Microsurgical Varicocelectomy Versus No Surgery in Men With a Palpable Varicocele and an Abnormal Semen Analysis (VIA)

This study has been terminated.
(The DSMB recommended stopping the study because of concerns about the dismal recruitment, the drain on network resources, and the need for a study redesign.)
Sponsor:
Collaborators:
Penn State University
University of Colorado, Denver
University of Michigan
University of Pennsylvania
University of Texas
University of Vermont
Wayne State University
Information provided by (Responsible Party):
Heping Zhang, Yale University
ClinicalTrials.gov Identifier:
NCT00767338
First received: October 3, 2008
Last updated: June 24, 2013
Last verified: June 2013
  Purpose

The primary research hypothesis is that microsurgical varicocelectomy will result in an increase in live birth in infertile couples where the male partner has a palpable varicocele and an abnormal semen analysis in comparison to male partners who do not have microsurgical varicocelectomy.

The secondary hypotheses include:

  1. To assess whether up to 4 cycles of intrauterine insemination confers any additional increase in live birth rates compared to timed intercourse;
  2. To examine spousal pregnancy rate as the secondary outcome; and
  3. To study the effect of varicocelectomy in men with infertility, an abnormal semen analysis, and a palpable varicocele on

    • Testicular semen analysis parameters;
    • Serological measures of FSH, LH, total and free testosterone and
    • Measures of quality of life and sexual function in both partners.

Condition Intervention Phase
Pregnancy
Infertility
Behavioral: Timed intercourse
Procedure: Microsurgical varicocelectomy
Procedure: Intrauterine insemination
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Study of Microsurgical Varicocelectomy Versus Observation in the Treatment of Male Partners With a Palpable Varicocele and an Abnormal Semen Analysis

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Number of Live Births After Eight Cycles of Infertility Treatment. [ Time Frame: January 2009 to January 2012 ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: May 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: No surgery + IUI
No microsurgical varicocelectomy plus up to four cycles each of alternating intrauterine insemination and timed intercourse starting with intrauterine insemination.
Behavioral: Timed intercourse
Timed intercourse
Other Name: TI
Procedure: Intrauterine insemination
Intrauterine insemination
Other Name: IUI
Active Comparator: No Surgery + TI
No microsurgical varicocelectomy plus up to four cycles each of alternating intrauterine insemination and timed intercourse starting with timed intercourse.
Behavioral: Timed intercourse
Timed intercourse
Other Name: TI
Procedure: Intrauterine insemination
Intrauterine insemination
Other Name: IUI
Active Comparator: Surgery + IUI
Microsurgical varicocelectomy plus up to four cycles each of alternating intrauterine insemination and timed intercourse starting with intrauterine insemination.
Behavioral: Timed intercourse
Timed intercourse
Other Name: TI
Procedure: Microsurgical varicocelectomy
Microsurgical varicocelectomy
Other Name: Surgery
Procedure: Intrauterine insemination
Intrauterine insemination
Other Name: IUI
Active Comparator: Surgery + TI
Microsurgical varicocelectomy plus up to four cycles each of alternating intrauterine insemination and timed intercourse starting with timed intercourse.
Behavioral: Timed intercourse
Timed intercourse
Other Name: TI
Procedure: Microsurgical varicocelectomy
Microsurgical varicocelectomy
Other Name: Surgery
Procedure: Intrauterine insemination
Intrauterine insemination
Other Name: IUI

Detailed Description:

Study Design

This will be a randomized controlled clinical trial to examine the effect of varicocelectomy in men with infertility, an abnormal semen analysis, and a palpable varicocele. This approach will allow us to compare (i) the effect of microsurgical varicocelectomy on live birth rates after up to four cycles of alternating intrauterine insemination and four cycles of timed intercourse over 8 months and (ii) the relative effectiveness of intrauterine insemination versus timed intercourse on live birth rates. Secondary analyses will explore the effect of the surgical intervention on pregnancy rates, semen analysis parameters, serological hormonal measures in the male subjects, and quality of life measures in both the male and female partners.

Treatment

Two hundred and thirty-two couples will be randomized to the two intervention groups (microsurgical varicocelectomy plus up to four cycles each of alternating intrauterine insemination and timed intercourse or no microsurgical varicocelectomy plus up to four cycles each of alternating intrauterine insemination and timed intercourse).

Timing

We anticipate that it will take 3 years to complete the study. Enrollment will begin in year 1 of the study. 34 couples will need to be recruited per site over the duration of the study to reach the enrollment goal of 232 couples. Participants will be enrolled in the study for one year, with the male partner undergoing periodic study assessments at two month intervals.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 6 months of infertility (primary or secondary - randomization will be stratified to allow equal numbers of primary and secondary infertility couples in the treatment vs. observation group), male partner > 18 years of age and < 50 years of age
  • Female partner > 18 years of age and <= 40 years of age - randomization will be stratified for two groups - female partner <35 and female partner >=35
  • Evidence of a hysterosalpingogram or Saline Infusion Sonogram with one patent tube and regular ovulatory cycles as defined by the recruiting site >25 days and <35 days in duration in the female partner
  • Evidence of a bilateral grade I or unilateral grade II-III varicocele on physical exam in the male partner
  • Abnormal semen analysis as defined by WHO II criteria with a sperm count of >5 X106 /ml or the presence of abnormal strict morphology as defined by Kruger criteria.

Exclusion Criteria:

  • The presence of retrograde ejaculation or uncorrectable ejaculatory dysfunction
  • Decreased ovarian reserve in the female partner as evidence by a day #3 FSH > 12 mIU/ml
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00767338

Locations
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06511
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Wayne State University
Detroit, Michigan, United States, 48201
United States, New Jersey
University of Medicine and Dentistry of New Jersey
Newark, New Jersey, United States, 07601
United States, Pennsylvania
Pennsylvania State University College of Medicine
Hershey, Pennsylvania, United States, 17033
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78207
United States, Vermont
University of Vermont
Burlington, Vermont, United States, 05405
Sponsors and Collaborators
Yale University
Penn State University
University of Colorado, Denver
University of Michigan
University of Pennsylvania
University of Texas
University of Vermont
Wayne State University
Investigators
Study Director: Esther Eisenberg, MD, MPH Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study Chair: Nanette Santoro, MD Albert Einstein College of Medicine of Yeshiva University
Principal Investigator: Gregory M Christman, MD University of Michigan
Principal Investigator: Dana A Ohl, MD University of Michigan
Study Director: Richard Legro, MD Pennsylvania State University College of Medicine
Study Director: Robert Brzyski, MD, PhD The University of Texas Health Science Center at San Antonio
Study Director: Peter Casson, MD University of Vermont
Study Director: Michael Diamond, MD Wayne State University
Study Director: Heping Zhang, PhD Yale University
Study Director: Christos Coutifaris, MD University of Pennsylvania
Study Director: William D Schlaff, MD University of Colorado Denver Health Science Center
  More Information

No publications provided by Yale University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Heping Zhang, Principal Investigator, Yale University
ClinicalTrials.gov Identifier: NCT00767338     History of Changes
Other Study ID Numbers: RMN-VIA, 5U10HD055925-02, 5U10HD055936
Study First Received: October 3, 2008
Results First Received: December 12, 2012
Last Updated: June 24, 2013
Health Authority: United States: Federal Government

Keywords provided by Yale University:
Infertility
Pregnancy
Men
Palpable varicocele
Abnormal semen analysis
Intrauterine insemination
Microsurgical varicocelectomy

Additional relevant MeSH terms:
Infertility
Varicocele
Genital Diseases, Male
Genital Diseases, Female
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 21, 2014