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Biomedical subjects

S J Silber

Publications and source records attributed to S J Silber.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence of premature ovarian failure in monozygotic and dizygotic twins.

BACKGROUND: Premature ovarian failure (POF) before 40 years of age from natural causes affects approximately 1% of adult women, with minor variations between ethnic groups. A recent case of ovarian transplantation between young monozygotic (MZ) twins in which one had undergone unexplained POF at 14 years has prompted a study of the prevalence of POF. METHODS: Menopausal ages of 832 Australian and UK female twin-pairs were extracted from volunteer national twin registry databases containing medical, reproductive and lifestyle data surveyed by mail questionnaire. Surgical menopause was an exclusion criterion. RESULTS: The prevalence of POF in both MZ and dizygotic (DZ) twins was similar in both registries and 3- to 5-fold greater than the general population at age thresholds 40 and 45 years. No specific factors were found to account for the higher risk of early menopause. Some twins of both zygosities were highly discordant for menopausal age (>or=10 years). Nevertheless, there was significant intra-twin dependence, especially for MZ twins, and the average age difference at last menses was greater in DZ twin-pairs. CONCLUSION: Both MZ and DZ twins are at higher risk of POF. Despite some striking differences within MZ twin-pairs, menopausal ages were more concordant than for DZ twin-pairs, confirming that the timing of menopause has a heritable component.

Adult↗
PubMed2000

New concepts in operative andrology: a review.

Several recently published, or about to be published, controversial issues in operative andrology are clarified and reviewed in this paper. The microsurgical technique for sperm retrieval for nonobstructive azoospermia, the round spermatid controversy and the varicocoele dilemma (why does everybody keep doing varicocoelectomy for male factor infertility?) are presented with salient points that have recently been presented elsewhere and referenced. Finally, at the end, we review briefly what is known about the likelihood of genetic transmission of infertility from male factor patients to their offspring as a result of the new ICSI technology.

Chromosome Deletion↗
PubMed2000

Microsurgical TESE and the distribution of spermatogenesis in non-obstructive azoospermia.

We wished to map the distribution of spermatogenesis in different regions of the testis in 58 men with non-obstructive azoospermia, and to develop a rational microsurgical strategy for the testicular sperm extraction (TESE) procedure. One goal was to maximize the chances for retrieving spermatozoa from such men, to minimize tissue loss and pain, and to preserve the chance for successful future procedures. Another goal was to expand upon the previously reported quantitative histological analysis of testicular tissue in 45 azoospermic men undergoing conventional TESE, this time using microsurgical as well as histological mapping. Tubular fullness observed at microsurgery and the presence of spermatozoa in the TESE specimen was compared with the quantitative histological analysis of spermatogenesis. Thus, our conclusions about the distribution of spermatogenesis are based on our experience with TESE in 103 consecutive cases of non-obstructive azoospermia. It was confirmed that men with non-obstructive azoospermia caused by germinal failure have a mean of 0 to 3 mature spermatids per seminiferous tubule in contrast to 17-35 mature spermatids per tubule in men with normal spermatogenesis and obstructive azoospermia. The former represented the threshold of quantitative spermatogenesis which must be exceeded in order for spermatozoa to 'spill over' into the ejaculate. Both testicular 'mapping' by multiple biopsy (n = 15) and microsurgical removal of contiguous strips of testicular tissue (n = 43) revealed a diffuse, rather than regional, quantitative distribution of spermatogenesis. A microsurgical approach resulted in the minimal amount of tissue loss and minimal-to-no pain (compared with the original 45 cases already reported). By this means it is often possible to immediately locate the few tubules with spermatogenesis at microsurgery, under local anaesthesia. But even in cases where greater amounts of tissue must be removed in order to find spermatozoa, the microsurgical TESE procedure prevents secondary testicular damage by protecting blood supply and preventing pain and atrophy from increased testicular pressure. Thus, future attempts at TESE-ICSI need not be compromised.

Biopsy↗
PubMed1998

Y chromosome deletions in azoospermic and severely oligozoospermic men undergoing intracytoplasmic sperm injection after testicular sperm extraction.

Y chromosome deletions encompassing the AZFc region have been reported in 13% of azoospermic men and 7% of severely oligozoospermic men. We examined the impact of these Y deletions on the severity of testicular defects in 51 azoospermic men undergoing intracytoplasmic sperm injection (ICSI) after testicular sperm extraction (TESE) and 30 men with severe oligozoospermia undergoing ICSI after ejaculation of spermatozoa. In addition, five azoospermic patients shown previously to have Y chromosome deletions underwent histological evaluation of their previously obtained testis biopsy specimens. A further 27 azoospermic men underwent TESE-ICSI, but not Y chromosome DNA testing. Ten of 51 azoospermic men (20%) who underwent TESE-ICSI and Y-DNA testing were found to be deleted for portions of the Y chromosome AZFc region. Of these 10, five had spermatozoa retrievable from the testis, and in two cases the wives became pregnant. Of the 41 azoospermic men with no Y chromosome deletion, 22 (54%) had spermatozoa retrievable from the testis, and in 12 cases (29%) the wives became pregnant. Four of 30 (13%) severely oligozoospermic patients were found to be deleted for AZFc and in three (75%) of these pregnancy was achieved. The other 26 severely oligozoospermic couples who had no AZFc deletions underwent ICSI, and 12 (46%) have an ongoing or delivered pregnancy. The embryo implantation rate was not significantly different for azoospermic (22%), oligozoospermic (16%), Y-deleted (14%) or Y-intact (18%) men. Of the total of 19 infertile men who had Y chromosome deletions, 14 had deletions within Y chromosome intervals 6D-6F, in the AZFc region. Twelve of those 14 had some spermatozoa (however few in number) in the ejaculate or testis. Five of the Y-deleted men had deletions that extended more proximally on the Y chromosome, and in none of these could any spermatozoa be observed in either ejaculate or testis. These results support the concept that, in azoospermic or oligozoospermic men with Y chromosome deletions limited to intervals 6D-6F (AZFc), there are generally very small numbers of testicular or ejaculated spermatozoa. Larger Y deletions, including and extending beyond the AZFc region and encompassing more Y genes, tend to be associated with a total absence of testicular spermatozoa. In those cases where spermatozoa were retrieved, the presence of Y deletions had no obvious impact on fertilization or pregnancy rate.

Adult↗
PubMed1998

Intracytoplasmic sperm injection today: a personal review.

There no longer seem to be any categories of male factor infertility that cannot be treated with intracytoplasmic sperm injection (ICSI). Even for men with azoospermia caused either by obstruction or by germinal failure, ICSI may be performed successfully. The only failures will be in azoospermic men who have neither spermatozoa nor spermatids retrievable from the testis, but these men comprise a small percentage of the cases with severe male factor. The source of the spermatozoa and the cause of the sperm defect appear to have no effect on the success of the procedure, whether the spermatozoon is epididymal, fresh or frozen, testicular, ejaculated, or from the testicles of men with severe defects in spermatogenesis. Maturation arrest, Sertoli cell-only, cryptorchidism, chemotherapy and mumps do not appear to have a major impact on the pregnancy rate. Of all the factors studied in couples where the male is severely infertile or azoospermic, the only factor that seems to matter (as long as spermatozoa are retrieved) is the age of the wife and, to a considerably lesser extent, her ovarian reserve. Extensive genetic and paediatric follow-up studies of ICSI pregnancies have revealed no increased risk of congenital malformation (2.6%), no increased risk of de-novo autosomal abnormalities, and a 1.0% risk of sex chromosomal abnormalities. These results are very reassuring, but point to the need for careful counselling of couples with male infertility.

Cystic Fibrosis↗
PubMed1997

The use of epididymal sperm for the treatment of male infertility.

Congenital absence of the vas deferens (CAV), failed vasoepididymostomy, and all irreparable obstructions were once very frustrating conditions, because these patients have normal spermatogenesis, but were previously untreatable (Silber SJ, Ord T, Balmaceda J et al (1990) New England Journal of Medicine 323: 1788-1792). Microsurgical epididymal sperm aspiration (MESA) together with in vitro fertilization was introduced in 1985 and in 1988 to treat these cases, but only modest success was achieved (Temple-Smith PD, Southwick GJ, Yates CA et al (1985) Journal of In Vitro Fertilization and Embryo Transfer 2: 119-122; Silber SJ, Asch R, Balmaceda J et al (1988) Fertility and Sterility 500: 525-528; Silber SJ, Ord T, Balmaceda J et al (1990) New England Journal of Medicine 323: 1788-1792). It is very difficult to predict in which cases epididymal sperm will fertilize and in which cases it will not. The reason for this problem may be either sperm maturation defects that are poorly defined or senescent and pathological changes caused by the obstruction. Thus, intracytoplasmic sperm injection (ICSI) became necessary to achieve consistently good results with MESA. The only factor in these couples which affected success had nothing to do with the sperm origin or quality but rather was simply the age and ovarian reserve of the wife. Clearly, whether sperm was from the epididymis or the testis, frozen or fresh, or whether the male had CAV, or irreparable obstruction from a variety of other causes, made no meaningful difference. The cystic fibrosis genotype, the sperm morphology and the quality of motility had no impact. Furthermore, the only factor in the wife that mattered was her age. It is crucial to screen for CF in both the husband with CAV and also his wife. If the wife is negative for any of the 36 common CF mutations, we feel that it is quite safe to perform MESA-ICSI on the couple. The chances of a male offspring's having CAV are very remote, and the chances of the child's having cystic fibrosis are probably less than in a normal, unscreened population. However, if the wife turns out to be a CF carrier herself (4% incidence in the general population), the couple can still undergo MESA-ICSI, but pre-implantation embryo diagnosis would then be mandatory. We have published the first case of successful pre-implantation embryo diagnosis in a CAV-MESA case in which both partners were carriers of the delta F508 mutation (Liu J, Lissens W, Silber SJ et al (1994) Journal of the American Medical Association 23: 1858-1860. We require this as a routine approach whenever the female is discovered, on screening, to be a CF carrier.

Adult↗
PubMed1997

Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure.

The aim of the study was to determine whether a prior diagnostic testicle biopsy can predict success or failure of testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI) in patients with non-obstructive azoospermia caused by testicular failure, and what is the minimum threshold of sperm production in the testis which must be surpassed for spermatozoa to reach the ejaculate. Forty-five patients with non-obstructive azoospermia caused by testicular failure underwent diagnostic testicle biopsy prior to a planned future TESE-ICSI procedure. The diagnostic testicle biopsy was analysed quantitatively, and correlated with the quantitative findings of spermatogenesis in patients with normal spermatogenesis, as well as with the results of subsequent attempts at TESE-ICSI. Men with non-obstructive azoospermia caused by germinal failure had a mean of 0-6 mature spermatids/seminiferous tubule seen on a diagnostic testicle biopsy, compared to 17-35 mature spermatids/tubule in men with normal spermatogenesis and obstructive azoospermia. These findings were the same for all types of testicular failure whether Sertoli cell only, maturation arrest, cryptorchidism, or post-chemotherapy azoospermia. Twenty-two of 26 men with mature spermatids found in the prior testis biopsy had successful retrieval of spermatozoa for ICSI, 12 of their partners became pregnant, and are either ongoing or delivered. The study suggests that 4-6 mature spermatids/tubule must be present in the testis biopsy for any spermatozoa to reach the ejaculate. More than half of azoospermic patients with germinal failure have minute foci of spermatogenesis which are insufficient to produce spermatozoa in the ejaculate. Prior diagnostic testicle biopsy analysed quantitatively (for the presence of mature spermatids) can predict subsequent success or failure with TESE-ICSI. Incomplete testicular failure may involve a sparse multi-focal distribution of spermatogenesis throughout the entire testicle, rather than a regional distribution. Therefore, it is possible that massive testicular sampling from many different regions of the testes may not be necessary for successful TESE-ICSI.

Biopsy↗
PubMed1997

The effect of female age and ovarian reserve on pregnancy rate in male infertility: treatment of azoospermia with sperm retrieval and intracytoplasmic sperm injection.

Factors other than spermatozoa could be the major determinant of the success of assisted reproduction treatment in cases of male infertility. Our aim was to evaluate the effect of the wife's age and ovarian reserve on assisted reproduction success rates in the most severe type of male infertility, i.e. azoospermia. A total of 249 consecutive couples suffering from male infertility caused by azoospermia underwent microsurgical epididymal sperm aspiration (MESA) or testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI). Of these men, 186 had irreparable obstructive azoospermia, and 63 had non-obstructive azoospermia due to testicular failure. Neither the pathology, the source, the quantity, nor the quality of spermatozoa had any effect on fertilization or pregnancy rates. Maternal age and ovarian reserve (number of eggs) had no effect on fertilization or embryo cleavage, but did dramatically affect the embryo implantation, pregnancy and delivery rates. Wives of azoospermic men who were in their 20s had a 46% live delivery rate per cycle, wives aged 30-36 years had a 34% live delivery rate per cycle, wives aged 37-39 years had a 13% live delivery rate per cycle, and wives > or = 40 years had only a 4% live delivery rate per cycle. The number of eggs retrieved also affected pregnancy and delivery rate, but to a lesser extent than age. In virtually all cases of obstructive azoospermia, and in 62% of cases with non-obstructive azoospermia caused by germinal failure, sufficient spermatozoa could be retrieved to perform ICSI, with normal fertilization and embryo cleavage. However, the pregnancy rate and the live delivery rate were dependent strictly on the age of the wife, and on her ovarian reserve. Unfortunately, exaggerated claims of high pregnancy rates can thus easily be made by manipulating, in a very simple way, selection for female factors.

Adult↗
PubMed1996

Normal pregnancies resulting from testicular sperm extraction and intracytoplasmic sperm injection for azoospermia due to maturation arrest.

OBJECTIVE: To see whether testicular sperm extraction could be used to perform intracytoplasmic sperm injection (ICSI) for men with nonobstructive azoospermia caused by maturation arrest. DESIGN: Uncontrolled prospective trial of an attempt to find occasional elongated spermatids or spermatozoa in testes of azoospermic patients with maturation arrest and to use these haploid cells for ICSI. SETTING: European university-based center for reproductive medicine and private American community hospital. PATIENTS: Thirty-eight azoospermic males without obstruction and with biopsy-documented maturation arrest, seven of whom elected, with their wives, to undergo scrotal exploration and testicular sperm extraction with ICSI in an attempt to become pregnant. INTERVENTIONS: Histologic evaluation of spermatid development in 38 patients with azoospermic maturation arrest. Testicular sperm extraction with ICSI in seven random volunteers from this group. MAIN OUTCOME MEASURES: Presence or absence of mature spermatids in the testis biopsy specimen of patients with azoospermic maturation arrest. Fertilization, cleavage, and pregnancy after testicular sperm extraction and ICSI in patients with azoospermic maturation arrest. RESULTS: All seven patients with azoospermic maturation arrest had occasional sperm found with testicular sperm extraction. Five had sufficient numbers (between 6 and 30) for ICSI, and those five had ETs. In four, the partners became pregnant. In all 38 patients examined, the maturation defect was in meiosis rather than in spermiogenesis. CONCLUSION: Nonobstructive azoospermia caused by maturation arrest may be treated with testicular sperm extraction with ICSI apparently as successfully as Sertoli cell only.

Cellular Senescence↗
PubMed1995

Fertilizing capacity of epididymal and testicular sperm using intracytoplasmic sperm injection (ICSI).

For men with uncorrectable obstructive azoospermia, their only hope of fathering a child is microsurgical epididymal sperm aspiration (MESA) combined with in vitro fertilization (IVF). In 1988, proximal epididymal sperm were demonstrated to have better motility than senescent sperm in the distal epididymis, and it was thought that retrieval of motile sperm from the proximal epididymis would yield reliable fertilization and pregnancy rates after conventional IVF. However, the results to date have been poor, and although a minority of patients achieved good fertilization rates with IVF, the vast majority (81%) had consistently poor or no fertilization and the pregnancy rate averaged only 9%. Recently, intracytoplasmic sperm injection (ICSI) has been successfully used to achieve fertilization and pregnancies for patients with extreme oligoasthenozoospermia. ICSI has therefore been applied to cases of obstructive azoospermia and, in this report, 67 MESA-IVF cases are compared with 72 MESA-ICSI cases. The principle that motile sperm from the proximal segments of the epididymis should be used for ICSI was followed, although in the most severe cases in which there was an absence of the epididymis (or absence of sperm in the epididymis), testicular sperm were obtained from macerated testicular biopsies. These sperm only exhibited a weak, twitching motion. In 72 consecutive MESA cases, ICSI resulted in fertilization and normal embryos for transfer in 90% of the cases, with an overall fertilization rate of 46%, a cleavage rate of 68%, and ongoing or delivered pregnancy rates of 46% per transfer and 42% per cycle. The pregnancy and take-home baby rates increased from 9% and 4.5% with IVF to 53% and 42% with ICSI. There were no differences between the results for fresh epididymal, frozen epididymal or testicular sperm, and the number of eggs collected did not affect the outcome. The results were also unaffected by the aetiology of the obstruction such as congenital absence of the vas deferens or failed vasoepididymostomy. The only significant factor which affected the pregnancy rate was female age. It is concluded that although complex mechanisms involving epididymal transport may be beneficial for conventional fertilization of human oocytes (in vivo or in vitro), none of these mechanisms are required for fertilization after ICSI. Given the excellent results with epididymal and testicular sperm, ICSI is obligatory for all future MESA patients. Finally, the use of ICSI with testicular sperm from men with non-obstructive azoospermia is also discussed.

Cytoplasm↗
PubMed1995

High fertilization and pregnancy rate after intracytoplasmic sperm injection with spermatozoa obtained from testicle biopsy.

In cases requiring microsurgical epididymal sperm aspiration (MESA) for congenital absence of the vas deferens (CAVD) or irreparable obstructive azoospermia, often no spermatozoa can be retrieved from the epididymis, or there may even be no epididymis present. We wished to see whether testicular biopsy with testicular sperm extraction (TESE) in such cases could yield spermatozoa that would result in successful fertilization and pregnancy (despite the absence of epididymal spermatozoa) using intracytoplasmic sperm injection (ICSI). In the same setting during the same 2-week period, 28 patients with CAVD or irreparable obstruction were treated; 16 consecutive fresh MESA-ICSI cycles and 12 cycles which required testicular biopsy with testicular sperm extraction (TESE-ICSI) were performed. Normal two-pronuclear fertilization rates were similar in both groups: 45% for epididymal spermatozoa and 46% for testicular biopsy-extracted spermatozoa. Cleavage rates were also similar (68% for epididymal and 65% for testicular spermatozoa). The ongoing pregnancy rates in this series were 50 and 43% respectively. We conclude that epididymal spermatozoa and testicular spermatozoa yield similar fertilization, cleavage and ongoing pregnancy rates using ICSI. When epididymal spermatozoa cannot be retrieved, a testicular biopsy can be performed and the few barely motile spermatozoa thus obtained can be used for ICSI. It appears that all cases of obstructive azoospermia can now be successfully treated.

Biopsy↗