Male subfertility: diagnostic and therapeutic advances.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to L I Lipshultz.
Explore the source record for details and available documents.
PURPOSE: We previously demonstrated that testis biopsy image analysis is an effective method for quantifying intratubular spermatogenic cells in the obstructed testis with normal spermatogenesis. As an extension of the initial report, we describe using the quantitative ploidy and morphological characteristics of cells counted with image analysis in abnormal testis biopsies obtained for a male infertility evaluation. MATERIALS AND METHODS: Image analysis using a specifically designed filter was performed on Feulgen stained 5 microns, sections of paraffin embedded testicular tissue. Archival testicular tissue had been obtained using standard biopsy techniques from patients with azoospermia or severe oligospermia. Qualitative classification was based on standard evaluation of hematoxylin and eosin processed tissue. RESULTS: There were 62 biopsies performed in 58 men. Significant differences in the intratubular content of haploid (spermatozoa and spermatids), diploid and tetraploid cells were found among the 5 categories of abnormalities: the Sertoli-cell-only syndrome, spermatocyte arrest, spermatid arrest, hypospermatogenesis and normal spermatogenesis. Moderate variability was found in the proportion of cell types in spermatid arrest and hypospermatogenesis. CONCLUSIONS: Testis biopsy image analysis provides a quantitative method for categorizing abnormalities of intratubular cell content present in male infertility states by using deoxyribonucleic acid content and morphology characteristics. The limitations of the present qualitative analysis system are emphasized by the moderate variability evident within the current categories of spermatid arrest and hypo-spermatogenesis states.
PURPOSE: Because the effects of mitoxantrone on human male fertility were unknown, we determined prospectively the effects of three courses of mitoxantrone (Novantrone), vincristine (Oncovin), vinblastine, prednisone (NOVP) chemotherapy on the potential for fertility of men with Hodgkin's disease (HD). PATIENTS AND METHODS: Semen analyses were performed on 58 patients with stages I-III HD before, during, and after chemotherapy and after the sperm count recovered from the effects of abdominal radiotherapy that was given after chemotherapy. RESULTS: Before the initiation of treatment, 84% of the patients were normospermic. Sperm counts declined significantly within 1 month after the start of NOVP chemotherapy. In the month after chemotherapy, 38% of patients were azoospermic, 52% had counts < 1 million/ mL, and 10% had counts between 1 and 3 million/mL. Between 2.6 and 4.5 months after the completion of chemotherapy, sperm counts recovered rapidly to normospermic levels in 63% of patients. In the remaining patients who were followed up for at least 1 year after standard upper abdominal radiotherapy, counts also recovered to normospermic levels. CONCLUSION: NOVP chemotherapy, like most other regimens, produced marked temporary effects or spermatogenesis. However, sperm production recovered very rapidly, within 3 to 4 months after the end of NOVP chemotherapy. This pattern was caused by killing differentiating spermatogenic cells, but there was little cytotoxicity or inhibition of stem cells from mitoxantrone or the other drugs. After the combination of NOVP plus abdominal radiotherapy, sperm counts and motility were restored in most patients to pretreatment levels, which were compatible with normal fertility.
PURPOSE: Men with azoospermia, markedly elevated serum follicle-stimulating hormone levels and testicular atrophy were previously considered irreversibly infertile. Thus, testicular biopsy in this patient population was considered unnecessary. However, presently men with even the most severe infertility disorders are potentially able to initiate a pregnancy with intracytoplasmic sperm injection provided sperm can be recovered in even relatively few numbers directly from the testicular tissue. For these reasons we sought to reevaluate the findings from testicular biopsies in these men in the era of advanced micromanipulation techniques. MATERIALS AND METHODS: Chart review identified men with azoospermia, confirmed on a pelleted specimen, and a serum follicle-stimulating hormone level of 3 or more times normal. Mature sperm in the touch preparation cytology and testis biopsy specimen were confirmed. RESULTS: A total of 57 men, most with testicular atrophy, underwent a testicular biopsy and in 17 (30%) mature sperm were identified. The most common diagnosis in these men was severe hypospermatogenesis. Men without sperm most commonly had a pure Sertoli-cell-only pattern. CONCLUSIONS: Men with azoospermia and testicular atrophy with significantly elevated follicle-stimulating hormone levels should undergo testicular biopsy if in vitro fertilization with intracytoplasmic sperm injection is an acceptable approach for the couple.
PURPOSE: Evaluation of the testis biopsy specimen in male infertility has been hampered by the qualitative rather than quantitative nature of routine histological techniques and interpretation. Although useful, flow cytometry has demonstrated significant limitations due to its inability to differentiate among haploid cell types, spermatozoa and spermatids. Thus, deoxyribonucleic acid image analysis was performed on testis biopsy specimens to combine the advantages of quantitative ploidy and morphological characteristics to develop a more effective quantitative system. MATERIALS AND METHODS: Image analysis using a specifically designed filter was performed on Feulgen stained 5 microns. sections of paraffin embedded testicular tissue. The archival testicular tissue had been obtained using standard biopsy techniques from patients with azoospermia and normal spermatogenesis on routine hematoxylin and eosin processed tissue. RESULTS: The overall findings (mean plus or minus standard deviation) in 20 biopsies from 18 men are haploid 54.2 +/- 5.6, diploid 31.2 +/- 5.2 and tetraploid 15.0 +/- 4.6%. Spermatozoa and spermatids contributed 23.2 +/- 5.7 and 30.9 +/- 7.6% to the total cell content, respectively. A mean of 2,462 +/- 254 cells were counted per case. CONCLUSIONS: We used image analysis to evaluate testicular biopsies. This technique can quantitatively determine the percentages of various cell types within the seminiferous tubules. Furthermore, it can differentiate between spermatozoa and spermatids based on morphological characteristics. This technique, which combines ploidy and cell morphology characteristics, represents a significant advancement in the interpretation of the testicular biopsy, and has implications for redefining the presently used system of qualitative interpretative assessment.
UNLABELLED: The use of microsurgical techniques (vasovasostomy and epididymovasostomy) for vasectomy reversal has now enabled surgeons to perform both procedures with certainly acceptable success rates. However, these operations are technically demanding and require special training in microsurgery. PURPOSE: A new method of performing these procedures using laser tissue soldering is described and results are evaluated. Laser tissue soldering is different from laser welding in that it involves the laser activation of a protein solder with a dye specific for the specific wavelength of laser light; therefore, surrounding tissue is not affected by the laser. MATERIALS AND METHODS: Ten rats underwent bilateral vasovasostomy and eleven underwent bilateral epididymovasostomy. In each rat, a sutured anastomosis was performed on one side while laser tissue soldering was performed on the other. Animals were sacrificed after one month and anastomoses were evaluated for patency and presence of sperm granulomas. Histologic analysis was also performed. RESULTS: Patency rates were 8/10 (80%) for sutured vasovasostomy versus 9/10 (90%) for the laser technique. Epididymovasostomy patency rates were 8/11 (73%) for sutured versus 9/11 (82%) for the laser technique. Mean operative times were significantly shorter for lasered anastomoses when compared to controls. The frequency of granuloma formation did not significantly differ between laser and control groups. CONCLUSIONS: Laser tissue soldering resulted in similar patency when compared to a conventional 2 layered sutured anastomosis while decreasing operative time. In addition, since fewer sutures are placed, the laser method is less technically demanding.
Intracytoplasmic sperm injection (ICSI) with in vitro fertilization represents one of the most significant advances in fertility technology. In this relatively new procedure, a single viable sperm is microinjected into an oocyte that has been extracted transvaginally. After fertilization occurs, the embryo is transferred into the uterus. This procedure now affords men who were previously thought to be irreversibly infertile the chance to initiate their own biologic pregnancy. However, because of the procedure's significant costs and its potential risk to the mother, careful selection of couples following a thorough male factor evaluation is mandatory.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The use of ultrasonography has become an important component in the evaluation and treatment of male reproductive tract disorders. From the use of color flow Doppler ultrasonography for the assessment of varicoceles to transrectal ultrasonography combined with seminal vesiculography for the evaluation of ejaculatory duct obstruction, ultrasonography has practical clinical applications. In this article, the authors review the indications and use of ultrasonography in the assessment and treatment of the infertile male. The recent advances in diagnostic transrectal ultrasonography for ejaculatory duct obstruction, in particular, are emphasized.
Explore the source record for details and available documents.
PURPOSE: We examined how transurethral resection of the ejaculatory ducts, performed for infertility, affects semen quality in patients with azoospermia and oligo-asthenospermia. MATERIALS AND METHODS: A retrospective review was done of 46 cases of transurethral resection of the ejaculatory ducts for ejaculatory duct obstruction, confirmed by transrectal ultrasound. Clinical course and semen quality were assessed by semen parameter indications. RESULTS: In 65% of the patients transurethral resection of the ejaculatory ducts improved semen quality (greater than a 50% increase in total motile sperm count) and 20% initiated a pregnancy an average of 6.1 months postoperatively. Statistically significant increases in total motile sperm count were achieved in men with azoospermia and those treated for oligo-asthenospermic indications; the improvement also was shown to be sustainable. Complications occurred in 20% of the men. CONCLUSIONS: Significant and durable semen quality improvement can be achieved after transurethral resection of the ejaculatory ducts for all surgical indications. In most unsuccessful cases the reason for failure is unclear.
PURPOSE: The applications, technique and limitations of testicular touch preparation cytology in evaluation of the infertile man are described. MATERIALS AND METHODS: The technique and histological results of testicular touch preparation cytology for normal specimens and various pathological conditions of male infertility are described in detail. RESULTS: Testicular touch preparation cytology is able to differentiate between late spermatids and mature spermatozoa, as well as to identify other spermatogenic elements. CONCLUSIONS: Touch preparation cytology has 2 important purposes: 1) distinguishing between maturation arrest at the late spermatid stage and normal spermatogenesis, and 2) determining whether obstruction is the cause of azoospermia. While testis biopsy is the gold standard, touch preparation cytology is an extremely important adjunct because of its ability to define whole sperm. The urologist and pathologist are better able to make a diagnosis when routine biopsy and touch preparation cytology are performed.
A retrospective study was performed to evaluate the ability to predict sperm-surface antisperm antibodies (ASA) in patients with primary infertility on the basis of semen analysis. In particular, the ability to predict ASA status on the basis of impaired sperm motility was assessed. The clinical and seminal characteristics of 70 consecutive ASA-positive infertility patients detected by routine screening were reviewed. Similar analysis was performed on 128 consecutive patients with infertility who were found on routine screening to be ASA-negative. The association between the presence of ASA and sperm motility, concentration, and clumping was examined using multivariate analysis. Two variables were found to have a significant joint association with the presence of ASAs. Patients with sperm concentrations of > 20 million/ml were significantly more likely to be ASA-positive (P = 0.002). Second, after adjustment for sperm concentration, patients with lower motilities were significantly more likely to be ASA-positive (P = 0.016). Although impaired motility was seen significantly more often in ASA-positive patients, this seminal defect alone should not be used for predictive screening, since 39% of ASA-positive patients had sperm motilities of > 60%. Furthermore, when a normal sperm concentration (> 20 million/ml) was combined with impaired sperm motility (< 60%) as an indication for ASA testing in this population, the result was a sensitivity of only 43%, a specificity of 77%, and positive and negative predictive values of 50% and 77%, respectively. Despite the association between normal sperm concentrations and impaired motility, it appears that the results of semen analysis cannot be used as a sole indication for ASA testing.
OBJECTIVE: To reanalyze data that were used in a linear model to predict that mean sperm counts have been reduced globally by approximately 50% in the last 50 years. DESIGN: The mean sperm counts and their temporal distribution were reanalyzed via several different statistical models (quadratic, spline fit, and stairstep). CONCLUSION: There are several reasons why a published linear regression model is inappropriate to infer a 50% reduction in mean sperm counts in the last 50 years. These include [1] the potential selection biases that may have occurred with the 61 assembled studies such that they are not representative of their underlying populations; [2] the likely variability in collection methods, in particular, the lack of adherence to a minimum prescribed abstinence period, as has been stated for the largest study, which contained 29.7% of all the subjects included in the analysis; [3] the paucity of data in the first 30 years of the 50-year trend analysis; [4] the fact that if the last 20 years of data are examined, which contains 78.7% of all the studies and 88.1% of the total number of subjects, there is no decrease in sperm counts, in fact, sperm counts were observed to have increased; [5] the conflicting data from a large individual laboratory, which was not prone to the collection variability that likely occurred between the 61 studies, that did not suggest a decline in mean sperm count or seminal volume during a comparable time period, even though this laboratory published the data that were largely responsible for the high historical values in the linear model; and, most importantly, [6] the variety of other mathematical models that perform statistically better at describing the recent data than the linear model and thus offer substantially different hypotheses. The data are only robust during the last 20 years of the analysis, in which all the models, except the linear model, suggest constant or slightly increasing sperm counts.
OBJECTIVE: To develop a quality control system for the optimized sperm penetration assay (SPA) and to use this system to monitor interassay variability and stability over time. DESIGN: Four semen donors were tested consecutively for a period of weeks (7 to 139 weeks) with the SPA. Their average semen analyses and SPA scores were evaluated to monitor natural biologic variation. Intra-assay variation was obtained by dividing 11 semen samples into three aliquots and testing each separately in the SPA. A single ejaculate from seven individuals was aliquoted and frozen to be used as a control. They were tested on different assay days in 1986 and subsequently in 1991 to evaluate the assay stability over time. MAIN OUTCOME MEASURES: Results were expressed as a sperm capacitation index (mean number of sperm penetrations per ovum). RESULTS: Consecutive weekly semen analyses and SPAs on donors exhibited coefficients of variation ranging from 20% to > 40%. In contrast, these variations were much greater than intra-assay variability. Analysis of frozen semen specimens tested in several SPAs also displayed a low coefficient of variation. When aliquots of these frozen samples were tested in the SPA 5 years later, there were no differences in the observed values, showing the remarkable stability of this assay over time. The lower limit of the normal fertile range did not change over a period of 2 years. CONCLUSIONS: Results show that using fresh semen samples as a positive control in the SPA is inadequate. This deficiency has been overcome with the use of frozen semen controls. With frozen semen for quality control, the optimized SPA developed in this laboratory is a highly reproducible assay that meets the strict criteria required for clinical laboratory certification.
OBJECTIVE: To determine the clinical and laboratory features associated with Sertoli cell-only testis histology. DESIGN: Case-controlled retrospective analysis. SETTING: University-based male infertility clinic. PATIENTS: Eighty-two patients with germ cell aplasia histology on testis biopsy from 1984 to 1994. Hormonal findings from a control group of 34 fertile men with normal semen analyses were used for comparison. MAIN OUTCOME MEASURES: History, physical examination, semen analysis, and endocrine findings. RESULTS: Sertoli cell-only histology was observed in 82 of 652 (13%) biopsies performed in infertile men with azoospermia. A major medical illness or genital anomaly (hypospadias, cryptorchidism) was found in 31 men (38%). On physical examination, 75% of patients had small testis (< 18 mL volume) and 45% had abnormally soft testis. On hormone evaluation only serum FSH concentration was elevated significantly (33 mIU/mL [33 IU/L]) compared with fertile controls (7.1 mIU/L [7.1 IU/L]). Patients (6%) with confirmed elevations in serum PRL had lower FSH values than those men with normal PRL levels. Normal ejaculate volumes were observed in all patients. CONCLUSIONS: In approximately 38% of patients, germ cell aplasia is associated with underlying disease states; in the remainder it is largely idiopathic. The physical examination is often characteristic, along with an elevated serum FSH concentration. Normal FSH levels tend to be associated with hyperprolactinemia in these men.
Explore the source record for details and available documents.