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L I Lipshultz

Publications and source records attributed to L I Lipshultz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Germ-cell nondisjunction in testes biopsies of men with idiopathic infertility.

Intracytoplasmic sperm injection (ICSI) has been used in combination with testicular sperm extraction to achieve pregnancies in couples with severe male-factor infertility, yet many of the underlying genetic mechanisms remain largely unknown. To investigate nondisjunction in mitotic and meiotic germ cells, we performed three-color FISH to detect numeric chromosome aberrations in testicular tissue samples from infertile men confirmed to have impaired spermatogenesis of unknown cause. FISH was employed to determine the rate of sex-chromosome aneuploidy in germ cells. Nuclei were distinguished as haploid or diploid, respectively. The overall incidence of sex-chromosome aneuploidy in germ cells was found to be significantly higher (P<.00001) in all three abnormal histopathologic patterns (range 39.0%-43.5%) as compared with normal controls (29.1%). The relative ratio of normal to aneuploid nuclei in the diploid cells of patients with impaired spermatogenesis was approximately 1.0, a >300% decrease when compared with the 4.42 ratio detected in patients with normal spermatogenesis. These results provide direct evidence of an increased incidence of sex-chromosome aneuploidy observed in germ cells of men with severely impaired spermatogenesis who might be candidates for ICSI with sperm obtained directly from the testis. The incidence of aneuploidy was significantly greater among the diploid nuclei, which suggests that chromosome instability is a result of altered genetic control during mitotic cell division and proliferation during spermatogenesis.

Biopsy↗
PubMed1999

Varicocele repair improves semen parameters in azoospermic men with spermatogenic failure.

PURPOSE: We analyzed the efficacy of varicocele repair in improving semen parameters in azoospermic men with spermatogenic failure. MATERIALS AND METHODS: After routine clinical evaluation with confirmatory pellet analysis testicular biopsy and varicocele repair were simultaneously performed in 28 azoospermic men with a primary diagnosis of unilateral or bilateral varicocele and spermatogenic failure. Semen analyses were obtained starting 4 months after varicocelectomy. RESULTS: Repair was bilateral repair in 20 men and unilateral in 8. Of the 28 men 12 (43%) had sperm in the ejaculate with a mean postoperative sperm count plus or minus standard deviation of 1.2+/-3.6x10(6)/ml. and an average followup of 24 months. Mean sperm motility was 19+/-24% (range 0 to 80). Testicular biopsy was predictive of outcome. Only 9 men with severe hypospermatogenesis and 5 with maturation arrest spermatid stage had improvement in sperm density. No improvement was seen in 3 men with the Sertoli-cell-only pattern or 3 with maturation arrest spermatocyte stage. No pregnancies by natural intercourse resulted. One couple used fresh ejaculate for intracytoplasmic sperm injection and 1 underwent testicular sperm extraction with intracytoplasmic sperm injection. Both pregnancies resulted in live births. No other predictive factors were identified. CONCLUSIONS: Varicocele repair can result in sperm in the ejaculate of azoospermic men when severe hypospermatogenesis or maturation arrest spermatid stage is present. Select men with spermatogenic failure and varicoceles may be candidates for varicocele repair, rather than resorting to testis biopsy for sperm extraction in preparation for intracytoplasmic sperm injection. However, the couple should be counseled that assisted reproductive technologies will most likely be required to initiate pregnancy.

Adult↗
PubMed1998

Absence of cyclic adenosine 3':5' monophosphate responsive element modulator expression at the spermatocyte arrest stage.

OBJECTIVE: To test the hypotheses that variations in the expression of adenosine 3':5' monophosphate (cAMP) responsive element modulator are found in human seminiferous epithelium in men with impaired testicular function and subsequent infertility and that variations in apoptosis frequency are associated with differential cAMP responsive element modulator expression in male infertility states. DESIGN: Standard immunohistochemical staining using a rabbit polyclonal antibody against the tau isoform of the cAMP responsive element modulator protein was performed on 5-microM sections of Bouin's fixed, paraffin-embedded testicular tissue obtained from azoospermic or severely oligozoospermic men for routine clinical purposes. Histologic diagnosis was confirmed with computerized image analysis of Feulgen-stained sections. SETTING: Tertiary male infertility referral center at a medical school. PATIENT(S): Forty-eight testis biopsies were performed in 38 azoospermic or severely oligozoospermic males. INTERVENTION(S): Rabbit polyclonal cAMP responsive element modulator tau antibody was applied to the paraffin-embedded testis sections. MAIN OUTCOME MEASURE(S): Testis immunoreactivity to polyclonal cAMP responsive element modulator tau antibody and apoptotic indices. RESULT(S): Although cAMP responsive element modulator immunoreactivity was present in the round spermatid stage of meiosis in testis biopsy specimens showing normal spermatogenesis, spermatid maturation arrest, and hypospermatogenesis, there was complete absence of expression in biopsy specimens from patients with Sertoli cell only and spermatocyte maturation arrest states. In addition, significantly increased apoptotic indices were observed in the spermatocyte maturation arrest state in comparison with normal spermatogenesis and Sertoli cell only pattern. CONCLUSION(S): These data suggest that cAMP responsive element modulator may be important for spermatid development and a stage-specific regulator of human spermatogenesis. Absence of cAMP responsive element modulator may be a cause of testicular failure in various types of male infertility.

Adult↗
PubMed1998

Unilateral testicular injury from external trauma: evaluation of semen quality and endocrine parameters.

PURPOSE: Because few studies have described the impact of unilateral testicular trauma on fertility parameters, we review the experience at the Ben Taub General Hospital during a 16-year period. Semen and endocrine profiles were analyzed to evaluate the influence on the outcomes of orchiectomy versus testicular salvage. MATERIALS AND METHODS: From 1979 to 1995, 67 patients were identified who sustained unilateral testicular trauma. Of these patients 12 were located and 10 agreed to be evaluated. Injuries included gunshot wounds, stab wounds and blunt trauma, and treatment consisted of unilateral orchiectomy or testicular repair. The study protocol comprised a history and physical examination, routine semen analysis, determination of semen and serum antisperm antibody titers (Immunobead* assay) and a modified gonadotropin stimulation test. Results were compared with a group of semen donors with proved fertility. RESULTS: In the 7 patients who underwent unilateral orchiectomy mean sperm density was normal but significantly decreased compared with that of the fertile controls (81.6 versus 132.6 x 10(6)/ml., p = 0.04). Sperm motility was not significantly affected. Baseline follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and post-stimulation LH were significantly increased in this group compared with controls (p < 0.01). In the group that underwent testicular repair sperm density, motility, and baseline and post-stimulation FSH and LH levels were not significantly different from controls. In all patients in both groups testosterone levels and contralateral testicular size were normal. Only 1 patient in the repair group had an elevated serum and semen antisperm titer. CONCLUSIONS: While the testicular salvage group had no significant seminal or endocrine abnormality, the orchiectomy group had a significant decrease in sperm density and elevation of baseline FSH and LH. These preliminary data suggest that testicular salvage is more protective of overall testicular function than orchiectomy.

Adult↗
PubMed1998

Sperm pellet analysis: a technique to detect the presence of sperm in men considered to have azoospermia by routine semen analysis.

PURPOSE: In men considered to have azoospermia by routine semen analyses sperm may be identified after centrifuging the semen. Because these sperm may be used for intracytoplasmic sperm injection, we describe our technique and findings of sperm pelleting. MATERIALS AND METHODS: Semen centrifugation for sperm pellet analysis was performed in 140 consecutive men in whom no sperm was identified on routine semen analysis and who were categorized as having obstructive or nonobstructive azoospermia. Obstructive azoospermia was defined as failed vasectomy reversal, failed reconstruction for congenital vasal or epididymal occlusion, or an acquired obstruction unrelated to ejaculatory duct obstruction. Patients with congenital absence of the vas deferens or who had undergone vasectomy were not included in the study. Nonobstructive azoospermia was defined as moderate to severe testicular atrophy with markedly elevated serum follicle-stimulating hormone (greater than 3 times normal), or a testicular biopsy that revealed maturational arrest, severe hypospermatogenesis or the Sertoli-cell-only pattern. Obstructive and nonobstructive azoospermia were present in 70 men who provided 109 samples and 70 who provided 103, respectively. RESULTS: Motile and nonmotile sperm was identified in 13 of the 70 patients (18.6%) with obstructive and in 16 of the 70 (22.8%) with nonobstructive azoospermia. Pellet variability, that is the absence of sperm in 1 specimen and its presence in another from the same patient, was noted in 7 of the 17 men (41.2%) with obstructive and 2 of the 17 (11.8%) with nonobstructive azoospermia (not statistically significant). Motile sperm was present in the pellets of 6 of the 70 men (8.6%) with obstructive and 15 of the 70 (21.4%) with nonobstructive azoospermia. The median number of motile sperm was lower in the obstructive than in the nonobstructive group (0 sperm in 17 samples versus 5 sperm in 41 samples, p <0.001). The median value of 0 in the obstructive azoospermia group reflects the finding that 9 of the 17 samples did not contain motile sperm. Similarly the median number of nonmotile sperm was lower in the obstructive than in the nonobstructive group (5 versus 8 sperm). CONCLUSIONS: We demonstrated the presence of motile and nonmotile sperm in a significant number of men considered to have azoospermia by routine semen analysis. Semen centrifugation (sperm pelleting) should be performed in all men considered to have this condition by routine semen analysis, especially those with testicular failure and those in whom intracytoplasmic sperm injection is possible.

Centrifugation↗
PubMed1998

Pathological epididymal obstruction unrelated to vasectomy: results with microsurgical reconstruction.

PURPOSE: We determine the success of end-to-side epididymovasostomy in patients presenting with obstructive azoospermia from primary epididymal obstruction and identify prognostic factors that could predict a successful outcome. MATERIALS AND METHODS: Of 256 consecutive patients undergoing end-to-side epididymovasostomy 49 had primary epididymal obstruction unrelated to prior vasectomy. Patients were excluded from study if they had a history of vasectomy, microsurgical reconstruction or ejaculatory duct obstruction. RESULTS: Followup was available in 43 of the 49 patients (88%). Patency rates were 87% in the bilateral epididymovasostomy group, 69% in the unilateral group and 81% overall. Pregnancy rates were 43% in the bilateral and 23% in the unilateral group. While higher patency rates were observed for proximal anastomoses, higher pregnancy rates were observed for distal anastomoses. Intraoperative epididymal fluid quality correlated with patency, that is motile sperm in the epididymal aspirate correlated with postoperative patency (p <0.05). There was no correlation between fluid quality and pregnancy rates. Postoperative semen analyses demonstrated higher sperm density and higher motility in the pregnant versus nonpregnant groups. CONCLUSIONS: Epididymovasostomy may be performed in patients with obstructive azoospermia unrelated to vasectomy with high patency and good pregnancy rates. Intraoperative epididymal fluid quality can be predictive of patency. There was a trend towards higher pregnancy rates for distal anastomosis. There were no pregnancies when anastomosis was at the caput epididymis on both sides.

Adult↗
PubMed1998

Genetic concerns for the subfertile male in the era of ICSI.

The treatment of severe male factor infertility has seen remarkable advances in the last five years with the introduction and widespread use of intracytoplasmic sperm injection (ICSI). Although ICSI represents one of the most important advances in the treatment of the subfertile male, significant concerns exist regarding the potential for transmission of abnormal genes to the offspring because many of the natural barriers to conception have been bypassed. Because these couples were not able to conceive prior to ICSI, the long-term genetic consequences in these offspring are largely undefined at this time. Genetic abnormalities related to male infertility need to be considered in terms of being (1) causative for male infertility and (2) potentially transmissible to the offspring. Reasons for pursuing a genetic evaluation include (1) establishing a diagnosis, (2) establishing a possible genetic origin, (3) clarifying the pattern of inheritance, and (4) providing information on natural history, variation and expression. The three most common known genetic factors related to male infertility are cystic fibrosis gene mutations leading to congenital absence of the vas deferens, Y-chromosome microdeletions leading to spermatogenic impairment, and karyotype abnormalities. When congenital bilateral absence of the vas deferens with azoospermia is encountered, cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations are commonly the underlying cause. When testicular failure is manifest by azoospermia or severe oligoszoospermia, Y-chromosome microdeletions may be present in approximately 10-15 per cent of otherwise normal appearing men. Karyotyping can uncover potentially transmissible genetic abnormalities in the infertile male including structural chromosomal disorders such as Klinefelter's (classic 47,XXY), mixed gonadal dysgenesis, chromosomal translocations and XYY syndromes. Finally, potential male infertility genes in animal models are reviewed. Without question, advances in clinical and basic research raise scientific and social issues that must be addressed.

Animals↗
PubMed1997

Advances in the evaluation and treatment of the infertile man.

Numerous advances in technology have been made in the last several years in the diagnosis and treatment of the infertile man. Using case presentations, this article highlights these important new developments and reviews the basics of a comprehensive male infertility evaluation. The use of ultrasound as a critical, indispensable, yet noninvasive tool in the evaluation of possible male reproductive tract obstruction is discussed. Since assisted reproductive techniques (ARTs) have become increasingly important in the management of the otherwise untreatable infertile man, specialized testing of sperm function, e.g., the sperm penetration assay (SPA), and strict morphology assessment are often useful prior to the initiation of some of these assisted reproductive procedures such as intrauterine insemination (IUI) or in vitro fertilization (IVF). Testicular touch preparation cytology and image analysis are also important additions to routine testicular biopsy for quantifying the extent of spermatogenesis. Finally, the revolutionary micromanipulation procedure of intracytoplasmic sperm injection (ICSI) has forever changed the practice of andrology by enabling men previously thought to be irreversibly infertile the chance to initiate their own biologic pregnancy.

Humans↗
PubMed1997

In situ end-labeling of human testicular tissue demonstrates increased apoptosis in conditions of abnormal spermatogenesis.

OBJECTIVE: To determine, using an in situ end-labeling technique, whether the frequency of apoptosis is increased in testis biopsy specimens that demonstrate abnormal spermatogenesis. DESIGN: Immunohistochemical analysis was performed on archived paraffin-embedded testis biopsy specimens. Apoptotic indices, defined as the number of apoptotic bodies per the total number of cells or the number of Sertoli cells, were calculated after counting all the intratubular spermatogenic cells and Sertoli cells in 20 tubules. SETTING: Major academic male factor infertility clinic. PATIENT(S): Forty-eight testis biopsy specimens were obtained for routine clinical purposes from 38 men with azoospermia or severe oligozoospermia. INTERVENTION(S): In situ end-labeling was performed on archived paraffin-embedded testis biopsy specimens using terminal deoxynucleotidyl transferase. MAIN OUTCOME MEASURE(S): Apoptotic indices. RESULT(S): Significantly increased apoptotic indices were observed in patients with spermatocyte arrest, spermatid arrest, and hypospermatogenesis compared with patients with normal spermatogenesis and the Sertoli cell-only pattern. CONCLUSION(S): In situ end-labeling of testis biopsy specimens from infertile men demonstrates increased apoptosis in maturation arrest and hypospermatogenesis states compared with normal spermatogenesis and the Sertoli cell-only pattern. This unique observation implicates a prominent role for this form of programmed cell death in the pathophysiology of maturation arrest and hypospermatogenesis states.

Adult↗
PubMed1997

Apoptotic frequency is increased in spermatogenic maturation arrest and hypospermatogenic states.

PURPOSE: Increased testicular apoptosis has been observed in maturation arrest and hyposper-matogenesis states in rodent models, but this process has not yet been characterized in humans. We hypothesized that increased cell death present with accelerated apoptosis is significant in pathophysiology of many male infertility states associated with abnormal spermatogenesis. We examined frequency of apoptotic bodies in human testis biopsy specimens from infertile men using morphometric analysis of hematoxylin and eosin stained paraffin sections. MATERIALS AND METHODS: Testis biopsy specimens were obtained for routine clinical purposes from azoospermic and severely oligozoospermic men and were stained with hematoxylin and eosin. Apoptotic bodies were identified using established morphometric criteria. Apoptotic indexes, defined as apoptotic bodies per total number of cells and per Sertoli cells, were calculated after counting all intratubular spermatogenic cells and Sertoli cells in 20 tubules. RESULTS: A total of 51 biopsies was performed in 50 men. Significantly increased apoptotic body per total cell and apoptotic body per Sertoli cell ratios were observed in maturation arrest and hypospermatogenesis states in comparison to Sertoli cell only and normal spermatogenesis (p < 0.05, Mann-Whitney test). CONCLUSIONS: Increased apoptosis in maturation arrest and hypospermatogenesis states compared to normal but obstructed spermatogenesis and Sertoli cell only were observed, indicating a prominent role for this form of programmed cell death in human male infertility.

Apoptosis↗
PubMed1997

Infertility.

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Humans↗