IVF Outcomes After Varicocele Repair
Primary Purpose
Infertility, Male, Varicocele, In Vitro Fertilization
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Varicocele embolization
Sponsored by
About this trial
This is an interventional treatment trial for Infertility, Male
Eligibility Criteria
Inclusion Criteria:
Patient complies to varicocele treatment indications as per ASRM 2014 guidelines
- Palpable varicocele on physical exam
- The female partner has normal fertility or a potentially treatable cause of infertility
- Male has abnormal semen parameters
Age of female partner < 35 years
Exclusion Criteria:
Sub-clinical varicocele
Isolated teratospermia
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
Varicocele embolization before IVF
IVF without varicocele embolization
Arm Description
Participants will have catheterization and embolization of varicoceles six months before beginning IVF
Participants will proceed from enrollment directly to IVF
Outcomes
Primary Outcome Measures
Live birth rate
The percentage of embryo transfers resulting in a live birth
Secondary Outcome Measures
Pregnancy rate
The percentage of embryo transfers resulting in a clinical pregnancy ((ultrasound visualization of a gestational sac with heartbeat)
Transfers per clinical pregnancy
Total transfers divided by total clinical pregnancies (excluding natural pregnancies) for each study group
Transfers per live birth
Total transfers divided by total live births (excluding natural pregnancies) for each study group
Ongoing pregnancy rate
Number of pregnancies (including natural) at 3 month time intervals
Ongoing live birth rate
Number of live births (including natural) at 3 month time intervals
Full Information
NCT ID
NCT03090438
First Posted
March 20, 2017
Last Updated
March 23, 2017
Sponsor
Shaare Zedek Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03090438
Brief Title
IVF Outcomes After Varicocele Repair
Official Title
The Effect of Preliminary Varicocele Repair on IVF Outcomes in Male Factor Infertility
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Unknown status
Study Start Date
May 2017 (Anticipated)
Primary Completion Date
May 2020 (Anticipated)
Study Completion Date
May 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shaare Zedek Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Infertility has been estimated to affect from 6-18% of couples trying to conceive. In 20-30% of cases, the problem is with the male. Varicocele is a common cause of male factor infertility (MFI) being responsible for 30-35 % of primary and 69-81 % of secondary MFI. Varicocele repair has been shown to improve sperm parameters and increase natural pregnancy rates and the results of assisted reproductive techniques (ART).
There are two possible treatment pathways for varicocele associated male factor infertility. 1) standard IVF/ICSI 2) varicocele repair followed by IVF/ICSI if there is no spontaneous pregnancy. There is however no consensus as to which pathway is preferable and no randomized comparative studies have been carried out.
IVF/ICSI is a standard treatment for infertility but frequently requires repeated treatments to achieve a live birth. The purpose of this study is to determine if the improved sperm parameters caused by prior treatment of the varicocele will result in improvements both in overall pregnancy/birth rates and in IVF/ICSI results.
Detailed Description
A varicocele is an abnormal dilation of the pampiniform plexus caused by incompetence of the valves in the internal spermatic vein. Varicocele has a prevalence of 10-15 % in the general population and is a common cause of male infertility, being present in 30-35% of men with primary, and 69-81% of men with secondary infertility. There is more than one approach to the treatment of varicocele associated MFI One common approach is to treat by assisted reproductive techniques (ART). Patients with a total motile sperm count of <10 million sperm are usually treated by IVF with or without ICSI. Fertilization of oocytes may be accomplished by isolating even a single adequate spermatozoa in the laboratory bypassing the majority of semen quality inadequacies in male factor infertility. The results of this treatment using fresh embryos with a maternal age of<35 are 46% pregnancies and 40% live births per cycle.
Alternatively, varicocele associated MFI can be treated by repairing the varicocele to improve sperm quality. Occlusion of the spermatic veins by surgical and radiological methods is commonly performed in these circumstances to improve fertility. A large body of literature exists demonstrating post-treatment improvements in semen parameters and sperm DNA quality as well as improved spontaneous pregnancy rates compared to no treatment. There are also studies demonstrating improved results of ART after varicocele repair.
Both approaches have their advocates. ART often provide a relatively quick result and have a known excellent track record for both pregnancy and live birth rates. Unfortunately, these techniques are not without risks such as ovarian hyperstimulation syndrome and procedural complications. Multiple pregnancies are common with increased risk of premature labour and low birth weight. In addition the treatments are expensive and multiple treatments increase the financial burden on the health care system.
Varicocele occlusion is a minor procedure. If performed radiologically, there is often immediate return to normal activity. The complication rate is very low, mostly due to radiological contrast medium allergy. Modern equipment and careful technique enable the procedure to be completed with very low radiation doses that are well below the level proven to have any adverse biological effect.
If varicocele repair can be demonstrated to improve pregnancy outcomes in varicocele related MFI by spontaneous pregnancies or by improving pregnancy and live birth rates per ART implantation, then there are compelling health care and economic reasons for incorporating it as an initial treatment.
At present there have been no well constructed randomized trials to compare the outcomes of these two approaches.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility, Male, Varicocele, In Vitro Fertilization
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
250 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Varicocele embolization before IVF
Arm Type
Active Comparator
Arm Description
Participants will have catheterization and embolization of varicoceles six months before beginning IVF
Arm Title
IVF without varicocele embolization
Arm Type
No Intervention
Arm Description
Participants will proceed from enrollment directly to IVF
Intervention Type
Procedure
Intervention Name(s)
Varicocele embolization
Other Intervention Name(s)
Varicocele repair, Varicocele occlusion
Intervention Description
Ultrasound guided right internal jugular vein access with placement of a vascular sheath. Fluoroscopically guided selective catheterization of the left and right (if bilateral) spermatic veins to the level of the inguinal ligament. Occlusion of the spermatic vein(s) by embolization coils and a sclerosing agent (sodium tetradecyl sulphate 3%).
Primary Outcome Measure Information:
Title
Live birth rate
Description
The percentage of embryo transfers resulting in a live birth
Time Frame
25 months
Secondary Outcome Measure Information:
Title
Pregnancy rate
Description
The percentage of embryo transfers resulting in a clinical pregnancy ((ultrasound visualization of a gestational sac with heartbeat)
Time Frame
18 months
Title
Transfers per clinical pregnancy
Description
Total transfers divided by total clinical pregnancies (excluding natural pregnancies) for each study group
Time Frame
18 months
Title
Transfers per live birth
Description
Total transfers divided by total live births (excluding natural pregnancies) for each study group
Time Frame
25 months
Title
Ongoing pregnancy rate
Description
Number of pregnancies (including natural) at 3 month time intervals
Time Frame
18 months
Title
Ongoing live birth rate
Description
Number of live births (including natural) at 3 month time intervals
Time Frame
25 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Patient complies to varicocele treatment indications as per ASRM 2014 guidelines
Palpable varicocele on physical exam
The female partner has normal fertility or a potentially treatable cause of infertility
Male has abnormal semen parameters
Age of female partner < 35 years
Exclusion Criteria:
Sub-clinical varicocele
Isolated teratospermia
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anthony G Verstandig, MD
Phone
972 508685879
Email
anthonyv@szmc.org.il
First Name & Middle Initial & Last Name or Official Title & Degree
Ruth Ronn, MD
Phone
972 549964878
Email
RuthRonn@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anthony G Verstandig, MD
Organizational Affiliation
C
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ruth Ronn, MD
Organizational Affiliation
V
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
8458466
Citation
Gorelick JI, Goldstein M. Loss of fertility in men with varicocele. Fertil Steril. 1993 Mar;59(3):613-6.
Results Reference
background
PubMed Identifier
17905111
Citation
Agarwal A, Deepinder F, Cocuzza M, Agarwal R, Short RA, Sabanegh E, Marmar JL. Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach. Urology. 2007 Sep;70(3):532-8. doi: 10.1016/j.urology.2007.04.011.
Results Reference
background
PubMed Identifier
21435155
Citation
Diegidio P, Jhaveri JK, Ghannam S, Pinkhasov R, Shabsigh R, Fisch H. Review of current varicocelectomy techniques and their outcomes. BJU Int. 2011 Oct;108(7):1157-72. doi: 10.1111/j.1464-410X.2010.09959.x. Epub 2011 Mar 24.
Results Reference
background
PubMed Identifier
25523457
Citation
Verstandig AG, Shamieh B, Shraibman V, Raveh D. Radiation dose reduction in fluoroscopic procedures: left varicocele embolization as a model. Eur Radiol. 2015 Jun;25(6):1639-45. doi: 10.1007/s00330-014-3556-4. Epub 2014 Dec 19.
Results Reference
background
PubMed Identifier
26510504
Citation
Esteves SC, Roque M, Agarwal A. Outcome of assisted reproductive technology in men with treated and untreated varicocele: systematic review and meta-analysis. Asian J Androl. 2016 Mar-Apr;18(2):254-8. doi: 10.4103/1008-682X.163269.
Results Reference
background
PubMed Identifier
24175046
Citation
Kim KH, Lee JY, Kang DH, Lee H, Seo JT, Cho KS. Impact of surgical varicocele repair on pregnancy rate in subfertile men with clinical varicocele and impaired semen quality: a meta-analysis of randomized clinical trials. Korean J Urol. 2013 Oct;54(10):703-9. doi: 10.4111/kju.2013.54.10.703. Epub 2013 Oct 15.
Results Reference
background
PubMed Identifier
22425089
Citation
Schauer I, Madersbacher S, Jost R, Hubner WA, Imhof M. The impact of varicocelectomy on sperm parameters: a meta-analysis. J Urol. 2012 May;187(5):1540-7. doi: 10.1016/j.juro.2011.12.084. Epub 2012 Mar 14.
Results Reference
background
PubMed Identifier
22979920
Citation
Li F, Yamaguchi K, Okada K, Matsushita K, Ando M, Chiba K, Yue H, Fujisawa M. Significant improvement of sperm DNA quality after microsurgical repair of varicocele. Syst Biol Reprod Med. 2012 Oct;58(5):274-7. doi: 10.3109/19396368.2012.692431. Epub 2012 Jul 2.
Results Reference
background
PubMed Identifier
1601152
Citation
The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. World Health Organization. Fertil Steril. 1992 Jun;57(6):1289-93.
Results Reference
background
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IVF Outcomes After Varicocele Repair
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