Simultaneous microsurgical vasal reconstruction and varicocele ligation: safety profile and outcomes.

OBJECTIVES: Simultaneous varicocele ligation and vasal reconstruction has previously been avoided because of concern regarding testicular devascularization. This study sought to investigate the safety of a simultaneous combined approach in the hands of an experienced microsurgeon. METHODS: A retrospective review was conducted of the records of 47 men who underwent vasal reconstruction, 10 (21%) of whom had simultaneous ligation of a clinically palpable varicocele. Specific attention was focused on the development of postoperative testicular atrophy and hydrocele and the analysis of postoperative semen parameters. RESULTS: No patient developed postoperative testicular atrophy or hydrocele. No statistically significant difference existed in postoperative seminal parameters between those patients who had vasal reconstruction alone and those who had a combined procedure. CONCLUSIONS: In the hands of an experienced microsurgeon, simultaneous vasal reconstruction and varicocele ligation is a management strategy that has an excellent safety profile. This approach is not recommended for the occasional microsurgeon.

Effect of level of anastomosis and quality of intraepididymal sperm on the outcome of end-to-side epididymovasostomy.

OBJECTIVES: Epididymovasostomy is commonly performed at the most distal site of the epididymis where whole sperm are present within the lumen, regardless of their motility status. Although more fresh and motile sperm can be found more proximally within the epididymis, it is believed that the outcome of epididymovasostomy is better more distally. Because the current results of epididymovasostomy are far from perfect, it would be ideal to be able to harvest motile sperm for cryopreservation at the time of surgery in case the patient remains azoospermic postoperatively. The objective of this study was to determine the effect of the level of epididymal anastomosis and quality of sperm on the outcome of surgery. METHODS: An end-to-side epididymovasostomy was performed on 131 azoospermic men with a mean age of 39 years and a mean obstructive interval of 18 years. The etiology of obstruction was vasectomy in 48%, infectious in 19%, congenital in 20%, and unknown in 13%. The average duration of follow-up was 32 months. The overall patency rate was 67% and pregnancy rate was 27%. Subgroups of patients with an anastomosis to the same level of the epididymis on all functional sides were identified as follows: caput (56), corpus (28), and cauda (13). These groups were compared in regard to the presence of motile sperm within the epididymal lumen at the time of surgery, patency rates, postoperative semen quality, and pregnancy rates. RESULTS: Motile sperm were present more often in both the caput (54%) and corpus (61%) than in the cauda epididymis (25%) (P < 0.05). The patency rates for the three subgroups were not significantly different. The postoperative total motile sperm count and pregnancy rate for the corpus epididymis (13 x 10(6) and 45%) was significantly (P < 0.05) better than for the caput (4.4 x 10(6) and 22%) but no different than that of the cauda (10 x 10(6) and 23%). The patency and pregnancy rates for anastomoses performed at levels demonstrating motile sperm were not significantly better than at sites with nonmotile sperm, but the postoperative total motile sperm count was better (P < 0.05). CONCLUSIONS: The results of this study suggest that the outcomes of epididymovasostomy to the corpus and cauda epididymis are roughly equivalent and superior to the caput. Therefore, it may be reasonable to move more proximally from the cauda to corpus in the search for motile sperm for cryopreservation during an end-to-side epididymovasostomy. In contrast, moving from the corpus to the caput epididymis has a significant adverse effect upon outcome; it is, therefore, not worthwhile to search for viable sperm for cryopreservation in this clinical setting.

Diagnosis of vasal obstruction with seminal vesiculography: an alternative to vasography in select patients.

OBJECTIVES: To determine whether the pelvic and inguinal portion of the vas deferens can be visualized during seminal vesiculography. DESIGN: Retrospective review of the seminal vesiculograms performed in six patients to determine the frequency of visualization of the vas deferens. A prospective evaluation to determine the amount of contrast necessary to visualize the vas deferens was performed in three patients. RESULTS: The vas deferens was visualized down to the level of the scrotum in four of the six initial studies examined retrospectively. The vas deferens was visualized adequately after the infusion of > or = 10 mL of contrast in all three studies performed prospectively. CONCLUSION: Seminal vesiculography is a minimally invasive diagnostic alternative to vasography that can be used to document the patency of the pelvic and inguinal portions of the vas deferens in select patients.

Pentoxifylline enhancement of post-thaw motility in cryopreserved semen of spinal cord-injured men.

OBJECTIVE: To investigate the effects of pentoxifylline on cryopreserved human semen of spinal cord injured men, in efforts to enhance post-thaw motility. DESIGN: Semen specimens were collected from: pregnancy-proven donors (n = 10), spinal cord injured (SCI) patients (n = 8), and infertility patients referred for white blood cell (WBC) screening of the semen (n = 18). Following at least 24 hours of freezing in 100% tes and tris-yolk buffer, 0.5-mL semen straws were thawed. Each sample was split into two equal aliquots, one of which was treated with 3.6 mM pentoxifylline. Following incubation, percent motility was recorded manually at 15 minutes, 1 hour, 2 hours, and 24 hours post-thaw. Percent original motility preserved (post-thaw motility/original motility X 100%) was calculated for each specimen. RESULTS: Statistically significant differences (P < .05) were noted in the SCI and WBC patients when samples with and without pentoxifylline were compared at 15 minutes, 1 hour, and 2 hours. No significant difference was noted in the donor population at any time interval, and no difference was seen in any group at 24 hours post-treatment with pentoxifylline. The greatest differential between treatment and control groups was noted at 1 hour in all three populations. CONCLUSIONS: Pentoxifylline enhances post-thaw motility of cryopreserved sperm in male infertility patients from 15 minutes to 2 hours post-treatment. Pentoxifylline appears to be most useful at 1 hour post-treatment in the cryopreserved samples of SCI patients obtained by electroejaculation. It does not appear to have any significant effect on the post-thaw motility of pregnancy- proven donors. Pentoxifylline loses its in vitro efficacy prior to 24 hours post-thaw.

Delayed appearance of sperm after end-to-side vasoepididymostomy.

The frequency and timing of the delayed appearance of sperm following an end-to-side vasoepididymostomy were determined in 89 patients. The surgical patency rate, defined as greater than 1 million sperm in the ejaculate, was 56% (50 of 89 consecutive patients). None of the 7 patients without sperm in the epididymal fluid at the anastomosis had sperm in the ejaculate postoperatively. Of the remaining 82 patients 31 had sperm on initial semen analysis within 3 months postoperatively. Seven of the 51 patients whose initial postoperative semen sample revealed azoospermia were lost to followup. Among the remaining 44 patients 18 (41%) had delayed appearance of sperm in the ejaculate (mean delay 6 months, range 3 to 15). The ultimate mean sperm count and motility in the patients with initially positive postoperative semen samples were not significantly different from those in patients with delayed appearance of sperm. In addition, the delayed anastomotic obstruction for both groups was the same (10% and 11%, respectively). Our results demonstrate that delayed appearance of sperm after end-to-side vasoepididymostomy is common and that the prognosis for patients with delayed appearance of sperm is not significantly worse than that for patients with sperm on the initial semen analysis.

Cryopreservation of microsurgically extracted ductal sperm: pentoxifylline enhancement of motility.

Microscopically extracted ductal sperm can be successfully cryopreserved using motility as the outcomes measure. The optimal regimen for cryopreservation of microscopically extracted ductal sperm awaits further determination. Pentoxifylline treatment improves initial post-thaw motility of cryopreserved microscopically extracted ductal sperm. The clinical efficacy of this practice awaits further determination. However, the best potential use for cryopreserved microscopically extracted ductal sperm may be IVF with subzonal or intracytoplasmic microinjection. If intracytoplasmic sperm injection becomes more widely available, then enhancement of motility with pentoxifylline may not be necessary. This approach allows for potential fertility insurance at the time of microsurgical bypass of obstruction, and it may preclude, the need for the andrologic surgeon to accurately time his sperm retrieval procedures with IVF. The latter potential advantage would significantly aid current logistical difficulties in the operating room.

Cytokines stimulate lipid membrane peroxidation of human sperm.

Reactive oxygen species production has been demonstrated to impair sperm function. We have noted the potential for the cytokines IL-1 alpha, IL-1 beta, and TNF alpha to stimulate reactive oxygen species production by fertile donor sperm at levels that are consistent with the levels of IL-1 occurring in human seminal plasma. Reactive oxygen species-related sperm membrane peroxidation may be one mechanism by which cytokines can exert a detrimental effect on male fertility. This study suggests a new mechanism by which cell-mediated immunological male infertility may occur.

Greatly improved sperm motility from vas deferens sperm retrieval: a case for accessory gland related subfertility in spinal cord injured man. Case report.

When sperm motility from vibratory or electroejaculates of spinal cord injured men reveals consistently poor motility (< 10%), one should consider accessory gland factors as a potential cause. Herein, we report the case of a 22 year old paraplegic male who consistently had motility of 1-2% on electroejaculates. He was evaluated in the office with vas deferens sperm retrieval, which revealed a 0.4 ml volume, 9 million/ml density, and 67% motility. We suggest that this significant percent motility differential can only be explained by an accessory gland factor impacting negatively upon this individual's fertility. We propose vas deferens sperm retrieval as a potentially diagnostic and therapeutic procedure in similar cases.

Live birth resulting from in-office vas deferens sperm retrieval combined with natural-cycle insemination.

In-office retrieval of spermatozoa from the vas deferens was successfully combined with intra-uterine insemination of the wife during her natural cycle in the case of a man with azoospermia due to a non-correctable obstruction of the vas deferens. The combined cost of both procedures (sperm retrieval and intra-uterine insemination with processed spermatozoa) was less than $1000. The cost and convenience compare quite favourably with that of epididymis sperm aspiration combined with in-vitro fertilization, which is the currently recommended alternative treatment in such cases. These alternative therapies are compared and discussed relative to their advantages and disadvantages. Our technique for in-office vas deferens sperm retrieval is also presented.

Sperm antibody status does not correlate with egg penetration ability.

During a 6-month period 59 semen specimens were subjected to the direct immunobead test and 12 were positive (15% or more of sperm bound by IgA or IgG to the head, mid piece or principal piece of the tail, for an incidence of 20%). Mean motility and forward progression (scale of 0 to 4) were 47% (range 10 to 80) and 1.7 (range 1 to 3), respectively, in the positive test group, whereas these values were 53% (range 1 to 90) and 2.2 (range 1 to 3), respectively, in the negative test group. Sperm penetration assay was performed on 11 of the 12 direct immunobead test positive specimens. A normal sperm penetration assay score was noted in 5 of the 11 specimens (46%), a subfertile score in 4 (36%) and an infertile score (no penetrations) in 2 (18%). The incidence of scores in these 3 subcategories of fertility status in the direct immunobead test positive group did not differ significantly from distribution of scores from all 87 sperm penetration assays performed at our laboratory during the same period: normal--39 of 87 (45%), subfertile--35 (40%) and infertile--13 (15%). Furthermore, there was no pathognomonic binding pattern for those antibody positive patients with subfertile or infertile scores. In conclusion, sperm antibody positivity is typically independent of egg penetration ability, there is no pathognomonic antibody binding pattern for poor egg penetration and there is a tendency for antibody positive sperm to have a lower percentage of motility and forward progression.

Evaluation and treatment of infertility in spinal cord injured men through rectal probe electroejaculation.

A total of 18 men older than 19 years with spinal cord injury was evaluated for fertility potential with testing of semen obtained by rectal probe electroejaculation. After fertility testing, including sperm penetration assay, semen cryopreservation and sperm antibody status, 6 of the 18 men proceeded with their partners to use rectal probe electroejaculation in efforts to conceive. Sperm was obtained in 16 of 18 cases. Average ejaculate total sperm count (306 million) was good but motility (22%) was poor. Adequate sperm retrieval after processing yielded a normal sperm penetration assay in 4 of 16 cases (25%) in which sperm were obtained. Favorable semen cryopreservation (greater than 33% of pre-freeze motility noted after thaw) was present in 5 of 16 cases (31%). Live births were achieved in 2 of 6 couples attempting conception. Despite the typically poor sperm motility noted in electroejaculates, rectal probe electroejaculation can result in pregnancies from couples involving spinal cord injured men. The sperm penetration assay data indicate that pregnancy should be achievable in at least 25% of spinal cord injured couples. Achieving these conceptions requires a team approach involving a urologist/andrologist, gynecologist/reproductive endocrinologist and a sperm-processing laboratory.

Custom cryopreservation of human semen.

OBJECTIVE: To design a protocol to evaluate individual variability in human semen cryoprotection by native seminal plasma. DESIGN: Post-thaw motility from the frozen semen of pregnancy-proven donors (n = 10) and patients referred for infertility screening (n = 10) was examined in three equal aliquots (per original ejaculate) that comprised varying ratios of native seminal plasma to TES and Tris (TEST)-yolk buffer (Irvine Scientific, Irvine, CA) in a dose-titration curve format. All aliquots from the same ejaculate contained final vol/vol 6% glycerol, had equal sperm density, and had undergone centrifugation for 5 minutes at 600 x g before buffer:semen ratio adjustment and standard precooling protocol for submersion in liquid nitrogen. Post-thaw measurement of percent original motility preserved (post-thaw percent motility/original percent motility x 100) was used for standardization of results. RESULTS: In 14 of 20 specimens (70%), the maximal yield of original motility was obtained in 50% seminal plasma, with an average post-thaw motile yield of 50%. In 6 of 20 specimens (30%), the best preservation of original motility was noted at 100% seminal plasma, with an average post-thaw motile yield of 58%. No specimen had a greatest percent motility preserved at 0% seminal plasma. Donor specimens have equal preference for either 50% or 100% seminal plasma, whereas patient specimens have a preference for 50% seminal plasma (P < 0.05). CONCLUSIONS: Native seminal plasma has variable cryoprotectant qualities for which custom cryopreservation can compensate. A simple two-point dose-titration test of cryopreservation buffer:seminal plasma ratio (i.e., 50:50 versus 0:100) can determine the optimal mixture for cryopreservation of a given individual's semen.

Variation in sperm penetration assay related to viral illness.

Semen specimens from a single pregnancy-proven fertile donor were evaluated in the SPA on a weekly basis over a 4-month period that included a febrile viral illness. This report documents the time course for recovery of decreased sperm density and decreased egg-penetrating ability of human sperm after a febrile viral illness. Observations from these data suggest that egg penetration ability monitored in the SPA is acquired in the testicle during early to midspermiogenesis. This finding contrasts with the more commonly held belief that fertilization capabilities are acquired during epididymal transit.

Evidence for altered receptor-binding activity of serum follicle-stimulating hormone in male infertility.

It is generally assumed that the immunological activity of the follicle-stimulating hormone (FSH) molecule, as reported in the radioimmunoassay (RIA), is identical to the molecule's biological activity. To test the validity of this assumption, the receptor-binding and immunological activities of FSH in the serum of 35 infertile males and 11 fertile males were determined by radioreceptor assay (RRA) and by the standard RIA. The results were analyzed in terms of the ratio of binding (RRA) to immunological (RIA) activity x 100%, referred to as the B/I%, for each patient based on data from the RRA and RIA, respectively. The B/I% for fertile men ranged from 44% to 113% (mean of 80%). In the group of 11 infertile men with normal FSH levels by RIA (50 to 300 ng/mL), there was no significant difference in B/I% (range of 27% to 99%, mean of 59%) from the fertile controls. However, a statistically significant decrease in B/I% (range of 7% to 35%, mean of 18%) was noted in the 24 hypergonadotropic infertile men with RIA levels of serum FSH greater than 300 ng/mL. These significant discrepancies between receptor-binding and immunological activities of serum FSH raise the question of whether RIAs alone are valid parameters for the endocrine evaluation of infertile men with elevated serum FSH levels.

Cost-benefit analysis of pharmacologic erection program (PEP) versus penile prosthesis.

We compared the current dollar inclusive costs of the two most commonly implanted penile prostheses with our pharmacologic erection program (PEP). The inclusive cost of implantation for the inflatable penile prosthesis (IPP) is $9,000 and for the malleable penile prosthesis (MPP) $3,150. The inclusive cost of PEP at maximal dose and maximal frequency of use over a five-year period is $3,450. Penile prosthesis was found to be more cost-effective for the long-term treatment of younger impotent men, whereas in the elderly group the use of PEP over a limited time span may be equally or more cost-effective.

Retroperitoneal mobilization of the vas deferens in the complex vasovasostomy.

Anatomic distances along retroperitoneal, inguinal, and infrainguinal segments of the vas deferens were measured in 14 formalin fixed cadavers and in 15 recently postmortem males. There were no significant differences in segment lengths between the two groups nor between the right and left vasa. Data from the recent postmortem group reveals a mean length of 5.83 +/- .65 cm to be gained from retroperitoneal mobilization of the vas deferens. This information is important to surgical decisions in cases of microsurgical repair of obstructive azoospermia resulting from damage to the inguinal segment of the vas deferens. Data on other vasal segment lengths is beneficial for planning repair in other complex cases of obstructive azoospermia as well.

Partial characterization of a unique growth factor secreted by human Sertoli cells.

Human Sertoli cells were grown in a serum-free environment, and the Sertoli cell conditioned medium (hSCCM) was tested for mitogenic activity. The presence of a potent growth factor(s), termed Sertoli cell secreted growth factor (SCSGF), in hSCCM was confirmed and supports previous observations based on experiments using rat SCCM. Mitogenicity of hSCSGF was demonstrated in cell proliferation assays with the A431 (human epidermoid carcinoma) cell line and in [methyl-3H]-thymidine incorporation (DNA synthesis) assays with the Swiss 3T3 (mouse embryo fibroblast) cell line. In a dose-dependent manner, hSCSGF stimulated A431 cell growth up to 4-fold over control values (P less than 0.0001) and stimulated thymidine incorporation up to 4.5-fold over control values (P less than 0.0002). Importantly, SCSGF stimulated A431 proliferation 2-fold over control values (P less than 0.0002) in the presence of 5% serum. With the exception of rat SCSGF, human SCSGF is the only growth factor known to stimulate A431 cells. SCSGF also demonstrated epidermal growth factor (EGF)-like activity based upon displacement of EGF from its receptor in a radioreceptor assay. However, SCSGF is not EGF since it is a potent stimulator of A431 cells, whereas EGF is inhibitory. The growth factor was stable to heat, freeze-thaw, acid (pH 3), and trypsin treatment. Furthermore, it did not bind heparin agarose and is thus distinct from the endothelial cell growth factor family. High-pressure liquid chromatography on size exclusion (TSK G2000 SW) columns revealed an approximate size of 8000 daltons. Human SCSGF is a unique growth factor and may play a key role in the regulation of normal spermatogenesis.

Evaluation and treatment of the preadolescent varicocele.

Varicocele is the most common surgically correctable cause of male infertility. In adult patients with varicocele and infertility, pregnancy rates following varicocelectomy range as high as 55 per cent in comparison with a pregnancy rate of only 7 per cent in unoperated controls. The initial presentation of varicocele occurs during puberty with the incidence in 13-year-old boys already equivalent to that in the general male population. This occurrence has been referred to as the childhood or adolescent varicocele. Varicocele is a progressive disorder in many if not in all cases, with an obvious individual variation in the time course of progression. The effects of a unilateral lesion are often noted in the contralateral testis. Based upon present knowledge, it is not possible to predict accurately the time course of progression in individual cases of childhood varicocele. However, significant prognostic features in adolescents with varicocele include the following: (1) testicular atrophy, or arrested testicular growth; (2) high-grade varicocele (grade II or III); (3) bilateral lesions; (4) pathologic GnRH stimulation test; and (5) histologic picture of Leydig-cell hyperplasia. The presence of these features either alone or in combination is an indication for treatment in our hands. Unlike adults with varicocele, it is not practical to follow children and adolescents with spermatograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of efficacy and safety of midazolam administered orally in sleep disorders. A dose-finding study.

Efficacy (sleep--sedation) and tolerance of 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) in a dosage of 10 mg to 30 mg p.o. were evaluated in a multi-center pilot study in 75 hospitalized patients, with an age range of 20 to 80 years. The patients suffered from mild to moderate insomnia, secondary to musculoskeletal disorders, peripheral nerve diseases and allergies. The optimal dose range was established on the basis of the relation between the degree of insomnia, age of the patients and the dose needed to obtain the optimal results for the sleep parameters. By this method it could be found that 10 mg was the optimal dose for patients over 60 years with mild to moderate insomnia; for patients less than 60 years old with moderate insomnia 15 mg to 20 mg midazolam was the optimal dose, and for patients with mild insomnia 10 mg was sufficient.