Long-term antipsychotic use and its association with outcomes in schizophrenia - the Northern Finland Birth Cohort 1966.

BACKGROUND: Due to the paucity of previous studies, we wanted to elucidate the pharmacoepidemiology of antipsychotics in schizophrenia in a general population sample, and the association between long-term antipsychotic use and outcomes. METHODS: The sample included 53 schizophrenia subjects from the Northern Finland Birth Cohort 1966 with at least ten years of follow-up (mean 18.6 years since illness onset). Data on lifetime medication and outcomes (remission, Clinical Global Impression [CGI], Social and Occupational Functioning Assessment Scale [SOFAS]) were collected from medical records, interviews, and national registers. RESULTS: During the first two years 22 (42%), between two to five years 17 (32%), and between five to ten years 14 (26%) subjects had used antipsychotics less than half of the time. Drug-free periods became rarer during the follow-up. The mean lifetime daily dose of antipsychotics was 319mg in chlorpromazine equivalents. A high lifetime average and cumulative dose and antipsychotic polypharmacy were associated with a poorer outcome in all measures, whereas having no drug-free periods was associated with a better SOFAS score and a low proportion of time on antipsychotics with a better CGI score. CONCLUSIONS: In our population-based sample, the use of antipsychotics increased during the first five years of illness and was relatively stable after that. Our results suggest that both low dose and proportion of use, and having no drug-free periods, are associated with better outcomes, which concords with current treatment recommendations and algorithms. High long-term doses and polypharmacy may relate to poor outcomes.

Flow cytometric analysis of semen preparation, and assessment of acrosome reaction, reactive oxygen species production and leucocyte contamination in subfertile men.

Reactive oxygen species (ROS) production, poor acrosome reaction ability, and leucocyte and round cell contamination of semen are associated with diminished male fertility. In addition to the assessment of these variables, the number of abnormal and round cells in semen preparation was studied by flow cytometry. Men with varying degree of fertility despite normal concentrations and motility of spermatozoa were investigated. Group 1 consisted of semen donor candidates (n = 25), group 2 of patients with acceptable fertilization in vitro, but diminished fertility in vivo (n = 56), and group 3 of patients with poor (< 25%) fertilization in vitro (n = 32). The subfertile men in groups 2 and 3 had lower concentrations and poorer rapid progressive motility of spermatozoa than the men in group 1. Using flow cytometry, the number of events in the round cell gate in the Percoll-prepared semen sample was higher in the subfertile men than in the donors, independently of the differences in other semen parameters. However, there were no significant differences between the groups in the number of round cells in native semen by microscopic analysis, or in ROS production or acrosome reaction. In conclusion, flow cytometric assessment of round cells may be a useful method in the investigation of male fertility.

Serum and follicular fluid leptin during in vitro fertilization: relationship among leptin increase, body fat mass, and reduced ovarian response.

The satiety factor leptin is expressed in several reproductive tissues, but its role in the control of reproductive physiology is not well understood. We studied leptin concentrations in the sera and follicle fluids of 52 women [body fat mass percentage (BFM%) range, 19.6-38.8%] undergoing pituitary down-regulation and ovarian hyperstimulation for in vitro fertilization (IVF) treatment. Fasting serum samples were collected 1) at maximal suppression before the initiation of gonadotropin treatment, 2) at maximal ovarian hyperstimulation, 3) at the time of oocyte retrieval, and 4) 16 days later when all subjects were under exogenous luteal support using 600 mg progesterone daily. Follicular fluid (FF) was obtained at oocyte retrieval from two representative preovulatory follicles in both ovaries. During ovarian hyperstimulation there was a significant 60% increase in serum leptin concentrations from 10.9 +/- 1.1 (SEM) to 15.7 +/- 1.5 ng/mL (P < 0.01) between suppression and maximal hyperstimulation, demonstrating that the ovarian functional state can affect serum leptin concentrations. A serum leptin increase of 22-198% during ovarian hyperstimulation was evident in 43 subjects, whereas in 9, leptin concentrations remained unchanged. A positive correlation between leptin change and BFM% (r = 0.55; P < 0.0005) was observed in the 43 leptin responders. The follicular fluid leptin level was similar to that in serum. In separate linear regression analysis, BFM% contributed to 59-64%, body mass index to 46-56%, and weight to 46-55% (all P < 0.001) of the variability in leptin concentrations at the 4 time points. The 20-fold increase in serum estradiol concentrations during IVF was not significantly correlated with changes in leptin concentrations. On the contrary, the relative serum leptin increase was negatively associated with the ovarian response to hyperstimulation, as revealed by the numbers of follicles (b = -0.28; r2 = 8.1%; P < 0.05) and oocytes retrieved (b = -0.39; r2 = 15.2%; P < 0.01). This relationship was further reflected in a positive correlation between the percent increases in leptin and FSH concentrations (r = 0.39; P < 0.01). The significant relationship of high leptin and reduced ovarian response was also maintained when the cumulative dose of FSH was used as a covariable. Reduced ovarian response was not a function of body mass index, BFM%, basal leptin levels, or insulin concentrations. Fasting serum insulin concentrations remained unchanged in response to IVF, but were positively correlated to serum leptin concentrations at all four time points. Our data suggest that leptin production may be influenced by the ovarian functional state. During IVF a high relative leptin increase is associated with adiposity and a reduced ovarian response. These observations support the possibility that high leptin concentrations might reduce ovarian responsiveness to gonadotropins. Hence, leptin might explain in part why obese individuals require higher amounts of gonadotropins than lean subjects to achieve ovarian hyperstimulation.

Fertilization, embryo quality, and cryosurvival in in vitro fertilization and intracytoplasmic sperm injection cycles.

PURPOSE: Our purpose was to investigate the influence of semen quality on fertilization, embryo morphology, cleavage, and cryosurvival in conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) programs. METHODS: A retrospective analysis of 513 couples undergoing IVF and 255 couples undergoing ICSI was done. RESULTS: Semen quality influenced fertilization in IVF and abnormal fertilization in IVF and ICSI, but no effects on the development, morphology, implantation capacity, or cryosurvival of embryos were found. Fertilization, embryo quality, and cryosurvival rates were similar after IVF and ICSI. The fertilization rate of mature oocytes in IVF was lower when cytoplasmic immaturity in the oocyte population was frequent. The speed of development of embryos was 2 hr faster after ICSI than after IVF. Two-cell-stage embryos survived best after cryopreservation with propanediol and sucrose on day 2. CONCLUSIONS: After fertilization, semen parameters had no effect on the quality or cryosurvival of embryos in either IVF or ICSI.

Flow cytometric light scattering analysis, acrosome reaction, reactive oxygen species production and leukocyte contamination of semen preparation in prediction of fertilization rate in vitro.

The effects on fertilization of the morphology of spermatozoa, acrosome reaction, reactive oxygen species (ROS) production, leukocyte contamination and the light scattering in flow cytometry of semen preparation were investigated in 73 couples undergoing their first in-vitro fertilization treatment. All men had normal concentrations of spermatozoa with sufficient motility (> or = 50%) and yield (> or = 6 x 10(6)) in the semen preparation on the day of oocyte retrieval. The light scattering properties of all cells present in the semen preparation, as assessed with flow cytometry, were correlated with fertilization. The proportion of metaphase I oocytes was also correlated with the fertilization rate of all collected oocytes and of metaphase II oocytes. ROS production, leukocyte contamination, spontaneous or calcium ionophore-stimulated acrosome reaction, percentage of normal morphology, and multiple anomalies index had no independent contribution.