images are very useful, for understanding the content of the website. Particularly the diagrams explaining the Varicocele and the mechanisms of Lycopene Treatment clarify a lot. The timeline of the development of gonadotropin preparations is also a great way to incorporate bits of the history of your topic without spending too much text on it. <br />
<br />
It might be useful to add another heading about current research and a glossary to help readers to understand the website. It is really great that you added a video to your website, particularly in the beginning as it will introduce to topic to readers and ease them into the topic. However, it might be reasonable to look for a video that only focuses on male infertility. If that cannot be found it would not be too bad, as the video is still relevant to the topic overall. Moreover, try to add a self-drawn image, maybe in the treatments part for the surgical interventions?.<br />
<br />
===9===<br />
<br />
Firstly, you have done an exceptionel job in creating such a well organised page with the right amount of images and videos. It is also evident that a lot of effort was taken to make sure each section is covered comprehensively which is a mark of great teamwork. <br />
<br />
You have added images and videos at the right places to make it easier for us to absorb the information, however I could not find an original image. Perhaps you could use a flowchart from one of the existing images to make your own simplified version using Word. <br />
<br />
The sub-headings are very appropriate and ensure that there are no big blocks of text. My only suggestion would be to cut down on the background information regarding spermatozoa and spermatogenesis. While this is important in providing us with an insight into male reproduction, a paragraph at most would suffice. Under Male Infertility Treatments with ARTs, there are a few sub-sub headings that don't have any text underneath them. <br />
<br />
I really liked the use of a table under Risks and Prevention as it breaks the monotonous style of reading paragraphs of text. <br />
<br />
At the end of the page, it would be helpful to include a glossary as there are a few terms that are hard to understand. <br />
<br />
I really commend you on being able to produce such a well crafted page that the readers can enjoy going through. Great team work!<br />
<br />
===10===<br />
<br />
This page is really with high quality. The key points relating to the topic are clearly described. The page is organized very well which is neat and easy to read. The headings and subheadings are appropriate and easy to follow. The video is relative to the content and the images are well chosen. The choice of background color of the tables is pretty good which makes the page nice but still easy to read. The video is well referenced. Other references and citations are appropriate as well. I will make the following suggestions:<br />
<br />
1. A glossary at the end of page will help those without background knowledge understanding the topic easier.<br />
<br />
2. An animal model and the current research may be included in your page.<br />
<br />
3. A hand-drawn image can be added.<br />
<br />
Overall, this is a good teamwork and you have made a great page.<br />
<br />
===11===<br />
<br />
I would like to say great work of find substantial information and images to go along with your wikipage. From the table of contents there seems to be a lot of topics being addressed and with your use of subheadings, it makes navigating the page much easier. The short introduction described the basic meaning of male infertility well as well as the inclusion of some basic statistics is a nice bit of information however it would be nice to have some information regarding what your wikipage will be covering in general<br />
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The background information is very useless as it provides the reader with some basic knowledge of where the male reproductive system and its components come into play in regard to the topic of male infertility. The images used are all referenced appropriately and assists in understanding where each component is located and what they look like. The tabulated data of the different types of male infertility allows the readers to easily understand the different kinds and what their relative symptoms are easily. Good job on that! The use of video is nice to see, it has relevance to your topic.<br />
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Regarding information within the section ‘Major Causes of Infertility’, the information provided is awesome, however there just seems to be too much information crammed into small paragraphs which makes it quite draining to read. There are many terms which some readers may not know or understand, so I recommend using a glossary to help sort this problem out maybe simplify the information (if you can) or break up into more paragraphs to make it easier to read and digest. There are some sections which have no information, however I know that these will be filled by the submission date. The large amount of references is indicative of how much work went into the wikipage for your group! <br />
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Good work guys!!<br />
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===12===<br />
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This group project is so far the most detailed, it has the most information included. Many topics followed by sub topics followed by even more sub topics is a clear indication of the amount of research they have undergone. Multiple diagrams, YouTube videos, flowcharts, microscopic images, histological slides, ultrasonography, timelines and tables were very useful in supporting the information they have and helps give a clear understanding of male infertility. 68 references included a vast search for research they did which is a general indication of reliability so as the multiple citations used throughout the report.<br />
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Lack of a glossary doesn’t help the reader as this report is a general but very large topic, with all the information they have included, the readers are bound to come across a fair amount of words or phrases they will not understand. No symptoms are recorded down, and also in the risk factors and prevention section, only one table is included. Perhaps more information regarding the prevention is required.<br />
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Overall the project is done quite well, although if a reader was to judge on its clarity they may find it a bit hard as there is a lot of information which could do with a bit of clarity, possibly but separating, bullet points or tables. A glossary should definitely be added as it plays a very important role for the reader’s benefit.<br />
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===13===<br />
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This Group Project is impressively detailed and provides a comprehensive view of male infertility detailing the normal process as well as the various disorder types and causes. The wikipedia page flows logically, provides excellent summaries and may well be an excellent educational resource. The video chosen is fantastic and tables have been used well to present information quickly.<br />
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I find that the Introduction is clear and concise. However, i feel it may be improved further by an introductory visual. Other than that, the page has many relevant diagrams and images. In terms of the 'development of gonadotropin preparations', it does seem a little out of place as it isn't particularly referred to in the text. I understand timelines add a richness to the text and can give perspective, but i feel that it may be of more relevance if given regarding male infertility treatments as a whole, rather than gonadotropin preparations. Of course, you can always have both.<br />
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Other than that, I am quite impressed with this wikipedia page. It is referenced well and information is backed with reference to the findings of various studies. A final tip may be to add a simple glossary for ease of reference as opposed to having to scroll back up to the section (e.g. varicocele) to remind oneself of the meaning. However, it should be commended that jargon was defined well throughout the article.<br />
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===14===<br />
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Great work guys, a lot of information in there.<br />
Well referenced and easily readable. Nicely broken up with some informative images. Tables are great and make it easy to find information on a big page. And the first embedded video I’ve seen which is nice.<br />
Looks like it all the information is there already just a couple of heading to finish off so well done.<br />
Stylistically the only things ill pick on are,<br />
The numbered list in treatments, doesn’t fit with the formatting of the rest of the page. Just turn them into subheading or tables like the others. <br />
Some of the tables are standalone ie. Male infertility disorder that should really have some intro text to them. Also make sure they have a description underneath each one describing what’s in table. And reference of where the information’s coming from.<br />
You could add a section on epidemiology/prevalence of types of infertility. But the intro could be enough if you flesh something out in there.<br />
Don’t forget to hyperlink some of the important words to the sites glossary and other pages so people can find extra reading or background. And I think you’ll have a really informative page. <br />
Fantastic work guys.<br />
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===15===<br />
*The structure of your page is extremely excellent! It flows very well, all headings and subheadings were chosen really well, the use of tables and diagrams are incredible!<br />
*The heading of “Background information” is VERY extensive, and also concise! The diagram placement is also excellent, and their use is also extremely excellent<br />
*The use of the video to explain the cause of infertility is absolutely amazing, it makes your page look good, keeps your explanation short, concise, and readable, and it also engages the audience<br />
*Each subheading under “Causes” is also very well outlined and explained, there is a lot of information there, and it is sure whatever information the reader may need would be found on your page as it has covered and explained a lot<br />
Overall, all I have for your group are good comments, as I couldn’t think of anything else that you will might need to add or change on it at all! Your information extends beyond what is expected, but also extensive, concise, and, most importantly, extremely readable and engaging! GOOD WORK!<br />
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===16===<br />
This topic clearly is extremely broad – and requires a whole lot of information to be covered. The students have done well in trying to reduce the denseness of the text as much as possible – however it is still quite hard to read the whole page at once and can get slightly tiresome. I think where possible you should just try and add a variety of media files, more videos and animations that will reduce the denseness of the whole page.<br />
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Most of the text used is relevant and necessary – so some time should be spent trying to cut down as much as possible, however it might be beneficial to adjust the position of the images within the text – just to seemingly break up the denseness of the text and the format of the page. <br />
The tables used in the page are relevant and informative – however there are quite a lot used.<br />
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A good page that tackles an extremely extensive amount of information needed to be covered. The page does well and there are just a few things that need fixing up to improve the page. The referencing throughout the page is well done and most of the images had correct copyright and referencing material.<br />
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===17===<br />
You guys did very well for such a large topic your content you effectively reported on a large scope of related topics, your report is very well structured, with the right amount of pictures and tapes used to break up the text. Extensive work was done and this is apparent in many of your sections especially in the background information section, perhaps more content could be added to the introduction and the sub heading of male infertility disorders with more research and possibly an image. <br />
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Overall the majority of your referencing is sound, with all images being correctly referenced. I would advise you to ensure that all your content especially the data and statistics in your content and tables are correctly referenced. Additionally, you may benefit from introducing some form of animal models perhaps in a new future research/ clinical trials section, or in the treatment section. <br />
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Whilst the use of the video is awesome, perhaps a different video should be selected, one that is more specific to your content and not infertility in general, as this the video is more about female infertility rather than males. The background information heading is great for establishing a common base knowledge for all of the site visitors - perhaps you could incorporate a link to Mark hills lectures on this topic or incorporate a video he used to teach the content in either the labs or the lecture. <br />
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Overall, your project is looking great you just need a few minor adjustments, and once you have finished adding the content I am confident that you will have a great project.</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=2015_Group_Project_4&diff=2076352015 Group Project 42015-10-22T12:58:03Z<p>Z3462833: /* Intracytoplasmic Sperm Injection (ICSI) */</p>
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<div>{{ANAT2341Project2015header}}<br />
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=Male Infertility=<br />
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Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male. <br />
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Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails. <br />
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==Spermatogenesis and Fertility==<br />
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]<br />
===Structure of spermatozoa===<br />
The shape of spermatozoa are suitable for its transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion <ref><pubmed>14617369</pubmed></ref>. Spermatozoa also consist of a flagellum for progressive motility during its movement through the epididymal ducts and within the female reproductive organ. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref><br />
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<br />
[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]<br />
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===Spermatogenesis===<br />
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis: <br />
<br />
1. Spermatogoniogenesis <br />
<br />
2. Maturation of spermatocytes <br />
<br />
3. Spermiogenesis (which is the cytodifferentiation of spermatids)<br />
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<b>Spermatogoniogenesis</b> is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of <b>meiosis</b> is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During <b>spermiogenesis</b> three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref><br />
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===Physiology of fertility in Males===<br />
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref><br />
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==Male infertility disorders==<br />
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Although infertility refers to the inability to conceive, there are numerous disorders that address particular reasons as to why this is the case. For males, the causes of infertility are endless and the most common factors have been discussed previously. Due to the range of aetiological factors, each one may effect a different aspect of the male's sperm including sperm count, morphology and motility rates. <br />
A fertile male is suggested have normospermia <ref><pubmed>PMC4156950</pubmed></ref> , in which the male's ejaculate contains normal sperm quality and quantity which are (based on the World Health Organisation (WHO)):<br />
*Ejaculate volume of approximately 1.5 to 5 mL <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Count of approximately 15 million to over 200 million spermatozoa per mL of ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Progressive motility of 32% or more spermatozoa <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Normal morphology present in 4% of the ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>, in which normal form refers to the spermatozoa containing the 3 fundamental parts; a head, midpiece and tail. <br />
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Based on WHO's normal semen analysis, the specific types of male infertility disorders have been categorised accordingly. <br />
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<span style="font-size:100%">'''Types of Male Infertility'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Type'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count of less than 15 million sperm/mL of ejaculate <ref><pubmed>23757979</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''<br />
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen with a progressive motility of less than 20% <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| More than 95% of spermatozoa in the ejaculate has abnormal morphology <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''<br />
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia) (referring to the statistics mentioned for each condition)<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa, despite normal spermatogenesis within the semen due to a blockage in the genital tract, obstructing the pathway for sperm to enter the penis from the testes <ref><pubmed>PMC3583161</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''<br />
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to the abnormal process or failure of spermatogenesis occurring, whereby sperm producing cells being damaged or destroyed <ref><pubmed>PMC3583162</pubmed></ref><br />
|}<br />
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==Causes of Infertility== <br />
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.<br />
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<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media><br />
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Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref><br />
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===Major Causes of Male Infertility===<br />
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]<br />
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====Varicocele====<br />
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).<br />
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====Male Reproductive Cancers====<br />
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Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref><br />
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====Chromosomal Abnormalities====<br />
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Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref><br />
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====Damage to DNA====<br />
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[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]<br />
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DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref><br />
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====Lifestyle Factors====<br />
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[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]<br />
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There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref><br />
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====Immunological Infertility====<br />
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Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref><br />
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==Diagnosis== <br />
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.<br />
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[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]<br />
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===Physical examination===<br />
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref><br />
<br />
Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
<br />
<span style="font-size:100%">'''Classifications of Valsalva manoeuvre'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Grade'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Grade 1''' <br />
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam<br />
* No dilationed instrascrotal veins<br />
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre<br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''<br />
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre<br />
* No major dilation in supine position <br />
* Dilated veins up to lower pole of testis seen only in standing position <br />
* Reflux at lower pole veins during Valsalva manoeuvre<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Grade 3''' <br />
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre<br />
* Dilated veins<br />
* Reflex without Valsalva manoeuvre<br />
|}<br />
<br />
===Semen Analysis===<br />
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.<br />
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]<br />
<br />
===Testicular Colour Doppler Ultrasound===<br />
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref><br />
<br />
<br />
<br />
==Risk Factors and Prevention==<br />
<br />
<span style="font-size:100%">'''Risk Factors of Male Infertility'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Risk Factors'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Smoking''' <br />
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''<br />
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity''' <br />
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''<br />
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma''' <br />
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref><br />
|}<br />
<br />
If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse. <br />
<br />
==Treatments==<br />
<br />
Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.<br />
<br />
===Non-surgical Treatments===<br />
<br />
In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available. <br />
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]<br />
<br />
====Injectable Hormones & Fertility Drugs====<br />
<br />
Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. The associated image demonstrates the development and availability of gonadotropins for commercial use. <br />
<br />
Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.<br />
<br />
====Antioxidants====<br />
<br />
There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. <br />
<br />
The following are a few antioxidants that have been proven to treat oxidative stress, and hence improves male fertility. <br />
<br />
=====1. Carotenoids===== <br />
*Naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. <br />
*Subtypes are divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref><br />
*Main source of carotenoids in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. <br />
*Have been suggested as daily supplements for the human body, and act as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. <br />
*Their antioxidant activity of is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.<br />
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]<br />
<br />
Two common carotenoids that have been strongly advised as treatments for male infertility include lycopenes and Astaxanthin, described below. <br />
<br />
======Lycopenes====== <br />
*Type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. <br />
*Possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. <br />
*Have a role in neutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. <br />
*Inhibit lipid peroxidation allowing for spermatozoal membranes to be retained and protected from further damage. <br />
*Suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents. <br />
<br />
======Astaxanthin======<br />
*Keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. it has been <br />
*Suggested as an effective treatment and supplement for male factor infertility due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine. <br />
*An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for increased motility concentration, improved sperm morphology and motility, and a decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels. <br />
<br />
<br />
<br />
[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]] <br />
=====2. Cerium dioxide nanoparticles (CNPs)=====<br />
*Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility.<br />
*They are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. <br />
*CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. <br />
*A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress. <br />
<br />
=====3. Vitamin E=====<br />
*A fat – soluble antioxidant that exists in 8 chemical forms of different biological activity.<br />
*The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>, found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. <br />
*The recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. <br />
*Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. <br />
*From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility . <br />
<br />
=====4. Vitamin C=====<br />
*A water-soluble antioxidant that neutralizes free radicals and also prevents ROS synthesis<ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. <br />
*The human body does not produce or store vitamin C, so daily intakes of vitamin C – containing foods are required to maintain its levels internally.The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.<br />
*Foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. <br />
*A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.<br />
<br />
====Traditional Chinese Medicine====<br />
<br />
More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. <br />
<br />
Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.<br />
<br />
<span style="font-size:100%">'''Examples of Chinese Herbal Therapies'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Herb'''<br />
! scope="col" width="500px"| '''Evidence'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction''' <br />
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''<br />
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang''' <br />
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref><br />
|}<br />
<br />
===Surgical Treatments===<br />
<br />
====Varicocelectomy====<br />
<br />
Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur. <br />
<br />
Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. <br />
<br />
As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus. <br />
<br />
<span style="font-size:100%">'''Surgical Approach to Varicocele Repair'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery ''' <br />
|style="height: 50px; background: #CCEEEE;"| <br />
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
*Allows preservation of lymphatic vessels<br />
*Takes longer to heal <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''<br />
|style="height: 50px; background: #EEEEEE;"| <br />
*Incision below external inguinal ring<br />
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery''' <br />
|style="height: 50px; background: #CCEEEE;"| <br />
*Ligation of the internal spermatic vein <br />
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''<br />
|style="height: 50px; background: #EEEEEE;"| <br />
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref><br />
*Allows for a more accurate identification of vessels within the area <br />
|}<br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media><br />
<br />
Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref><br />
<br />
====Ejaculatory Duct Resection====<br />
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]<br />
<br />
Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.<br />
<br />
===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===<br />
<br />
It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm. <br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media><br />
<br />
Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref><br />
<br />
<br />
====Intrauterine Insemination (IUI)====<br />
<br />
Intrauterine insemination (IUI) is a simple procedure performed by a medical practitioner where washed sperm is injected directly into the uterus with a catheter. This allows the sperm to get as close to the egg as possible, increasing the chances of reaching it. This method is known as in vivo fertilisation as it is performed within the body of the female. <br />
It has been shown that if the woman rests for up to 15 minutes after insemination the chance of pregnancy is greater than if they are mobilised immediately after the procedure.<ref><pubmed>19875843</pubmed></ref><br />
The optimal conditions for an IUI include; the female being less than age 30, the male having a total motile sperm count of more than 5 million per mL. A likely pregnancy will result from a cycle that produces two eggs of 16 mm or more and an oestrogen concentration of 500 pg/mL at the time of the procedure.<ref><pubmed>18996517</pubmed></ref><br />
<br />
====In Vitro Fertilisation (IVF)====<br />
<br />
Theoretically, all that is required for in vitro fertilisation is to combine the contents of a woman’s fallopian tubes and sperm, followed by re-inserting this mixture into the uterus. In practice, however, this process would be an oversimplification and not particularly successful. There are several major steps in the procedure that are necessary for pregnancy. <br />
The first step is hyperstimulation of the ovaries. The purpose of this step is to produce several oocytes to make sure there are enough suitable candidates for the procedure. This is achieved by injecting a GnRH antagonist and gonadotropins into the female. Careful monitoring of the concentrations of these hormones is essential for the safety and well-being of the patient and for the successful removal of adequate follicles. <br />
Next, after the follicles have reached an appropriate level of development, final maturation induction is performed, typically by injection of hCG and GnRH agonist. This step is to replace the natural surge of LH that would normally mature the ovarian follicles.<br />
Once the follicles have matured, they are retrieved from the ovaries by a process known as transvaginal oocyte retrieval. This involves a needle guided by ultra-sound to pierce the vaginal walls, reaching the ovaries and finally aspiration of the mature oocytes and follicular fluid. Typically, 10-30 oocytes are removed under general anaesthesia. <br />
The oocytes are then inspected and only those with the highest chance of successful pregnancy are chosen and the surrounding layer of cells is removed from the eggs. Semen is washed simultaneously by removing any seminal fluid and other proteins. <br />
The next step is for the oocytes and semen to undergo co-incubation. The sperm cells and oocytes are incubated in culture media at a ratio of 75 000:1. It is at this point that another ART may be used (ICSI) if the sperm count or motility is not optimal. Once fertilisation takes place, the egg is placed in special growth medium and left for approximately 2 days until the cell mass is around 6-8 cells.<br />
Following this the best 2-3 embryos are selected based on a morphokinetic scoring system to increase the chances of a successful pregnancy. Characteristics tested include the if the growth of the cells is even, the number of cells and the level of fragmentation. <br />
The best embryos are transferred to the patient with a plastic catheter to the uterus. More than one may be transferred to increase the chances of a successful pregnancy in older women or women who have infertility issues. <br />
In order to ensure the embryo grows normally and implants properly, the patient is given adjunctive medication. This involves injection of specific concentrations of progesterone and GnRH agonists which is performed to support the corpus luteum.<br />
<br />
====Intracytoplasmic Sperm Injection (ICSI)====<br />
<br />
ICSI is typically performed during the co-incubation stage of IVF to make sure an oocyte is properly fertilised if the sperm is immobile. <br />
The process involves several devices under a microscope, namely; micromanipulator, microinjectors and micropipettes), and is fully outlined below:<br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=h7uucZ7xpYs</html5media><br />
<br />
ICSI Procedure <ref>Mothercare Hosp. (2014, July 7) 3D Animation of how ICSI works. Retrieved from https://www.youtube.com/watch?v=h7uucZ7xpYs</ref><br />
<br />
<br />
Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.<br />
<br />
==Glossary==<br />
<br />
ARTs - Assisted Reproductive Technologies<br />
<br />
Aetiological factors - causative agents <br />
<br />
Aneuploidy - the presence of an abnormal number of chromosomes in a cell<br />
<br />
Cadmium - a soft, insoluble transition metal that is a byproduct of zinc production <br />
<br />
Clomiphene citrate - a non-steroidal medication that induces infertility by increasing the release of GnRH, LH and FSH required for spermatogenesis<br />
<br />
CNPs - Cerium dioxide nanoparticles<br />
<br />
FSH - Follicle stimulating hormone<br />
<br />
Gametogenesis - a biological process resulting in the formation of mature haploid male (spermatogenesis) and female (oogenesis) germ cells <br />
<br />
GnRH - Gonadotropin releasing hormone<br />
<br />
hCG - Human chorionic gonadotropin<br />
<br />
hMG - Human menopausal gonadotropin<br />
<br />
Hypogonadatropic hypogonadism - a condition characterised by a decrease in functional activity of the gonadH<br />
<br />
ICSI - Intracytoplasmic Sperm Injection<br />
<br />
IUI - Intrauterine Insemination<br />
<br />
IVF - In Vitro Fertilisation<br />
<br />
Kiss1 - KiSS-1 Metastasis-Suppressor; a gene that codes for Kisspeptin, a G protein coupled receptor associated with hypogonadotropic hypogonadism <br />
<br />
Klinefelter syndrome - genetic disorder whereby a male has an extra X chromosome <br />
<br />
LH - Luteinizing hormone<br />
<br />
Lipid peroxidation - the oxidation of lipids causing its degradation, usually caused by ROS <br />
<br />
Progressive motility - the swimming of sperm from one place to another rather than in circles or twitching <br />
<br />
Quenching - the deactivation of reactive oxygen forms <br />
<br />
RDA - Recommended dietary allowance<br />
<br />
ROS - Reactive oxygen species<br />
<br />
Spermatogenesis - the production of development of new sperm <br />
<br />
Sperm-reactive antibodies (SpAb) - antibodies present on the membrane of spermatozoa that result in adverse affects to reproduction and often infertility. <ref><pubmed>8194608</pubmed></ref><br />
<br />
TCM - Traditional Chinese medicine<br />
<br />
Testicular Dysgenesis Syndrome (TDS) - a syndrome resultant of the disruption of embryonal programming and gonadal development during fetal life that is related to poor semen quality and testicular cancer, <ref><pubmed>11331648 </pubmed></ref><br />
<br />
TMS - Total Motile Sperm<br />
<br />
TURED - Transurethral resection of ejaculatory ducts<br />
<br />
Varicocele - Abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood<br />
<br />
==References==<br />
<br />
<references/><br />
<br />
==External Resources==</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=2015_Group_Project_4&diff=2076332015 Group Project 42015-10-22T12:52:02Z<p>Z3462833: /* In Vitro Fertilisation (IVF) */</p>
<hr />
<div>{{ANAT2341Project2015header}}<br />
<br />
=Male Infertility=<br />
<br />
Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male. <br />
<br />
Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails. <br />
<br />
<br />
<br />
==Spermatogenesis and Fertility==<br />
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]<br />
===Structure of spermatozoa===<br />
The shape of spermatozoa are suitable for its transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion <ref><pubmed>14617369</pubmed></ref>. Spermatozoa also consist of a flagellum for progressive motility during its movement through the epididymal ducts and within the female reproductive organ. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref><br />
<br />
<br />
[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]<br />
<br />
===Spermatogenesis===<br />
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis: <br />
<br />
1. Spermatogoniogenesis <br />
<br />
2. Maturation of spermatocytes <br />
<br />
3. Spermiogenesis (which is the cytodifferentiation of spermatids)<br />
<br />
<b>Spermatogoniogenesis</b> is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of <b>meiosis</b> is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During <b>spermiogenesis</b> three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref><br />
<br />
<br />
<br />
<br />
<br />
===Physiology of fertility in Males===<br />
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref><br />
<br />
==Male infertility disorders==<br />
<br />
Although infertility refers to the inability to conceive, there are numerous disorders that address particular reasons as to why this is the case. For males, the causes of infertility are endless and the most common factors have been discussed previously. Due to the range of aetiological factors, each one may effect a different aspect of the male's sperm including sperm count, morphology and motility rates. <br />
A fertile male is suggested have normospermia <ref><pubmed>PMC4156950</pubmed></ref> , in which the male's ejaculate contains normal sperm quality and quantity which are (based on the World Health Organisation (WHO)):<br />
*Ejaculate volume of approximately 1.5 to 5 mL <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Count of approximately 15 million to over 200 million spermatozoa per mL of ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Progressive motility of 32% or more spermatozoa <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Normal morphology present in 4% of the ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>, in which normal form refers to the spermatozoa containing the 3 fundamental parts; a head, midpiece and tail. <br />
<br />
Based on WHO's normal semen analysis, the specific types of male infertility disorders have been categorised accordingly. <br />
<br />
<span style="font-size:100%">'''Types of Male Infertility'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Type'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count of less than 15 million sperm/mL of ejaculate <ref><pubmed>23757979</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''<br />
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen with a progressive motility of less than 20% <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| More than 95% of spermatozoa in the ejaculate has abnormal morphology <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''<br />
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia) (referring to the statistics mentioned for each condition)<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa, despite normal spermatogenesis within the semen due to a blockage in the genital tract, obstructing the pathway for sperm to enter the penis from the testes <ref><pubmed>PMC3583161</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''<br />
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to the abnormal process or failure of spermatogenesis occurring, whereby sperm producing cells being damaged or destroyed <ref><pubmed>PMC3583162</pubmed></ref><br />
|}<br />
<br />
==Causes of Infertility== <br />
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.<br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media><br />
<br />
Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref><br />
<br />
===Major Causes of Male Infertility===<br />
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]<br />
<br />
====Varicocele====<br />
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).<br />
<br />
<br />
<br />
====Male Reproductive Cancers====<br />
<br />
Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref><br />
<br />
====Chromosomal Abnormalities====<br />
<br />
Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref><br />
<br />
====Damage to DNA====<br />
<br />
[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]<br />
<br />
DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref><br />
<br />
====Lifestyle Factors====<br />
<br />
[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]<br />
<br />
There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref><br />
<br />
====Immunological Infertility====<br />
<br />
Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref><br />
<br />
==Diagnosis== <br />
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.<br />
<br />
[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]<br />
<br />
===Physical examination===<br />
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref><br />
<br />
Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
<br />
<span style="font-size:100%">'''Classifications of Valsalva manoeuvre'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Grade'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Grade 1''' <br />
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam<br />
* No dilationed instrascrotal veins<br />
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre<br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''<br />
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre<br />
* No major dilation in supine position <br />
* Dilated veins up to lower pole of testis seen only in standing position <br />
* Reflux at lower pole veins during Valsalva manoeuvre<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Grade 3''' <br />
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre<br />
* Dilated veins<br />
* Reflex without Valsalva manoeuvre<br />
|}<br />
<br />
===Semen Analysis===<br />
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.<br />
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]<br />
<br />
===Testicular Colour Doppler Ultrasound===<br />
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref><br />
<br />
<br />
<br />
==Risk Factors and Prevention==<br />
<br />
<span style="font-size:100%">'''Risk Factors of Male Infertility'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Risk Factors'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Smoking''' <br />
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''<br />
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity''' <br />
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''<br />
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma''' <br />
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref><br />
|}<br />
<br />
If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse. <br />
<br />
==Treatments==<br />
<br />
Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.<br />
<br />
===Non-surgical Treatments===<br />
<br />
In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available. <br />
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]<br />
<br />
====Injectable Hormones & Fertility Drugs====<br />
<br />
Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. The associated image demonstrates the development and availability of gonadotropins for commercial use. <br />
<br />
Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.<br />
<br />
====Antioxidants====<br />
<br />
There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. <br />
<br />
The following are a few antioxidants that have been proven to treat oxidative stress, and hence improves male fertility. <br />
<br />
=====1. Carotenoids===== <br />
*Naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. <br />
*Subtypes are divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref><br />
*Main source of carotenoids in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. <br />
*Have been suggested as daily supplements for the human body, and act as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. <br />
*Their antioxidant activity of is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.<br />
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]<br />
<br />
Two common carotenoids that have been strongly advised as treatments for male infertility include lycopenes and Astaxanthin, described below. <br />
<br />
======Lycopenes====== <br />
*Type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. <br />
*Possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. <br />
*Have a role in neutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. <br />
*Inhibit lipid peroxidation allowing for spermatozoal membranes to be retained and protected from further damage. <br />
*Suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents. <br />
<br />
======Astaxanthin======<br />
*Keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. it has been <br />
*Suggested as an effective treatment and supplement for male factor infertility due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine. <br />
*An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for increased motility concentration, improved sperm morphology and motility, and a decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels. <br />
<br />
<br />
<br />
[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]] <br />
=====2. Cerium dioxide nanoparticles (CNPs)=====<br />
*Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility.<br />
*They are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. <br />
*CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. <br />
*A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress. <br />
<br />
=====3. Vitamin E=====<br />
*A fat – soluble antioxidant that exists in 8 chemical forms of different biological activity.<br />
*The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>, found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. <br />
*The recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. <br />
*Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. <br />
*From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility . <br />
<br />
=====4. Vitamin C=====<br />
*A water-soluble antioxidant that neutralizes free radicals and also prevents ROS synthesis<ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. <br />
*The human body does not produce or store vitamin C, so daily intakes of vitamin C – containing foods are required to maintain its levels internally.The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.<br />
*Foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. <br />
*A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.<br />
<br />
====Traditional Chinese Medicine====<br />
<br />
More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. <br />
<br />
Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.<br />
<br />
<span style="font-size:100%">'''Examples of Chinese Herbal Therapies'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Herb'''<br />
! scope="col" width="500px"| '''Evidence'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction''' <br />
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''<br />
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang''' <br />
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref><br />
|}<br />
<br />
===Surgical Treatments===<br />
<br />
====Varicocelectomy====<br />
<br />
Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur. <br />
<br />
Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. <br />
<br />
As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus. <br />
<br />
<span style="font-size:100%">'''Surgical Approach to Varicocele Repair'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery ''' <br />
|style="height: 50px; background: #CCEEEE;"| <br />
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
*Allows preservation of lymphatic vessels<br />
*Takes longer to heal <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''<br />
|style="height: 50px; background: #EEEEEE;"| <br />
*Incision below external inguinal ring<br />
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery''' <br />
|style="height: 50px; background: #CCEEEE;"| <br />
*Ligation of the internal spermatic vein <br />
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''<br />
|style="height: 50px; background: #EEEEEE;"| <br />
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref><br />
*Allows for a more accurate identification of vessels within the area <br />
|}<br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media><br />
<br />
Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref><br />
<br />
====Ejaculatory Duct Resection====<br />
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]<br />
<br />
Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.<br />
<br />
===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===<br />
<br />
It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm. <br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media><br />
<br />
Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref><br />
<br />
<br />
====Intrauterine Insemination (IUI)====<br />
<br />
Intrauterine insemination (IUI) is a simple procedure performed by a medical practitioner where washed sperm is injected directly into the uterus with a catheter. This allows the sperm to get as close to the egg as possible, increasing the chances of reaching it. This method is known as in vivo fertilisation as it is performed within the body of the female. <br />
It has been shown that if the woman rests for up to 15 minutes after insemination the chance of pregnancy is greater than if they are mobilised immediately after the procedure.<ref><pubmed>19875843</pubmed></ref><br />
The optimal conditions for an IUI include; the female being less than age 30, the male having a total motile sperm count of more than 5 million per mL. A likely pregnancy will result from a cycle that produces two eggs of 16 mm or more and an oestrogen concentration of 500 pg/mL at the time of the procedure.<ref><pubmed>18996517</pubmed></ref><br />
<br />
====In Vitro Fertilisation (IVF)====<br />
<br />
Theoretically, all that is required for in vitro fertilisation is to combine the contents of a woman’s fallopian tubes and sperm, followed by re-inserting this mixture into the uterus. In practice, however, this process would be an oversimplification and not particularly successful. There are several major steps in the procedure that are necessary for pregnancy. <br />
The first step is hyperstimulation of the ovaries. The purpose of this step is to produce several oocytes to make sure there are enough suitable candidates for the procedure. This is achieved by injecting a GnRH antagonist and gonadotropins into the female. Careful monitoring of the concentrations of these hormones is essential for the safety and well-being of the patient and for the successful removal of adequate follicles. <br />
Next, after the follicles have reached an appropriate level of development, final maturation induction is performed, typically by injection of hCG and GnRH agonist. This step is to replace the natural surge of LH that would normally mature the ovarian follicles.<br />
Once the follicles have matured, they are retrieved from the ovaries by a process known as transvaginal oocyte retrieval. This involves a needle guided by ultra-sound to pierce the vaginal walls, reaching the ovaries and finally aspiration of the mature oocytes and follicular fluid. Typically, 10-30 oocytes are removed under general anaesthesia. <br />
The oocytes are then inspected and only those with the highest chance of successful pregnancy are chosen and the surrounding layer of cells is removed from the eggs. Semen is washed simultaneously by removing any seminal fluid and other proteins. <br />
The next step is for the oocytes and semen to undergo co-incubation. The sperm cells and oocytes are incubated in culture media at a ratio of 75 000:1. It is at this point that another ART may be used (ICSI) if the sperm count or motility is not optimal. Once fertilisation takes place, the egg is placed in special growth medium and left for approximately 2 days until the cell mass is around 6-8 cells.<br />
Following this the best 2-3 embryos are selected based on a morphokinetic scoring system to increase the chances of a successful pregnancy. Characteristics tested include the if the growth of the cells is even, the number of cells and the level of fragmentation. <br />
The best embryos are transferred to the patient with a plastic catheter to the uterus. More than one may be transferred to increase the chances of a successful pregnancy in older women or women who have infertility issues. <br />
In order to ensure the embryo grows normally and implants properly, the patient is given adjunctive medication. This involves injection of specific concentrations of progesterone and GnRH agonists which is performed to support the corpus luteum.<br />
<br />
====Intracytoplasmic Sperm Injection (ICSI)====<br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=h7uucZ7xpYs</html5media><br />
<br />
ICSI Procedure <ref>Mothercare Hosp. (2014, July 7) 3D Animation of how ICSI works. Retrieved from https://www.youtube.com/watch?v=h7uucZ7xpYs</ref><br />
<br />
<br />
Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.<br />
<br />
==Glossary==<br />
<br />
ARTs - Assisted Reproductive Technologies<br />
<br />
Aetiological factors - causative agents <br />
<br />
Aneuploidy - the presence of an abnormal number of chromosomes in a cell<br />
<br />
Cadmium - a soft, insoluble transition metal that is a byproduct of zinc production <br />
<br />
Clomiphene citrate - a non-steroidal medication that induces infertility by increasing the release of GnRH, LH and FSH required for spermatogenesis<br />
<br />
CNPs - Cerium dioxide nanoparticles<br />
<br />
FSH - Follicle stimulating hormone<br />
<br />
Gametogenesis - a biological process resulting in the formation of mature haploid male (spermatogenesis) and female (oogenesis) germ cells <br />
<br />
GnRH - Gonadotropin releasing hormone<br />
<br />
hCG - Human chorionic gonadotropin<br />
<br />
hMG - Human menopausal gonadotropin<br />
<br />
Hypogonadatropic hypogonadism - a condition characterised by a decrease in functional activity of the gonadH<br />
<br />
ICSI - Intracytoplasmic Sperm Injection<br />
<br />
IUI - Intrauterine Insemination<br />
<br />
IVF - In Vitro Fertilisation<br />
<br />
Kiss1 - KiSS-1 Metastasis-Suppressor; a gene that codes for Kisspeptin, a G protein coupled receptor associated with hypogonadotropic hypogonadism <br />
<br />
Klinefelter syndrome - genetic disorder whereby a male has an extra X chromosome <br />
<br />
LH - Luteinizing hormone<br />
<br />
Lipid peroxidation - the oxidation of lipids causing its degradation, usually caused by ROS <br />
<br />
Progressive motility - the swimming of sperm from one place to another rather than in circles or twitching <br />
<br />
Quenching - the deactivation of reactive oxygen forms <br />
<br />
RDA - Recommended dietary allowance<br />
<br />
ROS - Reactive oxygen species<br />
<br />
Spermatogenesis - the production of development of new sperm <br />
<br />
Sperm-reactive antibodies (SpAb) - antibodies present on the membrane of spermatozoa that result in adverse affects to reproduction and often infertility. <ref><pubmed>8194608</pubmed></ref><br />
<br />
TCM - Traditional Chinese medicine<br />
<br />
Testicular Dysgenesis Syndrome (TDS) - a syndrome resultant of the disruption of embryonal programming and gonadal development during fetal life that is related to poor semen quality and testicular cancer, <ref><pubmed>11331648 </pubmed></ref><br />
<br />
TMS - Total Motile Sperm<br />
<br />
TURED - Transurethral resection of ejaculatory ducts<br />
<br />
Varicocele - Abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood<br />
<br />
==References==<br />
<br />
<references/><br />
<br />
==External Resources==</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=2015_Group_Project_4&diff=2072732015 Group Project 42015-10-22T04:51:28Z<p>Z3462833: /* Intrauterine Insemination (IUI) */</p>
<hr />
<div>{{ANAT2341Project2015header}}<br />
<br />
=Male Infertility=<br />
<br />
Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male. <br />
<br />
Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails. <br />
<br />
<br />
<br />
==Spermatogenesis and Fertility==<br />
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]<br />
===Structure of spermatozoa===<br />
The shape of spermatozoa are suitable for the transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion. Spermatozoa also consist of a flagellum for progressive motility during the transport throughout the epididymal ducts. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref><pubmed>14617369</pubmed></ref> <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref><br />
<br />
<br />
[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]<br />
<br />
<br />
<br />
===Spermatogenesis===<br />
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis: <br />
<br />
1. Spermatogoniogenesis <br />
<br />
2. Maturation of spermatocytes <br />
<br />
3. Spermiogenesis (which is the cytodifferentiation of spermatids)<br />
<br />
<b>Spermatogoniogenesis</b> is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of <b>meiosis</b> is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During <b>spermiogenesis</b> three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref><br />
<br />
<br />
<br />
<br />
===Physiology of fertility in Males===<br />
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref><br />
<br />
==Male infertility disorders==<br />
<br />
Although infertility refers to the inability to conceive, there are numerous disorders that address particular reasons as to why this is the case. For males, the causes of infertility are endless and the most common factors have been discussed previously. Due to the range of aetiological factors, each one may effect a different aspect of the male's sperm including sperm count, morphology and motility rates. <br />
A fertile male is suggested have normospermia <ref><pubmed>PMC4156950</pubmed></ref> , in which the male's ejaculate contains normal sperm quality and quantity which are (based on the World Health Organisation (WHO)):<br />
*Ejaculate volume of approximately 1.5 to 5 mL <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Count of approximately 15 million to over 200 million spermatozoa per mL of ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Progressive motility of 32% or more spermatozoa <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Normal morphology present in 4% of the ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>, in which normal form refers to the spermatozoa containing the 3 fundamental parts; a head, midpiece and tail. <br />
<br />
Based on WHO's normal semen analysis, the specific types of male infertility disorders have been categorised accordingly. <br />
<br />
<span style="font-size:100%">'''Types of Male Infertility'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Type'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count of less than 15 million sperm/mL of ejaculate <ref><pubmed>23757979</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''<br />
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen with a progressive motility of less than 20% <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| More than 95% of spermatozoa in the ejaculate has abnormal morphology <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''<br />
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia) (referring to the statistics mentioned for each condition)<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa, despite normal spermatogenesis within the semen due to a blockage in the genital tract, obstructing the pathway for sperm to enter the penis from the testes <ref><pubmed>PMC3583161</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''<br />
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to the abnormal process or failure of spermatogenesis occurring, whereby sperm producing cells being damaged or destroyed <ref><pubmed>PMC3583162</pubmed></ref><br />
|}<br />
<br />
==Causes of Infertility== <br />
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.<br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media><br />
<br />
Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref><br />
<br />
===Major Causes of Male Infertility===<br />
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]<br />
<br />
====Varicocele====<br />
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).<br />
<br />
<br />
<br />
====Male Reproductive Cancers====<br />
<br />
Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref><br />
<br />
====Chromosomal Abnormalities====<br />
<br />
Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref><br />
<br />
====Damage to DNA====<br />
<br />
[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]<br />
<br />
DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref><br />
<br />
====Lifestyle Factors====<br />
<br />
[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]<br />
<br />
There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref><br />
<br />
====Immunological Infertility====<br />
<br />
Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref><br />
<br />
==Diagnosis== <br />
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.<br />
<br />
[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]<br />
<br />
===Physical examination===<br />
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref><br />
<br />
Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
<br />
<span style="font-size:100%">'''Classifications of Valsalva manoeuvre'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Grade'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Grade 1''' <br />
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam<br />
* No dilationed instrascrotal veins<br />
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre<br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''<br />
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre<br />
* No major dilation in supine position <br />
* Dilated veins up to lower pole of testis seen only in standing position <br />
* Reflux at lower pole veins during Valsalva manoeuvre<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Grade 3''' <br />
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre<br />
* Dilated veins<br />
* Reflex without Valsalva manoeuvre<br />
|}<br />
<br />
===Semen Analysis===<br />
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.<br />
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]<br />
<br />
===Testicular Colour Doppler Ultrasound===<br />
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref><br />
<br />
<br />
<br />
==Risk Factors and Prevention==<br />
<br />
<span style="font-size:100%">'''Risk Factors of Male Infertility'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Risk Factors'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Smoking''' <br />
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''<br />
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity''' <br />
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''<br />
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma''' <br />
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref><br />
|}<br />
<br />
If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse. <br />
<br />
==Treatments==<br />
<br />
Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.<br />
<br />
===Non-surgical Treatments===<br />
<br />
In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available. <br />
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]<br />
<br />
====Injectable Hormones & Fertility Drugs====<br />
<br />
Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. The associated image demonstrates the development and availability of gonadotropins for commercial use. <br />
<br />
Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.<br />
<br />
====Antioxidants====<br />
<br />
There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. <br />
<br />
The following are a few antioxidants that have been proven to treat oxidative stress, and hence improves male fertility. <br />
<br />
=====1. Carotenoids===== <br />
*Naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. <br />
*Subtypes are divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref><br />
*Main source of carotenoids in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. <br />
*Have been suggested as daily supplements for the human body, and act as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. <br />
*Their antioxidant activity of is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.<br />
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]<br />
<br />
Two common carotenoids that have been strongly advised as treatments for male infertility include lycopenes and Astaxanthin, described below. <br />
<br />
======Lycopenes====== <br />
*Type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. <br />
*Possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. <br />
*Have a role in neutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. <br />
*Inhibit lipid peroxidation allowing for spermatozoal membranes to be retained and protected from further damage. <br />
*Suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents. <br />
<br />
======Astaxanthin======<br />
*Keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. it has been <br />
*Suggested as an effective treatment and supplement for male factor infertility due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine. <br />
*An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for increased motility concentration, improved sperm morphology and motility, and a decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels. <br />
<br />
<br />
<br />
[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]] <br />
=====2. Cerium dioxide nanoparticles (CNPs)=====<br />
*Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility.<br />
*They are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. <br />
*CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. <br />
*A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress. <br />
<br />
=====3. Vitamin E=====<br />
*A fat – soluble antioxidant that exists in 8 chemical forms of different biological activity.<br />
*The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>, found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. <br />
*The recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. <br />
*Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. <br />
*From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility . <br />
<br />
=====4. Vitamin C=====<br />
*A water-soluble antioxidant that neutralizes free radicals and also prevents ROS synthesis<ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. <br />
*The human body does not produce or store vitamin C, so daily intakes of vitamin C – containing foods are required to maintain its levels internally.The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.<br />
*Foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. <br />
*A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.<br />
<br />
====Traditional Chinese Medicine====<br />
<br />
More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. <br />
<br />
Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.<br />
<br />
<span style="font-size:100%">'''Examples of Chinese Herbal Therapies'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Herb'''<br />
! scope="col" width="500px"| '''Evidence'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction''' <br />
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''<br />
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang''' <br />
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref><br />
|}<br />
<br />
===Surgical Treatments===<br />
<br />
====Varicocelectomy====<br />
<br />
Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur. <br />
<br />
Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. <br />
<br />
As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus. <br />
<br />
<span style="font-size:100%">'''Surgical Approach to Varicocele Repair'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery ''' <br />
|style="height: 50px; background: #CCEEEE;"| <br />
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
*Allows preservation of lymphatic vessels<br />
*Takes longer to heal <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''<br />
|style="height: 50px; background: #EEEEEE;"| <br />
*Incision below external inguinal ring<br />
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery''' <br />
|style="height: 50px; background: #CCEEEE;"| <br />
*Ligation of the internal spermatic vein <br />
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''<br />
|style="height: 50px; background: #EEEEEE;"| <br />
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref><br />
*Allows for a more accurate identification of vessels within the area <br />
|}<br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media><br />
<br />
Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref><br />
<br />
====Ejaculatory Duct Resection====<br />
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]<br />
<br />
Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.<br />
<br />
===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===<br />
<br />
It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm. <br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media><br />
<br />
Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref><br />
<br />
<br />
====Intrauterine Insemination (IUI)====<br />
<br />
Intrauterine insemination (IUI) is a simple procedure performed by a medical practitioner where washed sperm is injected directly into the uterus with a catheter. This allows the sperm to get as close to the egg as possible, increasing the chances of reaching it. This method is known as in vivo fertilisation as it is performed within the body of the female. <br />
It has been shown that if the woman rests for up to 15 minutes after insemination the chance of pregnancy is greater than if they are mobilised immediately after the procedure.[76]<br />
The optimal conditions for an IUI include; the female being less than age 30, the male having a TMS count of more than 5 million per mL. A likely pregnancy will result from a cycle that produces two eggs of 16 mm or more and an oestrogen concentration of 500 pg/mL at the time of the procedure.[77] <br />
<br />
Here are the 2 PMID's for this section:<br />
76: PMID: 19875843<br />
77: PMID: 18996517<br />
<br />
====In Vitro Fertilisation (IVF)====<br />
<br />
====Intracytoplasmic Sperm Injection (ICSI)====<br />
<br />
Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.<br />
<br />
==Glossary==<br />
<br />
ARTs - Assisted Reproductive Technologies<br />
<br />
Aetiological factors - causative agents <br />
<br />
Cadmium - a soft, insoluble transition metal that is a byproduct of zinc production <br />
<br />
Clomiphene citrate - a non-steroidal medication that induces infertility by increasing the release of GnRH, LH and FSH required for spermatogenesis<br />
<br />
CNPs - Cerium dioxide nanoparticles<br />
<br />
FSH - Follicle stimulating hormone<br />
<br />
Gametogenesis - a biological process resulting in the formation of mature haploid male (spermatogenesis) and female (oogenesis) germ cells <br />
<br />
GnRH - Gonadotropin releasing hormone<br />
<br />
hCG - Human chorionic gonadotropin<br />
<br />
hMG - Human menopausal gonadotropin<br />
<br />
Hypogonadatropic hypogonadism - a condition characterised by a decrease in functional activity of the gonadH<br />
<br />
ICSI - Intracytoplasmic Sperm Injection<br />
<br />
IUI - Intrauterine Insemination<br />
<br />
IVF - In Vitro Fertilisation<br />
<br />
Kiss1 - KiSS-1 Metastasis-Suppressor; a gene that codes for Kisspeptin, a G protein coupled receptor associated with hypogonadotropic hypogonadism <br />
<br />
Klinefelter syndrome - genetic disorder whereby a male has an extra X chromosome <br />
<br />
LH - Luteinizing hormone<br />
<br />
Lipid peroxidation - the oxidation of lipids causing its degradation, usually caused by ROS <br />
<br />
Progressive motility - the swimming of sperm from one place to another rather than in circles or twitching <br />
<br />
Quenching - the deactivation of reactive oxygen forms <br />
<br />
RDA - Recommended dietary allowance<br />
<br />
ROS - Reactive oxygen species<br />
<br />
SpAb - Sperm-reactive antibodies<br />
<br />
TCM - Traditional Chinese medicine<br />
<br />
TDS - Testicular Dysgenesis Syndrome<br />
<br />
TMS - Total Motile Sperm<br />
<br />
TURED - Transurethral resection of ejaculatory ducts<br />
<br />
Varicocele - Abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood<br />
<br />
==References==<br />
<br />
<references/><br />
<br />
==External Resources==</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=2015_Group_Project_4&diff=2072412015 Group Project 42015-10-22T04:31:03Z<p>Z3462833: /* Glossary */</p>
<hr />
<div>{{ANAT2341Project2015header}}<br />
<br />
=Male Infertility=<br />
<br />
Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male. <br />
<br />
Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails. <br />
<br />
<br />
<br />
==Spermatogenesis and Fertility==<br />
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]<br />
===Structure of spermatozoa===<br />
The shape of spermatozoa are suitable for the transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion. Spermatozoa also consist of a flagellum for progressive motility during the transport throughout the epididymal ducts. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref><pubmed>14617369</pubmed></ref> <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref><br />
<br />
<br />
[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]<br />
<br />
<br />
<br />
===Spermatogenesis===<br />
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis: <br />
<br />
1. Spermatogoniogenesis <br />
<br />
2. Maturation of spermatocytes <br />
<br />
3. Spermiogenesis (which is the cytodifferentiation of spermatids)<br />
<br />
<b>Spermatogoniogenesis</b> is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of <b>meiosis</b> is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During <b>spermiogenesis</b> three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref><br />
<br />
<br />
<br />
<br />
===Physiology of fertility in Males===<br />
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref><br />
<br />
==Male infertility disorders==<br />
<br />
Although infertility refers to the inability to conceive, there are numerous disorders that address particular reasons as to why this is the case. For males, the causes of infertility are endless and the most common factors have been discussed previously. Due to the range of aetiological factors, each one may effect a different aspect of the male's sperm including sperm count, morphology and motility rates. <br />
A fertile male is suggested have normospermia <ref><pubmed>PMC4156950</pubmed></ref> , in which the male's ejaculate contains normal sperm quality and quantity which are (based on the World Health Organisation (WHO)):<br />
*Ejaculate volume of approximately 1.5 to 5 mL <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Count of approximately 15 million to over 200 million spermatozoa per mL of ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Progressive motility of 32% or more spermatozoa <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.<br />
*Normal morphology present in 4% of the ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>, in which normal form refers to the spermatozoa containing the 3 fundamental parts; a head, midpiece and tail. <br />
<br />
Based on WHO's normal semen analysis, the specific types of male infertility disorders have been categorised accordingly. <br />
<br />
<span style="font-size:100%">'''Types of Male Infertility'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Type'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count of less than 15 million sperm/mL of ejaculate <ref><pubmed>23757979</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''<br />
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen with a progressive motility of less than 20% <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| More than 95% of spermatozoa in the ejaculate has abnormal morphology <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''<br />
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia) (referring to the statistics mentioned for each condition)<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia''' <br />
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa, despite normal spermatogenesis within the semen due to a blockage in the genital tract, obstructing the pathway for sperm to enter the penis from the testes <ref><pubmed>PMC3583161</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''<br />
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to the abnormal process or failure of spermatogenesis occurring, whereby sperm producing cells being damaged or destroyed <ref><pubmed>PMC3583162</pubmed></ref><br />
|}<br />
<br />
==Causes of Infertility== <br />
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.<br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media><br />
<br />
Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref><br />
<br />
===Major Causes of Male Infertility===<br />
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]<br />
<br />
====Varicocele====<br />
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).<br />
<br />
<br />
<br />
====Male Reproductive Cancers====<br />
<br />
Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref><br />
<br />
====Chromosomal Abnormalities====<br />
<br />
Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref><br />
<br />
====Damage to DNA====<br />
<br />
[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]<br />
<br />
DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref><br />
<br />
====Lifestyle Factors====<br />
<br />
[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]<br />
<br />
There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref><br />
<br />
====Immunological Infertility====<br />
<br />
Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref><br />
<br />
==Diagnosis== <br />
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.<br />
<br />
[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]<br />
<br />
===Physical examination===<br />
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref><br />
<br />
Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
<br />
<span style="font-size:100%">'''Classifications of Valsalva manoeuvre'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Grade'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Grade 1''' <br />
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam<br />
* No dilationed instrascrotal veins<br />
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre<br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''<br />
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre<br />
* No major dilation in supine position <br />
* Dilated veins up to lower pole of testis seen only in standing position <br />
* Reflux at lower pole veins during Valsalva manoeuvre<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Grade 3''' <br />
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre<br />
* Dilated veins<br />
* Reflex without Valsalva manoeuvre<br />
|}<br />
<br />
===Semen Analysis===<br />
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.<br />
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]<br />
<br />
===Testicular Colour Doppler Ultrasound===<br />
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref><br />
<br />
<br />
<br />
==Risk Factors and Prevention==<br />
<br />
<span style="font-size:100%">'''Risk Factors of Male Infertility'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Risk Factors'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Smoking''' <br />
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''<br />
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity''' <br />
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref> <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''<br />
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma''' <br />
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref><br />
|}<br />
<br />
If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse. <br />
<br />
==Treatments==<br />
<br />
Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.<br />
<br />
===Non-surgical Treatments===<br />
<br />
In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available. <br />
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]<br />
<br />
====Injectable Hormones & Fertility Drugs====<br />
<br />
Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. The associated image demonstrates the development and availability of gonadotropins for commercial use. <br />
<br />
Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.<br />
<br />
====Antioxidants====<br />
<br />
There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. <br />
<br />
The following are a few antioxidants that have been proven to treat oxidative stress, and hence improves male fertility. <br />
<br />
=====1. Carotenoids===== <br />
*Naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. <br />
*Subtypes are divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref><br />
*Main source of carotenoids in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. <br />
*Have been suggested as daily supplements for the human body, and act as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. <br />
*Their antioxidant activity of is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.<br />
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]<br />
<br />
Two common carotenoids that have been strongly advised as treatments for male infertility include lycopenes and Astaxanthin, described below. <br />
<br />
======Lycopenes====== <br />
*Type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. <br />
*Possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. <br />
*Have a role in neutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. <br />
*Inhibit lipid peroxidation allowing for spermatozoal membranes to be retained and protected from further damage. <br />
*Suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents. <br />
<br />
======Astaxanthin======<br />
*Keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. it has been <br />
*Suggested as an effective treatment and supplement for male factor infertility due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine. <br />
*An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for increased motility concentration, improved sperm morphology and motility, and a decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels. <br />
<br />
<br />
<br />
[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]] <br />
=====2. Cerium dioxide nanoparticles (CNPs)=====<br />
*Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility.<br />
*They are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. <br />
*CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. <br />
*A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress. <br />
<br />
=====3. Vitamin E=====<br />
*A fat – soluble antioxidant that exists in 8 chemical forms of different biological activity.<br />
*The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>, found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. <br />
*The recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. <br />
*Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. <br />
*From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility . <br />
<br />
=====4. Vitamin C=====<br />
*A water-soluble antioxidant that neutralizes free radicals and also prevents ROS synthesis<ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. <br />
*The human body does not produce or store vitamin C, so daily intakes of vitamin C – containing foods are required to maintain its levels internally.The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.<br />
*Foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. <br />
*A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.<br />
<br />
====Traditional Chinese Medicine====<br />
<br />
More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. <br />
<br />
Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.<br />
<br />
<span style="font-size:100%">'''Examples of Chinese Herbal Therapies'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Herb'''<br />
! scope="col" width="500px"| '''Evidence'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction''' <br />
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''<br />
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang''' <br />
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref><br />
|}<br />
<br />
===Surgical Treatments===<br />
<br />
====Varicocelectomy====<br />
<br />
Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur. <br />
<br />
Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. <br />
<br />
As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus. <br />
<br />
<span style="font-size:100%">'''Surgical Approach to Varicocele Repair'''</span> <br />
{| class="wikitable" style="text-align:center<br />
|-<br />
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''<br />
! scope="col" width="500px"| '''Description'''<br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery ''' <br />
|style="height: 50px; background: #CCEEEE;"| <br />
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
*Allows preservation of lymphatic vessels<br />
*Takes longer to heal <br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''<br />
|style="height: 50px; background: #EEEEEE;"| <br />
*Incision below external inguinal ring<br />
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
|-<br />
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery''' <br />
|style="height: 50px; background: #CCEEEE;"| <br />
*Ligation of the internal spermatic vein <br />
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref><br />
|-<br />
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''<br />
|style="height: 50px; background: #EEEEEE;"| <br />
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref><br />
*Allows for a more accurate identification of vessels within the area <br />
|}<br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media><br />
<br />
Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref><br />
<br />
====Ejaculatory Duct Resection====<br />
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]<br />
<br />
Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.<br />
<br />
===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===<br />
<br />
It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm. <br />
<br />
<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media><br />
<br />
Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref><br />
<br />
<br />
====Intrauterine Insemination (IUI)====<br />
<br />
====In Vitro Fertilisation (IVF)====<br />
<br />
====Intracytoplasmic Sperm Injection (ICSI)====<br />
<br />
Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.<br />
<br />
==Glossary==<br />
<br />
ARTs - Assisted Reproductive Technologies<br />
<br />
Aetiological factors - causative agents <br />
<br />
Cadmium - a soft, insoluble transition metal that is a byproduct of zinc production <br />
<br />
Clomiphene citrate - a non-steroidal medication that induces infertility by increasing the release of GnRH, LH and FSH required for spermatogenesis<br />
<br />
CNPs - Cerium dioxide nanoparticles<br />
<br />
FSH - Follicle stimulating hormone<br />
<br />
Gametogenesis - a biological process resulting in the formation of mature haploid male (spermatogenesis) and female (oogenesis) germ cells <br />
<br />
GnRH - Gonadotropin releasing hormone<br />
<br />
hCG - Human chorionic gonadotropin<br />
<br />
hMG - Human menopausal gonadotropin<br />
<br />
Hypogonadatropic hypogonadism - a condition characterised by a decrease in functional activity of the gonadH<br />
<br />
ICSI - Intracytoplasmic Sperm Injection<br />
<br />
IUI - Intrauterine Insemination<br />
<br />
IVF - In Vitro Fertilisation<br />
<br />
Kiss1 - KiSS-1 Metastasis-Suppressor; a gene that codes for Kisspeptin, a G protein coupled receptor associated with hypogonadotropic hypogonadism <br />
<br />
Klinefelter syndrome - genetic disorder whereby a male has an extra X chromosome <br />
<br />
LH - Luteinizing hormone<br />
<br />
Lipid peroxidation - the oxidation of lipids causing its degradation, usually caused by ROS <br />
<br />
Progressive motility - the swimming of sperm from one place to another rather than in circles or twitching <br />
<br />
Quenching - the deactivation of reactive oxygen forms <br />
<br />
RDA - Recommended dietary allowance<br />
<br />
ROS - Reactive oxygen species<br />
<br />
SpAb - Sperm-reactive antibodies<br />
<br />
TCM - Traditional Chinese medicine<br />
<br />
TDS - Testicular Dysgenesis Syndrome<br />
<br />
TMS - Total Motile Sperm<br />
<br />
TURED - Transurethral resection of ejaculatory ducts<br />
<br />
Varicocele - Abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood<br />
<br />
==References==<br />
<br />
<references/><br />
<br />
==External Resources==</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=205995User:Z34628332015-10-16T01:07:15Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
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--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:07, 16 October 2015 (AEDT)<br />
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{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=202063User:Z34628332015-09-25T02:56:27Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:56, 25 September 2015 (AEST)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=200291User:Z34628332015-09-18T02:03:49Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:04, 17 September 2015 (AEST) Where is your summary for this assessment and I had asked for 2 articles?<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:03, 18 September 2015 (AEST)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=198405User:Z34628332015-09-11T02:25:56Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:25, 11 September 2015 (AEST)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=196896User:Z34628332015-09-04T02:05:39Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:05, 4 September 2015 (AEST)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=196300User:Z34628332015-08-31T03:15:59Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
Sorry, forgot to sign in during the lab on the 28th of August<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:15, 31 August 2015 (AEST)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2015_Group_Project_4&diff=195680Talk:2015 Group Project 42015-08-27T13:38:13Z<p>Z3462833: </p>
<hr />
<div>{{ANAT2341Project2015discussionheader}}<br />
<br />
==Discussion==<br />
<br />
Hey guys, I have just had a really quick look on PubMed and I found a good starting article. Its a review article (I'm pretty sure) so I'm not sure if we can use it, but it discusses some interesting genetic causes of male infertility and also references a lot of primary articles. <br />
<br />
PMID 26178295 <br />
<br />
--[[User:Z3462124|Z3462124]] ([[User talk:Z3462124|talk]]) 13:38, 25 August 2015 (AEST)<br />
<br />
<br />
I can't seem to view anything but the first page of the article but the introduction gives a good idea on what male infertility is and how it arises. At the moment I have found 2 research articles that address factors that can increase male fertility. Although they do not address male infertility conditions specifically, in the discussion they imply that these methods can be applied to men who have them such as oligospermia and azoospermia. I feel as though we can use these articles when discussing alternative therapies for successful conception. Please have a read and share your opinions! <br />
<br />
PMID 22958644 - note that you can only view the condensed version of this article<br />
<br />
PMID 26097523 - you can view the whole article on biomed (subheadings in the discussion particularly addresses male infertility)<br />
<br />
--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 14:17, 25 August 2015 (AEST)<br />
<br />
<br />
<br />
Hey guys, it was pretty hard finding research articles from Pubmed regarding the epidemiology of male infertility. For now, I have found an article about sperm extraction which I thought could be an alternative for treatments. However I can't view the full article without paying, but the abstract from Pubmed seems to sum it up.<br />
So, I came across a research article addressing the epidemiology and aetiology of male infertility, through Pubmed it doesn't have a direct link to the full PDF article however I linked it you guys on Facebook so have a read!<br />
<br />
PMID 22128297<br />
<br />
PMID 9663768<br />
<br />
--[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 11:59, 26 August 2015 (AEST)<br />
<br />
<br />
Hello everyone! To get started, I just added a few headings on the page where you can add your research/review articles. Feel free to add more subheadings or change the wording of the titles - I'm sure we will need to as we research more. From looking at other groups' pages, I think it is also important we add a bit of 'Background Information" regarding the process of spermatogenesis and how any abnormalities can cause infertility so we can all look for articles as we go. Remember we are targeting this towards students like us, so a bit of key background info is essential. <br />
<br />
--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 00:06, 27 August 2015 (AEST)<br />
<br />
<br />
I just posted the articles that I found on male infertility. It was kind of hard to find ones because I stuck to studies in humans- but i found some good ones that were studies on rats (not sure if we can use them) and also some good secondary or review articles that we could use as background information maybe? So I'll just post the PMID's here..<br />
* PMID 26303086<br />
* PMID 23725463 <br />
* PMID 25160621<br />
* PMID 25142466<br />
--[[User:Z3462124|Z3462124]] ([[User talk:Z3462124|talk]]) 09:59, 27 August 2015 (AEST)<br />
<br />
<br />
Not sure if we are review articles are any good, but I thought that it's also important to talk about "detecting abnormalities". I came across this review article which talks about the "male genital tract - colour dopple ultrasound" is a useful tool to detect impaired reproductive health.<br />
<br />
PMID 25038770 <br />
<br />
--[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 19:59, 27 August 2015 (AEST)<br />
<br />
<br />
Good thinking! If anyone comes across more articles regarding this, please post them up! I'll add a 'diagnosis' sub-heading to the page <br />
<br />
--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 22:23, 27 August 2015 (AEST)<br />
<br />
<br />
Hey guys, found a couple of articles describing different methods of ARTs for male infertility:<br />
<br />
These 2 talk about Intrauterine Insemination (IUI)<br />
PMID 26294874<br />
PMID 26288981<br />
<br />
Also, another potential sub-heading to research might be the risks involved different ARTs<br />
E.g. the following article about the prevalence of birth defects after a number of different male-related ARTs<br />
PMID 26265143<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 23:38, 27 August 2015 (AEST)</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2015_Group_Project_4&diff=195678Talk:2015 Group Project 42015-08-27T13:37:53Z<p>Z3462833: /* Discussion */</p>
<hr />
<div>{{ANAT2341Project2015discussionheader}}<br />
<br />
==Discussion==<br />
<br />
Hey guys, I have just had a really quick look on PubMed and I found a good starting article. Its a review article (I'm pretty sure) so I'm not sure if we can use it, but it discusses some interesting genetic causes of male infertility and also references a lot of primary articles. <br />
<br />
PMID 26178295 <br />
<br />
--[[User:Z3462124|Z3462124]] ([[User talk:Z3462124|talk]]) 13:38, 25 August 2015 (AEST)<br />
<br />
<br />
I can't seem to view anything but the first page of the article but the introduction gives a good idea on what male infertility is and how it arises. At the moment I have found 2 research articles that address factors that can increase male fertility. Although they do not address male infertility conditions specifically, in the discussion they imply that these methods can be applied to men who have them such as oligospermia and azoospermia. I feel as though we can use these articles when discussing alternative therapies for successful conception. Please have a read and share your opinions! <br />
<br />
PMID 22958644 - note that you can only view the condensed version of this article<br />
<br />
PMID 26097523 - you can view the whole article on biomed (subheadings in the discussion particularly addresses male infertility)<br />
<br />
--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 14:17, 25 August 2015 (AEST)<br />
<br />
<br />
<br />
Hey guys, it was pretty hard finding research articles from Pubmed regarding the epidemiology of male infertility. For now, I have found an article about sperm extraction which I thought could be an alternative for treatments. However I can't view the full article without paying, but the abstract from Pubmed seems to sum it up.<br />
So, I came across a research article addressing the epidemiology and aetiology of male infertility, through Pubmed it doesn't have a direct link to the full PDF article however I linked it you guys on Facebook so have a read!<br />
<br />
PMID 22128297<br />
<br />
PMID 9663768<br />
<br />
--[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 11:59, 26 August 2015 (AEST)<br />
<br />
<br />
Hello everyone! To get started, I just added a few headings on the page where you can add your research/review articles. Feel free to add more subheadings or change the wording of the titles - I'm sure we will need to as we research more. From looking at other groups' pages, I think it is also important we add a bit of 'Background Information" regarding the process of spermatogenesis and how any abnormalities can cause infertility so we can all look for articles as we go. Remember we are targeting this towards students like us, so a bit of key background info is essential. <br />
<br />
--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 00:06, 27 August 2015 (AEST)<br />
<br />
<br />
I just posted the articles that I found on male infertility. It was kind of hard to find ones because I stuck to studies in humans- but i found some good ones that were studies on rats (not sure if we can use them) and also some good secondary or review articles that we could use as background information maybe? So I'll just post the PMID's here..<br />
* PMID 26303086<br />
* PMID 23725463 <br />
* PMID 25160621<br />
* PMID 25142466<br />
--[[User:Z3462124|Z3462124]] ([[User talk:Z3462124|talk]]) 09:59, 27 August 2015 (AEST)<br />
<br />
<br />
Not sure if we are review articles are any good, but I thought that it's also important to talk about "detecting abnormalities". I came across this review article which talks about the "male genital tract - colour dopple ultrasound" is a useful tool to detect impaired reproductive health.<br />
<br />
PMID 25038770 <br />
<br />
--[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 19:59, 27 August 2015 (AEST)<br />
<br />
<br />
Good thinking! If anyone comes across more articles regarding this, please post them up! I'll add a 'diagnosis' sub-heading to the page <br />
<br />
--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 22:23, 27 August 2015 (AEST)<br />
<br />
<br />
Hey guys, found a couple of articles describing different methods of ARTs for male infertility:<br />
<br />
These 2 talk about Intrauterine Insemination (IUI)<br />
PMID 26294874<br />
PMID 26288981<br />
<br />
Also, another potential sub-heading to research might be the risks involved different ARTs<br />
E.g. the following article about the prevalence of birth defects after a number of different male-related ARTs<br />
PMID 26265143</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=2015_Group_Project_4&diff=1947102015 Group Project 42015-08-21T03:55:43Z<p>Z3462833: </p>
<hr />
<div>{{ANAT2341Project2015header}}<br />
<br />
==Male Infertility==<br />
<br />
'''Major Causes of Infertility:'''<br />
<br />
'''Treatments/Alternative ARTs:'''<br />
<br />
'''Epidemiology:''''''<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:55, 21 August 2015 (AEST)</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=2015_Group_Project_4&diff=1947062015 Group Project 42015-08-21T03:55:15Z<p>Z3462833: </p>
<hr />
<div>{{ANAT2341Project2015header}}<br />
<br />
==Male Infertility==<br />
<br />
'''Major Causes of Infertility:<br />
<br />
Treatments/Alternative ARTs:<br />
<br />
Epidemiology:'''<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:55, 21 August 2015 (AEST)</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=2015_Group_Project_4&diff=1946762015 Group Project 42015-08-21T03:48:00Z<p>Z3462833: </p>
<hr />
<div>{{ANAT2341Project2015header}}<br />
<br />
==Male Infertility==</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=194614User:Z34628332015-08-21T02:44:34Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 12:44, 21 August 2015 (AEST)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=193086User:Z34628332015-08-14T03:38:52Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=193080User:Z34628332015-08-14T03:38:28Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=193074User:Z34628332015-08-14T03:38:09Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:38, 14 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=193058User:Z34628332015-08-14T03:32:46Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
==Lab 2 - Images==<br />
{{Uploading Images in 5 Easy Steps table}}<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=193042User:Z34628332015-08-14T03:31:55Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
==Lab 2 - Images==<br />
<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=193000User:Z34628332015-08-14T03:24:11Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=192818User:Z34628332015-08-14T01:41:01Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
[[Test Student 2015]]<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=192542User:Z34628332015-08-13T12:32:47Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
==Lab 1 Assessment==<br />
'''Article 1'''<br />
<br />
<br />
[[Test Student 2015]]<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=190684User:Z34628332015-08-07T04:02:00Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
[[Test Student 2015]]<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=190638User:Z34628332015-08-07T04:00:52Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
Reference List:<br />
<references/><br />
<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=190614User:Z34628332015-08-07T04:00:06Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref><br />
<pubmed>26244658</pubmed></ref><br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=190582User:Z34628332015-08-07T03:59:29Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref>pubmed>26244658</pubmed></ref><br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=190566User:Z34628332015-08-07T03:59:08Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
look at this<ref>pubmed>26244658</pubmed><ref><br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=190540User:Z34628332015-08-07T03:57:55Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
<pubmed>26244658</pubmed><br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=190524User:Z34628332015-08-07T03:56:26Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
==References==<br />
PMID 26244658<br />
<pubmed>26244658</pubmed><br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=190486User:Z34628332015-08-07T03:55:27Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
==References==<br />
PMID 26244658<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=190472User:Z34628332015-08-07T03:54:53Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
==References==<br />
PMID: 26244658<br />
<br />
==Lab Attendance==<br />
|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3462833&diff=190436User:Z34628332015-08-07T03:54:25Z<p>Z3462833: </p>
<hr />
<div>ANAT2341 - Embryology<br />
<br />
==Lab Attendance==<br />
<br />
==References==<br />
<br />
--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 13:46, 7 August 2015 (AEST)<br />
<br />
{{StudentPage2015}}</div>Z3462833