Anthony J. Thomas

VARICOCELE IS ASSOCIATED WITH ELEVATED SPERMATOZOAL REACTIVE OXYGEN SPECIES PRODUCTION AND DIMINISHED SEMINAL PLASMA ANTIOXIDANT CAPACITY

PURPOSE Because varicocele is seen often in infertile men and oxidative stress has been implicated in sperm dysfunction, we assessed spermatozoal reactive oxygen species and seminal total antioxidant capacity in men with and without varicocele. MATERIALS AND METHODS Levels of reactive oxygen species and total antioxidant capacity were measured in the semen of 21 infertile men with varicocele, 15 men with incidential varicocele and 17 normal donors without varicocele (controls). Men with leukocytospermia (more than 1 x 10(6) white blood cells per ml.) were excluded from study. Reactive oxygen species were measured in washed spermatozoa with a luminol dependent chemiluminescence assay. Total seminal antioxidant capacity was measured with an enhanced chemiluminescence assay, and the results were expressed as trolox equivalents. Sperm characteristics were assessed with a computer assisted semen analyzer, and sperm morphology was assessed using World Health Organization and Krugers strict criteria. RESULTS Patients with varicocele had significantly higher reactive oxygen species levels than controls (p = 0.02). Reactive oxygen species levels did not differ significantly between infertile and men with incidental varicocele. Total antioxidant levels were significantly lower among men with varicocele (p = 0.02) and those with incidental varicocele compared to controls (p = 0.05). Reactive oxygen species and total antioxidant capacity levels did not correlate in any group. CONCLUSIONS Our results suggest that elevated reactive oxygen species and depressed total antioxidant capacity levels are associated with varicocele. These changes may be related to functional sperm abnormalities and infertility seen commonly in these patients. These findings support a possible rationale for controlled clinical trials of antioxidant supplementation in infertile men with varicocele.

VARICOCELECTOMY IMPROVES INTRAUTERINE INSEMINATION SUCCESS RATES IN MEN WITH VARICOCELE

PURPOSE We determined whether varicocele treatment before intrauterine insemination significantly affects intrauterine insemination success rates. MATERIALS AND METHODS A total of 58 infertile couples, of whom the women had normal evaluations and men had abnormal semen analyses and a history of varicocele, were included in this study. They were identified after reviewing the charts of all women undergoing intrauterine insemination for male factor infertility at our center. Of the men 24 participated in 63 intrauterine insemination cycles without varicocele treatment, while in the remaining 34 varicocele was treated before a total of 101 intrauterine insemination cycles. Variables associated with pregnancy or live birth were analyzed using repeat measures logistic regression with generalized estimating equation techniques. An initial stepwise generalized estimating equation was performed without including varicocele treatment status. Subsequently varicocele treatment status and the significant associated factors were included in analysis. The semen characteristics of untreated and treated varicocele groups were compared with repeat measures analysis of variance. RESULTS On pre-wash semen analysis patients with untreated varicocele had significantly higher mean motility plus or minus standard error than patients whose varicoceles were treated (48.6% +/- 2.3% versus 38.1% +/- 1.8%, p = 0.02). However, no statistically significant difference was noted in the mean post-wash total motile sperm count in the treated and untreated groups (7.2 +/- 1.0 versus 14.8 +/- 2.6, p = 0.1). Despite these findings the pregnancy and live birth rates per cycle were significantly higher in patients in whom varicocele was treated than in those without varicocele treatment (11.8% versus 6.3%, p = 0.04 and 11.8% versus 1.6%, p = 0.007, respectively). CONCLUSIONS Varicocele treatment may not improve semen characteristics in all men but it appears to improve pregnancy and live birth rates among couples undergoing intrauterine insemination for male factor infertility. A functional factor not measured on routine semen analysis may affect pregnancy rates in this setting. Men should be screened for varicocele before intrauterine insemination is initiated for male factor infertility.

VASECTOMY REVERSAL FOR THE POST-VASECTOMY PAIN SYNDROME: : A CLINICAL AND HISTOLOGICAL EVALUATION

PURPOSE The cause of the post-vasectomy pain syndrome is unclear. Some postulated etiologies include epididymal congestion, tender sperm granuloma and/or nerve entrapment at the vasectomy site. To our knowledge nerve proliferation has not been evaluated previously as a cause of pain. Vasectomy reversal is reportedly successful for relieving pain in some patients. We report our experience and correlate histological findings in resected vasal segments with outcome to explain the mechanism of pain in these patients. MATERIALS AND METHODS We retrospectively reviewed the records of 13 men who underwent vasectomy reversal for the post-vasectomy pain syndrome. We compared blinded histological evaluations of the vasal ends excised at vasectomy reversal in these patients with those of pain-free controls who underwent vasectomy reversal to reestablish fertility. Controls were matched to patients for the interval since vasectomy. Histological features were graded according to the degree of severity of vasitis nodosum, chronic inflammation and nerve proliferation. RESULTS Mean time to pain onset after vasectomy was 2 years. Presenting symptoms included testicular pain in 9 cases, epididymal pain in 2, pain at ejaculation in 4 and pain during intercourse in 8. Physical examination demonstrated tender epididymides in 6 men, full epididymides in 6, a tender vasectomy site in 4 and a palpable nodule in 4. No patient had testicular tenderness on palpation. Unilateral and bilateral vasovasostomy was performed in 3 and 10 of the 13 patients, respectively. Postoperatively 9 of the 13 men (69%) became completely pain-free. Mean followup was 1.5 years. We observed no differences in vasectomy site histological features in patients with the post-vasectomy pain syndrome and matched controls, and no difference in histological findings in patients with the post-vasectomy pain syndrome who did and did not become pain-free postoperatively. CONCLUSIONS No histological features aid in identifying a cause of pain or provide prognostic value for subsequent pain relief. Vasectomy reversal appeared to be beneficial for relieving pain in the majority of select patients with the post-vasectomy pain syndrome.

INVESTIGATION OF FERTILIZING CAPACITY OF CRYOPRESERVED SPERMATOZOA FROM PATIENTS WITH CANCER

PURPOSE There are few published reports concerning fertilization and pregnancy outcomes achieved with cryopreserved spermatozoa from cancer patients. Controversy exists regarding the value of sperm banking for these patients before therapy, whether the spermatozoa are viable after long-term storage and whether they can fertilize the ovum. We assess fertilization and pregnancy outcomes achieved with cryopreserved spermatozoa from cancer patients using assisted reproductive techniques. MATERIALS AND METHODS We studied 10 cancer patients who transferred cryopreserved semen specimens from our sperm bank to outside in vitro fertilization programs for assisted reproductive technique. Of these patients 5 had Hodgkins disease, 2 testicular cancer, 1 leukemia and 2 prostate cancer. The length of specimen storage ranged from 14 to 135 months (median 49, interquartile range 24 and 82). RESULTS The median pre-freeze motility was 44% (interquartile range 36 and 55%) and the median total sperm count was 31.1 x 10(6) (interquartile range 6.3 and 53.9 x 10(6)). At 24 hours after banking the median post-thaw motility was 11% (interquartile range 6 and 35%) and the median total sperm count was 6.6 x 10(6) (1.2 and 17.1 x 10(6)). A total of 18 cycles of assisted reproductive technique were performed among 10 couples with an overall pregnancy rate of 50% per couple, with 2 deliveries, 1 ongoing pregnancy and 2 miscarriages. The pregnancy rate per cycle of in vitro fertilization and intracytoplasmic sperm injection was 36.4% with an implantation rate of 13%. CONCLUSIONS These results indicate that poor quality cryopreserved spermatozoa from cancer patients, irrespective of the length of storage, may provide successful results with the latest micromanipulative techniques such as intracytoplasmic sperm injection.

Intraoperative Observations During Vasovasostomy in 334 Patients

This initial report from the Vasovasostomy Study Group concerns intraoperative data obtained during vasovasostomy from 639 vasa in 334 patients. These data are related to the obstructive interval (time from vasectomy to vasovasostomy) and to the presence or absence of histologically proved sperm granuloma at the old transected testicular end of the vas (vasectomy site). Rates of sperm absence from vas fluid at the testicular end increased with longer obstructive intervals and with absence of a sperm granuloma. If sperm were present in fluid at the testicular end of the vas, the quality was poorer when the obstructive interval lengthened and when sperm granuloma was absent. Vas luminal diameters at the testicular end were smaller when a sperm granuloma was present. These observations support the theory that a sperm granuloma at the vasectomy site may have a beneficial, pressure-releasing effect that could be favorable prognostically for fertility after vasovasostomy.

Transient fertility after vasovasostomy in 892 patients.

We report on the low incidence of transient fertility in 892 patients who underwent microsurgical vasovasostomy. Of the 892 patients in whom fertile sperm concentrations (as defined by us) developed 2 to 8 months postoperatively 28 later suffered azoospermia or severe oligospermia. The wives of 5 of the 28 patients with such transient postoperative fertility became pregnant before the patients became azoospermic or severely oligospermic again.

1583: Identifying Infertile Men with Male-Factor Infertility with a Novel Semen Quality (SQ) Score

Introduction and Objective: Semen analysis constitutes the main component in the evaluation of male infertility. Semen Quality (SQ) score has been demonstrated as a better predictor of semen quality compared to the individual characteristics of sperm. The purpose of this study was to determine whether infertile patients with male-factor infertility (MFI) could be accurately identified using a well-defined SQ score. Methods: The study included results from 124 MFI patients. Healthy male volunteers with normal semen parameters (n = 70), according to World Health Organization guidelines, were used as controls. Manual semen analysis was performed and sperm motion kinetics were assessed using a computer assisted semen analyzer (CASA, IVOS, 10.7s, Hamilton Thorne Research, Beverly, Mass). Principal component analysis model was used to calculate SQ score that accounts for most of the variability observed among the battery of interrelated semen variables. Base 10 logarithms of nine sperm parameters (concentration, motility, sperm morphology according to WHO guidelines and Tygerbergs strict criteria, VCL, VSL, VAP, LIN, and ALH) were used. Results: In donors, the mean and standard deviation of SQ score was 99.39 ± 9 compared to 75.57 ± 18.55 in MFI patients (P< 0.0001). Amongst the patient population, 93% of men had SQ score <100, while 7% (9/133) had a SQ score >100. SQ score had a sensitivity of >93% when a cutoff of 100 was used, i.e. SQ score was able to correctly identify 93% of the patients as being MFI patients. The overall accuracy in identifying the donors and patients was 77%. Using a cutoff value of 95 and 90, the accuracy was 79% and 79% but there was a decrease in sensitivity. Conclusions: SQ score derived from patient’s semen analysis may be an easy and effective tool for clinicians in the initial evaluation of patients being examined for their infertility problem. Various predictors of semen quality in donors and MFI patients using different cutoff values of SQ