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

A Prospective, Randomized, Study of Microsurgical Varicocelectomy Versus Observation in the Treatment of Male Partners With a Palpable Varicocele and an Abnormal Semen Analysis

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.

Study Overview

• Status: Terminated
• Conditions: Infertility; Pregnancy
• Intervention / Treatment: Behavioral: Timed intercourse; Procedure: Intrauterine insemination; Procedure: Microsurgical varicocelectomy

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • New Jersey
    • Newark, New Jersey, United States, 07601
      • University of Medicine and Dentistry of New Jersey
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Pennsylvania State University College of Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • San Antonio, Texas, United States, 78207
      • University of Texas Health Science Center at San Antonio
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: TI; Procedure: Intrauterine insemination; Intrauterine insemination; Other Names: 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 Names: TI; Procedure: Intrauterine insemination; Intrauterine insemination; Other Names: 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 Names: TI; Procedure: Intrauterine insemination; Intrauterine insemination; Other Names: IUI; Procedure: Microsurgical varicocelectomy; Microsurgical varicocelectomy; Other Names: Surgery
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 Names: TI; Procedure: Intrauterine insemination; Intrauterine insemination; Other Names: IUI; Procedure: Microsurgical varicocelectomy; Microsurgical varicocelectomy; Other Names: Surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Live Births After Eight Cycles of Infertility Treatment.	January 2009 to January 2012

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: University of Colorado, Denver; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of Pennsylvania; Wayne State University; University of Michigan; University of Vermont; Penn State University; University of Texas
• Investigators: Principal Investigator: Dana A Ohl, MD, University of Michigan; Study Director: Michael Diamond, MD, Wayne State University; Study Director: William D Schlaff, MD, University of Colorado Denver Health Science Center; Principal Investigator: Gregory M Christman, MD, University of Michigan

Publications and helpful links

General Publications

• Trussell JC, Christman GM, Ohl DA, Legro RS, Krawetz SA, Snyder PJ, Patrizio P, Polotsky AJ, Diamond MP, Casson PR, Coutifaris C, Barnhart K, Brzyski RG, Schlaff WD, Meacham R, Shin D, Thomas T, Zhang M, Santoro N, Eisenberg E, Zhang H; Reproductive Medicine Network. Recruitment challenges of a multicenter randomized controlled varicocelectomy trial. Fertil Steril. 2011 Dec;96(6):1299-305. doi: 10.1016/j.fertnstert.2011.10.025.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: October 3, 2008
• First Submitted That Met QC Criteria: October 6, 2008
• First Posted (Estimate): October 7, 2008

Study Record Updates

• Last Update Posted (Estimate): July 2, 2013
• Last Update Submitted That Met QC Criteria: June 24, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Infertility; Pregnancy; Men; Intrauterine insemination; Palpable varicocele; Abnormal semen analysis; Microsurgical varicocelectomy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Infertility; Varicocele
• Other Study ID Numbers: RMN-VIA; 5U10HD055925-02 (U.S. NIH Grant/Contract); 5U10HD055936 (U.S. NIH Grant/Contract)