Formulae Based on Biomathematics to Estimate the Standard Value of Fetal Growth of Japanese.

We devised biomathematics-based formulae to estimate the standard values of fetal growth of Japanese after 22 weeks' gestation. The growth rates of bi-parietal diameter (BPD), abdominal circumference (AC), femur length (FL), and estimated fetal body weight (EFBW) at the time of gestation were assumed to be proportional to the product of the value at the time and the rest value of an unknown maximum value, respectively. The EFBW was also assumed to follow a multiple logistic function of BPD, AC and FL to fit the standard values of Japanese fetuses published by the Japan Society of Ultrasonics in Medicine. The Mann-Whitney test was used for statistical analysis. The values as a function of gestational day, t, were as follows: BPD(t)=99.6/(1+exp (2.725-0.01837＊t)) (mm); AC(t)=39.7/(1+exp (2.454-0.01379＊t)) (cm); FL(t)=79.6/(1+exp (2.851-0.01710＊t)) (mm); EFBW(t)=8045.1/(1+exp (6.028-0.06582＊BPD(t)-0.1469＊AC(t)+ 0.07377＊FL(t))) (g). EFBW as a function of BPD, AC and FL was as follows: EFBW=8045.1/(1+exp (4.747+ 0.02584＊BPD+0.1010＊AC-0.1416＊FL)) (g). When the BPD, AC and FL were at -2 standard deviation (SD), -1SD, mean and + 2SD, the EFBW values calculated by the formula were statistically closer to the standard values than conventional formulas with p-values of 4.871×10-7, 4.228×10-7, 9.777×10-7 and 0.028, respectively. The formulae based on biomathematics might be useful to estimate the fetal growth standard values.

Successful advanced maternal age pregnancy with mosaic turner syndrome conceived after ovulation induction with clomiphene citrate: a case report.

Turner women typically experience gonadal dysfunction that results in amenorrhea and sterility. We encountered a case of mosaic Turner syndrome where conception was possible after ovulation induction with clomiphene citrate (CC). The patient's ovaries were overresponsive to induction with CC. The challenges and successful outcome are reported.

Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure.

Intrauterine administration of autologous peripheral blood mononuclear cells (PBMC) activated by HCG in vitro are reported to improve implantation rates in patients with repeated failure of IVF-ET. In this study, we examined the effects of intrauterine administration of freshly isolated PBMC on clinical pregnancy and the implantation rates of patients who received frozen/thawed embryo transfer by prospective cohort study. Patients who had not achieved a successful pregnancy despite at least one or more IVF-ET sessions were enrolled in this study (n = 253, 253 cycles). Based on the patient's treatment preferences, PBMC were freshly isolated from each patient and then administered to the intrauterine cavity of that patient. Frozen/thawed embryo transfer was performed and the success of implantation in the PBMC-treated group (n = 83, 83 cycles) was compared with that in the non-treated control groups (n = 170, 170 cycles). There were no significant differences in the clinical pregnancy rate (34.9% vs. 32.9%), implantation rate (21.6% vs. 21.1%) and live birth delivery rate (21.7% vs. 21.8%) between PBMC-treated and non-treated groups. However, when the analyses were restricted to patients who had three or more implantation failures, the clinical pregnancy rate and the implantation rate in the PBMC-treated group (42.1% and 25.0%, p<0.05; n = 19 and 32, respectively) were significantly higher than those in the non-treated group (16.7% and 9.4%, p<0.05; n = 36 and 64, respectively). These findings indicate that intrauterine administration of autologous PBMC freshly isolated from patients, effectively improves embryo implantation in patients with three or more IVF failures.

Neuropeptide Y mediates orexin A-mediated suppression of pulsatile gonadotropin-releasing hormone secretion in ovariectomized rats.

OBJECTIVES: Reproductive functions are influenced by various feeding regulators. Orexin, which is one of orexinergic peptides, suppresses the pulsatile secretion of luteinizing hormone (LH) in bilaterally ovariectomized (OVX) rats. However, the mechanism of this effect is still not clear. To investigate whether neuropeptide Y (NPY) is involved in the orexin A-mediated suppression of pulsatile LH secretion, we evaluated the effects of NPY antibody on the suppressive effect of orexin A. METHODS: Orexin A was administered intracerebroventricularly (icv) and NPY antibody (NPY-Ab) was injected before icv administration of orexin A in OVX rats. Pulsatile LH secretion was analyzed by measuring serum LH concentrations in the next 2 h in blood samples drawn at 6-min intervals by radioimmunoassay. RESULTS: Administration of orexin A significantly reduced the mean LH concentration and LH pulse frequency. Co-administration of NPY antibody with orexin A significantly restored the suppressive effect of orexin A on the mean LH concentration and LH pulse frequency. CONCLUSION: NPY mediated the suppressive effect of intracerebroventricularly injected orexin A on pulsatile LH secretion, suggesting that hypothalamic orexin suppressed pulsatile gonadotropin-releasing hormone (GnRH) secretion via NPY in the hypothalamus of female rats.

Investigation of the factors affecting the perinatal outcome of monochorionic diamniotic twins.

PURPOSE: To investigate the factors affecting the perinatal outcome in monochorionic diamniotic (MD) twins. METHODS: We conducted a retrospective study of MD twins treated in our hospital between April 1, 2006 and February 28, 2010. The neonatal outcomes of MD twins conceived by assisted reproductive technology or ovulation induction were compared to the outcomes of those conceived naturally. RESULTS: In MD twins with twin-to-twin transfusion syndrome (TTTS), fetoscopic laser photocoagulation (FLP) resulted in the survival of at least one twin. In naturally conceived MD twins with two live births, we found that there was a higher discordance rate and the incidence of intrauterine growth retardation was higher in twins born to nulliparous women than multiparous women. CONCLUSIONS: Further FLP treatment can be performed on twins with TTTS so that prognosis may be improved. Since the risk of discordant growth is significantly greater in twins of nulliparous women, they should be monitored more carefully than multiparous women.

Neonatal LPS injection alters the body weight regulation systems of rats under non-stress and immune stress conditions.

It has been reported that prenatal immune stress induced by lipopolysaccharides or cytokines increases food intake and leads to obesity and other features of metabolic syndrome in adulthood. Using Sprague-Dawley rats, we evaluated whether neonatal LPS injection altered their body weight regulation systems under non-stress and immune stress conditions. On Day 10 after birth, all pups were injected with LPS (100 microg/kg, i.p.) (PND(10)LPS) or saline (PND(10)Saline). After weaning, body weight was significantly elevated in PND(10)LPS compared with PND(10)Saline. Thereafter, the rats were injected with LPS (100 microg/kg, i.p.) or saline (used as a basal condition) from 7 to 8 weeks of age. Under basal conditions, cumulative food intake were significantly higher, serum leptin concentration was significantly increased, and hypothalamic NPY mRNA expression was significantly decreased in PND(10)LPS compared with PND(10)Saline. Under adult LPS injected conditions, body weight gain and cumulative food intake were suppressed in both the PND(10)LPS and PND(10)Saline groups compared with those observed under basal adult saline-injected conditions. The suppressive effects induced by adult LPS injection were less evident in the PND(10)LPS group than in the PND(10)Saline group. Adult LPS injection increased the serum leptin concentration in the PND(10)Saline rats, but not in the PND(10)LPS rats. In addition, adult LPS injection increased the mRNA expression of anorexinergic factors (IL-1beta, and TNF-alpha), and decreased that of the orexinergic factor NPY in both groups. However, the influence of adult LPS injection upon these factors was less evident in the PND(10)LPS group than in the PND(10)Saline group. These results suggest that neonatal LPS injection alters body weight regulation under both non-stress and immune stress conditions in male rats. Changes in the endocrine, neuropeptide, and cytokine regulation systems might be involved in these alterations.

Hypothalamic Ghrelin suppresses pulsatile secretion of luteinizing hormone via beta-endorphin in ovariectomized rats.

OBJECTIVES: Ghrelin, an endogenous growth hormone secretagogue, is a known accelerator of feeding behavior and suppresses pulsatile secretion of luteinizing hormone (LH) in ovariectomized rats. However, the mechanisms underlying this action remain unclear. We examined the effects of naloxone (NAL), a specific opioid antagonist, on the suppression of pulsatile LH secretion by ghrelin to determine whether beta-endorphin (beta-END) is involved in this suppressive effect. METHODS: Ghrelin was administered intracerebroventricularly, and NAL was injected intravenously in ovariectomized rats; then, serum LH concentrations were measured by radioimmunoassay in blood samples drawn every 6 min for 2 h to analyze pulsatile secretion. RESULTS: Administration of ghrelin significantly reduced mean LH concentration and pulse frequency. Coadministration of NAL with ghrelin significantly restored mean LH concentration and pulse frequency. CONCLUSION: Suppressive effect of intracerebroventricular injection of ghrelin on pulsatile LH secretion was mediated by beta-END, suggesting that hypothalamic ghrelin suppressed pulsatile gonadotropin-releasing hormone secretion via beta-END in female rats.

Comparison and problems of measured values of LH, FSH, and PRL among measurement systems.

Several measurement systems are used for LH, FSH, and PRL in Japan, but the comparison of the measured values is difficult in some cases. In this study, we compared the measured values of 3 types of measurement systems widely used in Japan, SPAC-S, ARCHITECT, and Centaur, in females with a normal menstrual cycle and with various ovulatory disorders. Variant LH was discriminated by the criterion, SPAC-S LH/ARCHITECT LH ratio <0.5. Excluding the variant LH, the correlation of the measured LH values among the measurement systems was high, 0.94-0.99, and the value measured by ARCHITECT LH and Centaur LH was slightly higher than that measured by SPAC-S LH. As for FSH, the correlation was also high, 0.94-1.00, and the value measured by ARCHITECT FSH and Centaur FSH was slightly lower than that measured by SPAC-S FSH. The important judgment criterion of polycystic ovary syndrome (PCOS), a high level of LH relative to FSH, has been set to 1.0 or higher LH/FSH using SPAC-S. When the regression line of the LH/FSH ratio among the measurement systems was investigated, it can be said that 1.25 or higher by ARCHITECT and 1.40 or higher by Centaur are appropriate for the judgment criteria of a high level of LH relative to FSH. As for PRL, the correlation was high, 0.96-0.99, but the value showed large differences among the systems. For the diagnosis of hyperprolactinemia, the higher limit of the normal range may be 15 ng/mL for SPAC-S, 30 ng/mL for ARCHITECT, and 24 ng/mL for Centaur.

The herbal medicine Unkei-to stimulates the secretion of a cytokine-induced neutrophil chemoattractant, CINC/gro, in the rat ovarian cell culture.

PROBLEM AND METHOD OF STUDY: We investigated the ovulation-inducing effects of Unkei-to, a Japanese herbal medicine, in relation to the production of sex steroid hormones (17beta-estradiol and progesterone), cytokine-induced neutrophil chemoattractant (CINC/gro), interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) in the rat ovarian cell culture. RESULTS: Unkei-to at a concentration of 100 microg/mL significantly stimulated the secretions of 17beta-estradiol and progesterone (P < 0.01) in cultured whole ovarian dispersates. Unkei-to also enhanced the secretion of CINC/gro in a dose-dependent manner, and the secretions of CINC/gro increased significantly at concentrations of 10 and 100 microg/mL (P < 0.01). These stimulatory effects of Unkei-to on steroidgenesis and CINC/gro production are very similar to those of another Japanese herbal medicine, Toki-Shakuyaku-san. In addition, Unkei-to significantly (P < 0.01) enhanced the secretions of both IL-1beta and TNF-alpha, which are known to stimulate the secretion of CINC/gro in the ovulatory process, at concentrations of 10 and 100 microg/mL. The stimulatory effect of Unkei-to at a concentration of 100 microg/mL on IL-1beta/was significantly (P < 0.01) lower than that of Toki-Shakuyaku-san, while the stimulatory effects of these two herbal medicines at a concentration of 100 microg/mL on TNF-alpha were similar. CONCLUSIONS: These results show that Unkei-to can stimulate ovarian steroidgenesis and the ovulatory process by inducing the secretion of CINC/gro with IL-1beta and TNF-alpha in vitro. Unkei-to has stimulatory effects on both steroidgenesis and the ovulatory process in the ovary as well as a stimulatory effect on the hypothalamus-pituitary axis, and it may be useful for treating patients with ovulatory disorders.

Effects of leptin on gonadotropin secretion in juvenile female rat pituitary cells.

OBJECTIVE: Leptin is an adipocyte-derived hormone, which is the product of the obese gene and it is thought to play important roles in pubertal development and maintenance of reproductive function in the female. In a study using adult male or female rats, it was found that leptin stimulated the secretion of gonadotropin directly from the pituitary in a dose-related manner. However, there is no study in juvenile female rats before puberty. METHODS: In this study, we cultured pituitary cells from 4-, 6- and 8-week-old female Wistar rats with leptin (0-10(-7)mol/l) and gonadotropin-releasing hormone (GnRH) (0 or 10(-8) mol/l). Basal or GnRH-stimulated secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and their synthesis within cells were determined by radioimmunoassay (RIA). RESULTS: Leptin induced bell-shaped dose--response curves of basal LH and FSH secretion from cultured cells of every age-group of rats studied. The most effective concentration of leptin on the basal secretion of LH and FSH from 6- and 8-week-old cultured pituitary cells was 10(-10) mol/l. This leptin concentration was consistent with circulating physiological serum leptin levels at each age. As for juvenile 4-week-old pituitary cells, the most effective concentration was 10(-11) mol/l which was lower than that of 6- and 8-week-old rats. It was consistent with the circulating serum leptin levels of 4-week-old rats. Also, the synthesis and the GnRH-stimulated secretion of LH and FSH were effectively controlled by leptin at concentrations similar to the serum leptin levels of given ages. CONCLUSIONS: Leptin induced pituitary cells to synthesize and secrete both LH and FSH regardless of the presence or absence of GnRH. The concentration of leptin that induced the greatest synthesis and secretion of gonadotropins from pituitary cells changed around the pubertal period. The most effective leptin concentrations in each experiment were similar to the physiological serum leptin level at each animal age. These results indicate that leptin stimulates gonadotrophs not only in the pubertal and the mature period but also in the juvenile period before puberty. It is also conceivable that leptin may modulate the sensitivity of gonadotrophs until the appearance of GnRH stimulation, and may be the factor that brings about puberty onset.