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.

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 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.

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