Breast tissues in transsexual women--a nonprostatic source of androgen up-regulated production of prostate-specific antigen.

The present study made use of the female transsexual model and sought to evaluate the contributions of the ovarian, endometrial, and breast tissues to the androgen up-regulated production of prostate specific antigen (PSA). Serum levels of PSA were significantly raised in female transsexuals before surgery, after long-term androgen therapy (mean +/- SE = 35.3 +/- 6.2 pg/mL) when compared with female transsexuals before surgery, but with no androgen therapy (mean +/- SE = 1.53 +/- 0.25 pg/mL). In addition, in androngenized female transsexuals, after surgery, concentrations of PSA (mean +/- SE = 14.5 +/- 2.8 pg/mL) were significantly lowered compared with androngenized female transsexuals after surgery, but the levels were, nevertheless, significantly higher than in normal females. Monthly i.m. injection of 250 mg Sustanon-250 to female transsexuals had raised serum testosterone levels to within the male range. In five subjects, in whom serial measurements were taken, serum testosterone levels were greatly raised 24 h after the testosterone therapy; the mean level (+/-SE) was 19.5 +/- 2.1 ng/mL. But in spite of these high testosterone levels, serum PSA levels (mean +/- SE = 2.2 +/- 0.9 pg/mL) were not significantly raised. However, after 12 months of androgen therapy, the mean (+/- SE) PSA level in these five subjects was 47 +/- 11.6 pg/mL and was significantly higher than the mean level in nonandrogenized female transsexuals. The present study confirmed that high levels of testosterone were able to up-regulate PSA production in women. This up-regulation of PSA production is both a dose- and time-dependent process. Furthermore, the evidence indicates that breast tissues are possibly a nonprostatic source of androgen up-regulated production of PSA women.

Effects of chronic exposure to low doses of trichloroethylene on steroid hormone and insulin levels in normal men.

The aim of this study was to examine the serum levels of insulin and some adrenal steroid hormones in men chronically exposed to low doses of trichloroethylene (TCE). A total of 85 workers participated in this study. Each worker had urine collected and analyzed for trichloroacetic acids (UTCA) on the same day that a blood sample was taken for analyses of serum testosterone, sex hormone-binding globulin (SHBG), androstenedione, cortisol, aldosterone, and insulin. The mean concentration of environmental TCE was 29.6 ppm and the mean UTCA was 22.4 mg/g creatinine (range 0.8-136.4). TCE exposure did not cause any significant changes to the adrenal steroid hormone productions. The results showed that UTCA was significantly correlated to serum insulin levels. Insulin and SHBG responded in tandem, with the highest levels found in workers exposed to TCE for less than 2 years; levels of both parameters were significantly lowered in those exposed for more than 2 years. A triphasic response in insulin levels to TCE, which depended on the duration of exposure, was noted. Initial exposure caused an acute rise in insulin levels. This was followed by a fall to normal levels in those exposed 2-4 years and then a slight rise in those exposed for more than 6 years. The mechanism for this pattern of response to TCE exposure is yet unknown.

Successful in vitro growth of rat two-cell embryos to blastocysts using a simple chemically defined medium.

The aim of the present study was to formulate a simple chemically defined medium for the in vitro growth of rat two-cell embryos to blastocysts. Embryos from day 2 pregnant rats were retrieved and placed in paraffin oil-covered droplets of "rat two-cell embryo culture medium" (R2ECM) containing combinations of various serum supplements, glucose, L-glutamine, and cultured up to 96 h in a CO(2) incubator. Embryos cultured in the basic medium (R2ECM), as well as those supplemented either with fetal bovine serum (FBS) or male rat serum (MRS) did not develop beyond the two- to four-cell stage. In R2ECM with 0.3% bovine serum albumin (BSA) and 7.5 mM glucose, 44% of embryos reached the blastocyst stage by 96 h in culture, and the blastulation rate increased to about 83% when 1 mM of L-glutamine was added. To evaluate the effects of varying doses of glucose, two-cell embryos were cultured in R2ECM supplemented with 0.3% BSA, 1 mM L-glutamine, and 2.5, 5.0, or 7.5 mM of glucose. The percentage of embryos reaching the blastocyst stage for 2.5, 5.0, and 7.5 mM glucose was 64.6%, 65.3%, and 82.9%, respectively. The present study showed that the modified medium (R2ECM) is a simple chemically defined medium that is capable of supporting in vitro growth of rat two-cell embryos to blastocysts in high proportion (greater than 80%) without the need for change of medium within 96 h of culture.

Clinical, endocrinologic, and ultrasonographic features of polycystic ovary syndrome in Singaporean adolescents.

The study sought to evaluate the clinical, endocrinologic, and ultrasonographic features in 150 Singaporean adolescent girls with polycystic ovary syndrome (PCOS) before and after treatment, which was composed primarily of a combined hormone therapy of estrogen and cyproterone acetate. The patients' ages ranged from 12 to 22 years with the majority between 15 and 18 years of age. Most of these girls were seen between their third and fifth gynecologic year. A considerable proportion of them had matured early, experiencing menarche between 9 and 12 years of age. Tanner staging was normal except for a greater proportion at higher stages for pubic and axillary hair, most likely a reflection of the substantial degree of androgenization commonly found in subjects with PCOS. All 150 patients presented with menstrual disorders including secondary amenorrhea, menarche only, anovulatory uterine bleeding, oligomenorrhea, and primary amenorrhea. The majority had normal body weight; 10% to 27% were either underweight or overweight, respectively. On ultrasound, patients presented with enlarged ovaries; enlargement was more pronounced in the right ovary with dense stroma and multiple subcapsular cysts. Many subjects had elevated androgen, luteinizing hormone (LH), and LH/ follicle-stimulating hormone (FSH) levels. Although characteristic of PCOS, FSH levels were either low or normal. Prolactin, estradiol, dehydroepiandrosterone sulfate (DHEAS), and androstenedione were generally normal. A substantial proportion of the study group had elevated cortisol levels. It was noted that adolescent girls with PCOS responded well to treatment; more than 60% showed improvement in cycle profiles following at least 1 year of treatment. Our current opinion is that adolescents with PCOS should be managed early, and that treatment should include medical correction of any hormonal or body-weight imbalance and include psychologic intervention when necessary.

Circadian disturbances after night-shift work onboard a naval ship.

The aim of the present study was to investigate how night duties can affect the circadian rhythms of military personnel working onboard a naval ship. Twenty individuals on a regular day-work schedule from 9:00 a.m. to 6:00 p.m. (serving as controls) and 40 individuals on night-shift duties participated in the study. Salivary melatonin and cortisol profiles were established within two 24-hour periods from 2-hour saliva samplings. Under the condition of abrupt shift in work/rest schedule, the majority of the navy officers (52%) retained their normal melatonin profiles. Twelve percent displayed a right phase shift in melatonin rhythm after night work. Nineteen percent exhibited distortions in the form of abnormal peaks or troughs, and 17% showed signs of disrupted rhythm in the form of low daytime levels of melatonin throughout the sampling period. No consistent relationship was found between the melatonin changes and various work stations of the ship. Prominent changes in the cortisol profile included unexpected peaks or troughs that may be related to the conditions that individuals were exposed to, i.e., high noise level in the engine room, as well as to performing intense tracking operations. The findings of this study (1) show the possible detrimental effects of shift duties on circadian rhythms, (2) highlight a wide interindividual variation in the manner in which the circadian systems respond to an abrupt phase shift in work/rest schedules, and (3) form the basis for further investigations into effective strategies to help military personnel cope with shift work, thereby maintaining health and high working standards while on duty.

The rotary pursuit test is not an index of normal psychomotor function in humans.

OBJECTIVE: This study sought to assess whether the rotary pursuit test is a good indication of the psychomotor performance of human subjects during normal working hours. Circadian hormonal profiles of salivary melatonin and cortisol were also established for correlation with performance. METHODS: Ten healthy individuals working in the Department of Obstetrics and Gynecology laboratory participated in this study. The experiment was conducted during a normal 8.5-hour working day in which routine laboratory tasks such as running radioimmunoassays were performed. Saliva samples were collected every 2 hours starting at 8:00 a.m. Simultaneously, self-rated questionnaires on mood states, sleepiness, stress, and types of food and drinks consumed were also recorded. At 10:00 a.m., 12:00 noon, 2:00 p.m., and 4:00 p.m., the subjects' were tested on the rotary pursuit machine, on which their ability to track a rotating target with a stylus was tested by means of measuring the time the stylus stays on target. RESULTS: The circadian profiles of salivary melatonin and cortisol were similar to what previous studies have shown. Increases in cortisol levels were associated with food intake, work stress, or spontaneous awakening. Tracking performance (time on target) improved significantly from 10:00 a.m. to 2:00 p.m. and then decreased nonsignificantly at 4:00 p.m. only at the speed setting of 60 rpm. There was no correlation between the three parameters measured. SUMMARY: Variation of psychomotor performance during a normal working day and in noncircadian disrupted individuals cannot be measured by the rotary pursuit test. Furthermore, a learning effect could mask any variation in performance.

Effects of one night of sleep deprivation on hormone profiles and performance efficiency.

This study examined the effects of one night of sleep deprivation on melatonin and cortisol profiles, as well as performance efficiency of military service members. Sleep intervention consisted of total lack of sleep (N = 7) or 8 hours of sleep (control group; N = 7) during the night. All parameters were measured at selected time intervals before (day 1), during (only in sleep-deprived individuals), and after (day 2) sleep intervention. Rotary pursuit scores and handgrip strength data were used as indices of psychomotor and physical performance, respectively. In sleep-deprived individuals, more salivary melatonin, but not cortisol, was secreted than in subjects who slept adequately. Significant increases in melatonin and cortisol were noted, especially at 1:30 p.m. on the day after nighttime sleep deprivation. In contrast, the tracking scores for rotary pursuit and grip strength among sleep-deprived and rested individuals were comparable. Across a normal working day (day 1), all parameters studied revealed time-specific fluctuations in both control and sleep-deprived groups. Irrespective of nighttime sleep schedule, the patterns of performance on day 2 differed from those on day 1. The tracking performance improved on day 2, whereas grip strength worsened, which may reflect inherent learning and muscle fatigue, respectively. During the night of sleep deprivation, performance declined. In conclusion, the present study showed that one night of sleep deprivation (8 hours) resulted in significant hormonal changes on the next afternoon but did not modify tracking and muscular strength performance.

Sleep/wake cycle and circadian disturbances in shift work: strategies for their management--a review.

INTRODUCTION: There has been a growing concern about the ability of individuals to maintain adequate levels of performance over long work shifts, particularly when those shifts span night-time hours. It has, therefore, become expeditious to understand and apply principles of circadian rhythms in order to establish simple, rational and appropriate strategies to help our shift workers maximise their performance and minimise their health problems under the various shift work regimes. This review sought to outline several principles of circadian rhythms and the sleep/wake cycle and some possible strategies to manage disturbances in the sleep and performance arising from shift works. METHODS: Many studies in this field had been carried out. The present review concerns studies which elucidate the general circadian principles as well as those which may provide helpful information applicable for us in the work environment we are living in. RESULTS: It has been found that shift workers invariably suffer from a constellation of symptoms, which can sometime severely compromise their ability to perform optimally during their shift work. There are many factors that influence the sleep/wake cycle and thus, the performance of shift work. These include 1) circadian factors, 2) type of shift work, 3) how a person adapt to circadian disruption, 4) ageing, 5) sleep factors and 6) social and domestic factors. CONCLUSIONS: Several possible strategies could be adopted to improve sleep and performance. These include 1) appropriate scheduling of shift work, 2) proper consideration of the speed of shift rotation, 3) strategies for sleep and napping, 4) installing appropriate lighting at the workplace, 5) the use of sleeping pills/hypnotics such as melatonin and melatonin agonists.

Does a positive oestrogen feedback on the hypothalamic-pituitary axis exist concurrently with a defective testosterone feedback in Klinefelter's syndrome?

The oestrogen provocation and GnRH challenge tests were carried out in 5 subjects with Klinefelter's syndrome who had no history of previous hormonal therapy. The oestrogen provocation test consisted of an intramuscular injection of 10 mg of oestradiol valerate and blood samples were collected daily from day 0 to day 5. In 2 subjects, three GnRH challenge tests were carried out before (day 0) and on days 2 and 4 after the intramuscular injection of oestradiol valerate. During each GnRH challenge test, 7 blood samples were collected at 30-min intervals, 30 min and immediately before and for 150 min after the bolus dose of GnRH. Plasma concentrations of FSH, LH, testosterone and oestradiol were measured by established radioimmunoassays. Plasma levels of oestradiol rose significantly a day following the intramuscular injection of 10 mg of oestradiol valerate, reaching a peak on day 2 and then falling significantly to lower levels by days 4 and 5, although these levels were still significantly higher than the corresponding baseline levels. In the presence of high levels of oestradiol, the high basal levels of FSH were significantly suppressed, and remained suppressed throughout the 5 days of the study. LH, on the other hand, had a biphasic response; an initial significant suppression by day 1 persisting to day 3, but by days 4 and 5 a rebound in basal LH levels was noted. However, the levels on day 5 were not significantly higher than baseline levels. The pituitary responsiveness as far as the LH and FSH secretions were concerned reflected the baseline levels. The results of the present study refuted the claim that a positive oestrogen feedback exists in men including Klinefelter's syndrome as a result of the removal of or reduced testosterone. In addition, the attenuated testosterone feedback in Klinefelter's syndrome is responsible for the greatly amplified pituitary responsiveness to the trophic action of GnRH and this, in part, may be responsible for the elevated levels of FSH and LH seen in such patients.

Effects of 4-hydroxyandrostenedione and hyperstimulation with pregnant mare serum gonadotrophin on early embryonic development in rats.

A possible role of high oestradiol levels in mediating the adverse effects of hyperstimulation with pregnant mare serum gonadotrophin (PMSG) on early embryonic development in the rat was investigated using an aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA), to inhibit endogenous oestradiol production. Three experiments were conducted in this study. In the first, varying doses of 4-OHA were administered either concurrently with human chorionic gonadotropin (hCG) to pro-oestrus female rats hyperstimulated at early di-oestrus stage with 20 IU PMSG or alone into nonhyperstimulated pro-oestrus females. At high doses of 1000, 2000, or 5000 microg/rat, 4-OHA substantially improved the survival of embryos in hyperstimulated females, while low doses of 100 and 500 microg/rat were ineffective. The protective effect of 4-OHA on embryo count was optimum at 2000 microg. When administered alone, only the highest dose of 5000 microg/rat 4-OHA increased embryo count. In the second experiment, higher doses of PMSG were studied (30 or 40 IU), with or without 5000 microg/rat 4-OHA given at the time of hCG injection. PMSG proved to be more detrimental with increasing dose, and 5000 microg/rat 4-OHA was able to rescue embryos from death in the 30, but not 40, PMSG group. In the third experiment, the influence of the timing of 4-OHA treatment on its ability to improve the embryo count in hyperstimulated females was examined by introducing 4-OHA 24 h earlier, rather than at the time of hCG treatment. The results showed the importance of timing of 4-OHA administration, as 5000 microg/rat 4-OHA was able to restore embryo survival in the 40 PMSG hyperstimulated group only when it was administered 24 h before hCG injection. Together, these results highlighted that 4-OHA, when administered at the appropriate time and dose, could reverse the negative effects of hyperstimulation from PMSG on early embryonic development. This may be due to its potent aromatase inhibiting properties that lead to the suppression of oestrogen production, thereby alleviating the supraphysiological level of oestradiol, which is typically present in PMSG-treated females. Interestingly, 4-OHA treatment on its own was able to positively influence embryo count when given at a high dose of 5000 microg/rat, and this may be associated with its weak androgenic properties. In conclusion, this study supports the hypothesis that excessive oestradiol is responsible for the negative effects of hyperstimulation with PMSG on early embryonic development.

Relationship between gestational age and frequency of fetal trophoblasts and nucleated erythrocytes in maternal peripheral blood.

The relationship between gestational age and frequency of fetal cells in the maternal blood was studied in order to determine the optimal time for cell recovery. The immunomagnetic colloid system was used to enrich nucleated erythrocytes (NRBCs) and trophoblasts from 20 ml maternal blood samples obtained between 9 and 35 weeks' gestation (n=41). Nested polymerase chain reaction (PCR) for the Y chromosome of enriched NRBCs and trophoblasts showed decreasing negative predictive values with increasing gestational age. The sensitivity and the overall frequency for correct fetal gender diagnosis were the lowest in the third trimester. Fluorescence in situ hybridisation (FISH) using XY DNA-specific probes was used to determine the fetal gender of the trophoblast-enriched fraction. The fetal origin of enriched NRBCs was determined using simultaneous immunophenotyping for fetal hemoglobin and FISH with XY probes. The mean number and mean percentage purity for both fetal trophoblasts and NRBCs showed decreasing values with increasing gestational age. However, statistical analysis showed no relationship between gestational age and frequency of fetal cells even though more fetal cells tend to exist during the first trimester. Nevertheless, the first trimester appears to offer the most optimal time for fetal cell recovery from maternal blood for the purpose of prenatal diagnosis.

Endocrine profiles of male workers with exposure to trichloroethylene.

The objective of this study was to examine the endocrine profiles of a group of male workers chronically exposed to trichloroethylene (TCE) in an electronics factory. A total of 124 workers participated in a preliminary study, for which 85 satisfied the selection criteria and were recruited to take part in a more detailed study. Each of the 85 workers had urine collected and analyzed for trichloroacetic acids (TCA) on the day blood was taken for analysis of serum testosterone (T), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulphate (DHEAS), and sex-hormone binding globulin (SHBG). Environmental TCE exposures were conducted for 12 workers. The geometric mean concentration of environmental TCE was 29.6 ppm (range 9-131) and the mean urine TCA was 22.4 mg/g creatinine (range 0.8-136.4). The results showed that years of exposure to TCE were significantly correlated with DHEAS and negatively correlated with SHBG and T levels. Serum FSH, T, and SHBG levels showed a gradual decline with increasing years of exposure to TCE. This dose-response decrease indicated that there was a disruption of peripheral endocrine function. This disruption could be a result of TCE-induced liver malfunction. The most dramatic change was that the increase in DHEAS concentration was associated with years of exposure to TCE, rising from 255 to 717.8 ng/ml for < 3 to > or = 7 years exposure, respectively. This evidence suggests that chronic exposure to TCE may also affect adrenal function. These findings, however, must be confirmed by further investigations.

Effects of hyperstimulation with gonadotrophins and age of females on oocytes and their metaphase II status in rats.

The present study was undertaken to evaluate the effects of hyperstimulation and aging on the number and proportion of oocytes in the metaphase II stage in female Wistar rats. It explored the validity of the hypothesis that a combination of hyperstimulation with pregnant mare serum gonadotrophins (PMSG) and age could compromise, to a greater extent, the oocyte quality as indicated by the proportion of ovulated oocytes in the metaphase II stage. Female Wistar rats were stimulated with varying doses of PMSG and human chorionic gonadotrophins (hCG) and the number and proportion of ovulated oocytes in the metaphase II stage were examined and compared between different groups of young adult (8-10 weeks old) and aging (30-32 weeks old) female rats. While spontaneous ovulation occurred in all young adult rats, only 50% of the aging rats did. The ovulation rate in aging rats was increased from 50 to 93% when non-PMSG-stimulated rats were given a dose of 10 IU of hCG at proestrus. The lower number of ovulated oocytes noted, even in those hyperstimulated with high doses of PMSG/hCG, also indicated a reduction in fertility in aging rats. Under the influence of high doses of PMSG, all aging rats ovulated, but as with the young adult rats, a higher dose of hCG was needed to achieve the maximum number of ovulated oocytes from the PMSG-induced expanded pool of preovulatory follicles. However, the average number of ovulated oocytes in aging rats was, nevertheless, still significantly lower than in young adult rats even when approximation of weight was considered. No consistent significant difference in proportion of normal oocytes was noted within groups and between young adult and aging rats. A lower proportion of ovulated oocytes was arrested at the metaphase II stages when rats, whether they were young adult or aging, were hyperstimulated with 40 IU of PMSG. However, this proportion was restored to normal (about 100%) when a higher dose of hCG, which is a signal responsible for initiating oocyte maturation, was used. Results of the present study showed that there appears to be an age-related reduction of sensitivity of the preovulatory follicles to the ovulation induction signal of hCG and thus higher doses of hCG were needed to ovulate the PMSG-induced expanded pool of dominant follicles. In older rats, apart from the obvious depletion of the pool of follicles, the evidence from the present study suggests that some of these older rats do have follicles, but that these were unable to develop to preovulatory follicles, probably because of the absence of sufficiently high levels of gonadotrophins essential for the initiation of folliculogenesis. PMSG-hyperstimulation can affect nuclear maturation; the proportion of ovulated oocytes not arrested at the metaphase II stage was higher. However, the proportion of ovulated oocytes at the metaphase II was restored to normal by increasing the dose of hCG use. Hence, meiotic aberration in rats is not age-dependent but rather dependent on the amplitude of the luteinizing hormone (LH)/hCG surge present. The results from this study nullified the hypothesis that hyperstimulation in combination with aging would lead to a higher proportion of abnormality in ovulated oocytes with respect to their being at inappropriate meiotic stages.

Enrichment of fetal trophoblasts and nucleated erythrocytes from maternal blood by an immunomagnetic colloid system.

The aim of this study was to isolate fetal trophoblasts and nucleated erythrocytes from maternal blood using the immunomagnetic colloid system. About 25 ml of maternal blood was collected from pregnant women between of 14 and 20 weeks gestation. Nucleated erythrocytes (NRBCs) were isolated from 5 ml of maternal blood and a nested polymerase chain reaction for the Y chromosome was used to determine fetal origin. The sensitivity of the fetal gender diagnosis was 80% and the specificity was 86%. Both fetal trophoblasts and NRBCs were isolated from the remaining 20 ml of maternal blood. The fetal gender of the trophoblast-enriched fraction was determined using fluorescence in situ hybridisation (FISH) with dual-colour XY-specific DNA probes. XY-specific signals were observed in 0.38% of cells sorted from all pregnant women carrying male fetuses (n = 10). Simultaneous immunophenotyping for the fetal haemoglobin and FISH using XY probes were used to evaluate the fetal origin of cells enriched with anti-CD71. The mean percentage of male fetal erythroblasts was 0.24% and the number of fetal erythroblasts was estimated to be about 672 in 20 ml of maternal blood. The number of fetal erythroblasts detected in our study was greater than that detected by most other separation techniques. Our study shows that it would be feasible to use the immunomagnetic colloid system for the isolation of both trophoblasts and NRBCs from the same maternal blood sample with relatively good efficiency.

Direct effects of varying doses of oestradiol on early embryonic development in in vitro culture of rat's two-cell embryos.

Hyperstimulation in the rat using pregnant mares' serum gonadotrophin (PMSG) has been known to cause death in pre-implantation embryos, as well as enhancement of oestradiol production. This study examines the effect of oestradiol, in levels that are found in hyperstimulated pregnant rats, on pre-implantation embryonic development. Using a simplified in vitro system, 2-cell embryos retrieved from rats on the 2nd day of pregnancy were cultured in rat two-cell embryo culture medium (R2ECM) containing pharmacological doses of oestradiol for 96 h and scored daily in the morning. Three ngxmL(-1) oestradiol reduced the incidence of >8-cell embryos to morulae on the 5th day and blastocysts on the 6th day of development. Most embryos were retarded at the lower cell stages on the 5th day and degenerated by the 6th day. None of the blastocysts expanded on the last day of culture. Fifteen ngxmL(-1) oestradiol accelerated embryo development on the 3rd day but retarded development on the 4th day, and increased the incidence of degenerated embryos by the 5th and 6th day of development. These results suggest that the elevated oestradiol may constitute a mechanism by which PMSG induces death in pre-implantation rat embryos, possibly via a direct action on the embryos.

Microscopic assessment of pronuclear embryos is not definitive.

The microscopic classification of embryos, especially unipronuclear embryos, is not very precise. A number of undocumented and unipronuclear embryos were determined to be diploid following karyotyping and fluorescence in situ hybridization (FISH). Accelerated and asynchronous pronuclear dismantling at the time of checking for embryo fertilization accounts for this disparity. Diploid embryos were also observed among tripronuclear embryos. However, not all embryos ascertained as diploid by FISH were karyotypically normal following full karyotype analysis. By taking into account the "background" abnormality rate, the rate of diploid embryo wastage was estimated to be about 40% among undocumented embryos and about 58% in total. A high percentage of misclassification infers an unintended loss of otherwise transferable embryos. Such a discrepancy is particularly important to older women who have fewer embryos. If these are a woman's only embryos, preimplantation genetic diagnosis might be applicable in determining those that are diploid and suitable for transfer. This could potentially reduce the number of wasted embryos and cycles. The present study has also shown that mosaicism is common but it is still unclear whether mosaicism is indicative of embryonic abnormality or is a fairly common phenomenon among healthy embryos. Bipronuclear embryos that present with abnormal or delayed cleavage are often chaotic in their chromosomal constitution. Such embryos should not be transferred.

Managing aging men in Asia: a strategic approach.

We have established a comprehensive diagnostic paradigm for the management of aging men which seeks to evaluate the various determinants of the aging process in five major health areas: cardio-health, bone health, sex health, general health and endocrine state. This paradigm appears to be useful for the management of the problem of aging in our local population. It could be used for the management of individuals as well as for population research. When combined with the establishment of evidence-based management modalities, it will provide a useful tool for the holistic management of aging in Asia.