Testicular sperm retrieval and intra cytoplasmic sperm injection provide favorable outcome in spinal cord injury patients, failing conservative reproductive treatment.

STUDY DESIGN: Retrospective cohort analysis. OBJECTIVES: The objective of this study was to determine the in vitro fertilization (IVF) outcome after testicular sperm extraction (TESE) in a group of spinal cord injury (SCI) male patients not compatible with conservative fertility treatment. SETTING: University-affiliated medical center. METHODS: Thirty two SCI patients (C2 to L2) were referred to IVF after repeated trials of electroejaculation (EEJ) or penile vibratory stimulation (PVS), and full andrological evaluation. Testicular sperm aspiration (TESA) was the method of choice for sperm extraction. Open TESE was performed only after a negative TESA attempt. Clinical pregnancy and live birth rates were determined. RESULTS: A total of 106 testicular procedures were performed. Sperm was found in 95 cycles (89.6%). The average metaphase II (MII) oocyte number was 11.0±4.2, an average of 5.1±2.3 oocytes became normally fertilized after Intra Cytoplasmic Sperm Injection (ICSI) (fertilization rate 57.1%). On average, 2.7±1.2 embryos were replaced. The clinical pregnancy rate was 32/106 (30.2%) per cycle and 19/32 (59.3%) per couple. Live birth rate was 62.5% (20/32). CONCLUSIONS: TESA/E and IVF can provide excellent prognosis for SCI patients that cannot be treated by EEJ or PVS.

IVF outcome with cryopreserved testicular sperm.

The introduction of intracytoplasmic sperm injection and the use of spermatozoa extracted from the testicles have changed the option for conception for azoospermic patients. The purpose of the present study was to evaluate the IVF outcome after using cryopreserved testicular sperm samples in comparison with fresh ones. A total of 667 in vitro fertilisation cycles with fresh or cryopreserved testicular sperm obtained by an open biopsy and testicular needle aspiration were evaluated. Sperm motility was present in 70.9% of the cycles in Group-I, 77.8% cycles in Group-II and in 83.3% In Group-III (NS). The fertilisation rates were similar in the three study groups (50%, 48.6% and 54.8% respectively). The pregnancy rates were 26.7%, 22.2% and 16.3% respectively (NS). The delivery rate, however, was significantly lower in Group-III (4.1%) than in Group-I and -II (18.4% and 15.9%, respectively, P < 0.05). The IVF results after use of cryopreserved testicular sperm are comparable with those obtained with the fresh specimens. Lack of sperm motility before cryopreservation does not exclude favourable outcome and therefore testicular sperm freezing is feasible whenever there are enough sperm cells in the extracted testicular tissue.

Does age at orchidopexy impact on the results of testicular sperm extraction?

The aim of this study was to evaluate the affect of age at the time of orchidopexy on testicular sperm extraction (TESE) results among patients with a history of cryptorchidism and azoospermia. This retrospective study compared TESE results for couples undergoing IVF treatment, among two groups of patients. Group A included patients who underwent orchidopexy at age 10 and younger, and group B included patients who had the procedure above the age of 10. A total of 42 patients were included in the study. Forty patients had bilateral cryptorchidism and two had unilateral. The overall rate of sperm recovery was 59.5%. No differences were found in the sperm retrieval, fertilization, implantation, pregnancy, or live birth rates between the groups. The results suggest that age at orchidopexy, either at 10 years of age or younger or above 10 years of age, was not a predictive factor for successful TESE. Although bilateral cryptorchidism is usually considered a testicular secretory dysfunction, it was found that sperm retrieval attempts yielded spermatozoa in almost 60% of patients with azoospermia and a history of cryptorchidism.

Older single mothers assisted by sperm donation and their children.

BACKGROUND: Knowledge about the lives of single women who choose to become mothers by sperm donation is very limited. METHODS: This study comprises 62 families headed by formally single women who, following their decision to give birth to a child with the aid of sperm donation, by means of insemination or in vitro fertilization (IVF), used the services of one sperm bank in Israel. RESULTS: The findings of the study, based on the reports obtained from the mothers in face-to-face interviews by structured questionnaires with closed-ended scales and single item open questions, present a complex picture of formally single-mother families assisted by sperm donation. They shed light on socio-demographic and conception related information of the mothers in the sample, on mothers' and children's health, on the children's socio-emotional development and mother-child relationship and on the mothers' difficulties and needs encountered in their function as single parents. CONCLUSIONS: Although the currently young children's socio-emotional development seems to be within the normal range, the mean age of 43 years at first birth of the mothers, the fact that about one-fifth of them gave birth to twins, the health condition of some of the mothers and children, and the difficulties they encounter, may raise some concerns.

Genotyping of Israeli infertile men with idiopathic oligozoospermia.

Microdeletions of the long arm of the Y chromosome involving the azoospermia factor (AZF) region are associated with severe oligo- or azoospermia. Abnormal androgen receptor (AR) structure or function has also been implicated in male infertility. To assess the contribution of these genetic defects to male infertility, 61 Israeli men with severe oligo- (n = 15) or azoospermia (n = 46), were screened for Y chromosome microdeletions, and the AR-(CAG)n repeat length. Fifty fertile Israeli men were similarly analyzed. PCR amplification of 20-54 simple tag sequences (STSs) located at Yq was used to determine the rate and extent of Y chromosome microdeletions. PCR with primers flanking the AR-(CAG)n region and subsequent size fractionation on gradient acrylamide gels were used to determine AR-(CAG)n length. Five azoospermic individuals (5/61-8.2% and 5/46-10.8% of azoospermic patients) displayed Y chromosome microdeletions. The mean CAG repeat number in infertile men was 18.6 +/- 3.0 compared with 16.6 + 2.7 in fertile men (n = 50), a statistically significant difference (p = 0.003). Y chromosome microdeletions contribute to male infertility in our azoospermic population, and the mean length of the AR-CAG is significantly longer in our infertile population than in fertile men.

Studies on sperm chromosomes in patients with severe male factor infertility undergoing assisted reproductive technology treatment.

The aim of the study was to determine the rate of chromosome abnormalities in testicular sperm after intracytoplasmic sperm injection due to severe male factor infertility. The study groups included patient with non-obstructive azoospermia (n=9), obstructive azoospermia (n=10), Klinefelter's syndrome (n=5) and normal controls (n=6, groups I-VI, respectively). The mean serum levels of FSH 17.5+/-8.2 (P<0.05), 3.5+/-2.6, 29.8+/-13.0 (P<0.05) and 3.1+/-0.4 mIU/ml, respectively. The rates of chromosome abnormalities were 19.6% (P<0.001), 8.2% (P<0.001), 6.3 and 1.6%, respectively. Chromosomes X and Y were significantly more involved in the aneuploidy than chromosome 18 in groups I and II. The present findings demonstrate a linkage between gonadal failure (high serum FSH levels) and sperm chromosome abnormalities. Our findings may explain the increased incidence of perinatal sex chromosome abnormalities found in severe male factor patients. Patients with non-mosaic Klinefelter's syndrome have comparable risk for sex chromosomes aneuploidy as the rest of the patients with azoospermia. Therefore, genetic screening during pregnancy or before embryo replacement should be carefully considered in severe male factor patient following in vitro fertilization (IVF).

Donor insemination in Israel. Recipients' choice of donor.

OBJECTIVE: To study the physiognomic preferences of Israeli Jewish recipients of donor insemination. STUDY DESIGN: Donors were "scaled" by both their general popularity and their popularity among single women and married recipients. Following this procedure, the donors' physiognomic features were analyzed and interpreted in terms of Israel's sociopolitical system and the influences of the media. RESULTS: The preferred donor was an educated Ashkenazi Jew who was about 180 cm tall and weighed 72 kg, with straight, light-brown hair and light-colored eyes. This profile deviates from the average features of Israeli men, who are significantly shorter and heavier. The recipients' preferences were noticeably homogeneous, with relatively minor differences between Oriental and Ashkenazi recipients. CONCLUSION: The recipients' preferences reproduce Israel's class system, in which the Ashkenazi section is dominant. They also are influenced by the media and adopt prevailing body images.

Sperm chromosome abnormalities in men with severe male factor infertility who are undergoing in vitro fertilization with intracytoplasmic sperm injection.

OBJECTIVE: To investigate the potential paternal contribution to the risk of fetal chromosomal anomalies after intracytoplasmic sperm injection (ICSI). DESIGN: Spermatozoa isolated from testicular tissue and ejaculated specimens of consenting patients undergoing testicular biopsy and ICSI were analyzed for chromosomes X, Y, and 18 by FISH. SETTING: Assisted reproductive technology program. PATIENT(S): Consenting patients undergoing testicular biopsy and ICSI, severe oligozoospermic patients, and normal fertile donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The rate of chromosome abnormalities in testicular sperm with regard to the type of azoospermia and ejaculated sperm compared to healthy men. RESULT(S): The mean serum levels of FSH in the groups with nonobstructive azoospermia (n = 9), obstructive azoospermia (n = 10), severe oligozoospermia (n = 9), and the normal donors (n = 6) were 17.5 +/- 8.2 (P<.05), 3.5 +/- 2.6, 14.6 +/- 3.5 (P<.05), and 3.1 +/- 0.4 IU/mL, respectively. The corresponding rates of sperm chromosome abnormalities among these groups were 19.6% (P<.001), 8.2% (P<.001), 13.0% (P<.001), and 1.6%, respectively. The corresponding rates of disomy among these groups were 7.8% (12 of 153 spermatozoa), 4.9% (18 of 367), 6.2% (109 of 1,751), and 1% (5 of 500 spermatozoa), respectively. Errors in chromosomes X and Y were significantly more common than in chromosome 18. CONCLUSION(S): The present findings demonstrate a linkage between gonadal failure (high serum FSH levels) and the occurrence of sperm chromosome aneuploidies. Our findings may explain the increased incidence of sex chromosome abnormalities found after IVF in the severe male factor patient population. Genetic screening during pregnancy or before embryo replacement should be considered carefully.

Intratesticular Doppler flow, seminal plasma nitrites/nitrates, and nonobstructive sperm extraction from patients with obstructive and nonobstructive azoospermia.

OBJECTIVE: To prospectively evaluate the role of intratesticular vascular flow in modulating sperm function in men with obstructive and nonobstructive azoospermia. The correlation of testicular Doppler values with nitric oxide and testicular sperm extraction was further evaluated. DESIGN: Prospective study. SETTING: Assisted reproduction unit at a university center. PATIENT(S): Twenty-eight men with azoospermia undergoing sperm extraction for intracytoplasmic sperm injection. INTERVENTION(S): Ultrasound and color Doppler scanning of the testes. Testicular sperm retrieval and nitrite/nitrate assay. MAIN OUTCOME MEASURE(S): Doppler analysis of testicular transmediastinal artery, plasma and seminal plasma nitrite/nitrate values, and sperm extraction histopathology. RESULT(S): The pulsatility index (PI) of the transmediastinal artery was higher in patients with nonobstructive azoospermia (PI = 1.40 +/- 0.13) than in those with obstructive azoospermia (PI = 1.09 +/- 0.15; P=.011). Seminal plasma nitrite/nitrate concentrations were more elevated in cases of obstructive azoospermia than in gonadal failure. Unsuccessful sperm recovery was observed in four patients who showed the worst indices of gonadal failure. In this subgroup, a transmediastinal PI value >1.50 was always observed. CONCLUSION(S): Doppler analysis of the transmediastinal artery and nitrite/nitrate seminal plasma concentrations are useful for distinguishing between obstructive and nonobstructive azoospermia and allow the identification of the presence of spermatozoa within the testes.

Management of varicocele in military obligatory service: Israel Defense Forces Medical Corps policy.

Varicocele is a well-known and highly prevalent medical problem in young obligatory service recruits. Still, there are many questions regarding its management. Is there a clear relation between varicocele and infertility? Can early varicocelectomy in young soldiers prevent future infertility? Is there a role for varicocelectomy in pain relief in physically active soldiers? And finally, what are the pros and cons of the open surgical, laparoscopic, or radiographic techniques in this specific population? Answering these questions should help military physicians in varicocele patients' care. It should also help decision makers to build cost-effective and evidence-based health policy. In this article, we review the literature regarding the controversies in the management of varicocele in young adults and delineate the current policy of the Israel Defense Forces Medical Corps.

Inception and Five-year Run of a Semen Cryobank. Clinical and Behavioral Aspects.

Recent developments in infertility treatment, as well as medical and ethical concern to preserve the fertilizing ability of male subjects potentially at risk, led to the inception of a sperm cryobank in our medical center in 1996. Up to the end of the year 2000, 64 young men displaying higher semen values than generally required were accepted as donors, while 305 married (mean age 32.5, range 22-54) and 381 single women (mean age 41.2, range 27-50) were treated by artificial insemination donor (AID), resulting in 251 conceptions. Besides, 437 male subjects aged 15-61 requested sperm cryopreservation. Methodological considerations about sperm cryopreservation, and behavioral implications therefrom, are evaluated.

Sperm chromosome analysis and outcome of IVF in patients with non-mosaic Klinefelter's syndrome.

OBJECTIVE: The aim of the study was to determine the potential risk for fetal chromosomal anomalies in non-mosaic Klinefelter's syndrome patients undergoing IVF and intracytoplasmic sperm injection. DESIGN: Individually collected spermatozoa were isolated from wet testicular tissue preparations and fixed on glass slides using micromanipulation. Their nuclei were analyzed for chromosomes X, Y, and 18 by fluorescent in situ hybridization. SETTING: Assisted reproductive technology program. PATIENT(S): Consenting patients with non-mosaic Klinefelter's syndrome undergoing testicular biopsy and IVF (fresh specimens) or following such treatment (cryopreserved specimens). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The rates of numerical chromosome abnormalities for chromosomes X, Y, and 18 among spare testicular sperm and the pregnancy outcome following treatment. RESULT(S): Testicular sperm were found in 8 of 20 patients. Four couples became pregnant following embryo replacement. Sperm chromosomes were analyzed in five patients. One hundred and five sperm of 112 analyzed (93.7%) were normal with X to Y ratio of 50:55 (NS) respectively. Among the 112 sperm tested, seven (6.3%) demonstrated chromosomal abnormalities, of which five were related to the sex chromosomes and two to chromosome 18. One set of triplets, one set of twins, and two singletons (four males and three females) with normal karyotypes were born. CONCLUSION(S): Most of the testicular sperm retrieved from Klinefelter's syndrome patients demonstrates a normal pattern of sex chromosome segregation. Therefore, the risk of transmitting numerical sex chromosome abnormalities is relatively low and probably comparable with the rates found in other severe male factor infertility patient groups.

In-vitro fertilization treatment for severe male factor: the fertilization potential of immotile spermatozoa obtained by testicular extraction.

A retrospective analysis in 50 couples of 53 cycles of intracytoplasmic sperm injection (ICSI) with immotile spermatozoa from testicular-retrieved spermatozoa was performed to evaluate whether total immotile spermatozoa achieved after testicular sperm extraction could fertilize ova and result in pregnancies. We assessed the efficacy of ICSI with totally immotile testicular spermatozoa extracted from the testes of azoospermic patients with severe spermatogenic failure (group 1) and compared these results with those from spermatozoa which were recovered after several hours of incubation and were motile (group 2) at the time of injection. In 19 cycles, only totally immotile spermatozoa were injected at the time of ICSI. For the remaining 34 cycles, at least one motile spermatozoon was found for injection. The oocyte fertilization rates were 51% for group 1 and 62% for group 2 (P < 0.02). Eighteen of 19 cycles in group 1 (90%) and all 34 (100%) cycles in group 2 had embryos for replacement. The mean number of embryos per cycle was 5.2 +/- 0.8 and 7.5 +/- 0.9 in groups 1 and 2 respectively; this and the embryo quality (cumulative embryo scoring = 40 +/- 8 for group 1 and 50 +/- 7 for group 2), and clinical pregnancy rates (15.8% per oocyte retrieval in group 1 and 23.5% in group 2) were not significantly different between groups. Fertilization, cleavage and pregnancy can be achieved with intracytoplasmic testicular sperm injection from patients with immotile spermatozoa, at levels comparable with those of ICSI using motile spermatozoa.

The human Pim-2 proto-oncogene and its testicular expression.

In this study we describe the cloning of a human gene, encoding a protein that shares 90% identity and 93% similarity at the primary structure level, with the mouse Pim-2 gene. The gene was designated hPim-2. Structural features suggest that like the mouse Pim-2, hPim-2 is also a serine threonine kinase. At the RNA level, two hPim-2 transcripts were identified. The first, 2.2 kb, is highly expressed in hematopoietic tissues and in leukemic and lymphoma cell lines (K-562, HL-60 and RAJI). It also shows considerable high levels in testis, small intestine, colon and human colorectal adenocarcinoma cells (SW480). A second transcript, 5.0 kb in size, could be detected only in spleen, thymus, small intestine and colon and in the K-562 and RAJI cell lines. In situ hybridization analysis of biopsies taken from testes of men with complete or partial spermatogenesis revealed that the gene is expressed in primary spermatocytes. In the absence of germ cells, signal could be detected over specific cells in the well developed interstitial region. These results suggest a role for hPim-2 in proliferating cells as well as during meiosis. A possible connection between hPim-2 and apoptosis is discussed.

Outcome of in vitro fertilization and intracytoplasmic injection of epididymal and testicular sperm extracted from patients with obstructive and nonobstructive azoospermia.

OBJECTIVE: To evaluate IVF outcome after epididymal and testicular sperm retrieval in patients with obstructive or nonobstructive azoospermia. DESIGN: Retrospective clinical analysis. SETTING: Public university-affiliated IVF unit. PATIENT(S): One hundred twenty-three azoospermic patients (178 cycles). INTERVENTION(S): Sixty-three patients (103 cycles) with obstructive azoospermia (group 1) underwent either epididymal or testicular sperm retrieval, and 60 patients (75 cycles) with nonobstructive azoospermia (group 2) underwent testicular sperm retrieval combined with IVF treatment. Mature oocytes were fertilized using intracytoplasmic sperm injection. After sperm preparation, supernumerary spermatozoa were cryopreserved. MAIN OUTCOME MEASURE(S): Oocyte fertilization rate and clinical pregnancy rate (PR). RESULT(S): The oocyte fertilization rate was 48.4% (534/1,104) in group 1 and 41.5% (312/751) in group 2 (not significant [NS] difference). A total of 100 cycles (97.1%) and 62 cycles (82.7%) in the obstructive and nonobstructive groups, respectively, had embryos for replacement (NS difference). The clinical PRs per ET cycle were 24% (24/100) and 17.7% (11/62) in the two groups, respectively. Oocyte fertilization rates, when fresh (46.4%) or frozen-thawed (41.8%) spermatozoa were used, were not significantly different in the two groups. The PR when fresh sperm were used was 23.6% (30/127), versus 14.3% (5/35) when frozen sperm were used (NS difference). The PR for women aged < or = 35 years was similar to that for women >35 years of age (20.7% or 29/140 and 18.2% or 4/25, respectively). CONCLUSION(S): Epididymal and testicular sperm obtained in azoospermic patients can fertilize oocytes successfully and may lead to high fertilization rates and PRs. Freezing of these spermatozoa does not reduce the outcome of treatment significantly.

Concurrent use of flow cytometry and fluorescence in-situ hybridization techniques for detecting faulty meiosis in a human sperm sample.

Routine semen analysis in an infertile patient revealed severe teratospermia associated with malformation of head and tail in 100% of the sperm cells. Flow cytometry and fluorescence in-situ hybridization (FISH) were shown to supplement routine semen analysis by providing information on the sperm chromatin. Using flow cytometry, propidium iodide-stained spermatozoa from the same sperm sample were compared with a normal reference pool, and with human lymphocytes. The results point to a population of diploid sperm cells rather than to mature haploid spermatozoa. Numerical chromosomal abnormalities of the spermatozoa were subsequently evaluated using FISH. A total of 1000 sperm cells were scored for X and Y chromosomes, and an additional 1128 sperm cells for chromosome 18. Aneuploidy of chromosomes X and Y was revealed in 96.9% of the cells and of chromosome 18 in 90.3% of the cells. Non-disjunction of chromosome X and Y in meiosis I and II occurred in 54.8 and 2.7% of the sperm cells respectively. Non-disjunction in both meiosis I and II occurred in 39.4% of the sperm cells. A normal haploid pattern for chromosomes X and Y was observed in only 3.1%, and for chromosome 18 in 9.7%, of the cells. Using three colour FISH for the sex chromosomes and for chromosome 18, diploidy was demonstrated in 19.4% of 500 sperm cells and aneuploidy in virtually all sperm cells (99.2%). The use of flow cytometry and FISH in cases where genetic and developmental chromatin abnormalities are suspected is a valuable adjunct to other available techniques, and can guide the clinicians to decide which samples are unsuitable for intracytoplasmic injection.

A cystic fibrosis transmembrane conductance regulator splice variant with partial penetrance associated with variable cystic fibrosis presentations.

Some patients express various features of cystic fibrosis (CF) even though essential characteristics of the disease might be absent. Such patients may suffer from respiratory disease without pancreatic insufficiency and normal sweat chloride levels. Others may present as male infertility because of congenital bilateral aplasia of the vas deferens (CBAVD) with no other signs of CF. The 5T allele, a DNA variant in a noncoding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene that reduces the level of the normal CFTR transcripts, was found in increased frequency among male patients with CBAVD. The purpose of this study was to investigate the possibility that the 5T allele is associated with dysfunction of organs other than the male reproductive system, leading to CF or atypical CF. Analysis of the 5T allele was performed on 148 subjects (29 with CF, 61 with atypical CF, and 58 with CBAVD) carrying 232 chromosomes with unidentified CFTR mutations, and on 142 non-CF chromosomes from healthy subjects of Ashkenazi origin. The frequency of the 5T allele among chromosomes from patients of Jewish Ashkenazi origin with CF and atypical CF (six of 33; 18%) was significantly higher than the frequency in the normal Ashkenazi population (eight of 142; 6%; p = 0.03). Analysis of the clinical presentation of the five patients with CF and the 12 patients with atypical CF carrying the 5T allele indicated that most patients suffered from respiratory disease presenting as asthma like symptoms, nasal polyposis, chronic sinusitis, chronic bronchitis, or bronchiectasis. Six patients had pancreatic insufficiency, two with meconium ileus. Sweat Cl- levels ranged from normal to elevated. Of the six male patients with respiratory disease who were old enough to be evaluated for fertility status, five were fertile and one had pancreatic insufficiency. Among male patients with CBAVD, 41% suffered from respiratory symptoms. Thus, the 5T allele is a variant with partial penetrance causing disease with an extreme variability of clinical presentation: from normal healthy fertile subjects or male patients with CBAVD to those with atypical or typical clinical phenotype of CF.

Micromanipulation improves in-vitro fertilization results after epididymal or testicular sperm aspiration in patients with congenital absence of the vas deferens.

In all, 58 couples suffering from infertility because of congenital bilateral absence of the vas deferens underwent a total of 67 combined microsurgical epididymal aspiration or testicular sperm extraction (TESE) and in-vitro fertilization (IVF) treatments. The oocytes recovered were inseminated by either the microdroplet IVF technique (N = 20), subzonal insemination (SUZI; n = 10) or intracytoplasmic sperm injection (ICSI; n = 37). Of the ICSI cycles, 12 were performed using spermatozoa obtained by TESE. Fertilization rates for epididymal spermatozoa were significantly higher for SUZI (17.9%, 17/95) and ICSI (34.4%), 137/398) than for microdroplet IVF (5.2%, 18/343) cycles. The proportion of cycles in which fertilization was achieved was higher in the SUZI (80%) and ICSI (95%) cycles than in the IVF cycles (45%). Delivery or an ongoing pregnancy was achieved in one (5%) IVF cycle, two (20%) SUZI cycles and seven (18.95) ICSI cycles. SUZI or ICSI using epididymal or testicular spermatozoa significantly improved the oocyte fertility rate. The ICSI procedure was especially advantageous in patients for whom spermatozoa were obtained from a testicular biopsy.

High levels of soluble p55-TNF receptors in seminal and prostatic fluids of normal and infertile men.

PURPOSE: To study the role of tumor necrosis factor (TNF) in the male reproductive systems by examining the occurrence, source, and possible functional significance of soluble TNF receptors in seminal fluids of normal and infertile men. MATERIALS AND METHODS: Concentrations of soluble TNF receptors (p55-sTNF-R and p75-sTNF-R) were measured by ELISA in human sera, seminal fluids, prostatic fluid and fluid obtained from an epididymal spermatocele. RESULTS: The level of p55-sTNF-R in seminal fluids of normospermic men was approximately equal to 20-fold higher than in normal serum (13.9 +/- 6.9 ng./ml. versus 0.7 +/- 0.2 ng./ml.). In contrast, p75-sTNF-R, which occurs in serum at amounts higher than p55-sTNF-R, was almost indiscernible in the seminal fluids (<0.18 +/- 0.28 ng./ml. versus 1.9 +/- 0.6 ng./ml. in sera). Concentrations of p55-sTNF-R in seminal fluids of oligoasthenospermic and azoospermic men were similar to those of normospermic men (15.6 +/- 8.5 ng./ml. and 14.9 +/- 6.5 ng./ml., respectively). Higher p55-sTNF-R concentrations were found in prostatic fluids and first split ejaculates (39.8 +/- 1.2 ng./ml. and 32 +/- 1.7 ng./ml., respectively), while second split ejaculates and the fluid from an epididymal spermatocele were found to contain p55-sTNF-R at lower levels (10.8 +/- 1 ng./ml. and 1 ng./ml., respectively). CONCLUSIONS: These findings suggest intense local biosynthesis of p55-sTNF-R in the prostate occurring independently of spermatogenesis. Possible functional implications are: 1) shielding of spermatozoa from the inhibitory effect of TNF in the female reproductive tract; 2) a role for TNF in the normal physiology of the prostate; and 3) blocking TNF-mediated immune response in the prostate, which may have bearings on the development of prostatic hypertrophy or cancer.

CFTR haplotype analysis reveals genetic heterogeneity in the etiology of congenital bilateral aplasia of the vas deferens.

Congenital bilateral aplasia of the vas deferens (CBAVD) was suggested to be a mild form of cystic fibrosis (CF). Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in males with CBAVD revealed that in some males CBAVD is caused by two defective CFTR alleles. The genetic basis of CBAVD in the other males and its association with CF remained unclear. We undertook this study to test the hypothesis of commonality of CBAVD and CF by haplotype analysis, in the CFTR locus, of males suffering from CBAVD and of their families. According to the hypothesis of commonality of CBAVD and CF, two brothers with CBAVD are expected to carry the same two CFTR alleles, while their fertile brothers are expected to carry at least one different allele. Eleven families were studied, of which two families, with unidentified CFTR mutations, did not support this hypothesis. In these families two brothers with CBAVD inherited different CFTR alleles. Their fertile brothers inherited the same CFTR alleles as their brothers with CBAVD. These results provide evidence for genetic heterogeneity in CBAVD. Though in some families CBAVD is associated with two CFTR mutations, we suggest that in others it is caused by other mechanisms, such as mutations at other loci or homozygosity or heterozygosity for partially penetrant CFTR mutations.