Benjamin N. Hendin

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.

MICROSURGICAL REPAIR OF IATROGENIC INJURY TO THE VAS DEFERENS

PURPOSE We determined the incidence of iatrogenic injuries to the vas deferens at a tertiary care university infertility center and the results of surgical repair. MATERIALS AND METHODS Records of 472 patients surgically explored for obstructive azoospermia between 1984 to 1996 were reviewed. Enrollment criteria included history of inguinal, pelvic and scrotal (other than vasectomy) surgery. Conventional ipsilateral and crossover vasovasostomies and vasoepididymostomies were performed. Patency rate was defined as presence of complete sperm with tails in a postoperative semen analysis. Followup included a minimum of 2 semen analyses. Only naturally conceived pregnancies were included. RESULTS Of 472 patients 34 (7.2%) had an iatrogenic injury to the vas deferens with a mean obstruction interval of 20.5 +/- 1.9 years. Mean patient age was 36.7 +/- 1.8 years. Iatrogenic injury to the vas deferens was secondary to bilateral inguinal hernia repair in 19 patients, unilateral hernia repair in 11, renal transplantation in 2, appendectomy in 1 and spermatocelectomy in 1. Pediatric inguinal hernia repair was the most common etiology of the vasal injury (20 patients), followed by adult inguinal hernia repair (10). A total of 36 microsurgical reconstructive procedures were performed, including 20 ipsilateral and 16 crossed vasovasostomies and vasoepididymostomies. There were 26 patients (29 procedures) available for followup (mean 21.0 +/- 3.7 months). Total patency rate per procedure was 65% and pregnancy rate was 39%. Patency and pregnancy rates per conventional ipsilateral procedures were 62.5 and 35.7% and per crossover procedures 64.2 and 42.8%, respectively. CONCLUSIONS Pediatric inguinal hernia repair is the most common cause of iatrogenic injury to the vas deferens. Results of treatment of iatrogenic injury to the vas deferens are somewhat lower than for patients with obstructive azoospermia due to vasectomy. Iatrogenic injuries are associated with longer vasal defects, impaired blood supply and longer obstructive intervals frequently resulting in secondary epididymal obstruction. Crossover reconstruction is particularly useful when contralateral testicular atrophy is present. Intraoperatively aspirated sperm should be cryopreserved for later use in case the reconstruction fails.

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.

IMPACT OF DIAGNOSTIC URETEROSCOPY ON LONG-TERM SURVIVAL IN PATIENTS WITH UPPER TRACT TRANSITIONAL CELL CARCINOMA

PURPOSE We determine whether diagnostic retrograde ureteroscopy for evaluation of upper tract transitional cell carcinoma adversely affects survival outcomes in terms of urothelial and metastatic tumor recurrence, and tumor-free and overall survival. MATERIALS AND METHODS A total of 96 patients underwent total nephroureterectomy or resection of the distal ureter with a bladder cuff for upper tract transitional cell carcinoma. Of the patients 48 (study group) had undergone preoperative diagnostic ureteroscopy while 48 (control group) had not. Grade and stage of disease were compared, and time to recurrence, and disease-free and overall survival were analyzed. RESULTS Grade and stage of disease were equivalent in both groups. There were no significant differences in recurrence rates, time to recurrence or mortality between the groups. Metastases developed in 9 patients (18.8%) in the control group and 6 (12.5%) in the study group (p = 0.58), while 5 (10.4%) in each group died of metastases of upper tract carcinoma (p = 1.00). Kaplan-Meier estimates were 0.67 and 0.71 for metastasis-free survival at 5 years (p = 0.25, not significant) and 0.87 and 0.76 for overall 5-year survival (p = 0.75, not significant) for the study and control groups, respectively. CONCLUSIONS Diagnostic ureteroscopy has no clinically apparent adverse effect on long-term or disease specific survival of patients with upper tract transitional cell carcinoma who subsequently undergo standard definitive surgical management.

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.

The effect of patient and semen characteristics on live birth rates following intrauterine insemination: a retrospective study.

AbstractPurpose: To identify characteristics of female patients andof semen that were associated with live birth followingintra-uterine insemination (IUI). Methods: Retrospective review of medical and laboratoryresults from 533 women who underwent IUI with partnerssperm from 1993 through 1995. Results: Among 1728 cycles, 116 (6.7%) resulted in livedeliveries. Among the 38 patient and semen variablesanalyzed, only 3 were associated with successful IUI outcome:female age <37.7 years at the time of treatment (P = 0.02);the absence of any corrective pelvic surgery (P < 0.001);and postwash sperm motility (P = 0.006). Couples withnone of these three risk factors achieved per-cycle pregnancyrates of 12.4%. Women with two risk factors (age and pelvicsurgery) achieved per-cycle pregnancy rates of 4.6% whensperm had good postwash motility. No pregnancies wereachieved when low postwash motility was combined withany other risk factor. Conclusions: Advanced female age, poor postwash spermmotility, and a history of corrective pelvic surgery aresignificant risk factors for poor IUI success rates. Poor postwashsperm motility in combination with either of these other tworisk factors resulted in no successful pregnancies.

Relationship of total motile sperm count and percentage motile sperm to successful pregnancy rates following intrauterine insemination

Purpose:This study sought (i) to investigate the relationship between postwash total motile sperm count and postwash percentage motile sperm in predicting successful intrauterine insemination and (ii) to determine the minimal postwash total motile sperm count required to achieve pregnancy with intrauterine insemination.Methods:Five hundred four women, who underwent 1636 intrauterine insemination cycles with their partners sperm for infertility treatment from 1993 through 1995, were included in this retrospective study. All patient charts were reviewed for age, infertility etiology, ovarian stimulation regimens, semen characteristics, and treatment outcome. To determine the relationship between total motile sperm count and intrauterine insemination outcome, patients were grouped as (1) less than 0.5 million, (2) 0.5 to 1 million, (3) 1 to 5 million, (4) greater than 5 million, and (5) greater than 20 million.Results:Similar live birth rates (per cycle) were seen among the postwash total motile sperm count groups: group 1, 3.5%; group 2, 2.4%; group 3, 7.0%; group 4, 6.9%; and group 5, 7.0% (P = 0.37). However, regardless of the postwash total motile sperm count, the postwash motility predicted intrauterine insemination success at a cutoff value of 40%.Conclusions:The percentage of postwash sperm motility, and not the postwash total motile sperm count, can predict successful intrauterine insemination outcome. Such information can be useful in counseling patients regarding their chance of success with intrauterine insemination and in determining when alternate methods of assisted reproduction may be a better approach.

Effect of Clinical and Semen Characteristics on Efficacy of Ovulatory Stimulation in Patients Undergoing Intrauterine Insemination

AbstractPurpose: We measured the effect of ovulatory stimulation(OS) upon intrauterine insemination (IUI) success rates,particularly among patients with risk factors for IUI failure. Methods: Retrospective review of medical and laboratoryresults from 512 patients who underwent 1576 cycles ofIUI with partners sperm over a 3 year period. Data werecollected on 3 risk factors for IUI failure (advanced femaleage >37.7 years, prior corrective pelvic surgery, and poorpost-wash sperm motility), and on method of OS (none,clomiphene citrate, or gonadotropin). Results: Patients who underwent OS had significantly higherpregnancy rates (7.6;pc) than those who did not (4.7%, p =0.02). However, when patients were stratified by their riskfactors, OS made a significant difference only for patientswithout risk factors. These patients had a 15.5% per cyclepregnancy rate with OS, compared to 7.9% in unstimulatedIUI cycles (p = 0.04). Conclusions: Ovulatory stimulation doubles IUI pregnancyrates among young patients without a prior pelvic surgeryand with good post-wash semen quality. The benefit of OSfor patients with risk factors for IUI failure is unclear. Thesepatients should be counseled that their chances for successwith IUI are limited, with or without OS.

Identification of Spermatozoa and Round Spermatids in the Ejaculates of Men with Spermatogenic Failure

OBJECTIVES As many as 10% of infertile men have azoospermia caused by spermatogenic failure or ductal obstruction. The histologic diagnoses associated with spermatogenic failure--Sertoli cell-only syndrome, maturation arrest, and hypospermatogenesis--do not necessarily represent global changes in the affected testis, as occasional seminiferous tubules may still produce mature germ cells. Intracytoplasmic sperm injection (ICSI) allows individual sperm that have been isolated from testicular tissue to fertilize oocytes. This study assessed whether mature germ cells (either round spermatids or spermatozoa) were present in the ejaculates of patients with spermatogenic failure. METHODS All semen analyses performed at our tertiary care institution from January 1993 through December 1995 were reviewed to identify azoospermic men with spermatogenic failure. During this period, our laboratory employed Nuclear-Fast Red and picroindigocarmine staining (NF-PICS) of cytospin slides to identify rare spermatozoa and spermatids in otherwise azoospermic ejaculates. RESULTS Of 3005 analyses reviewed, 20 azoospermic men whose infertility was solely attributable to spermatogenic failure were identified. The histologic diagnoses were germinal cell aplasia (n = 7), complete maturation arrest (n = 6), incomplete maturation arrest (n = 3), and hypospermatogenesis (n = 4). Using the NF-PICS technique, mature germ cells were identified in the ejaculates of 15 men (75%), and 9 men (45%) had fully formed spermatozoa present. CONCLUSIONS In the clinical management of azoospermic infertile men, the NF-PICS technique may be used to identify men who have some degree of testicular spermatogenesis. This might obviate the need for the purely diagnostic testis biopsy that is performed before therapeutic biopsy for testicular sperm extraction in conjunction with ICSI.