Infertility, Pregnancy
Conditions
Keywords
Infertility, Pregnancy, Men, Palpable varicocele, Abnormal semen analysis, Intrauterine insemination, Microsurgical varicocelectomy
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.
Interventions
BEHAVIORALTimed intercourse
Timed intercourse
PROCEDUREMicrosurgical varicocelectomy
Microsurgical varicocelectomy
PROCEDUREIntrauterine insemination
Intrauterine insemination
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Penn State University
University of Colorado, Denver
University of Michigan
University of Pennsylvania
University of Texas
University of Vermont
Wayne State University
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Live Births After Eight Cycles of Infertility Treatment. | January 2009 to January 2012 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| No Surgery + IUI No microsurgical varicocelectomy plus up to four cycles each of alternating intrauterine insemination and timed intercourse starting with intrauterine insemination. | 1 |
| No Surgery + TI No microsurgical varicocelectomy plus up to four cycles each of alternating intrauterine insemination and timed intercourse starting with timed intercourse. | 2 |
| Surgery + IUI Microsurgical varicocelectomy plus up to four cycles each of alternating intrauterine insemination and timed intercourse starting with intrauterine insemination. | 0 |
| Surgery + TI Microsurgical varicocelectomy plus up to four cycles each of alternating intrauterine insemination and timed intercourse starting with timed intercourse. | 0 |
| Total | 3 |
Baseline characteristics
| Characteristic | Total | No Surgery + IUI | No Surgery + TI |
|---|---|---|---|
| Age Categorical <=18 years | 0 participants | 0 participants | 0 participants |
| Age Categorical >=65 years | 0 participants | 0 participants | 0 participants |
| Age Categorical Between 18 and 65 years | 3 participants | 1 participants | 2 participants |
| Age Continuous | 32 years STANDARD_DEVIATION 2 | 30 years STANDARD_DEVIATION 0 | 33 years STANDARD_DEVIATION 1 |
| Gender Female | 0 participants | 0 participants | 0 participants |
| Gender Male | 3 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 3 participants | 1 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 2 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 2 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Live Births After Eight Cycles of Infertility Treatment.
Time frame: January 2009 to January 2012
Population: The participants analyzed correspond to the number of participants who completed the study. In two of the arms, the study was terminated before participants were randomized to those arms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| No Surgery + IUI | Number of Live Births After Eight Cycles of Infertility Treatment. | 0 participants |
| No Surgery + TI | Number of Live Births After Eight Cycles of Infertility Treatment. | 0 participants |