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Biomedical subjects

L I Lipshultz

Publications and source records attributed to L I Lipshultz.

At least 19 recordsLinked to original sources

Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas.

BACKGROUND: Treatment of cancer with multiple-drug chemotherapy regimens or radiation therapy can cause either temporary azoospermia of various durations or permanent azoospermia in young men. METHODS: To identify which drugs in which doses contribute to long-term or permanent azoospermia, semen analyses were done on patients with Ewing and soft tissue sarcomas before, during, and after treatment with either CYADIC (cyclophosphamide, doxorubicin, and dacarbazine), or CYVADIC (vincristine added to CYADIC). Some patients also received other drugs or radiation therapy. RESULTS: From pretreatment levels that were similar to those of control subjects, sperm production declined to azoospermia within 4 months of treatment. Sperm production returned in some patients after treatment; 40% of men recovered to normospermic levels by 5 years after treatment. Few patients showed continued recovery of sperm production after that time. The cumulative dose of cyclophosphamide was the most significant determinant of recovery to normospermic levels; approximately 70% of those who had received doses less than 7.5 g/m2 (median, 4.1 g/m2) recovered, but only 10% recovered when doses exceeded 7.5 g/m2. CONCLUSIONS: Thus, a risk of permanent sterility is associated with the use of the CYADIC and CYVADIC regimens in young men, especially when the cumulative dose of cyclophosphamide is greater than 7.5 mg/m2.

Adult

Transrectal ultrasound and partial ejaculatory duct obstruction in male infertility.

Partial ejaculatory duct obstruction, due to either a congenital or an acquired cyst or ejaculatory duct stenosis secondary to calcification, chronic inflammation, can produce a wide spectrum of seminal fluid abnormalities. Sperm density may range from azoospermia to normospermia while ejaculate volume can be low to normal. Sperm motility is consistently diminished (less than 30%). We have treated 2 patients with ejaculatory duct stenosis whose diagnosis was accurately made with transrectal ultrasonography (TRUS). We now suggest that TRUS be used when there is a low semen volume (less than 1.0 cc), or low motility (less than 30%), or oligospermia (less than 20 million sperm/mL), and normal findings on physical examination with normal serum gonadotropin values in the absence of any other explanation.

Adult

Incidence of sperm with two fluorescent bodies in men with impaired fertility.

OBJECTIVE: To determine the two fluorescent body (2FLB) frequency in males with impaired fertility. DESIGN: Males of couples were evaluated along with their female partners for reproductive function. They were classified as having the potential for fertility (control group) or as infertile (test group). This was based on the evaluation of both members of the couple. Semen parameters were determined and analyzed for differences among diagnostic groups. SETTING: The setting was clinical secondary care in both private and institutional practice. PATIENTS, PARTICIPANTS: The study population was composed of males of couples who were being evaluated for infertility. Classification as to reproductive potential and categories of abnormality was based on measurement of semen parameters and clinical judgment. INTERVENTIONS: Semen specimens were obtained and analyzed from 78 control and 93 test subjects. MAIN OUTCOME MEASURES: Semen parameters including volume, sperm count, sperm motility, percent morphologically abnormal sperm, and percent of quinacrine-stained sperm containing zero, one, or two FLBs were determined. RESULTS: The test group was found to have a 2FLB frequency that was significantly different from that of the control group. The data were then analyzed for significant differences in 2FLB frequencies in subpopulations. When subjects from all diagnostic subgroups that included varicocele were compared with the controls, the 2FLB frequency was significantly elevated (median percent of 2FLB was 1.2 versus 0.7). The 2FLB frequency in the remaining diagnostic groups was not elevated. CONCLUSIONS: This is the first report of an elevated 2FLB frequency associated with a biological abnormality. The cause of the elevated 2FLB frequency is not known. However, other anomalies that have been identified in varicocele patients have been associated with elevated intrascrotal temperatures. There are data available that associates elevated temperature with aneuploidy in mouse oocytes.

Humans

The effect of semen quality of the electrical current and heat generated during rectal probe electroejaculation.

Rectal probe electroejaculation is effective in procuring sperm from spinal cord injured patients with ejaculatory incompetence. The seminal quality in these patients is usually suboptimal and the motility is almost always low. We conducted an in vitro experiment to determine whether the heat and current generated during rectal probe electroejaculation impaired sperm motility or forward progression, or if the poor semen quality is the result of existing testicular dysfunction.

Ejaculation

Semen quality and endocrine parameters after acute testicular torsion.

Of 16 postpubertal patients evaluated following testicular torsion 9 were treated with detorsion and bilateral orchiopexy (detorsion group), and 7 were treated with ipsilateral orchiectomy and contralateral orchiopexy (orchiectomy group). Each patient was evaluated with regard to semen quality, endocrine parameters (follicle-stimulating hormone, luteinizing hormone and testosterone) and the presence or absence of semen antisperm antibodies. These data were compared to similar data from a group of proved fertile semen donors. The semen quality in the detorsion group did not differ significantly from that of controls (p = 0.25) but follicle-stimulating hormone was significantly elevated compared with that of controls before and after stimulation with gonadotropin-releasing hormone. The orchiectomy group, which had been subjected to prolonged torsion (mean 69 hours), demonstrated a significant decrease in semen quality compared with semen quality in controls (p = 0.001), with average sperm density of only 29.0 million per ml. Baseline and post-stimulation levels of follicle-stimulating hormone in the orchiectomy group were also significantly abnormal when compared with those in controls and in the detorsion group. Our study demonstrates that testicular damage (changes in semen quality and/or endocrine parameters) occurs in the ipsilateral and contralateral testis following torsion, regardless of treatment modality. However, with early intervention by detorsion and testicular salvage, subsequent semen quality is likely to remain within normal limits. Late surgical intervention, even with removal of the nonviable testes, may result in significant impairment of semen quality.

Acute Disease

Diagnosing male factors of infertility.

The male factor is responsible for failure to conceive in approximately 50% of infertile couples. We considered the most appropriate plan for the evaluation of the male in this review. A comprehensive evaluation includes determination of the couple's history of infertility, their sexual habits, the husband's developmental, medical, and surgical histories, family history, exposure to gonadotoxins, and a thorough review of systems. Laboratory tests include endocrine evaluation, semen analysis, quantitation of leukocytes in semen, and antisperm antibodies. Tests of sperm function can include evaluation of cervical mucus interaction, ova penetration, and the hemizona assay. Additional tests may include transrectal ultrasonography, venography, and testis biopsy.

Humans

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.

Adult

The microsperm penetration assay: development of a sperm penetration assay suitable for oligospermic males.

OBJECTIVE: To develop a specialized sperm penetration assay (SPA) for the evaluation of sperm from oligospermic patients. DESIGN: The development of the assay is in four parts: determine optimal sperm number; demonstrate quality control; establish statistical limits for fertile population; compare results to in vitro fertilization (IVF) outcome. SETTING AND PATIENTS: A group of 63 patients with oligospermia and/or poor motility and a group of 17 fertile donors were compared using the optimized SPA and the micro-SPA. Sperm from a third group of 35 patients were simultaneously incubated with human ova (IVF) and hamster ova (micro-SPA). MAIN OUTCOME MEASURES: Both types of SPA scores are expressed as a sperm capacitation index (penetrations per ovum). Outcome of IVF is expressed as a percent of ova fertilized. RESULTS: Using 25,000 sperm was found to be optimal. The normal fertile range was statistically determined to have a lower limit (-2 SD) of 2.0 penetrations per ovum. When scores from 63 male factor patients were compared using the optimized SPA, only 43% had sufficient swim-up sperm. However, the micro-SPA could accurately test 100% of the samples because it requires only one tenth the number of sperm. CONCLUSION: The micro-SPA provides a valuable diagnostic test for the evaluation of the male factor patient.

Animals

Assisted reproductive technologies for male factor infertility.

Experience in the diagnosis and treatment of infertility has led to an increased understanding of the prominent role male factors play in many couples' inability to conceive. While many forms of male factor infertility are amenable to treatment, for some patients there is no corrective therapy available. For this reason, a great deal of attention has been focused on developing technologies for semen processing and sperm utilization in cases of decreased semen quality. One area of research is the development of more sophisticated methods of assessing sperm function, as well as methods of sperm preparation. Progress is also being made in the application of technologies such as intrauterine insemination and in vitro fertilization in the treatment of male factor infertility. Such developments have improved prospects for fertility among patients suffering from decreased semen quality, as well as those suffering from such disorders as ejaculatory failure and congenital vasal agenesis. Current research also offers promise for future applications such as gamete micromanipulation. This technology holds potential for improving fertility even among patients suffering from profound male factor disorders. The following is a summary of recent publications pertaining to the application of these assisted reproductive technologies in the management of male factor infertility.

Fertilization in Vitro

Simplified gonadotropin-releasing hormone (GnRH) stimulation test.

Provocative gonadotropin-releasing hormone (GnRH) stimulation testing indirectly assesses testicular function with more sensitivity than determination of basal gonadotropin levels alone. Unfortunately, the drawbacks of multiple blood sampling and high cost have limited the clinical usefulness of this test. We herein present a simplified, two-point, thirty-minute GnRH stimulation test. Statistical analysis of data from 55 men with normal baseline gonadotropin levels, reveal that this simplified test is just as accurate as the traditional test (p less than 0.0001) without the latter's attendant difficulties. In addition, we found that normal basal gonadotropin levels had little correlation to the actual responses obtained from GnRH stimulation testing (r = 0.20 and r = 0.39 for luteinizing hormone and follicle-stimulating hormone, respectively).

Adolescent

Artificial insemination with donor semen: the necessity of frequent donor screening.

Artificial insemination with donor semen has become a well established alternative for couples with untreatable male factor infertility. Because of the widespread use of donor insemination, and the increasing awareness and prevalence of sexually transmitted diseases, the American Fertility Society recently redrafted procedural guidelines for the use of donor screening for insemination. Our series of donor screenings is reported to emphasize the necessity of donor evaluations at frequent intervals. From June 1986 through August 1987, 48 healthy male volunteers presented as potential semen donors for our donor program. Each was evaluated with a careful medical history, physical examination and 2 semen analyses for evidence of sexually transmitted disease. On initial evaluation, no donor presented with a positive human immunodeficiency virus antibody, abnormal karyotype, elevated serum glutamic oxaloacetic transaminase, rapid plasma reagent, or positive cultures for Chlamydia or Mycoplasma. One potential donor was excluded because of a positive hepatitis B-core antibody and 1 because of a positive IgM test for cytomegalovirus. At initial examination 3 potential donors had a positive culture for Ureaplasma; all 3 were treated with 3 weeks of tetracycline, and repeat cultures were all negative. Routine followup screening was performed on all donors at 3-month intervals for all sexually transmitted diseases. During this 14-month period cultures converted to positive for Ureaplasma in 4 donors. Furthermore, 1 donor at 6 months contracted gonorrhea. He was treated but no longer used as a donor. Since initiation of the outlined protocol more than 800 inseminations have been performed using fresh semen with no case of sexually transmitted diseases reported from our recipients. We conclude that careful sexual history, and frequent donor and semen evaluation are necessary for prevention of diseases that might be transmitted sexually. If these precautions are strictly observed use of donor semen is safe and effective.

Acquired Immunodeficiency Syndrome

Recovery of sperm production after chemotherapy for osteosarcoma.

Because treatment with surgery and combination chemotherapy produces a high cure rate in young men with osteosarcoma, their subsequent reproductive function is an important concern. Semen analyses of osteosarcoma patients, therefore, were performed before, during, and after treatment with the PADIC regimen consisting of cisplatin, Adriamycin (doxorubicin), and dacarbazine or, in some cases, the PADIC regimen plus additional drugs. Results showed that semen volume was not affected and that sperm motility was reduced only during treatment. Although nearly all patients were rendered azoospermic during treatment, sperm production resumed in 30 of 32 patients examined at least 2 years after treatment. Analysis with correction for censored data indicates that, in 78% of treated men, sperm counts will return to more than 10 million/ml. The percentage of men whose sperm counts recovered to normal was lower for those receiving cisplatin dosages greater than or equal to 600 mg/m2; no trends were observed with Adriamycin and dacarbazine dosages. The inclusion of additional drugs such as methotrexate, bleomycin, dactinomycin, or cyclophosphamide (less than 4 g/m2) did not significantly affect the recovery of spermatogenesis. We conclude that the risk of long-term infertility from treatment with the PADIC regimen is low.

Adolescent

Evaluation of the azoospermic patient.

Azoospermia is found in up to 10 to 20 per cent of the men who present to an infertility clinic. The main causes are testicular failure and ductal obstruction. Testicular biopsy remains the definitive test used to differentiate these 2 disorders. A retrospective study of 133 azoospermic men was performed to determine the accuracy and limitations of noninvasive variables in predicting testicular failure in an effort to limit the need for diagnostic testicular biopsy. Of 49 patients (37 per cent) with ductal obstruction a third had bilateral vasal agenesis. The remaining 84 azoospermic patients (63 per cent) had testicular failure. The results of the complete evaluation of these patients are described. Among the 101 patients with a testicular biopsy confirmed diagnosis there was a significant difference in testicular size (p less than 0.001), ejaculate volume (p less than 0.001) and serum follicle-stimulating hormone (p less than 0.001) between patients with testicular failure and those with ductal obstruction. The sensitivity and specificity of various parameters were determined. The best criteria to predict ductal obstruction preoperatively are a serum follicle-stimulating hormone level of less than 2 times greater than normal and the absence of bilateral testicular atrophy (100 per cent sensitivity and 71 per cent specificity). An algorithm for evaluation of the azoospermic patient is described such that all men with ductal obstruction and a minimal number with testicular failure undergo testicular biopsy.

Adult

Transrectal ultrasonography in disorders of the seminal vesicles and ejaculatory ducts.

Ultrasonography is an inexpensive, noninvasive, and reliable means of evaluating the integrity of the distal seminal tract. A variety of rare congenital anomalies can be demonstrated by ultrasound applied either transabdominally or by the transrectal route. Ultrasonography provides a unique insight into the function and pathology of ejaculation that may affect fertility and may well produce new diagnostic criteria to explain some of the more unusual symptoms encountered by urologists in general practice.

Constriction, Pathologic

Fluorescent body distribution in spermatozoa in the male with exclusively female offspring.

Fluorescent (F) body distribution was determined in a group of men who did not have a fertility problem, but rather had fathered exclusively female offspring. The study was designed to analyze spermatozoa for the frequency of zero F-body (X-bearing) and one F-body (Y-bearing) spermatozoa. Semen samples were separated (processed) for Y-bearing spermatozoa enrichment and reanalyzed for fluorescent body distribution. The study consisted of 50 control (10 males) samples (unprocessed), 35 preseparation (35 patients) samples (unprocessed), and 18 postseparation (18 patients) samples (processed). A significantly higher frequency (P less than 0.05) of zero F-body spermatozoa were observed in the preseparation samples when compared with the control samples. The presence of more spermatozoa without fluorescent body correlates with the occurrence of more female births.

Fathers

Clinical electroejaculation.

Anejaculation is a disorder that occurs infrequently in the general population, but it occurs in some cases of spinal cord injury and dissection of retroperitoneal lymph nodes for testicular cancer. It is associated with multiple sclerosis, transverse myelitis, and diabetes mellitus. Electroejaculation, which involves electrodes in a probe placed in the rectum, electrically stimulates emission of seminal fluid. Semen thus obtained can be used for artificial insemination if a patient and his spouse wish to become natural parents.

Ejaculation