Clinical trial NCT00767338: Microsurgical Varicocelectomy Versus No Surgery in Men With a Palpable Varicocele and an Abnormal Semen Analysis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pregnancy
Infertility
Keywords: Infertility
Pregnancy
Men
Palpable varicocele
Abnormal semen analysis
Intrauterine insemination
Microsurgical varicocelectomy
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Penn State University
name: University of Colorado, Denver
name: University of Michigan
name: University of Pennsylvania
name: University of Texas
name: University of Vermont
name: Wayne State University
First posted: 2008-10-07
Enrollment: 3
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Number of Live Births After Eight Cycles of Infertility Treatment.
timeFrame: January 2009 to January 2012
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Newark
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: Hershey
country: United States
facility: Pennsylvania State University College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
Study officials:
affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Esther Eisenberg, MD, MPH
role: STUDY_DIRECTOR
affiliation: Albert Einstein College of Medicine
name: Nanette Santoro, MD
role: STUDY_CHAIR
affiliation: University of Michigan
name: Gregory M Christman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Dana A Ohl, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pennsylvania State University College of Medicine
name: Richard Legro, MD
role: STUDY_DIRECTOR
affiliation: The University of Texas Health Science Center at San Antonio
name: Robert Brzyski, MD, PhD
role: STUDY_DIRECTOR
affiliation: University of Vermont
name: Peter Casson, MD
role: STUDY_DIRECTOR
affiliation: Wayne State University
name: Michael Diamond, MD
role: STUDY_DIRECTOR
affiliation: Yale University
name: Heping Zhang, PhD
role: STUDY_DIRECTOR
affiliation: University of Pennsylvania
name: Christos Coutifaris, MD
role: STUDY_DIRECTOR
affiliation: University of Colorado Denver Health Science Center
name: William D Schlaff, MD
role: STUDY_DIRECTOR
References:
citation: 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.