Peter N. Kolettis

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.

Vasoepididymostomy for Vasectomy Reversal: A Critical Assessment in the Era of Intracytoplasmic Sperm Injection

PURPOSE We compared vasoepididymostomy to microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection for treatment of epididymal obstruction secondary to vasectomy. MATERIALS AND METHODS Results in patients who underwent vasoepididymostomy for vasectomy reversal at our institution were compared to those reported previously for microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection performed for obstructive azoospermia. The pregnancy rates, delivery rates, complications, cost per procedure and cost per delivery were compared. A cost per newborn analysis was performed using pregnancy and delivery rates, and reported cost estimates for the complications of assisted reproductive techniques. RESULTS A total of 55 men underwent 58 vasoepididymostomies in an attempt to restore fertility after vasectomy. Median followup was 19 months (range 0 to 115). Median obstructive interval was 12 years. There were no major complications. The patency rate after 6 months was 85%. Of the couples 20 achieved 24 pregnancies and 16 had 17 live births. The pregnancy rate at 1 year was 44%. There were 4 miscarriages and there are 3 ongoing pregnancies. The live delivery rate was 36%. Assuming a 29% delivery rate for microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection, the cost per newborn was

Sperm cryopreservation in patients with testicular cancer.

51,024, compared to

Effect of seminal oxidative stress on fertility after vasectomy reversal

31,099 for vasoepididymostomy. CONCLUSIONS Vasoepididymostomy is more successful and more cost-effective than microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection for vasectomy reversal. It does not expose the women to complications in the treatment of a male problem and it is indicated for treatment of epididymal obstruction secondary to vasectomy. Microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection should be reserved for cases not amenable to surgical reconstruction.

SIGNIFICANT MEDICAL PATHOLOGY DISCOVERED DURING A MALE INFERTILITY EVALUATION

OBJECTIVES To review a large experience with sperm cryopreservation in patients with testicular cancer and determine the effect of clinical stage and tumor histologic features on semen quality. METHODS The prefreeze and post-thaw sperm quality of 157 patients with testicular cancer was compared with that of 50 normal donors. The impact of tumor stage and histologic features (pure seminoma, pure embryonal, or mixed germ cell) was also determined. A computer-assisted semen analysis was performed before and after cryopreservation. The motile sperm count (MSC), motility, and motion characteristics were measured before and after cryopreservation and compared between groups. RESULTS Patients with testicular cancer had lower prefreeze and post-thaw MSC and motility compared with normal donors (P = 0.0001 for both). The curvilinear velocity and linearity were also significantly less in patients with testicular cancer (P <0.05 for both). The percentage of change in the semen characteristics did not differ between patients and donors, indicating that sperm from both patients and donors withstood the cryopreservation process equally well. Tumor stage (n = 143) and histologic features (n = 136) did not significantly influence semen quality. No individual histologic component significantly influenced MSC or motility. CONCLUSIONS The effect of cryopreservation on sperm was similar in patients with testicular cancer and donors. Patients with poor prefreeze semen quality have poor post-thaw semen quality, and the effects of cryopreservation were not significantly affected by histologic features or stage. Our results indicate that routine sperm banking should be recommended for men with a diagnosis of testicular cancer to preserve future fertility potential.

Clinical and genetic features of patients with congenital unilateral absence of the vas deferens

OBJECTIVE To evaluate seminal oxidative stress in men after vasectomy reversal and to determine whether seminal oxidative stress could predict fertility after vasectomy reversal. DESIGN Measurement of seminal reactive oxygen species (ROS) and total antioxidant capacity (TAC) in normal donors, men who were fertile after vasectomy reversal, and men who were infertile after vasectomy reversal. SETTING A male infertility clinic of a tertiary care center. PATIENT(S) Thirty men who underwent vasectomy reversal and 17 normal donors. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Semen characteristics, seminal ROS, and TAC were measured with chemiluminescence assays in samples from donors and reversal patients. RESULT(S) Mean adjusted seminal ROS (log [ROS+1]) was higher in infertile reversal patients (2.38+/-0.25) than in normal donors (1.30+/-0.14). Seminal ROS was also higher in all (fertile and infertile reversal combined) reversal patients than in donors. Total antioxidant capacity did not differ between groups. The ROS-TAC score, a composite index of seminal oxidative stress, was a significant predictor of fertility. A ROS-TAC score of 45 or greater had a positive predictive value of 73% in predicting fertility. CONCLUSION(S) Seminal oxidative stress is associated with vasectomy reversal. The ROS-TAC score is a possible predictor of infertility after vasectomy reversal.

Cryopreservation of sperm from patients with leukemia: is it worth the effort?

PURPOSE Because a pregnancy can be achieved without a male infertility evaluation, some have questioned its usefulness. However, by bypassing a urological evaluation the man might not learn the cause of infertility and not be offered specific corrective therapy. In addition, men with subfertility may have a serious underlying medical or genetic problem that could also be overlooked. We determine the incidence of significant medical pathology discovered during a male infertility evaluation at 2 academic infertility practices. MATERIALS AND METHODS All men examined for either primary or secondary infertility were included in our study, while men seen for vasectomy reversal were not. All patients underwent evaluation, consisting of a complete history, physical examination, semen analysis, hormone testing, urinalysis and genetic testing when appropriate. RESULTS Significant medical pathology was discovered in 33 of 536 (6%) patients. A total of 27 patients had genetic abnormalities, including cystic fibrosis mutations in 24 and karyotypic abnormalities in 3. Of the remaining 6 patients 1 had testis cancer, 1 prostate cancer, 3 diabetes mellitus and 1 hypothyroidism. CONCLUSIONS Significant medical pathology can be detected by a male infertility evaluation. In addition to identifying the cause of infertility, the evaluation may uncover conditions that threaten the health of the male partner or any potential offspring.

THE CONTEMPORARY ROLE OF EXTRA-ANATOMICAL SURGICAL RENAL REVASCULARIZATION IN PATIENTS WITH ATHEROSCLEROTIC RENAL ARETERY DISEASE

OBJECTIVES To review the clinical and genetic findings in men with congenital unilateral absence of the vas deferens (CUAVD). CUAVD is important because of its association with renal anomalies and cystic fibrosis transmembrane conductance regulator gene mutations. METHODS A retrospective review of two urologic practices, both with subspecialty interest in male infertility, was performed. Renal imaging and cystic fibrosis (CF) testing were recommended to all men found to have CUAVD. RESULTS Fifteen men with CUAVD were identified. Only the 12 men with sufficient clinical data were selected for this study. Three patients had CF mutations, and all had obstruction of the contralateral vas deferens in either the pelvis or retroperitoneum. One patient had obstruction of the contralateral pelvic vas deferens and was negative for all CF mutations tested. Four patients (33%) had renal agenesis. Three patients had ipsilateral renal agenesis, and one had contralateral renal agenesis. No patient with CF mutations had renal agenesis. One had polycystic kidney disease, which was considered an incidental finding. CONCLUSIONS Patients with CUAVD may have CF mutations and renal agenesis. Renal ultrasonography and CF testing are therefore recommended for these patients. Patients of reproductive age found to have CUAVD should be counseled about the potential risk of transmission of renal anomalies and CF mutations.

Testicular lesions other than germ cell tumours: feasibility of testis‐sparing surgery

Intracytoplasmic sperm injection (ICSI) allows pregnancies to be established with a single sperm, improving the chances for men with severely impaired sperm quality to cause a pregnancy. Men with leukemia typically are of reproductive age and their fertility is threatened by initially impaired semen quality and cytotoxic chemotherapy. The authors examined the feasibility of sperm cryopreservation in men with leukemia before treatment and whether the type of leukemia is related to prefreeze or postthaw semen quality.

The Le Bag Orthotopic Urinary Diversion

We delineate the current role of extra-anatomical revascularization techniques in the treatment of patients with atherosclerotic renal artery stenosis. There are 2 components to this study. In part 1 all abdominal aortograms performed between 1989 and 1993 were reviewed to document the presence of significant abdominal aortic and visceral arterial atherosclerosis in patients with atherosclerotic renal artery stenosis. A total of 254 patients with atherosclerotic renal artery stenosis was identified. Among 44 patients with severe unilateral disease the incidence of significant abdominal aortic atherosclerosis was 75%. The incidence of significant (greater than 50%) stenosis of the celiac, right common iliac and left common iliac arteries was 52%, 32% and 27%, respectively. In 129 patients with severe atherosclerotic renal artery stenosis bilaterally or in a solitary kidney the incidence of significant abdominal aortic atherosclerosis was 81%, and the incidence of significant (greater than 50%) stenosis of the celiac, right common iliac and left common iliac arteries was 59%, 57% and 59%, respectively. These data indicate that hepatorenal, splenorenal and iliorenal bypass cannot be performed in many patients with atherosclerotic renal artery stenosis due to significant disease involving the donor vessels for these operations. In part 2, all patients undergoing surgical renal revascularization with an extra-anatomical bypass operation between 1980 and 1992 were reviewed. A total of 175 operations was done in 171 patients, including hepatorenal bypass in 59, splenorenal bypass in 54, iliorenal bypass in 37, thoracic aortorenal bypass in 23, renal autotransplantation in 1 and superior mesentero-renal bypass in 1. There were 5 operative deaths (2.9%) and 7 cases of postoperative graft thrombosis (4%). All patients with poorly controlled hypertension were cured or improved postoperatively. Among patients with ischemic nephropathy, postoperative renal function improved in 35%, remained stable in 47% and deteriorated in 18%. Extra-anatomical techniques remain an important component of the surgical armamentarium for atherosclerotic renal artery stenosis. Thoracic aortorenal bypass is a useful new approach in patients with significant celiac and iliac occlusive disease.