<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03750370</url>
  </required_header>
  <id_info>
    <org_study_id>doppler in varicocelectomy</org_study_id>
    <nct_id>NCT03750370</nct_id>
  </id_info>
  <brief_title>Color Doppler in Varicocelectomy in Infertile Patient</brief_title>
  <official_title>Role of Colored Doppler Sonography in Evaluation of Testicular Perfusion Before and After Varicocelectomy in Patients With Infertility</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the long-term effects of varicocelectomy on testicular arterial flow via Color&#xD;
      Doppler Sonography Parameters; The arterial flow velocities (peak systolic velocity [PSV] and&#xD;
      end diastolic velocity [EDV]) and the resistance indices against this flow (resistive index&#xD;
      [RI] and pulsatility index [PI]) of the testicular artery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction Varicocele, an abnormal dilatation of the internal spermatic veins, is&#xD;
      considered the major reversible cause of male infertility. It is observed in 35%-40% of all&#xD;
      men with primary infertility and in up to 80% of those with secondary infertility.&#xD;
&#xD;
      The higher incidence of varicocele in men with secondary infertility suggests its progressive&#xD;
      nature, which might be explained by a progressive testicular dysfunction involving both&#xD;
      spermatogenesis and steroidogenesis. The negative impact of varicocele on spermatogenesis has&#xD;
      been documented by a progressive reduction in the size of testicle ipsilateral to the&#xD;
      varicocele.&#xD;
&#xD;
      Semen parameters improvement after varicocele treatment were first reported by Tulloch in the&#xD;
      mid-20th century, who performed high surgical ligation of varicose veins in 30 patients with&#xD;
      infertility. The author showed a marked improvement in postoperative seminal parameters in&#xD;
      66% of the treated subjects.&#xD;
&#xD;
      Several theories have been formulated to explain the testicular impairment caused by&#xD;
      varicocele, including hypoxia, autoimmunity, elevated testicular temperature, reflux of&#xD;
      catecholamine, and increased oxidative stress. However, none of them can completely explain&#xD;
      the variable modulating effect of varicocele on male fertility. Recently, the oxidative&#xD;
      stress theory has emerged as an important contributory factor due to findings of an&#xD;
      association between elevated reactive oxygen species and impaired sperm function in men with&#xD;
      varicocele. Additionally, reduction of oxidative stress markers has been noted after&#xD;
      varicocele repair.&#xD;
&#xD;
      It is hypothesized that impaired venous drainage causes an increase in venous stasis and a&#xD;
      decrease in arterial blood flow, thus inducing hypoxia and deficiency in testicular&#xD;
      microcirculation . Also, it is thought that this hypoxia could be responsible for defective&#xD;
      energy metabolism at mitochondrial levels, causing dysfunction of both Leydig and germinal&#xD;
      cells.&#xD;
&#xD;
      The arterial supply to the human testis has 3 major components: the testicular artery, the&#xD;
      cremasteric artery, and the vasal artery. Two-thirds of total blood is supplied by the&#xD;
      testicular artery. The testicular artery divides into 2 branches in the testis; the capsular&#xD;
      branch continues in the surface of the testis, the intratesticular branch continues in the&#xD;
      parenchyma and deep into the testis.&#xD;
&#xD;
      Colored Doppler Sonography is well established to illustrate microvascularity and therefore&#xD;
      perfusion of the testis. The arterial flow velocities (peak systolic velocity [PSV] and end&#xD;
      diastolic velocity [EDV]) and the resistance indices against this flow (resistive index [RI]&#xD;
      and pulsatility index [PI]) in the testis can be measured with this technique.&#xD;
&#xD;
      The encouraging benefits of varicocele repair to the semen parameters of subfertile men were&#xD;
      ratified by three recent meta-analyses:&#xD;
&#xD;
      Agarwal et al. pooled 17 studies that included only infertile men with clinical varicocele&#xD;
      and with at least one abnormal semen parameter. The intervention was either high ligation of&#xD;
      the veins or subinguinal microsurgical varicocelectomy. There was a consistent improvement in&#xD;
      sperm concentration and motility after both high ligation and microsurgical subinguinal&#xD;
      techniques, with better results after microsurgical approach. Sperm morphology change was not&#xD;
      stratified according to the type of intervention; nevertheless, there was an increment of&#xD;
      3.16% on the average of normal forms.&#xD;
&#xD;
      Baazeem et al. have also evaluated the role of varicocele repair on semen analysis. They&#xD;
      pooled 22 studies of various designs, including meta-analyses as well as randomized and&#xD;
      nonrandomized prospective controlled studies, and analyzed sperm concentration before and&#xD;
      after repair of clinical varicoceles in men with infertility and abnormal semen parameters.&#xD;
      The authors found an overall increase in sperm concentration of 12.32 × 106 ml-1 from before&#xD;
      to after interventions. In their study, sperm motility data were available from 17&#xD;
      prospective studies. Using the random-effects model a combined increment of 10.86% in&#xD;
      motility was demonstrated. They also evaluated five prospective studies reporting the&#xD;
      percentage of progressive motile sperm and confirmed that a significant improvement has&#xD;
      occurred as well. The pooled improvement in progressive sperm motility was 9.69% using the&#xD;
      random-effects model.&#xD;
&#xD;
      Finally, Schauer et al. published a meta-analysis aiming to determine the impact of each type&#xD;
      of intervention; namely, high ligation, inguinal varicocelectomy, and subinguinal&#xD;
      varicocelectomy on the semen parameters of subfertile men. The aforementioned study pooled 14&#xD;
      articles including randomized controlled trials, interventional trials, and cohort studies,&#xD;
      which accounted for 1476 subjects. Inclusion criteria comprised subfertility and/or at least&#xD;
      one abnormal semen parameter, clinical varicocele, and 19 years of age or older. All the&#xD;
      studied techniques led to a significant improvement in sperm count and motility. Only minimal&#xD;
      differences were observed between intervention groups. The higher increment in sperm count&#xD;
      and sperm motility was achieved by inguinal approaches, albeit of no clinical significance&#xD;
      when compared to other techniques. The results of this meta-analysis indicated that&#xD;
      varicocelectomy leads to significant improvements in sperm count and motility regardless of&#xD;
      the chosen surgical technique.&#xD;
&#xD;
      Impaired venous drainage causes an increase in venous stasis and a decrease in arterial blood&#xD;
      flow, thus inducing hypoxia, deficiency in testicular microcirculation and subsequent&#xD;
      accumulation of oxygen free radicals.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Anticipated">April 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluate testicular perfusion before and after varicocelectomy</measure>
    <time_frame>baseline</time_frame>
    <description>Evaluation of testicular perfusion is done by Comparison between Doppler sonographic Parameters Peak systolic velocity ( Cm / sec) , End diastolic velocity ( Cm / sec) , Pulsatility index , And Resistive index Values Before and after varicocelectomy Operation.</description>
  </primary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Varicocelectomy</condition>
  <condition>Doppler</condition>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Doppler ultrasound</intervention_name>
    <description>Colored Doppler Sonography is well established to illustrate microvascularity and therefore perfusion of the testis. The arterial flow velocities (peak systolic velocity [PSV] and end diastolic velocity [EDV]) and the resistance indices against this flow (resistive index [RI] and pulsatility index [PI]) in the testis can be measured with this technique.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Egyptian Population , Random Selection of 50 patients with varicocele in the waiting list&#xD;
        of varicocelectomy either open or laparoscopic approaches&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        • Patients with subfertility in different age groups with either unilateral or bilateral&#xD;
        clinical varicoceles and at least one abnormal semen parameter.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with varicocele with normal semen parameters.&#xD;
&#xD;
          -  Fertile Patients with varicoceles seeking operation only to relieve pain and&#xD;
             heaviness.&#xD;
&#xD;
          -  Patients with recurrent varicoceles after operation.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Mahmoud Mohammad Aly, M.B.B.CH</last_name>
    <phone>00201011367958</phone>
    <email>am.8892@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Eman Abu- EL-Hamd, Professor</last_name>
    <phone>01001980793</phone>
    <email>dr.eman_08@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Faculty of Medicine of Assuit</name>
      <address>
        <city>Assiut</city>
        <zip>71515</zip>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Tarhan S, Ucer O, Sahin MO, Gumus B. Long-term effect of microsurgical inguinal varicocelectomy on testicular blood flow. J Androl. 2011 Jan-Feb;32(1):33-9. doi: 10.2164/jandrol.109.009977. Epub 2010 Jul 29.</citation>
    <PMID>20671143</PMID>
  </reference>
  <reference>
    <citation>Zhang M, Du L, Liu Z, Qi H, Chu Q. The effects of varicocelectomy on testicular arterial blood flow: laparoscopic surgery versus microsurgery. Urol J. 2014 Nov 1;11(5):1900-6.</citation>
    <PMID>25361712</PMID>
  </reference>
  <reference>
    <citation>Akand M, Koplay M, Islamoglu N, Altintas E, Kilic O, Gul M, Kulaksizoglu H, Sivri M, Goktas S. Color Doppler ultrasound characteristics after subinguinal microscopic varicocelectomy. Med Ultrason. 2017 Jan 31;19(1):59-65. doi: 10.11152/mu-920.</citation>
    <PMID>28180198</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>November 18, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>January 18, 2019</last_update_submitted>
  <last_update_submitted_qc>January 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Mahmoud Mohammad Aly</investigator_full_name>
    <investigator_title>Resident</investigator_title>
  </responsible_party>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03750370
org study id: doppler in varicocelectomy
nct id: NCT03750370
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
To evaluate the long-term effects of varicocelectomy on testicular arterial flow via Color
      Doppler Sonography Parameters; The arterial flow velocities (peak systolic velocity [PSV] and
      end diastolic velocity [EDV]) and the resistance indices against this flow (resistive index
      [RI] and pulsatility index [PI]) of the testicular artery.
Introduction Varicocele, an abnormal dilatation of the internal spermatic veins, is
      considered the major reversible cause of male infertility. It is observed in 35%-40% of all
      men with primary infertility and in up to 80% of those with secondary infertility.

      The higher incidence of varicocele in men with secondary infertility suggests its progressive
      nature, which might be explained by a progressive testicular dysfunction involving both
      spermatogenesis and steroidogenesis. The negative impact of varicocele on spermatogenesis has
      been documented by a progressive reduction in the size of testicle ipsilateral to the
      varicocele.

      Semen parameters improvement after varicocele treatment were first reported by Tulloch in the
      mid-20th century, who performed high surgical ligation of varicose veins in 30 patients with
      infertility. The author showed a marked improvement in postoperative seminal parameters in
      66% of the treated subjects.

      Several theories have been formulated to explain the testicular impairment caused by
      varicocele, including hypoxia, autoimmunity, elevated testicular temperature, reflux of
      catecholamine, and increased oxidative stress. However, none of them can completely explain
      the variable modulating effect of varicocele on male fertility. Recently, the oxidative
      stress theory has emerged as an important contributory factor due to findings of an
      association between elevated reactive oxygen species and impaired sperm function in men with
      varicocele. Additionally, reduction of oxidative stress markers has been noted after
      varicocele repair.

      It is hypothesized that impaired venous drainage causes an increase in venous stasis and a
      decrease in arterial blood flow, thus inducing hypoxia and deficiency in testicular
      microcirculation . Also, it is thought that this hypoxia could be responsible for defective
      energy metabolism at mitochondrial levels, causing dysfunction of both Leydig and germinal
      cells.

      The arterial supply to the human testis has 3 major components: the testicular artery, the
      cremasteric artery, and the vasal artery. Two-thirds of total blood is supplied by the
      testicular artery. The testicular artery divides into 2 branches in the testis; the capsular
      branch continues in the surface of the testis, the intratesticular branch continues in the
      parenchyma and deep into the testis.

      Colored Doppler Sonography is well established to illustrate microvascularity and therefore
      perfusion of the testis. The arterial flow velocities (peak systolic velocity [PSV] and end
      diastolic velocity [EDV]) and the resistance indices against this flow (resistive index [RI]
      and pulsatility index [PI]) in the testis can be measured with this technique.

      The encouraging benefits of varicocele repair to the semen parameters of subfertile men were
      ratified by three recent meta-analyses:

      Agarwal et al. pooled 17 studies that included only infertile men with clinical varicocele
      and with at least one abnormal semen parameter. The intervention was either high ligation of
      the veins or subinguinal microsurgical varicocelectomy. There was a consistent improvement in
      sperm concentration and motility after both high ligation and microsurgical subinguinal
      techniques, with better results after microsurgical approach. Sperm morphology change was not
      stratified according to the type of intervention; nevertheless, there was an increment of
      3.16% on the average of normal forms.

      Baazeem et al. have also evaluated the role of varicocele repair on semen analysis. They
      pooled 22 studies of various designs, including meta-analyses as well as randomized and
      nonrandomized prospective controlled studies, and analyzed sperm concentration before and
      after repair of clinical varicoceles in men with infertility and abnormal semen parameters.
      The authors found an overall increase in sperm concentration of 12.32 × 106 ml-1 from before
      to after interventions. In their study, sperm motility data were available from 17
      prospective studies. Using the random-effects model a combined increment of 10.86% in
      motility was demonstrated. They also evaluated five prospective studies reporting the
      percentage of progressive motile sperm and confirmed that a significant improvement has
      occurred as well. The pooled improvement in progressive sperm motility was 9.69% using the
      random-effects model.

      Finally, Schauer et al. published a meta-analysis aiming to determine the impact of each type
      of intervention; namely, high ligation, inguinal varicocelectomy, and subinguinal
      varicocelectomy on the semen parameters of subfertile men. The aforementioned study pooled 14
      articles including randomized controlled trials, interventional trials, and cohort studies,
      which accounted for 1476 subjects. Inclusion criteria comprised subfertility and/or at least
      one abnormal semen parameter, clinical varicocele, and 19 years of age or older. All the
      studied techniques led to a significant improvement in sperm count and motility. Only minimal
      differences were observed between intervention groups. The higher increment in sperm count
      and sperm motility was achieved by inguinal approaches, albeit of no clinical significance
      when compared to other techniques. The results of this meta-analysis indicated that
      varicocelectomy leads to significant improvements in sperm count and motility regardless of
      the chosen surgical technique.

      Impaired venous drainage causes an increase in venous stasis and a decrease in arterial blood
      flow, thus inducing hypoxia, deficiency in testicular microcirculation and subsequent
      accumulation of oxygen free radicals.
observational model: Other
time perspective: Other
measure: Evaluate testicular perfusion before and after varicocelectomy
time frame: baseline
description: Evaluation of testicular perfusion is done by Comparison between Doppler sonographic Parameters Peak systolic velocity ( Cm / sec) , End diastolic velocity ( Cm / sec) , Pulsatility index , And Resistive index Values Before and after varicocelectomy Operation.
intervention type: Device
intervention name: Doppler ultrasound
description: Colored Doppler Sonography is well established to illustrate microvascularity and therefore perfusion of the testis. The arterial flow velocities (peak systolic velocity [PSV] and end diastolic velocity [EDV]) and the resistance indices against this flow (resistive index [RI] and pulsatility index [PI]) in the testis can be measured with this technique.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Mahmoud Mohammad Aly, M.B.B.CH
phone: 00201011367958
email: am.8892@gmail.com
last name: Eman Abu- EL-Hamd, Professor
phone: 01001980793
email: dr.eman_08@yahoo.com
facility: 
status: Recruiting
country: Egypt
citation: Tarhan S, Ucer O, Sahin MO, Gumus B. Long-term effect of microsurgical inguinal varicocelectomy on testicular blood flow. J Androl. 2011 Jan-Feb;32(1):33-9. doi: 10.2164/jandrol.109.009977. Epub 2010 Jul 29.
PMID: 20671143
citation: Zhang M, Du L, Liu Z, Qi H, Chu Q. The effects of varicocelectomy on testicular arterial blood flow: laparoscopic surgery versus microsurgery. Urol J. 2014 Nov 1;11(5):1900-6.
PMID: 25361712
citation: Akand M, Koplay M, Islamoglu N, Altintas E, Kilic O, Gul M, Kulaksizoglu H, Sivri M, Goktas S. Color Doppler ultrasound characteristics after subinguinal microscopic varicocelectomy. Med Ultrason. 2017 Jan 31;19(1):59-65. doi: 10.11152/mu-920.
PMID: 28180198
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Mahmoud Mohammad Aly
investigator title: Resident